8701013|t|Famotidine-associated delirium. A series of six cases.
8701013|a|Famotidine is a histamine H2-receptor antagonist used in inpatient settings for prevention of stress ulcers and is showing increasing popularity because of its low cost. Although all of the currently available H2-receptor antagonists have shown the propensity to cause delirium, only two previously reported cases have been associated with famotidine. The authors report on six cases of famotidine-associated delirium in hospitalized patients who cleared completely upon removal of famotidine. The pharmacokinetics of famotidine are reviewed, with no change in its metabolism in the elderly population seen. The implications of using famotidine in elderly persons are discussed.
8701013	0	10	Famotidine	Chemical	D015738
8701013	22	30	delirium	Disease	D003693
8701013	55	65	Famotidine	Chemical	D015738
8701013	156	162	ulcers	Disease	D014456
8701013	324	332	delirium	Disease	D003693
8701013	395	405	famotidine	Chemical	D015738
8701013	442	452	famotidine	Chemical	D015738
8701013	464	472	delirium	Disease	D003693
8701013	537	547	famotidine	Chemical	D015738
8701013	573	583	famotidine	Chemical	D015738
8701013	689	699	famotidine	Chemical	D015738
8701013	CID	D015738	D003693

439781|t|Indomethacin induced hypotension in sodium and volume depleted rats.
439781|a|After a single oral dose of 4 mg/kg indomethacin (IDM) to sodium and volume depleted rats plasma renin activity (PRA) and systolic blood pressure fell significantly within four hours. In sodium repleted animals indomethacin did not change systolic blood pressure (BP) although plasma renin activity was decreased. Thus, indomethacin by inhibition of prostaglandin synthesis may diminish the blood pressure maintaining effect of the stimulated renin-angiotensin system in sodium and volume depletion.
439781	0	12	Indomethacin	Chemical	D007213
439781	21	32	hypotension	Disease	D007022
439781	36	42	sodium	Chemical	D012964
439781	105	117	indomethacin	Chemical	D007213
439781	119	122	IDM	Chemical	D007213
439781	127	133	sodium	Chemical	D012964
439781	256	262	sodium	Chemical	D012964
439781	280	292	indomethacin	Chemical	D007213
439781	389	401	indomethacin	Chemical	D007213
439781	419	432	prostaglandin	Chemical	D011453
439781	518	529	angiotensin	Chemical	D000809
439781	540	546	sodium	Chemical	D012964
439781	CID	D007213	D007022

22836123|t|Late-onset scleroderma renal crisis induced by tacrolimus and prednisolone: a case report.
22836123|a|Scleroderma renal crisis (SRC) is a rare complication of systemic sclerosis (SSc) but can be severe enough to require temporary or permanent renal replacement therapy. Moderate to high dose corticosteroid use is recognized as a major risk factor for SRC. Furthermore, there have been reports of thrombotic microangiopathy precipitated by cyclosporine in patients with SSc. In this article, we report a patient with SRC induced by tacrolimus and corticosteroids. The aim of this work is to call attention to the risk of tacrolimus use in patients with SSc.
22836123	11	35	scleroderma renal crisis	Disease	D007674
22836123	47	57	tacrolimus	Chemical	D016559
22836123	62	74	prednisolone	Chemical	D011239
22836123	91	115	Scleroderma renal crisis	Disease	D007674
22836123	117	120	SRC	Disease	D007674
22836123	148	166	systemic sclerosis	Disease	D012595
22836123	168	171	SSc	Disease	D012595
22836123	281	295	corticosteroid	Chemical	D000305
22836123	341	344	SRC	Disease	D007674
22836123	386	412	thrombotic microangiopathy	Disease	D057049
22836123	429	441	cyclosporine	Chemical	D016572
22836123	459	462	SSc	Disease	D012595
22836123	506	509	SRC	Disease	D007674
22836123	521	531	tacrolimus	Chemical	D016559
22836123	536	551	corticosteroids	Chemical	D000305
22836123	610	620	tacrolimus	Chemical	D016559
22836123	642	645	SSc	Disease	D012595
22836123	CID	D016572	D057049
22836123	CID	D000305	D012595
22836123	CID	D016559	D012595

23433219|t|The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia.
23433219|a|OBJECTIVE: The objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. METHODS: This was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. RESULTS: Of 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612-19.708), bipolar disorder (OR=13.807, 95 CI=5.194-36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702-23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154-7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375-7.914) were the only factors associated with current psychosis. CONCLUSION: There was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms.
23433219	35	50	methamphetamine	Chemical	D008694
23433219	51	60	psychosis	Disease	D011605
23433219	64	79	methamphetamine	Chemical	D008694
23433219	201	216	methamphetamine	Chemical	D008694
23433219	225	234	psychosis	Disease	D011605
23433219	252	267	methamphetamine	Chemical	D008694
23433219	333	348	methamphetamine	Chemical	D008694
23433219	357	366	psychosis	Disease	D011605
23433219	550	565	methamphetamine	Chemical	D008694
23433219	670	685	methamphetamine	Chemical	D008694
23433219	694	703	psychosis	Disease	D011605
23433219	721	742	psychiatric disorders	Disease	D001523
23433219	930	948	psychotic symptoms	Disease	D011605
23433219	995	1013	psychotic symptoms	Disease	D011605
23433219	1031	1050	depressive disorder	Disease	D003866
23433219	1082	1098	bipolar disorder	Disease	D001714
23433219	1132	1163	antisocial personality disorder	Disease	D000987
23433219	1206	1221	methamphetamine	Chemical	D008694
23433219	1271	1286	methamphetamine	Chemical	D008694
23433219	1295	1304	psychosis	Disease	D011605
23433219	1339	1364	Major depressive disorder	Disease	D003865
23433219	1396	1427	antisocial personality disorder	Disease	D000987
23433219	1504	1513	psychosis	Disease	D011605
23433219	1552	1561	psychosis	Disease	D011605
23433219	1579	1594	methamphetamine	Chemical	D008694
23433219	1640	1658	affective disorder	Disease	D019964
23433219	1660	1682	antisocial personality	Disease	D000987
23433219	1694	1709	methamphetamine	Chemical	D008694
23433219	1751	1766	methamphetamine	Chemical	D008694
23433219	1801	1819	psychotic symptoms	Disease	D011605
23433219	CID	D008694	D011605
23433219	CID	D008694	D001714
23433219	CID	D008694	D000987

23535177|t|Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson's disease: clues from dyskinetic patients.
23535177|a|The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently reported in young healthy subjects that inhibitory cerebellar stimulation enhanced the sensorimotor plasticity of M1 that was induced by paired associative stimulation (PAS). This study demonstrates that the deficient sensorimotor M1 plasticity in 16 patients with LIDs could be reinstated by a single session of real inhibitory cerebellar stimulation but not sham stimulation. This was evident only when a sensory component was involved in the induction of plasticity, indicating that cerebellar sensory processing function is involved in the resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on LIDs is known. To explore whether this benefit is linked to the restoration of sensorimotor plasticity of M1, we conducted an additional study looking at changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral, real inhibitory cerebellar stimulation or sham stimulation. Only real and not sham stimulation had an antidyskinetic effect and it was paralleled by a resurgence in the sensorimotor plasticity of M1. These results suggest that alterations in cerebellar sensory processing function, occurring secondary to abnormal basal ganglia signals reaching it, may be an important element contributing to the maladaptive sensorimotor plasticity of M1 and the emergence of abnormal involuntary movements.
23535177	78	97	Parkinson's disease	Disease	D010300
23535177	110	120	dyskinetic	Disease	D004409
23535177	192	211	Parkinson's disease	Disease	D010300
23535177	213	215	PD	Disease	D010300
23535177	221	229	levodopa	Chemical	D007980
23535177	238	249	dyskinesias	Disease	D004409
23535177	251	255	LIDs	Disease	D004409
23535177	556	560	LIDs	Disease	D004409
23535177	916	920	LIDs	Disease	D004409
23535177	1081	1085	LIDs	Disease	D004409
23535177	1612	1642	abnormal involuntary movements	Disease	D004409
23535177	CID	D007980	D004409

23666265|t|The function of P2X3 receptor and NK1 receptor antagonists on cyclophosphamide-induced cystitis in rats.
23666265|a|PURPOSE: The purpose of the study is to explore the function of P2X3 and NK1 receptors antagonists on cyclophosphamide (CYP)-induced cystitis in rats. METHODS: Sixty female Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the control group were intraperitoneally (i.p.) injected with 0.9% saline (4 ml/kg); the rats in the model group were i.p. injected with CYP (150 mg/kg); and the rats in the intervention group were i.p. injected with CYP with subsequently perfusion of bladder with P2X3 and NK1 receptors' antagonists, Suramin and GR 82334. Spontaneous pain behaviors following the administration of CYP were observed. Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder. RESULTS: Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (X(2) = 7.619, P = 0.007) and control group (X(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower. CONCLUSIONS: In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder function.
23666265	62	78	cyclophosphamide	Chemical	D003520
23666265	87	95	cystitis	Disease	D003556
23666265	207	223	cyclophosphamide	Chemical	D003520
23666265	225	228	CYP	Chemical	D003520
23666265	238	246	cystitis	Disease	D003556
23666265	493	496	CYP	Chemical	D003520
23666265	573	576	CYP	Chemical	D003520
23666265	658	665	Suramin	Chemical	D013498
23666265	670	678	GR 82334	Chemical	C079014
23666265	692	696	pain	Disease	D010146
23666265	739	742	CYP	Chemical	D003520
23666265	1053	1069	Cyclophosphamide	Chemical	D003520
23666265	1106	1110	pain	Disease	D010146
23666265	1501	1506	edema	Disease	D004487
23666265	1776	1779	CYP	Chemical	D003520
23666265	1788	1796	cystitis	Disease	D003556
23666265	CID	D003520	D003556
23666265	CID	D003520	D010146
23666265	CID	D003520	D004487

23846525|t|Acute hepatitis associated with clopidogrel: a case report and review of the literature.
23846525|a|Drug-induced hepatotoxicity is a common cause of acute hepatitis, and the recognition of the responsible drug may be difficult. We describe a case of clopidogrel-related acute hepatitis. The diagnosis is strongly suggested by an accurate medical history and liver biopsy. Reports about cases of hepatotoxicity due to clopidogrel are increasing in the last few years, after the increased use of this drug. In conclusion, we believe that physicians should carefully consider the risk of drug-induced hepatic injury when clopidogrel is prescribed.
23846525	6	15	hepatitis	Disease	D056486
23846525	32	43	clopidogrel	Chemical	C055162
23846525	102	116	hepatotoxicity	Disease	D056486
23846525	144	153	hepatitis	Disease	D056486
23846525	239	250	clopidogrel	Chemical	C055162
23846525	265	274	hepatitis	Disease	D056486
23846525	384	398	hepatotoxicity	Disease	D056486
23846525	406	417	clopidogrel	Chemical	C055162
23846525	587	601	hepatic injury	Disease	D056486
23846525	607	618	clopidogrel	Chemical	C055162
23846525	CID	C055162	D056486

23864035|t|Bortezomib and dexamethasone as salvage therapy in patients with relapsed/refractory multiple myeloma: analysis of long-term clinical outcomes.
23864035|a|Bortezomib (bort)-dexamethasone (dex) is an effective therapy for relapsed/refractory (R/R) multiple myeloma (MM). This retrospective study investigated the combination of bort (1.3 mg/m(2) on days 1, 4, 8, and 11 every 3 weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment in 85 patients with R/R MM after prior autologous stem cell transplantation or conventional chemotherapy. The median number of prior lines of therapy was 2. Eighty-seven percent of the patients had received immunomodulatory drugs included in some line of therapy before bort-dex. The median number of bort-dex cycles was 6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the patients achieved at least partial response, including 19 % CR and 35 % achieved at least very good partial response. Median durations of response, time to next therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively. The most relevant adverse event was peripheral neuropathy, which occurred in 78 % of the patients (grade II, 38 %; grade III, 21 %) and led to treatment discontinuation in 6 %. With a median follow up of 22 months, median time to progression, progression-free survival (PFS) and overall survival (OS) were 8.9, 8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was an effective salvage treatment for MM patients, particularly for those in first relapse.
23864035	0	10	Bortezomib	Chemical	C400082
23864035	15	28	dexamethasone	Chemical	D003907
23864035	85	101	multiple myeloma	Disease	D009101
23864035	144	154	Bortezomib	Chemical	C400082
23864035	156	160	bort	Chemical	C400082
23864035	162	175	dexamethasone	Chemical	D003907
23864035	177	180	dex	Chemical	D003907
23864035	236	252	multiple myeloma	Disease	D009101
23864035	254	256	MM	Disease	D009101
23864035	316	320	bort	Chemical	C400082
23864035	377	380	dex	Chemical	D003907
23864035	420	424	bort	Chemical	C400082
23864035	471	473	MM	Disease	D009101
23864035	717	721	bort	Chemical	C400082
23864035	722	725	dex	Chemical	D003907
23864035	748	752	bort	Chemical	C400082
23864035	753	756	dex	Chemical	D003907
23864035	1122	1143	peripheral neuropathy	Disease	D010523
23864035	1505	1509	bort	Chemical	C400082
23864035	1510	1513	dex	Chemical	D003907
23864035	1546	1550	Bort	Chemical	C400082
23864035	1551	1554	dex	Chemical	D003907
23864035	1594	1596	MM	Disease	D009101
23864035	CID	D003907	D010523
23864035	CID	C400082	D010523

23871786|t|Pubertal exposure to Bisphenol A increases anxiety-like behavior and decreases acetylcholinesterase activity of hippocampus in adult male mice.
23871786|a|The negative effects of Bisphenol A (BPA) on neurodevelopment and behaviors have been well established. Acetylcholinesterase (AChE) is a regulatory enzyme which is involved in anxiety-like behavior. This study investigated behavioral phenotypes and AChE activity in male mice following BPA exposure during puberty. On postnatal day (PND) 35, male mice were exposed to 50mg BPA/kg diet per day for a period of 35 days. On PND71, a behavioral assay was performed using the elevated plus maze (EPM) and the light/dark test. In addition, AChE activity was measured in the prefrontal cortex, hypothalamus, cerebellum and hippocampus. Results from our behavioral phenotyping indicated that anxiety-like behavior was increased in mice exposed to BPA. AChE activity was significantly decreased in the hippocampus of mice with BPA compared to control mice, whereas no difference was found in the prefrontal cortex, hypothalamus and cerebellum. Our findings showed that pubertal BPA exposure increased anxiety-like behavior, which may be associated with decreased AChE activity of the hippocampus in adult male mice. Further studies are necessary to investigate the cholinergic signaling of the hippocampus in PBE induced anxiety-like behaviors.
23871786	21	32	Bisphenol A	Chemical	C006780
23871786	43	50	anxiety	Disease	D001008
23871786	168	179	Bisphenol A	Chemical	C006780
23871786	181	184	BPA	Chemical	C006780
23871786	320	327	anxiety	Disease	D001008
23871786	430	433	BPA	Chemical	C006780
23871786	517	520	BPA	Chemical	C006780
23871786	828	835	anxiety	Disease	D001008
23871786	883	886	BPA	Chemical	C006780
23871786	962	965	BPA	Chemical	C006780
23871786	1113	1116	BPA	Chemical	C006780
23871786	1136	1143	anxiety	Disease	D001008
23871786	1356	1363	anxiety	Disease	D001008
23871786	CID	C006780	D001008

23872883|t|Biochemical effects of Solidago virgaurea extract on experimental cardiotoxicity.
23872883|a|Cardiovascular diseases (CVDs) are the major health problem of advanced as well as developing countries of the world. The aim of the present study was to investigate the protective effect of the Solidago virgaurea extract on isoproterenol-induced cardiotoxicity in rats. The subcutaneous injection of isoproterenol (30 mg/kg) into rats twice at an interval of 24 h, for two consecutive days, led to a significant increase in serum lactate dehydrogenase, creatine phosphokinase, alanine transaminase, aspartate transaminase, and angiotensin-converting enzyme activities, total cholesterol, triglycerides, free serum fatty acid, cardiac tissue malondialdehyde (MDA), and nitric oxide levels and a significant decrease in levels of glutathione and superoxide dismutase in cardiac tissue as compared to the normal control group (P < 0.05). Pretreatment with S. virgaurea extract for 5 weeks at a dose of 250 mg/kg followed by isoproterenol injection significantly prevented the observed alterations. Captopril (50 mg/kg/day, given orally), an inhibitor of angiotensin-converting enzyme used as a standard cardioprotective drug, was used as a positive control in this study. The data of the present study suggest that S. virgaurea extract exerts its protective effect by decreasing MDA level and increasing the antioxidant status in isoproterenol-treated rats. The study emphasizes the beneficial action of S. virgaurea extract as a cardioprotective agent.
23872883	66	80	cardiotoxicity	Disease	D066126
23872883	82	105	Cardiovascular diseases	Disease	D002318
23872883	107	111	CVDs	Disease	D002318
23872883	307	320	isoproterenol	Chemical	D007545
23872883	329	343	cardiotoxicity	Disease	D066126
23872883	383	396	isoproterenol	Chemical	D007545
23872883	513	520	lactate	Chemical	D019344
23872883	536	544	creatine	Chemical	D003401
23872883	560	567	alanine	Chemical	D000409
23872883	582	591	aspartate	Chemical	D001224
23872883	610	621	angiotensin	Chemical	D000809
23872883	658	669	cholesterol	Chemical	D002784
23872883	671	684	triglycerides	Chemical	D014280
23872883	697	707	fatty acid	Chemical	D005227
23872883	724	739	malondialdehyde	Chemical	D008315
23872883	741	744	MDA	Chemical	D008315
23872883	751	763	nitric oxide	Chemical	D009569
23872883	811	822	glutathione	Chemical	D005978
23872883	827	837	superoxide	Chemical	D013481
23872883	1004	1017	isoproterenol	Chemical	D007545
23872883	1078	1087	Captopril	Chemical	D002216
23872883	1134	1145	angiotensin	Chemical	D000809
23872883	1359	1362	MDA	Chemical	D008315
23872883	1410	1423	isoproterenol	Chemical	D007545
23872883	CID	D007545	D066126

23892921|t|"Real-world" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group.
23892921|a|Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the "real world" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (>PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2(nd)-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease.
23892921	48	60	lenalidomide	Chemical	C467567
23892921	65	78	dexamethasone	Chemical	D003907
23892921	116	132	multiple myeloma	Disease	D009101
23892921	216	223	Myeloma	Disease	D009101
23892921	237	249	Lenalidomide	Chemical	C467567
23892921	254	267	dexamethasone	Chemical	D003907
23892921	269	271	RD	Chemical	C467567|D003907
23892921	319	335	multiple myeloma	Disease	D009101
23892921	337	341	RRMM	Disease	D009101
23892921	542	546	RRMM	Disease	D009101
23892921	569	571	RD	Chemical	C467567|D003907
23892921	769	771	RD	Chemical	C467567|D003907
23892921	939	950	thalidomide	Chemical	D013792
23892921	954	964	bortezomib	Chemical	C400082
23892921	1054	1056	RD	Chemical	C467567|D003907
23892921	1306	1322	myelosuppression	Disease	D001855
23892921	1381	1402	Peripheral neuropathy	Disease	D010523
23892921	1446	1466	deep vein thrombosis	Disease	D020246
23892921	1660	1672	lenalidomide	Chemical	C467567
23892921	1799	1801	RD	Chemical	C467567|D003907
23892921	1827	1831	RRMM	Disease	D009101
23892921	CID	D003907	D010523
23892921	CID	D003907	D001855
23892921	CID	D003907	D020246
23892921	CID	C467567	D001855
23892921	CID	C467567	D010523
23892921	CID	C467567	D020246

23949582|t|The cytogenetic action of ifosfamide, mesna, and their combination on peripheral rabbit lymphocytes: an in vivo/in vitro cytogenetic study.
23949582|a|Ifosfamide (IFO) is an alkylating nitrogen mustard, administrated as an antineoplasmic agent. It is characterized by its intense urotoxic action, leading to hemorrhagic cystitis. This side effect of IFO raises the requirement for the co-administration with sodium 2-sulfanylethanesulfonate (Mesna) aiming to avoid or minimize this effect. IFO and Mesna were administrated separately on rabbit's lymphocytes in vivo, which were later developed in vitro. Cytogenetic markers for sister chromatid exchanges (SCEs), proliferation rate index (PRI) and Mitotic Index were recorded. Mesna's action, in conjunction with IFO reduces the frequency of SCEs, in comparison with the SCEs recordings obtained when IFO is administered alone. In addition to this, when high concentrations of Mesna were administered alone significant reductions of the PRI were noted, than with IFO acting at the same concentration on the lymphocytes. Mesna significantly reduces IFO's genotoxicity, while when administered in high concentrations it acts in an inhibitory fashion on the cytostatic action of the drug.
23949582	26	36	ifosfamide	Chemical	D007069
23949582	38	43	mesna	Chemical	D015080
23949582	140	150	Ifosfamide	Chemical	D007069
23949582	152	155	IFO	Chemical	D007069
23949582	174	182	nitrogen	Chemical	D009584
23949582	297	317	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
23949582	339	342	IFO	Chemical	D007069
23949582	397	429	sodium 2-sulfanylethanesulfonate	Chemical	D015080
23949582	431	436	Mesna	Chemical	D015080
23949582	479	482	IFO	Chemical	D007069
23949582	487	492	Mesna	Chemical	D015080
23949582	716	721	Mesna	Chemical	D015080
23949582	752	755	IFO	Chemical	D007069
23949582	840	843	IFO	Chemical	D007069
23949582	916	921	Mesna	Chemical	D015080
23949582	1002	1005	IFO	Chemical	D007069
23949582	1059	1064	Mesna	Chemical	D015080
23949582	1087	1090	IFO	Chemical	D007069
23949582	1093	1105	genotoxicity	Disease	D030342
23949582	CID	D007069	D003556
23949582	CID	D007069	D006470

23952588|t|Risk factors and predictors of levodopa-induced dyskinesia among multiethnic Malaysians with Parkinson's disease.
23952588|a|Chronic pulsatile levodopa therapy for Parkinson's disease (PD) leads to the development of motor fluctuations and dyskinesia. We studied the prevalence and predictors of levodopa-induced dyskinesia among multiethnic Malaysian patients with PD. METHODS: This is a cross-sectional study involving 95 patients with PD on uninterrupted levodopa therapy for at least 6 months. The instrument used was the UPDRS questionnaires. The predictors of dyskinesia were determined using multivariate logistic regression analysis. RESULTS: The mean age was 65.6 + 8.5 years. The mean onset age was 58.5 + 9.8 years. The median disease duration was 6 (7) years. Dyskinesia was present in 44% (n = 42) with median levodopa therapy of 3 years. There were 64.3% Chinese, 31% Malays, and 3.7% Indians and other ethnic groups. Eighty-one percent of patients with dyskinesia had clinical fluctuations. Patients with dyskinesia had lower onset age ( p < 0.001), longer duration of levodopa therapy ( p < 0.001), longer disease duration ( p < 0.001), higher total daily levodopa dose ( p < 0.001), and higher total UPDRS scores ( p = 0.005) than patients without dyskinesia. The three significant predictors of dyskinesia were duration of levodopa therapy, onset age, and total daily levodopa dose. CONCLUSIONS: The prevalence of levodopa-induced dyskinesia in our patients was 44%. The most significant predictors were duration of levodopa therapy, total daily levodopa dose, and onset age.
23952588	31	39	levodopa	Chemical	D007980
23952588	48	58	dyskinesia	Disease	D004409
23952588	93	112	Parkinson's disease	Disease	D010300
23952588	132	140	levodopa	Chemical	D007980
23952588	153	172	Parkinson's disease	Disease	D010300
23952588	174	176	PD	Disease	D010300
23952588	229	239	dyskinesia	Disease	D004409
23952588	285	293	levodopa	Chemical	D007980
23952588	302	312	dyskinesia	Disease	D004409
23952588	355	357	PD	Disease	D010300
23952588	427	429	PD	Disease	D010300
23952588	447	455	levodopa	Chemical	D007980
23952588	555	565	dyskinesia	Disease	D004409
23952588	761	771	Dyskinesia	Disease	D004409
23952588	812	820	levodopa	Chemical	D007980
23952588	957	967	dyskinesia	Disease	D004409
23952588	1009	1019	dyskinesia	Disease	D004409
23952588	1073	1081	levodopa	Chemical	D007980
23952588	1161	1169	levodopa	Chemical	D007980
23952588	1254	1264	dyskinesia	Disease	D004409
23952588	1302	1312	dyskinesia	Disease	D004409
23952588	1330	1338	levodopa	Chemical	D007980
23952588	1375	1383	levodopa	Chemical	D007980
23952588	1421	1429	levodopa	Chemical	D007980
23952588	1438	1448	dyskinesia	Disease	D004409
23952588	1523	1531	levodopa	Chemical	D007980
23952588	1553	1561	levodopa	Chemical	D007980
23952588	CID	D007980	D004409

24040781|t|An unexpected diagnosis in a renal-transplant patient with proteinuria treated with everolimus: AL amyloidosis.
24040781|a|Proteinuria is an expected complication in transplant patients treated with mammalian target of rapamycin inhibitors (mTOR-i). However, clinical suspicion should always be supported by histological evidence in order to investigate potential alternate diagnoses such as acute or chronic rejection, interstitial fibrosis and tubular atrophy, or recurrent or de novo glomerulopathy. In this case we report the unexpected diagnosis of amyloidosis in a renal-transplant patient with pre-transplant monoclonal gammapathy of undetermined significance who developed proteinuria after conversion from tacrolimus to everolimus.
24040781	59	70	proteinuria	Disease	D011507
24040781	84	94	everolimus	Chemical	C107135
24040781	96	98	AL	Disease	D000686
24040781	99	110	amyloidosis	Disease	D000686
24040781	112	123	Proteinuria	Disease	D011507
24040781	208	217	rapamycin	Chemical	D020123
24040781	422	430	fibrosis	Disease	D005355
24040781	443	450	atrophy	Disease	D001284
24040781	476	490	glomerulopathy	Disease	D007674
24040781	543	554	amyloidosis	Disease	D000686
24040781	670	681	proteinuria	Disease	D011507
24040781	704	714	tacrolimus	Chemical	D016559
24040781	718	728	everolimus	Chemical	C107135
24040781	CID	C107135	D000686
24040781	CID	C107135	D011507

24067251|t|An investigation of the pattern of kidney injury in HIV-positive persons exposed to tenofovir disoproxil fumarate: an examination of a large population database (MHRA database).
24067251|a|The potential for tenofovir to cause a range of kidney syndromes has been established from mechanistic and randomised clinical trials. However, the exact pattern of kidney involvement is still uncertain. We undertook a descriptive analysis of Yellow Card records of 407 HIV-positive persons taking tenofovir disoproxil fumarate (TDF) as part of their antiretroviral therapy regimen and submitted to the Medicines and Healthcare Products Regulatory Agency (MHRA) with suspected kidney adverse effects. Reports that satisfy defined criteria were classified as acute kidney injury, kidney tubular dysfunction and Fanconi syndrome. Of the 407 Yellow Card records analysed, 106 satisfied criteria for TDF-related kidney disease, of which 53 (50%) had features of kidney tubular dysfunction, 35 (33%) were found to have features of glomerular dysfunction and 18 (17%) had Fanconi syndrome. The median TDF exposure was 316 days (interquartile range 120-740). The incidence of hospitalisation for TDF kidney adverse effects was high, particularly amongst patients with features of Fanconi syndrome. The pattern of kidney syndromes in this population series mirrors that reported in randomised clinical trials. Cessation of TDF was associated with complete restoration of kidney function in up half of the patients in this report.
24067251	35	48	kidney injury	Disease	D007674
24067251	84	113	tenofovir disoproxil fumarate	Chemical	C418563
24067251	196	205	tenofovir	Chemical	C096918
24067251	476	505	tenofovir disoproxil fumarate	Chemical	C418563
24067251	507	510	TDF	Chemical	C418563
24067251	736	755	acute kidney injury	Disease	D058186
24067251	757	783	kidney tubular dysfunction	Disease	D007674
24067251	788	804	Fanconi syndrome	Disease	D005198
24067251	874	877	TDF	Chemical	C418563
24067251	886	900	kidney disease	Disease	D007674
24067251	936	962	kidney tubular dysfunction	Disease	D007674
24067251	1004	1026	glomerular dysfunction	Disease	D007674
24067251	1044	1060	Fanconi syndrome	Disease	D005198
24067251	1073	1076	TDF	Chemical	C418563
24067251	1167	1170	TDF	Chemical	C418563
24067251	1251	1267	Fanconi syndrome	Disease	D005198
24067251	1393	1396	TDF	Chemical	C418563
24067251	CID	C418563	D058186
24067251	CID	C418563	D005198

24068571|t|Incidence of postoperative delirium is high even in a population without known risk factors.
24068571|a|PURPOSE: Postoperative delirium is a recognized complication in populations at risk. The aim of this study is to assess the prevalence of early postoperative delirium in a population without known risk factors admitted to the ICU for postoperative monitoring after elective major surgery. The secondary outcome investigated is to identify eventual independent risk factors among demographic data and anesthetic drugs used. METHODS: An observational, prospective study was conducted on a consecutive cohort of patients admitted to our ICU within and for at least 24 h after major surgical procedures. Exclusion criteria were any preexisting predisposing factor for delirium or other potentially confounding neurological dysfunctions. Patients were assessed daily using the confusion assessment method for the ICU scale for 3 days after the surgical procedure. Early postoperative delirium incidence risk factors were then assessed through three different multiple regression models. RESULTS: According to the confusion assessment method for the ICU scale, 28 % of patients were diagnosed with early postoperative delirium. The use of thiopentone was significantly associated with an eight-fold-higher risk for delirium compared to propofol (57.1% vs. 7.1%, RR = 8.0, X2 = 4.256; df = 1; 0.05 < p < 0.02). CONCLUSION: In this study early postoperative delirium was found to be a very common complication after major surgery, even in a population without known risk factors. Thiopentone was independently associated with an increase in its relative risk.
24068571	13	35	postoperative delirium	Disease	D011183
24068571	102	124	Postoperative delirium	Disease	D011183
24068571	237	259	postoperative delirium	Disease	D011183
24068571	757	765	delirium	Disease	D003693
24068571	799	824	neurological dysfunctions	Disease	D009422
24068571	865	874	confusion	Disease	D003221
24068571	958	980	postoperative delirium	Disease	D011183
24068571	1191	1213	postoperative delirium	Disease	D011183
24068571	1226	1237	thiopentone	Chemical	D013874
24068571	1302	1310	delirium	Disease	D003693
24068571	1323	1331	propofol	Chemical	D015742
24068571	1429	1451	postoperative delirium	Disease	D011183
24068571	1565	1576	Thiopentone	Chemical	D013874
24068571	CID	D013874	D011183
24068571	CID	D013874	D003693

24072398|t|A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice.
24072398|a|Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis.
24072398	9	19	neurotoxic	Disease	D020258
24072398	28	43	methamphetamine	Chemical	D008694
24072398	67	77	depressive	Disease	D003866
24072398	102	117	Methamphetamine	Chemical	D008694
24072398	119	123	METH	Chemical	D008694
24072398	179	183	METH	Chemical	D008694
24072398	235	254	depressive symptoms	Disease	D003866
24072398	341	345	METH	Chemical	D008694
24072398	373	383	depressive	Disease	D003866
24072398	459	469	depressive	Disease	D003866
24072398	548	552	METH	Chemical	D008694
24072398	576	580	METH	Chemical	D008694
24072398	765	769	METH	Chemical	D008694
24072398	885	895	depressive	Disease	D003866
24072398	920	924	METH	Chemical	D008694
24072398	1072	1080	dopamine	Chemical	D004298
24072398	1082	1087	DOPAC	Chemical	D015102
24072398	1092	1095	HVA	Chemical	D006719
24072398	1097	1105	tyrosine	Chemical	D014443
24072398	1122	1131	serotonin	Chemical	D012701
24072398	1231	1241	depression	Disease	D003866
24072398	1503	1507	METH	Chemical	D008694
24072398	1529	1539	depressive	Disease	D003866
24072398	CID	D008694	D003866

24088636|t|Linezolid-induced optic neuropathy.
24088636|a|Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.
24088636	0	9	Linezolid	Chemical	C098010
24088636	18	34	optic neuropathy	Disease	D009901
24088636	270	284	loss of vision	Disease	D014786
24088636	301	310	linezolid	Chemical	C098010
24088636	427	436	linezolid	Chemical	C098010
24088636	441	451	ethambutol	Chemical	D004977
24088636	456	495	extensively drug-resistant tuberculosis	Disease	D054908
24088636	497	503	XDR-TB	Disease	D054908
24088636	547	561	loss of vision	Disease	D014786
24088636	635	651	optic disc edema	Disease	C531767
24088636	666	676	Ethambutol	Chemical	D004977
24088636	685	707	toxic optic neuropathy	Disease	D009901
24088636	733	743	ethambutol	Chemical	D004977
24088636	759	782	Deterioration of vision	Disease	D015354
24088636	814	824	ethambutol	Chemical	D004977
24088636	845	854	linezolid	Chemical	C098010
24088636	987	996	linezolid	Chemical	C098010
24088636	CID	C098010	D009901
24088636	CID	C098010	C531767

24091473|t|Resuscitation with lipid, epinephrine, or both in levobupivacaine-induced cardiac toxicity in newborn piglets.
24091473|a|BACKGROUND: The optimal dosing regimens of lipid emulsion, epinephrine, or both are not yet determined in neonates in cases of local anaesthetic systemic toxicity (LAST). METHODS: Newborn piglets received levobupivacaine until cardiovascular collapse occurred. Standard cardiopulmonary resuscitation was started and electrocardiogram (ECG) was monitored for ventricular tachycardia, fibrillation, or QRS prolongation. Piglets were then randomly allocated to four groups: control (saline), Intralipid( ) alone, epinephrine alone, or a combination of Intralipd plus epinephrine. Resuscitation continued for 30 min or until there was a return of spontaneous circulation (ROSC) accompanied by a mean arterial pressure at or superior to the baseline pressure and normal sinus rhythm for a period of 30 min. RESULTS: ROSC was achieved in only one of the control piglets compared with most of the treated piglets. Mortality was not significantly different between the three treatment groups, but was significantly lower in all the treatment groups compared with control. The number of ECG abnormalities was zero in the Intralipid only group, but 14 and 17, respectively, in the epinephrine and epinephrine plus lipid groups (P<0.05). CONCLUSIONS: Lipid emulsion with or without epinephrine, or epinephrine alone were equally effective in achieving a return to spontaneous circulation in this model of LAST. Epinephrine alone or in combination with lipid was associated with an increased number of ECG abnormalities compared with lipid emulsion alone.
24091473	26	37	epinephrine	Chemical	D004837
24091473	50	65	levobupivacaine	Chemical	C476513
24091473	74	90	cardiac toxicity	Disease	D066126
24091473	170	181	epinephrine	Chemical	D004837
24091473	265	273	toxicity	Disease	D064420
24091473	316	331	levobupivacaine	Chemical	C476513
24091473	338	361	cardiovascular collapse	Disease	D002318
24091473	469	492	ventricular tachycardia	Disease	D017180
24091473	494	506	fibrillation	Disease	D001281
24091473	621	632	epinephrine	Chemical	D004837
24091473	675	686	epinephrine	Chemical	D004837
24091473	1282	1293	epinephrine	Chemical	D004837
24091473	1298	1309	epinephrine	Chemical	D004837
24091473	1382	1393	epinephrine	Chemical	D004837
24091473	1398	1409	epinephrine	Chemical	D004837
24091473	1511	1522	Epinephrine	Chemical	D004837
24091473	CID	C476513	D002318

24100055|t|Incidence of heparin-induced thrombocytopenia type II and postoperative recovery of platelet count in liver graft recipients: a retrospective cohort analysis.
24100055|a|BACKGROUND: Thrombocytopenia in patients with end-stage liver disease is a common disorder caused mainly by portal hypertension, low levels of thrombopoetin, and endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type II (HIT type II) as a cause of thrombocytopenia after liver transplantation is not yet understood, with few literature citations reporting contradictory results. The aim of our study was to demonstrate the perioperative course of thrombocytopenia after liver transplantation and determine the occurrence of clinical HIT type II. METHOD: We retrospectively evaluated the medical records of 205 consecutive adult patients who underwent full-size liver transplantation between January 2006 and December 2010 due to end-stage or malignant liver disease. Preoperative platelet count, postoperative course of platelets, and clinical signs of HIT type II were analyzed. RESULTS: A total of 155 (75.6%) of 205 patients had thrombocytopenia before transplantation, significantly influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The platelet count exceeded 100,000/uL in most of the patients (n = 193) at a medium of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of HIT type II. CONCLUSIONS: The incidence of HIT in patients with end-stage hepatic failure is, with about 1.95%, rare. For further reduction of HIT type II, the use of intravenous heparin should be avoided and the prophylactic anticoagulation should be performed with low-molecular-weight heparin after normalization of platelet count.
24100055	13	20	heparin	Chemical	D006493
24100055	29	53	thrombocytopenia type II	Disease	D013921
24100055	171	187	Thrombocytopenia	Disease	D013921
24100055	205	228	end-stage liver disease	Disease	D058625
24100055	267	286	portal hypertension	Disease	D006975
24100055	321	332	endotoxemia	Disease	D019446
24100055	364	371	heparin	Chemical	D006493
24100055	380	404	thrombocytopenia type II	Disease	D013921
24100055	406	417	HIT type II	Disease	D013921
24100055	433	449	thrombocytopenia	Disease	D013921
24100055	632	648	thrombocytopenia	Disease	D013921
24100055	718	729	HIT type II	Disease	D013921
24100055	914	950	end-stage or malignant liver disease	Disease	D058625|D017114	end-stage liver disease|malignant liver disease
24100055	1038	1049	HIT type II	Disease	D013921
24100055	1117	1133	thrombocytopenia	Disease	D013921
24100055	1195	1218	End-Stage Liver Disease	Disease	D058625
24100055	1229	1244	liver cirrhosis	Disease	D008103
24100055	1349	1355	HIT II	Disease	D013921
24100055	1411	1422	HIT type II	Disease	D013921
24100055	1454	1457	HIT	Disease	D013921
24100055	1475	1500	end-stage hepatic failure	Disease	D058625
24100055	1554	1565	HIT type II	Disease	D013921
24100055	1590	1597	heparin	Chemical	D006493
24100055	1699	1706	heparin	Chemical	D006493
24100055	CID	D006493	D013921

24100257|t|Takotsubo syndrome (or apical ballooning syndrome) secondary to Zolmitriptan.
24100257|a|Takotsubo syndrome (TS), also known as broken heart syndrome, is characterized by left ventricle apical ballooning with elevated cardiac biomarkers and electrocardiographic changes suggestive of an acute coronary syndrome (ie, ST-segment elevation, T wave inversions, and pathologic Q waves). We report a case of 54-year-old woman with medical history of mitral valve prolapse and migraines, who was admitted to the hospital for substernal chest pain and electrocardiogram demonstrated 1/2 mm ST-segment elevation in leads II, III, aVF, V5, and V6 and positive troponin I. Emergent coronary angiogram revealed normal coronary arteries with moderately reduced left ventricular ejection fraction with wall motion abnormalities consistent with TS. Detailed history obtained retrospectively revealed that the patient took zolmitriptan sparingly only when she had migraines. But before this event, she was taking zolmitriptan 2-3 times daily for several days because of a persistent migraine headache. She otherwise reported that she is quite active, rides horses, and does show jumping without any limitations in her physical activity. There was no evidence of any recent stress or status migrainosus. Extensive literature search revealed multiple cases of coronary artery vasospasm secondary to zolmitriptan, but none of the cases were associated with TS.
24100257	0	18	Takotsubo syndrome	Disease	D054549
24100257	23	49	apical ballooning syndrome	Disease	D054549
24100257	64	76	Zolmitriptan	Chemical	C089750
24100257	78	96	Takotsubo syndrome	Disease	D054549
24100257	98	100	TS	Disease	D054549
24100257	117	138	broken heart syndrome	Disease	D054549
24100257	276	299	acute coronary syndrome	Disease	D054058
24100257	433	454	mitral valve prolapse	Disease	D008945
24100257	459	468	migraines	Disease	D008881
24100257	518	528	chest pain	Disease	D002637
24100257	819	821	TS	Disease	D054549
24100257	896	908	zolmitriptan	Chemical	C089750
24100257	937	946	migraines	Disease	D008881
24100257	986	998	zolmitriptan	Chemical	C089750
24100257	1056	1073	migraine headache	Disease	D008881
24100257	1256	1274	status migrainosus	Disease	D008881
24100257	1331	1356	coronary artery vasospasm	Disease	D003329
24100257	1370	1382	zolmitriptan	Chemical	C089750
24100257	1427	1429	TS	Disease	D054549
24100257	CID	C089750	D003329
24100257	CID	C089750	D054549

24114426|t|Depression, impulsiveness, sleep, and memory in past and present polydrug users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).
24114426|a|RATIONALE: Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide recreational drug of abuse. Unfortunately, the results from human research investigating its psychological effects have been inconsistent. OBJECTIVES: The present study aimed to be the largest to date in sample size and 5HT-related behaviors; the first to compare present ecstasy users with past users after an abstinence of 4 or more years, and the first to include robust controls for other recreational substances. METHODS: A sample of 997 participants (52 % male) was recruited to four control groups (non-drug (ND), alcohol/nicotine (AN), cannabis/alcohol/nicotine (CAN), non-ecstasy polydrug (PD)), and two ecstasy polydrug groups (present (MDMA) and past users (EX-MDMA). Participants completed a drug history questionnaire, Beck Depression Inventory, Barratt Impulsiveness Scale, Pittsburgh Sleep Quality Index, and Wechsler Memory Scale-Revised which, in total, provided 13 psychometric measures. RESULTS: While the CAN and PD groups tended to record greater deficits than the non-drug controls, the MDMA and EX-MDMA groups recorded greater deficits than all the control groups on ten of the 13 psychometric measures. Strikingly, despite prolonged abstinence (mean, 4.98; range, 4-9 years), past ecstasy users showed few signs of recovery. Compared with present ecstasy users, the past users showed no change for ten measures, increased impairment for two measures, and improvement on just one measure. CONCLUSIONS: Given this record of impaired memory and clinically significant levels of depression, impulsiveness, and sleep disturbance, the prognosis for the current generation of ecstasy users is a major cause for concern.
24114426	0	10	Depression	Disease	D003866
24114426	12	25	impulsiveness	Disease	D010554
24114426	83	116	3,4-methylenedioxymethamphetamine	Chemical	D018817
24114426	118	122	MDMA	Chemical	D018817
24114426	124	131	ecstasy	Chemical	D018817
24114426	145	152	Ecstasy	Chemical	D018817
24114426	154	187	3,4-methylenedioxymethamphetamine	Chemical	D018817
24114426	189	193	MDMA	Chemical	D018817
24114426	482	489	ecstasy	Chemical	D018817
24114426	731	738	alcohol	Chemical	D000431
24114426	739	747	nicotine	Chemical	D009538
24114426	749	751	AN	Chemical	D000431|D009538
24114426	754	762	cannabis	Chemical	D002188
24114426	763	770	alcohol	Chemical	D000431
24114426	771	779	nicotine	Chemical	D009538
24114426	781	784	CAN	Chemical	D002188|D000431|D009538
24114426	791	798	ecstasy	Chemical	D018817
24114426	823	830	ecstasy	Chemical	D018817
24114426	857	861	MDMA	Chemical	D018817
24114426	882	886	MDMA	Chemical	D018817
24114426	947	957	Depression	Disease	D003866
24114426	977	990	Impulsiveness	Disease	D010554
24114426	1135	1138	CAN	Chemical	D002188|D000431|D009538
24114426	1219	1223	MDMA	Chemical	D018817
24114426	1231	1235	MDMA	Chemical	D018817
24114426	1415	1422	ecstasy	Chemical	D018817
24114426	1481	1488	ecstasy	Chemical	D018817
24114426	1656	1671	impaired memory	Disease	D008569
24114426	1709	1719	depression	Disease	D003866
24114426	1721	1734	impulsiveness	Disease	D010554
24114426	1740	1757	sleep disturbance	Disease	D020920
24114426	1803	1810	ecstasy	Chemical	D018817
24114426	CID	D018817	D020920
24114426	CID	D018817	D010554
24114426	CID	D018817	D003866

24126708|t|Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients.
24126708|a|Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER1 gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR)=0.615, 95% confidence interval (CI) 0.426-0.887, P=0.009) and visual hallucinations (PR=0.515, 95% CI 0.295-0.899, P=0.020). Our data suggest that HOMER1 rs4704559 G allele has a protective role for the development of levodopa adverse effects.
24126708	59	67	levodopa	Chemical	D007980
24126708	87	106	Parkinson's disease	Disease	D010300
24126708	117	125	Levodopa	Chemical	D007980
24126708	172	191	Parkinson's disease	Disease	D010300
24126708	281	291	dyskinesia	Disease	D004409
24126708	296	317	visual hallucinations	Disease	D006212
24126708	364	373	glutamate	Chemical	D018698
24126708	603	611	levodopa	Chemical	D007980
24126708	650	680	idiopathic Parkinson's disease	Disease	D010300
24126708	875	885	dyskinesia	Disease	D004409
24126708	971	992	visual hallucinations	Disease	D006212
24126708	1127	1135	levodopa	Chemical	D007980
24126708	CID	D007980	D006212
24126708	CID	D007980	D004409

24132704|t|Crocin improves lipid dysregulation in subacute diazinon exposure through ERK1/2 pathway in rat liver.
24132704|a|INTRODUCTION: Diazinon Yis one of the most broadly used organophosphorus insecticides in agriculture. It has been shown that exposure to diazinon may interfere with lipid metabolism. Moreover, the hypolipidemic effect of crocin has been established. Earlier studies revealed the major role of Extracellular signal-regulated kinase (ERK) pathways in low-density lipoprotein receptor (LDLr) expression. The aim of this study was to evaluate changes in the regulation of lipid metabolism, ERK and LDLr expression in the liver of rats exposed to subacute diazinon. Furthermore ameliorating effect of crocin on diazinon induced disturbed cholesterol homeostasis was studied. METHODS: 24 Rats were divided into 4 groups and received following treatments for 4 weeks; Corn oil (control), diazinon (15mg/kg per day, orally) and crocin (12.5 and 25mg/kg per day, intraperitoneally) in combination with diazinon (15 mg/kg). The levels of cholesterol, triglyceride and LDL in blood of rats were analyzed. Moreover mRNA levels of LDLr and ERK1/2 as well as protein levels of total and activated forms of ERK1/2 in rat liver were evaluated by Western blotting and quantitative real time polymerase chain reaction analysis. RESULTS: Our data showed that subacute exposure to diazinon significantly increased concentrations of cholesterol, triglyceride and LDL. Moreover diazinon decreased ERK1/2 protein phosphorylation and LDLr transcript. Crocin reduced inhibition of ERK activation and diazinon-induced hyperlipemia and increased levels of LDLr transcript. CONCLUSIONS: Crocin may be considered as a novel protective agent in diazinon-induced hyperlipemia through modulating of ERK pathway and increase of LDLr expression.
24132704	0	6	Crocin	Chemical	C029036
24132704	48	56	diazinon	Chemical	D003976
24132704	117	125	Diazinon	Chemical	D003976
24132704	159	175	organophosphorus	Chemical	D010755
24132704	240	248	diazinon	Chemical	D003976
24132704	324	330	crocin	Chemical	C029036
24132704	654	662	diazinon	Chemical	D003976
24132704	699	705	crocin	Chemical	C029036
24132704	709	717	diazinon	Chemical	D003976
24132704	736	747	cholesterol	Chemical	D002784
24132704	884	892	diazinon	Chemical	D003976
24132704	923	929	crocin	Chemical	C029036
24132704	996	1004	diazinon	Chemical	D003976
24132704	1031	1042	cholesterol	Chemical	D002784
24132704	1044	1056	triglyceride	Chemical	D014280
24132704	1364	1372	diazinon	Chemical	D003976
24132704	1415	1426	cholesterol	Chemical	D002784
24132704	1428	1440	triglyceride	Chemical	D014280
24132704	1459	1467	diazinon	Chemical	D003976
24132704	1530	1536	Crocin	Chemical	C029036
24132704	1578	1586	diazinon	Chemical	D003976
24132704	1595	1607	hyperlipemia	Disease	D006949
24132704	1662	1668	Crocin	Chemical	C029036
24132704	1718	1726	diazinon	Chemical	D003976
24132704	1735	1747	hyperlipemia	Disease	D006949
24132704	CID	D003976	D006949

24158386|t|GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma.
24158386|a|Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m(2) day (D)1, D8 and D15; methylprednisolone 1,000 mg D1-5; and cisplatin 100 mg/m(2) D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1-6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30-62 %) and 5-year overall survival was 59 % (95 % CI, 43-74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.
24158386	0	3	GEM	Chemical	C056507
24158386	58	74	Hodgkin lymphoma	Disease	D006689
24158386	76	92	Hodgkin lymphoma	Disease	D006689
24158386	94	96	HL	Disease	D006689
24158386	129	139	malignancy	Disease	D009369
24158386	429	437	toxicity	Disease	D064420
24158386	439	450	Gemcitabine	Chemical	C056507
24158386	455	464	cisplatin	Chemical	D002945
24158386	482	484	HL	Disease	D006689
24158386	502	510	toxicity	Disease	D064420
24158386	676	678	HL	Disease	D006689
24158386	692	703	gemcitabine	Chemical	C056507
24158386	740	758	methylprednisolone	Chemical	D008775
24158386	778	787	cisplatin	Chemical	D002945
24158386	820	823	GEM	Chemical	C056507
24158386	878	886	toxicity	Disease	D064420
24158386	1004	1007	GEM	Chemical	C056507
24158386	1105	1108	GEM	Chemical	C056507
24158386	1207	1210	GEM	Chemical	C056507
24158386	1419	1429	toxicities	Disease	D064420
24158386	1451	1462	neutropenia	Disease	D009503
24158386	1472	1488	thrombocytopenia	Disease	D013921
24158386	1530	1533	GEM	Chemical	C056507
24158386	1561	1564	GEM	Chemical	C056507
24158386	1777	1780	GEM	Chemical	C056507
24158386	1952	1954	HL	Disease	D006689
24158386	CID	D008775	D009503
24158386	CID	C056507	D013921
24158386	CID	D008775	D013921
24158386	CID	C056507	D009503

24190587|t|Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users.
24190587|a|RATIONALE: Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. OBJECTIVES: The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. METHOD: Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. RESULTS: Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. CONCLUSIONS: The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.
24190587	110	117	ecstasy	Chemical	D018817
24190587	145	152	Ecstasy	Chemical	D018817
24190587	154	158	MDMA	Chemical	D018817
24190587	224	252	psychobiological dysfunction	Disease	D008107
24190587	481	488	ecstasy	Chemical	D018817
24190587	601	609	cortisol	Chemical	D006854
24190587	693	700	ecstasy	Chemical	D018817
24190587	726	733	ecstasy	Chemical	D018817
24190587	867	875	cortisol	Chemical	D006854
24190587	1133	1140	anxiety	Disease	D001008
24190587	1145	1155	depression	Disease	D003866
24190587	1218	1226	cortisol	Chemical	D006854
24190587	1372	1379	ecstasy	Chemical	D018817
24190587	1525	1533	cortisol	Chemical	D006854
24190587	1556	1564	cortisol	Chemical	D006854
24190587	1621	1628	anxiety	Disease	D001008
24190587	1633	1643	depression	Disease	D003866
24190587	1699	1706	ecstasy	Chemical	D018817
24190587	1744	1752	cortisol	Chemical	D006854
24190587	1948	1955	ecstasy	Chemical	D018817
24190587	CID	D018817	D003866

24209900|t|Ifosfamide related encephalopathy: the need for a timely EEG evaluation.
24209900|a|BACKGROUND: Ifosfamide is an alkylating agent useful in the treatment of a wide range of cancers including sarcomas, lymphoma, gynecologic and testicular cancers. Encephalopathy has been reported in 10-40% of patients receiving high-dose IV ifosfamide. OBJECTIVE: To highlight the role of electroencephalogram (EEG) in the early detection and management of ifosfamide related encephalopathy. METHODS: Retrospective chart review including clinical data and EEG recordings was done on five patients, admitted to MD Anderson Cancer Center between years 2009 and 2012, who developed ifosfamide related acute encephalopathy. RESULTS: All five patients experienced symptoms of encephalopathy soon after (within 12 h-2 days) receiving ifosfamide. Two patients developed generalized convulsions while one patient developed continuous non-convulsive status epilepticus (NCSE) that required ICU admission and intubation. Initial EEG showed epileptiform discharges in three patients; run of triphasic waves in one patient and moderate degree diffuse generalized slowing. Mixed pattern with the presence of both sharps and triphasic waves were also noted. Repeat EEGs within 24_h of symptom onset showed marked improvement that was correlated with clinical improvement. CONCLUSIONS: Severity of ifosfamide related encephalopathy correlates with EEG changes. We suggest a timely EEG evaluation for patients receiving ifosfamide who develop features of encephalopathy.
24209900	0	10	Ifosfamide	Chemical	D007069
24209900	19	33	encephalopathy	Disease	D001927
24209900	85	95	Ifosfamide	Chemical	D007069
24209900	162	169	cancers	Disease	D009369
24209900	180	188	sarcomas	Disease	D012509
24209900	190	198	lymphoma	Disease	D008223
24209900	200	234	gynecologic and testicular cancers	Disease	D009369
24209900	236	250	Encephalopathy	Disease	D001927
24209900	314	324	ifosfamide	Chemical	D007069
24209900	430	440	ifosfamide	Chemical	D007069
24209900	449	463	encephalopathy	Disease	D001927
24209900	595	601	Cancer	Disease	D009369
24209900	652	662	ifosfamide	Chemical	D007069
24209900	677	691	encephalopathy	Disease	D001927
24209900	744	758	encephalopathy	Disease	D001927
24209900	801	811	ifosfamide	Chemical	D007069
24209900	848	859	convulsions	Disease	D012640
24209900	899	932	non-convulsive status epilepticus	Disease	D013226
24209900	934	938	NCSE	Disease	D013226
24209900	1356	1366	ifosfamide	Chemical	D007069
24209900	1375	1389	encephalopathy	Disease	D001927
24209900	1477	1487	ifosfamide	Chemical	D007069
24209900	1512	1526	encephalopathy	Disease	D001927
24209900	CID	D007069	D012640
24209900	CID	D007069	D013226

24220752|t|Incidence of contrast-induced nephropathy in hospitalised patients with cancer.
24220752|a|OBJECTIVES: To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer. METHODS: Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast-enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated. RESULTS: CIN was detected in 18/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P = 0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P = 0.005); it was also an independent risk factor (P = 0.017). CIN was significantly more after treatment with bevacizumab/irinotecan (P = 0.021) and in patients with hypertension (P = 0.044). CONCLUSIONS: The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab/irinotecan may be additional risk factors for CIN development. KEY POINTS: . Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. . CIN occurs more often when CT is performed <45 days after chemotherapy. . Hypertension and treatment with bevacizumab appear to be additional risk factors.
24220752	13	21	contrast	Chemical	D003287
24220752	30	41	nephropathy	Disease	D007674
24220752	72	78	cancer	Disease	D009369
24220752	154	162	contrast	Chemical	D003287
24220752	171	182	nephropathy	Disease	D007674
24220752	219	225	cancer	Disease	D009369
24220752	304	323	acute renal failure	Disease	D058186
24220752	382	390	contrast	Chemical	D003287
24220752	501	511	creatinine	Chemical	D003404
24220752	513	515	Cr	Chemical	D002857
24220752	555	557	Cr	Chemical	D002857
24220752	1027	1038	bevacizumab	Chemical	-1
24220752	1039	1049	irinotecan	Chemical	C051890
24220752	1083	1095	hypertension	Disease	D006973
24220752	1256	1262	cancer	Disease	D009369
24220752	1302	1314	Hypertension	Disease	D006973
24220752	1338	1349	bevacizumab	Chemical	-1
24220752	1350	1360	irinotecan	Chemical	C051890
24220752	1427	1435	Contrast	Chemical	D003287
24220752	1444	1455	nephropathy	Disease	D007674
24220752	1591	1603	Hypertension	Disease	D006973
24220752	1623	1634	bevacizumab	Chemical	-1
24220752	CID	D003287	D007674
24220752	CID	C051890	D007674

24234943|t|Syndrome of inappropriate antidiuretic hormone secretion associated with desvenlafaxine.
24234943|a|OBJECTIVE: To report a case of syndrome of inappropriate anti-diuretic hormone (SIADH) secretion associated with desvenlafaxine. CASE SUMMARY: A 57-year old female with hyponatraemia. Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion. The serum sodium at this time was 120 mmol/L, serum osmolality was 263 mosmol/kg, urine osmolality 410 mosmol/kg and urine sodium 63 mmol/L, consistent with a diagnosis of SIADH. Desvenlafaxine was ceased and fluid restriction implemented. After 4 days the sodium increased to 128 mmol/L and fluid restriction was relaxed. During her further 3 weeks inpatient admission the serum sodium ranged from 134 to 137 mmol/L during treatment with mirtazapine. DISCUSSION: SIADH has been widely reported with a range of antidepressants. This case report suggests that desvenlafaxine might cause clinically significant hyponatremia. CONCLUSIONS: Clinicians should be aware of the potential for antidepressants to cause hyponatremia,and take appropriate corrective action where necessary.
24234943	0	46	Syndrome of inappropriate antidiuretic hormone	Disease	D007177
24234943	73	87	desvenlafaxine	Chemical	C086816
24234943	120	167	syndrome of inappropriate anti-diuretic hormone	Disease	D007177
24234943	169	174	SIADH	Disease	D007177
24234943	202	216	desvenlafaxine	Chemical	C086816
24234943	258	271	hyponatraemia	Disease	D007010
24234943	298	312	desvenlafaxine	Chemical	C086816
24234943	336	342	nausea	Disease	D009325
24234943	344	351	anxiety	Disease	D001008
24234943	356	365	confusion	Disease	D003221
24234943	377	383	sodium	Chemical	D012964
24234943	490	496	sodium	Chemical	D012964
24234943	539	544	SIADH	Disease	D007177
24234943	546	560	Desvenlafaxine	Chemical	C086816
24234943	624	630	sodium	Chemical	D012964
24234943	747	753	sodium	Chemical	D012964
24234943	806	817	mirtazapine	Chemical	C035133
24234943	831	836	SIADH	Disease	D007177
24234943	926	940	desvenlafaxine	Chemical	C086816
24234943	976	988	hyponatremia	Disease	D007010
24234943	1076	1088	hyponatremia	Disease	D007010
24234943	CID	C086816	D007177
24234943	CID	C086816	D001008
24234943	CID	C086816	D007010
24234943	CID	C086816	D003221
24234943	CID	C086816	D009325

24275640|t|Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin.
24275640|a|The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial. Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly assigned to 2 experimental protocols: (1) rats were killed before (-24 h, n = 8) and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg/kg body weight) to determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX (4 mg/kg body weight/week) and were killed before the first injection (M0) and 1 week after each injection (M1, M2, M3, and M4) to determine the chronological effects. Animals used at M0 (n = 8) were also used at moment -24 h of acute study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology analyses were carried out at each time point. Single dose of DOX was associated with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed an effect of a cumulative dose on body weight (R = -0.99, p = 0.011), necrosis (R = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = -0.95, p = 0.049). DNA SBs damage was negatively associated with TAP (R = -0.98, p = 0.018), and necrosis (R = -0.97, p = 0.027). Our results suggest that oxidative damage is associated with acute cardiotoxicity induced by a single dose of DOX only. Increased resistance to the oxidative stress is plausible for the multiple dose of DOX. Thus, different mechanisms may be involved in acute toxicity versus chronic toxicity.
24275640	20	34	cardiotoxicity	Disease	D066126
24275640	85	96	doxorubicin	Chemical	D004317
24275640	115	126	doxorubicin	Chemical	D004317
24275640	128	131	DOX	Chemical	D004317
24275640	141	155	cardiotoxicity	Disease	D066126
24275640	209	212	DOX	Chemical	D004317
24275640	388	391	DOX	Chemical	D004317
24275640	431	434	DOX	Chemical	D004317
24275640	495	498	DOX	Chemical	D004317
24275640	874	877	DOX	Chemical	D004317
24275640	908	930	cardiac disarrangement	Disease	D006331
24275640	932	940	necrosis	Disease	D009336
24275640	1124	1132	necrosis	Disease	D009336
24275640	1297	1305	necrosis	Disease	D009336
24275640	1397	1411	cardiotoxicity	Disease	D066126
24275640	1440	1443	DOX	Chemical	D004317
24275640	1533	1536	DOX	Chemical	D004317
24275640	1590	1598	toxicity	Disease	D064420
24275640	1614	1622	toxicity	Disease	D064420
24275640	CID	D004317	D066126
24275640	CID	D004317	D009336

24283660|t|Tacrolimus-related seizure after pediatric liver transplantation--a single-center experience.
24283660|a|To identify the risk factors for new-onset seizures after pediatric LT and to assess their clinical implications and long-term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non-seizures group. Pre-operative, intra-operative, and post-operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic-clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end-stage liver disease score before surgery, Child-Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure-free without anti-epileptic drugs over a mean follow-up period of 33.7 + 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post-operative period after pediatric LT. High PELD and Child-Pugh scores before LT and high post-operative serum Tbil may be contributory risk factors for TAC-related seizures.
24283660	0	10	Tacrolimus	Chemical	D016559
24283660	19	26	seizure	Disease	D012640
24283660	137	145	seizures	Disease	D012640
24283660	416	424	seizures	Disease	D012640
24283660	441	449	seizures	Disease	D012640
24283660	529	537	Seizures	Disease	D012640
24283660	614	635	tonic-clonic seizures	Disease	D004830
24283660	735	743	seizures	Disease	D012640
24283660	790	813	end-stage liver disease	Disease	D058625
24283660	881	890	bilirubin	Chemical	D001663
24283660	917	920	TAC	Chemical	D016559
24283660	969	972	TAC	Chemical	D016559
24283660	1036	1044	seizures	Disease	D012640
24283660	1075	1083	seizures	Disease	D012640
24283660	1131	1138	seizure	Disease	D012640
24283660	1157	1166	epileptic	Disease	D004827
24283660	1237	1240	TAC	Chemical	D016559
24283660	1294	1302	seizures	Disease	D012640
24283660	1472	1475	TAC	Chemical	D016559
24283660	1484	1492	seizures	Disease	D012640
24283660	CID	D016559	D012640

24284476|t|The flavonoid apigenin delays forgetting of passive avoidance conditioning in rats.
24284476|a|The present experiments were performed to study the effect of the flavonoid apigenin (20 mg/kg intraperitoneally (i.p.), 1 h before acquisition), on 24 h retention performance and forgetting of a step-through passive avoidance task, in young male Wistar rats. There were no differences between saline- and apigenin-treated groups in the 24 h retention trial. Furthermore, apigenin did not prevent the amnesia induced by scopolamine (1mg/kg, i.p., 30 min before the acquisition). The saline- and apigenin-treated rats that did not step through into the dark compartment during the cut-off time (540 s) were retested weekly for up to eight weeks. In the saline treated group, the first significant decline in passive avoidance response was observed at four weeks, and complete memory loss was found five weeks after the acquisition of the passive avoidance task. At the end of the experimental period, 60% of the animals treated with apigenin still did not step through. These data suggest that 1) apigenin delays the long-term forgetting but did not modulate the 24 h retention of fear memory and 2) the obtained beneficial effect of apigenin on the passive avoidance conditioning is mediated by mechanisms that do not implicate its action on the muscarinic cholinergic system.
24284476	4	13	flavonoid	Chemical	D005419
24284476	14	22	apigenin	Chemical	D047310
24284476	150	159	flavonoid	Chemical	D005419
24284476	160	168	apigenin	Chemical	D047310
24284476	390	398	apigenin	Chemical	D047310
24284476	456	464	apigenin	Chemical	D047310
24284476	485	492	amnesia	Disease	D000647
24284476	504	515	scopolamine	Chemical	D012601
24284476	579	587	apigenin	Chemical	D047310
24284476	859	870	memory loss	Disease	D008569
24284476	1016	1024	apigenin	Chemical	D047310
24284476	1080	1088	apigenin	Chemical	D047310
24284476	1217	1225	apigenin	Chemical	D047310
24284476	CID	D012601	D000647

24309294|t|Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats.
24309294|a|Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1ug, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1ug, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10ug, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10ug, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.
24309294	0	27	Cholecystokinin-octapeptide	Chemical	D012844
24309294	37	45	morphine	Chemical	D009020
24309294	109	136	Cholecystokinin-octapeptide	Chemical	D012844
24309294	138	143	CCK-8	Chemical	D012844
24309294	293	298	CCK-8	Chemical	D012844
24309294	324	332	morphine	Chemical	D009020
24309294	341	348	amnesia	Disease	D000647
24309294	426	434	morphine	Chemical	D009020
24309294	489	494	CCK-8	Chemical	D012844
24309294	629	637	morphine	Chemical	D009020
24309294	759	767	morphine	Chemical	D009020
24309294	839	844	CCK-8	Chemical	D012844
24309294	911	919	morphine	Chemical	D009020
24309294	962	967	CCK-8	Chemical	D012844
24309294	1168	1173	CCK-8	Chemical	D012844
24309294	1278	1283	CCK-8	Chemical	D012844
24309294	1309	1317	morphine	Chemical	D009020
24309294	1400	1405	CCK-8	Chemical	D012844
24309294	1409	1417	morphine	Chemical	D009020
24309294	1426	1443	memory impairment	Disease	D008569
24309294	CID	D009020	D000647

24333387|t|Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats.
24333387|a|In the present study the role of glial activation and post synaptic toxicity in ICV Streptozotocin (STZ) induced memory impaired rats was explored. In experiment set up 1: Memory deficit was found in Morris water maze test on 14-16 days after STZ (ICV; 3mg/Kg) administration. STZ causes increased expression of GFAP, CD11b and TNF-a indicating glial activation and neuroinflammation. STZ also significantly increased the level of ROS, nitrite, Ca(2+) and reduced the mitochondrial activity in synaptosomal preparation illustrating free radical generation and excitotoxicity. Increased expression and activity of Caspase-3 was also observed in STZ treated rat which specify apoptotic cell death in hippocampus and cortex. STZ treatment showed decrease expression of post synaptic markers CaMKIIa and PSD-95, while, expression of pre synaptic markers (synaptophysin and SNAP-25) remains unaltered indicating selective post synaptic neurotoxicity. Oral treatment with Memantine (10mg/kg) and Ibuprofen (50 mg/kg) daily for 13 days attenuated STZ induced glial activation, apoptotic cell death and post synaptic neurotoxicity in rat brain. Further, in experiment set up 2: where memory function was not affected i.e. 7-9 days after STZ treatment. The level of GFAP, CD11b, TNF-a, ROS and nitrite levels were increased. On the other hand, apoptotic marker, synaptic markers, mitochondrial activity and Ca(2+) levels remained unaffected. Collective data indicates that neuroinflammatory process and oxidative stress occurs earlier to apoptosis and does not affect memory function. Present study clearly suggests that glial activation and post synaptic neurotoxicity are the key factors in STZ induced memory impairment and neuronal cell death.
24333387	35	48	neurotoxicity	Disease	D020258
24333387	68	82	Streptozotocin	Chemical	D013311
24333387	97	114	memory impairment	Disease	D008569
24333387	192	200	toxicity	Disease	D064420
24333387	208	222	Streptozotocin	Chemical	D013311
24333387	224	227	STZ	Chemical	D013311
24333387	237	252	memory impaired	Disease	D008569
24333387	296	310	Memory deficit	Disease	D008569
24333387	367	370	STZ	Chemical	D013311
24333387	401	404	STZ	Chemical	D013311
24333387	490	507	neuroinflammation	Disease	D007249
24333387	509	512	STZ	Chemical	D013311
24333387	560	567	nitrite	Chemical	D009573
24333387	569	571	Ca	Chemical	D002118
24333387	684	698	excitotoxicity	Disease	D064420
24333387	768	771	STZ	Chemical	D013311
24333387	846	849	STZ	Chemical	D013311
24333387	1055	1068	neurotoxicity	Disease	D020258
24333387	1090	1099	Memantine	Chemical	D008559
24333387	1114	1123	Ibuprofen	Chemical	D007052
24333387	1164	1167	STZ	Chemical	D013311
24333387	1233	1246	neurotoxicity	Disease	D020258
24333387	1353	1356	STZ	Chemical	D013311
24333387	1409	1416	nitrite	Chemical	D009573
24333387	1522	1524	Ca	Chemical	D002118
24333387	1588	1605	neuroinflammatory	Disease	D007249
24333387	1771	1784	neurotoxicity	Disease	D020258
24333387	1808	1811	STZ	Chemical	D013311
24333387	1820	1837	memory impairment	Disease	D008569
24333387	CID	D013311	D007249
24333387	CID	D013311	D008569

24341598|t|Comparison of effects of isotonic sodium chloride with diltiazem in prevention of contrast-induced nephropathy.
24341598|a|INTRODUCTION AND OBJECTIVE: Contrast-induced nephropathy (CIN) significantly increases the morbidity and mortality of patients. The aim of this study is to investigate and compare the protective effects of isotonic sodium chloride with sodium bicarbonate infusion and isotonic sodium chloride infusion with diltiazem, a calcium channel blocker, in preventing CIN. MATERIALS AND METHODS: Our study included patients who were administered 30-60 mL of iodinated contrast agent for percutaneous coronary angiography (PCAG), all with creatinine values between 1.1 and 3.1 mg/dL. Patients were divided into three groups and each group had 20 patients. The first group of patients was administered isotonic sodium chloride; the second group was administered a solution that of 5% dextrose and sodium bicarbonate, while the third group was administered isotonic sodium chloride before and after the contrast injection. The third group received an additional injection of diltiazem the day before and first 2 days after the contrast injection. All of the patients' plasma blood urea nitrogen (BUN) and creatinine levels were measured on the second and seventh day after the administration of intravenous contrast material. RESULTS: The basal creatinine levels were similar for all three groups (p > 0.05). Among a total of 60 patients included in the study, 16 patients developed acute renal failure (ARF) on the second day after contrast material was injected (26.6%). The number of patients who developed ARF on the second day after the injection in the first group was five (25%), in the second group was six (30%) and the third group was five (25%) (p > 0.05). CONCLUSION: There was no significant difference between isotonic sodium chloride, sodium bicarbonate and isotonic sodium chloride with diltiazem application in prevention of CIN.
24341598	34	49	sodium chloride	Chemical	D012965
24341598	55	64	diltiazem	Chemical	D004110
24341598	82	90	contrast	Chemical	D003287
24341598	99	110	nephropathy	Disease	D007674
24341598	140	148	Contrast	Chemical	D003287
24341598	157	168	nephropathy	Disease	D007674
24341598	327	342	sodium chloride	Chemical	D012965
24341598	348	366	sodium bicarbonate	Chemical	D017693
24341598	389	404	sodium chloride	Chemical	D012965
24341598	419	428	diltiazem	Chemical	D004110
24341598	432	439	calcium	Chemical	D002118
24341598	571	579	contrast	Chemical	D003287
24341598	641	651	creatinine	Chemical	D003404
24341598	812	827	sodium chloride	Chemical	D012965
24341598	885	893	dextrose	Chemical	D005947
24341598	898	916	sodium bicarbonate	Chemical	D017693
24341598	966	981	sodium chloride	Chemical	D012965
24341598	1003	1011	contrast	Chemical	D003287
24341598	1075	1084	diltiazem	Chemical	D004110
24341598	1127	1135	contrast	Chemical	D003287
24341598	1175	1194	blood urea nitrogen	Chemical	D001806
24341598	1196	1199	BUN	Chemical	D001806
24341598	1205	1215	creatinine	Chemical	D003404
24341598	1307	1315	contrast	Chemical	D003287
24341598	1345	1355	creatinine	Chemical	D003404
24341598	1483	1502	acute renal failure	Disease	D058186
24341598	1504	1507	ARF	Disease	D058186
24341598	1533	1541	contrast	Chemical	D003287
24341598	1610	1613	ARF	Disease	D058186
24341598	1833	1848	sodium chloride	Chemical	D012965
24341598	1850	1868	sodium bicarbonate	Chemical	D017693
24341598	1882	1897	sodium chloride	Chemical	D012965
24341598	1903	1912	diltiazem	Chemical	D004110
24341598	CID	D003287	D058186

24345882|t|Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children's Oncology Group.
24345882|a|Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with "standard-risk" acute lymphoblastic leukemia, 1.00 to 9.99 years at diagnosis, without evidence of CNS leukemia at diagnosis were enrolled on ACCL0131: 28 from P9201 and 38 from P9605. Magnetic resonance imaging scans and standard neuropsychological tests were performed >2.6 years after the end of treatment. Significantly more P9605 patients developed leukoencephalopathy compared with P9201 patients (68%, 95% confidence interval 49%-83% vs. 22%, 95% confidence interval 5%-44%; P=0.001) identified as late as 7.7 years after the end of treatment. Overall, 40% of patients scored <85 on either Verbal or Performance IQ. Children on both studies had significant attention problems, but P9605 children scored below average on more neurocognitive measures than those treated on P9201 (82%, 14/17 measures vs. 24%, 4/17 measures). This supports ongoing concerns about intensive MTX exposure as a major contributor to CNS late effects.
24345882	171	199	acute lymphoblastic leukemia	Disease	D054198
24345882	224	236	methotrexate	Chemical	D008727
24345882	320	332	methotrexate	Chemical	D008727
24345882	334	337	MTX	Chemical	D008727
24345882	339	352	neurotoxicity	Disease	D020258
24345882	461	464	MTX	Chemical	D008727
24345882	497	525	acute lymphoblastic leukemia	Disease	D054198
24345882	598	617	leukoencephalopathy	Disease	D056784
24345882	906	934	acute lymphoblastic leukemia	Disease	D054198
24345882	993	1001	leukemia	Disease	D007938
24345882	1244	1263	leukoencephalopathy	Disease	D056784
24345882	1554	1572	attention problems	Disease	D003072
24345882	1767	1770	MTX	Chemical	D008727
24345882	CID	D008727	D003072
24345882	CID	D008727	D056784

24434397|t|Tranexamic acid overdosage-induced generalized seizure in renal failure.
24434397|a|We report a 45-year-old lady with chronic kidney disease stage 4 due to chronic tubulointerstial disease. She was admitted to our center for severe anemia due to menorrhagia and deterioration of renal function. She was infused three units of packed cells during a session of hemodialysis. Tranexamic acid (TNA) 1 g 8-hourly was administered to her to control bleeding per vaginum. Two hours after the sixth dose of TNA, she had an episode of generalized tonic clonic convulsions. TNA was discontinued. Investigations of the patient revealed no biochemical or structural central nervous system abnormalities that could have provoked the convulsions. She did not require any further dialytic support. She had no further episodes of convulsion till dis-charge and during the two months of follow-up. Thus, the precipitating cause of convulsions was believed to be an overdose of TNA.
24434397	0	15	Tranexamic acid	Chemical	D014148
24434397	47	54	seizure	Disease	D012640
24434397	58	71	renal failure	Disease	D051437
24434397	107	129	chronic kidney disease	Disease	D051436
24434397	153	177	tubulointerstial disease	Disease	D004194
24434397	221	227	anemia	Disease	D000740
24434397	235	246	menorrhagia	Disease	D008595
24434397	251	282	deterioration of renal function	Disease	D051437
24434397	362	377	Tranexamic acid	Chemical	D014148
24434397	379	382	TNA	Chemical	D014148
24434397	432	440	bleeding	Disease	D006470
24434397	488	491	TNA	Chemical	D014148
24434397	527	551	tonic clonic convulsions	Disease	D004830
24434397	553	556	TNA	Chemical	D014148
24434397	651	679	nervous system abnormalities	Disease	D009421
24434397	709	720	convulsions	Disease	D012640
24434397	803	813	convulsion	Disease	D012640
24434397	903	914	convulsions	Disease	D012640
24434397	937	945	overdose	Disease	D062787
24434397	949	952	TNA	Chemical	D014148
24434397	CID	D014148	D004830

24438483|t|Pre-treatment of bupivacaine-induced cardiovascular depression using different lipid formulations of propofol.
24438483|a|BACKGROUND: Pre-treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine-induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine-induced cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0.5 mg/kg/min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg/kg/min bupivacaine 0.5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole. RESULTS: The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C. CONCLUSION: We conclude that pre-treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine-induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice.
24438483	17	28	bupivacaine	Chemical	D002045
24438483	37	62	cardiovascular depression	Disease	D002318
24438483	101	109	propofol	Chemical	D015742
24438483	201	212	bupivacaine	Chemical	D002045
24438483	239	247	propofol	Chemical	D015742
24438483	262	273	bupivacaine	Chemical	D002045
24438483	282	296	cardiotoxicity	Disease	D066126
24438483	353	361	propofol	Chemical	D015742
24438483	403	414	bupivacaine	Chemical	D002045
24438483	423	437	cardiotoxicity	Disease	D066126
24438483	477	485	ketamine	Chemical	D007649
24438483	515	523	propofol	Chemical	D015742
24438483	549	557	propofol	Chemical	D015742
24438483	640	651	bupivacaine	Chemical	D002045
24438483	696	707	dysrhythmia	Disease	D001145
24438483	825	833	asystole	Disease	D006323
24438483	854	865	bupivacaine	Chemical	D002045
24438483	929	937	asystole	Disease	D006323
24438483	966	977	dysrhythmia	Disease	D001145
24438483	1040	1048	asystole	Disease	D006323
24438483	1110	1121	bupivacaine	Chemical	D002045
24438483	1184	1195	bupivacaine	Chemical	D002045
24438483	1256	1267	Bupivacaine	Chemical	D002045
24438483	1411	1419	propofol	Chemical	D015742
24438483	1449	1457	propofol	Chemical	D015742
24438483	1504	1515	bupivacaine	Chemical	D002045
24438483	1524	1535	cardiotoxic	Disease	D066126
24438483	1570	1581	bupivacaine	Chemical	D002045
24438483	1635	1646	bupivacaine	Chemical	D002045
24438483	1657	1665	propofol	Chemical	D015742
24438483	CID	D002045	D006323
24438483	CID	D002045	D066126

24451297|t|Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.
24451297|a|Although statins are generally well-tolerated drugs, recent cases of drug-induced liver injury associated with their use have been reported. A 52-year-old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.
24451297	0	31	Drug-Induced Acute Liver Injury	Disease	D056486
24451297	54	65	Fluvastatin	Chemical	C065180
24451297	84	91	statins	Chemical	D019161
24451297	144	169	drug-induced liver injury	Disease	D056486
24451297	256	268	liver damage	Disease	D056486
24451297	325	336	fluvastatin	Chemical	C065180
24451297	386	392	nausea	Disease	D009325
24451297	394	402	anorexia	Disease	D000855
24451297	414	428	abdominal pain	Disease	D015746
24451297	468	476	creatine	Chemical	D003401
24451297	627	638	fluvastatin	Chemical	C065180
24451297	696	710	hepatic damage	Disease	D056486
24451297	CID	C065180	D015746
24451297	CID	C065180	D056486
24451297	CID	C065180	D000855
24451297	CID	C065180	D009325

24459006|t|Fluconazole associated agranulocytosis and thrombocytopenia.
24459006|a|CASE: We describe a second case of fluconazole associated agranulocytosis with thrombocytopenia and recovery upon discontinuation of therapy. The patient began to have changes in white blood cells and platelets within 48 h of administration of fluconazole and began to recover with 48 h of discontinuation. This case highlights that drug-induced blood dyscrasias can occur unexpectedly as a result of treatment with a commonly used drug thought to be "safe". CONCLUSION: According to Naranjo's algorithm the likelihood that our patient's agranulocytosis and thrombocytopenia occurred as a result of therapy with fluconazole is probable, with a total of six points. We feel that the weight of the overall evidence of this evidence is strong. In particular the temporal relationship of bone marrow suppression to the initiation of fluconazole and the abatement of symptoms that rapidly reversed immediately following discontinuation.
24459006	0	11	Fluconazole	Chemical	D015725
24459006	23	38	agranulocytosis	Disease	D000380
24459006	43	59	thrombocytopenia	Disease	D013921
24459006	96	107	fluconazole	Chemical	D015725
24459006	119	134	agranulocytosis	Disease	D000380
24459006	140	156	thrombocytopenia	Disease	D013921
24459006	305	316	fluconazole	Chemical	D015725
24459006	407	423	blood dyscrasias	Disease	D006402
24459006	599	614	agranulocytosis	Disease	D000380
24459006	619	635	thrombocytopenia	Disease	D013921
24459006	673	684	fluconazole	Chemical	D015725
24459006	845	868	bone marrow suppression	Disease	D001855
24459006	890	901	fluconazole	Chemical	D015725
24459006	CID	D015725	D000380
24459006	CID	D015725	D013921

24464946|t|Two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine-based chemotherapy.
24464946|a|AIMS: To investigate whether alterations of myocardial strain and high-sensitive cardiac troponin T (cTnT) could predict future cardiac dysfunction in patients after epirubicin exposure. METHODS: Seventy-five patients with non-Hodgkin lymphoma treated with epirubicin were studied. Blood collection and echocardiography were performed at baseline, 1 day after the third cycle, and 1 day after completion of chemotherapy. Patients were studied using echocardiography during follow-up. Global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were calculated using speckle tracking echocardiography. Left ventricular ejection fraction was analysed by real-time 3D echocardiography. Cardiotoxicity was defined as a reduction of the LVEF of >5% to <55% with symptoms of heart failure or an asymptomatic reduction of the LVEF of >10% to <55%. RESULTS: Fourteen patients (18.67%) developed cardiotoxicity after treatment. GLS (-18.48 + 1.72% vs. -15.96 + 1.6%), GCS (-20.93 + 2.86% vs. -19.20 + 3.21%), and GRS (39.23 + 6.44% vs. 34.98 + 6.2%) were markedly reduced and cTnT was elevated from 0.0010 + 0.0020 to 0.0073 + 0.0038 ng/mL (P all < 0.01) at the completion of chemotherapy compared with baseline values. A >15.9% decrease in GLS [sensitivity, 86%; specificity, 75%; area under the curve (AUC) = 0.815; P = 0.001] and a >0.004 ng/mL elevation in cTnT (sensitivity, 79%; specificity, 64%; AUC = 0.757; P = 0.005) from baseline to the third cycle of chemotherapy predicted later cardiotoxicity. The decrease in GLS remained the only independent predictor of cardiotoxicity (P = 0.000). CONCLUSIONS: GLS combined with cTnT may provide a reliable and non-invasive method to predict cardiac dysfunction in patients receiving anthracycline-based chemotherapy.
24464946	135	149	cardiotoxicity	Disease	D066126
24464946	157	168	epirubicine	Chemical	D015251
24464946	233	250	myocardial strain	Disease	D009202
24464946	317	336	cardiac dysfunction	Disease	D006331
24464946	355	365	epirubicin	Chemical	D015251
24464946	412	432	non-Hodgkin lymphoma	Disease	D008228
24464946	446	456	epirubicin	Chemical	D015251
24464946	886	900	Cardiotoxicity	Disease	D066126
24464946	972	985	heart failure	Disease	D006333
24464946	1090	1104	cardiotoxicity	Disease	D066126
24464946	1686	1700	cardiotoxicity	Disease	D066126
24464946	1765	1779	cardiotoxicity	Disease	D066126
24464946	1887	1906	cardiac dysfunction	Disease	D006331
24464946	1929	1942	anthracycline	Chemical	D018943
24464946	CID	D015251	D066126
24464946	CID	D015251	D006333

24535067|t|Prevention of etomidate-induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study.
24535067|a|BACKGROUND: In this retrospective comparative study, we aimed to compare the effectiveness of fentanyl, midazolam, and a combination of fentanyl and midazolam to prevent etomidate-induced myoclonus. MATERIAL AND METHODS: This study was performed based on anesthesia records. Depending on the drugs that would be given before the induction of anesthesia with etomidate, the patients were separated into 4 groups: no pretreatment (Group NP), fentanyl 1 ug.kg-1 (Group F), midazolam 0.03 mg.kg-1 (Group M), and midazolam 0.015 mg.kg-1 + fentanyl 0.5 ug.kg-1 (Group FM). Patients who received the same anesthetic procedure were selected: 2 minutes after intravenous injections of the pretreatment drugs, anesthesia is induced with 0.3 mg.kg-1 etomidate injected intravenously over a period of 20-30 seconds. Myoclonic movements are evaluated, which were observed and graded according to clinical severity during the 2 minutes after etomidate injection. The severity of pain due to etomidate injection, mean arterial pressure, heart rate, and adverse effects were also evaluated. RESULTS: Study results showed that myoclonus incidence was 85%, 40%, 70%, and 25% in Group NP, Group F, Group M, and Group FM, respectively, and were significantly lower in Group F and Group FM. CONCLUSIONS: We conclude that pretreatment with fentanyl or combination of fentanyl and midazolam was effective in preventing etomidate-induced myoclonus.
24535067	14	23	etomidate	Chemical	D005045
24535067	32	41	myoclonus	Disease	D009207
24535067	62	70	Fentanyl	Chemical	D005283
24535067	72	81	midazolam	Chemical	D008874
24535067	230	238	fentanyl	Chemical	D005283
24535067	240	249	midazolam	Chemical	D008874
24535067	272	280	fentanyl	Chemical	D005283
24535067	285	294	midazolam	Chemical	D008874
24535067	306	315	etomidate	Chemical	D005045
24535067	324	333	myoclonus	Disease	D009207
24535067	494	503	etomidate	Chemical	D005045
24535067	576	584	fentanyl	Chemical	D005283
24535067	606	615	midazolam	Chemical	D008874
24535067	644	653	midazolam	Chemical	D008874
24535067	670	678	fentanyl	Chemical	D005283
24535067	875	884	etomidate	Chemical	D005045
24535067	940	959	Myoclonic movements	Disease	D009069
24535067	1064	1073	etomidate	Chemical	D005045
24535067	1101	1105	pain	Disease	D010146
24535067	1113	1122	etomidate	Chemical	D005045
24535067	1246	1255	myoclonus	Disease	D009207
24535067	1454	1462	fentanyl	Chemical	D005283
24535067	1481	1489	fentanyl	Chemical	D005283
24535067	1494	1503	midazolam	Chemical	D008874
24535067	1532	1541	etomidate	Chemical	D005045
24535067	1550	1559	myoclonus	Disease	D009207
24535067	CID	D005045	D009207

24554916|t|Cholestatic presentation of yellow phosphorus poisoning.
24554916|a|Yellow phosphorus, a component of certain pesticide pastes and fireworks, is well known to cause hepatotoxicity. Poisoning with yellow phosphorus classically manifests with acute hepatitis leading to acute liver failure which may need liver transplantation. We present a case of yellow phosphorus poisoning in which a patient presented with florid clinical features of cholestasis highlighting the fact that cholestasis can rarely be a presenting feature of yellow phosphorus hepatotoxicity.
24554916	0	11	Cholestatic	Disease	D002779
24554916	35	45	phosphorus	Chemical	D010758
24554916	46	55	poisoning	Disease	D011041
24554916	64	74	phosphorus	Chemical	D010758
24554916	154	168	hepatotoxicity	Disease	D056486
24554916	170	179	Poisoning	Disease	D011041
24554916	192	202	phosphorus	Chemical	D010758
24554916	230	245	acute hepatitis	Disease	D006505
24554916	257	276	acute liver failure	Disease	D017114
24554916	343	353	phosphorus	Chemical	D010758
24554916	354	363	poisoning	Disease	D011041
24554916	426	437	cholestasis	Disease	D002779
24554916	465	476	cholestasis	Disease	D002779
24554916	522	532	phosphorus	Chemical	D010758
24554916	533	547	hepatotoxicity	Disease	D056486
24554916	CID	D010758	D006505
24554916	CID	D010758	D002779
24554916	CID	D010758	D017114

24571687|t|Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for pediatric procedural sedation.
24571687|a|We report syncope and bradycardia in an 11-year-old girl following administration of intranasal dexmedetomidine for sedation for a voiding cystourethrogram. Following successful completion of VCUG and a 60-min recovery period, the patient's level of consciousness and vital signs returned to presedation levels. Upon leaving the sedation area, the patient collapsed, with no apparent inciting event. The patient quickly regained consciousness and no injury occurred. The primary abnormality found was persistent bradycardia, and she was admitted to the hospital for telemetric observation. The bradycardia lasted ~2 h, and further cardiac workup revealed no underlying abnormality. Unanticipated and previously unreported outcomes may be witnessed as we expand the use of certain sedatives to alternative routes of administration.
24571687	0	17	Vasovagal syncope	Disease	D019462
24571687	29	40	bradycardia	Disease	D001919
24571687	62	77	dexmedetomidine	Chemical	D020927
24571687	123	130	syncope	Disease	D013575
24571687	135	146	bradycardia	Disease	D001919
24571687	209	224	dexmedetomidine	Chemical	D020927
24571687	625	636	bradycardia	Disease	D001919
24571687	707	718	bradycardia	Disease	D001919
24571687	CID	D020927	D001919
24571687	CID	D020927	D019462

24582773|t|Paradoxical severe agitation induced by add-on high-doses quetiapine in schizo-affective disorder.
24582773|a|We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.
24582773	19	28	agitation	Disease	D011595
24582773	58	68	quetiapine	Chemical	C069541
24582773	72	97	schizo-affective disorder	Disease	D011618
24582773	158	183	schizo-affective disorder	Disease	D011618
24582773	272	286	zuclopenthixol	Chemical	D003006
24582773	304	311	lithium	Chemical	D008094
24582773	333	340	lithium	Chemical	D008094
24582773	385	405	personality disorder	Disease	D010554
24582773	423	442	antisocial disorder	Disease	D000987
24582773	451	475	substance abuse disorder	Disease	D019966
24582773	531	541	quetiapine	Chemical	C069541
24582773	591	600	agitation	Disease	D011595
24582773	684	698	aggressiveness	Disease	D010554
24582773	702	722	personality disorder	Disease	D010554
24582773	741	746	manic	Disease	D001714
24582773	757	766	akathisia	Disease	D017109
24582773	832	842	quetiapine	Chemical	C069541
24582773	886	895	agitation	Disease	D011595
24582773	925	934	agitation	Disease	D011595
24582773	951	961	quetiapine	Chemical	C069541
24582773	CID	C069541	D011595

24587916|t|Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension in rat.
24587916|a|Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30  u g/kg/day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300 mg/kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail-cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered (P < 0.01) and dose dependently prevented (P < 0.001) Dex-induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex-induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF.
24587916	45	58	dexamethasone	Chemical	D003907
24587916	67	79	hypertension	Disease	D006973
24587916	88	101	Dexamethasone	Chemical	D003907
24587916	104	107	Dex	Chemical	D003907
24587916	118	130	hypertension	Disease	D006973
24587916	200	204	iron	Chemical	D007501
24587916	358	370	hypertension	Disease	D006973
24587916	376	379	Dex	Chemical	D003907
24587916	429	432	Dex	Chemical	D003907
24587916	644	647	Dex	Chemical	D003907
24587916	823	840	hydrogen peroxide	Chemical	D006861
24587916	842	846	H2O2	Chemical	D006861
24587916	930	943	Dexamethasone	Chemical	D003907
24587916	983	987	H2O2	Chemical	D006861
24587916	1098	1101	Dex	Chemical	D003907
24587916	1110	1122	hypertension	Disease	D006973
24587916	1142	1153	weight loss	Disease	D015431
24587916	1200	1204	H2O2	Chemical	D006861
24587916	1356	1359	Dex	Chemical	D003907
24587916	1368	1380	hypertension	Disease	D006973
24587916	CID	D003907	D006973
24587916	CID	D003907	D015431

24588023|t|The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients.
24588023|a|Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in-hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26 (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative seizures.
24588023	24	39	tranexamic acid	Chemical	D014148
24588023	44	54	convulsive	Disease	D012640
24588023	55	63	seizures	Disease	D012640
24588023	180	188	seizures	Disease	D012640
24588023	381	391	convulsive	Disease	D012640
24588023	392	399	seizure	Disease	D012640
24588023	480	516	abnormal involuntary motor movements	Disease	D004409
24588023	617	625	seizures	Disease	D012640
24588023	682	692	convulsive	Disease	D012640
24588023	693	701	seizures	Disease	D012640
24588023	703	733	Generalised and focal seizures	Disease	D012640
24588023	840	847	seizure	Disease	D012640
24588023	1031	1039	seizures	Disease	D012640
24588023	1122	1146	congestive heart failure	Disease	D006333
24588023	1153	1164	hypothermic	Disease	D007035
24588023	1220	1235	tranexamic acid	Chemical	D014148
24588023	1288	1303	tranexamic acid	Chemical	D014148
24588023	1342	1350	seizures	Disease	D012640
24588023	1404	1414	convulsive	Disease	D012640
24588023	1415	1423	seizures	Disease	D012640
24588023	1542	1552	convulsive	Disease	D012640
24588023	1553	1561	seizures	Disease	D012640
24588023	1669	1679	convulsive	Disease	D012640
24588023	1680	1688	seizures	Disease	D012640
24588023	1746	1754	seizures	Disease	D012640
24588023	1768	1778	Convulsive	Disease	D012640
24588023	1779	1787	seizures	Disease	D012640
24588023	1802	1828	postoperative complication	Disease	D011183
24588023	1855	1870	tranexamic acid	Chemical	D014148
24588023	2020	2028	seizures	Disease	D012640
24588023	CID	D014148	D012640

24595967|t|Dysfunctional overnight memory consolidation in ecstasy users.
24595967|a|Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naive healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users.
24595967	0	30	Dysfunctional overnight memory	Disease	D008569
24595967	48	55	ecstasy	Chemical	D018817
24595967	223	230	ecstasy	Chemical	D018817
24595967	283	308	sleep-related impairments	Disease	D012893
24595967	392	399	ecstasy	Chemical	D018817
24595967	692	699	Ecstasy	Chemical	D018817
24595967	719	744	impaired overnight memory	Disease	D008569
24595967	845	852	ecstasy	Chemical	D018817
24595967	1083	1090	ecstasy	Chemical	D018817
24595967	1180	1198	memory impairments	Disease	D008569
24595967	1210	1217	ecstasy	Chemical	D018817
24595967	CID	D018817	D012893
24595967	CID	D018817	D008569

24614773|t|Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?
24614773|a|A 77-year-old woman presented with subacute onset progressive confusion, aggression, auditory hallucinations and delusions. In the preceding months, the patient had a number of admissions with transient unilateral hemiparesis with facial droop, and had been started on valproate for presumed hemiplegic migraine. Valproate was withdrawn soon after admission and her cognitive abilities have gradually improved over 3 months of follow-up. Valproate levels taken prior to withdrawal were subtherapeutic and the patient was normoammonaemic. EEG undertaken during inpatient stay showed changes consistent with encephalopathy, and low titre N-methyl-D-aspartate (NMDA) receptor antibodies were present in this patient. The possible aetiologies of valproate-induced encephalopathy and NMDA receptor-associated encephalitis present a diagnostic dilemma. We present a putative combinatorial hypothesis to explain this patient's symptoms.
24614773	15	29	encephalopathy	Disease	D001927
24614773	38	47	valproate	Chemical	D014635
24614773	142	151	confusion	Disease	D003221
24614773	153	163	aggression	Disease	D001523
24614773	165	188	auditory hallucinations	Disease	D006212
24614773	193	202	delusions	Disease	D003072
24614773	294	305	hemiparesis	Disease	D010291
24614773	349	358	valproate	Chemical	D014635
24614773	372	391	hemiplegic migraine	Disease	D020325
24614773	393	402	Valproate	Chemical	D014635
24614773	518	527	Valproate	Chemical	D014635
24614773	686	700	encephalopathy	Disease	D001927
24614773	716	736	N-methyl-D-aspartate	Chemical	D016202
24614773	738	742	NMDA	Chemical	D016202
24614773	822	831	valproate	Chemical	D014635
24614773	840	854	encephalopathy	Disease	D001927
24614773	859	863	NMDA	Chemical	D016202
24614773	884	896	encephalitis	Disease	D004660
24614773	CID	D014635	D003072
24614773	CID	D014635	D003221
24614773	CID	D014635	D006212

24618873|t|Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine.
24618873|a|Pethidine is an opioid that gains its popularity for the effective pain control through acting on the opioid-receptors. However, rapid pain relief sometimes brings about unfavourable side effects that largely limit its clinical utility. Common side effects include nausea, vomiting and hypotension. In patients with impaired renal and liver function, and those who need long-term pain control, pethidine may cause excitatory central nervous system (CNS) effects through its neurotoxic metabolite, norpethidine, resulting in irritability and seizure attack. On the contrary, though not clinically apparent, pethidine potentially causes inhibitory impacts on the CNS and impairs normal cerebellar and oculomotor function in the short term. In this case report, we highlight opioid's inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity.
24618873	0	37	Cerebellar and oculomotor dysfunction	Disease	D002526|D005128	Cerebellar dysfunction|oculomotor dysfunction
24618873	67	76	pethidine	Chemical	D008614
24618873	78	87	Pethidine	Chemical	D008614
24618873	145	149	pain	Disease	D010146
24618873	213	217	pain	Disease	D010146
24618873	343	349	nausea	Disease	D009325
24618873	351	359	vomiting	Disease	D014839
24618873	364	375	hypotension	Disease	D007022
24618873	394	427	impaired renal and liver function	Disease	D051437|D017093	impaired renal function|impaired liver function
24618873	458	462	pain	Disease	D010146
24618873	472	481	pethidine	Chemical	D008614
24618873	552	562	neurotoxic	Disease	D020258
24618873	575	587	norpethidine	Chemical	C002752
24618873	602	614	irritability	Disease	D001523
24618873	619	626	seizure	Disease	D012640
24618873	684	693	pethidine	Chemical	D008614
24618873	923	932	dysmetria	Disease	D002524
24618873	934	944	dysarthria	Disease	D004401
24618873	CID	D008614	D002524
24618873	CID	D008614	D009325
24618873	CID	C002752	D012640
24618873	CID	D008614	D004401
24618873	CID	D008614	D014839
24618873	CID	D008614	D007022

24641119|t|Baboon syndrome induced by ketoconazole.
24641119|a|A 27-year-old male patient presented with a maculopapular eruption on the flexural areas and buttocks after using oral ketoconazole. The patient was diagnosed with drug-induced baboon syndrome based on his history, which included prior sensitivity to topical ketoconazole, a physical examination, and histopathological findings. Baboon syndrome is a drug- or contact allergen-related maculopapular eruption that typically involves the flexural and gluteal areas. To the best of our knowledge, this is the first reported case of ketoconazole-induced baboon syndrome in the English literature.
24641119	0	15	Baboon syndrome	Disease	-1
24641119	27	39	ketoconazole	Chemical	D007654
24641119	85	107	maculopapular eruption	Disease	D003875
24641119	160	172	ketoconazole	Chemical	D007654
24641119	218	233	baboon syndrome	Disease	-1
24641119	300	312	ketoconazole	Chemical	D007654
24641119	370	385	Baboon syndrome	Disease	-1
24641119	425	447	maculopapular eruption	Disease	D003875
24641119	569	581	ketoconazole	Chemical	D007654
24641119	590	605	baboon syndrome	Disease	-1
24641119	CID	D007654	D003875

24653743|t|A Case of Sudden Cardiac Death due to Pilsicainide-Induced Torsades de Pointes.
24653743|a|An 84-year-old male received oral pilsicainide, a pure sodium channel blocker with slow recovery kinetics, to convert his paroxysmal atrial fibrillation to a sinus rhythm; the patient developed sudden cardiac death two days later. The Holter electrocardiogram, which was worn by chance, revealed torsade de pointes with gradually prolonged QT intervals. This drug is rapidly absorbed from the gastrointestinal tract, and most of it is excreted from the kidney. Although the patient's renal function was not highly impaired and the dose of pilsicainide was low, the plasma concentration of pilsicainide may have been high, which can produce torsades de pointes in the octogenarian. Although the oral administration of class IC drugs, including pilsicainide, is effective to terminate atrial fibrillation, careful consideration must be taken before giving these drugs to octogenarians.
24653743	10	30	Sudden Cardiac Death	Disease	D016757
24653743	38	50	Pilsicainide	Chemical	C042288
24653743	59	78	Torsades de Pointes	Disease	D016171
24653743	114	126	pilsicainide	Chemical	C042288
24653743	135	141	sodium	Chemical	D012964
24653743	213	232	atrial fibrillation	Disease	D001281
24653743	274	294	sudden cardiac death	Disease	D016757
24653743	376	394	torsade de pointes	Disease	D016171
24653743	619	631	pilsicainide	Chemical	C042288
24653743	669	681	pilsicainide	Chemical	C042288
24653743	720	739	torsades de pointes	Disease	D016171
24653743	823	835	pilsicainide	Chemical	C042288
24653743	863	882	atrial fibrillation	Disease	D001281
24653743	CID	C042288	D016171
24653743	CID	C042288	D016757

24658375|t|All-trans retinoic acid-induced inflammatory myositis in a patient with acute promyelocytic leukemia.
24658375|a|All-trans retinoic acid (ATRA), a component of standard therapy for acute promyelocytic leukemia (APL), is associated with potentially serious but treatable adverse effects involving numerous organ systems, including rare skeletal muscle involvement. Only a handful of cases of ATRA-induced myositis in children have been reported, and none in the radiology literature. We present such a case in a 15-year-old boy with APL, where recognition of imaging findings played a crucial role in making the diagnosis and facilitated prompt, effective treatment.
24658375	0	23	All-trans retinoic acid	Chemical	D014212
24658375	45	53	myositis	Disease	D009220
24658375	72	100	acute promyelocytic leukemia	Disease	D015473
24658375	102	125	All-trans retinoic acid	Chemical	D014212
24658375	127	131	ATRA	Chemical	D014212
24658375	170	198	acute promyelocytic leukemia	Disease	D015473
24658375	200	203	APL	Disease	D015473
24658375	380	384	ATRA	Chemical	D014212
24658375	393	401	myositis	Disease	D009220
24658375	521	524	APL	Disease	D015473
24658375	CID	D014212	D009220

24659727|t|Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma.
24659727|a|This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg + 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg + 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.
24659727	16	25	lomustine	Chemical	D008130
24659727	46	62	cyclophosphamide	Chemical	D003520
24659727	76	84	lymphoma	Disease	D008223
24659727	121	129	toxicity	Disease	D064420
24659727	160	169	lomustine	Chemical	D008130
24659727	171	175	CCNU	Chemical	D008130
24659727	181	197	cyclophosphamide	Chemical	D003520
24659727	199	202	CTX	Chemical	D003520
24659727	217	225	lymphoma	Disease	D008223
24659727	227	231	CCNU	Chemical	D008130
24659727	324	327	CTX	Chemical	D003520
24659727	530	541	Neutropenia	Disease	D009503
24659727	611	622	neutropenia	Disease	D009503
24659727	652	656	CCNU	Chemical	D008130
24659727	657	660	CTX	Chemical	D003520
24659727	746	757	neutropenia	Disease	D009503
24659727	864	875	neutropenia	Disease	D009503
24659727	964	978	hepatotoxicity	Disease	D056486
24659727	1011	1025	renal toxicity	Disease	D007674
24659727	1029	1049	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
24659727	1169	1173	CCNU	Chemical	D008130
24659727	1203	1206	CTX	Chemical	D003520
24659727	1252	1257	tumor	Disease	D009369
24659727	CID	D003520	D009503
24659727	CID	D008130	D009503

24664478|t|Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature.
24664478|a|Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal (IT) chemotherapy is reported. A 37-year-old Caucasian woman with a history of T-cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally treated with induction chemotherapy followed by an autologous transplant. She developed relapsed disease 10 months later with leukemic involvement. She was re-induced with nelarabine 1500 mg/m(2) on days 1, 3, and 5 with 1 dose of IT cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the time of treatment, she was on continuous renal replacement therapy due to sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a complete remission, and recovered her renal function. She received a second cycle of nelarabine without additional IT prophylaxis one month later. A week after this second cycle, she noted numbness in her lower extremities. Predominantly sensory, though also motor and autonomic, peripheral neuropathy started in her feet, ascended proximally to the mid-thoracic region, and eventually included her distal upper extremities. A magnetic resonance imaging (MRI) of her spine demonstrated changes from C2 to C6 consistent with subacute combined degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy stabilized and showed slight improvement and ultimately received an unrelated, reduced-intensity allogeneic transplant while in complete remission, but relapsed disease 10 weeks later. She is currently being treated with best supportive care. To our knowledge, this is the first published case report of severe neurotoxicity caused by nelarabine in a patient who received concurrent IT chemotherapy.
24664478	0	10	Nelarabine	Chemical	C104457
24664478	11	24	neurotoxicity	Disease	D020258
24664478	112	122	nelarabine	Chemical	C104457
24664478	123	136	neurotoxicity	Disease	D020258
24664478	265	294	T-cell lymphoblastic lymphoma	Disease	D054218
24664478	475	483	leukemic	Disease	D007938
24664478	521	531	nelarabine	Chemical	C104457
24664478	583	593	cytarabine	Chemical	D003561
24664478	748	768	tumor lysis syndrome	Disease	D015275
24664478	770	773	TLS	Disease	D015275
24664478	899	909	nelarabine	Chemical	C104457
24664478	1094	1115	peripheral neuropathy	Disease	D010523
24664478	1370	1380	Nelarabine	Chemical	C104457
24664478	1427	1437	neuropathy	Disease	D009422
24664478	1749	1762	neurotoxicity	Disease	D020258
24664478	1773	1783	nelarabine	Chemical	C104457
24664478	CID	C104457	D010523

24665854|t|Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient.
24665854|a|Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.
24665854	0	9	Valproate	Chemical	D014635
24665854	18	32	hyperammonemic	Disease	D022124
24665854	33	47	encephalopathy	Disease	D001927
24665854	81	107	Neurological complications	Disease	D009422
24665854	287	296	Valproate	Chemical	D014635
24665854	305	319	hyperammonemic	Disease	D022124
24665854	320	334	encephalopathy	Disease	D001927
24665854	372	381	valproate	Chemical	D014635
24665854	478	487	valproate	Chemical	D014635
24665854	495	503	epilepsy	Disease	D004827
24665854	517	539	impaired consciousness	Disease	D003244
24665854	545	559	hyperammonemia	Disease	D022124
24665854	615	624	valproate	Chemical	D014635
24665854	740	749	valproate	Chemical	D014635
24665854	CID	D014635	D003244
24665854	CID	D014635	D022124

24671324|t|Necrotising fasciitis after bortezomib and dexamethasone-containing regimen in an elderly patient of Waldenstrom macroglobulinaemia.
24671324|a|Bortezomib and high-dose dexamethasone-containing regimens are considered to be generally tolerable with few severe bacterial infections in patients with B-cell malignancies. However, information is limited concerning the safety of the regimen in elderly patients. We report a case of a 76-year-old man with Waldenstrom macroglobulinaemia who suffered necrotising fasciitis without neutropenia after the combination treatment with bortezomib, high-dose dexamethasone and rituximab. Despite immediate intravenous antimicrobial therapy, he succumbed 23 h after the onset. Physicians should recognise the possibility of fatal bacterial infections related to bortezomib plus high-dose dexamethasone in elderly patients, and we believe this case warrants further investigation.
24671324	0	21	Necrotising fasciitis	Disease	D019115
24671324	28	38	bortezomib	Chemical	C400082
24671324	43	56	dexamethasone	Chemical	D003907
24671324	101	131	Waldenstrom macroglobulinaemia	Disease	D008258
24671324	133	143	Bortezomib	Chemical	C400082
24671324	158	171	dexamethasone	Chemical	D003907
24671324	249	269	bacterial infections	Disease	D001424
24671324	294	306	malignancies	Disease	D009369
24671324	441	471	Waldenstrom macroglobulinaemia	Disease	D008258
24671324	485	506	necrotising fasciitis	Disease	D019115
24671324	515	526	neutropenia	Disease	D009503
24671324	564	574	bortezomib	Chemical	C400082
24671324	586	599	dexamethasone	Chemical	D003907
24671324	756	776	bacterial infections	Disease	D001424
24671324	788	798	bortezomib	Chemical	C400082
24671324	814	827	dexamethasone	Chemical	D003907
24671324	CID	D003907	D019115
24671324	CID	C400082	D019115

24675088|t|An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity.
24675088|a|Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.25 mg/kg DOX weekly for 8 weeks followed by a 4 week off-dosing "recovery" period. Electron microscopy of the myocardium revealed subcellular degeneration and marked mitochondrial changes after a single dose. Histopathological analysis revealed progressive cardiomyocyte degeneration, hypertrophy/cytomegaly, and extensive vacuolation after two doses. Extensive replacement fibrosis (quantified by Sirius red staining) developed during the off-dosing period. Functional indices assessed by cardiac MRI (including left ventricular ejection fraction (LVEF), cardiac output, and E/A ratio) declined progressively, reaching statistical significance after two doses and culminating in "clinical" LV dysfunction by 12 weeks. Significant increases in peak myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged after eight doses, importantly preceding the LVEF decline to <50%. Troponin I levels positively correlated with delayed and peak gadolinium contrast enhancement, histopathological grading, and diastolic dysfunction. In summary, subcellular cardiomyocyte degeneration was the earliest marker, followed by progressive functional decline and histopathological manifestations. Myocardial contrast enhancement and elevations in cTnI occurred later. However, all indices predated "clinical" LV dysfunction and thus warrant further evaluation as predictive biomarkers.
24675088	86	97	doxorubicin	Chemical	D004317
24675088	106	120	cardiotoxicity	Disease	D066126
24675088	139	145	cancer	Disease	D009369
24675088	367	378	doxorubicin	Chemical	D004317
24675088	380	383	DOX	Chemical	D004317
24675088	393	407	cardiomyopathy	Disease	D009202
24675088	636	644	toxicity	Disease	D064420
24675088	694	697	DOX	Chemical	D004317
24675088	815	839	subcellular degeneration	Disease	D009410
24675088	942	968	cardiomyocyte degeneration	Disease	D009410
24675088	970	981	hypertrophy	Disease	D006984
24675088	1059	1067	fibrosis	Disease	D005355
24675088	1376	1390	LV dysfunction	Disease	D018487
24675088	1645	1655	gadolinium	Chemical	D005682
24675088	1709	1730	diastolic dysfunction	Disease	D018754
24675088	1756	1782	cardiomyocyte degeneration	Disease	D009410
24675088	2001	2015	LV dysfunction	Disease	D018487
24675088	CID	D004317	D005355
24675088	CID	D004317	D009202
24675088	CID	D004317	D018487

24684312|t|Intradermal glutamate and capsaicin injections: intra- and interindividual variability of provoked hyperalgesia and allodynia.
24684312|a|Intradermal injections of glutamate and capsaicin are attractive to use in human experimental pain models because hyperalgesia and allodynia mimic isolated aspects of clinical pain disorders. The aim of the present study was to investigate the reproducibility of these models. Twenty healthy male volunteers (mean age 24 years; range 18-38 years) received intradermal injections of glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick hyperalgesia and brush-evoked allodynia were investigated using von Frey filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary hyperalgesia and allodynia were quantified immediately after injection and after 15, 30 and 60 min. Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter- and intra-individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71). Intra-individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena.
24684312	12	21	glutamate	Chemical	D018698
24684312	26	35	capsaicin	Chemical	D002211
24684312	99	111	hyperalgesia	Disease	D006930
24684312	116	125	allodynia	Disease	D006930
24684312	153	162	glutamate	Chemical	D018698
24684312	167	176	capsaicin	Chemical	D002211
24684312	221	225	pain	Disease	D010146
24684312	241	253	hyperalgesia	Disease	D006930
24684312	258	267	allodynia	Disease	D006930
24684312	303	317	pain disorders	Disease	D013001
24684312	509	518	glutamate	Chemical	D018698
24684312	523	532	capsaicin	Chemical	D002211
24684312	588	600	hyperalgesia	Disease	D006930
24684312	618	627	allodynia	Disease	D006930
24684312	729	751	secondary hyperalgesia	Disease	D006930
24684312	756	765	allodynia	Disease	D006930
24684312	1123	1135	hyperalgesia	Disease	D006930
24684312	1264	1273	glutamate	Chemical	D018698
24684312	1289	1298	capsaicin	Chemical	D002211
24684312	1319	1331	hyperalgesia	Disease	D006930
24684312	1383	1392	Glutamate	Chemical	D018698
24684312	1494	1503	Capsaicin	Chemical	D002211
24684312	1535	1557	secondary hyperalgesia	Disease	D006930
24684312	1575	1584	allodynia	Disease	D006930
24684312	1714	1736	secondary hyperalgesia	Disease	D006930
24684312	1741	1750	allodynia	Disease	D006930
24684312	1767	1776	glutamate	Chemical	D018698
24684312	1781	1790	capsaicin	Chemical	D002211
24684312	1810	1822	hyperalgesic	Disease	D006930
24684312	1827	1836	allodynic	Disease	D006930
24684312	CID	D002211	D006930

24691439|t|Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma.
24691439|a|Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma.
24691439	44	52	glaucoma	Disease	D005901
24691439	86	94	glaucoma	Disease	D005901
24691439	138	157	ocular hypertension	Disease	D009798
24691439	229	237	glaucoma	Disease	D005901
24691439	253	280	primary open-angle glaucoma	Disease	C562750
24691439	282	286	POAG	Disease	C562750
24691439	340	348	glaucoma	Disease	D005901
24691439	486	494	glaucoma	Disease	D005901
24691439	509	517	glaucoma	Disease	D005901
24691439	604	617	dexamethasone	Chemical	D003907
24691439	700	716	retinal ganglion	Disease	D012173
24691439	728	747	axonal degeneration	Disease	D009410
24691439	783	791	glaucoma	Disease	D005901
24691439	824	837	dexamethasone	Chemical	D003907
24691439	846	865	ocular hypertension	Disease	D009798
24691439	972	985	dexamethasone	Chemical	D003907
24691439	1053	1066	Dexamethasone	Chemical	D003907
24691439	1240	1253	dexamethasone	Chemical	D003907
24691439	1262	1281	ocular hypertension	Disease	D009798
24691439	1334	1357	sodium 4-phenylbutyrate	Chemical	C075773
24691439	1368	1381	dexamethasone	Chemical	D003907
24691439	1390	1409	ocular hypertension	Disease	D009798
24691439	1493	1512	ocular hypertension	Disease	D009798
24691439	1625	1633	glaucoma	Disease	D005901
24691439	CID	D003907	D005901
24691439	CID	D003907	D009410
24691439	CID	D003907	D009798

24709919|t|Effects of ginsenosides on opioid-induced hyperalgesia in mice.
24709919|a|Opioid-induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid-induced writhing test. Re (300 mg/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.
24709919	11	23	ginsenosides	Chemical	D036145
24709919	42	54	hyperalgesia	Disease	D006930
24709919	79	91	hyperalgesia	Disease	D006930
24709919	93	96	OIH	Disease	D006930
24709919	191	194	OIH	Disease	D006930
24709919	274	290	opioid addiction	Disease	D009293
24709919	338	367	Re, Rg1, and Rb1 ginsenosides	Chemical	C049864|C035054|C442759	Re ginsenosides|Rg1 ginsenosides|Rb1 ginsenosides
24709919	409	412	OIH	Disease	D006930
24709919	414	417	OIH	Disease	D006930
24709919	476	484	morphine	Chemical	D009020
24709919	592	594	Re	Chemical	C049864
24709919	596	599	Rg1	Chemical	C035054
24709919	604	607	Rb1	Chemical	C442759
24709919	730	741	acetic acid	Chemical	D019342
24709919	765	767	Re	Chemical	C049864
24709919	790	793	OIH	Disease	D006930
24709919	839	850	acetic acid	Chemical	D019342
24709919	887	911	Rg1 and Rb1 ginsenosides	Chemical	C035054|C442759	Rg1 ginsenosides|Rb1 ginsenosides
24709919	930	933	OIH	Disease	D006930
24709919	963	966	Rg1	Chemical	C035054
24709919	998	1001	OIH	Disease	D006930
24709919	1009	1020	acetic acid	Chemical	D019342
24709919	1072	1086	ginsenoside Re	Chemical	C049864
24709919	1096	1099	Rg1	Chemical	C035054
24709919	1103	1106	Rb1	Chemical	C442759
24709919	1142	1145	OIH	Disease	D006930
24709919	CID	D009020	D006930

24717468|t|A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients.
24717468|a|OBJECTIVE: Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol. DESIGN: Multicenter, retrospective, propensity-matched cohort study. SETTING: Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board-certified neurointensivists. PATIENTS: Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics. INTERVENTIONS: Continuous sedation with dexmedetomidine or propofol. MEASUREMENTS AND MAIN RESULTS: A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure < 60 mm Hg) and bradycardia (heart rate < 50 beats/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts. CONCLUSIONS: Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.
24717468	56	71	dexmedetomidine	Chemical	D020927
24717468	76	84	propofol	Chemical	D015742
24717468	141	156	Dexmedetomidine	Chemical	D020927
24717468	161	169	propofol	Chemical	D015742
24717468	487	502	dexmedetomidine	Chemical	D020927
24717468	507	515	propofol	Chemical	D015742
24717468	948	963	dexmedetomidine	Chemical	D020927
24717468	967	975	propofol	Chemical	D015742
24717468	1037	1052	dexmedetomidine	Chemical	D020927
24717468	1061	1069	propofol	Chemical	D015742
24717468	1219	1230	hypotension	Disease	D007022
24717468	1271	1282	bradycardia	Disease	D001919
24717468	1571	1582	hypotension	Disease	D007022
24717468	1586	1597	bradycardia	Disease	D001919
24717468	1662	1673	hypotension	Disease	D007022
24717468	1678	1689	bradycardia	Disease	D001919
24717468	1761	1776	dexmedetomidine	Chemical	D020927
24717468	1780	1788	propofol	Chemical	D015742
24717468	1844	1855	hypotension	Disease	D007022
24717468	1859	1870	bradycardia	Disease	D001919
24717468	CID	D015742	D001919
24717468	CID	D020927	D007022
24717468	CID	D020927	D001919
24717468	CID	D015742	D007022

24727461|t|Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer.
24727461|a|Oxidative stress is involved in several processes including cancer, aging and cardiovascular disease, and has been shown to potentiate the therapeutic effect of drugs such as doxorubicin. Doxorubicin causes significant cardiotoxicity characterized by marked increases in oxidative stress and mitochondrial dysfunction. Herein, we investigate whether doxorubicin-associated chronic cardiac toxicity can be ameliorated with the antioxidant hydroxytyrosol in rats with breast cancer. Thirty-six rats bearing breast tumors induced chemically were divided into 4 groups: control, hydroxytyrosol (0.5mg/kg, 5days/week), doxorubicin (1mg/kg/week), and doxorubicin plus hydroxytyrosol. Cardiac disturbances at the cellular and mitochondrial level, mitochondrial electron transport chain complexes I-IV and apoptosis-inducing factor, and oxidative stress markers have been analyzed. Hydroxytyrosol improved the cardiac disturbances enhanced by doxorubicin by significantly reducing the percentage of altered mitochondria and oxidative damage. These results suggest that hydroxytyrosol improve the mitochondrial electron transport chain. This study demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin decreasing oxidative damage and mitochondrial alterations.
24727461	0	14	Hydroxytyrosol	Chemical	C005975
24727461	48	73	mitochondrial dysfunction	Disease	D028361
24727461	77	88	doxorubicin	Chemical	D004317
24727461	97	111	cardiotoxicity	Disease	D066126
24727461	125	138	breast cancer	Disease	D001943
24727461	200	206	cancer	Disease	D009369
24727461	218	240	cardiovascular disease	Disease	D002318
24727461	315	326	doxorubicin	Chemical	D004317
24727461	328	339	Doxorubicin	Chemical	D004317
24727461	359	373	cardiotoxicity	Disease	D066126
24727461	432	457	mitochondrial dysfunction	Disease	D028361
24727461	490	501	doxorubicin	Chemical	D004317
24727461	521	537	cardiac toxicity	Disease	D066126
24727461	578	592	hydroxytyrosol	Chemical	C005975
24727461	606	619	breast cancer	Disease	D001943
24727461	645	658	breast tumors	Disease	D001943
24727461	715	729	hydroxytyrosol	Chemical	C005975
24727461	754	765	doxorubicin	Chemical	D004317
24727461	785	796	doxorubicin	Chemical	D004317
24727461	802	816	hydroxytyrosol	Chemical	C005975
24727461	818	838	Cardiac disturbances	Disease	D006331
24727461	1014	1028	Hydroxytyrosol	Chemical	C005975
24727461	1042	1062	cardiac disturbances	Disease	D006331
24727461	1075	1086	doxorubicin	Chemical	D004317
24727461	1201	1215	hydroxytyrosol	Chemical	C005975
24727461	1297	1311	hydroxytyrosol	Chemical	C005975
24727461	1324	1336	heart damage	Disease	D006331
24727461	1349	1360	doxorubicin	Chemical	D004317
24727461	CID	D004317	D006331

24729111|t|Amiodarone-induced myxoedema coma.
24729111|a|A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 uIU/mL (nl. 0.3-5 uIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 ug of intravenous levothyroxine in the first 18 h of therapy, and 150 ug intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease.
24729111	0	10	Amiodarone	Chemical	D000638
24729111	19	33	myxoedema coma	Disease	D007037|D003128	myxoedema|coma
24729111	71	82	bradycardia	Disease	D001919
24729111	84	95	hypothermia	Disease	D007035
24729111	100	119	respiratory failure	Disease	D012131
24729111	148	158	amiodarone	Chemical	D000638
24729111	171	190	atrial fibrillation	Disease	D001281
24729111	275	284	thyroxine	Chemical	D013974
24729111	395	403	steroids	Chemical	D013256
24729111	497	510	levothyroxine	Chemical	D013974
24729111	772	785	levothyroxine	Chemical	D013974
24729111	885	891	iodine	Chemical	D007455
24729111	944	954	amiodarone	Chemical	D000638
24729111	963	977	myxoedema coma	Disease	D007037|D003128	myxoedema|coma
24729111	1139	1149	amiodarone	Chemical	D000638
24729111	1158	1172	myxoedema coma	Disease	D007037|D003128	myxoedema|coma
24729111	1216	1231	thyroid disease	Disease	D013959
24729111	CID	D000638	D007037
24729111	CID	D000638	D001919
24729111	CID	D000638	D007035
24729111	CID	D000638	D012131
24729111	CID	D000638	D003128

24733133|t|Use of argatroban and catheter-directed thrombolysis with alteplase in an oncology patient with heparin-induced thrombocytopenia with thrombosis.
24733133|a|PURPOSE: The case of an oncology patient who developed heparin-induced thrombocytopenia with thrombosis (HITT) and was treated with argatroban plus catheter-directed thrombolysis (CDT) with alteplase is presented. SUMMARY: A 63-year-old Caucasian man with renal amyloidosis undergoing peripheral blood stem cell collection for an autologous stem cell transplant developed extensive bilateral upper-extremity deep venous thrombosis (DVT) and pulmonary embolism secondary to heparin-induced thrombocytopenia. A continuous i.v. infusion of argatroban was initiated, and the patient was managed on the general medical floor. After one week of therapy, he was transferred to the intensive care unit with cardiopulmonary compromise related to superior vena cava (SVC) syndrome. A percutaneous mechanical thrombectomy and CDT with alteplase were attempted, but the procedure was aborted due to epistaxis. The epistaxis resolved the next day, and the patient was restarted on argatroban. A second percutaneous mechanical thrombectomy was performed six days later and resulted in partial revascularization of the SVC and central veins. Postthrombectomy continuous CDT with alteplase was commenced while argatroban was withheld, and complete patency of the SVC and central veins was achieved after three days of therapy. Alteplase was discontinued, and the patient was reinitiated on argatroban; ultimately, he was transitioned to warfarin for long-term anticoagulation. Although the patient recovered, he experienced permanent vision and hearing loss, as well as end-stage renal disease. CONCLUSION: A 63-year-old man with renal amyloidosis and SVC syndrome secondary to HITT was successfully treated with argatroban and CDT with alteplase.
24733133	7	17	argatroban	Chemical	C031942
24733133	40	52	thrombolysis	Disease	D055499
24733133	96	103	heparin	Chemical	D006493
24733133	112	128	thrombocytopenia	Disease	D013921
24733133	134	144	thrombosis	Disease	D013927
24733133	201	208	heparin	Chemical	D006493
24733133	217	233	thrombocytopenia	Disease	D013921
24733133	239	249	thrombosis	Disease	D013927
24733133	251	255	HITT	Disease	D013921|D013927
24733133	278	288	argatroban	Chemical	C031942
24733133	312	324	thrombolysis	Disease	D055499
24733133	408	419	amyloidosis	Disease	D000686
24733133	538	576	upper-extremity deep venous thrombosis	Disease	D056824
24733133	578	581	DVT	Disease	D020246
24733133	587	605	pulmonary embolism	Disease	D011655
24733133	619	626	heparin	Chemical	D006493
24733133	635	651	thrombocytopenia	Disease	D013921
24733133	683	693	argatroban	Chemical	C031942
24733133	883	916	superior vena cava (SVC) syndrome	Disease	D013479
24733133	1033	1042	epistaxis	Disease	D004844
24733133	1048	1057	epistaxis	Disease	D004844
24733133	1114	1124	argatroban	Chemical	C031942
24733133	1340	1350	argatroban	Chemical	C031942
24733133	1520	1530	argatroban	Chemical	C031942
24733133	1567	1575	warfarin	Chemical	D014859
24733133	1664	1687	vision and hearing loss	Disease	D014786|D034381	vision loss|hearing loss
24733133	1700	1723	end-stage renal disease	Disease	D007676
24733133	1766	1777	amyloidosis	Disease	D000686
24733133	1782	1794	SVC syndrome	Disease	D013479
24733133	1808	1812	HITT	Disease	D013921|D013927
24733133	1843	1853	argatroban	Chemical	C031942
24733133	CID	D006493	D013921
24733133	CID	D006493	D011655
24733133	CID	D006493	D020246

24739405|t|Effects of dehydroepiandrosterone in amphetamine-induced schizophrenia models in mice.
24739405|a|OBJECTIVE: To examine the effects of dehydroepiandrosterone (DHEA) on animal models of schizophrenia. METHODS: Seventy Swiss albino female mice (25-35 g) were divided into 4 groups: amphetamine-free (control), amphetamine, 50, and 100 mg/kg DHEA. The DHEA was administered intraperitoneally (ip) for 5 days. Amphetamine (3 mg/kg ip) induced hyper locomotion, apomorphine (1.5 mg/kg subcutaneously [sc]) induced climbing, and haloperidol (1.5 mg/kg sc) induced catalepsy tests were used as animal models of schizophrenia. The study was conducted at the Animal Experiment Laboratories, Department of Pharmacology, Medical School, Eskisehir Osmangazi University, Eskisehir, Turkey between March and May 2012. Statistical analysis was carried out using Kruskal-Wallis test for hyper locomotion, and one-way ANOVA for climbing and catalepsy tests. RESULTS: In the amphetamine-induced locomotion test, there were significant increases in all movements compared with the amphetamine-free group. Both DHEA 50 mg/kg (p<0.05), and 100 mg/kg (p<0.01) significantly decreased all movements compared with the amphetamine-induced locomotion group. There was a significant difference between groups in the haloperidol-induced catalepsy test (p<0.05). There was no significant difference between groups in terms of total climbing time in the apomorphine-induced climbing test (p>0.05). CONCLUSION: We observed that DHEA reduced locomotor activity and increased catalepsy at both doses, while it had no effect on climbing behavior. We suggest that DHEA displays typical neuroleptic-like effects, and may be used in the treatment of schizophrenia.
24739405	11	33	dehydroepiandrosterone	Chemical	D003687
24739405	37	48	amphetamine	Chemical	D000661
24739405	57	70	schizophrenia	Disease	D012559
24739405	124	146	dehydroepiandrosterone	Chemical	D003687
24739405	148	152	DHEA	Chemical	D003687
24739405	174	187	schizophrenia	Disease	D012559
24739405	269	280	amphetamine	Chemical	D000661
24739405	297	308	amphetamine	Chemical	D000661
24739405	328	332	DHEA	Chemical	D003687
24739405	338	342	DHEA	Chemical	D003687
24739405	395	406	Amphetamine	Chemical	D000661
24739405	428	433	hyper	Disease	D006948
24739405	446	457	apomorphine	Chemical	D001058
24739405	512	523	haloperidol	Chemical	D006220
24739405	547	556	catalepsy	Disease	D002375
24739405	593	606	schizophrenia	Disease	D012559
24739405	860	865	hyper	Disease	D006948
24739405	913	922	catalepsy	Disease	D002375
24739405	946	957	amphetamine	Chemical	D000661
24739405	1051	1062	amphetamine	Chemical	D000661
24739405	1080	1084	DHEA	Chemical	D003687
24739405	1183	1194	amphetamine	Chemical	D000661
24739405	1278	1289	haloperidol	Chemical	D006220
24739405	1298	1307	catalepsy	Disease	D002375
24739405	1413	1424	apomorphine	Chemical	D001058
24739405	1486	1490	DHEA	Chemical	D003687
24739405	1532	1541	catalepsy	Disease	D002375
24739405	1618	1622	DHEA	Chemical	D003687
24739405	1702	1715	schizophrenia	Disease	D012559
24739405	CID	D001058	D012559
24739405	CID	D000661	D012559
24739405	CID	D006220	D002375
24739405	CID	D006220	D012559

24742750|t|Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation.
24742750|a|Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K(+) channel and Ca(2+) channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2min every 10min for 30min after drug exposure for the vehicle and each drug concentration. IKr and IKs blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca(2+) channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the IKr blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential.
24742750	111	126	QT prolongation	Disease	D008133
24742750	331	332	K	Chemical	D011188
24742750	348	350	Ca	Chemical	D002118
24742750	509	524	QT prolongation	Disease	D008133
24742750	623	638	QT prolongation	Disease	D008133
24742750	907	909	Ca	Chemical	D002118
24742750	1005	1015	Amiodarone	Chemical	D000638
24742750	1017	1027	Paroxetine	Chemical	D017374
24742750	1029	1040	Terfenadine	Chemical	D016593
24742750	1045	1055	Citalopram	Chemical	D015283
24742750	1135	1146	Terfenadine	Chemical	D016593
24742750	1151	1161	Citalopram	Chemical	D015283
24742750	1191	1209	Torsade de Pointes	Disease	D016171
24742750	1211	1214	TdP	Disease	D016171
24742750	1447	1450	TdP	Disease	D016171
24742750	CID	D015283	D016171
24742750	CID	D016593	D016171

24753331|t|Dermal developmental toxicity of N-phenylimide herbicides in rats.
24753331|a|BACKGROUND: S-53482 and S-23121 are N-phenylimide herbicides and produced embryolethality, teratogenicity (mainly ventricular septal defects and wavy ribs), and growth retardation in rats in conventional oral developmental toxicity studies. Our objective in this study was to investigate whether the compounds induce developmental toxicity via the dermal route, which is more relevant to occupational exposure, hence better addressing human health risks. METHODS: S-53482 was administered dermally to rats at 30, 100, and 300 mg/kg during organogenesis, and S-23121 was administered at 200, 400, and 800 mg/kg (the maximum applicable dose level). Fetuses were obtained by a Cesarean section and examined for external, visceral, and skeletal alterations. RESULTS: Dermal exposure of rats to S-53482 at 300 mg/kg produced patterns of developmental toxicity similar to those resulting from oral exposure. Toxicity included embryolethality, teratogenicity, and growth retardation. Dermal administration of S-23121 at 800 mg/kg resulted in an increased incidence of embryonic death and ventricular septal defect, but retarded fetal growth was not observed as it was following oral exposure to S-23121. CONCLUSIONS: Based on the results, S-53482 and S-23121 were teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Thus, investigation of the mechanism and its human relevancy become more important.
24753331	21	29	toxicity	Disease	D064420
24753331	79	86	S-53482	Chemical	C106487
24753331	91	98	S-23121	Chemical	C083440
24753331	141	156	embryolethality	Disease	D020964
24753331	158	172	teratogenicity	Disease	D064793
24753331	181	207	ventricular septal defects	Disease	D006345
24753331	228	246	growth retardation	Disease	D005317
24753331	290	298	toxicity	Disease	D064420
24753331	398	406	toxicity	Disease	D064420
24753331	531	538	S-53482	Chemical	C106487
24753331	625	632	S-23121	Chemical	C083440
24753331	857	864	S-53482	Chemical	C106487
24753331	913	921	toxicity	Disease	D064420
24753331	969	977	Toxicity	Disease	D064420
24753331	987	1002	embryolethality	Disease	D020964
24753331	1004	1018	teratogenicity	Disease	D064793
24753331	1024	1042	growth retardation	Disease	D005317
24753331	1069	1076	S-23121	Chemical	C083440
24753331	1128	1143	embryonic death	Disease	D020964
24753331	1148	1173	ventricular septal defect	Disease	D006345
24753331	1255	1262	S-23121	Chemical	C083440
24753331	1299	1306	S-53482	Chemical	C106487
24753331	1311	1318	S-23121	Chemical	C083440
24753331	1324	1335	teratogenic	Disease	D064793
24753331	CID	C106487	D005317
24753331	CID	C083440	D005317
24753331	CID	C083440	D064793
24753331	CID	C083440	D020964
24753331	CID	C106487	D020964
24753331	CID	C106487	D064793
24753331	CID	C083440	D006345
24753331	CID	C106487	D006345

24778426|t|Rates of Renal Toxicity in Cancer Patients Receiving Cisplatin With and Without Mannitol.
24778426|a|BACKGROUND: Cisplatin is a widely used antineoplastic. One of the major complications of cisplatin use is dose-limiting nephrotoxicity. There are many strategies to prevent this toxicity, including the use of mannitol as a nephroprotectant in combination with hydration. OBJECTIVE: We aimed to evaluate the rates of cisplatin-induced nephrotoxicity in cancer patients receiving single-agent cisplatin with and without mannitol. METHODS: This single-center retrospective analysis was a quasi experiment created by the national mannitol shortage. Data were collected on adult cancer patients receiving single-agent cisplatin as an outpatient from January 2011 to September 2012. The primary outcome was acute kidney injury (AKI). RESULTS: We evaluated 143 patients who received single-agent cisplatin; 97.2% of patients had head and neck cancer as their primary malignancy. Patients who did not receive mannitol were more likely to develop nephrotoxicity: odds ratio [OR] = 2.646 (95% CI = 1.008, 6.944; P = 0.048). Patients who received the 100 mg/m(2) dosing and patients who had a history of hypertension also had a higher likelihood of developing nephrotoxicity: OR = 11.494 (95% CI = 4.149, 32.258; P < 0.0001) and OR = 3.219 (95% CI = 1.228, 8.439; P = 0.017), respectively. CONCLUSIONS: When limited quantities of mannitol are available, it should preferentially be given to patients at particularly high risk of nephrotoxicity. Our analysis suggests that those patients receiving the dosing schedule of 100 mg/m(2) cisplatin every 3 weeks and those with hypertension are at the greatest risk of nephrotoxicity and would benefit from the addition of mannitol.
24778426	9	23	Renal Toxicity	Disease	D007674
24778426	27	33	Cancer	Disease	D009369
24778426	53	62	Cisplatin	Chemical	D002945
24778426	80	88	Mannitol	Chemical	D008353
24778426	102	111	Cisplatin	Chemical	D002945
24778426	179	188	cisplatin	Chemical	D002945
24778426	210	224	nephrotoxicity	Disease	D007674
24778426	268	276	toxicity	Disease	D064420
24778426	299	307	mannitol	Chemical	D008353
24778426	406	415	cisplatin	Chemical	D002945
24778426	424	438	nephrotoxicity	Disease	D007674
24778426	442	448	cancer	Disease	D009369
24778426	481	490	cisplatin	Chemical	D002945
24778426	508	516	mannitol	Chemical	D008353
24778426	616	624	mannitol	Chemical	D008353
24778426	664	670	cancer	Disease	D009369
24778426	703	712	cisplatin	Chemical	D002945
24778426	791	810	acute kidney injury	Disease	D058186
24778426	812	815	AKI	Disease	D058186
24778426	879	888	cisplatin	Chemical	D002945
24778426	912	932	head and neck cancer	Disease	D006258
24778426	950	960	malignancy	Disease	D009369
24778426	991	999	mannitol	Chemical	D008353
24778426	1028	1042	nephrotoxicity	Disease	D007674
24778426	1183	1195	hypertension	Disease	D006973
24778426	1239	1253	nephrotoxicity	Disease	D007674
24778426	1409	1417	mannitol	Chemical	D008353
24778426	1508	1522	nephrotoxicity	Disease	D007674
24778426	1611	1620	cisplatin	Chemical	D002945
24778426	1650	1662	hypertension	Disease	D006973
24778426	1691	1705	nephrotoxicity	Disease	D007674
24778426	1745	1753	mannitol	Chemical	D008353
24778426	CID	D002945	D058186

24802403|t|Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice.
24802403|a|Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.
24802403	0	9	Metformin	Chemical	D008687
24802403	27	35	seizures	Disease	D012640
24802403	37	68	learning and memory impairments	Disease	D007859|D008569	learning impairments|memory impairments
24802403	101	119	pentylenetetrazole	Chemical	D010433
24802403	146	166	Cognitive impairment	Disease	D003072
24802403	210	218	epilepsy	Disease	D004827
24802403	307	315	epilepsy	Disease	D004827
24802403	428	436	seizures	Disease	D012640
24802403	441	459	cognition deficits	Disease	D003072
24802403	541	559	cognitive deficits	Disease	D003072
24802403	619	628	Metformin	Chemical	D008687
24802403	775	784	metformin	Chemical	D008687
24802403	788	796	seizures	Disease	D012640
24802403	798	818	cognitive impairment	Disease	D003072
24802403	866	884	pentylenetetrazole	Chemical	D010433
24802403	974	992	pentylenetetrazole	Chemical	D010433
24802403	1045	1054	Metformin	Chemical	D008687
24802403	1131	1134	PTZ	Chemical	D010433
24802403	1150	1159	metformin	Chemical	D008687
24802403	1216	1236	cognitive impairment	Disease	D003072
24802403	1313	1322	metformin	Chemical	D008687
24802403	1369	1377	epilepsy	Disease	D004827
24802403	1419	1439	cognitive impairment	Disease	D003072
24802403	1451	1459	seizures	Disease	D012640
24802403	CID	D010433	D008569
24802403	CID	D010433	D007859
24802403	CID	D010433	D003072
24802403	CID	D010433	D012640

24812279|t|P53 inhibition exacerbates late-stage anthracycline cardiotoxicity.
24812279|a|AIMS: Doxorubicin (DOX) is an effective anti-cancer therapeutic, but is associated with both acute and late-stage cardiotoxicity. Children are particularly sensitive to DOX-induced heart failure. Here, the impact of p53 inhibition on acute vs. late-stage DOX cardiotoxicity was examined in a juvenile model. METHODS AND RESULTS: Two-week-old MHC-CB7 mice (which express dominant-interfering p53 in cardiomyocytes) and their non-transgenic (NON-TXG) littermates received weekly DOX injections for 5 weeks (25 mg/kg cumulative dose). One week after the last DOX treatment (acute stage), MHC-CB7 mice exhibited improved cardiac function and lower levels of cardiomyocyte apoptosis when compared with the NON-TXG mice. Surprisingly, by 13 weeks following the last DOX treatment (late stage), MHC-CB7 exhibited a progressive decrease in cardiac function and higher rates of cardiomyocyte apoptosis when compared with NON-TXG mice. p53 inhibition blocked transient DOX-induced STAT3 activation in MHC-CB7 mice, which was associated with enhanced induction of the DNA repair proteins Ku70 and Ku80. Mice with cardiomyocyte-restricted deletion of STAT3 exhibited worse cardiac function, higher levels of cardiomyocyte apoptosis, and a greater induction of Ku70 and Ku80 in response to DOX treatment during the acute stage when compared with control animals. CONCLUSION: These data support a model wherein a p53-dependent cardioprotective pathway, mediated via STAT3 activation, mitigates DOX-induced myocardial stress during drug delivery. Furthermore, these data suggest an explanation as to how p53 inhibition can result in cardioprotection during drug treatment and, paradoxically, enhanced cardiotoxicity long after the cessation of drug treatment.
24812279	38	51	anthracycline	Chemical	D018943
24812279	52	66	cardiotoxicity	Disease	D066126
24812279	74	85	Doxorubicin	Chemical	D004317
24812279	87	90	DOX	Chemical	D004317
24812279	113	119	cancer	Disease	D009369
24812279	182	196	cardiotoxicity	Disease	D066126
24812279	237	240	DOX	Chemical	D004317
24812279	249	262	heart failure	Disease	D006333
24812279	323	326	DOX	Chemical	D004317
24812279	327	341	cardiotoxicity	Disease	D066126
24812279	545	548	DOX	Chemical	D004317
24812279	624	627	DOX	Chemical	D004317
24812279	828	831	DOX	Chemical	D004317
24812279	1027	1030	DOX	Chemical	D004317
24812279	1345	1348	DOX	Chemical	D004317
24812279	1548	1551	DOX	Chemical	D004317
24812279	1754	1768	cardiotoxicity	Disease	D066126
24812279	CID	D004317	D006333

24816962|t|Metronidazole-induced encephalopathy: an uncommon scenario.
24816962|a|Metronidazole can produce neurological complications although it is not a common scenario. We present a case where a patient developed features of encephalopathy following prolonged metronidazole intake. Magnetic resonance imaging (MRI) brain showed abnormal signal intensity involving both dentate nuclei of cerebellum and splenium of corpus callosum. The diagnosis of metronidazole toxicity was made by the MRI findings and supported clinically.
24816962	0	13	Metronidazole	Chemical	D008795
24816962	22	36	encephalopathy	Disease	D001927
24816962	60	73	Metronidazole	Chemical	D008795
24816962	207	221	encephalopathy	Disease	D001927
24816962	242	255	metronidazole	Chemical	D008795
24816962	430	443	metronidazole	Chemical	D008795
24816962	444	452	toxicity	Disease	D064420
24816962	CID	D008795	D001927

24840785|t|Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats.
24840785|a|Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na(+) channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca(2+) in aconitine poisoning. In this study, we explored the importance of pathological Ca(2+) signaling in aconitine poisoning in vitro and in vivo. We found that Ca(2+) overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca(2+) handling proteins demonstrated that aconitine promoted Ca(2+) overload through the expression regulation of Ca(2+) handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca(2+) overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase.
24840785	0	9	Aconitine	Chemical	D000157
24840785	18	20	Ca	Chemical	D002118
24840785	39	49	arrhythmia	Disease	D001145
24840785	117	126	Aconitine	Chemical	D000157
24840785	275	277	Na	Chemical	D012964
24840785	316	330	cardiotoxicity	Disease	D066126
24840785	334	343	aconitine	Chemical	D000157
24840785	394	396	Ca	Chemical	D002118
24840785	404	413	aconitine	Chemical	D000157
24840785	414	423	poisoning	Disease	D011041
24840785	483	485	Ca	Chemical	D002118
24840785	503	512	aconitine	Chemical	D000157
24840785	513	522	poisoning	Disease	D011041
24840785	559	561	Ca	Chemical	D002118
24840785	655	665	arrhythmia	Disease	D001145
24840785	725	734	aconitine	Chemical	D000157
24840785	738	755	myocardial injury	Disease	D009202
24840785	770	782	cytotoxicity	Disease	D064420
24840785	855	862	lactate	Chemical	D019344
24840785	987	996	aconitine	Chemical	D000157
24840785	1009	1026	myocardial injury	Disease	D009202
24840785	1254	1258	dUTP	Chemical	-1
24840785	1259	1265	biotin	Chemical	D001710
24840785	1315	1324	aconitine	Chemical	D000157
24840785	1391	1393	Ca	Chemical	D002118
24840785	1434	1443	aconitine	Chemical	D000157
24840785	1453	1455	Ca	Chemical	D002118
24840785	1506	1508	Ca	Chemical	D002118
24840785	1869	1878	aconitine	Chemical	D000157
24840785	1904	1906	Ca	Chemical	D002118
24840785	1931	1941	arrhythmia	Disease	D001145
24840785	CID	D000157	D011041
24840785	CID	D000157	D066126
24840785	CID	D000157	D001145

24842192|t|Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction.
24842192|a|Acute treatment with metformin has a protective effect in myocardial infarction by suppression of inflammatory responses due to activation of AMP-activated protein kinase (AMPK). In the present study, the effect of chronic pre-treatment with metformin on cardiac dysfunction and toll-like receptor 4 (TLR4) activities following myocardial infarction and their relation with AMPK were assessed. Male Wistar rats were randomly assigned to one of 5 groups (n=6): normal control and groups were injected isoproterenol after chronic pre-treatment with 0, 25, 50, or 100mg/kg of metformin twice daily for 14 days. Isoproterenol (100mg/kg) was injected subcutaneously on the 13th and 14th days to induce acute myocardial infarction. Isoproterenol alone decreased left ventricular systolic pressure and myocardial contractility indexed as LVdp/dtmax and LVdp/dtmin. The left ventricular dysfunction was significantly lower in the groups treated with 25 and 50mg/kg of metformin. Metfromin markedly lowered isoproterenol-induced elevation in the levels of TLR4 mRNA, myeloid differentiation protein 88 (MyD88), tumor necrosis factor-alpha (TNF-a), and interleukin 6 (IL-6) in the heart tissues. Similar changes were also seen in the serum levels of TNF-a and IL-6. However, the lower doses of 25 and 50mg/kg were more effective than 100mg/kg. Phosphorylated AMPKa (p-AMPK) in the myocardium was significantly elevated by 25mg/kg of metformin, slightly by 50mg/kg, but not by 100mg/kg. Chronic pre-treatment with metformin reduces post-myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities. This mechanism can be considered as a target to protect infarcted myocardium.
24842192	23	32	metformin	Chemical	D008687
24842192	90	118	left ventricular dysfunction	Disease	D018487
24842192	129	150	myocardial infarction	Disease	D009203
24842192	173	182	metformin	Chemical	D008687
24842192	210	231	myocardial infarction	Disease	D009203
24842192	294	297	AMP	Chemical	D000667
24842192	394	403	metformin	Chemical	D008687
24842192	407	426	cardiac dysfunction	Disease	D006331
24842192	480	501	myocardial infarction	Disease	D009203
24842192	652	665	isoproterenol	Chemical	D007545
24842192	725	734	metformin	Chemical	D008687
24842192	760	773	Isoproterenol	Chemical	D007545
24842192	849	876	acute myocardial infarction	Disease	D009203
24842192	878	891	Isoproterenol	Chemical	D007545
24842192	1014	1042	left ventricular dysfunction	Disease	D018487
24842192	1112	1121	metformin	Chemical	D008687
24842192	1150	1163	isoproterenol	Chemical	D007545
24842192	1254	1259	tumor	Disease	D009369
24842192	1260	1268	necrosis	Disease	D009336
24842192	1575	1584	metformin	Chemical	D008687
24842192	1655	1664	metformin	Chemical	D008687
24842192	1678	1699	myocardial infarction	Disease	D009203
24842192	CID	D007545	D009203
24842192	CID	D007545	D018487

24881749|t|Neuroleptic malignant syndrome induced by combination therapy with tetrabenazine and tiapride in a Japanese patient with Huntington's disease at the terminal stage of recurrent breast cancer.
24881749|a|We herein describe the case of an 81-year-old Japanese woman with neuroleptic malignant syndrome that occurred 36 days after the initiation of combination therapy with tiapride (75 mg/day) and tetrabenazine (12.5 mg/day) for Huntington's disease. The patient had been treated with tiapride or tetrabenazine alone without any adverse effects before the administration of the combination therapy. She also had advanced breast cancer when the combination therapy was initiated. To the best of our knowledge, the occurrence of neuroleptic malignant syndrome due to combination therapy with tetrabenazine and tiapride has not been previously reported. Tetrabenazine should be administered very carefully in combination with other neuroleptic drugs, particularly in patients with a worsening general condition.
24881749	0	30	Neuroleptic malignant syndrome	Disease	D009459
24881749	67	80	tetrabenazine	Chemical	D013747
24881749	85	93	tiapride	Chemical	D063325
24881749	121	141	Huntington's disease	Disease	D006816
24881749	177	190	breast cancer	Disease	D001943
24881749	258	288	neuroleptic malignant syndrome	Disease	D009459
24881749	360	368	tiapride	Chemical	D063325
24881749	385	398	tetrabenazine	Chemical	D013747
24881749	417	437	Huntington's disease	Disease	D006816
24881749	473	481	tiapride	Chemical	D063325
24881749	485	498	tetrabenazine	Chemical	D013747
24881749	609	622	breast cancer	Disease	D001943
24881749	715	745	neuroleptic malignant syndrome	Disease	D009459
24881749	778	791	tetrabenazine	Chemical	D013747
24881749	796	804	tiapride	Chemical	D063325
24881749	839	852	Tetrabenazine	Chemical	D013747
24881749	917	934	neuroleptic drugs	Chemical	D014150
24881749	CID	D013747	D009459
24881749	CID	D063325	D009459

24894748|t|A metoprolol-terbinafine combination induced bradycardia.
24894748|a|To report a sinus bradycardia induced by metoprolol and terbinafine drug-drug interaction and its management. A 63 year-old Caucasian man on metoprolol 200 mg/day for stable coronary artery disease was prescribed a 90-day course of oral terbinafine 250 mg/day for onychomycosis. On the 49th day of terbinafine therapy, he was brought to the emergency room for a decrease of his global health status, confusion and falls. The electrocardiogram revealed a 37 beats/min sinus bradycardia. A score of 7 on the Naranjo adverse drug reaction probability scale indicates a probable relationship between the patient's sinus bradycardia and the drug interaction between metoprolol and terbinafine. The heart rate ameliorated first with a decrease in the dose of metoprolol. It was subsequently changed to bisoprolol and the heart rate remained normal. By inhibiting the cytochrome P450 2D6, terbinafine had decreased metoprolol's clearance, leading in metoprolol accumulation which has resulted in clinically significant sinus bradycardia.
24894748	2	12	metoprolol	Chemical	D008790
24894748	13	24	terbinafine	Chemical	C041359
24894748	45	56	bradycardia	Disease	D001919
24894748	70	87	sinus bradycardia	Disease	D012804
24894748	99	109	metoprolol	Chemical	D008790
24894748	114	125	terbinafine	Chemical	C041359
24894748	199	209	metoprolol	Chemical	D008790
24894748	232	255	coronary artery disease	Disease	D003324
24894748	295	306	terbinafine	Chemical	C041359
24894748	322	335	onychomycosis	Disease	D014009
24894748	356	367	terbinafine	Chemical	C041359
24894748	458	467	confusion	Disease	D003221
24894748	525	542	sinus bradycardia	Disease	D012804
24894748	572	593	adverse drug reaction	Disease	D064420
24894748	668	685	sinus bradycardia	Disease	D012804
24894748	719	729	metoprolol	Chemical	D008790
24894748	734	745	terbinafine	Chemical	C041359
24894748	811	821	metoprolol	Chemical	D008790
24894748	854	864	bisoprolol	Chemical	D017298
24894748	940	951	terbinafine	Chemical	C041359
24894748	966	976	metoprolol	Chemical	D008790
24894748	1001	1011	metoprolol	Chemical	D008790
24894748	1070	1087	sinus bradycardia	Disease	D012804
24894748	CID	D008790	D001919
24894748	CID	C041359	D001919

24897009|t|Optochiasmatic and peripheral neuropathy due to ethambutol overtreatment.
24897009|a|Ethambutol is known to cause optic neuropathy and, more rarely, axonal polyneuropathy. We characterize the clinical, neurophysiological, and neuroimaging findings in a 72-year-old man who developed visual loss and paresthesias after 11 weeks of exposure to a supratherapeutic dose of ethambutol. This case demonstrates the selective vulnerability of the anterior visual pathways and peripheral nerves to ethambutol toxicity.
24897009	19	40	peripheral neuropathy	Disease	D010523
24897009	48	58	ethambutol	Chemical	D004977
24897009	74	84	Ethambutol	Chemical	D004977
24897009	103	119	optic neuropathy	Disease	D009901
24897009	145	159	polyneuropathy	Disease	D011115
24897009	272	283	visual loss	Disease	D014786
24897009	288	300	paresthesias	Disease	D010292
24897009	358	368	ethambutol	Chemical	D004977
24897009	478	488	ethambutol	Chemical	D004977
24897009	489	497	toxicity	Disease	D064420
24897009	CID	D004977	D011115
24897009	CID	D004977	D014786
24897009	CID	D004977	D009901
24897009	CID	D004977	D010292

24902786|t|Testosterone ameliorates streptozotocin-induced memory impairment in male rats.
24902786|a|AIM: To study the effects of testosterone on streptozotocin (STZ)-induced memory impairment in male rats. METHODS: Adult male Wistar rats were intracerebroventricularly (icv) infused with STZ (750 ug) on d 1 and d 3, and a passive avoidance task was assessed 2 weeks after the first injection of STZ. Castration surgery was performed in another group of rats, and the passive avoidance task was assessed 4 weeks after the operation. Testosterone (1 mg.kg(-1).d(-1), sc), the androgen receptor antagonist flutamide (10 mg.kg(-1).d(-1), ip), the estrogen receptor antagonist tamoxifen (1 mg.kg(-1).d(-1), ip) or the aromatase inhibitor letrozole (4 mg.kg(-1).d(-1), ip) were administered for 6 d after the first injection of STZ. RESULTS: STZ administration and castration markedly decreased both STL1 (the short memory) and STL2 (the long memory) in passive avoidance tests. Testosterone replacement almost restored the STL1 and STL2 in castrated rats, and significantly prolonged the STL1 and STL2 in STZ-treated rats. Administration of flutamide, letrozole or tamoxifen significantly impaired the memory in intact rats, and significantly attenuated the testosterone replacement in improving STZ- and castration-induced memory impairment. CONCLUSION: Testosterone administration ameliorates STZ- and castration-induced memory impairment in male Wistar rats.
24902786	0	12	Testosterone	Chemical	D013739
24902786	25	39	streptozotocin	Chemical	D013311
24902786	48	65	memory impairment	Disease	D008569
24902786	109	121	testosterone	Chemical	D013739
24902786	125	139	streptozotocin	Chemical	D013311
24902786	141	144	STZ	Chemical	D013311
24902786	154	171	memory impairment	Disease	D008569
24902786	268	271	STZ	Chemical	D013311
24902786	376	379	STZ	Chemical	D013311
24902786	513	525	Testosterone	Chemical	D013739
24902786	555	563	androgen	Chemical	D000728
24902786	584	593	flutamide	Chemical	D005485
24902786	624	632	estrogen	Chemical	D004967
24902786	653	662	tamoxifen	Chemical	D013629
24902786	714	723	letrozole	Chemical	C067431
24902786	803	806	STZ	Chemical	D013311
24902786	817	820	STZ	Chemical	D013311
24902786	954	966	Testosterone	Chemical	D013739
24902786	1081	1084	STZ	Chemical	D013311
24902786	1117	1126	flutamide	Chemical	D005485
24902786	1128	1137	letrozole	Chemical	C067431
24902786	1141	1150	tamoxifen	Chemical	D013629
24902786	1165	1184	impaired the memory	Disease	D008569
24902786	1234	1246	testosterone	Chemical	D013739
24902786	1272	1275	STZ	Chemical	D013311
24902786	1300	1317	memory impairment	Disease	D008569
24902786	1331	1343	Testosterone	Chemical	D013739
24902786	1371	1374	STZ	Chemical	D013311
24902786	1399	1416	memory impairment	Disease	D008569
24902786	CID	D013311	D008569
24902786	CID	D005485	D008569
24902786	CID	C067431	D008569
24902786	CID	D013629	D008569

24911645|t|Behavioral and neurochemical studies in mice pretreated with garcinielliptone FC in pilocarpine-induced seizures.
24911645|a|Garcinielliptone FC (GFC) isolated from hexanic fraction seed extract of species Platonia insignis Mart. It is widely used in folk medicine to treat skin diseases in both humans and animals as well as the seed decoction has been used to treat diarrheas and inflammatory diseases. However, there is no research on GFC effects in the central nervous system of rodents. The present study aimed to evaluate the GFC effects at doses of 25, 50 or 75 mg/kg on seizure parameters to determine their anticonvulsant activity and its effects on amino acid (r-aminobutyric acid (GABA), glutamine, aspartate and glutathione) levels as well as on acetylcholinesterase (AChE) activity in mice hippocampus after seizures. GFC produced an increased latency to first seizure, at doses 25mg/kg (20.12 + 2.20 min), 50mg/kg (20.95 + 2.21 min) or 75 mg/kg (23.43 + 1.99 min) when compared with seized mice. In addition, GABA content of mice hippocampus treated with GFC75 plus P400 showed an increase of 46.90% when compared with seized mice. In aspartate, glutamine and glutamate levels detected a decrease of 5.21%, 13.55% and 21.80%, respectively in mice hippocampus treated with GFC75 plus P400 when compared with seized mice. Hippocampus mice treated with GFC75 plus P400 showed an increase in AChE activity (63.30%) when compared with seized mice. The results indicate that GFC can exert anticonvulsant activity and reduce the frequency of installation of pilocarpine-induced status epilepticus, as demonstrated by increase in latency to first seizure and decrease in mortality rate of animals. In conclusion, our data suggest that GFC may influence in epileptogenesis and promote anticonvulsant actions in pilocarpine model by modulating the GABA and glutamate contents and of AChE activity in seized mice hippocampus. This compound may be useful to produce neuronal protection and it can be considered as an anticonvulsant agent.
24911645	61	80	garcinielliptone FC	Chemical	C573355
24911645	84	95	pilocarpine	Chemical	D010862
24911645	104	112	seizures	Disease	D012640
24911645	114	133	Garcinielliptone FC	Chemical	C573355
24911645	135	138	GFC	Chemical	C573355
24911645	263	276	skin diseases	Disease	D012871
24911645	357	366	diarrheas	Disease	D003967
24911645	371	392	inflammatory diseases	Disease	D007249
24911645	427	430	GFC	Chemical	C573355
24911645	521	524	GFC	Chemical	C573355
24911645	567	574	seizure	Disease	D012640
24911645	648	658	amino acid	Chemical	D000596
24911645	660	679	r-aminobutyric acid	Chemical	D005680
24911645	681	685	GABA	Chemical	D005680
24911645	688	697	glutamine	Chemical	D018698
24911645	699	708	aspartate	Chemical	D001224
24911645	713	724	glutathione	Chemical	D005978
24911645	810	818	seizures	Disease	D012640
24911645	820	823	GFC	Chemical	C573355
24911645	863	870	seizure	Disease	D012640
24911645	1012	1016	GABA	Chemical	D005680
24911645	1138	1147	aspartate	Chemical	D001224
24911645	1149	1158	glutamine	Chemical	D018698
24911645	1163	1172	glutamate	Chemical	D018698
24911645	1472	1475	GFC	Chemical	C573355
24911645	1554	1565	pilocarpine	Chemical	D010862
24911645	1574	1592	status epilepticus	Disease	D013226
24911645	1642	1649	seizure	Disease	D012640
24911645	1730	1733	GFC	Chemical	C573355
24911645	1805	1816	pilocarpine	Chemical	D010862
24911645	1841	1845	GABA	Chemical	D005680
24911645	1850	1859	glutamate	Chemical	D018698
24911645	CID	D010862	D012640
24911645	CID	D010862	D013226

24923469|t|Standard operating procedures for antibiotic therapy and the occurrence of acute kidney injury: a prospective, clinical, non-interventional, observational study.
24923469|a|INTRODUCTION: Acute kidney injury (AKI) occurs in 7% of hospitalized and 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures (SOP)) for potentially nephrotoxic antibiotics and the occurrence of AKI. METHODS: This study was carried out as a prospective, clinical, non-interventional, observational study. Data collection was performed over a total of 170 days in three ICUs at Charite - Universitaetsmedizin Berlin. A total of 675 patients were included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin; were >18 years; and treated in the ICU for >24 hours. Patients with an adherence to SOP >70% were classified into the high adherence group (HAG) and patients with an adherence of <70% into the low adherence group (LAG). AKI was defined according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective expert audit. Development of AKI was compared between groups with exact Chi2-test and multivariate logistic regression analysis (two-sided P <0.05). RESULTS: LAG consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P = 0.039). CONCLUSION: Low adherence to SOPs for potentially nephrotoxic antibiotics was associated with a higher occurrence of AKI. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54598675. Registered 17 August 2007.
24923469	75	94	acute kidney injury	Disease	D058186
24923469	176	195	Acute kidney injury	Disease	D058186
24923469	197	200	AKI	Disease	D058186
24923469	498	509	nephrotoxic	Disease	D007674
24923469	544	547	AKI	Disease	D058186
24923469	834	844	vancomycin	Chemical	D014640
24923469	846	856	gentamicin	Chemical	D005839
24923469	861	871	tobramycin	Chemical	D014031
24923469	1093	1096	AKI	Disease	D058186
24923469	1216	1219	AKI	Disease	D058186
24923469	1410	1413	AKI	Disease	D058186
24923469	1574	1584	infections	Disease	D007239
24923469	1669	1672	AKI	Disease	D058186
24923469	1794	1805	nephrotoxic	Disease	D007674
24923469	1861	1864	AKI	Disease	D058186
24923469	CID	D014031	D058186
24923469	CID	D014640	D058186
24923469	CID	D005839	D058186

24927617|t|Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin.
24927617|a|A 46-year old man with a chronic hepatitis C virus infection received triple therapy with ribavirin, pegylated interferon and telaprevir. The patient also received simvastatin. One month after starting the antiviral therapy, the patient was admitted to the hospital because he developed rhabdomyolysis. At admission simvastatin and all antiviral drugs were discontinued because toxicity due to a drug-drug interaction was suspected. The creatine kinase peaked at 62,246 IU/L and the patient was treated with intravenous normal saline. The patient's renal function remained unaffected. Fourteen days after hospitalization, creatine kinase level had returned to 230 IU/L and the patient was discharged. Telaprevir was considered the probable causative agent of an interaction with simvastatin according to the Drug Interaction Probability Scale. The interaction is due to inhibition of CYP3A4-mediated simvastatin clearance. Simvastatin plasma concentration increased 30 times in this patient and statin induced muscle toxicity is related to the concentration of the statin in blood. In conclusion, with this case we illustrate that telaprevir as well as statins are susceptible to clinical relevant drug-drug interactions.
24927617	0	14	Rhabdomyolysis	Disease	D012206
24927617	20	46	hepatitis C virus infected	Disease	D006526
24927617	68	78	telaprevir	Chemical	C486464
24927617	83	94	simvastatin	Chemical	D019821
24927617	129	156	hepatitis C virus infection	Disease	D006526
24927617	186	195	ribavirin	Chemical	D012254
24927617	197	217	pegylated interferon	Chemical	C417083
24927617	222	232	telaprevir	Chemical	C486464
24927617	260	271	simvastatin	Chemical	D019821
24927617	383	397	rhabdomyolysis	Disease	D012206
24927617	412	423	simvastatin	Chemical	D019821
24927617	474	482	toxicity	Disease	D064420
24927617	533	541	creatine	Chemical	D003401
24927617	718	726	creatine	Chemical	D003401
24927617	797	807	Telaprevir	Chemical	C486464
24927617	875	886	simvastatin	Chemical	D019821
24927617	996	1007	simvastatin	Chemical	D019821
24927617	1019	1030	Simvastatin	Chemical	D019821
24927617	1091	1097	statin	Chemical	D019821
24927617	1106	1121	muscle toxicity	Disease	D009135
24927617	1161	1167	statin	Chemical	D019821
24927617	1227	1237	telaprevir	Chemical	C486464
24927617	1249	1256	statins	Chemical	D019821
24927617	CID	C486464	D012206
24927617	CID	D019821	D012206
24927617	CID	D019821	D009135

24928523|t|Combination of bortezomib, thalidomide, and dexamethasone (VTD) as a consolidation therapy after autologous stem cell transplantation for symptomatic multiple myeloma in Japanese patients.
24928523|a|Consolidation therapy for patients with multiple myeloma (MM) has been widely adopted to improve treatment response following autologous stem cell transplantation. In this study, we retrospectively analyzed the safety and efficacy of combination regimen of bortezomib, thalidomide, and dexamethasone (VTD) as consolidation therapy in 24 Japanese patients with newly diagnosed MM. VTD consisted of bortezomib at a dose of 1.3 mg/m(2) and dexamethasone at a dose of 40 mg/day on days 1, 8, 15, and 22 of a 35-day cycle, with daily oral thalidomide at a dose of 100 mg/day. Grade 3-4 neutropenia and thrombocytopenia were documented in four and three patients (17 and 13 %), respectively, but drug dose reduction due to cytopenia was not required in any case. Peripheral neuropathy was common (63 %), but severe grade 3-4 peripheral neuropathy was not observed. Very good partial response or better response (>VGPR) rates before and after consolidation therapy were 54 and 79 %, respectively. Patients had a significant probability of improving from <VGPR before consolidation therapy to >VGPR after consolidation therapy (p = 0.041). The VTD regimen may be safe and effective as a consolidation therapy in the treatment of MM in Japanese population.
24928523	15	25	bortezomib	Chemical	C400082
24928523	27	38	thalidomide	Chemical	D013792
24928523	44	57	dexamethasone	Chemical	D003907
24928523	150	166	multiple myeloma	Disease	D009101
24928523	229	245	multiple myeloma	Disease	D009101
24928523	247	249	MM	Disease	D009101
24928523	446	456	bortezomib	Chemical	C400082
24928523	458	469	thalidomide	Chemical	D013792
24928523	475	488	dexamethasone	Chemical	D003907
24928523	565	567	MM	Disease	D009101
24928523	586	596	bortezomib	Chemical	C400082
24928523	626	639	dexamethasone	Chemical	D003907
24928523	723	734	thalidomide	Chemical	D013792
24928523	770	781	neutropenia	Disease	D009503
24928523	786	802	thrombocytopenia	Disease	D013921
24928523	906	915	cytopenia	Disease	D006402
24928523	946	967	Peripheral neuropathy	Disease	D010523
24928523	1008	1029	peripheral neuropathy	Disease	D010523
24928523	CID	D003907	D010523
24928523	CID	D013792	D010523
24928523	CID	C400082	D009503
24928523	CID	D013792	D013921
24928523	CID	C400082	D013921
24928523	CID	D013792	D009503
24928523	CID	C400082	D010523
24928523	CID	D003907	D013921
24928523	CID	D003907	D009503

24971338|t|Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat: focus on serum, urine, gene, and protein renal expression biomarkers.
24971338|a|Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n = 6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-b, NF- kb, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF- b and IL-7, TBARs clearance, and kidney TGF-b and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL.
24971338	14	23	sirolimus	Chemical	D020123
24971338	36	48	cyclosporine	Chemical	D016572
24971338	57	68	nephropathy	Disease	D007674
24971338	180	193	cyclosporin A	Chemical	D016572
24971338	195	198	CsA	Chemical	D016572
24971338	203	212	sirolimus	Chemical	D020123
24971338	214	217	SRL	Chemical	D020123
24971338	291	294	CsA	Chemical	D016572
24971338	303	314	nephropathy	Disease	D007674
24971338	467	470	CsA	Chemical	D016572
24971338	474	477	SRL	Chemical	D020123
24971338	569	572	CsA	Chemical	D016572
24971338	574	577	SRL	Chemical	D020123
24971338	595	598	CsA	Chemical	D016572
24971338	623	626	SRL	Chemical	D020123
24971338	751	764	Renal lesions	Disease	D007674
24971338	782	793	hematoxylin	Chemical	D006416
24971338	798	803	eosin	Chemical	D004801
24971338	858	861	SRL	Chemical	D020123
24971338	885	896	proteinuria	Disease	D011507
24971338	949	965	renal impairment	Disease	D007674
24971338	973	976	CsA	Chemical	D016572
24971338	1019	1033	kidney lesions	Disease	D007674
24971338	1135	1138	CsA	Chemical	D016572
24971338	1159	1171	renal damage	Disease	D007674
24971338	1325	1328	SRL	Chemical	D020123
24971338	1339	1342	CsA	Chemical	D016572
24971338	1351	1363	renal damage	Disease	D007674
24971338	1471	1474	CsA	Chemical	D016572
24971338	1490	1493	SRL	Chemical	D020123
24971338	CID	D016572	D007674
24971338	CID	D020123	D011507

24975837|t|Kinin B2 receptor deletion and blockage ameliorates cisplatin-induced acute renal injury.
24975837|a|Cisplatin treatment has been adopted in some chemotherapies; however, this drug can induce acute kidney injury due its ability to negatively affect renal function, augment serum levels of creatinine and urea, increase the acute tubular necrosis score and up-regulate cytokines (e.g., IL-1b and TNF-a). The kinin B2 receptor has been associated with the inflammation process, as well as the regulation of cytokine expression, and its deletion resulted in an improvement in the diabetic nephropathy status. To examine the role of the kinin B2 receptor in cisplatin-induced acute kidney injury, kinin B2 receptor knockout mice were challenged with cisplatin. Additionally, WT mice were treated with a B2 receptor antagonist after cisplatin administration. B2 receptor-deficient mice were less sensitive to this drug than the WT mice, as shown by reduced weight loss, better preservation of kidney function, down regulation of inflammatory cytokines and less acute tubular necrosis. Moreover, treatment with the kinin B2 receptor antagonist effectively reduced the levels of serum creatinine and blood urea after cisplatin administration. Thus, our data suggest that the kinin B2 receptor is involved in cisplatin-induced acute kidney injury by mediating the necrotic process and the expression of inflammatory cytokines, thus resulting in declined renal function. These results highlight the kinin B2 receptor antagonist treatment in amelioration of nephrotoxicity induced by cisplatin therapy.
24975837	52	61	cisplatin	Chemical	D002945
24975837	70	88	acute renal injury	Disease	D058186
24975837	90	99	Cisplatin	Chemical	D002945
24975837	181	200	acute kidney injury	Disease	D058186
24975837	278	288	creatinine	Chemical	D003404
24975837	293	297	urea	Chemical	D014508
24975837	312	334	acute tubular necrosis	Disease	D007683
24975837	443	455	inflammation	Disease	D007249
24975837	566	586	diabetic nephropathy	Disease	D003928
24975837	643	652	cisplatin	Chemical	D002945
24975837	661	680	acute kidney injury	Disease	D058186
24975837	735	744	cisplatin	Chemical	D002945
24975837	817	826	cisplatin	Chemical	D002945
24975837	941	952	weight loss	Disease	D015431
24975837	1045	1067	acute tubular necrosis	Disease	D007683
24975837	1167	1177	creatinine	Chemical	D003404
24975837	1188	1192	urea	Chemical	D014508
24975837	1199	1208	cisplatin	Chemical	D002945
24975837	1290	1299	cisplatin	Chemical	D002945
24975837	1308	1327	acute kidney injury	Disease	D058186
24975837	1345	1353	necrotic	Disease	D009336
24975837	1537	1551	nephrotoxicity	Disease	D007674
24975837	1563	1572	cisplatin	Chemical	D002945
24975837	CID	D002945	D007683
24975837	CID	D002945	D058186
24975837	CID	D002945	D015431

24999722|t|Safety and efficacy of fluocinolone acetonide intravitreal implant (0.59 mg) in birdshot retinochoroidopathy.
24999722|a|PURPOSE: To report the treatment outcomes of the fluocinolone acetonide intravitreal implant (0.59 mg) in patients with birdshot retinochoroidopathy whose disease is refractory or intolerant to conventional immunomodulatory therapy. METHODS: A retrospective case series involving 11 birdshot retinochoroidopathy patients (11 eyes). Eleven patients (11 eyes) underwent surgery for fluocinolone acetonide implant (0.59 mg). Treatment outcomes of interest were noted at baseline, before fluocinolone acetonide implant, and then at 6 months, 1 year, 2 years, 3 years, and beyond 3 years. Disease activity markers, including signs of ocular inflammation, evidence of retinal vasculitis, Swedish interactive threshold algorithm-short wavelength automated perimetry Humphrey visual field analysis, electroretinographic parameters, and optical coherence tomography were recorded. Data on occurrence of cataract and raised intraocular pressure were collected in all eyes. RESULTS: Intraocular inflammation was present in 54.5, 9.9, 11.1, and 0% of patients at baseline, 6 months, 1 year, 2 years, 3 years, and beyond 3 years after receiving the implant, respectively. Active vasculitis was noted in 36.3% patients at baseline and 0% at 3 years of follow-up. More than 20% (47.61-67.2%) reduction in central retinal thickness was noted in all patients with cystoid macular edema at 6 months, 1 year, 2 years, and 3 years postimplant. At baseline, 54.5% patients were on immunomodulatory agents. This percentage decreased to 45.45, 44.4, and 14.28% at 1 year, 2 years, and 3 years postimplant, respectively. Adverse events included increased intraocular pressure (54.5%) and cataract formation (100%). CONCLUSION: The data suggest that fluocinolone acetonide implant (0.59 mg) helps to control inflammation in otherwise treatment-refractory cases of birdshot retinochoroidopathy. It is associated with significant side effects of cataract and ocular hypertension requiring treatment.
24999722	23	45	fluocinolone acetonide	Chemical	D005446
24999722	80	108	birdshot retinochoroidopathy	Disease	C537630
24999722	159	181	fluocinolone acetonide	Chemical	D005446
24999722	230	258	birdshot retinochoroidopathy	Disease	C537630
24999722	393	421	birdshot retinochoroidopathy	Disease	C537630
24999722	490	512	fluocinolone acetonide	Chemical	D005446
24999722	594	616	fluocinolone acetonide	Chemical	D005446
24999722	746	758	inflammation	Disease	D007249
24999722	772	790	retinal vasculitis	Disease	D031300
24999722	1004	1012	cataract	Disease	D002386
24999722	1017	1044	raised intraocular pressure	Disease	D009798
24999722	1094	1106	inflammation	Disease	D007249
24999722	1276	1286	vasculitis	Disease	D014657
24999722	1457	1478	cystoid macular edema	Disease	D008269
24999722	1731	1761	increased intraocular pressure	Disease	D009798
24999722	1774	1782	cataract	Disease	D002386
24999722	1835	1857	fluocinolone acetonide	Chemical	D005446
24999722	1893	1905	inflammation	Disease	D007249
24999722	1949	1977	birdshot retinochoroidopathy	Disease	C537630
24999722	2029	2037	cataract	Disease	D002386
24999722	2042	2061	ocular hypertension	Disease	D009798
24999722	CID	D005446	D009798
24999722	CID	D005446	D002386

25006369|t|Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.
25006369|a|BACKGROUND: Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. METHODS: This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. RESULTS: The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). CONCLUSIONS: Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.
25006369	30	40	rocuronium	Chemical	C061870
25006369	53	66	fasciculation	Disease	D005207
25006369	71	78	myalgia	Disease	D063806
25006369	89	104	succinylcholine	Chemical	D013390
25006369	133	148	Succinylcholine	Chemical	D013390
25006369	203	223	muscle fasciculation	Disease	D005207
25006369	228	235	myalgia	Disease	D063806
25006369	286	296	rocuronium	Chemical	C061870
25006369	308	323	succinylcholine	Chemical	D013390
25006369	332	345	fasciculation	Disease	D005207
25006369	350	357	myalgia	Disease	D063806
25006369	389	399	rocuronium	Chemical	C061870
25006369	434	449	succinylcholine	Chemical	D013390
25006369	659	669	rocuronium	Chemical	C061870
25006369	894	909	succinylcholine	Chemical	D013390
25006369	1008	1022	fasciculations	Disease	D005207
25006369	1030	1037	myalgia	Disease	D063806
25006369	1125	1145	muscle fasciculation	Disease	D005207
25006369	1221	1231	rocuronium	Chemical	C061870
25006369	1254	1261	myalgia	Disease	D063806
25006369	1339	1349	rocuronium	Chemical	C061870
25006369	1412	1427	succinylcholine	Chemical	D013390
25006369	1505	1515	rocuronium	Chemical	C061870
25006369	1574	1584	rocuronium	Chemical	C061870
25006369	1665	1678	fasciculation	Disease	D005207
25006369	1683	1690	myalgia	Disease	D063806
25006369	CID	D013390	D005207
25006369	CID	D013390	D063806

25006961|t|Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.
25006961|a|Lithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in  40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCa KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCa KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCa KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCa KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCa KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCa KO mice. Our data show that ablation of PKCa preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy.
25006961	32	39	lithium	Chemical	D008094
25006961	48	78	nephrogenic diabetes insipidus	Disease	D018500
25006961	80	87	Lithium	Chemical	D008094
25006961	125	155	nephrogenic diabetes insipidus	Disease	D018500
25006961	157	160	NDI	Disease	D018500
25006961	244	251	lithium	Chemical	D008094
25006961	275	279	cAMP	Chemical	D000242
25006961	313	317	urea	Chemical	D014508
25006961	511	518	lithium	Chemical	D008094
25006961	527	535	polyuria	Disease	D011141
25006961	628	635	lithium	Chemical	D008094
25006961	1061	1068	lithium	Chemical	D008094
25006961	1082	1089	Lithium	Chemical	D008094
25006961	1254	1261	lithium	Chemical	D008094
25006961	1391	1397	sodium	Chemical	D012964
25006961	1399	1408	potassium	Chemical	D011188
25006961	1413	1420	calcium	Chemical	D002118
25006961	1438	1445	lithium	Chemical	D008094
25006961	1464	1471	lithium	Chemical	D008094
25006961	1590	1597	lithium	Chemical	D008094
25006961	1606	1609	NDI	Disease	D018500
25006961	1654	1662	polyuria	Disease	D011141
25006961	1679	1686	lithium	Chemical	D008094
25006961	CID	D008094	D011141
25006961	CID	D008094	D018500

25031906|t|Is Dysguesia Going to be a Rare or a Common Side-effect of Amlodipine?
25031906|a|A very rare side-effect of amlodipine is dysguesia. A review of the literature produced only one case. We report a case about a female with essential hypertension on drug treatment with amlodipine developed loss of taste sensation. Condition moderately improved on stoppage of the drug for 25 days. We conclude that amlodipine can cause dysguesia. Here, we describe the clinical presentation and review the relevant literature on amlodipine and dysguesia.
25031906	3	12	Dysguesia	Disease	D004408
25031906	59	69	Amlodipine	Chemical	D017311
25031906	98	108	amlodipine	Chemical	D017311
25031906	112	121	dysguesia	Disease	D004408
25031906	221	233	hypertension	Disease	D006973
25031906	257	267	amlodipine	Chemical	D017311
25031906	278	301	loss of taste sensation	Disease	D012678
25031906	387	397	amlodipine	Chemical	D017311
25031906	408	417	dysguesia	Disease	D004408
25031906	501	511	amlodipine	Chemical	D017311
25031906	516	525	dysguesia	Disease	D004408
25031906	CID	D017311	D004408

25041770|t|Rhabdomyolysis in association with simvastatin and dosage increment in clarithromycin.
25041770|a|Clarithromycin is the most documented cytochrome P450 3A4 (CYP3A4) inhibitor to cause an adverse interaction with simvastatin. This particular case is of interest as rhabdomyolysis only occurred after an increase in the dose of clarithromycin. The patient developed raised cardiac biomarkers without any obvious cardiac issues, a phenomenon that has been linked to rhabdomyolysis previously. To date, there has been no reported effect of rhabdomyolysis on the structure and function of cardiac muscle. Clinicians need to be aware of prescribing concomitant medications that increase the risk of myopathy or inhibit the CYP3A4 enzyme. Our case suggests that troponin elevation could be associated with statin induced rhabdomyolysis, which may warrant further studies.
25041770	0	14	Rhabdomyolysis	Disease	D012206
25041770	35	46	simvastatin	Chemical	D019821
25041770	71	85	clarithromycin	Chemical	D017291
25041770	87	101	Clarithromycin	Chemical	D017291
25041770	201	212	simvastatin	Chemical	D019821
25041770	253	267	rhabdomyolysis	Disease	D012206
25041770	315	329	clarithromycin	Chemical	D017291
25041770	452	466	rhabdomyolysis	Disease	D012206
25041770	525	539	rhabdomyolysis	Disease	D012206
25041770	682	690	myopathy	Disease	D009135
25041770	788	794	statin	Chemical	D019821
25041770	803	817	rhabdomyolysis	Disease	D012206
25041770	CID	D017291	D012206
25041770	CID	D019821	D012206

25054547|t|Characterization of a novel BCHE "silent" allele: point mutation (p.Val204Asp) causes loss of activity and prolonged apnea with suxamethonium.
25054547|a|Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a "silent" phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 uM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD) simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels.
25054547	117	122	apnea	Disease	D001049
25054547	128	141	suxamethonium	Chemical	D013390
25054547	143	175	Butyrylcholinesterase deficiency	Disease	C537417
25054547	206	211	apnea	Disease	D001049
25054547	247	260	suxamethonium	Chemical	D013390
25054547	264	274	mivacurium	Chemical	C049430
25054547	405	418	suxamethonium	Chemical	D013390
25054547	725	743	butyrylthiocholine	Chemical	D002092
25054547	745	748	BTC	Chemical	D002092
25054547	754	768	benzoylcholine	Chemical	D001588
25054547	784	793	dibucaine	Chemical	D003992
25054547	798	806	fluoride	Chemical	D005459
25054547	1222	1225	BTC	Chemical	D002092
25054547	1286	1289	BTC	Chemical	D002092
25054547	1409	1422	suxamethonium	Chemical	D013390
25054547	1535	1543	hydrogen	Chemical	D006859
25054547	CID	C049430	D001049
25054547	CID	D013390	D001049
25054547	CID	C049430	C537417
25054547	CID	D013390	C537417

25071004|t|Delayed anemia after treatment with injectable artesunate in the Democratic Republic of the Congo: a manageable issue.
25071004|a|Cases of delayed hemolytic anemia have been described after treatment with injectable artesunate, the current World Health Organization (WHO)-recommended first-line drug for the treatment of severe malaria. A total of 350 patients (215 [61.4%] < 5 years of age and 135 [38.6%] > 5 years of age) were followed-up after treatment with injectable artesunate for severe malaria in hospitals and health centers of the Democratic Republic of the Congo. Complete series of hemoglobin (Hb) measurements were available for 201 patients. A decrease in Hb levels between 2 and 5 g/dL was detected in 23 (11.4%) patients during the follow-up period. For five patients, Hb levels decreased below 5 g/dL during at least one follow-up visit. All cases of delayed anemia were clinically manageable and resolved within one month.
25071004	8	14	anemia	Disease	D000740
25071004	47	57	artesunate	Chemical	C039726
25071004	136	152	hemolytic anemia	Disease	D000743
25071004	205	215	artesunate	Chemical	C039726
25071004	317	324	malaria	Disease	D008288
25071004	463	473	artesunate	Chemical	C039726
25071004	485	492	malaria	Disease	D008288
25071004	867	873	anemia	Disease	D000740
25071004	CID	C039726	D000743

25080425|t|Regulation of signal transducer and activator of transcription 3 and apoptotic pathways by betaine attenuates isoproterenol-induced acute myocardial injury in rats.
25080425|a|The present study was designed to investigate the cardioprotective effects of betaine on acute myocardial ischemia induced experimentally in rats focusing on regulation of signal transducer and activator of transcription 3 (STAT3) and apoptotic pathways as the potential mechanism underlying the drug effect. Male Sprague Dawley rats were treated with betaine (100, 200, and 400 mg/kg) orally for 40 days. Acute myocardial ischemic injury was induced in rats by subcutaneous injection of isoproterenol (85 mg/kg), for two consecutive days. Serum cardiac marker enzyme, histopathological variables and expression of protein levels were analyzed. Oral administration of betaine (200 and 400 mg/kg) significantly reduced the level of cardiac marker enzyme in the serum and prevented left ventricular remodeling. Western blot analysis showed that isoproterenol-induced phosphorylation of STAT3 was maintained or further enhanced by betaine treatment in myocardium. Furthermore, betaine (200 and 400 mg/kg) treatment increased the ventricular expression of Bcl-2 and reduced the level of Bax, therefore causing a significant increase in the ratio of Bcl-2/Bax. The protective role of betaine on myocardial damage was further confirmed by histopathological examination. In summary, our results showed that betaine pretreatment attenuated isoproterenol-induced acute myocardial ischemia via the regulation of STAT3 and apoptotic pathways.
25080425	91	98	betaine	Chemical	D001622
25080425	110	123	isoproterenol	Chemical	D007545
25080425	138	155	myocardial injury	Disease	D009202
25080425	243	250	betaine	Chemical	D001622
25080425	260	279	myocardial ischemia	Disease	D017202
25080425	517	524	betaine	Chemical	D001622
25080425	577	603	myocardial ischemic injury	Disease	D017202
25080425	653	666	isoproterenol	Chemical	D007545
25080425	833	840	betaine	Chemical	D001622
25080425	950	972	ventricular remodeling	Disease	D020257
25080425	1008	1021	isoproterenol	Chemical	D007545
25080425	1093	1100	betaine	Chemical	D001622
25080425	1139	1146	betaine	Chemical	D001622
25080425	1344	1351	betaine	Chemical	D001622
25080425	1355	1372	myocardial damage	Disease	D009202
25080425	1465	1472	betaine	Chemical	D001622
25080425	1497	1510	isoproterenol	Chemical	D007545
25080425	1525	1544	myocardial ischemia	Disease	D017202
25080425	CID	D007545	D017202
25080425	CID	D007545	D020257

25084821|t|Quetiapine-induced neutropenia in a bipolar patient with hepatocellular carcinoma.
25084821|a|OBJECTIVE: Quetiapine is a dibenzothiazepine derivative, similar to clozapine, which has the highest risk of causing blood dyscrasias, especially neutropenia. There are some case reports about this side effect of quetiapine, but possible risk factors are seldom discussed and identified. A case of a patient with hepatocellular carcinoma that developed neutropenia after treatment with quetiapine is described here. CASE REPORT: A 62-year-old Taiwanese widow with bipolar disorder was diagnosed with hepatocellular carcinoma at age 60. She developed leucopenia after being treated with quetiapine. After quetiapine was discontinued, her white blood cell count returned to normal. CONCLUSIONS: Although neutropenia is not a common side effect of quetiapine, physicians should be cautious about its presentation and associated risk factors. Hepatic dysfunction may be one of the possible risk factors, and concomitant fever may be a diagnostic marker for adverse reaction to quetiapine.
25084821	0	10	Quetiapine	Chemical	C069541
25084821	19	30	neutropenia	Disease	D009503
25084821	36	43	bipolar	Disease	D001714
25084821	57	81	hepatocellular carcinoma	Disease	D006528
25084821	94	104	Quetiapine	Chemical	C069541
25084821	151	160	clozapine	Chemical	D003024
25084821	200	216	blood dyscrasias	Disease	D006402
25084821	229	240	neutropenia	Disease	D009503
25084821	296	306	quetiapine	Chemical	C069541
25084821	396	420	hepatocellular carcinoma	Disease	D006528
25084821	436	447	neutropenia	Disease	D009503
25084821	469	479	quetiapine	Chemical	C069541
25084821	547	563	bipolar disorder	Disease	D001714
25084821	583	607	hepatocellular carcinoma	Disease	D006528
25084821	633	643	leucopenia	Disease	D007970
25084821	669	679	quetiapine	Chemical	C069541
25084821	687	697	quetiapine	Chemical	C069541
25084821	785	796	neutropenia	Disease	D009503
25084821	828	838	quetiapine	Chemical	C069541
25084821	922	941	Hepatic dysfunction	Disease	D008107
25084821	999	1004	fever	Disease	D005334
25084821	1056	1066	quetiapine	Chemical	C069541
25084821	CID	C069541	D009503
25084821	CID	C069541	D007970
25084821	CID	C069541	D005334

25096313|t|Lateral antebrachial cutaneous neuropathy after steroid injection at lateral epicondyle.
25096313|a|BACKGROUND AND OBJECTIVES: This report aimed to present a case of lateral antebrachial cutaneous neuropathy (LACNP) that occurred after a steroid injection in the lateral epicondyle to treat lateral epicondylitis in a 40-year-old woman. MATERIAL AND METHOD: A 40-year-old woman presented with decreased sensation and paresthesia over her right lateral forearm; the paresthesia had occurred after a steroid injection in the right lateral epicondyle 3 months before. Her sensation of light touch and pain was diminished over the lateral side of the right forearm and wrist area. RESULTS: The sensory action potential amplitude of the right lateral antebrachial cutaneous nerve (LACN) (6.2 uV) was lower than that of the left (13.1 uV). The difference of amplitude between both sides was significant because there was more than a 50% reduction. She was diagnosed with right LACNP (mainly axonal involvement) on the basis of the clinical manifestation and the electrodiagnostic findings. Her symptoms improved through physical therapy but persisted to some degree. CONCLUSION: This report describes the case of a woman with LACNP that developed after a steroid injection for the treatment of lateral epicondylitis. An electrodiagnostic study, including a nerve conduction study of the LACN, was helpful to diagnose right LACNP and to find the passage of the LACN on the lateral epicondyle.
25096313	31	41	neuropathy	Disease	D009422
25096313	48	55	steroid	Chemical	D013256
25096313	186	196	neuropathy	Disease	D009422
25096313	227	234	steroid	Chemical	D013256
25096313	280	301	lateral epicondylitis	Disease	D013716
25096313	406	417	paresthesia	Disease	D010292
25096313	454	465	paresthesia	Disease	D010292
25096313	487	494	steroid	Chemical	D013256
25096313	587	591	pain	Disease	D010146
25096313	1238	1245	steroid	Chemical	D013256
25096313	1277	1298	lateral epicondylitis	Disease	D013716
25096313	CID	D013256	D010292

25119790|t|Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.
25119790|a|The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl b-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.
25119790	0	8	Curcumin	Chemical	D003474
25119790	18	25	maleate	Chemical	C030272
25119790	34	48	nephrotoxicity	Disease	D007674
25119790	119	125	oxygen	Chemical	D010100
25119790	236	244	curcumin	Chemical	D003474
25119790	284	296	renal injury	Disease	D007674
25119790	308	315	maleate	Chemical	C030272
25119790	339	350	proteinuria	Disease	D011507
25119790	410	417	maleate	Chemical	C030272
25119790	439	446	Maleate	Chemical	C030272
25119790	455	467	renal injury	Disease	D007674
25119790	562	569	glucose	Chemical	D005947
25119790	571	577	sodium	Chemical	D012964
25119790	685	698	kidney injury	Disease	D007674
25119790	782	790	necrosis	Disease	D009336
25119790	1086	1093	Maleate	Chemical	C030272
25119790	1127	1133	oxygen	Chemical	D010100
25119790	1201	1208	maleate	Chemical	C030272
25119790	1227	1233	oxygen	Chemical	D010100
25119790	1249	1252	ADP	Chemical	D000244
25119790	1329	1335	malate	Chemical	C030298
25119790	1336	1345	glutamate	Chemical	D018698
25119790	1483	1491	curcumin	Chemical	D003474
25119790	1514	1522	curcumin	Chemical	D003474
25119790	1552	1559	maleate	Chemical	C030272
25119790	1568	1579	nephropathy	Disease	D007674
25119790	1716	1722	oxygen	Chemical	D010100
25119790	CID	C030272	D011507
25119790	CID	C030272	D009336
25119790	CID	C030272	D007674

25907210|t|Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis.
25907210|a|OBJECTIVE: Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS. METHODS: Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993-1997) and follow-up (1998-2005); cancer incidence was assessed through 2010(North Carolina)/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with >10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure). RESULTS: We observed elevated lung cancer risks (N=283) among applicators with the greatest number of LT (RR=1.60; 95% CI 1.11 to 2.31; Ptrend=0.02) and IW days of diazinon use (RR=1.41; 95% CI 0.98 to 2.04; Ptrend=0.08). Kidney cancer (N=94) risks were non-significantly elevated (RRLT days=1.77; 95% CI 0.90 to 3.51; Ptrend=0.09; RRIW days 1.37; 95% CI 0.64 to 2.92; Ptrend=0.50), as were risks for aggressive prostate cancer (N=656). CONCLUSIONS: Our updated evaluation of diazinon provides additional evidence of an association with lung cancer risk. Newly identified links to kidney cancer and associations with aggressive prostate cancer require further evaluation.
25907210	19	26	tumours	Disease	D009369
25907210	70	85	organophosphate	Chemical	D010755
25907210	98	106	diazinon	Chemical	D003976
25907210	173	181	Diazinon	Chemical	D003976
25907210	192	207	organophosphate	Chemical	D010755
25907210	278	289	lung cancer	Disease	D008175
25907210	389	397	diazinon	Chemical	D003976
25907210	409	415	cancer	Disease	D009369
25907210	438	446	diazinon	Chemical	D003976
25907210	460	466	cancer	Disease	D009369
25907210	507	513	tumour	Disease	D009369
25907210	612	620	diazinon	Chemical	D003976
25907210	677	683	cancer	Disease	D009369
25907210	921	927	cancer	Disease	D009369
25907210	1120	1131	lung cancer	Disease	D008175
25907210	1254	1262	diazinon	Chemical	D003976
25907210	1312	1325	Kidney cancer	Disease	D007680
25907210	1502	1517	prostate cancer	Disease	D011471
25907210	1566	1574	diazinon	Chemical	D003976
25907210	1627	1638	lung cancer	Disease	D008175
25907210	1671	1684	kidney cancer	Disease	D007680
25907210	1718	1733	prostate cancer	Disease	D011471
25907210	CID	D003976	D008175

25951420|t|Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study.
25951420|a|OBJECTIVE: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. METHODS: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. RESULTS: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. CONCLUSIONS: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed.
25951420	16	21	Ozone	Chemical	D010126
25951420	52	71	Parkinson's Disease	Disease	D010300
25951420	173	178	ozone	Chemical	D010126
25951420	188	206	particulate matter	Chemical	D052638
25951420	212	231	Parkinson's disease	Disease	D010300
25951420	407	426	Parkinson's disease	Disease	D010300
25951420	625	644	Parkinson's disease	Disease	D010300
25951420	650	655	ozone	Chemical	D010126
25951420	707	725	particulate matter	Chemical	D052638
25951420	895	914	Parkinson's disease	Disease	D010300
25951420	CID	D052638	D010300
25951420	CID	D010126	D010300

25986755|t|Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.
25986755|a|UNASSIGNED: Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis.
25986755	78	96	glomerulosclerosis	Disease	D005921
25986755	136	144	caffeine	Chemical	D002110
25986755	214	222	caffeine	Chemical	D002110
25986755	251	282	intrauterine growth retardation	Disease	D005317
25986755	284	288	IUGR	Disease	D005317
25986755	335	339	IUGR	Disease	D005317
25986755	361	379	glomerulosclerosis	Disease	D005921
25986755	415	433	glomerulosclerosis	Disease	D005921
25986755	529	547	glomerulosclerosis	Disease	D005921
25986755	634	638	IUGR	Disease	D005317
25986755	826	844	glomerulosclerosis	Disease	D005921
25986755	856	877	interstitial fibrosis	Disease	D005355
25986755	919	929	creatinine	Chemical	D003404
25986755	955	969	angiotensin II	Chemical	D000804
25986755	1066	1080	angiotensin II	Chemical	D000804
25986755	1720	1728	tyrosine	Chemical	D014443
25986755	1821	1847	dysplasia of fetal kidneys	Disease	D007674
25986755	1859	1877	glomerulosclerosis	Disease	D005921
25986755	1995	2013	glomerulosclerosis	Disease	D005921
25986755	CID	D002110	D007674
25986755	CID	D002110	D005355
25986755	CID	D002110	D005317

26002693|t|1,3-Butadiene, CML and the t(9:22) translocation: A reality check.
26002693|a|UNASSIGNED: Epidemiological studies of 1,3-butadiene have suggest that exposures to humans are associated with chronic myeloid leukemia (CML). CML has a well-documented association with ionizing radiation, but reports of associations with chemical exposures have been questioned. Ionizing radiation is capable of inducing the requisite CML-associated t(9:22) translocation (Philadelphia chromosome) in appropriate cells in vitro but, thus far, chemicals have not shown this capacity. We have proposed that 1,3-butadiene metabolites be so tested as a reality check on the epidemiological reports. In order to conduct reliable testing in this regard, it is essential that a positive control for induction be available. We have used ionizing radiation to develop such a control. Results described here demonstrate that this agent does in fact induce pathogenic t(9:22) translocations in a human myeloid cell line in vitro, but does so at low frequencies. Conditions that will be required for studies of 1,3-butadiene are discussed.
26002693	0	13	1,3-Butadiene	Chemical	C031763
26002693	15	18	CML	Disease	D015464
26002693	106	119	1,3-butadiene	Chemical	C031763
26002693	178	202	chronic myeloid leukemia	Disease	D015464
26002693	204	207	CML	Disease	D015464
26002693	210	213	CML	Disease	D015464
26002693	403	406	CML	Disease	D015464
26002693	441	464	Philadelphia chromosome	Disease	D010677
26002693	573	586	1,3-butadiene	Chemical	C031763
26002693	1067	1080	1,3-butadiene	Chemical	C031763
26002693	CID	C031763	D010677

26033014|t|Cancer incidence and metolachlor use in the Agricultural Health Study: An update.
26033014|a|UNASSIGNED: Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-1997. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n = 5,701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors.
26033014	0	6	Cancer	Disease	D009369
26033014	21	32	metolachlor	Chemical	C051786
26033014	94	105	Metolachlor	Chemical	C051786
26033014	233	248	liver neoplasms	Disease	D008113
26033014	312	323	metolachlor	Chemical	C051786
26033014	533	539	cancer	Disease	D009369
26033014	632	643	metolachlor	Chemical	C051786
26033014	717	728	metolachlor	Chemical	C051786
26033014	787	793	cancer	Disease	D009369
26033014	835	846	metolachlor	Chemical	C051786
26033014	872	879	cancers	Disease	D009369
26033014	941	948	cancers	Disease	D009369
26033014	954	966	liver cancer	Disease	D008113
26033014	1169	1179	metolachor	Chemical	C051786
26033014	1298	1322	follicular cell lymphoma	Disease	D008224
26033014	1337	1345	lymphoma	Disease	D008223
26033014	1391	1402	lung cancer	Disease	D008175
26033014	1426	1437	metolachlor	Chemical	C051786
26033014	1533	1544	metolachlor	Chemical	C051786
26033014	1549	1561	liver cancer	Disease	D008113
26033014	1645	1660	liver neoplasms	Disease	D008113
26033014	1716	1728	liver cancer	Disease	D008113
26033014	1749	1757	lymphoma	Disease	D008223
26033014	1811	1822	metolachlor	Chemical	C051786
26033014	CID	C051786	D008224
26033014	CID	C051786	D008113

26115410|t|Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps.
26115410|a|BACKGROUND: Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. OBJECTIVES: This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. DISCUSSION: Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. CONCLUSIONS: Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes.
26115410	69	76	Arsenic	Chemical	D001151
26115410	269	286	inorganic arsenic	Chemical	D001152
26115410	288	291	iAs	Chemical	D001152
26115410	318	330	Inorganic As	Chemical	D001152
26115410	569	572	iAs	Chemical	D001152
26115410	659	665	cancer	Disease	D009369
26115410	773	779	cancer	Disease	D009369
26115410	840	843	iAs	Chemical	D001152
26115410	962	968	cancer	Disease	D009369
26115410	1058	1061	iAs	Chemical	D001152
26115410	1166	1169	iAs	Chemical	D001152
26115410	1183	1189	cancer	Disease	D009369
26115410	CID	D001152	D009369

44072|t|On the antiarrhythmic activity of one N-substituted piperazine derivative of trans-2-amino-3-hydroxy-1, 2, 3, 4-tetrahydroanaphthalene.
44072|a|The antiarrhythmic activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride, referred to as P11, is studied on anaesthesized cats and Wistar albino rats, as well as on non-anaesthesized rabbits. Four types of experimental arrhythmia are used--with BaCl2, with chloroform-adrenaline, with strophantine G and with aconitine. The compound P11 is introduced in doses of 0.25 and 0.50 mg/kg intravenously and 10 mg/kg orally. The compound manifests antiarrhythmic activity in all models of experimental arrhythmia used, causing greatest inhibition on the arrhythmia induced by chloroform-adrenaline (in 90 per cent) and with BaCl2 (in 84 per cent). The results obtained are associated with the beta-adrenoblocking and with the membrane-stabilizing action of the compound.
44072	52	62	piperazine	Chemical	C034930
44072	77	134	trans-2-amino-3-hydroxy-1, 2, 3, 4-tetrahydroanaphthalene	Chemical	-1
44072	180	288	N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride	Chemical	C013741
44072	305	308	P11	Chemical	C013741
44072	435	445	arrhythmia	Disease	D001145
44072	461	466	BaCl2	Chemical	C024986
44072	473	483	chloroform	Chemical	D002725
44072	484	494	adrenaline	Chemical	D004837
44072	501	515	strophantine G	Chemical	D010042
44072	525	534	aconitine	Chemical	D000157
44072	549	552	P11	Chemical	C013741
44072	711	721	arrhythmia	Disease	D001145
44072	763	773	arrhythmia	Disease	D001145
44072	785	795	chloroform	Chemical	D002725
44072	796	806	adrenaline	Chemical	D004837
44072	833	838	BaCl2	Chemical	C024986
44072	CID	D002725	D001145
44072	CID	C024986	D001145
44072	CID	D000157	D001145
44072	CID	D004837	D001145
44072	CID	D010042	D001145

753803|t|Experimental progressive muscular dystrophy and its treatment with high doses anabolizing agents.
753803|a|We are still a long way from discovering an unequivocal pathogenetic interpretation of progressive muscular dystrophy in man. Noteworthy efforts have been made in the experimental field; a recessive autosomic form found in the mouse seems to bear the closest resemblance to the human form from the genetic point of view. Myopathy due to lack of vitamin E and myopathy induced by certain viruses have much in common anatomically and pathologically with the human form. The authors induced myodystrophy in the rat by giving it a diet lacking in vitamin E. The pharmacological characteristics of vitamin E and the degenerative changes brought about by its deficiency, especially in the muscles, are illustrated. It is thus confirmed that the histological characteristics of myopathic rat muscle induced experimentally are extraordinarily similar to those of human myopathy as confirmed during biopsies performed at the Orthopaedic Traumatological Centre, Florence. The encouraging results obtained in various authoratative departments in myopathic patients by using anabolizing steroids have encouraged the authors to investigate the beneficial effects of one anabolizing agent (Dianabol, CIBA) at high doses in rats rendered myopathic by a diet deficient in vitamin E. In this way they obtained appreciable changes in body weight (increased from 50 to 70 g after forty days at a dose of 5 mg per day of anabolizing agent), but most of all they found histological changes due to "regenerative" changes in the muscle tissue, which however maintained its myopathic characteristics in the control animals that were not treated with the anabolizing agent. The authors conclude by affirming the undoubted efficacy of the anabolizing steroids in experimental myopathic disease, but they have reservations as to the transfer of the results into the human field, where high dosage cannot be carried out continuously because of the effects of the drug on virility; because the tissue injury too often occurs at an irreversible stage vis-a-vis the "regeneration" of the muscle tissue; and finally because the dystrophic injurious agent is certainly not the lack of vitamin E but something as yet unknown.
753803	25	43	muscular dystrophy	Disease	D009136
753803	197	215	muscular dystrophy	Disease	D009136
753803	419	427	Myopathy	Disease	D009135
753803	443	452	vitamin E	Chemical	D014810
753803	457	465	myopathy	Disease	D009135
753803	586	598	myodystrophy	Disease	D009136
753803	641	650	vitamin E	Chemical	D014810
753803	691	700	vitamin E	Chemical	D014810
753803	869	878	myopathic	Disease	D009135
753803	959	967	myopathy	Disease	D009135
753803	1133	1142	myopathic	Disease	D009135
753803	1173	1181	steroids	Chemical	D013256
753803	1274	1282	Dianabol	Chemical	D008696
753803	1284	1288	CIBA	Chemical	-1
753803	1321	1330	myopathic	Disease	D009135
753803	1354	1363	vitamin E	Chemical	D014810
753803	1648	1657	myopathic	Disease	D009135
753803	1823	1831	steroids	Chemical	D013256
753803	1848	1865	myopathic disease	Disease	D009135
753803	2250	2259	vitamin E	Chemical	D014810
753803	CID	D008696	D009136
753803	CID	D014810	D009136

920167|t|Fetal risks due to warfarin therapy during pregnancy.
920167|a|Two mothers with heart valve prosthesis were treated with warfarin during pregnancy. In the first case a caesarean section was done one week after replacement of warfarin with heparin. The baby died of cerebral and pulmonary hemorrhage. The second mother had a male infant by caesarean section. The baby showed warfarin-induced embryopathy with nasal hypoplasia and stippled epiphyses (chondrodysplasia punctata). Nasal hypoplasia with or without stippled epiphyses has now been reported in 11 infants born to mothers treated with warfarin during the first trimester, and a causal association is probable. In view of the risks to both mother and fetus in women with prosthetic cardiac valves it is recommended that therapeutic abortion be advised as the first alternative.
920167	19	27	warfarin	Chemical	D014859
920167	112	120	warfarin	Chemical	D014859
920167	216	224	warfarin	Chemical	D014859
920167	230	237	heparin	Chemical	D006493
920167	256	289	cerebral and pulmonary hemorrhage	Disease	D002543|D008171|D006470	cerebral hemorrhage|pulmonary hemorrhage|hemorrhage
920167	365	373	warfarin	Chemical	D014859
920167	382	393	embryopathy	Disease	D005315
920167	399	415	nasal hypoplasia	Disease	-1
920167	420	438	stippled epiphyses	Disease	D002806
920167	440	465	chondrodysplasia punctata	Disease	D002806
920167	468	484	Nasal hypoplasia	Disease	-1
920167	501	519	stippled epiphyses	Disease	D002806
920167	585	593	warfarin	Chemical	D014859
920167	CID	D014859	D006470
920167	CID	D014859	D008171
920167	CID	D014859	D002543
920167	CID	D014859	D002806

1451544|t|Isradipine treatment for hypertension in general practice in Hong Kong.
1451544|a|A 6-week open study of the introduction of isradipine treatment was conducted in general practice in Hong Kong. 303 Chinese patients with mild to moderate hypertension entered the study. Side effects were reported in 21% of patients and caused withdrawal from the study in 3 patients. The main side-effects were headache, dizziness, palpitation and flushing and these were not more frequent than reported in other studies with isradipine or with placebo. Supine blood pressure was reduced (P less than 0.01) from 170 +/- 20/102 +/- 6 mmHg to 153 +/- 19/92 +/- 8, 147 +/- 18/88 +/- 7 and 144 +/- 14/87 +/- 6 mmHg at 2, 4 and 6 weeks respectively in evaluable patients. Similar reductions occurred in standing blood pressure and there was no evidence of postural hypotension. Normalization and responder rates at 6 weeks were 86% and 69% respectively. Dosage was increased from 2.5 mg b.d. to 5 mg b.d. at 4 weeks in patients with diastolic blood pressure greater than 90 mmHg and their further response was greater than those remaining on 2.5 mg b.d.
1451544	0	10	Isradipine	Chemical	D017275
1451544	25	37	hypertension	Disease	D006973
1451544	115	125	isradipine	Chemical	D017275
1451544	227	239	hypertension	Disease	D006973
1451544	384	392	headache	Disease	D006261
1451544	394	403	dizziness	Disease	D004244
1451544	405	416	palpitation	Disease	-1
1451544	421	429	flushing	Disease	D005483
1451544	499	509	isradipine	Chemical	D017275
1451544	824	844	postural hypotension	Disease	D007024
1451544	CID	D017275	D006261
1451544	CID	D017275	D004244
1451544	CID	D017275	D005483

2782734|t|Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics.
2782734|a|High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma, and are associated with dose-dependent systemic beta-adrenoceptor responses. The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol. Twelve asthmatic patients (FEV1, 81 +/- 4% predicted), requiring only occasional inhaled beta-agonists as their sole therapy, were given a 14-day treatment with high dose inhaled salbutamol (HDS), 4,000 micrograms daily, low dose inhaled salbutamol (LDS), 800 micrograms daily, or placebo (PI) by metered-dose inhaler in a double-blind, randomized crossover design. During the 14-day run-in and during washout periods, inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purposes. At the end of each 14-day treatment, a dose-response curve (DRC) was performed, and airway (FEV1, FEF25-75) chronotropic (HR), tremor, and metabolic (K, Glu) responses were measured at each step (from 100 to 4,000 micrograms). Treatment had no significant effect on baseline values. There were dose-dependent increases in FEV1 and FEF25-75 (p less than 0.001), and pretreatment with HDS did not displace the DRC to the right. DRC for HR (p less than 0.001), K (p less than 0.001), and Glu (p less than 0.005) were attenuated after treatment with HDS compared with PI. There were also differences between HDS and LDS for HR (p less than 0.001) and Glu (p less than 0.05) responses. Frequency and severity of subjective adverse effects were also reduced after HDS: tremor (p less than 0.001), palpitations (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
2782734	102	112	salbutamol	Chemical	D000420
2782734	116	126	asthmatics	Disease	D001249
2782734	150	160	salbutamol	Chemical	D000420
2782734	230	236	asthma	Disease	D001249
2782734	446	456	salbutamol	Chemical	D000420
2782734	465	474	asthmatic	Disease	D001249
2782734	637	647	salbutamol	Chemical	D000420
2782734	696	706	salbutamol	Chemical	D000420
2782734	917	936	ipratropium bromide	Chemical	D009241
2782734	1101	1107	tremor	Disease	D014202
2782734	1124	1125	K	Chemical	D011188
2782734	1127	1130	Glu	Chemical	D005947
2782734	1432	1433	K	Chemical	D011188
2782734	1459	1462	Glu	Chemical	D005947
2782734	1621	1624	Glu	Chemical	D005947
2782734	1737	1743	tremor	Disease	D014202
2782734	1765	1777	palpitations	Disease	-1
2782734	CID	D000420	D014202

2983630|t|Increased anxiogenic effects of caffeine in panic disorders.
2983630|a|The effects of oral administration of caffeine (10 mg/kg) on behavioral ratings, somatic symptoms, blood pressure and plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and cortisol were determined in 17 healthy subjects and 21 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder. Caffeine produced significantly greater increases in subject-rated anxiety, nervousness, fear, nausea, palpitations, restlessness, and tremors in the patients compared with healthy subjects. In the patients, but not the healthy subjects, these symptoms were significantly correlated with plasma caffeine levels. Seventy-one percent of the patients reported that the behavioral effects of caffeine were similar to those experienced during panic attacks. Caffeine did not alter plasma MHPG levels in either the healthy subjects or patients. Caffeine increased plasma cortisol levels equally in the patient and healthy groups. Because caffeine is an adenosine receptor antagonist, these results suggest that some panic disorder patients may have abnormalities in neuronal systems involving adenosine. Patients with anxiety disorders may benefit by avoiding caffeine-containing foods and beverages.
2983630	32	40	caffeine	Chemical	D002110
2983630	44	59	panic disorders	Disease	D016584
2983630	99	107	caffeine	Chemical	D002110
2983630	196	233	3-methoxy-4-hydroxyphenethyleneglycol	Chemical	D008734
2983630	235	239	MHPG	Chemical	D008734
2983630	245	253	cortisol	Chemical	D006854
2983630	338	349	agoraphobia	Disease	D000379
2983630	355	368	panic attacks	Disease	D016584
2983630	372	386	panic disorder	Disease	D016584
2983630	388	396	Caffeine	Chemical	D002110
2983630	455	462	anxiety	Disease	D001008
2983630	483	489	nausea	Disease	D009325
2983630	491	503	palpitations	Disease	-1
2983630	505	517	restlessness	Disease	D011595
2983630	523	530	tremors	Disease	D014202
2983630	683	691	caffeine	Chemical	D002110
2983630	776	784	caffeine	Chemical	D002110
2983630	826	839	panic attacks	Disease	D016584
2983630	841	849	Caffeine	Chemical	D002110
2983630	871	875	MHPG	Chemical	D008734
2983630	927	935	Caffeine	Chemical	D002110
2983630	953	961	cortisol	Chemical	D006854
2983630	1020	1028	caffeine	Chemical	D002110
2983630	1035	1044	adenosine	Chemical	D000241
2983630	1098	1112	panic disorder	Disease	D016584
2983630	1131	1164	abnormalities in neuronal systems	Disease	D009421
2983630	1175	1184	adenosine	Chemical	D000241
2983630	1200	1217	anxiety disorders	Disease	D001008
2983630	1242	1250	caffeine	Chemical	D002110
2983630	CID	D002110	D014202
2983630	CID	D002110	D009325
2983630	CID	D002110	D001008

3711722|t|Human and canine ventricular vasoactive intestinal polypeptide: decrease with heart failure.
3711722|a|Vasoactive intestinal polypeptide (VIP) is a systemic and coronary vasodilator that may have positive inotropic properties. Myocardial levels of VIP were assayed before and after the development of heart failure in two canine models. In the first, cobalt cardiomyopathy was induced in eight dogs; VIP (by radioimmunoassay) decreased from 35 +/- 11 pg/mg protein (mean +/- SD) to 5 +/- 4 pg/mg protein (P less than 0.05). In six dogs with doxorubicin-induced heart failure, VIP decreased from 31 +/- 7 to 11 +/- 4 pg/mg protein (P less than 0.05). In addition, VIP content of left ventricular muscle of resected failing hearts in 10 patients receiving a heart transplant was compared with the papillary muscles in 14 patients (five with rheumatic disease, nine with myxomatous degeneration) receiving mitral valve prostheses. The lowest myocardial VIP concentration was found in the hearts of patients with coronary disease (one patient receiving a transplant and three receiving mitral prostheses) (6.3 +/- 1.9 pg/mg protein). The other patients undergoing transplantation had an average ejection fraction of 17% +/- 6% and a VIP level of 8.8 +/- 3.9 pg/mg protein. The hearts without coronary artery disease (average ejection fraction of this group 62% +/- 10%) had a VIP concentration of 14.1 +/- 7.9 pg/mg protein, and this was greater than in hearts of the patients with coronary disease and the hearts of patients receiving a transplant (P less than 0.05). Myocardial catecholamines were also determined in 14 subjects; a weak correlation (r = 0.57, P less than 0.05) between the tissue concentrations of VIP and norepinephrine was noted.(ABSTRACT TRUNCATED AT 250 WORDS)
3711722	78	91	heart failure	Disease	D006333
3711722	291	304	heart failure	Disease	D006333
3711722	341	347	cobalt	Chemical	D003035
3711722	348	362	cardiomyopathy	Disease	D009202
3711722	531	542	doxorubicin	Chemical	D004317
3711722	551	564	heart failure	Disease	D006333
3711722	829	846	rheumatic disease	Disease	D012216
3711722	858	881	myxomatous degeneration	Disease	-1
3711722	999	1015	coronary disease	Disease	D003327
3711722	1278	1301	coronary artery disease	Disease	D003324
3711722	1468	1484	coronary disease	Disease	D003327
3711722	1566	1580	catecholamines	Chemical	D002395
3711722	1711	1725	norepinephrine	Chemical	D009638
3711722	CID	D004317	D006333
3711722	CID	D003035	D009202

6728873|t|Interstrain variation in acute toxic response to caffeine among inbred mice.
6728873|a|Acute toxic dosage-dependent behavioral effects of caffeine were compared in adult males from seven inbred mouse strains (A/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J, SWR/J). C57BL/6J, chosen as a "prototypic" mouse strain, was used to determine behavioral responses to a broad range (5-500 mg/kg) of caffeine doses. Five phenotypic characteristics--locomotor activity, righting ability, clonic seizure induction, stress-induced lethality, death without external stress--were scored at various caffeine doses in drug-naive animals under empirically optimized, rigidly constant experimental conditions. Mice (n = 12 for each point) received single IP injections of a fixed volume/g body weight of physiological saline carrier with or without caffeine in doses ranging from 125-500 mg/kg. Loss of righting ability was scored at 1, 3, 5 min post dosing and at 5 min intervals thereafter for 20 min. In the same animals the occurrence of clonic seizures was scored as to time of onset and severity for 20 min after drug administration. When these proceeded to tonic seizures, death occurred in less than 20 min. Animals surviving for 20 min were immediately stressed by a swim test in 25 degrees C water, and death-producing tonic seizures were scored for 2 min. In other animals locomotor activity was measured 15 or 60 min after caffeine administration. By any single behavioral criterion or a combination of these criteria, marked differences in response to toxic caffeine doses were observed between strains. These results indicate that behavioral toxicity testing of alkylxanthines in a single mouse strain may be misleading and suggest that toxic responses of the central nervous system to this class of compounds are genetically influenced in mammals.
6728873	49	57	caffeine	Chemical	D002110
6728873	128	136	caffeine	Chemical	D002110
6728873	381	389	caffeine	Chemical	D002110
6728873	468	482	clonic seizure	Disease	D012640
6728873	574	582	caffeine	Chemical	D002110
6728873	821	829	caffeine	Chemical	D002110
6728873	1014	1029	clonic seizures	Disease	D012640
6728873	1136	1150	tonic seizures	Disease	D012640
6728873	1301	1315	tonic seizures	Disease	D012640
6728873	1407	1415	caffeine	Chemical	D002110
6728873	1543	1551	caffeine	Chemical	D002110
6728873	1628	1636	toxicity	Disease	D064420
6728873	1648	1662	alkylxanthines	Chemical	-1
6728873	CID	D002110	D012640

7248895|t|Invasive carcinoma of the renal pelvis following cyclophosphamide therapy for nonmalignant disease.
7248895|a|A 47-year-old woman with right hydroureteronephrosis due to ureterovesical junction obstruction had gross hematuria after being treated for five years wtih cyclophosphamide for cerebral vasculitis. A right nephroureterectomy was required for control of bleeding. The pathology specimen contained clinically occult invasive carcinoma of the renal pelvis. Although the ability of cyclophosphamide to cause hemorrhagic cystitis and urine cytologic abnormalities indistinguishable from high grade carcinoma is well known, it is less widely appreciated that it is also associated with carcinoma of the urinary tract. Twenty carcinomas of the urinary bladder and one carcinoma of the prostate have been reported in association with its use. The present case is the first carcinoma of the renal pelvis reported in association with cyclophosphamide treatment. It is the third urinary tract cancer reported in association with cyclophosphamide treatment for nonmalignant disease. The association of the tumor with preexisting hydroureteronephrosis suggests that stasis prolonged and intensified exposure of upper urinary tract epithelium to cyclophosphamide. Patients who are candidates for long-term cyclophosphamide treatment should be routinely evaluated for obstructive uropathy.
7248895	9	38	carcinoma of the renal pelvis	Disease	D010386
7248895	49	65	cyclophosphamide	Chemical	D003520
7248895	131	152	hydroureteronephrosis	Disease	D006869
7248895	206	215	hematuria	Disease	D006417
7248895	256	272	cyclophosphamide	Chemical	D003520
7248895	277	296	cerebral vasculitis	Disease	D020293
7248895	353	361	bleeding	Disease	D006470
7248895	423	452	carcinoma of the renal pelvis	Disease	D010386
7248895	478	494	cyclophosphamide	Chemical	D003520
7248895	504	524	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
7248895	593	602	carcinoma	Disease	D002277
7248895	680	710	carcinoma of the urinary tract	Disease	D014571
7248895	719	752	carcinomas of the urinary bladder	Disease	D001749
7248895	761	786	carcinoma of the prostate	Disease	D011471
7248895	865	894	carcinoma of the renal pelvis	Disease	D010386
7248895	924	940	cyclophosphamide	Chemical	D003520
7248895	968	988	urinary tract cancer	Disease	D014571
7248895	1018	1034	cyclophosphamide	Chemical	D003520
7248895	1094	1099	tumor	Disease	D009369
7248895	1117	1138	hydroureteronephrosis	Disease	D006869
7248895	1232	1248	cyclophosphamide	Chemical	D003520
7248895	1292	1308	cyclophosphamide	Chemical	D003520
7248895	1353	1373	obstructive uropathy	Disease	-1
7248895	CID	D003520	D006417
7248895	CID	D003520	D002277
7248895	CID	D003520	D001749

9578276|t|Ascending dose tolerance study of intramuscular carbetocin administered after normal vaginal birth.
9578276|a|OBJECTIVE: To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term. MATERIALS AND METHODS: Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM). RESULTS: All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg. CONCLUSION: The MTD was calculated to be at 200 microg carbetocin.
9578276	48	58	carbetocin	Chemical	C020731
9578276	160	170	carbetocin	Chemical	C020731
9578276	208	216	oxytocin	Chemical	D010121
9578276	304	314	Carbetocin	Chemical	C020731
9578276	550	560	carbetocin	Chemical	C020731
9578276	809	830	hyper- or hypotension	Disease	D006973|D007022
9578276	847	861	abdominal pain	Disease	D015746
9578276	867	875	vomiting	Disease	D014839
9578276	884	901	retained placenta	Disease	D018457
9578276	973	983	blood loss	Disease	D006473
9578276	1134	1144	blood loss	Disease	D006473
9578276	1265	1275	blood loss	Disease	D006473
9578276	1574	1584	carbetocin	Chemical	C020731
9578276	CID	C020731	D018457
9578276	CID	C020731	D014839
9578276	CID	C020731	D006473
9578276	CID	C020731	D015746
9578276	CID	C020731	D006973
9578276	CID	C020731	D007022

11423811|t|A pilot study to assess the safety of dobutamine stress echocardiography in the emergency department evaluation of cocaine-associated chest pain.
11423811|a|STUDY OBJECTIVE: Chest pain in the setting of cocaine use poses a diagnostic dilemma. Dobutamine stress echocardiography (DSE) is a widely available and sensitive test for evaluating cardiac ischemia. Because of the theoretical concern regarding administration of dobutamine in the setting of cocaine use, we conducted a pilot study to assess the safety of DSE in emergency department patients with cocaine-associated chest pain. METHODS: A prospective case series was conducted in the intensive diagnostic and treatment unit in the ED of an urban tertiary-care teaching hospital. Patients were eligible for DSE if they had used cocaine within 24 hours preceding the onset of chest pain and had a normal ECG and tropinin I level. Patients exhibiting signs of continuing cocaine toxicity were excluded from the study. All patients were admitted to the hospital for serial testing after the DSE testing in the intensive diagnostic and treatment unit. RESULTS: Twenty-four patients were enrolled. Two patients had inadequate resting images, one DSE was terminated because of inferior hypokinesis, another DSE was terminated because of a rate-related atrial conduction deficit, and 1 patient did not reach the target heart rate. Thus, 19 patients completed a DSE and reached their target heart rates. None of the patients experienced signs of exaggerated adrenergic response, which was defined as a systolic blood pressure of greater than 200 mm Hg or the occurrence of tachydysrhythmias (excluding sinus tachycardia). Further suggesting lack of exaggerated adrenergic response, 13 (65%) of 20 patients required supplemental atropine to reach their target heart rates. CONCLUSION: No exaggerated adrenergic response was detected when dobutamine was administered to patients with cocaine-related chest pain.
11423811	38	48	dobutamine	Chemical	D004280
11423811	115	122	cocaine	Chemical	D003042
11423811	134	144	chest pain	Disease	D002637
11423811	163	173	Chest pain	Disease	D002637
11423811	192	199	cocaine	Chemical	D003042
11423811	232	242	Dobutamine	Chemical	D004280
11423811	337	345	ischemia	Disease	D007511
11423811	410	420	dobutamine	Chemical	D004280
11423811	439	446	cocaine	Chemical	D003042
11423811	545	552	cocaine	Chemical	D003042
11423811	564	574	chest pain	Disease	D002637
11423811	775	782	cocaine	Chemical	D003042
11423811	822	832	chest pain	Disease	D002637
11423811	916	923	cocaine	Chemical	D003042
11423811	924	932	toxicity	Disease	D064420
11423811	1227	1238	hypokinesis	Disease	D018476
11423811	1612	1629	tachydysrhythmias	Disease	-1
11423811	1641	1658	sinus tachycardia	Disease	D013616
11423811	1767	1775	atropine	Chemical	D001285
11423811	1876	1886	dobutamine	Chemical	D004280
11423811	1921	1928	cocaine	Chemical	D003042
11423811	1937	1947	chest pain	Disease	D002637
11423811	CID	D003042	D002637

12678199|t|Amiodarone-induced torsade de pointes during bladder irrigation: an unusual presentation--a case report.
12678199|a|The authors present a case of early (within 4 days) development of torsade de pointes (TdP) associated with oral amiodarone therapy. Consistent with other reports this case of TdP occurred in the context of multiple exacerbating factors including hypokalemia and digoxin excess. Transient prolongation of the QT during bladder irrigation prompted the episode of TdP. It is well known that bradycardia exacerbates acquired TdP. The authors speculate that the increased vagal tone during bladder irrigation, a vagal maneuver, in the context of amiodarone therapy resulted in amiodarone-induced proarrhythmia. In the absence of amiodarone therapy, a second bladder irrigation did not induce TdP despite hypokalemia and hypomagnesemia.
12678199	0	10	Amiodarone	Chemical	D000638
12678199	19	37	torsade de pointes	Disease	D016171
12678199	172	190	torsade de pointes	Disease	D016171
12678199	192	195	TdP	Disease	D016171
12678199	218	228	amiodarone	Chemical	D000638
12678199	281	284	TdP	Disease	D016171
12678199	352	363	hypokalemia	Disease	D007008
12678199	368	375	digoxin	Chemical	D004077
12678199	467	470	TdP	Disease	D016171
12678199	494	505	bradycardia	Disease	D001919
12678199	527	530	TdP	Disease	D016171
12678199	647	657	amiodarone	Chemical	D000638
12678199	678	688	amiodarone	Chemical	D000638
12678199	697	710	proarrhythmia	Disease	-1
12678199	730	740	amiodarone	Chemical	D000638
12678199	793	796	TdP	Disease	D016171
12678199	805	816	hypokalemia	Disease	D007008
12678199	821	835	hypomagnesemia	Disease	C537153
12678199	CID	D000638	D016171

15696449|t|Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation.
15696449|a|BACKGROUND: Patients with primary systemic amyloidosis (AL) have a poor prognosis. Median survival time from standard treatments is only 17 months. High-dose intravenous melphalan followed by peripheral blood stem cell transplant (PBSCT) appears to be the most promising therapy, but treatment mortality can be high. The authors have noted the development of acute renal insufficiency immediately after melphalan conditioning. This study was undertaken to further examine its risk factors and impact on posttransplant mortality. METHODS: Consecutive AL patients who underwent PBSCT were studied retrospectively. Acute renal insufficiency (ARI) after high-dose melphalan was defined by a minimum increase of 0.5 mg/dL (44 micromol/L) in the serum creatinine level that is greater than 50% of baseline immediately after conditioning. Urine sediment score was the sum of the individual types of sediment identified on urine microscopy. RESULTS: Of the 80 patients studied, ARI developed in 18.8% of the patients after high-dose melphalan. Univariate analysis identified age, hypoalbuminemia, heavy proteinuria, diuretic use, and urine sediment score (>3) as risk factors. Age and urine sediment score remained independently significant risk factors in the multivariate analysis. Patients who had ARI after high-dose melphalan underwent dialysis more often (P = 0.007), and had a worse 1-year survival (P = 0.03). CONCLUSION: The timing of renal injury strongly suggests melphalan as the causative agent. Ongoing tubular injury may be a prerequisite for renal injury by melphalan as evidenced by the active urinary sediment. Development of ARI adversely affected the outcome after PBSCT. Effective preventive measures may help decrease the treatment mortality of PBSCT in AL patients.
15696449	0	25	Acute renal insufficiency	Disease	D058186
15696449	42	51	melphalan	Chemical	D008558
15696449	69	97	primary systemic amyloidosis	Disease	C531616
15696449	158	186	primary systemic amyloidosis	Disease	C531616
15696449	188	190	AL	Disease	D000686
15696449	302	311	melphalan	Chemical	D008558
15696449	491	516	acute renal insufficiency	Disease	D058186
15696449	535	544	melphalan	Chemical	D008558
15696449	682	684	AL	Disease	D000686
15696449	744	769	Acute renal insufficiency	Disease	D058186
15696449	771	774	ARI	Disease	D058186
15696449	792	801	melphalan	Chemical	D008558
15696449	878	888	creatinine	Chemical	D003404
15696449	1102	1105	ARI	Disease	D058186
15696449	1157	1166	melphalan	Chemical	D008558
15696449	1204	1219	hypoalbuminemia	Disease	D034141
15696449	1227	1238	proteinuria	Disease	D011507
15696449	1425	1428	ARI	Disease	D058186
15696449	1445	1454	melphalan	Chemical	D008558
15696449	1568	1580	renal injury	Disease	D058186
15696449	1599	1608	melphalan	Chemical	D008558
15696449	1641	1655	tubular injury	Disease	-1
15696449	1682	1694	renal injury	Disease	D058186
15696449	1698	1707	melphalan	Chemical	D008558
15696449	1768	1771	ARI	Disease	D058186
15696449	1900	1902	AL	Disease	D000686
15696449	CID	D008558	D058186

17554526|t|Impaired fear recognition in regular recreational cocaine users.
17554526|a|INTRODUCTION: The ability to read facial expressions is essential for normal human social interaction. The aim of the present study was to conduct the first investigation of facial expression recognition performance in recreational cocaine users. MATERIALS AND METHODS: Three groups, comprised of 21 cocaine naive participants (CN),  30 occasional cocaine (OC), and 48 regular recreational cocaine (RC) users, were compared. An emotional facial expression (EFE) task consisting of a male and female face expressing six basic emotions (happiness, surprise, sadness, anger, fear, and disgust) was administered. Mean percent accuracy and latencies for correct responses across eight presentations of each basic emotion were derived. Participants were also assessed with the "Eyes task" to investigate their ability to recognize more complex emotional states and the Symptom CheckList-90-Revised to measure psychopathology. RESULTS: There were no group differences in psychopathology or "eyes task" performance, but the RC group, who otherwise had similar illicit substance use histories to the OC group, exhibited impaired fear recognition accuracy compared to the OC and CN groups. The RC group also correctly identified anger, fear, happiness, and surprise, more slowly than CN, but not OC participants. The OC group was slower than CN when correctly identifying disgust. The selective deficit in fear recognition accuracy manifested by the RC group cannot be explained by the subacute effects of cocaine, or ecstasy, because recent and less recent users of these drugs within this group were similarly impaired. Possible parallels between RC users and psychopaths with respect to impaired fear recognition, amygdala dysfunction, and etiology are discussed.
17554526	0	25	Impaired fear recognition	Disease	D001925
17554526	50	57	cocaine	Chemical	D003042
17554526	297	304	cocaine	Chemical	D003042
17554526	365	372	cocaine	Chemical	D003042
17554526	413	420	cocaine	Chemical	D003042
17554526	455	462	cocaine	Chemical	D003042
17554526	1176	1201	impaired fear recognition	Disease	D001925
17554526	1450	1477	deficit in fear recognition	Disease	D001925
17554526	1561	1568	cocaine	Chemical	D003042
17554526	1573	1580	ecstasy	Chemical	D018817
17554526	1717	1728	psychopaths	Disease	D001523
17554526	1745	1770	impaired fear recognition	Disease	D001925
17554526	1772	1792	amygdala dysfunction	Disease	-1
17554526	CID	D003042	D001925

17721298|t|Corneal ulcers associated with aerosolized crack cocaine use.
17721298|a|PURPOSE: We report 4 cases of corneal ulcers associated with drug abuse. The pathogenesis of these ulcers and management of these patients are also reviewed. METHODS: Review of all cases of corneal ulcers associated with drug abuse seen at our institution from July 2006 to December 2006. RESULTS: Four patients with corneal ulcers associated with crack cocaine use were reviewed. All corneal ulcers were cultured, and the patients were admitted to the hospital for intensive topical antibiotic treatment. Each patient received comprehensive health care, including medical and substance abuse consultations. Streptococcal organisms were found in 3 cases and Capnocytophaga and Brevibacterium casei in 1 patient. The infections responded to antibiotic treatment. Two patients needed a lateral tarsorrhaphy for persistent epithelial defects. CONCLUSIONS: Aerosolized crack cocaine use can be associated with the development of corneal ulcers. Drug abuse provides additional challenges for management. Not only treatment of their infections but also the overall poor health of the patients and increased risk of noncompliance need to be addressed. Comprehensive care may provide the patient the opportunity to discontinue their substance abuse, improve their overall health, and prevent future corneal complications.
17721298	0	14	Corneal ulcers	Disease	D003320
17721298	43	56	crack cocaine	Chemical	D016578
17721298	92	106	corneal ulcers	Disease	D003320
17721298	123	133	drug abuse	Disease	D019966
17721298	161	167	ulcers	Disease	D014456
17721298	252	266	corneal ulcers	Disease	D003320
17721298	283	293	drug abuse	Disease	D019966
17721298	379	393	corneal ulcers	Disease	D003320
17721298	410	423	crack cocaine	Chemical	D016578
17721298	447	461	corneal ulcers	Disease	D003320
17721298	639	654	substance abuse	Disease	D019966
17721298	778	788	infections	Disease	D007239
17721298	882	900	epithelial defects	Disease	-1
17721298	927	940	crack cocaine	Chemical	D016578
17721298	987	1001	corneal ulcers	Disease	D003320
17721298	1003	1013	Drug abuse	Disease	D019966
17721298	1089	1099	infections	Disease	D007239
17721298	1287	1302	substance abuse	Disease	D019966
17721298	CID	D016578	D003320

18341442|t|Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy.
18341442|a|OBJECTIVE: To assess pharmacokinetics, efficacy, and tolerability of oral levetiracetam administered as an adjunct to phenobarbital treatment in cats with poorly controlled suspected idiopathic epilepsy. DESIGN-Open-label, noncomparative clinical trial. ANIMALS: 12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects when treated with phenobarbital. PROCEDURES: Cats were treated with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded. RESULTS: Median maximum serum levetiracetam concentration was 25.5 microg/mL, median minimum serum levetiracetam concentration was 8.3 microg/mL, and median elimination half-life was 2.9 hours. Median seizure frequency prior to treatment with levetiracetam (2.1 seizures/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures/mo), and 7 of 10 cats were classified as having responded to levetiracetam treatment (ie, reduction in seizure frequency of >or=50%). Two cats had transient lethargy and inappetence. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that levetiracetam is well tolerated in cats and may be useful as an adjunct to phenobarbital treatment in cats with idiopathic epilepsy.
18341442	0	13	Levetiracetam	Chemical	C026098
18341442	31	44	phenobarbital	Chemical	D010634
18341442	78	97	idiopathic epilepsy	Disease	C562694
18341442	173	186	levetiracetam	Chemical	C026098
18341442	217	230	phenobarbital	Chemical	D010634
18341442	282	301	idiopathic epilepsy	Disease	C562694
18341442	388	407	idiopathic epilepsy	Disease	C562694
18341442	440	453	phenobarbital	Chemical	D010634
18341442	513	526	phenobarbital	Chemical	D010634
18341442	563	576	levetiracetam	Chemical	C026098
18341442	658	671	levetiracetam	Chemical	C026098
18341442	845	852	Seizure	Disease	D012640
18341442	896	909	levetiracetam	Chemical	C026098
18341442	1000	1013	levetiracetam	Chemical	C026098
18341442	1069	1082	levetiracetam	Chemical	C026098
18341442	1171	1178	seizure	Disease	D012640
18341442	1213	1226	levetiracetam	Chemical	C026098
18341442	1232	1240	seizures	Disease	D012640
18341442	1282	1289	seizure	Disease	D012640
18341442	1320	1333	levetiracetam	Chemical	C026098
18341442	1350	1358	seizures	Disease	D012640
18341442	1420	1433	levetiracetam	Chemical	C026098
18341442	1462	1469	seizure	Disease	D012640
18341442	1516	1524	lethargy	Disease	D053609
18341442	1529	1540	inappetence	Disease	-1
18341442	1601	1614	levetiracetam	Chemical	C026098
18341442	1676	1689	phenobarbital	Chemical	D010634
18341442	1713	1732	idiopathic epilepsy	Disease	C562694
18341442	CID	C026098	D053609

19681452|t|Bilateral haemorrhagic infarction of the globus pallidus after cocaine and alcohol intoxication.
19681452|a|Cocaine is a risk factor for both ischemic and haemorrhagic stroke. We present the case of a 31-year-old man with bilateral ischemia of the globus pallidus after excessive alcohol and intranasal cocaine use. Drug-related globus pallidus infarctions are most often associated with heroin. Bilateral basal ganglia infarcts after the use of cocaine, without concurrent heroin use, have never been reported. In our patient, transient cardiac arrhythmia or respiratory dysfunction related to cocaine and/or ethanol use were the most likely causes of cerebral hypoperfusion.
19681452	10	56	haemorrhagic infarction of the globus pallidus	Disease	D002543|D020520	haemorrhagic|infarction of the globus pallidus
19681452	63	70	cocaine	Chemical	D003042
19681452	75	82	alcohol	Chemical	D000431
19681452	97	104	Cocaine	Chemical	D003042
19681452	131	163	ischemic and haemorrhagic stroke	Disease	D002544|D020521	ischemic stroke|haemorrhagic stroke
19681452	221	252	ischemia of the globus pallidus	Disease	D002545
19681452	269	276	alcohol	Chemical	D000431
19681452	292	299	cocaine	Chemical	D003042
19681452	318	345	globus pallidus infarctions	Disease	D020520
19681452	377	383	heroin	Chemical	D003932
19681452	395	417	basal ganglia infarcts	Disease	D020520
19681452	435	442	cocaine	Chemical	D003042
19681452	463	469	heroin	Chemical	D003932
19681452	527	545	cardiac arrhythmia	Disease	D001145
19681452	549	572	respiratory dysfunction	Disease	D012131
19681452	584	591	cocaine	Chemical	D003042
19681452	599	606	ethanol	Chemical	D000431
19681452	642	664	cerebral hypoperfusion	Disease	-1
19681452	CID	D003932	D020520
19681452	CID	D003042	D002545
19681452	CID	D000431	D002544
19681452	CID	D000431	D020521

20009434|t|Acute renal failure after high-dose methotrexate therapy in a patient with ileostomy.
20009434|a|High-dose methotrexate (HD-MTX) is an important treatment for Burkitt lymphoma, but can cause hepatic and renal toxicity when its clearance is delayed. We report a case of acute renal failure after HD-MTX therapy in a patient with ileostomy, The patient was a 3-year-old boy who had received a living-related liver transplantation for congenital biliary atresia. At day 833 after the transplantation, he was diagnosed with PTLD (post-transplantation lymphoproliferative disorder, Burkitt-type malignant lymphoma). During induction therapy, he suffered ileal perforation and ileostomy was performed. Subsequent HD-MTX therapy caused acute renal failure that required continuous hemodialysis. We supposed that intravascular hypovolemia due to substantial drainage from the ileostoma caused acute prerenal failure. After recovery of his renal function, we could safely treat the patient with HD-MTX therapy by controlling drainage from ileostoma with total parenteral nutrition.
20009434	0	19	Acute renal failure	Disease	D058186
20009434	36	48	methotrexate	Chemical	D008727
20009434	96	108	methotrexate	Chemical	D008727
20009434	113	116	MTX	Chemical	D008727
20009434	148	164	Burkitt lymphoma	Disease	D002051
20009434	180	206	hepatic and renal toxicity	Disease	D056486|D007674	hepatic toxicity|renal toxicity
20009434	258	277	acute renal failure	Disease	D058186
20009434	287	290	MTX	Chemical	D008727
20009434	432	447	biliary atresia	Disease	D001656
20009434	509	513	PTLD	Disease	D008232
20009434	515	564	post-transplantation lymphoproliferative disorder	Disease	D008232
20009434	566	597	Burkitt-type malignant lymphoma	Disease	D002051
20009434	699	702	MTX	Chemical	D008727
20009434	718	737	acute renal failure	Disease	D058186
20009434	808	819	hypovolemia	Disease	D020896
20009434	874	896	acute prerenal failure	Disease	-1
20009434	978	981	MTX	Chemical	D008727
20009434	CID	D008727	D058186

20431083|t|Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies.
20431083|a|BACKGROUND AND PURPOSE: Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA). METHODS: We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB. RESULTS: In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3-3.5) in nonantithrombotic users to 5.7 (range, 3.4-9.7) in antiplatelet users and 8.0 (range, 3.5-17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6-4.4; P<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9-1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3-2.3; P<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2-1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4-42.5; P<0.001). CONCLUSIONS: The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.
20431083	25	45	cerebral microbleeds	Disease	-1
20431083	51	75	intracerebral hemorrhage	Disease	D002543
20431083	159	179	Cerebral microbleeds	Disease	-1
20431083	181	183	MB	Disease	-1
20431083	216	240	intracerebral hemorrhage	Disease	D002543
20431083	242	245	ICH	Disease	D002543
20431083	372	374	MB	Disease	-1
20431083	434	437	ICH	Disease	D002543
20431083	442	457	ischemic stroke	Disease	D002544
20431083	459	461	IS	Disease	D002544
20431083	463	488	transient ischemic attack	Disease	D002546
20431083	490	493	TIA	Disease	D002546
20431083	590	596	stroke	Disease	D020521
20431083	600	603	TIA	Disease	D002546
20431083	631	633	MB	Disease	-1
20431083	695	698	ICH	Disease	D002543
20431083	742	744	IS	Disease	D002544
20431083	745	748	TIA	Disease	D002546
20431083	758	761	ICH	Disease	D002543
20431083	765	773	ischemic	Disease	D007511
20431083	898	901	ICH	Disease	D002543
20431083	931	933	MB	Disease	-1
20431083	973	976	ICH	Disease	D002543
20431083	986	988	IS	Disease	D002544
20431083	989	992	TIA	Disease	D002546
20431083	994	996	MB	Disease	-1
20431083	1019	1022	ICH	Disease	D002543
20431083	1026	1028	IS	Disease	D002544
20431083	1029	1032	TIA	Disease	D002546
20431083	1223	1231	warfarin	Chemical	D014859
20431083	1287	1289	MB	Disease	-1
20431083	1293	1301	warfarin	Chemical	D014859
20431083	1325	1328	ICH	Disease	D002543
20431083	1377	1385	warfarin	Chemical	D014859
20431083	1397	1399	IS	Disease	D002544
20431083	1400	1403	TIA	Disease	D002546
20431083	1489	1491	MB	Disease	-1
20431083	1531	1534	ICH	Disease	D002543
20431083	1626	1628	IS	Disease	D002544
20431083	1629	1632	TIA	Disease	D002546
20431083	1756	1758	MB	Disease	-1
20431083	1836	1839	ICH	Disease	D002543
20431083	1906	1908	MB	Disease	-1
20431083	1912	1920	warfarin	Chemical	D014859
20431083	1932	1935	ICH	Disease	D002543
20431083	1975	1977	MB	Disease	-1
20431083	1999	2007	warfarin	Chemical	D014859
20431083	2019	2022	ICH	Disease	D002543
20431083	CID	D014859	D002543

20595935|t|Verapamil stimulation test in hyperprolactinemia: loss of prolactin response in anatomic or functional stalk effect.
20595935|a|AIM: Verapamil stimulation test was previously investigated as a tool for differential diagnosis of hyperprolactinemia, but with conflicting results. Macroprolactinemia was never considered in those previous studies. Here, we aimed to re-investigate the diagnostic value of verapamil in a population who were all screened for macroprolactinemia. Prolactin responses to verapamil in 65 female patients (age: 29.9 +/- 8.1 years) with hyperprolactinemia were tested in a descriptive, matched case-control study. METHODS: Verapamil 80 mg, p.o. was administered, and then PRL levels were measured at 8th and 16th hours, by immunometric chemiluminescence. Verapamil responsiveness was determined by peak percent change in basal prolactin levels (PRL). RESULTS: Verapamil significantly increased PRL levels in healthy controls (N. 8, PRL: 183%), macroprolactinoma (N. 8, PRL: 7%), microprolactinoma (N. 19, PRL: 21%), macroprolactinemia (N. 23, PRL: 126%), but not in pseudoprolactinoma (N. 8, PRL: 0.8%), and risperidone-induced hyperprolactinemia (N. 7, PRL: 3%). ROC curve analysis revealed that unresponsiveness to verapamil defined as PRL <7%, discriminated anatomical or functional stalk effect (sensitivity: 74%, specificity: 73%, AUC: 0.855+/-0.04, P <0.001, CI: 0.768-0.942) associated with pseudoprolactinoma or risperidone-induced hyperprolactinemia, respectively. CONCLUSION: Verapamil responsiveness is not a reliable finding for the differential diagnosis of hyperprolactinemia. However, verapamil unresponsiveness discriminates stalk effect (i.e., anatomically or functionally inhibited dopaminergic tonus) from other causes of hyperprolactinemia with varying degrees of responsiveness.
20595935	0	9	Verapamil	Chemical	D014700
20595935	30	48	hyperprolactinemia	Disease	D006966
20595935	122	131	Verapamil	Chemical	D014700
20595935	217	235	hyperprolactinemia	Disease	D006966
20595935	267	285	Macroprolactinemia	Disease	D015175
20595935	391	400	verapamil	Chemical	D014700
20595935	443	461	macroprolactinemia	Disease	D015175
20595935	486	495	verapamil	Chemical	D014700
20595935	549	567	hyperprolactinemia	Disease	D006966
20595935	635	644	Verapamil	Chemical	D014700
20595935	767	776	Verapamil	Chemical	D014700
20595935	872	881	Verapamil	Chemical	D014700
20595935	956	973	macroprolactinoma	Disease	D015175
20595935	991	1008	microprolactinoma	Disease	D015175
20595935	1028	1046	macroprolactinemia	Disease	D015175
20595935	1078	1096	pseudoprolactinoma	Disease	-1
20595935	1120	1131	risperidone	Chemical	D018967
20595935	1140	1158	hyperprolactinemia	Disease	D006966
20595935	1229	1238	verapamil	Chemical	D014700
20595935	1410	1428	pseudoprolactinoma	Disease	-1
20595935	1432	1443	risperidone	Chemical	D018967
20595935	1452	1470	hyperprolactinemia	Disease	D006966
20595935	1498	1507	Verapamil	Chemical	D014700
20595935	1583	1601	hyperprolactinemia	Disease	D006966
20595935	1612	1621	verapamil	Chemical	D014700
20595935	1753	1771	hyperprolactinemia	Disease	D006966
20595935	CID	D018967	D006966

35781|t|Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats.
35781|a|The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics.
35781	126	135	clonidine	Chemical	D003000
35781	137	148	naphazoline	Chemical	D009278
35781	153	167	xylometazoline	Chemical	C009695
35781	192	200	morphine	Chemical	D009020
35781	202	209	codeine	Chemical	D003061
35781	211	219	fentanyl	Chemical	D005283
35781	224	235	pentazocine	Chemical	D010423
35781	244	254	cataleptic	Disease	D002375
35781	265	273	morphine	Chemical	D009020
35781	275	281	codine	Chemical	D003061
35781	286	294	fentanyl	Chemical	D005283
35781	418	431	noradrenaline	Chemical	D009638
35781	433	435	NA	Chemical	D009638
35781	508	510	NA	Chemical	D009638
35781	605	614	catalepsy	Disease	D002375
35781	626	634	morphine	Chemical	D009020
35781	639	647	fentanyl	Chemical	D005283
35781	649	656	Codeine	Chemical	D003061
35781	657	666	catalepsy	Disease	D002375
35781	684	693	clonidine	Chemical	D003000
35781	711	722	naphazoline	Chemical	D009278
35781	727	741	xylometazoline	Chemical	C009695
35781	770	772	NA	Chemical	D009638
35781	792	800	morphine	Chemical	D009020
35781	805	813	fentanyl	Chemical	D005283
35781	839	846	codeine	Chemical	D003061
35781	880	891	Pentazocine	Chemical	D010423
35781	938	940	NA	Chemical	D009638
35781	954	956	NA	Chemical	D009638
35781	1026	1034	fentanyl	Chemical	D005283
35781	1084	1086	NA	Chemical	D009638
35781	1249	1251	NA	Chemical	D009638
35781	1299	1309	monoamines	Chemical	D015306
35781	CID	D003000	D002375
35781	CID	D005283	D002375
35781	CID	D009278	D002375
35781	CID	D003061	D002375
35781	CID	C009695	D002375
35781	CID	D009020	D002375

48835|t|Modification by propranolol of cardiovascular effects of induced hypoglycaemia.
48835|a|The cardiovascular effects of hypoglycaemia, with and without beta-blockade, were compared in fourteen healthy men. Eight received insulin alone, and eight, including two of the original insulin-only group, were given propranolol and insulin. In the insulin-group the period of hypoglycaemia was associated with an increase in heart-rate and a fall in diastolic blood-pressure. In the propranolol-insulin group there was a significant fall in heart-rate in most subjects and an increase in diastolic pressure. Typical S-T/T changes occurred in the insulin-group but in none of the propranolol-insulin group. Hypertension in diabetics prone to hypoglycaemia attacks should not be treated with beta-blockers because these drugs may cause a sharp rise in blood-pressure in such patients.
48835	16	27	propranolol	Chemical	D011433
48835	65	78	hypoglycaemia	Disease	D007003
48835	110	123	hypoglycaemia	Disease	D007003
48835	298	309	propranolol	Chemical	D011433
48835	358	371	hypoglycaemia	Disease	D007003
48835	465	476	propranolol	Chemical	D011433
48835	661	672	propranolol	Chemical	D011433
48835	688	700	Hypertension	Disease	D006973
48835	704	713	diabetics	Disease	D003920
48835	723	736	hypoglycaemia	Disease	D007003
48835	CID	D011433	D006973

89511|t|Prevention and treatment of endometrial disease in climacteric women receiving oestrogen therapy.
89511|a|The treatment regimens are described in 74 patients with endometrial disease among 850 climacteric women receiving oestrogen therapy. Cystic hyperplasia was associated with unopposed oestrogen therapy without progestagen. Two courses of 21 days of 5 mg norethisterone daily caused reversion to normal in all 57 cases of cystic hyperplasia and 6 of the 8 cases of atypical hyperplasia. 4 cases of endometrial carcinoma referred from elsewhere demonstrated the problems of inappropriate and unsupervised unopposed oestrogen therapy and the difficulty in distinguishing severe hyperplasia from malignancy. Cyclical low-dose oestrogen therapy with 7--13 days of progestagen does not seem to increase the risk of endometrial hyperplasia or carcinoma.
89511	28	47	endometrial disease	Disease	D014591
89511	79	88	oestrogen	Chemical	D004967
89511	155	174	endometrial disease	Disease	D014591
89511	213	222	oestrogen	Chemical	D004967
89511	239	250	hyperplasia	Disease	D006965
89511	281	290	oestrogen	Chemical	D004967
89511	307	318	progestagen	Chemical	D011372
89511	351	365	norethisterone	Chemical	D009640
89511	425	436	hyperplasia	Disease	D006965
89511	470	481	hyperplasia	Disease	D006965
89511	494	515	endometrial carcinoma	Disease	D016889
89511	610	619	oestrogen	Chemical	D004967
89511	672	683	hyperplasia	Disease	D006965
89511	689	699	malignancy	Disease	D009369
89511	719	728	oestrogen	Chemical	D004967
89511	756	767	progestagen	Chemical	D011372
89511	806	829	endometrial hyperplasia	Disease	D004714
89511	833	842	carcinoma	Disease	D002277
89511	CID	D004967	D006965

146391|t|Pure red cell aplasia, toxic dermatitis and lymphadenopathy in a patient taking diphenylhydantoin.
146391|a|A patient taking diphenylhydantoin for 3 weeks developed a generalized skin rash, lymphadenopathy and pure red cell aplasia. After withdrawal of the pharmacon all symptoms disappeared spontaneously. Skin rash is a well-known complication of diphenylhydantoin treatment as is benign and malignant lymphadenopathy. Pure red cell aplasia associated with diphenylhydantoin medication has been reported in 3 patients. The exact mechanism by which diphenylhydantoin exerts its toxic effects is not known. In this patient the time relation between the ingestion of diphenylhydantoin and the occurrence of the skin rash, lymphadenopathy and pure red cell aplasia is very suggestive of a direct connection.
146391	0	21	Pure red cell aplasia	Disease	D012010
146391	23	39	toxic dermatitis	Disease	D003875
146391	44	59	lymphadenopathy	Disease	D008206
146391	80	97	diphenylhydantoin	Chemical	D010672
146391	116	133	diphenylhydantoin	Chemical	D010672
146391	170	179	skin rash	Disease	D005076
146391	181	196	lymphadenopathy	Disease	D008206
146391	201	222	pure red cell aplasia	Disease	D012010
146391	298	307	Skin rash	Disease	D005076
146391	340	357	diphenylhydantoin	Chemical	D010672
146391	395	410	lymphadenopathy	Disease	D008206
146391	412	433	Pure red cell aplasia	Disease	D012010
146391	450	467	diphenylhydantoin	Chemical	D010672
146391	541	558	diphenylhydantoin	Chemical	D010672
146391	657	674	diphenylhydantoin	Chemical	D010672
146391	701	710	skin rash	Disease	D005076
146391	712	727	lymphadenopathy	Disease	D008206
146391	732	753	pure red cell aplasia	Disease	D012010
146391	CID	D010672	D003875
146391	CID	D010672	D008206
146391	CID	D010672	D012010

256433|t|Continuous infusion tobramycin combined with carbenicillin for infections in cancer patients.
256433|a|The cure rate of infections in cancer patients is adversely affected by neutropenia (less than 1,000/mm3). In particular, patients with severe neutropenia (less than 100/mm3) have shown a poor response to antibiotics. To overcome the adverse effects of neutropenia, tobramycin was given by continuous infusion and combined with intermittent carbenicillin. Tobramycin was given to a total daily dose of 300 mg/m2 and carbenicillin was given at a dose of 5 gm every four hours. There were 125 infectious episodes in 116 cancer patients receiving myelosuppressive chemotherapy. The overall cure rate was 70%. Pneumonia was the most common infection and 61% of 59 episodes were cured. Gram-negative bacilli were the most common causative organisms and 69% of these infections were cured. The most common pathogen was Klebsiella pneumoniae and this, together with Escherichia coli and Pseudomonas aeruginosa, accounted for 74% of all gram-negative bacillary infections. Response was not influenced by the initial neutrophil count, with a 62% cure rate for 39 episodes associated with severe neutropenia. However, failure of the neutrophil count to increase during therapy adversely affected response. Azotemia was the major side effect recognized, and it occurred in 11% of episodes. Major azotemia (serum creatinine greater than 2.5 mg/dl or BUN greater than 50 mg/dl) occurred in only 2%. Azotemia was not related to duration of therapy or serum tobramycin concentration. This antibiotic regimen showed both therapeutic efficacy and acceptable renal toxicity for these patients.
256433	20	30	tobramycin	Chemical	D014031
256433	45	58	carbenicillin	Chemical	D002228
256433	63	73	infections	Disease	D007239
256433	77	83	cancer	Disease	D009369
256433	111	121	infections	Disease	D007239
256433	125	131	cancer	Disease	D009369
256433	166	177	neutropenia	Disease	D009503
256433	237	248	neutropenia	Disease	D009503
256433	347	358	neutropenia	Disease	D009503
256433	360	370	tobramycin	Chemical	D014031
256433	435	448	carbenicillin	Chemical	D002228
256433	450	460	Tobramycin	Chemical	D014031
256433	510	523	carbenicillin	Chemical	D002228
256433	612	618	cancer	Disease	D009369
256433	700	709	Pneumonia	Disease	D011014
256433	730	739	infection	Disease	D007239
256433	855	865	infections	Disease	D007239
256433	918	928	pneumoniae	Disease	D011014
256433	1023	1057	gram-negative bacillary infections	Disease	D016905
256433	1180	1191	neutropenia	Disease	D009503
256433	1290	1298	Azotemia	Disease	D053099
256433	1379	1387	azotemia	Disease	D053099
256433	1395	1405	creatinine	Chemical	D003404
256433	1480	1488	Azotemia	Disease	D053099
256433	1537	1547	tobramycin	Chemical	D014031
256433	1635	1649	renal toxicity	Disease	D007674
256433	CID	D014031	D053099
256433	CID	D002228	D053099

448423|t|Recurrent subarachnoid hemorrhage associated with aminocaproic acid therapy and acute renal artery thrombosis. Case report.
448423|a|Epsilon aminocaproic acid (EACA) has been used to prevent rebleeding in patients with subarachnoid hemorrhage (SAH). Although this agent does decrease the frequency of rebleeding, several reports have described thrombotic complications of EACA therapy. These complications have included clinical deterioration and intracranial vascular thrombosis in patients with SAH, arteriolar and capillary fibrin thrombi in patients with fibrinolytic syndromes treated with EACA, or other thromboembolic phenomena. Since intravascular fibrin thrombi are often observed in patients with fibrinolytic disorders, EACA should not be implicated in the pathogenesis of fibrin thrombi in patients with disseminated intravascular coagulation or other "consumption coagulopathies." This report describes subtotal infarction of the kidney due to thrombosis of a normal renal artery. This occlusion occurred after EACA therapy in a patient with SAH and histopathological documentation of recurrent SAH. The corresponding clinical event was characterized by marked hypertension and abrupt neurological deterioration.
448423	10	33	subarachnoid hemorrhage	Disease	D013345
448423	50	67	aminocaproic acid	Chemical	D000614
448423	80	109	acute renal artery thrombosis	Disease	D007674
448423	124	149	Epsilon aminocaproic acid	Chemical	D015119
448423	151	155	EACA	Chemical	D015119
448423	210	233	subarachnoid hemorrhage	Disease	D013345
448423	235	238	SAH	Disease	D013345
448423	335	345	thrombotic	Disease	D013927
448423	363	367	EACA	Chemical	D015119
448423	438	470	intracranial vascular thrombosis	Disease	D020767
448423	488	491	SAH	Disease	D013345
448423	525	532	thrombi	Disease	D013927
448423	586	590	EACA	Chemical	D015119
448423	601	625	thromboembolic phenomena	Disease	D013923
448423	654	661	thrombi	Disease	D013927
448423	722	726	EACA	Chemical	D015119
448423	782	789	thrombi	Disease	D013927
448423	807	845	disseminated intravascular coagulation	Disease	D004211
448423	856	882	consumption coagulopathies	Disease	D004211
448423	916	926	infarction	Disease	D007238
448423	948	983	thrombosis of a normal renal artery	Disease	D007674
448423	1015	1019	EACA	Chemical	D015119
448423	1046	1049	SAH	Disease	D013345
448423	1099	1102	SAH	Disease	D013345
448423	1165	1177	hypertension	Disease	D006973
448423	CID	D015119	D013345
448423	CID	D015119	D007674
448423	CID	D015119	D013927
448423	CID	D015119	D020767
448423	CID	D015119	D006973

573555|t|Long-term propranolol therapy in pregnancy: maternal and fetal outcome.
573555|a|Propranolol, a beta-adrenergic blocking agent, has found an important position in the practice of medicine. Its use in pregnancy, however, is an open question as a number of detrimental side effects have been reported in the fetus and neonate. Ten patients and 12 pregnancies are reported where chronic propranolol has been administered. Five patients with serial pregnancies with and without propranolol therapy are also examined. Maternal, fetal, and neonatal complications are examined. An attempt is made to differentiate drug-related complications from maternal disease--related complications. We conclude that previously reported hypoglycemia, hyperbilirubinemia, polycythemia, neonatal apnea, and bradycardia are not invariable and cannot be statistically correlated with chronic propranolol therapy. Growth retardation, however, appears to be significant in both of our series.
573555	10	21	propranolol	Chemical	D011433
573555	72	83	Propranolol	Chemical	D011433
573555	375	386	propranolol	Chemical	D011433
573555	465	476	propranolol	Chemical	D011433
573555	708	720	hypoglycemia	Disease	D007003
573555	722	740	hyperbilirubinemia	Disease	D006932
573555	742	754	polycythemia	Disease	D011086
573555	756	770	neonatal apnea	Disease	D001049
573555	776	787	bradycardia	Disease	D001919
573555	859	870	propranolol	Chemical	D011433
573555	880	898	Growth retardation	Disease	D005317
573555	CID	D011433	D005317

611664|t|Use of propranolol in the treatment of idiopathic orthostatic hypotension.
611664|a|Five patients with idiopathic orthostatic hypotension who had physiologic and biochemical evidence of severe autonomic dysfunction were included in the study. They all exhibited markedly reduced plasma catecholamines and plasma renin activity in both recumbent and upright positions and had marked hypersensitivity to the pressor effects of infused norepinephrine. Treatment with propanolol administered intravenously (1-5 mg) produced increases in supine and upright blood pressure in 4 of the 5 individuals with rises ranging from 11/6 to 22/11 mmHg. Chronic oral administration of propranolol (40-160 mg/day) also elevated the blood pressures of these individuals with increases in the order of 20-35/15-25 mmg being observed. In 1 patient, marked hypertension was induced by propranolol and the drug had to be withdrawn. It otherwise was well tolerated and no important side effects were observed. Treatment has been continued in 3 individuals for 6-13 months with persistence of the pressor effect, although there appears to have been some decrease in the degree of response with time. Hemodynamic measurements in 1 of the patients demonstrated an increase in total peripheral resistance and essentially no change in cardiac output following propranolol therapy. The studies suggest that propranolol is a useful drug in selected patients with severe idiopathic orthostatic hypotension.
611664	7	18	propranolol	Chemical	D011433
611664	39	73	idiopathic orthostatic hypotension	Disease	C544351
611664	94	128	idiopathic orthostatic hypotension	Disease	C544351
611664	277	291	catecholamines	Chemical	D002395
611664	373	389	hypersensitivity	Disease	D004342
611664	424	438	norepinephrine	Chemical	D009638
611664	455	465	propanolol	Chemical	D011433
611664	659	670	propranolol	Chemical	D011433
611664	826	838	hypertension	Disease	D006973
611664	854	865	propranolol	Chemical	D011433
611664	1322	1333	propranolol	Chemical	D011433
611664	1368	1379	propranolol	Chemical	D011433
611664	1430	1464	idiopathic orthostatic hypotension	Disease	C544351
611664	CID	D011433	D006973

612112|t|Total intravenous anesthesia with etomidate. III. Some observations in adults.
612112|a|An investigation was undertaken to determine the dosage of etomidate required to maintain sleep in adults undergoing surgery under regional local anesthesia. Premedication of diazepam 10 mg and atropine 0.5 mg was given, and sleep was induced and maintained by intermittent intravenous injections of etomidate 0.1/mg/kg, given whenever the patient would open his eyes on request. A mean overall dose of etomidate 17.4 microgram/kg/min. was required to maintain sleep, but great individual variation occurred, with older patients requiring less drug. The investigation was discontinued after 18 patients because of the frequency and intensity of side-effects, particularly pain and myoclonia, which caused the technique to be abandoned in two cases. It is considered unlikely that etomidate will prove to be the hypnotic of choice for a totally intravenous anesthetic technique in adults because of the high incidence of myoclonia after prolonged administration. In several patients uncontrollable muscle movements persisted for many minutes after complete recovery of consciousness.
612112	34	43	etomidate	Chemical	D005045
612112	138	147	etomidate	Chemical	D005045
612112	254	262	diazepam	Chemical	D003975
612112	273	281	atropine	Chemical	D001285
612112	379	388	etomidate	Chemical	D005045
612112	482	491	etomidate	Chemical	D005045
612112	751	755	pain	Disease	D010146
612112	760	769	myoclonia	Disease	D009207
612112	859	868	etomidate	Chemical	D005045
612112	999	1008	myoclonia	Disease	D009207
612112	CID	D005045	D009207
612112	CID	D005045	D010146

689020|t|A method for the measurement of tremor, and a comparison of the effects of tocolytic beta-mimetics.
689020|a|A method permitting measurement of finger tremor as a displacement-time curve is described, using a test system with simple amplitude calibration. The coordinates of the inversion points of the displacement-time curves were transferred through graphical input equipment to punched tape. By means of a computer program, periods and amplitudes of tremor oscillations were calculated and classified. The event frequency for each class of periods and amplitudes was determined. The actions of fenoterol-hydrobromide, ritodrin-HCl and placebo given to 10 healthy subjects by intravenous infusion in a double-blind crossover study were tested by this method. At therapeutic doses both substances raised the mean tremor amplitude to about three times the control level. At the same time, the mean period within each class of amplitudes shortened by 10--20 ms, whereas the mean periods calculated from all oscillations together did not change significantly. After the end of fenoterol-hydrobromide infusion, tremor amplitudes decreased significantly faster than those following ritodrin-HCl infusion.
689020	32	38	tremor	Disease	D014202
689020	142	148	tremor	Disease	D014202
689020	445	451	tremor	Disease	D014202
689020	589	611	fenoterol-hydrobromide	Chemical	D005280
689020	613	625	ritodrin-HCl	Chemical	D012312
689020	806	812	tremor	Disease	D014202
689020	1067	1089	fenoterol-hydrobromide	Chemical	D005280
689020	1100	1106	tremor	Disease	D014202
689020	1170	1182	ritodrin-HCl	Chemical	D012312
689020	CID	D005280	D014202
689020	CID	D012312	D014202

733189|t|Bilateral retinal artery and choriocapillaris occlusion following the injection of long-acting corticosteroid suspensions in combination with other drugs: I. Clinical studies.
733189|a|Two well-documented cases of bilateral retinal artery and choriocapillaris occlusions with blindness following head and neck soft-tissue injection with methylprednisolone acetate in combination with lidocaine, epinephrine, or penicillin are reported. One case had only a unilateral injection. The acute observations included hazy sensorium, superior gaze palsy, pupillary abnormalities, and conjunctival hemorrhages with edema. Follow-up changes showed marked visual loss, constricted visual fields, optic nerve pallor, vascular attenuation, and chorioretinal atrophy. The literature is reviewed, and possible causes are discussed.
733189	10	55	retinal artery and choriocapillaris occlusion	Disease	D015356
733189	95	109	corticosteroid	Chemical	D000305
733189	215	261	retinal artery and choriocapillaris occlusions	Disease	D015356
733189	267	276	blindness	Disease	D001766
733189	328	354	methylprednisolone acetate	Chemical	C000873
733189	375	384	lidocaine	Chemical	D008012
733189	386	397	epinephrine	Chemical	D004837
733189	402	412	penicillin	Chemical	D010406
733189	531	536	palsy	Disease	D010243
733189	538	561	pupillary abnormalities	Disease	D011681
733189	580	591	hemorrhages	Disease	D006470
733189	597	602	edema	Disease	D004487
733189	636	647	visual loss	Disease	D014786
733189	722	743	chorioretinal atrophy	Disease	C566236
733189	CID	C000873	D015356

816141|t|Cephalothin-induced immune hemolytic anemia.
816141|a|A patient with renal disease developed Coombs-positive hemolytic anemia while receiving cephalothin therapy. An anti-cephalothin IgG antibody was detected in the patient's serum and in the eluates from her erythrocytes. In addition, nonimmunologic binding of normal and patient's serum proteins to her own and cephalothin-coated normal red cells was demonstrated. Skin tests and in vitro lymphocyte stimulation revealed that the patient was sensitized to cephalothin and also to ampicillin. Careful investigation of drug-induced hemolytic anemias reveals the complexity of the immune mechanisms involved.
816141	0	11	Cephalothin	Chemical	D002512
816141	27	43	hemolytic anemia	Disease	D000743
816141	60	73	renal disease	Disease	D007674
816141	100	116	hemolytic anemia	Disease	D000743
816141	133	144	cephalothin	Chemical	D002512
816141	162	173	cephalothin	Chemical	D002512
816141	355	366	cephalothin	Chemical	D002512
816141	500	511	cephalothin	Chemical	D002512
816141	524	534	ampicillin	Chemical	D000667
816141	574	591	hemolytic anemias	Disease	D000743
816141	CID	D002512	D000743

851038|t|Kaliuretic effect of L-dopa treatment in parkinsonian patients.
851038|a|Hypokalemia, sometimes severe, was observed in some L-dopa-treated parkinsonian patients. The influence of L-dopa on the renal excretion of potassium was studied in 3 patients with hypokalemia and in 5 normokalemic patients by determination of renal plasma flow, glomerular filtration rate, plasma concentration of potassium and sodium as well as urinary excretion of potassium, sodium and aldosterone. L-Dopa intake was found to cause an increased excretion of potassium, and sometimes also of sodium, in the hypokalemic but not in the normokalemic patients. This effect on the renal function could be prohibited by the administration of a peripheral dopa decarbodylase inhibitor. It is not known why this effect occurred in some individuals but not in others, but our results indicate a correlation between aldosterone production and this renal effect of L-dopa.
851038	21	27	L-dopa	Chemical	D007980
851038	41	53	parkinsonian	Disease	D010300
851038	64	75	Hypokalemia	Disease	D007008
851038	116	122	L-dopa	Chemical	D007980
851038	131	143	parkinsonian	Disease	D010300
851038	171	177	L-dopa	Chemical	D007980
851038	204	213	potassium	Chemical	D011188
851038	245	256	hypokalemia	Disease	D007008
851038	379	388	potassium	Chemical	D011188
851038	393	399	sodium	Chemical	D012964
851038	432	441	potassium	Chemical	D011188
851038	443	449	sodium	Chemical	D012964
851038	454	465	aldosterone	Chemical	D000450
851038	467	473	L-Dopa	Chemical	D007980
851038	526	535	potassium	Chemical	D011188
851038	559	565	sodium	Chemical	D012964
851038	873	884	aldosterone	Chemical	D000450
851038	921	927	L-dopa	Chemical	D007980
851038	CID	D007980	D007008

891494|t|Phenytoin encephalopathy as probable idiosyncratic reaction: case report.
891494|a|A case of phenytoin (DPH) encephalopathy with increasing seizures and EEG and mental changes is described. Despite adequate oral dosage of DPH (5 mg/kg/daily) the plasma level was very low (2.8 microgramg/ml). The encephalopathy was probably an idiosyncratic and not toxic or allergic reaction. In fact the concentration of free DPH was normal, the patient presented a retarded morbilliform rash during DPH treatment, the protidogram was normal, and an intradermic DPH injection had no local effect. The authors conclude that in a patient starting DPH treatment an unexpected increase in seizures, with EEG and mental changes occurring simultaneously, should alert the physician to the possible need for eliminating DPH from the therapeutic regimen, even if plasma concentrations are low.
891494	0	9	Phenytoin	Chemical	D010672
891494	10	24	encephalopathy	Disease	D001927
891494	84	93	phenytoin	Chemical	D010672
891494	95	98	DPH	Chemical	D010672
891494	100	114	encephalopathy	Disease	D001927
891494	131	139	seizures	Disease	D012640
891494	213	216	DPH	Chemical	D010672
891494	288	302	encephalopathy	Disease	D001927
891494	403	406	DPH	Chemical	D010672
891494	465	469	rash	Disease	D005076
891494	477	480	DPH	Chemical	D010672
891494	539	542	DPH	Chemical	D010672
891494	622	625	DPH	Chemical	D010672
891494	662	670	seizures	Disease	D012640
891494	790	793	DPH	Chemical	D010672
891494	CID	D010672	D001927

895432|t|Effects of exercise on the severity of isoproterenol-induced myocardial infarction.
895432|a|The effect of exercise on the severity of isoproterenol-induced myocardial infarction was studied in male rats. Ninety-three rats were randomly divided into three groups. The exercise-isoproterenol (E-1) and exercise control (EC) groups exercised daily for thirty days on a treadmill at 1 mph, 2% grade while animals of the sedentary-isoproterenol (S-I) group remained sedentary. Eight animals were assigned to the sedentary control (SC) group which remained sedentary throughout the experimental period. Forty-eight hours after the final exercise period, S-I and E-I animals received a single subcutaneous injection of isoproterenol (250 mg/kg body weight). Animals of the S-I group exhibited significantly (Pp less than 0.05) greater mortality from the effects of isoproterenol than animals of the E-I group. Serum CPK activity for E-I animals was significantly (p less than 0.05) greater than for animals in the S-I and EC groups twenty hours following isoproterenol injection. No statistically significant differences were observed between the two isoproterenol treated groups for severity of the induced lesions, changes in heart weight, or heart weight to body weight ratios. The results indicated that exercise reduced the mortality associated with the effects of large dosages of isoproterenol but had little on the severity of the infarction.
895432	39	52	isoproterenol	Chemical	D007545
895432	61	82	myocardial infarction	Disease	D009203
895432	126	139	isoproterenol	Chemical	D007545
895432	148	169	myocardial infarction	Disease	D009203
895432	268	281	isoproterenol	Chemical	D007545
895432	418	431	isoproterenol	Chemical	D007545
895432	704	717	isoproterenol	Chemical	D007545
895432	850	863	isoproterenol	Chemical	D007545
895432	1040	1053	isoproterenol	Chemical	D007545
895432	1136	1149	isoproterenol	Chemical	D007545
895432	1372	1385	isoproterenol	Chemical	D007545
895432	1424	1434	infarction	Disease	D007238
895432	CID	D007545	D009203

931801|t|Effect of D-Glucarates on basic antibiotic-induced renal damage in rats.
931801|a|Dehydrated rats regularly develop acute renal failure following single injection of aminoglycoside antibiotics combined with dextran or of antibiotics only. Oral administration of 2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone protected rats against renal failure induced by kanamycin-dextran. The protective effect was prevalent among D-glucarates, and also to other saccharic acid, hexauronic acids and hexaaldonic acids, although to a lesser degree, but not to a hexaaldose, sugar alcohols, substances inthe TCA cycle and other acidic compounds. D-Glucarates were effective against renal damage induced by peptide antibiotics as well as various aminoglycoside antibitocis. Dose-responses were observed in the protective effect of D-Glucarates. With a D-glucarate of a fixed size of dose, approximately the same degree of protection was obtained against renal damages induced by different basic antibiotics despite large disparities in administration doses of different antibiotics. D-Glucarates had the ability to prevent renal damage but not to cure it. Rats excreted acidic urine when they were spared from renal lesions by monosaccharides. The reduction effect of D-glucarates against nephrotoxicity of basic antibiotics was discussed.
931801	10	22	D-Glucarates	Chemical	D005937
931801	51	63	renal damage	Disease	D007674
931801	73	83	Dehydrated	Disease	D003681
931801	107	126	acute renal failure	Disease	D058186
931801	157	171	aminoglycoside	Chemical	D000617
931801	253	296	2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone	Chemical	C038936
931801	320	333	renal failure	Disease	D051437
931801	345	354	kanamycin	Chemical	D007612
931801	406	418	D-glucarates	Chemical	D005937
931801	438	452	saccharic acid	Chemical	D005937
931801	454	470	hexauronic acids	Chemical	D006603
931801	475	492	hexaaldonic acids	Chemical	-1
931801	548	562	sugar alcohols	Chemical	D013402
931801	581	584	TCA	Chemical	D002952
931801	619	631	D-Glucarates	Chemical	D005937
931801	655	667	renal damage	Disease	D007674
931801	718	732	aminoglycoside	Chemical	D000617
931801	803	815	D-Glucarates	Chemical	D005937
931801	824	835	D-glucarate	Chemical	D005937
931801	926	939	renal damages	Disease	D007674
931801	1055	1067	D-Glucarates	Chemical	D005937
931801	1095	1107	renal damage	Disease	D007674
931801	1182	1195	renal lesions	Disease	D007674
931801	1199	1214	monosaccharides	Chemical	D009005
931801	1240	1252	D-glucarates	Chemical	D005937
931801	1261	1275	nephrotoxicity	Disease	D007674
931801	CID	D000617	D058186
931801	CID	D007612	D058186

946593|t|Paraplegia following intrathecal methotrexate: report of a case and review of the literature.
946593|a|A patient who developed paraplegia following the intrathecal instillation of methotrexate is discribed. The ten previously reported cases of this unusual complication are reviewed. The following factors appear to predispose to the development of this complication: abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia, and epidural cerebrospinal leakage; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents; and the use of methotrexate diluents of unphysiologic pH, ionic content and osmolarity. The role of methotrexate contaminants, local folate deficiency, and cranial irradiation in the pathogenesis of intrathecal methotrexate toxicity is unclear. The incidence of neurotoxicity may be reduced by employing lower doses of methotrexate in the presence of central nervous system leukemia, in older children and adults, and in the presence of epidural leakage. Only preservative-free methotrexate in Elliott's B Solution at a concentration of not more than 1 mg/ml should be used for intrathecal administration. Periodic monitoring of cerebruspinal fluid methotrexate levels may be predictive of the development of serious neurotoxicity.
946593	0	10	Paraplegia	Disease	D010264
946593	33	45	methotrexate	Chemical	D008727
946593	118	128	paraplegia	Disease	D010264
946593	171	183	methotrexate	Chemical	D008727
946593	418	449	central nervous system leukemia	Disease	D002493
946593	516	528	methothexate	Chemical	D008727
946593	620	632	methotrexate	Chemical	D008727
946593	725	735	neurotoxic	Disease	D020258
946593	776	788	methotrexate	Chemical	D008727
946593	831	843	methotrexate	Chemical	D008727
946593	916	928	methotrexate	Chemical	D008727
946593	949	966	folate deficiency	Disease	C536409
946593	1027	1039	methotrexate	Chemical	D008727
946593	1040	1048	toxicity	Disease	D064420
946593	1078	1091	neurotoxicity	Disease	D020258
946593	1135	1147	methotrexate	Chemical	D008727
946593	1167	1198	central nervous system leukemia	Disease	D002493
946593	1294	1306	methotrexate	Chemical	D008727
946593	1465	1477	methotrexate	Chemical	D008727
946593	1533	1546	neurotoxicity	Disease	D020258
946593	CID	D008727	D010264

978847|t|Centrally mediated cardiovascular effects of intracisternal application of carbachol in anesthetized rats.
978847|a|The pressor response to the intracisternal (i.c.) injection of carbachol (1 mug) in anesthetized rats was analyzed. This response was significantly reduced by the intravenous (i.v.) injection of guanethidine (5 mg), hexamethonium (10 mg) or phentolamine (5 mg), and conversely, potentiated by i.v. desmethylimipramine (0.3 mg), while propranolol (0.5 mg) i.v. selectively inhibited the enlargement of pulse pressure and the tachycardia following i.c. carbachol (1 mug). On the other hand, the pressor response to i.c. carbachol (1 mug) was almost completely blocked by i.c. atropine (3 mug) or hexamethonium (500 mug), and significantly reduced by i.c. chlorpromazine (50 mug) but significantly potentiated by i.c. desmethylimipramine (30 mug). The pressor response to i.c. carbachol (1 mug) remained unchanged after sectioning of the bilateral cervical vagal nerves but disappeared after sectioning of the spinal cord (C7-C8). From the above result it is suggested that the pressor response to i.c. carbachol ortral and peripheral adrenergic mechanisms, and that the sympathetic trunk is the main pathway.
978847	75	84	carbachol	Chemical	D002217
978847	170	179	carbachol	Chemical	D002217
978847	302	314	guanethidine	Chemical	D006145
978847	323	336	hexamethonium	Chemical	D018738
978847	348	360	phentolamine	Chemical	D010646
978847	405	424	desmethylimipramine	Chemical	D003891
978847	441	452	propranolol	Chemical	D011433
978847	493	522	enlargement of pulse pressure	Disease	D006973
978847	531	542	tachycardia	Disease	D013610
978847	558	567	carbachol	Chemical	D002217
978847	625	634	carbachol	Chemical	D002217
978847	681	689	atropine	Chemical	D001285
978847	701	714	hexamethonium	Chemical	D018738
978847	760	774	chlorpromazine	Chemical	D002746
978847	822	841	desmethylimipramine	Chemical	D003891
978847	881	890	carbachol	Chemical	D002217
978847	1107	1116	carbachol	Chemical	D002217
978847	CID	D002217	D013610
978847	CID	D002217	D006973
978847	CID	D003891	D006973

1117341|t|Hyperglycemic effect of amino compounds structurally related to caproate in rats.
1117341|a|The chronic feeding of small amounts (0.3-3% of diet weight) of certain amino derivatives of caproate resulted in hyperglycemia, an elevated glucose tolerance curve and, occasionally, glucosuria. Effective compounds included norleucine, norvaline, glutamate, epsilon-aminocaproate, methionine, and leucine.
1117341	0	13	Hyperglycemic	Disease	D006943
1117341	24	29	amino	Chemical	D015119
1117341	64	72	caproate	Chemical	C037652
1117341	154	159	amino	Chemical	D015119
1117341	175	183	caproate	Chemical	C037652
1117341	196	209	hyperglycemia	Disease	D006943
1117341	223	230	glucose	Chemical	D005947
1117341	266	276	glucosuria	Disease	D006030
1117341	307	317	norleucine	Chemical	-1
1117341	319	328	norvaline	Chemical	-1
1117341	330	339	glutamate	Chemical	D018698
1117341	341	362	epsilon-aminocaproate	Chemical	-1
1117341	364	374	methionine	Chemical	D008715
1117341	380	387	leucine	Chemical	-1
1117341	CID	D015119	D006943

1158089|t|Fatty liver induced by tetracycline in the rat. Dose-response relationships and effect of sex.
1158089|a|Dose-response relationships, biochemical mechanisms, and sex differences in the experimental fatty liver induced by tetracycline were studied in the intact rat and with the isolated perfused rat liver in vitro. In the intact male and female rat, no direct relationship was observed between dose of tetracycline and hepatic accumulation of triglyceride. With provision of adequate oleic acid as a substrate for the isolated perfused liver, a direct relationship was observed between dose of tetracycline and both accumulation of triglyceride in the liver and depression of output of triglyceride by livers from male and female rats. Marked differences were observed between female and male rats with regard to base line (control) hepatic concentration of triglyceride and output of triglyceride. Accumulation of hepatic triglyceride, as a per cent of control values, in response to graded doses of tetracycline, did not differ significantly between male, female and pregnant rat livers. However, livers from female, and especially pregnant female rats, were strikingly resistant to the effects of tetracycline on depression of output of triglyceride under these experimental conditions. These differences between the sexes could not be related to altered disposition of tetracycline or altered uptake of oleic acid. Depressed hepatic secretion of triglyceride accounted only for 30 to 50% of accumulated hepatic triglyceride, indicating that additional mechanisms must be involved in the production of the triglyceride-rich fatty liver in response to tetracycline.
1158089	0	11	Fatty liver	Disease	D005234
1158089	23	35	tetracycline	Chemical	D013752
1158089	188	199	fatty liver	Disease	D005234
1158089	211	223	tetracycline	Chemical	D013752
1158089	393	405	tetracycline	Chemical	D013752
1158089	434	446	triglyceride	Chemical	D014280
1158089	475	485	oleic acid	Chemical	D019301
1158089	585	597	tetracycline	Chemical	D013752
1158089	623	635	triglyceride	Chemical	D014280
1158089	653	663	depression	Disease	D003866
1158089	677	689	triglyceride	Chemical	D014280
1158089	849	861	triglyceride	Chemical	D014280
1158089	876	888	triglyceride	Chemical	D014280
1158089	914	926	triglyceride	Chemical	D014280
1158089	992	1004	tetracycline	Chemical	D013752
1158089	1191	1203	tetracycline	Chemical	D013752
1158089	1207	1217	depression	Disease	D003866
1158089	1231	1243	triglyceride	Chemical	D014280
1158089	1364	1376	tetracycline	Chemical	D013752
1158089	1398	1408	oleic acid	Chemical	D019301
1158089	1441	1453	triglyceride	Chemical	D014280
1158089	1506	1518	triglyceride	Chemical	D014280
1158089	1600	1612	triglyceride	Chemical	D014280
1158089	1618	1629	fatty liver	Disease	D005234
1158089	1645	1657	tetracycline	Chemical	D013752
1158089	CID	D013752	D005234

1280054|t|Fatal myeloencephalopathy due to intrathecal vincristine administration.
1280054|a|Vincristine was accidentally given intrathecally to a child with leukaemia, producing sensory and motor dysfunction followed by encephalopathy and death. Separate times for administering vincristine and intrathecal therapy is recommended.
1280054	6	25	myeloencephalopathy	Disease	D001927
1280054	45	56	vincristine	Chemical	D014750
1280054	73	84	Vincristine	Chemical	D014750
1280054	138	147	leukaemia	Disease	D007938
1280054	159	188	sensory and motor dysfunction	Disease	D007049
1280054	201	215	encephalopathy	Disease	D001927
1280054	260	271	vincristine	Chemical	D014750
1280054	CID	D014750	D007049
1280054	CID	D014750	D001927

1280707|t|Progesterone potentiation of bupivacaine arrhythmogenicity in pentobarbital-anesthetized rats and beating rat heart cell cultures.
1280707|a|The effects of progesterone treatment on bupivacaine arrhythmogenicity in beating rat heart myocyte cultures and on anesthetized rats were determined. After determining the bupivacaine AD50 (the concentration of bupivacaine that caused 50% of all beating rat heart myocyte cultures to become arrhythmic), we determined the effect of 1-hour progesterone HCl exposure on myocyte contractile rhythm. Each concentration of progesterone (6.25, 12.5, 25, and 50 micrograms/ml) caused a significant and concentration-dependent reduction in the AD50 for bupivacaine. Estradiol treatment also increased the arrhythmogenicity of bupivacaine in myocyte cultures, but was only one fourth as potent as progesterone. Neither progesterone nor estradiol effects on bupivacaine arrhythmogenicity were potentiated by epinephrine. Chronic progesterone pretreatment (5 mg/kg/day for 21 days) caused a significant increase in bupivacaine arrhythmogenicity in intact pentobarbital-anesthetized rats. There was a significant decrease in the time to onset of arrhythmia as compared with control nonprogesterone-treated rats (6.2 +/- 1.3 vs. 30.8 +/- 2.5 min, mean +/- SE). The results of this study indicate that progesterone can potentiate bupivacaine arrhythmogenicity both in vivo and in vitro. Potentiation of bupivacaine arrhythmia in myocyte cultures suggests that this effect is at least partly mediated at the myocyte level.
1280707	0	12	Progesterone	Chemical	D011374
1280707	29	40	bupivacaine	Chemical	D002045
1280707	62	75	pentobarbital	Chemical	D010424
1280707	146	158	progesterone	Chemical	D011374
1280707	172	183	bupivacaine	Chemical	D002045
1280707	304	315	bupivacaine	Chemical	D002045
1280707	343	354	bupivacaine	Chemical	D002045
1280707	423	433	arrhythmic	Disease	D001145
1280707	471	483	progesterone	Chemical	D011374
1280707	484	487	HCl	Chemical	D006851
1280707	550	562	progesterone	Chemical	D011374
1280707	677	688	bupivacaine	Chemical	D002045
1280707	690	699	Estradiol	Chemical	D004958
1280707	750	761	bupivacaine	Chemical	D002045
1280707	820	832	progesterone	Chemical	D011374
1280707	842	854	progesterone	Chemical	D011374
1280707	859	868	estradiol	Chemical	D004958
1280707	880	891	bupivacaine	Chemical	D002045
1280707	930	941	epinephrine	Chemical	D004837
1280707	951	963	progesterone	Chemical	D011374
1280707	1036	1047	bupivacaine	Chemical	D002045
1280707	1076	1089	pentobarbital	Chemical	D010424
1280707	1166	1176	arrhythmia	Disease	D001145
1280707	1320	1332	progesterone	Chemical	D011374
1280707	1348	1359	bupivacaine	Chemical	D002045
1280707	1421	1432	bupivacaine	Chemical	D002045
1280707	1433	1443	arrhythmia	Disease	D001145
1280707	CID	D002045	D001145
1280707	CID	D004958	D001145
1280707	CID	D011374	D001145

1289188|t|Acute renal failure occurring during intravenous desferrioxamine therapy: recovery after haemodialysis.
1289188|a|A patient with transfusion-dependent thalassemia was undergoing home intravenous desferrioxamine (DFX) treatment by means of a totally implanted system because of his poor compliance with the nightly subcutaneous therapy. Due to an accidental malfunctioning of the infusion pump, the patient was inadvertently administered a toxic dosage of the drug which caused renal insufficiency. Given the progressive deterioration of the symptoms and of the laboratory values, despite adequate medical treatment, a decision was made to introduce haemodialytical therapy in order to remove the drug and therapy reduce the nephrotoxicity. From the results obtained, haemodialysis can therefore be suggested as a useful therapy in rare cases of progressive acute renal failure caused by desferrioxamine.
1289188	0	19	Acute renal failure	Disease	D058186
1289188	49	64	desferrioxamine	Chemical	D003676
1289188	141	152	thalassemia	Disease	D013789
1289188	185	200	desferrioxamine	Chemical	D003676
1289188	202	205	DFX	Chemical	D003676
1289188	467	486	renal insufficiency	Disease	D051437
1289188	714	728	nephrotoxicity	Disease	D007674
1289188	847	866	acute renal failure	Disease	D058186
1289188	877	892	desferrioxamine	Chemical	D003676
1289188	CID	D003676	D051437

1359137|t|Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine?
1359137|a|Six stable psychiatric outpatients with hyperprolactinemia and amenorrhea/oligomenorrhea associated with their neuroleptic medications were treated with bromocriptine. Daily dosages of 5-10 mg corrected the hyperprolactinemia and restored menstruation in four of the six patients. One woman, however, developed worsened psychiatric symptoms while taking bromocriptine, and it was discontinued. Thus, three of six patients had their menstrual irregularity successfully corrected with bromocriptine. This suggests that bromocriptine should be further evaluated as potential therapy for neuroleptic-associated hyperprolactinemia and amenorrhea/galactorrhea.
1359137	0	11	Neuroleptic	Chemical	D014150
1359137	23	41	hyperprolactinemia	Disease	D006966
1359137	66	79	bromocriptine	Chemical	D001971
1359137	121	139	hyperprolactinemia	Disease	D006966
1359137	144	154	amenorrhea	Disease	D000568
1359137	155	169	oligomenorrhea	Disease	D009839
1359137	192	215	neuroleptic medications	Chemical	D014150
1359137	234	247	bromocriptine	Chemical	D001971
1359137	288	306	hyperprolactinemia	Disease	D006966
1359137	401	421	psychiatric symptoms	Disease	D011618
1359137	435	448	bromocriptine	Chemical	D001971
1359137	564	577	bromocriptine	Chemical	D001971
1359137	598	611	bromocriptine	Chemical	D001971
1359137	665	676	neuroleptic	Chemical	D014150
1359137	688	706	hyperprolactinemia	Disease	D006966
1359137	711	721	amenorrhea	Disease	D000568
1359137	722	734	galactorrhea	Disease	D005687
1359137	CID	D001971	D011618
1359137	CID	D014150	D000568
1359137	CID	D014150	D009839
1359137	CID	D014150	D006966

1360900|t|Ethacrynic acid-induced convulsions and brain neurotransmitters in mice.
1360900|a|Intracerebroventricular injection of ethacrynic acid (50% convulsive dose; 50 micrograms/mouse) accelerated the synthesis/turnover of 5-hydroxytryptamine (5-HT) but suppressed the synthesis of gamma-aminobutyric acid and acetylcholine in mouse brain. These effects were completely antagonized by pretreatment with a glutamate/N-methyl-D-aspartate antagonist, aminophosphonovaleric acid. In ethacrynic acid-induced convulsions, these neurotransmitter systems may be differentially modulated, probably through activation of glutaminergic neurons in the brain.
1360900	0	15	Ethacrynic acid	Chemical	D004976
1360900	24	35	convulsions	Disease	D012640
1360900	110	125	ethacrynic acid	Chemical	D004976
1360900	131	141	convulsive	Disease	D012640
1360900	207	226	5-hydroxytryptamine	Chemical	D012701
1360900	228	232	5-HT	Chemical	D012701
1360900	266	289	gamma-aminobutyric acid	Chemical	D005680
1360900	294	307	acetylcholine	Chemical	D000109
1360900	389	398	glutamate	Chemical	D018698
1360900	399	419	N-methyl-D-aspartate	Chemical	D016202
1360900	432	458	aminophosphonovaleric acid	Chemical	-1
1360900	463	478	ethacrynic acid	Chemical	D004976
1360900	487	498	convulsions	Disease	D012640
1360900	CID	D004976	D012640

1361574|t|Pharmacology of gamma-aminobutyric acidA receptor complex after the in vivo administration of the anxioselective and anticonvulsant beta-carboline derivative abecarnil.
1361574|a|In rodents, the effect of the beta-carboline derivative isopropyl-6- benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate (abecarrnil), a new ligand for benzodiazepine receptors possessing anxiolytic and anticonvulsant properties, was evaluated on the function of central gamma-aminobutyric acid (GABA)A receptor complex, both in vitro and in vivo. Added in vitro to rat cortical membrane preparation, abecarnil increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced the binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS). These effects were similar to those induced by diazepam, whereas the partial agonist Ro 16-6028 (tert-butyl-(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H- imidazo[1,5-a]-pyrrolo-[2,1-c][1,4]benzodiazepine-1-carboxylate) showed very weak efficacy in these biochemical tests. After i.p. injection to rats, abecarnil and diazepam decreased in a time-dependent and dose-related (0.25-20 mg/kg i.p.) manner [35S]TBPS binding measured ex vivo in the cerebral cortex. Moreover, both drugs at the dose of 0.5 mg/kg antagonized completely the convulsant activity and the increase of [35S]TBPS binding induced by isoniazide (350 mg/kg s.c.) as well as the increase of [35S]TBPS binding induced by foot-shock stress. To better correlate the biochemical and the pharmacological effects, we studied the action of abecarnil on [35S]TBPS binding, exploratory motility and on isoniazid-induced biochemical and pharmacological effects in mice. In these animals, abecarnil produced a paralleled dose-dependent (0.05-1 mg/kg i.p.) reduction of both motor behavior and cortical [35S]TBPS binding. Moreover, 0.05 mg/kg of this beta-carboline reduced markedly the increase of [35S]TBPS binding and the convulsions induced by isoniazid (200 mg/kg s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)
1361574	16	39	gamma-aminobutyric acid	Chemical	D005680
1361574	132	146	beta-carboline	Chemical	D002243
1361574	158	167	abecarnil	Chemical	C062769
1361574	199	213	beta-carboline	Chemical	D002243
1361574	225	292	isopropyl-6- benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate	Chemical	C062769
1361574	294	304	abecarrnil	Chemical	C062769
1361574	324	338	benzodiazepine	Chemical	D001569
1361574	443	466	gamma-aminobutyric acid	Chemical	D005680
1361574	468	472	GABA	Chemical	D005680
1361574	573	582	abecarnil	Chemical	C062769
1361574	597	601	GABA	Chemical	D005680
1361574	620	628	muscimol	Chemical	D009118
1361574	680	716	t-[35S]butylbicyclophosphorothionate	Chemical	C037476
1361574	718	727	[35S]TBPS	Chemical	C037476
1361574	777	785	diazepam	Chemical	D003975
1361574	815	825	Ro 16-6028	Chemical	C054626
1361574	827	947	tert-butyl-(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H- imidazo[1,5-a]-pyrrolo-[2,1-c][1,4]benzodiazepine-1-carboxylate	Chemical	C054626
1361574	1033	1042	abecarnil	Chemical	C062769
1361574	1047	1055	diazepam	Chemical	D003975
1361574	1131	1140	[35S]TBPS	Chemical	C037476
1361574	1303	1312	[35S]TBPS	Chemical	C037476
1361574	1332	1342	isoniazide	Chemical	D007538
1361574	1387	1396	[35S]TBPS	Chemical	C037476
1361574	1529	1538	abecarnil	Chemical	C062769
1361574	1542	1551	[35S]TBPS	Chemical	C037476
1361574	1589	1598	isoniazid	Chemical	D007538
1361574	1674	1683	abecarnil	Chemical	C062769
1361574	1835	1849	beta-carboline	Chemical	D002243
1361574	1883	1892	[35S]TBPS	Chemical	C037476
1361574	1909	1920	convulsions	Disease	D012640
1361574	1932	1941	isoniazid	Chemical	D007538
1361574	CID	D007538	D012640

1395192|t|Recurrent myocardial infarction in a postpartum patient receiving bromocriptine.
1395192|a|Myocardial infarction in puerperium is infrequently reported. Spasm, coronary dissection, or atheromatous etiology has been described. Bromocriptine has been implicated in several previous case reports of myocardial infarction in the puerperium. Our case (including an inadvertent rechallenge) suggests such a relationship. Although generally regarded as "safe," possible serious cardiac effects of bromocriptine should be acknowledged.
1395192	10	31	myocardial infarction	Disease	D009203
1395192	66	79	bromocriptine	Chemical	D001971
1395192	81	102	Myocardial infarction	Disease	D009203
1395192	143	148	Spasm	Disease	D013035
1395192	216	229	Bromocriptine	Chemical	D001971
1395192	286	307	myocardial infarction	Disease	D009203
1395192	480	493	bromocriptine	Chemical	D001971
1395192	CID	D001971	D009203

1420650|t|Asterixis induced by carbamazepine therapy.
1420650|a|There are very few reports about asterixis as a side effect of treatment with psychopharmacologic agents. In this report we present four patients treated with a combination of different psychotropic drugs, in whom asterixis was triggered either by adding carbamazepine (CBZ) to a treatment regimen, or by increasing its dosage. Neither dosage nor serum levels of CBZ were in a higher range. We consider asterixis to be an easily overlooked sign of neurotoxicity, which may occur even at low or moderate dosage levels, if certain drugs as lithium or clozapine are used in combination with CBZ.
1420650	0	9	Asterixis	Disease	D020820
1420650	21	34	carbamazepine	Chemical	D002220
1420650	77	86	asterixis	Disease	D020820
1420650	258	267	asterixis	Disease	D020820
1420650	299	312	carbamazepine	Chemical	D002220
1420650	314	317	CBZ	Chemical	D002220
1420650	407	410	CBZ	Chemical	D002220
1420650	447	456	asterixis	Disease	D020820
1420650	492	505	neurotoxicity	Disease	D020258
1420650	582	589	lithium	Chemical	D008094
1420650	593	602	clozapine	Chemical	D003024
1420650	632	635	CBZ	Chemical	D002220
1420650	CID	D008094	D020820
1420650	CID	D003024	D020820

1423336|t|Pharmacodynamics of the hypotensive effect of levodopa in parkinsonian patients.
1423336|a|Blood pressure effects of i.v. levodopa were examined in parkinsonian patients with stable and fluctuating responses to levodopa. The magnitude of the hypotensive effect of levodopa was concentration dependent and was fit to an Emax model in fluctuating responders. Stable responders demonstrated a small hypotensive response. Baseline blood pressures were higher in fluctuating patients; a higher baseline blood pressure correlated with greater hypotensive effects. Antiparkinsonian effects of levodopa temporally correlated with blood pressure changes. Phenylalanine, a large neutral amino acid (LNAA) competing with levodopa for transport across the blood-brain barrier, reduced the hypotensive and antiparkinsonian effects of levodopa. We conclude that levodopa has a central hypotensive action that parallels the motor effects in fluctuating patients. The hypotensive effect appears to be related to the higher baseline blood pressure we observed in fluctuating patients relative to stable patients.
1423336	24	35	hypotensive	Disease	D007022
1423336	46	54	levodopa	Chemical	D007980
1423336	58	70	parkinsonian	Disease	D010300
1423336	112	120	levodopa	Chemical	D007980
1423336	138	150	parkinsonian	Disease	D010300
1423336	201	209	levodopa	Chemical	D007980
1423336	232	243	hypotensive	Disease	D007022
1423336	254	262	levodopa	Chemical	D007980
1423336	386	397	hypotensive	Disease	D007022
1423336	527	538	hypotensive	Disease	D007022
1423336	576	584	levodopa	Chemical	D007980
1423336	636	649	Phenylalanine	Chemical	D010649
1423336	667	677	amino acid	Chemical	D000596
1423336	700	708	levodopa	Chemical	D007980
1423336	767	778	hypotensive	Disease	D007022
1423336	811	819	levodopa	Chemical	D007980
1423336	838	846	levodopa	Chemical	D007980
1423336	861	872	hypotensive	Disease	D007022
1423336	942	953	hypotensive	Disease	D007022
1423336	CID	D007980	D007022

1424076|t|Syndrome of inappropriate secretion of antidiuretic hormone after infusional vincristine.
1424076|a|A 77-year-old woman with refractory multiple myeloma was treated with a 4-day continuous intravenous infusion of vincristine and doxorubicin and 4 days of oral dexamethasone. Nine days after her second cycle she presented with lethargy and weakness associated with hyponatremia. Evaluation revealed the syndrome of inappropriate secretion of antidiuretic hormone, which was attributed to the vincristine infusion. After normal serum sodium levels returned, further doxorubicin and dexamethasone chemotherapy without vincristine did not produce this complication.
1424076	0	59	Syndrome of inappropriate secretion of antidiuretic hormone	Disease	D007177
1424076	77	88	vincristine	Chemical	D014750
1424076	126	142	multiple myeloma	Disease	D009101
1424076	203	214	vincristine	Chemical	D014750
1424076	219	230	doxorubicin	Chemical	D004317
1424076	250	263	dexamethasone	Chemical	D003907
1424076	317	325	lethargy	Disease	D053609
1424076	330	338	weakness	Disease	D018908
1424076	355	367	hyponatremia	Disease	D007010
1424076	393	452	syndrome of inappropriate secretion of antidiuretic hormone	Disease	D007177
1424076	482	493	vincristine	Chemical	D014750
1424076	523	529	sodium	Chemical	D012964
1424076	555	566	doxorubicin	Chemical	D004317
1424076	571	584	dexamethasone	Chemical	D003907
1424076	606	617	vincristine	Chemical	D014750
1424076	CID	D014750	D007177

1449452|t|Heart failure: to digitalise or not? The view against.
1449452|a|Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy.
1449452	0	13	Heart failure	Disease	D006333
1449452	105	112	digoxin	Chemical	D004077
1449452	157	176	atrial fibrillation	Disease	D001281
1449452	177	184	digoxin	Chemical	D004077
1449452	262	275	heart failure	Disease	D006333
1449452	305	312	Digoxin	Chemical	D004077
1449452	410	417	digoxin	Chemical	D004077
1449452	519	530	arrhythmias	Disease	D001145
1449452	758	765	digoxin	Chemical	D004077
1449452	990	997	digoxin	Chemical	D004077
1449452	1027	1048	myocardial infarction	Disease	D009203
1449452	1050	1052	MI	Disease	D009203
1449452	1055	1066	Angiotensin	Chemical	D000809
1449452	1316	1323	digoxin	Chemical	D004077
1449452	1410	1417	digoxin	Chemical	D004077
1449452	CID	D004077	D001145

1522360|t|Intravascular hemolysis and acute renal failure following intermittent rifampin therapy.
1522360|a|Renal failure is a rare complication associated with the use of rifampin. Intravascular hemolysis leading to acute renal failure following rifampin therapy is extremely rare. Two patients with leprosy who developed hemolysis and acute renal failure following rifampin are reported.
1522360	14	23	hemolysis	Disease	D006461
1522360	28	47	acute renal failure	Disease	D058186
1522360	71	79	rifampin	Chemical	D012293
1522360	89	102	Renal failure	Disease	D051437
1522360	153	161	rifampin	Chemical	D012293
1522360	177	186	hemolysis	Disease	D006461
1522360	198	217	acute renal failure	Disease	D058186
1522360	228	236	rifampin	Chemical	D012293
1522360	282	289	leprosy	Disease	D007918
1522360	304	313	hemolysis	Disease	D006461
1522360	318	337	acute renal failure	Disease	D058186
1522360	348	356	rifampin	Chemical	D012293
1522360	CID	D012293	D058186
1522360	CID	D012293	D006461

1556529|t|Zidovudine-induced hepatitis.
1556529|a|A case of acute hepatitis induced by zidovudine in a 38-year-old patient with AIDS is presented. The mechanism whereby the hepatitis was induced is not known. However, the patient tolerated well an alternative reverse transcriptase inhibitor, 2'3' dideoxyinosine. Physicians caring for patients with AIDS should be aware of this hitherto rarely reported complication.
1556529	0	10	Zidovudine	Chemical	D015215
1556529	19	28	hepatitis	Disease	D056486
1556529	46	55	hepatitis	Disease	D056486
1556529	67	77	zidovudine	Chemical	D015215
1556529	108	112	AIDS	Disease	D000163
1556529	153	162	hepatitis	Disease	D056486
1556529	273	292	2'3' dideoxyinosine	Chemical	D016049
1556529	330	334	AIDS	Disease	D000163
1556529	CID	D015215	D056486

1563460|t|Thoracic hematomyelia secondary to coumadin anticoagulant therapy: a case report.
1563460|a|A case of thoracic hematomyelia secondary to anticoagulant therapy is presented. Clinical features, similar to 2 other previously reported cases, are discussed. A high index of suspicion may lead to a quick diagnostic procedure and successful decompressive surgery.
1563460	0	21	Thoracic hematomyelia	Disease	D020758
1563460	35	43	coumadin	Chemical	D014859
1563460	92	113	thoracic hematomyelia	Disease	D020758
1563460	CID	D014859	D020758

1564030|t|Mania associated with fluoxetine treatment in adolescents.
1564030|a|Fluoxetine, a selective serotonin reuptake inhibitor, is gaining increased acceptance in the treatment of adolescent depression. Generally safe and well tolerated by adults, fluoxetine has been reported to induce mania. The cases of five depressed adolescents, 14-16 years of age, who developed mania during pharmacotherapy with fluoxetine, are reported here. Apparent risk factors for the development of mania or hypomania during fluoxetine pharmacotherapy in this population were the combination of attention-deficit hyperactivity disorder and affective instability; major depression with psychotic features; a family history of affective disorder, especially bipolar disorder; and a diagnosis of bipolar disorder. Further study is needed to determine the optimal dosage and to identify risk factors that increase individual vulnerability to fluoxetine induced mania in adolescents.
1564030	0	5	Mania	Disease	D001714
1564030	22	32	fluoxetine	Chemical	D005473
1564030	59	69	Fluoxetine	Chemical	D005473
1564030	83	92	serotonin	Chemical	D012701
1564030	176	186	depression	Disease	D003866
1564030	233	243	fluoxetine	Chemical	D005473
1564030	272	277	mania	Disease	D001714
1564030	297	306	depressed	Disease	D003866
1564030	354	359	mania	Disease	D001714
1564030	388	398	fluoxetine	Chemical	D005473
1564030	464	469	mania	Disease	D001714
1564030	473	482	hypomania	Disease	D001714
1564030	490	500	fluoxetine	Chemical	D005473
1564030	560	600	attention-deficit hyperactivity disorder	Disease	D001289
1564030	634	644	depression	Disease	D003866
1564030	650	659	psychotic	Disease	D011618
1564030	690	708	affective disorder	Disease	D019964
1564030	721	737	bipolar disorder	Disease	D001714
1564030	758	774	bipolar disorder	Disease	D001714
1564030	903	913	fluoxetine	Chemical	D005473
1564030	922	927	mania	Disease	D001714
1564030	CID	D005473	D001714

1615846|t|Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias.
1615846|a|The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
1615846	0	11	Gemfibrozil	Chemical	D015248
1615846	12	22	lovastatin	Chemical	D008148
1615846	43	64	hyperlipoproteinemias	Disease	D006951
1615846	206	217	gemfibrozil	Chemical	D015248
1615846	218	228	lovastatin	Chemical	D008148
1615846	273	287	hyperlipidemia	Disease	D006949
1615846	305	337	atherosclerotic vascular disease	Disease	D002340
1615846	416	427	cholesterol	Chemical	D002784
1615846	480	491	cholesterol	Chemical	D002784
1615846	524	535	cholesterol	Chemical	D002784
1615846	540	551	cholesterol	Chemical	D002784
1615846	603	614	gemfibrozil	Chemical	D015248
1615846	627	637	lovastatin	Chemical	D008148
1615846	847	855	creatine	Chemical	D003401
1615846	1039	1047	creatine	Chemical	D003401
1615846	1191	1202	cholesterol	Chemical	D002784
1615846	1240	1252	triglyceride	Chemical	D014280
1615846	1301	1312	cholesterol	Chemical	D002784
1615846	1364	1375	cholesterol	Chemical	D002784
1615846	1380	1391	cholesterol	Chemical	D002784
1615846	1465	1473	Myositis	Disease	D009220
1615846	1613	1621	creatine	Chemical	D003401
1615846	1667	1681	rhabdomyolysis	Disease	D012206
1615846	1685	1698	myoglobinuria	Disease	D009212
1615846	CID	D015248	D009220
1615846	CID	D008148	D009220

1655018|t|Hepatocellular carcinoma in Fanconi's anemia treated with androgen and corticosteroid.
1655018|a|The case of an 11-year-old boy is reported who was known to have Fanconi's anemia for 3 years and was treated with androgens, corticosteroids and transfusions. Two weeks before his death he was readmitted because of aplastic crisis with septicemia and marked abnormalities in liver function and died of hemorrhagic bronchopneumonia. At autopsy peliosis and multiple hepatic tumors were found which histologically proved to be well-differentiated hepatocellular carcinoma. This case contributes to the previous observations that non-metastasizing hepatic neoplasms and peliosis can develop in patients with androgen- and corticosteroid-treated Fanconi's anemia.
1655018	0	24	Hepatocellular carcinoma	Disease	D006528
1655018	28	44	Fanconi's anemia	Disease	D005199
1655018	58	66	androgen	Chemical	D000728
1655018	71	85	corticosteroid	Chemical	D000305
1655018	152	168	Fanconi's anemia	Disease	D005199
1655018	202	211	androgens	Chemical	D000728
1655018	213	228	corticosteroids	Chemical	D000305
1655018	324	334	septicemia	Disease	D018805
1655018	390	418	hemorrhagic bronchopneumonia	Disease	D001996
1655018	431	439	peliosis	Disease	D010382
1655018	453	467	hepatic tumors	Disease	D008113
1655018	533	557	hepatocellular carcinoma	Disease	D006528
1655018	633	650	hepatic neoplasms	Disease	D008113
1655018	655	663	peliosis	Disease	D010382
1655018	693	701	androgen	Chemical	D000728
1655018	707	721	corticosteroid	Chemical	D000305
1655018	730	746	Fanconi's anemia	Disease	D005199
1655018	CID	D000305	D010382
1655018	CID	D000728	D010382
1655018	CID	D000305	D006528
1655018	CID	D000728	D006528

1735570|t|Chronic lesion of rostral ventrolateral medulla in spontaneously hypertensive rats.
1735570|a|We studied the effects of chronic selective neuronal lesion of rostral ventrolateral medulla on mean arterial pressure, heart rate, and neurogenic tone in conscious, unrestrained spontaneously hypertensive rats. The lesions were placed via bilateral microinjections of 30 nmol/200 nl N-methyl-D-aspartic acid. The restimulation of this area with N-methyl-D-aspartic acid 15 days postlesion failed to produce a pressor response. One day postlesion, the resting mean arterial pressure was significantly decreased in lesioned rats when compared with sham rats (100 +/- 7 versus 173 +/- 4 mm Hg, p less than 0.05). Fifteen days later, the lesioned group still showed values significantly lower than the sham group (150 +/- 6 versus 167 +/- 5 mm Hg, p less than 0.05). No significant heart rate differences were observed between the sham and lesioned groups. The ganglionic blocker trimethaphan (5 mg/kg i.v.) caused similar reductions in mean arterial pressure in both lesioned and sham groups. The trimethaphan-induced hypotension was accompanied by a significant bradycardia in lesioned rats (-32 +/- 13 beats per minute) but a tachycardia in sham rats (+33 +/- 12 beats per minute) 1 day postlesion. Therefore, rostral ventrolateral medulla neurons appear to play a significant role in maintaining hypertension in conscious spontaneously hypertensive rats. Spinal or suprabulbar structures could be responsible for the gradual recovery of the hypertension in the lesioned rats.
1735570	65	77	hypertensive	Disease	D006973
1735570	277	289	hypertensive	Disease	D006973
1735570	368	392	N-methyl-D-aspartic acid	Chemical	D016202
1735570	430	454	N-methyl-D-aspartic acid	Chemical	D016202
1735570	961	973	trimethaphan	Chemical	D014294
1735570	1079	1091	trimethaphan	Chemical	D014294
1735570	1100	1111	hypotension	Disease	D007022
1735570	1145	1156	bradycardia	Disease	D001919
1735570	1210	1221	tachycardia	Disease	D013610
1735570	1381	1393	hypertension	Disease	D006973
1735570	1421	1433	hypertensive	Disease	D006973
1735570	1526	1538	hypertension	Disease	D006973
1735570	CID	D014294	D007022
1735570	CID	D014294	D013610

1756784|t|Damage of substantia nigra pars reticulata during pilocarpine-induced status epilepticus in the rat: immunohistochemical study of neurons, astrocytes and serum-protein extravasation.
1756784|a|The substantia nigra has a gating function controlling the spread of epileptic seizure activity. Additionally, in models of prolonged status epilepticus the pars reticulata of substantia nigra (SNR) suffers from a massive lesion which may arise from a massive metabolic derangement and hyperexcitation developing in the activated SNR. In this study, status epilepticus was induced by systemic injection of pilocarpine in rats. The neuropathology of SNR was investigated using immunohistochemical techniques with the major emphasis on the time-course of changes in neurons and astrocytes. Animals surviving 20, 30, 40, 60 min, 2, 3, 6 hours, 1, 2, and 3 days after induction of status epilepticus were perfusion-fixed, and brains processed for immunohistochemical staining of SNR. Nissl-staining and antibodies against the neuron-specific calcium-binding protein, parvalbumin, served to detect neuronal damage in SNR. Antibodies against the astroglia-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP), and against the glial calcium-binding protein, S-100 protein, were used to assess the status of astrocytes. Immunohistochemical staining for serum-albumin and immunoglobulins in brain tissue was taken as indicator of blood-brain barrier disturbances and vasogenic edema formation. Immunohistochemical staining indicated loss of GFAP-staining already at 30 min after induction of seizures in an oval focus situated in the center of SNR while sparing medial and lateral aspects. At 1 h there was additional vacuolation in S-100 protein staining. By 2 hours, parvalbumin-staining changed in the central SNR indicating neuronal damage, and Nissl-staining visualized some neuronal distortion. Staining for serum-proteins occurred in a patchy manner throughout the forebrain during the first hours. By 6 h, vasogenic edema covered the lesioned SNR. By 24 h, glial and neuronal markers indicated a massive lesion in the center of SNR. By 48-72 h, astrocytes surrounding the lesion increased in size, and polymorphic phagocytotic cells invaded the damaged area. In a further group of animals surviving 1 to 5 days, conventional paraffin-sections confirmed the neuronal and glial damage of SNR. Additional pathology of similar quality was found in the globus pallidus. Since astrocytes were always damaged in parallel with neurons in SNR it is proposed that the anatomical and functional interrelationship between neurons and astrocytes is particularly tight in SNR. Both cell elements may suffer in common from metabolic disturbance and neurotransmitter dysfunction as occur during massive status epilepticus.
1756784	0	42	Damage of substantia nigra pars reticulata	Disease	D001930
1756784	50	61	pilocarpine	Chemical	D010862
1756784	70	88	status epilepticus	Disease	D013226
1756784	252	269	epileptic seizure	Disease	D004827
1756784	307	335	prolonged status epilepticus	Disease	D013226
1756784	443	464	metabolic derangement	Disease	D008659
1756784	533	551	status epilepticus	Disease	D013226
1756784	589	600	pilocarpine	Chemical	D010862
1756784	860	878	status epilepticus	Disease	D013226
1756784	1021	1028	calcium	Chemical	D002118
1756784	1076	1091	neuronal damage	Disease	D009422
1756784	1226	1233	calcium	Chemical	D002118
1756784	1458	1473	vasogenic edema	Disease	D001929
1756784	1583	1591	seizures	Disease	D012640
1756784	1819	1834	neuronal damage	Disease	D009422
1756784	2005	2020	vasogenic edema	Disease	D001929
1756784	2033	2045	lesioned SNR	Disease	D001930
1756784	2375	2388	damage of SNR	Disease	D001930
1756784	2733	2761	neurotransmitter dysfunction	Disease	D001480
1756784	2786	2804	status epilepticus	Disease	D013226
1756784	CID	D010862	D001930
1756784	CID	D010862	D013226
1756784	CID	D010862	D001480

1760851|t|Reduced cardiotoxicity of doxorubicin given in the form of N-(2-hydroxypropyl)methacrylamide conjugates: and experimental study in the rat.
1760851|a|A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg/kg doxorubicin (DOX) given either as free drug or in the form of three N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly-Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg/kg) was significantly lower than that observed in those that received free DOX (4 mg/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg/kg; P less than 0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of approximately 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was approximately 12% lower than that measured in age-matched control rats (P less than 0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P less than 0.05). In addition, no significant histological change was observed in the heart of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
1760851	8	22	cardiotoxicity	Disease	D066126
1760851	26	37	doxorubicin	Chemical	D004317
1760851	59	92	N-(2-hydroxypropyl)methacrylamide	Chemical	C032976
1760851	191	199	toxicity	Disease	D064420
1760851	213	227	cardiotoxicity	Disease	D066126
1760851	239	250	doxorubicin	Chemical	D004317
1760851	252	255	DOX	Chemical	D004317
1760851	307	340	N-(2-hydroxypropyl)methacrylamide	Chemical	C032976
1760851	342	346	HPMA	Chemical	C032976
1760851	379	383	HPMA	Chemical	C032976
1760851	396	399	DOX	Chemical	D004317
1760851	527	542	Gly-Phe-Leu-Gly	Chemical	C504380
1760851	597	610	galactosamine	Chemical	D005688
1760851	740	743	DOX	Chemical	D004317
1760851	892	895	DOX	Chemical	D004317
1760851	977	980	DOX	Chemical	D004317
1760851	1029	1033	HPMA	Chemical	C032976
1760851	1053	1056	DOX	Chemical	D004317
1760851	1137	1151	cardiotoxicity	Disease	D066126
1760851	1208	1211	DOX	Chemical	D004317
1760851	1230	1234	HPMA	Chemical	C032976
1760851	1254	1257	DOX	Chemical	D004317
1760851	1366	1369	DOX	Chemical	D004317
1760851	1378	1392	cardiotoxicity	Disease	D066126
1760851	1483	1486	DOX	Chemical	D004317
1760851	1505	1509	HPMA	Chemical	C032976
1760851	1529	1532	DOX	Chemical	D004317
1760851	1793	1797	HPMA	Chemical	C032976
1760851	1830	1833	DOX	Chemical	D004317
1760851	2024	2027	DOX	Chemical	D004317
1760851	2043	2047	HPMA	Chemical	C032976
1760851	CID	D004317	D066126

1779253|t|Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course.
1779253|a|In order to evaluate the efficacy, time-course of action and predictors of response to topical capsaicin, 39 patients with chronic post-herpetic neuralgia (PHN), median duration 24 months, were treated with 0.025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow-up investigation was performed 10-12 months after study onset on the patients who had improved. Nineteen patients (48.7%) substantially improved after the 8-week trial; 5 (12.8%) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations (4) or mastitis (1); 15 (38.5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72.2% were still improved at the follow-up; only one-third of them had continued application irregularly. Treatment effect was not dependent on patient's age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time-course or severity of capsaicin-induced burning. If confirmed in controlled trials, the long-term results of this open, non-randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents.
1779253	15	24	capsaicin	Chemical	D002211
1779253	36	59	post-herpetic neuralgia	Disease	D051474
1779253	211	220	capsaicin	Chemical	D002211
1779253	247	270	post-herpetic neuralgia	Disease	D051474
1779253	272	275	PHN	Disease	D051474
1779253	330	339	capsaicin	Chemical	D002211
1779253	399	403	pain	Disease	D010146
1779253	714	723	capsaicin	Chemical	D002211
1779253	758	766	mastitis	Disease	D008413
1779253	1094	1097	PHN	Disease	D051474
1779253	1137	1156	sensory disturbance	Disease	-1
1779253	1160	1164	pain	Disease	D010146
1779253	1261	1270	capsaicin	Chemical	D002211
1779253	1424	1433	capsaicin	Chemical	D002211
1779253	1437	1440	PHN	Disease	D051474
1779253	CID	D002211	D010146
1779253	CID	D002211	D008413

1837756|t|Serotonin reuptake inhibitors, paranoia, and the ventral basal ganglia.
1837756|a|Antidepressants have previously been associated with paranoid reactions in psychiatric patients. Five cases of paranoid exacerbation with the serotonin reuptake inhibitors fluoxetine and amitriptyline are reported here. Elements common to these cases included a history of paranoid symptomatology and the concomitant occurrence of depressive and psychotic symptoms. Complicated depressive disorders (including atypicality of course and symptomatology, chronicity, psychosis, bipolarity, and secondary onset in the course of a primary psychosis) may present particular vulnerability to paranoid exacerbations associated with serotonin reuptake inhibitors. Although the pharmacology and neurobiology of paranoia remain cryptic, several mechanisms, including 5HT3 receptor-mediated dopamine release, beta-noradrenergic receptor downregulation, or GABAB receptor upregulation acting in the vicinity of the ventral basal ganglia (possibly in lateral orbitofrontal or anterior cingulate circuits), might apply to this phenomenon. These cases call attention to possible paranoid exacerbations with serotonin reuptake blockers in select patients and raise neurobiological considerations regarding paranoia.
1837756	0	9	Serotonin	Chemical	D012701
1837756	31	39	paranoia	Disease	D010259
1837756	125	133	paranoid	Disease	D010259
1837756	183	191	paranoid	Disease	D010259
1837756	214	223	serotonin	Chemical	D012701
1837756	244	254	fluoxetine	Chemical	D005473
1837756	259	272	amitriptyline	Chemical	D000639
1837756	345	353	paranoid	Disease	D010259
1837756	403	436	depressive and psychotic symptoms	Disease	D003866|D011618	depressive symptoms|psychotic symptoms
1837756	450	470	depressive disorders	Disease	D003866
1837756	536	545	psychosis	Disease	D011605
1837756	606	615	psychosis	Disease	D011605
1837756	657	665	paranoid	Disease	D010259
1837756	696	705	serotonin	Chemical	D012701
1837756	773	781	paranoia	Disease	D010259
1837756	851	859	dopamine	Chemical	D004298
1837756	1135	1143	paranoid	Disease	D010259
1837756	1163	1172	serotonin	Chemical	D012701
1837756	1261	1269	paranoia	Disease	D010259
1837756	CID	D005473	D010259
1837756	CID	D000639	D010259

1858969|t|Five cases of encephalitis during treatment of loiasis with diethylcarbamazine.
1858969|a|Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i.e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti-allergic treatment. This type of drug-induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature.
1858969	14	26	encephalitis	Disease	D004660
1858969	47	54	loiasis	Disease	D008118
1858969	60	78	diethylcarbamazine	Chemical	D004049
1858969	94	106	encephalitis	Disease	D004660
1858969	132	150	diethylcarbamazine	Chemical	D004049
1858969	152	155	DEC	Chemical	D004049
1858969	206	216	filariasis	Disease	D005368
1858969	497	500	DEC	Chemical	D004049
1858969	802	814	encephalitis	Disease	D004660
1858969	835	849	microfilaremia	Disease	-1
1858969	CID	D004049	D004660

1905439|t|Delirium in an elderly woman possibly associated with administration of misoprostol.
1905439|a|Misoprostol has been associated with adverse reactions, including gastrointestinal symptoms, gynecologic problems, and headache. Changes in mental status, however, have not been reported. We present a case in which an 89-year-old woman in a long-term care facility became confused after the initiation of misoprostol therapy. The patient's change in mental status was first reported nine days after the initiation of therapy. Her delirium significantly improved after misoprostol was discontinued and her mental status returned to normal within a week. Because no other factors related to this patient changed significantly, the delirium experienced by this patient possibly resulted from misoprostol therapy.
1905439	0	8	Delirium	Disease	D003693
1905439	72	83	misoprostol	Chemical	D016595
1905439	85	96	Misoprostol	Chemical	D016595
1905439	204	212	headache	Disease	D006261
1905439	390	401	misoprostol	Chemical	D016595
1905439	515	523	delirium	Disease	D003693
1905439	553	564	misoprostol	Chemical	D016595
1905439	714	722	delirium	Disease	D003693
1905439	774	785	misoprostol	Chemical	D016595
1905439	CID	D016595	D003693

1943082|t|Hepatocellular oxidant stress following intestinal ischemia-reperfusion injury.
1943082|a|Reperfusion of ischemic intestine results in acute liver dysfunction characterized by hepatocellular enzyme release into plasma, reduction in bile flow rate, and neutrophil sequestration within the liver. The pathophysiology underlying this acute hepatic injury is unknown. This study was undertaken to determine whether oxidants are associated with the hepatic injury and to determine the relative value of several indirect methods of assessing oxidant exposure in vivo. Rats were subjected to a standardized intestinal ischemia-reperfusion injury. Hepatic tissue was assayed for lipid peroxidation products and oxidized and reduced glutathione. There was no change in hepatic tissue total glutathione following intestinal ischemia-reperfusion injury. Oxidized glutathione (GSSG) increased significantly following 30 and 60 min of reperfusion. There was no increase in any of the products of lipid peroxidation associated with this injury. An increase in GSSG within hepatic tissue during intestinal reperfusion suggests exposure of hepatocytes to an oxidant stress. The lack of a significant increase in products of lipid peroxidation suggests that the oxidant stress is of insufficient magnitude to result in irreversible injury to hepatocyte cell membranes. These data also suggest that the measurement of tissue GSSG may be a more sensitive indicator of oxidant stress than measurement of products of lipid peroxidation.
1943082	51	59	ischemia	Disease	D007511
1943082	60	78	reperfusion injury	Disease	D015427
1943082	95	103	ischemic	Disease	D007511
1943082	131	148	liver dysfunction	Disease	D017093
1943082	327	341	hepatic injury	Disease	D056486
1943082	434	448	hepatic injury	Disease	D056486
1943082	601	609	ischemia	Disease	D007511
1943082	610	628	reperfusion injury	Disease	D015427
1943082	693	725	oxidized and reduced glutathione	Chemical	D019803|D005978	oxidized glutathione|reduced glutathione
1943082	771	782	glutathione	Chemical	D005978
1943082	804	812	ischemia	Disease	D007511
1943082	813	831	reperfusion injury	Disease	D015427
1943082	833	853	Oxidized glutathione	Chemical	D019803
1943082	855	859	GSSG	Chemical	D019803
1943082	1036	1040	GSSG	Chemical	D019803
1943082	1397	1401	GSSG	Chemical	D019803
1943082	CID	D019803	D015427

2021990|t|Diphenhydramine prevents the haemodynamic changes of cimetidine in ICU patients.
2021990|a|Cimetidine, a histamine 2 (H2) antagonist, produces a decrease in arterial pressure due to vasodilatation, especially in critically ill patients. This may be because cimetidine acts as a histamine agonist. We, therefore, investigated the effects of the histamine 1(H1) receptor antagonist, diphenhydramine, on the haemodynamic changes observed after cimetidine in ICU patients. Each patient was studied on two separate days. In a random fashion, they received cimetidine 200 mg iv on one day, and on the other, a pretreatment of diphenhydramine 40 mg iv with cimetidine 200 mg iv. In the non-pretreatment group, mean arterial pressure (MAP) decreased from 107.4 +/- 8.4 mmHg to 86.7 +/- 11.4 mmHg (P less than 0.01) two minutes after cimetidine. Also, systemic vascular resistance (SVR) decreased during the eight-minute observation period (P less than 0.01). In contrast, in the pretreatment group, little haemodynamic change was seen. We conclude that an H1 antagonist may be useful in preventing hypotension caused by iv cimetidine, since the vasodilating activity of cimetidine is mediated, in part, through the H1 receptor.
2021990	0	15	Diphenhydramine	Chemical	D004155
2021990	53	63	cimetidine	Chemical	D002927
2021990	81	91	Cimetidine	Chemical	D002927
2021990	95	104	histamine	Chemical	D006632
2021990	247	257	cimetidine	Chemical	D002927
2021990	268	277	histamine	Chemical	D006632
2021990	334	343	histamine	Chemical	D006632
2021990	371	386	diphenhydramine	Chemical	D004155
2021990	431	441	cimetidine	Chemical	D002927
2021990	541	551	cimetidine	Chemical	D002927
2021990	610	625	diphenhydramine	Chemical	D004155
2021990	640	650	cimetidine	Chemical	D002927
2021990	815	825	cimetidine	Chemical	D002927
2021990	1080	1091	hypotension	Disease	D007022
2021990	1105	1115	cimetidine	Chemical	D002927
2021990	1152	1162	cimetidine	Chemical	D002927
2021990	CID	D002927	D007022

2083961|t|Acute renal failure due to rifampicin.
2083961|a|A 23-year-old male patient with bacteriologically proven pulmonary tuberculosis was treated with the various regimens of antituberculosis drugs for nearly 15 months. Rifampicin was administered thrice as one of the 3-4 drug regimen and each time he developed untoward side effects like nausea, vomiting and fever with chills and rigors. The last such episode was of acute renal failure at which stage the patient was seen by the authors of this report. The patient, however, made a full recovery.
2083961	0	19	Acute renal failure	Disease	D058186
2083961	27	37	rifampicin	Chemical	D012293
2083961	96	118	pulmonary tuberculosis	Disease	D014397
2083961	205	215	Rifampicin	Chemical	D012293
2083961	325	331	nausea	Disease	D009325
2083961	333	341	vomiting	Disease	D014839
2083961	346	351	fever	Disease	D005334
2083961	CID	D012293	D058186

2131034|t|Severe polyneuropathy and motor loss after intrathecal thiotepa combination chemotherapy: description of two cases.
2131034|a|Two cases of severe delayed neurologic toxicity related to the administration of intrathecal (IT) combination chemotherapy including thiotepa (TSPA) are presented. Both cases developed axonal neuropathy with motor predominance in the lower extremities 1 and 6 months after IT chemotherapy was administered. Neurologic toxicities have been described with IT-methotrexate, IT-cytosine arabinoside and IT-TSPA. To our knowledge, however, axonal neuropathy following administration of these three agents has not been previously described. In spite of the fact that TSPA is a useful IT agent, its combination with MTX, ara-C and radiotherapy could cause severe neurotoxicity. This unexpected complication indicates the need for further toxicology research on IT-TSPA.
2131034	7	21	polyneuropathy	Disease	D011115
2131034	55	63	thiotepa	Chemical	D013852
2131034	144	163	neurologic toxicity	Disease	D020258
2131034	249	257	thiotepa	Chemical	D013852
2131034	259	263	TSPA	Chemical	D013852
2131034	301	318	axonal neuropathy	Disease	D056768
2131034	423	444	Neurologic toxicities	Disease	D020258
2131034	473	485	methotrexate	Chemical	D008727
2131034	490	510	cytosine arabinoside	Chemical	D003561
2131034	518	522	TSPA	Chemical	D013852
2131034	551	568	axonal neuropathy	Disease	D056768
2131034	677	681	TSPA	Chemical	D013852
2131034	725	728	MTX	Chemical	D008727
2131034	730	735	ara-C	Chemical	D003561
2131034	772	785	neurotoxicity	Disease	D020258
2131034	873	877	TSPA	Chemical	D013852
2131034	CID	D003561	D011115
2131034	CID	D008727	D011115
2131034	CID	D013852	D011115
2131034	CID	D003561	D020258
2131034	CID	D008727	D020258
2131034	CID	D013852	D020258

2173761|t|Effects of cromakalim and pinacidil on large epicardial and small coronary arteries in conscious dogs.
2173761|a|The effects of i.v. bolus administration of cromakalim (1-10 micrograms/kg) and pinacidil (3-100 micrograms/kg) on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs and compared to those of nitroglycerin (0.03-10 micrograms/kg). Nitroglycerin, up to 0.3 micrograms/kg, selectively increased circumflex artery diameter (CxAD) without simultaneously affecting any other cardiac or systemic hemodynamic parameter. In contrast, cromakalim and pinacidil at all doses and nitroglycerin at doses higher than 0.3 micrograms/kg simultaneously and dose-dependently increased CxAD, coronary blood flow and heart rate and decreased coronary vascular resistance and aortic pressure. Cromakalim was approximately 8- to 9.5-fold more potent than pinacidil in increasing CxAD. Vasodilation of large and small coronary vessels and hypotension induced by cromakalim and pinacidil were not affected by prior combined beta adrenergic and muscarinic receptors blockade but drug-induced tachycardia was abolished. When circumflex artery blood flow was maintained constant, the increases in CxAD induced by cromakalim (10 micrograms/kg), pinacidil (30 micrograms/kg) and nitroglycerin (10 micrograms/kg) were reduced by 68 +/- 7, 54 +/- 9 and 1 +/- 1%, respectively. Thus, whereas nitroglycerin preferentially and flow-independently dilates large coronary arteries, cromakalim and pinacidil dilate both large and small coronary arteries and this effect is not dependent upon the simultaneous beta adrenoceptors-mediated rise in myocardial metabolic demand. Finally, two mechanisms at least, direct vasodilation and flow dependency, are involved in the cromakalim- and pinacidil-induced increase in CxAD.
2173761	11	21	cromakalim	Chemical	D019806
2173761	26	35	pinacidil	Chemical	D020110
2173761	147	157	cromakalim	Chemical	D019806
2173761	183	192	pinacidil	Chemical	D020110
2173761	387	400	nitroglycerin	Chemical	D005996
2173761	426	439	Nitroglycerin	Chemical	D005996
2173761	621	631	cromakalim	Chemical	D019806
2173761	636	645	pinacidil	Chemical	D020110
2173761	663	676	nitroglycerin	Chemical	D005996
2173761	867	877	Cromakalim	Chemical	D019806
2173761	928	937	pinacidil	Chemical	D020110
2173761	1011	1022	hypotension	Disease	D007022
2173761	1034	1044	cromakalim	Chemical	D019806
2173761	1049	1058	pinacidil	Chemical	D020110
2173761	1095	1144	beta adrenergic and muscarinic receptors blockade	Chemical	D000319|D018727	beta adrenergic receptors blockade|muscarinic receptors blockade
2173761	1162	1173	tachycardia	Disease	D013610
2173761	1281	1291	cromakalim	Chemical	D019806
2173761	1312	1321	pinacidil	Chemical	D020110
2173761	1345	1358	nitroglycerin	Chemical	D005996
2173761	1455	1468	nitroglycerin	Chemical	D005996
2173761	1540	1550	cromakalim	Chemical	D019806
2173761	1555	1564	pinacidil	Chemical	D020110
2173761	1826	1836	cromakalim	Chemical	D019806
2173761	1842	1851	pinacidil	Chemical	D020110
2173761	CID	D019806	D007022
2173761	CID	D020110	D013610
2173761	CID	D019806	D013610
2173761	CID	D020110	D007022

2217015|t|Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.
2217015|a|We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.
2217015	0	14	Mefenamic acid	Chemical	D008528
2217015	23	34	neutropenia	Disease	D009503
2217015	39	52	renal failure	Disease	D051437
2217015	77	91	hypothyroidism	Disease	D007037
2217015	103	117	mefenamic acid	Chemical	D008528
2217015	139	152	renal failure	Disease	D051437
2217015	164	175	neutropenia	Disease	D009503
2217015	229	240	neutropenia	Disease	D009503
2217015	332	343	hypothyroid	Disease	D007037
2217015	493	507	mefenamic acid	Chemical	D008528
2217015	511	522	hypothyroid	Disease	D007037
2217015	542	556	hypothyroidism	Disease	D007037
2217015	CID	D008528	D009503
2217015	CID	D008528	D051437

2239937|t|Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy.
2239937|a|Fourteen of 39 dialysis patients (36%) became hypercalcemic after switching to calcium carbonate as their principal phosphate binder. In order to identify risk factors associated with the development of hypercalcemia, indirect parameters of intestinal calcium reabsorption and bone turnover rate in these 14 patients were compared with results in 14 eucalcemic patients matched for age, sex, length of time on dialysis, and etiology of renal disease. In addition to experiencing hypercalcemic episodes with peak calcium values of 2.7 to 3.8 mmol/L (10.7 to 15.0 mg/dL), patients in the hypercalcemic group exhibited a significant increase in the mean calcium concentration obtained during 6 months before the switch, compared with the mean value obtained during the 7 months of observation after the switch (2.4 +/- 0.03 to 2.5 +/- 0.03 mmol/L [9.7 +/- 0.2 to 10.2 +/- 0.1 mg/dL], P = 0.006). In contrast, eucalcemic patients exhibited no change in mean calcium values over the same time period (2.3 +/- 0.05 to 2.3 +/- 0.05 mmol/L [9.2 +/- 0.2 to 9.2 +/- 0.2 mg/dL]). CaCO3 dosage, calculated dietary calcium intake, and circulating levels of vitamin D metabolites were similar in both groups. Physical activity index and predialysis serum bicarbonate levels also were similar in both groups. However, there was a significant difference in parameters reflecting bone turnover rates between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
2239937	12	25	hypercalcemia	Disease	D006934
2239937	54	71	calcium carbonate	Chemical	D002119
2239937	127	140	hypercalcemic	Disease	D006934
2239937	160	177	calcium carbonate	Chemical	D002119
2239937	197	206	phosphate	Chemical	D010710
2239937	284	297	hypercalcemia	Disease	D006934
2239937	333	340	calcium	Chemical	D002118
2239937	517	530	renal disease	Disease	D007674
2239937	560	573	hypercalcemic	Disease	D006934
2239937	593	600	calcium	Chemical	D002118
2239937	667	680	hypercalcemic	Disease	D006934
2239937	732	739	calcium	Chemical	D002118
2239937	1035	1042	calcium	Chemical	D002118
2239937	1150	1155	CaCO3	Chemical	D002119
2239937	1183	1190	calcium	Chemical	D002118
2239937	1225	1234	vitamin D	Chemical	D014807
2239937	1322	1333	bicarbonate	Chemical	D001639
2239937	CID	D002119	D006934

2320485|t|Methyldopa-induced hemolytic anemia in a 15 year old presenting as near-syncope.
2320485|a|Methyldopa is an antihypertensive medication which is available generically and under the trade name Aldomet that is widely prescribed in the adult population and infrequently used in children. Methyldopa causes an autoimmune hemolytic anemia in a small percentage of patients who take the drug. We report a case of methyldopa-induced hemolytic anemia in a 15-year-old boy who presented to the emergency department with near-syncope. The boy had been treated with intravenous methyldopa during a trauma admission seven weeks prior to presentation. Evaluation revealed a hemoglobin of three grams, 3+ Coombs' test with polyspecific anti-human globulin and monospecific IgG reagents, and a warm reacting autoantibody. Transfusion and corticosteroid therapy resulted in a complete recovery of the patient. Emergency physicians treating children must be aware of this syndrome in order to diagnose and treat it correctly. A brief review of autoimmune and drug-induced hemolytic anemias is provided.
2320485	0	10	Methyldopa	Chemical	D008750
2320485	19	35	hemolytic anemia	Disease	D000743
2320485	72	79	syncope	Disease	D013575
2320485	81	91	Methyldopa	Chemical	D008750
2320485	182	189	Aldomet	Chemical	D008750
2320485	275	285	Methyldopa	Chemical	D008750
2320485	296	323	autoimmune hemolytic anemia	Disease	D000744
2320485	397	407	methyldopa	Chemical	D008750
2320485	416	432	hemolytic anemia	Disease	D000743
2320485	475	495	emergency department	Disease	D004630
2320485	506	513	syncope	Disease	D013575
2320485	557	567	methyldopa	Chemical	D008750
2320485	577	583	trauma	Disease	D014947
2320485	813	827	corticosteroid	Chemical	D000305
2320485	1045	1062	hemolytic anemias	Disease	D000743
2320485	CID	D008750	D000743

2358093|t|The long-term safety of danazol in women with hereditary angioedema.
2358093|a|Although the short-term safety (less than or equal to 6 months) of danazol has been established in a variety of settings, no information exists as to its long-term safety. We therefore investigated the long-term safety of danazol by performing a retrospective chart review of 60 female patients with hereditary angioedema treated with danazol for a continuous period of 6 months or longer. The mean age of the patients was 35.2 years and the mean duration of therapy was 59.7 months. Virtually all patients experienced one or more adverse reactions. Menstrual abnormalities (79%), weight gain (60%), muscle cramps/myalgias (40%), and transaminase elevations (40%) were the most common adverse reactions. The drug was discontinued due to adverse reactions in 8 patients. No patient has died or suffered any apparent long-term sequelae that were directly attributable to the drug. We conclude that, despite a relatively high incidence of adverse reactions, danazol has proven to be remarkably safe over the long-term in this group of patients.
2358093	24	31	danazol	Chemical	D003613
2358093	46	67	hereditary angioedema	Disease	D054179
2358093	136	143	danazol	Chemical	D003613
2358093	291	298	danazol	Chemical	D003613
2358093	369	390	hereditary angioedema	Disease	D054179
2358093	404	411	danazol	Chemical	D003613
2358093	619	642	Menstrual abnormalities	Disease	D008599
2358093	650	661	weight gain	Disease	D015430
2358093	669	682	muscle cramps	Disease	D009120
2358093	683	691	myalgias	Disease	D063806
2358093	1024	1031	danazol	Chemical	D003613
2358093	CID	D003613	D015430
2358093	CID	D003613	D009120
2358093	CID	D003613	D008599

2383364|t|Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns.
2383364|a|Effective topical antimicrobial agents decrease infection and mortality in burn patients. Chlorhexidine phosphanilate (CHP), a new broad-spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application. This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy. Twenty-nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12-h intervals over a 3-day period. One burn site was treated with each of four different CHP concentrations, from 0.25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds. The other site was always treated with AgSD cream. There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale. The 0.25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other. In addition, ease of application of CHP creams was less satisfactory than that of AgSD. It was concluded that formulations at or below 0.5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use.
2383364	35	64	chlorhexidine diphosphanilate	Chemical	C048279
2383364	90	95	burns	Disease	D002056
2383364	145	154	infection	Disease	D007239
2383364	172	176	burn	Disease	D002056
2383364	187	214	Chlorhexidine phosphanilate	Chemical	C048279
2383364	216	219	CHP	Chemical	C048279
2383364	296	300	burn	Disease	D002056
2383364	456	459	CHP	Chemical	C048279
2383364	576	580	burn	Disease	D002056
2383364	613	618	burns	Disease	D002056
2383364	739	743	burn	Disease	D002056
2383364	789	792	CHP	Chemical	C048279
2383364	873	893	silver sulphadiazine	Chemical	D012837
2383364	895	899	AgSD	Chemical	D012837
2383364	972	976	burn	Disease	D002056
2383364	1024	1028	AgSD	Chemical	D012837
2383364	1076	1079	CHP	Chemical	C048279
2383364	1119	1123	pain	Disease	D010146
2383364	1164	1167	CHP	Chemical	C048279
2383364	1189	1193	AgSD	Chemical	D012837
2383364	1197	1201	pain	Disease	D010146
2383364	1273	1277	AgSD	Chemical	D012837
2383364	1334	1337	CHP	Chemical	C048279
2383364	1380	1384	AgSD	Chemical	D012837
2383364	1446	1449	CHP	Chemical	C048279
2383364	CID	C048279	D010146

2400986|t|Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study.
2400986|a|Busulfan is known to be neurotoxic in animals and humans, but its acute neurotoxicity remains poorly characterized in children. We report here a retrospective study of 123 children (median age, 6.5 years) receiving high-dose busulfan in combined chemotherapy before bone marrow transplantation for malignant solid tumors, brain tumors excluded. Busulfan was given p.o., every 6 hours for 16 doses over 4 days. Two total doses were consecutively used: 16 mg/kg, then 600 mg/m2. The dose calculation on the basis of body surface area results in higher doses in young children than in older patients (16 to 28 mg/kg). Ninety-six patients were not given anticonvulsive prophylaxis; 7 (7.5%) developed seizures during the 4 days of the busulfan course or within 24 h after the last dosing. When the total busulfan dose was taken into account, there was a significant difference in terms of neurotoxicity incidence among patients under 16 mg/kg (1 of 57, 1.7%) and patients under 600 mg/m2 (6 of 39, 15.4%) (P less than 0.02). Twenty-seven patients were given a 600-mg/m2 busulfan total dose with continuous i.v. infusion of clonazepam; none had any neurological symptoms. Busulfan levels were measured by a gas chromatographic-mass spectrometry assay in the plasma and cerebrospinal fluid of 9 children without central nervous system disease under 600 mg/m2 busulfan with clonazepam:busulfan cerebrospinal fluid:plasma ratio was 1.39. This was significantly different (P less than 0.02) from the cerebrospinal fluid:plasma ratio previously defined in children receiving a 16-mg/kg total dose of busulfan. This study shows that busulfan neurotoxicity is dose-dependent in children and efficiently prevented by clonazepam. A busulfan dose calculated on the basis of body surface area, resulting in higher doses in young children, was followed by increased neurotoxicity, close to neurotoxicity incidence observed in adults. Since plasma pharmacokinetic studies showed a faster busulfan clearance in children than in adults, this new dose may approximate more closely the adult systemic exposure obtained after the usual 16-mg/kg total dose, with potential inferences in terms of anticancer or myeloablative effects. The busulfan dose in children and infants undergoing bone marrow transplantation should be reconsidered on the basis of pharmacokinetic studies.
2400986	15	28	neurotoxicity	Disease	D020258
2400986	42	50	busulfan	Chemical	D002066
2400986	102	110	Busulfan	Chemical	D002066
2400986	126	136	neurotoxic	Disease	D020258
2400986	174	187	neurotoxicity	Disease	D020258
2400986	327	335	busulfan	Chemical	D002066
2400986	416	422	tumors	Disease	D009369
2400986	424	436	brain tumors	Disease	D001932
2400986	447	455	Busulfan	Chemical	D002066
2400986	799	807	seizures	Disease	D012640
2400986	833	841	busulfan	Chemical	D002066
2400986	902	910	busulfan	Chemical	D002066
2400986	987	1000	neurotoxicity	Disease	D020258
2400986	1168	1176	busulfan	Chemical	D002066
2400986	1221	1231	clonazepam	Chemical	D002998
2400986	1246	1267	neurological symptoms	Disease	D009461
2400986	1269	1277	Busulfan	Chemical	D002066
2400986	1408	1438	central nervous system disease	Disease	D002493
2400986	1455	1463	busulfan	Chemical	D002066
2400986	1469	1479	clonazepam	Chemical	D002998
2400986	1480	1488	busulfan	Chemical	D002066
2400986	1692	1700	busulfan	Chemical	D002066
2400986	1724	1732	busulfan	Chemical	D002066
2400986	1733	1746	neurotoxicity	Disease	D020258
2400986	1806	1816	clonazepam	Chemical	D002998
2400986	1820	1828	busulfan	Chemical	D002066
2400986	1951	1964	neurotoxicity	Disease	D020258
2400986	1975	1988	neurotoxicity	Disease	D020258
2400986	2072	2080	busulfan	Chemical	D002066
2400986	2315	2323	busulfan	Chemical	D002066
2400986	CID	D002066	D012640

2429800|t|Histamine antagonists and d-tubocurarine-induced hypotension in cardiac surgical patients.
2429800|a|Hemodynamic effects and histamine release by bolus injection of 0.35 mg/kg of d-tubocurarine were studied in 24 patients. H1- and H2-histamine antagonists or placebo were given before dosing with d-tubocurarine in a randomized double-blind fashion to four groups: group 1--placebo; group 2--cimetidine, 4 mg/kg, plus placebo; group 3--chlorpheniramine, 0.1 mg/kg, plus placebo; and group 4--cimetidine plus chlorpheniramine. Histamine release occurred in most patients, the highest level 2 minutes after d-tubocurarine dosing. Group 1 had a moderate negative correlation between plasma histamine change and systemic vascular resistance (r = 0.58; P less than 0.05) not present in group 4. Prior dosing with antagonists partially prevented the fall in systemic vascular resistance. These data demonstrate that the hemodynamic changes associated with d-tubocurarine dosing are only partially explained by histamine release. Thus prior dosing with H1- and H2-antagonists provides only partial protection.
2429800	0	9	Histamine	Chemical	D006632
2429800	26	40	d-tubocurarine	Chemical	D014403
2429800	49	60	hypotension	Disease	D007022
2429800	115	124	histamine	Chemical	D006632
2429800	169	183	d-tubocurarine	Chemical	D014403
2429800	224	233	histamine	Chemical	D006632
2429800	287	301	d-tubocurarine	Chemical	D014403
2429800	382	392	cimetidine	Chemical	D002927
2429800	426	442	chlorpheniramine	Chemical	D002744
2429800	482	492	cimetidine	Chemical	D002927
2429800	498	514	chlorpheniramine	Chemical	D002744
2429800	516	525	Histamine	Chemical	D006632
2429800	595	609	d-tubocurarine	Chemical	D014403
2429800	677	686	histamine	Chemical	D006632
2429800	940	954	d-tubocurarine	Chemical	D014403
2429800	994	1003	histamine	Chemical	D006632
2429800	CID	D014403	D007022

2453942|t|Convulsant effect of lindane and regional brain concentration of GABA and dopamine.
2453942|a|Lindane (gamma-hexachlorocyclohexane) is an organochlorine insecticide with known neurotoxic effects. Its mechanism of action is not well understood although it has been proposed that lindane acts as a non-competitive antagonist at the gamma-aminobutyric acid (GABA)-A receptor. We studied the effect of lindane (150 mg/kg) on the GABAergic and dopaminergic systems by measuring the concentration of GABA, dopamine and its metabolites in 7 brain areas at the onset of seizures. All animals suffered tonic convulsions at 18.3 +/- 1.4 min after lindane administration. The concentration of GABA was only slightly but significantly decreased in the colliculi without modifications in the other areas. The concentration of dopamine was increased in the mesencephalon and that of its metabolite DOPAC was also increased in the mesencephalon and the striatum.
2453942	21	28	lindane	Chemical	D001556
2453942	65	69	GABA	Chemical	D005680
2453942	74	82	dopamine	Chemical	D004298
2453942	84	91	Lindane	Chemical	D001556
2453942	93	120	gamma-hexachlorocyclohexane	Chemical	D001556
2453942	166	176	neurotoxic	Disease	D020258
2453942	268	275	lindane	Chemical	D001556
2453942	320	343	gamma-aminobutyric acid	Chemical	D005680
2453942	345	349	GABA	Chemical	D005680
2453942	388	395	lindane	Chemical	D001556
2453942	484	488	GABA	Chemical	D005680
2453942	490	498	dopamine	Chemical	D004298
2453942	552	560	seizures	Disease	D012640
2453942	589	600	convulsions	Disease	D012640
2453942	627	634	lindane	Chemical	D001556
2453942	672	676	GABA	Chemical	D005680
2453942	803	811	dopamine	Chemical	D004298
2453942	874	879	DOPAC	Chemical	D015102
2453942	CID	D001556	D012640

2484903|t|Unusual complications of antithyroid drug therapy: four case reports and review of literature.
2484903|a|Two cases of propylthiouracil-associated acute hepatitis, one case of fatal methimazole-associated hepatocellular necrosis and one case of propylthiouracil-associated lupus-like syndrome are described. The literature related to antithyroid drug side effects and the mechanisms for their occurrence are reviewed and the efficacy and complications of thyroidectomy and radioiodine compared to those of antithyroid drugs. It is concluded that in most circumstances 131I is the therapy of choice for hyperthyroidism.
2484903	108	124	propylthiouracil	Chemical	D011441
2484903	142	151	hepatitis	Disease	D056486
2484903	171	182	methimazole	Chemical	D008713
2484903	194	217	hepatocellular necrosis	Disease	D047508
2484903	234	250	propylthiouracil	Chemical	D011441
2484903	262	281	lupus-like syndrome	Disease	D008180
2484903	591	606	hyperthyroidism	Disease	D006980
2484903	CID	D011441	D008180
2484903	CID	D008713	D047508
2484903	CID	D011441	D056486

2553470|t|Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats.
2553470|a|MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, was tested for anticonvulsant effects in rats using two seizure models, coadministration of lithium and pilocarpine and administration of a high dose of pilocarpine alone. Three major results are reported. First, pretreatment with MK-801 produced an effective and dose-dependent anticonvulsant action with the lithium-pilocarpine model but not with rats treated with pilocarpine alone, suggesting that different biochemical mechanisms control seizures in these two models. Second, the anticonvulsant effect of MK-801 in the lithium-pilocarpine model only occurred after initial periods of seizure activity. This observation is suggested to be an in vivo demonstration of the conclusion derived from in vitro experiments that MK-801 binding requires agonist-induced opening of the channel sites of the NMDA receptor. Third, although it is relatively easy to block seizures induced by lithium and pilocarpine by administration of anticonvulsants prior to pilocarpine, it is more difficult to terminate ongoing status epilepticus and block the lethality of the seizures. Administration of MK-801 30 or 60 min after pilocarpine, i.e., during status epilepticus, gradually reduced electrical and behavioral seizure activity and greatly enhanced the survival rate. These results suggest that activation of NMDA receptors plays an important role in status epilepticus and brain damage in the lithium-pilocarpine model. This was further supported by results showing that nonconvulsive doses of NMDA and pilocarpine were synergistic, resulting in status epilepticus and subsequent mortality.
2553470	26	32	MK-801	Chemical	D016291
2553470	40	47	lithium	Chemical	D008094
2553470	48	59	pilocarpine	Chemical	D010862
2553470	69	87	status epilepticus	Disease	D013226
2553470	97	103	MK-801	Chemical	D016291
2553470	122	142	N-methyl-D-aspartate	Chemical	D016202
2553470	144	148	NMDA	Chemical	D016202
2553470	227	234	seizure	Disease	D012640
2553470	263	270	lithium	Chemical	D008094
2553470	275	286	pilocarpine	Chemical	D010862
2553470	324	335	pilocarpine	Chemical	D010862
2553470	402	408	MK-801	Chemical	D016291
2553470	481	488	lithium	Chemical	D008094
2553470	489	500	pilocarpine	Chemical	D010862
2553470	538	549	pilocarpine	Chemical	D010862
2553470	614	622	seizures	Disease	D012640
2553470	681	687	MK-801	Chemical	D016291
2553470	695	702	lithium	Chemical	D008094
2553470	703	714	pilocarpine	Chemical	D010862
2553470	760	767	seizure	Disease	D012640
2553470	896	902	MK-801	Chemical	D016291
2553470	972	976	NMDA	Chemical	D016202
2553470	1034	1042	seizures	Disease	D012640
2553470	1054	1061	lithium	Chemical	D008094
2553470	1066	1077	pilocarpine	Chemical	D010862
2553470	1124	1135	pilocarpine	Chemical	D010862
2553470	1179	1197	status epilepticus	Disease	D013226
2553470	1229	1237	seizures	Disease	D012640
2553470	1257	1263	MK-801	Chemical	D016291
2553470	1283	1294	pilocarpine	Chemical	D010862
2553470	1309	1327	status epilepticus	Disease	D013226
2553470	1373	1380	seizure	Disease	D012640
2553470	1471	1475	NMDA	Chemical	D016202
2553470	1513	1531	status epilepticus	Disease	D013226
2553470	1536	1548	brain damage	Disease	D001930
2553470	1556	1563	lithium	Chemical	D008094
2553470	1564	1575	pilocarpine	Chemical	D010862
2553470	1657	1661	NMDA	Chemical	D016202
2553470	1666	1677	pilocarpine	Chemical	D010862
2553470	1709	1727	status epilepticus	Disease	D013226
2553470	CID	D010862	D013226
2553470	CID	D008094	D013226

2614930|t|Nifedipine induced bradycardia in a patient with autonomic neuropathy.
2614930|a|An 80 year old diabetic male with evidence of peripheral and autonomic neuropathy was admitted with chest pain. He was found to have atrial flutter at a ventricular rate of 70/min which slowed down to 30-40/min when nifedipine (60 mg) in 3 divided doses, during which he was paced at a rate of 70/min. This is inconsistent with the well-established finding that nifedipine induces tachycardia in normally innervated hearts. However, in hearts deprived of compensatory sympathetic drive, it may lead to bradycardia.
2614930	0	10	Nifedipine	Chemical	D009543
2614930	19	30	bradycardia	Disease	D001919
2614930	49	69	autonomic neuropathy	Disease	D009422
2614930	86	94	diabetic	Disease	D003920
2614930	117	152	peripheral and autonomic neuropathy	Disease	D010523|D009422	peripheral neuropathy|autonomic neuropathy
2614930	171	181	chest pain	Disease	D002637
2614930	204	218	atrial flutter	Disease	D001282
2614930	287	297	nifedipine	Chemical	D009543
2614930	433	443	nifedipine	Chemical	D009543
2614930	452	463	tachycardia	Disease	D013610
2614930	573	584	bradycardia	Disease	D001919
2614930	CID	D009543	D013610
2614930	CID	D009543	D001919

2625524|t|The effect of haloperidol in cocaine and amphetamine intoxication.
2625524|a|The effectiveness of haloperidol pretreatment in preventing the toxic effects of high doses of amphetamine and cocaine was studied in rats. In this model, toxic effects were induced by intraperitoneal (i.p.) injection of amphetamine 75 mg/kg (100% death rate) or cocaine 70 mg/kg (82% death rate). Haloperidol failed to prevent amphetamine-induced seizures, but did lower the mortality rate at most doses tested. Haloperidol decreased the incidence of cocaine-induced seizures at the two highest doses, but the lowering of the mortality rate did not reach statistical significance at any dose. These data suggest a protective role for the central dopamine blocker haloperidol against death from high-dose amphetamine exposure without reducing the incidence of seizures. In contrast, haloperidol demonstrated an ability to reduce cocaine-induced seizures without significantly reducing mortality.
2625524	14	25	haloperidol	Chemical	D006220
2625524	29	36	cocaine	Chemical	D003042
2625524	41	52	amphetamine	Chemical	D000661
2625524	88	99	haloperidol	Chemical	D006220
2625524	162	173	amphetamine	Chemical	D000661
2625524	178	185	cocaine	Chemical	D003042
2625524	288	299	amphetamine	Chemical	D000661
2625524	330	337	cocaine	Chemical	D003042
2625524	365	376	Haloperidol	Chemical	D006220
2625524	395	406	amphetamine	Chemical	D000661
2625524	415	423	seizures	Disease	D012640
2625524	480	491	Haloperidol	Chemical	D006220
2625524	519	526	cocaine	Chemical	D003042
2625524	535	543	seizures	Disease	D012640
2625524	714	722	dopamine	Chemical	D004298
2625524	731	742	haloperidol	Chemical	D006220
2625524	772	783	amphetamine	Chemical	D000661
2625524	827	835	seizures	Disease	D012640
2625524	850	861	haloperidol	Chemical	D006220
2625524	896	903	cocaine	Chemical	D003042
2625524	912	920	seizures	Disease	D012640
2625524	CID	D003042	D012640
2625524	CID	D000661	D012640

2650911|t|Autoradiographic evidence of estrogen binding sites in nuclei of diethylstilbesterol induced hamster renal carcinomas.
2650911|a|Estrogen binding sites were demonstrated by autoradiography in one transplantable and five primary diethylstilbesterol induced renal carcinomas in three hamsters. Radiolabelling, following the in vivo injection of 3H-17 beta estradiol, was increased only over the nuclei of tumor cells; stereologic analysis revealed a 4.5- to 6.7-times higher concentration of reduced silver grains over nuclei than cytoplasm of these cells. Despite rapid tubular excretion of estradiol which peaked in less than 1 h, the normal cells did not appear to bind the ligand. This is the first published report documenting the preferential in vivo binding of estrogen to nuclei of cells in estrogen induced hamster renal carcinomas.
2650911	29	37	estrogen	Chemical	D004967
2650911	65	84	diethylstilbesterol	Chemical	D004054
2650911	101	117	renal carcinomas	Disease	D002292
2650911	119	127	Estrogen	Chemical	D004967
2650911	218	237	diethylstilbesterol	Chemical	D004054
2650911	246	262	renal carcinomas	Disease	D002292
2650911	344	353	estradiol	Chemical	D004958
2650911	393	398	tumor	Disease	D009369
2650911	488	494	silver	Chemical	D012834
2650911	580	589	estradiol	Chemical	D004958
2650911	756	764	estrogen	Chemical	D004967
2650911	787	795	estrogen	Chemical	D004967
2650911	812	828	renal carcinomas	Disease	D002292
2650911	CID	D004054	D002292

2710809|t|Bradycardia due to biperiden.
2710809|a|In a 38-year-old male patient suffering from a severe postzosteric trigeminal neuralgia, intravenous application of 10 mg biperiden lactate led to a long-lasting paradoxical reaction characterized by considerable bradycardia, dysarthria, and dysphagia. The heart rate was back to normal within 12 hours upon administration of orciprenaline under cardiac monitoring in an intensive care unit. Bradycardia induced by biperiden is attributed to the speed of injection and to a dose-related dual effect of atropine-like drugs on muscarine receptors.
2710809	0	11	Bradycardia	Disease	D001919
2710809	19	28	biperiden	Chemical	D001712
2710809	84	96	postzosteric	Disease	D006562
2710809	97	117	trigeminal neuralgia	Disease	D014277
2710809	152	169	biperiden lactate	Chemical	C036432
2710809	243	254	bradycardia	Disease	D001919
2710809	256	266	dysarthria	Disease	D004401
2710809	272	281	dysphagia	Disease	D003680
2710809	356	369	orciprenaline	Chemical	D009921
2710809	422	433	Bradycardia	Disease	D001919
2710809	445	454	biperiden	Chemical	D001712
2710809	532	540	atropine	Chemical	D001285
2710809	555	564	muscarine	Chemical	D009116
2710809	CID	D001712	D001919
2710809	CID	D001712	D003680
2710809	CID	D001712	D004401

2718706|t|Deliberate hypotension induced by labetalol with halothane, enflurane or isoflurane for middle-ear surgery.
2718706|a|The feasibility of using labetalol, an alpha- and beta-adrenergic blocking agent, as a hypotensive agent in combination with inhalation anaesthetics (halothane, enflurane or isoflurane) was studied in 23 adult patients undergoing middle-ear surgery. The mean arterial pressure was decreased from 86 +/- 5 (s.e. mean) mmHg to 52 +/- 1 mmHg (11.5 +/- 0.7 to 6.9 +/- 0.1 kPa) for 98 +/- 10 min in the halothane (H) group, from 79 +/- 5 to 53 +/- 1 mmHg (10.5 +/- 0.7 to 7.1 +/- 0.1 kPa) for 129 +/- 11 min in the enflurane (E) group, and from 80 +/- 4 to 49 +/- 1 mmHg (10.7 +/- 0.5 to 6.5 +/- 0.1 kPa) for 135 +/- 15 min in the isoflurane (I) group. The mean H concentration during hypotension in the inspiratory gas was 0.7 +/- 0.1 vol%, the mean E concentration 1.6 +/- 0.2 vol%, and the mean I concentration 1.0 +/- 0.1 vol%. In addition, the patients received fentanyl and d-tubocurarine. The initial dose of labetalol for lowering blood pressure was similar, 0.52-0.59 mg/kg, in all the groups. During hypotension, the heart rate was stable without tachy- or bradycardia. The operating conditions regarding bleeding were estimated in a double-blind manner, and did not differ significantly between the groups. During hypotension, the serum creatinine concentration rose significantly in all groups from the values before hypotension and returned postoperatively to the initial level in the other groups, except the isoflurane group. After hypotension there was no rebound phenomenon in either blood pressure or heart rate. These results indicate that labetalol induces easily adjustable hypotension without compensatory tachycardia and rebound hypertension.
2718706	11	22	hypotension	Disease	D007022
2718706	34	43	labetalol	Chemical	D007741
2718706	49	58	halothane	Chemical	D006221
2718706	60	69	enflurane	Chemical	D004737
2718706	73	83	isoflurane	Chemical	D007530
2718706	133	142	labetalol	Chemical	D007741
2718706	195	206	hypotensive	Disease	D007022
2718706	258	267	halothane	Chemical	D006221
2718706	269	278	enflurane	Chemical	D004737
2718706	282	292	isoflurane	Chemical	D007530
2718706	506	515	halothane	Chemical	D006221
2718706	517	518	H	Chemical	D006221
2718706	618	627	enflurane	Chemical	D004737
2718706	629	630	E	Chemical	D004737
2718706	734	744	isoflurane	Chemical	D007530
2718706	746	747	I	Chemical	D007530
2718706	765	766	H	Chemical	D006221
2718706	788	799	hypotension	Disease	D007022
2718706	854	855	E	Chemical	D004737
2718706	901	902	I	Chemical	D007530
2718706	970	978	fentanyl	Chemical	D005283
2718706	983	997	d-tubocurarine	Chemical	D014403
2718706	1019	1028	labetalol	Chemical	D007741
2718706	1113	1124	hypotension	Disease	D007022
2718706	1160	1181	tachy- or bradycardia	Disease	D013610|D001919
2718706	1218	1226	bleeding	Disease	D006470
2718706	1328	1339	hypotension	Disease	D007022
2718706	1351	1361	creatinine	Chemical	D003404
2718706	1432	1443	hypotension	Disease	D007022
2718706	1526	1536	isoflurane	Chemical	D007530
2718706	1550	1561	hypotension	Disease	D007022
2718706	1662	1671	labetalol	Chemical	D007741
2718706	1698	1709	hypotension	Disease	D007022
2718706	1731	1742	tachycardia	Disease	D013610
2718706	1755	1767	hypertension	Disease	D006973
2718706	CID	D004737	D007022
2718706	CID	D007530	D007022
2718706	CID	D006221	D007022
2718706	CID	D007741	D007022

2765447|t|Convulsion following intravenous fluorescein angiography.
2765447|a|Tonic-clonic seizures followed intravenous fluorescein injection for fundus angiography in a 47-year-old male. Despite precautions this adverse reaction recurred on re-exposure to intravenous fluorescein.
2765447	0	10	Convulsion	Disease	D012640
2765447	33	44	fluorescein	Chemical	D019793
2765447	58	79	Tonic-clonic seizures	Disease	D004830
2765447	101	112	fluorescein	Chemical	D019793
2765447	250	261	fluorescein	Chemical	D019793
2765447	CID	D019793	D004830

2767010|t|Pharmacology of ACC-9653 (phenytoin prodrug).
2767010|a|ACC-9653, the disodium phosphate ester of 3-hydroxymethyl-5,5-diphenylhydantoin, is a prodrug of phenytoin with advantageous physicochemical properties. ACC-9653 is rapidly converted enzymatically to phenytoin in vivo. ACC-9653 and phenytoin sodium have equivalent anticonvulsant activity against seizures induced by maximal electroshock (MES) in mice following i.p., oral, or i.v. administration. The ED50 doses were 16 mg/kg for i.v. ACC-9653 and 8 mg/kg for i.v. phenytoin sodium. ACC-9653 and phenytoin sodium have similar antiarrhythmic activity against ouabain-induced ventricular tachycardia in anesthetized dogs. The total doses of ACC-9653 or phenytoin sodium necessary to convert the arrhythmia to a normal sinus rhythm were 24 +/- 6 and 14 +/- 3 mg/kg, respectively. Only phenytoin sodium displayed in vitro antiarrhythmic activity against strophanthidin-induced arrhythmias in guinea pig right atria. In anesthetized dogs, a high dose of ACC-9653 (31 mg/kg) was infused over 15, 20, and 30 min and the responses were compared to an equimolar dose of phenytoin sodium (21 mg/kg). The ACC-9653 and phenytoin sodium treatments produced similar marked reductions in diastolic blood pressure and contractile force (LVdP/dt). The maximum effects of each treatment occurred at the time of maximum phenytoin sodium levels. Acute toxicity studies of ACC-9653 and phenytoin sodium were carried out in mice, rats, rabbits, and dogs by i.v., i.m., and i.p. routes of administration. The systemic toxic signs of both agents were similar and occurred at approximately equivalent doses. Importantly, the local irritation of ACC-9653 was markedly less than phenytoin sodium following i.m. administration.(ABSTRACT TRUNCATED AT 250 WORDS)
2767010	16	24	ACC-9653	Chemical	C043114
2767010	26	35	phenytoin	Chemical	D010672
2767010	46	54	ACC-9653	Chemical	C043114
2767010	60	84	disodium phosphate ester	Chemical	-1
2767010	88	125	3-hydroxymethyl-5,5-diphenylhydantoin	Chemical	C043104
2767010	143	152	phenytoin	Chemical	D010672
2767010	199	207	ACC-9653	Chemical	C043114
2767010	246	255	phenytoin	Chemical	D010672
2767010	265	273	ACC-9653	Chemical	C043114
2767010	278	294	phenytoin sodium	Chemical	C043114
2767010	343	351	seizures	Disease	D012640
2767010	482	490	ACC-9653	Chemical	C043114
2767010	512	528	phenytoin sodium	Chemical	C043114
2767010	530	538	ACC-9653	Chemical	C043114
2767010	543	559	phenytoin sodium	Chemical	C043114
2767010	605	612	ouabain	Chemical	D010042
2767010	621	644	ventricular tachycardia	Disease	D017180
2767010	686	694	ACC-9653	Chemical	C043114
2767010	698	714	phenytoin sodium	Chemical	C043114
2767010	740	750	arrhythmia	Disease	D001145
2767010	829	845	phenytoin sodium	Chemical	C043114
2767010	897	911	strophanthidin	Chemical	D013327
2767010	920	931	arrhythmias	Disease	D001145
2767010	996	1004	ACC-9653	Chemical	C043114
2767010	1108	1124	phenytoin sodium	Chemical	C043114
2767010	1141	1149	ACC-9653	Chemical	C043114
2767010	1154	1170	phenytoin sodium	Chemical	C043114
2767010	1348	1364	phenytoin sodium	Chemical	C043114
2767010	1379	1387	toxicity	Disease	D064420
2767010	1399	1407	ACC-9653	Chemical	C043114
2767010	1412	1428	phenytoin sodium	Chemical	C043114
2767010	1667	1675	ACC-9653	Chemical	C043114
2767010	1699	1715	phenytoin sodium	Chemical	C043114
2767010	CID	D010042	D017180
2767010	CID	D013327	D001145

2818777|t|Phenytoin induced fatal hepatic injury.
2818777|a|A 61 year old female developed fatal hepatic failure after phenytoin administration. A typical multisystem clinical pattern precedes the manifestations of hepatic injury. The hematologic, biochemical and pathologic features indicate a mixed hepatocellular damage due to drug hypersensitivity. In a patient receiving phenytoin who presents a viral-like illness, early recognition and discontinuation of the drug are mandatory.
2818777	0	9	Phenytoin	Chemical	D010672
2818777	24	38	hepatic injury	Disease	D056486
2818777	77	92	hepatic failure	Disease	D017093
2818777	99	108	phenytoin	Chemical	D010672
2818777	195	209	hepatic injury	Disease	D056486
2818777	281	302	hepatocellular damage	Disease	D056486
2818777	310	331	drug hypersensitivity	Disease	D004342
2818777	356	365	phenytoin	Chemical	D010672
2818777	CID	D010672	D017093
2818777	CID	D010672	D004342

2884595|t|Treatment of lethal pertussis vaccine reaction with histamine H1 antagonists.
2884595|a|We studied mortality after pertussis immunization in the mouse. Without treatment, 73 of 92 animals (80%) died after injection of bovine serum albumin (BSA) on day +7 of pertussis immunization. After pretreatment with 3 mg of cyproheptadine, 2 mg mianserin, or 2 mg chlorpheniramine, only 5 of 105 animals (5%) died after receiving BSA on day +7 (p less than 0.001). Blockade of histamine H1 receptors may reduce mortality in pertussis immunization-induced encephalopathy in mice.
2884595	20	37	pertussis vaccine	Chemical	D010567
2884595	52	61	histamine	Chemical	D006632
2884595	105	114	pertussis	Disease	D014917
2884595	248	257	pertussis	Disease	D014917
2884595	304	318	cyproheptadine	Chemical	D003533
2884595	325	334	mianserin	Chemical	D008803
2884595	344	360	chlorpheniramine	Chemical	D002744
2884595	457	466	histamine	Chemical	D006632
2884595	504	513	pertussis	Disease	D014917
2884595	535	549	encephalopathy	Disease	D001927
2884595	CID	D010567	D001927

2904523|t|Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion.
2904523|a|In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, "stress" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man.
2904523	12	22	adrenaline	Chemical	D004837
2904523	23	35	hypertension	Disease	D006973
2904523	85	95	adrenaline	Chemical	D004837
2904523	158	168	adrenaline	Chemical	D004837
2904523	204	217	noradrenaline	Chemical	D009638
2904523	262	270	dextrose	Chemical	D005947
2904523	491	501	Adrenaline	Chemical	D004837
2904523	511	524	noradrenaline	Chemical	D009638
2904523	710	718	dextrose	Chemical	D005947
2904523	781	791	adrenaline	Chemical	D004837
2904523	901	911	adrenaline	Chemical	D004837
2904523	912	924	hypertension	Disease	D006973
2904523	CID	D004837	D006973

2907577|t|Effect of alkylxanthines on gentamicin-induced acute renal failure in the rat.
2907577|a|Adenosine antagonists have been previously shown to be of benefit in some ischaemic and nephrotoxic models of acute renal failure (ARF). In the present study, the effects of three alkylxanthines with different potencies as adenosine antagonists 8-phenyltheophylline, theophylline and enprofylline, were examined in rats developing acute renal failure after 4 daily injections of gentamicin (200 mg kg-1). Renal function was assessed by biochemical (plasma urea and creatinine), functional (urine analysis and [3H]inulin and [14C]p-aminohippuric acid clearances) and morphological (degree of necrosis) indices. The various drug treatments produced improvements in some, but not all, measurements of renal function. However, any improvement produced by drug treatment was largely a result of a beneficial effect exerted by its vehicle (polyethylene glycol and NaOH). The lack of any consistent protective effect noted with the alkylxanthines tested in the present study indicates that adenosine plays little, if any, pathophysiological role in gentamicin-induced ARF.
2907577	10	24	alkylxanthines	Chemical	-1
2907577	28	38	gentamicin	Chemical	D005839
2907577	47	66	acute renal failure	Disease	D058186
2907577	79	88	Adenosine	Chemical	D000241
2907577	153	162	ischaemic	Disease	D007511
2907577	167	178	nephrotoxic	Disease	D007674
2907577	189	208	acute renal failure	Disease	D058186
2907577	210	213	ARF	Disease	D058186
2907577	259	273	alkylxanthines	Chemical	-1
2907577	302	311	adenosine	Chemical	D000241
2907577	324	344	8-phenyltheophylline	Chemical	C028322
2907577	346	358	theophylline	Chemical	D013806
2907577	363	375	enprofylline	Chemical	C034347
2907577	410	429	acute renal failure	Disease	D058186
2907577	458	468	gentamicin	Chemical	D005839
2907577	535	539	urea	Chemical	D014508
2907577	544	554	creatinine	Chemical	D003404
2907577	608	628	p-aminohippuric acid	Chemical	D010130
2907577	670	678	necrosis	Disease	D009336
2907577	913	932	polyethylene glycol	Chemical	D011092
2907577	937	941	NaOH	Chemical	D012972
2907577	1004	1018	alkylxanthines	Chemical	-1
2907577	1062	1071	adenosine	Chemical	D000241
2907577	1121	1131	gentamicin	Chemical	D005839
2907577	1140	1143	ARF	Disease	D058186
2907577	CID	D005839	D058186

2931989|t|Adverse ocular reactions possibly associated with isotretinoin.
2931989|a|A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia).
2931989	50	62	isotretinoin	Chemical	D015474
2931989	142	154	isotretinoin	Chemical	D015474
2931989	211	215	acne	Disease	D000152
2931989	217	239	Blepharoconjunctivitis	Disease	D003231
2931989	266	274	dry eyes	Disease	D014985
2931989	276	290	blurred vision	Disease	D014786
2931989	322	337	photodermatitis	Disease	D010787
2931989	413	424	papilledema	Disease	D010211
2931989	426	445	pseudotumor cerebri	Disease	D011559
2931989	479	496	corneal opacities	Disease	D003318
2931989	624	636	Isotretinoin	Chemical	D015474
2931989	698	722	congenital abnormalities	Disease	D000013
2931989	753	767	microphthalmos	Disease	D008850
2931989	777	790	hypertelorism	Disease	D006972
2931989	796	818	optic nerve hypoplasia	Disease	C563492
2931989	CID	D015474	D014786
2931989	CID	D015474	D003318
2931989	CID	D015474	D010211
2931989	CID	D015474	D003231
2931989	CID	D015474	D011559
2931989	CID	D015474	D014985
2931989	CID	D015474	D010787

2933998|t|Procaterol and terbutaline in bronchial asthma. A double-blind, placebo-controlled, cross-over study.
2933998|a|Procaterol, a new beta-2 adrenoceptor stimulant, was studied in a double-blind, placebo-controlled, cross-over trial in patients with bronchial asthma. Oral procaterol 50 micrograms b.d., procaterol 100 micrograms b.d., and terbutaline 5 mg t.i.d., were compared when given randomly in 1-week treatment periods. The best clinical effect was found with terbutaline. Both anti-asthmatic and tremorgenic effects of procaterol were dose-related. Procaterol appeared effective in the doses tested, and a twice daily regimen would appear to be suitable with this drug.
2933998	0	10	Procaterol	Chemical	D017265
2933998	15	26	terbutaline	Chemical	D013726
2933998	30	46	bronchial asthma	Disease	D001249
2933998	102	112	Procaterol	Chemical	D017265
2933998	236	252	bronchial asthma	Disease	D001249
2933998	259	269	procaterol	Chemical	D017265
2933998	290	300	procaterol	Chemical	D017265
2933998	326	337	terbutaline	Chemical	D013726
2933998	454	465	terbutaline	Chemical	D013726
2933998	477	486	asthmatic	Disease	D001249
2933998	491	502	tremorgenic	Disease	D014202
2933998	514	524	procaterol	Chemical	D017265
2933998	544	554	Procaterol	Chemical	D017265
2933998	CID	D017265	D014202

2974281|t|Subacute effects of propranolol and B 24/76 on isoproterenol-induced rat heart hypertrophy in correlation with blood pressure.
2974281|a|We compared the potential beta-receptor blocker, B 24/76 i.e. 1-(2,4-dichlorophenoxy)-3[2-3,4-dimethoxyphenyl)ethanolamino]-prop an-2-ol, which is characterized by beta 1-adrenoceptor blocking and beta 2-adrenoceptor stimulating properties with propranolol. The studies were performed using an experimental model of isoproterenol-induced heart hypertrophy in rats. A correlation of the blood pressure was neither found in the development nor in the attempt to suppress the development of heart hypertrophy with the two beta-receptor blockers. Both beta-blockers influenced the development of hypertrophy to a different, but not reproducible extent. It was possible to suppress the increased ornithine decarboxylase activity with both beta-blockers in hypertrophied hearts, but there was no effect on the heart mass. Neither propranolol nor B 24/76 could stop the changes in the characteristic myosin isoenzyme pattern of the hypertrophied rat heart. Thus, the investigations did not provide any evidence that the beta-receptor blockers propranolol and B 24/76 have the potency to prevent isoproterenol from producing heart hypertrophy.
2974281	20	31	propranolol	Chemical	D011433
2974281	47	60	isoproterenol	Chemical	D007545
2974281	73	90	heart hypertrophy	Disease	D006332
2974281	372	383	propranolol	Chemical	D011433
2974281	443	456	isoproterenol	Chemical	D007545
2974281	465	482	heart hypertrophy	Disease	D006332
2974281	615	632	heart hypertrophy	Disease	D006332
2974281	719	730	hypertrophy	Disease	D006984
2974281	818	827	ornithine	Chemical	D009952
2974281	878	898	hypertrophied hearts	Disease	D006332
2974281	951	962	propranolol	Chemical	D011433
2974281	1052	1065	hypertrophied	Disease	D006984
2974281	1163	1174	propranolol	Chemical	D011433
2974281	1215	1228	isoproterenol	Chemical	D007545
2974281	1244	1261	heart hypertrophy	Disease	D006332
2974281	CID	D007545	D006332

3074291|t|Comparison of the effect of oxitropium bromide and of slow-release theophylline on nocturnal asthma.
3074291|a|The effects of a new inhaled antimuscarinic drug, oxitropium bromide, and of a slow-release theophylline preparation upon nocturnal asthma were compared in a placebo-controlled double-blind study. Two samples were studied: 12 patients received oxitropium at 600 micrograms (6 subjects) or at 400 micrograms t.i.d. (6 subjects) whereas 11 received theophylline at 300 mg b.i.d. Morning dipping, assessed by the fall in peak flow overnight, was significantly reduced in the periods when either active drug was taken, whereas no difference was noticed during the placebo administration. No significant difference was noticed between results obtained with either active drug, as well as with either dosage of oxitropium. No subject reported side effects of oxitropium, as compared to three subjects reporting nausea, vomiting and tremors after theophylline. Oxitropium proves to be a valuable alternative to theophylline in nocturnal asthma, since it is equally potent, safer and does not require the titration of dosage.
3074291	28	46	oxitropium bromide	Chemical	C017590
3074291	67	79	theophylline	Chemical	D013806
3074291	93	99	asthma	Disease	D001249
3074291	151	169	oxitropium bromide	Chemical	C017590
3074291	193	205	theophylline	Chemical	D013806
3074291	233	239	asthma	Disease	D001249
3074291	345	355	oxitropium	Chemical	C017590
3074291	448	460	theophylline	Chemical	D013806
3074291	806	816	oxitropium	Chemical	C017590
3074291	854	864	oxitropium	Chemical	C017590
3074291	906	912	nausea	Disease	D009325
3074291	914	922	vomiting	Disease	D014839
3074291	927	934	tremors	Disease	D014202
3074291	941	953	theophylline	Chemical	D013806
3074291	955	965	Oxitropium	Chemical	C017590
3074291	1005	1017	theophylline	Chemical	D013806
3074291	1031	1037	asthma	Disease	D001249
3074291	CID	D013806	D014202
3074291	CID	D013806	D009325
3074291	CID	D013806	D014839

3083835|t|Penicillin anaphylaxis.
3083835|a|A case of oral penicillin anaphylaxis is described, and the terminology, occurrence, clinical manifestations, pathogenesis, prevention, and treatment of anaphylaxis are reviewed. Emergency physicians should be aware of oral penicillin anaphylaxis in order to prevent its occurrence by prescribing the antibiotic judiciously and knowledgeably and to offer optimal medical therapy once this life-threatening reaction has begun.
3083835	0	10	Penicillin	Chemical	D010406
3083835	11	22	anaphylaxis	Disease	D000707
3083835	39	49	penicillin	Chemical	D010406
3083835	50	61	anaphylaxis	Disease	D000707
3083835	177	188	anaphylaxis	Disease	D000707
3083835	248	258	penicillin	Chemical	D010406
3083835	259	270	anaphylaxis	Disease	D000707
3083835	CID	D010406	D000707

3084231|t|Reversible valproic acid-induced dementia: a case report.
3084231|a|Reversible valproic acid-induced dementia was documented in a 21-year-old man with epilepsy who had a 3-year history of insidious progressive decline in global cognitive abilities documented by serial neuropsychological studies. Repeat neuropsychological testing 7 weeks after discontinuation of the drug revealed dramatic improvement in IQ, memory, naming, and other tasks commensurate with clinical recovery in his intellectual capacity. Possible pathophysiological mechanisms which may have been operative in this case include: a direct central nervous system (CNS) toxic effect of valproic acid; a paradoxical epileptogenic effect secondary to the drug; and an indirect CNS toxic effect mediated through valproic acid-induced hyperammonemia.
3084231	11	24	valproic acid	Chemical	D014635
3084231	33	41	dementia	Disease	D003704
3084231	69	82	valproic acid	Chemical	D014635
3084231	91	99	dementia	Disease	D003704
3084231	141	149	epilepsy	Disease	D004827
3084231	643	656	valproic acid	Chemical	D014635
3084231	766	779	valproic acid	Chemical	D014635
3084231	788	802	hyperammonemia	Disease	D022124
3084231	CID	D014635	D003704
3084231	CID	D014635	D022124

3088653|t|Reversal of scopolamine-induced amnesia of passive avoidance by pre- and post-training naloxone.
3088653|a|In a series of five experiments, the modulating role of naloxone on a scopolamine-induced retention deficit in a passive avoidance paradigm was investigated in mice. Scopolamine, but not methyl scopolamine (1 and 3 mg/kg), induced an amnesia as measured by latency and duration parameters. Naloxone (0.3, 1, 3, and 10 mg/kg) injected prior to training attenuated the retention deficit with a peak of activity at 3 mg/kg. The effect of naloxone could be antagonized with morphine (1, 3, and 10 mg/kg), demonstrating the opioid specificity of the naloxone effect. Post-training administration of naloxone (3 mg/kg) as a single or as a split dose also attenuated the scopolamine-induced amnesia. Control experiments indicated that neither an increase in pain sensitivity (pre-training naloxone) nor an induced aversive state (post-training naloxone) appear to be responsible for the influence of naloxone on the scopolamine-induced retention deficit. These results extend previous findings implicating a cholinergic-opioid interaction in memory processes. A possible mechanism for this interaction involving the septo-hippocampal cholinergic pathway is discussed.
3088653	12	23	scopolamine	Chemical	D012601
3088653	32	39	amnesia	Disease	D000647
3088653	87	95	naloxone	Chemical	D009270
3088653	153	161	naloxone	Chemical	D009270
3088653	167	178	scopolamine	Chemical	D012601
3088653	187	204	retention deficit	Disease	D008569
3088653	263	274	Scopolamine	Chemical	D012601
3088653	284	302	methyl scopolamine	Chemical	D019832
3088653	331	338	amnesia	Disease	D000647
3088653	387	395	Naloxone	Chemical	D009270
3088653	464	481	retention deficit	Disease	D008569
3088653	532	540	naloxone	Chemical	D009270
3088653	567	575	morphine	Chemical	D009020
3088653	642	650	naloxone	Chemical	D009270
3088653	691	699	naloxone	Chemical	D009270
3088653	761	772	scopolamine	Chemical	D012601
3088653	781	788	amnesia	Disease	D000647
3088653	848	852	pain	Disease	D010146
3088653	879	887	naloxone	Chemical	D009270
3088653	934	942	naloxone	Chemical	D009270
3088653	990	998	naloxone	Chemical	D009270
3088653	1006	1017	scopolamine	Chemical	D012601
3088653	1026	1043	retention deficit	Disease	D008569
3088653	CID	D012601	D000647

3109094|t|Electron microscopic investigations of the cyclophosphamide-induced lesions of the urinary bladder of the rat and their prevention by mesna.
3109094|a|Fully developed cyclophosphamide-induced cystitis is characterized by nearly complete detachment of the urothelium, severe submucosal edema owing to damage to the microvascular bed and focal muscle necroses. The initial response to the primary attack by the cyclophosphamide metabolites seems to be fragmentation of the luminal membrane. This damages the cellular barrier against the hypertonic urine. Subsequent breaks in the lateral cell membranes of the superficial cells and in all the plasma membranes of the intermediate and basal cells, intercellular and intracellular edema and disintegration of the desmosomes and hemidesmosomes lead to progressive degeneration and detachment of the epithelial cells with exposure and splitting of the basal membrane. The morphological changes of the endothelial cells, which become more pronounced in the later stages of the experiment, the involvement of blood vessels regardless of their diameter and the location-dependent extent of the damage indicate a direct type of damage which is preceded by a mediator-induced increase in permeability, the morphological correlate of which is the formation of gaps in the interendothelial cell connections on the venules. These changes can be effectively prevented by mesna. The only sign of a possible involvement is the increase in the number of specific granules with a presumed lysosomal function in the superficial cells.
3109094	43	59	cyclophosphamide	Chemical	D003520
3109094	68	98	lesions of the urinary bladder	Disease	D001745
3109094	134	139	mesna	Chemical	D015080
3109094	157	173	cyclophosphamide	Chemical	D003520
3109094	182	190	cystitis	Disease	D003556
3109094	275	280	edema	Disease	D004487
3109094	339	347	necroses	Disease	D009336
3109094	399	415	cyclophosphamide	Chemical	D003520
3109094	461	468	luminal	Chemical	D010634
3109094	717	722	edema	Disease	D004487
3109094	1396	1401	mesna	Chemical	D015080
3109094	CID	D003520	D001745

3125850|t|Increase in intragastric pressure during suxamethonium-induced muscle fasciculations in children: inhibition by alfentanil.
3125850|a|Changes in intragastric pressure after the administration of suxamethonium 1.5 mg kg-1 i.v. were studied in 32 children (mean age 6.9 yr) pretreated with either physiological saline or alfentanil 50 micrograms kg-1. Anaesthesia was induced with thiopentone 5 mg kg-1. The incidence and intensity of muscle fasciculations caused by suxamethonium were significantly greater in the control than in the alfentanil group. The intragastric pressure during muscle fasciculations was significantly higher in the control group (16 +/- 0.7 (SEM) cm H2O) than in the alfentanil group (7.7 +/- 1.5 (SEM) cm H2O). The increase in intragastric pressure was directly related to the intensity of muscle fasciculations (regression line: y = 0.5 + 4.78x with r of 0.78). It is concluded that intragastric pressure increases significantly during muscle fasciculations caused by suxamethonium in healthy children. Alfentanil 50 micrograms kg-1 effectively inhibits the incidence and intensity of suxamethonium-induced muscle fasciculations; moreover, intragastric pressure remains at its control value.
3125850	41	54	suxamethonium	Chemical	D013390
3125850	63	84	muscle fasciculations	Disease	D005207
3125850	112	122	alfentanil	Chemical	D015760
3125850	185	198	suxamethonium	Chemical	D013390
3125850	309	319	alfentanil	Chemical	D015760
3125850	369	380	thiopentone	Chemical	D013874
3125850	423	444	muscle fasciculations	Disease	D005207
3125850	455	468	suxamethonium	Chemical	D013390
3125850	523	533	alfentanil	Chemical	D015760
3125850	574	595	muscle fasciculations	Disease	D005207
3125850	663	666	H2O	Chemical	D014867
3125850	680	690	alfentanil	Chemical	D015760
3125850	719	722	H2O	Chemical	D014867
3125850	804	825	muscle fasciculations	Disease	D005207
3125850	951	972	muscle fasciculations	Disease	D005207
3125850	983	996	suxamethonium	Chemical	D013390
3125850	1018	1028	Alfentanil	Chemical	D015760
3125850	1100	1113	suxamethonium	Chemical	D013390
3125850	1122	1143	muscle fasciculations	Disease	D005207
3125850	CID	D013390	D005207

3155884|t|Acute insulin treatment normalizes the resistance to the cardiotoxic effect of isoproterenol in streptozotocin diabetic rats. A morphometric study of isoproterenol induced myocardial fibrosis.
3155884|a|The acute effect of insulin treatment on the earlier reported protective effect of streptozotocin diabetes against the cardiotoxic effect of high doses of isoproterenol (ISO) was investigated in rats. Thirty to 135 min after the injection of crystalline insulin, ISO was given subcutaneously and when ISO induced fibrosis in the myocardium was morphometrically analyzed 7 days later, a highly significant correlation (r = 0.83, 2 p = 0.006) to the slope of the fall in blood glucose after insulin treatment appeared. The myocardial content of catecholamines was estimated in these 8 day diabetic rats. The norepinephrine content was significantly increased while epinephrine remained unchanged. An enhanced sympathetic nervous system activity with a consequent down regulation of the myocardial beta-adrenergic receptors could, therefore, explain this catecholamine resistance. The rapid reversion after insulin treatment excludes the possibility that streptozotocin in itself causes the ISO resistance and points towards a direct insulin effect on myocardial catecholamine sensitivity in diabetic rats. The phenomenon described might elucidate pathogenetic mechanisms behind toxic myocardial cell degeneration and may possibly have relevance for acute cardiovascular complications in diabetic patients.
3155884	57	68	cardiotoxic	Disease	D066126
3155884	79	92	isoproterenol	Chemical	D007545
3155884	96	110	streptozotocin	Chemical	D013311
3155884	111	119	diabetic	Disease	D003920
3155884	150	163	isoproterenol	Chemical	D007545
3155884	183	191	fibrosis	Disease	D005355
3155884	276	290	streptozotocin	Chemical	D013311
3155884	291	299	diabetes	Disease	D003920
3155884	312	323	cardiotoxic	Disease	D066126
3155884	348	361	isoproterenol	Chemical	D007545
3155884	363	366	ISO	Chemical	D007545
3155884	456	459	ISO	Chemical	D007545
3155884	494	497	ISO	Chemical	D007545
3155884	506	514	fibrosis	Disease	D005355
3155884	668	675	glucose	Chemical	D005947
3155884	736	750	catecholamines	Chemical	D002395
3155884	780	788	diabetic	Disease	D003920
3155884	799	813	norepinephrine	Chemical	D009638
3155884	856	867	epinephrine	Chemical	D004837
3155884	1045	1058	catecholamine	Chemical	D002395
3155884	1145	1159	streptozotocin	Chemical	D013311
3155884	1181	1184	ISO	Chemical	D007545
3155884	1253	1266	catecholamine	Chemical	D002395
3155884	1282	1290	diabetic	Disease	D003920
3155884	1478	1486	diabetic	Disease	D003920
3155884	CID	D007545	D005355
3155884	CID	D013311	D003920

3191389|t|Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.
3191389|a|The muscarinic cholinergic agonist pilocarpine induces in rats seizures and status epilepticus followed by widespread damage to the forebrain. The present study was designed to investigate the effect of 5 non-steroidal anti-inflammatory drugs, sodium salicylate, phenylbutazone, indomethacin, ibuprofen and mefenamic acid, on seizures produced by pilocarpine. Pretreatment of rats with sodium salicylate, ED50 103 mg/kg (60-174), and phenylbutazone, 59 mg/kg (50-70) converted the non-convulsant dose of pilocarpine, 200 mg/kg, to a convulsant one. Indomethacin, 1-10 mg/kg, and ibuprofen, 10-100 mg/kg, failed to modulate seizures produced by pilocarpine. Mefenamic acid, 26 (22-30) mg/kg, prevented seizures and protected rats from seizure-related brain damage induced by pilocarpine, 380 mg/kg. These results indicate that non-steroidal anti-inflammatory drugs differentially modulate the threshold for pilocarpine-induced seizures.
3191389	65	73	seizures	Disease	D012640
3191389	86	97	pilocarpine	Chemical	D010862
3191389	142	153	pilocarpine	Chemical	D010862
3191389	170	178	seizures	Disease	D012640
3191389	183	201	status epilepticus	Disease	D013226
3191389	351	368	sodium salicylate	Chemical	D012980
3191389	370	384	phenylbutazone	Chemical	D010653
3191389	386	398	indomethacin	Chemical	D007213
3191389	400	409	ibuprofen	Chemical	D007052
3191389	414	428	mefenamic acid	Chemical	D008528
3191389	433	441	seizures	Disease	D012640
3191389	454	465	pilocarpine	Chemical	D010862
3191389	493	510	sodium salicylate	Chemical	D012980
3191389	541	555	phenylbutazone	Chemical	D010653
3191389	611	622	pilocarpine	Chemical	D010862
3191389	656	668	Indomethacin	Chemical	D007213
3191389	686	695	ibuprofen	Chemical	D007052
3191389	730	738	seizures	Disease	D012640
3191389	751	762	pilocarpine	Chemical	D010862
3191389	764	778	Mefenamic acid	Chemical	D008528
3191389	808	816	seizures	Disease	D012640
3191389	841	848	seizure	Disease	D012640
3191389	857	869	brain damage	Disease	D001930
3191389	881	892	pilocarpine	Chemical	D010862
3191389	1013	1024	pilocarpine	Chemical	D010862
3191389	1033	1041	seizures	Disease	D012640
3191389	CID	D010653	D012640
3191389	CID	D012980	D012640
3191389	CID	D010862	D012640
3191389	CID	D010862	D013226

3289726|t|Acute neurologic dysfunction after high-dose etoposide therapy for malignant glioma.
3289726|a|Etoposide (VP-16-213) has been used in the treatment of many solid tumors and hematologic malignancies. When used in high doses and in conjunction with autologous bone marrow transplantation, this agent has activity against several treatment-resistant cancers including malignant glioma. In six of eight patients (75%) who we treated for recurrent or resistant glioma, sudden severe neurologic deterioration occurred. This developed a median of 9 days after initiation of high-dose etoposide therapy. Significant clinical manifestations have included confusion, papilledema, somnolence, exacerbation of motor deficits, and sharp increase in seizure activity. These abnormalities resolved rapidly after initiation of high-dose intravenous dexamethasone therapy. In all patients, computerized tomographic (CT) brain scans demonstrated stability in tumor size and peritumor edema when compared with pretransplant scans. This complication appears to represent a significant new toxicity of high-dose etoposide therapy for malignant glioma.
3289726	0	28	Acute neurologic dysfunction	Disease	D009422
3289726	45	54	etoposide	Chemical	D005047
3289726	67	83	malignant glioma	Disease	D005910
3289726	85	94	Etoposide	Chemical	D005047
3289726	96	105	VP-16-213	Chemical	D005047
3289726	152	158	tumors	Disease	D009369
3289726	163	187	hematologic malignancies	Disease	D019337
3289726	337	344	cancers	Disease	D009369
3289726	355	371	malignant glioma	Disease	D005910
3289726	446	452	glioma	Disease	D005910
3289726	468	492	neurologic deterioration	Disease	D009422
3289726	567	576	etoposide	Chemical	D005047
3289726	636	645	confusion	Disease	D003221
3289726	647	658	papilledema	Disease	D010211
3289726	660	670	somnolence	Disease	D006970
3289726	688	702	motor deficits	Disease	-1
3289726	726	733	seizure	Disease	D012640
3289726	823	836	dexamethasone	Chemical	D003907
3289726	931	936	tumor	Disease	D009369
3289726	956	961	edema	Disease	D004487
3289726	1059	1067	toxicity	Disease	D064420
3289726	1081	1090	etoposide	Chemical	D005047
3289726	1103	1119	malignant glioma	Disease	D005910
3289726	CID	D005047	D003221
3289726	CID	D005047	D012640
3289726	CID	D005047	D010211

3297909|t|Progressive bile duct injury after thiabendazole administration.
3297909|a|A 27-yr-old man developed jaundice 2 wk after exposure to thiabendazole. Cholestasis persisted for 3 yr, at which time a liver transplant was performed. Two liver biopsy specimens and the hepatectomy specimen were remarkable for almost complete disappearance of interlobular bile ducts. Prominent fibrosis and hepatocellular regeneration were also present; however, the lobular architecture was preserved. This case represents an example of "idiosyncratic" drug-induced liver damage in which the primary target of injury is the bile duct. An autoimmune pathogenesis of the bile duct destruction is suggested.
3297909	12	28	bile duct injury	Disease	D001649
3297909	35	48	thiabendazole	Chemical	D013827
3297909	91	99	jaundice	Disease	D007565
3297909	123	136	thiabendazole	Chemical	D013827
3297909	138	149	Cholestasis	Disease	D002779
3297909	362	370	fibrosis	Disease	D005355
3297909	522	547	drug-induced liver damage	Disease	D056486
3297909	638	659	bile duct destruction	Disease	D001649
3297909	CID	D013827	D056486
3297909	CID	D013827	D002779

3323259|t|Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications.
3323259|a|Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.
3323259	24	43	1,4-dihydropyridine	Chemical	C038806
3323259	44	68	calcium channel blockers	Chemical	D002121
3323259	140	147	calcium	Chemical	D002118
3323259	171	193	cardiovascular disease	Disease	D002318
3323259	234	265	calcium channel blocking agents	Chemical	D002121
3323259	296	319	cardiovascular diseases	Disease	D002318
3323259	456	480	calcium channel blockers	Chemical	D002121
3323259	531	540	verapamil	Chemical	D014700
3323259	545	554	diltiazem	Chemical	D004110
3323259	647	662	dihydropyridine	Chemical	C038806
3323259	663	687	calcium channel blockers	Chemical	D002121
3323259	838	853	dihydropyridine	Chemical	C038806
3323259	894	904	nifedipine	Chemical	D009543
3323259	914	920	angina	Disease	D000787
3323259	925	937	hypertension	Disease	D006973
3323259	1019	1043	calcium channel blockers	Chemical	D002121
3323259	1190	1202	nitrendipine	Chemical	D009568
3323259	1207	1218	nisoldipine	Chemical	D015737
3323259	1324	1336	hypertension	Disease	D006973
3323259	1378	1389	nisoldipine	Chemical	D015737
3323259	1445	1451	angina	Disease	D000787
3323259	1499	1509	nimodipine	Chemical	D009553
3323259	1549	1572	subarachnoid hemorrhage	Disease	D013345
3323259	1574	1591	migraine headache	Disease	D008881
3323259	1593	1601	dementia	Disease	D003704
3323259	1607	1613	stroke	Disease	D020521
3323259	1631	1646	dihydropyridine	Chemical	C038806
3323259	1647	1671	calcium channel blockers	Chemical	D002121
3323259	1705	1713	headache	Disease	D006261
3323259	1722	1730	flushing	Disease	D005483
3323259	1732	1744	palpitations	Disease	-1
3323259	1746	1751	edema	Disease	D004487
3323259	1753	1759	nausea	Disease	D009325
3323259	1761	1769	anorexia	Disease	D000855
3323259	1775	1784	dizziness	Disease	D004244
3323259	CID	D002121	D000855
3323259	CID	D002121	D004244
3323259	CID	D002121	D004487
3323259	CID	D002121	D006261
3323259	CID	D002121	D009325
3323259	CID	D002121	D005483

3323599|t|The enhancement of aminonucleoside nephrosis by the co-administration of protamine.
3323599|a|An experimental model of focal segmental glomerular sclerosis (FSGS) was developed in rats by the combined administration of puromycin-aminonucleoside (AMNS) and protamine sulfate (PS). Male Sprague-Dawley rats, uninephrectomized three weeks before, received daily injections of subcutaneous AMNS (1 mg/100 g body wt) and intravenous PS (2 separated doses of 2.5 mg/100 g body wt) for four days. The series of injections were repeated another three times at 10 day intervals. The animals were sacrificed on days 24, 52, and 80. They developed nephrotic syndrome and finally renal failure. The time-course curve of creatinine clearance dropped and showed significant difference (P less than 0.01) from that of each control group, such as, AMNS alone, PS alone or saline injected. Their glomeruli showed changes of progressive FSGS. The ultrastructural studies in the initial stage revealed significant lack of particles of perfused ruthenium red on the lamina rara externa and marked changes in epithelial cell cytoplasm. Therefore, it is suggested that the administration of PS enhances the toxicity of AMNS on the glomerulus and readily produces progressive FSGS in rats resulting in the end-stage renal disease.
3323599	19	34	aminonucleoside	Chemical	D011692
3323599	35	44	nephrosis	Disease	D009401
3323599	109	145	focal segmental glomerular sclerosis	Disease	D005923
3323599	147	151	FSGS	Disease	D005923
3323599	209	234	puromycin-aminonucleoside	Chemical	D011692
3323599	236	240	AMNS	Chemical	D011692
3323599	246	263	protamine sulfate	Chemical	D011479
3323599	265	267	PS	Chemical	D011479
3323599	376	380	AMNS	Chemical	D011692
3323599	418	420	PS	Chemical	D011479
3323599	627	645	nephrotic syndrome	Disease	D009404
3323599	658	671	renal failure	Disease	D051437
3323599	698	708	creatinine	Chemical	D003404
3323599	822	826	AMNS	Chemical	D011692
3323599	834	836	PS	Chemical	D011479
3323599	909	913	FSGS	Disease	D005923
3323599	1015	1024	ruthenium	Chemical	D012428
3323599	1159	1161	PS	Chemical	D011479
3323599	1175	1183	toxicity	Disease	D064420
3323599	1187	1191	AMNS	Chemical	D011692
3323599	1243	1247	FSGS	Disease	D005923
3323599	1273	1296	end-stage renal disease	Disease	D007676
3323599	CID	D011692	D005923
3323599	CID	D011692	D009404
3323599	CID	D011692	D007676

3339945|t|Theophylline neurotoxicity in pregnant rats.
3339945|a|The purpose of this investigation was to determine whether the neurotoxicity of theophylline is altered in advanced pregnancy. Sprague-Dawley rats that were 20 days pregnant and nonpregnant rats of the same age and strain received infusions of aminophylline until onset of maximal seizures which occurred after 28 and 30 minutes respectively. Theophylline concentrations at this endpoint in serum (total) and CSF were similar but serum (free) and brain concentrations were slightly different in pregnant rats. Theophylline serum protein binding determined by equilibrium dialysis was lower in pregnant rats. Fetal serum concentrations at onset of seizures in the mother were similar to maternal brain and CSF concentrations and correlated significantly with the former. It is concluded that advanced pregnancy has a negligible effect on the neurotoxic response to theophylline in rats.
3339945	0	12	Theophylline	Chemical	D013806
3339945	13	26	neurotoxicity	Disease	D020258
3339945	108	121	neurotoxicity	Disease	D020258
3339945	125	137	theophylline	Chemical	D013806
3339945	289	302	aminophylline	Chemical	D000628
3339945	326	334	seizures	Disease	D012640
3339945	388	400	Theophylline	Chemical	D013806
3339945	555	567	Theophylline	Chemical	D013806
3339945	692	700	seizures	Disease	D012640
3339945	886	896	neurotoxic	Disease	D020258
3339945	909	921	theophylline	Chemical	D013806
3339945	CID	D000628	D012640

3375885|t|Hyperkalemia induced by indomethacin and naproxen and reversed by fludrocortisone.
3375885|a|We have described a patient with severe rheumatoid arthritis and a history of mefenamic acid nephropathy in whom hyperkalemia and inappropriate hypoaldosteronism were caused by both indomethacin and naproxen, without major decline in renal function. It is likely that preexisting renal disease predisposed this patient to type IV renal tubular acidosis with prostaglandin synthetase inhibitors. Because he was unable to discontinue nonsteroidal anti-inflammatory drug therapy, fludrocortisone was added, correcting the hyperkalemia and allowing indomethacin therapy to be continued safely.
3375885	0	12	Hyperkalemia	Disease	D006947
3375885	24	36	indomethacin	Chemical	D007213
3375885	41	49	naproxen	Chemical	D009288
3375885	66	81	fludrocortisone	Chemical	D005438
3375885	123	143	rheumatoid arthritis	Disease	D001172
3375885	161	175	mefenamic acid	Chemical	D008528
3375885	176	187	nephropathy	Disease	D007674
3375885	196	208	hyperkalemia	Disease	D006947
3375885	227	244	hypoaldosteronism	Disease	D006994
3375885	265	277	indomethacin	Chemical	D007213
3375885	282	290	naproxen	Chemical	D009288
3375885	363	376	renal disease	Disease	D007674
3375885	405	435	type IV renal tubular acidosis	Disease	D006994
3375885	441	454	prostaglandin	Chemical	D011453
3375885	560	575	fludrocortisone	Chemical	D005438
3375885	602	614	hyperkalemia	Disease	D006947
3375885	628	640	indomethacin	Chemical	D007213
3375885	CID	D008528	D007674
3375885	CID	D007213	D006947
3375885	CID	D009288	D006994
3375885	CID	D009288	D006947
3375885	CID	D007213	D006994

3383127|t|Hypotension as a manifestation of cardiotoxicity in three patients receiving cisplatin and 5-fluorouracil.
3383127|a|Cardiac symptoms, including hypotension, developed in three patients with advanced colorectal carcinoma while being treated with cisplatin (CDDP) and 5-fluorouracil (5-FU). In two patients, hypotension was associated with severe left ventricular dysfunction. All three patients required therapy discontinuation. Cardiac enzymes remained normal despite transient electrocardiographic (EKG) changes. The presentation and cardiac evaluation (hemodynamic, echocardiographic, and scintigraphic) of these patients suggest new manifestations of 5-FU cardiotoxicity that may be influenced by CDDP. The possible pathophysiologic mechanisms are discussed.
3383127	0	11	Hypotension	Disease	D007022
3383127	34	48	cardiotoxicity	Disease	D066126
3383127	77	86	cisplatin	Chemical	D002945
3383127	91	105	5-fluorouracil	Chemical	D005472
3383127	135	146	hypotension	Disease	D007022
3383127	190	210	colorectal carcinoma	Disease	D015179
3383127	236	245	cisplatin	Chemical	D002945
3383127	247	251	CDDP	Chemical	D002945
3383127	257	271	5-fluorouracil	Chemical	D005472
3383127	273	277	5-FU	Chemical	D005472
3383127	297	308	hypotension	Disease	D007022
3383127	336	364	left ventricular dysfunction	Disease	D018487
3383127	645	649	5-FU	Chemical	D005472
3383127	650	664	cardiotoxicity	Disease	D066126
3383127	691	695	CDDP	Chemical	D002945
3383127	CID	D005472	D007022
3383127	CID	D005472	D018487
3383127	CID	D002945	D007022
3383127	CID	D002945	D018487

3409843|t|Fatal aplastic anemia in a patient treated with carbamazepine.
3409843|a|A case of fatal aplastic anemia due to carbamazepine treatment in an epileptic woman is reported. Despite concerns of fatal bone marrow toxicity due to carbamazepine, this is only the fourth documented and published report. Carbamazepine is a safe drug, but physicians and patients should be aware of the exceedingly rare but potentially fatal side effects, better prevented by clinical than by laboratory monitoring.
3409843	6	21	aplastic anemia	Disease	D000741
3409843	48	61	carbamazepine	Chemical	D002220
3409843	79	94	aplastic anemia	Disease	D000741
3409843	102	115	carbamazepine	Chemical	D002220
3409843	132	141	epileptic	Disease	D004827
3409843	187	207	bone marrow toxicity	Disease	D001855
3409843	215	228	carbamazepine	Chemical	D002220
3409843	287	300	Carbamazepine	Chemical	D002220
3409843	CID	D002220	D000741

3423103|t|Participation of a bulbospinal serotonergic pathway in the rat brain in clonidine-induced hypotension and bradycardia.
3423103|a|The effects of microinjection of clonidine (1-10 micrograms in 1 microliter) into a region adjacent to the ventrolateral surface of the medulla oblongata on cardiovascular function were assessed in urethane-anesthetized rats. Intramedullary administration of clonidine, but not saline vehicle, caused a dose-dependent decrease in both the mean arterial pressure and the heart rate. The clonidine-induced hypotension was antagonized by prior spinal transection, but not bilateral vagotomy. On the other hand, the clonidine-induced bradycardia was antagonized by prior bilateral vagotomy, but not spinal transection. Furthermore, selective destruction of the spinal 5-HT nerves, produced by bilateral spinal injection of 5,7-dihydroxytryptamine, reduced the magnitude of the vasodepressor or the bradycardiac responses to clonidine microinjected into the area near the ventrolateral surface of the medulla oblongata in rats. The data indicate that a bulbospinal serotonergic pathway is involved in development of clonidine-induced hypotension and bradycardia. The induced hypotension is brought about by a decrease in sympathetic efferent activity, whereas the induced bradycardia was due to an increase in vagal efferent activity.
3423103	72	81	clonidine	Chemical	D003000
3423103	90	101	hypotension	Disease	D007022
3423103	106	117	bradycardia	Disease	D001919
3423103	152	161	clonidine	Chemical	D003000
3423103	317	325	urethane	Chemical	D014520
3423103	378	387	clonidine	Chemical	D003000
3423103	505	514	clonidine	Chemical	D003000
3423103	523	534	hypotension	Disease	D007022
3423103	631	640	clonidine	Chemical	D003000
3423103	649	660	bradycardia	Disease	D001919
3423103	783	787	5-HT	Chemical	D012701
3423103	838	861	5,7-dihydroxytryptamine	Chemical	D015116
3423103	913	925	bradycardiac	Disease	D001919
3423103	939	948	clonidine	Chemical	D003000
3423103	1130	1139	clonidine	Chemical	D003000
3423103	1148	1159	hypotension	Disease	D007022
3423103	1164	1175	bradycardia	Disease	D001919
3423103	1189	1200	hypotension	Disease	D007022
3423103	1286	1297	bradycardia	Disease	D001919
3423103	CID	D003000	D007022
3423103	CID	D003000	D001919

3439580|t|Hypertension in neuroblastoma induced by imipramine.
3439580|a|Hypertension is a well-known finding in some patients with neuroblastoma. However, it has not previously been described in association with the use of Imipramine. We report the occurrence of severe hypertension (blood pressure 190/160) in a 4-year-old girl with neuroblastoma who was given Imipramine to control a behavior disorder. It was determined later that this patient's tumor was recurring at the time of her hypertensive episode. Since she had no blood pressure elevation at initial diagnosis and none following discontinuation of the Imipramine (when she was in florid relapse), we believe that this drug rather than her underlying disease alone caused her hypertension. The mechanism for this reaction is believed to be increased levels of vasoactive catecholamines due to interference of their physiologic inactivation by Imipramine. From this experience, we urge extreme caution in the use of tricyclic antidepressants in children with active neuroblastoma.
3439580	0	12	Hypertension	Disease	D006973
3439580	16	29	neuroblastoma	Disease	D009447
3439580	41	51	imipramine	Chemical	D007099
3439580	53	65	Hypertension	Disease	D006973
3439580	112	125	neuroblastoma	Disease	D009447
3439580	204	214	Imipramine	Chemical	D007099
3439580	251	263	hypertension	Disease	D006973
3439580	315	328	neuroblastoma	Disease	D009447
3439580	343	353	Imipramine	Chemical	D007099
3439580	367	384	behavior disorder	Disease	D002653
3439580	430	435	tumor	Disease	D009369
3439580	469	481	hypertensive	Disease	D006973
3439580	596	606	Imipramine	Chemical	D007099
3439580	719	731	hypertension	Disease	D006973
3439580	814	828	catecholamines	Chemical	D002395
3439580	886	896	Imipramine	Chemical	D007099
3439580	1008	1021	neuroblastoma	Disease	D009447
3439580	CID	D007099	D006973

3475563|t|Rechallenge of patients who developed oral candidiasis or hoarseness with beclomethasone dipropionate.
3475563|a|Of 158 asthmatic patients who were placed on inhaled beclomethasone, 15 (9.5%) developed either hoarseness (8), oral thrush (6), or both (1). When their adverse reactions subsided, seven of these 15 patients were rechallenged with inhaled beclomethasone. These included five cases who developed hoarseness and three who developed Candidiasis. One patient had both. Oral thrush did not recur, but 60% (3/5) of patients with hoarseness had recurrence. We conclude that patients may be restarted on inhaled beclomethasone when clinically indicated; however, because of the high recurrence rate, patients who develop hoarseness should not be re-challenged. Concomitant use of oral prednisone and topical beclomethasone may increase the risk of developing hoarseness or candidiasis.
3475563	38	54	oral candidiasis	Disease	D002180
3475563	58	68	hoarseness	Disease	D006685
3475563	74	101	beclomethasone dipropionate	Chemical	D001507
3475563	110	119	asthmatic	Disease	D001249
3475563	156	170	beclomethasone	Chemical	D001507
3475563	199	209	hoarseness	Disease	D006685
3475563	220	226	thrush	Disease	D002180
3475563	342	356	beclomethasone	Chemical	D001507
3475563	398	408	hoarseness	Disease	D006685
3475563	433	444	Candidiasis	Disease	D002177
3475563	473	479	thrush	Disease	D002180
3475563	526	536	hoarseness	Disease	D006685
3475563	607	621	beclomethasone	Chemical	D001507
3475563	716	726	hoarseness	Disease	D006685
3475563	780	790	prednisone	Chemical	D011241
3475563	803	817	beclomethasone	Chemical	D001507
3475563	854	864	hoarseness	Disease	D006685
3475563	868	879	candidiasis	Disease	D002177
3475563	CID	D001507	D002180
3475563	CID	D001507	D006685

3533179|t|Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor.
3533179|a|Patients who undergo bone marrow transplantation are generally immunosuppressed with a dose of cyclophosphamide (CYA) which is usually calculated based on the patient's weight. At these high doses of CYA, serious cardiotoxicity may occur, but definitive risk factors for the development of such cardiotoxicity have not been described. Since chemotherapeutic agent toxicity generally correlates with dose per body surface area, we retrospectively calculated the dose of CYA in patients transplanted at our institution to determine whether the incidence of CYA cardiotoxicity correlated with the dose per body surface area. Eighty patients who were to receive CYA 50 mg/kg/d for four days as preparation for marrow grafting underwent a total of 84 transplants for aplastic anemia, Wiskott-Aldrich syndrome, or severe combined immunodeficiency syndrome. Fourteen of 84 (17%) patients had symptoms and signs consistent with CYA cardiotoxicity within ten days of receiving 1 to 4 doses of CYA. Six of the 14 patients died with congestive heart failure. The dose of CYA per body surface area was calculated for all patients and the patients were divided into two groups based on daily CYA dose: Group 1, CYA less than or equal to 1.55 g/m2/d; Group 2, CYA greater than 1.55 g/m2/d. Cardiotoxicity that was thought to be related to CYA occurred in 1/32 (3%) of patients in Group 1 and in 13/52 (25%) patients in Group 2 (P less than 0.025). Congestive heart failure caused or contributed to death in 0/32 patients in Group 1 v 6/52 (12%) of patients in Group 2 (P less than 0.25). There was no difference in the rate of engraftment of evaluable patients in the two groups (P greater than 0.5). We conclude that the CYA cardiotoxicity correlates with CYA dosage as calculated by body surface area, and that patients with aplastic anemia and immunodeficiencies can be effectively prepared for bone marrow grafting at a CYA dose of 1.55 g/m2/d for four days with a lower incidence of cardiotoxicity than patients whose CYA dosage is calculated based on weight. This study reaffirms the principle that drug toxicity correlates with dose per body surface area.
3533179	0	16	Cyclophosphamide	Chemical	D003520
3533179	17	31	cardiotoxicity	Disease	D066126
3533179	168	184	cyclophosphamide	Chemical	D003520
3533179	186	189	CYA	Chemical	D003520
3533179	273	276	CYA	Chemical	D003520
3533179	286	300	cardiotoxicity	Disease	D066126
3533179	368	382	cardiotoxicity	Disease	D066126
3533179	437	445	toxicity	Disease	D064420
3533179	542	545	CYA	Chemical	D003520
3533179	628	631	CYA	Chemical	D003520
3533179	632	646	cardiotoxicity	Disease	D066126
3533179	731	734	CYA	Chemical	D003520
3533179	835	850	aplastic anemia	Disease	D000741
3533179	852	876	Wiskott-Aldrich syndrome	Disease	D014923
3533179	881	922	severe combined immunodeficiency syndrome	Disease	D016511
3533179	993	996	CYA	Chemical	D003520
3533179	997	1011	cardiotoxicity	Disease	D066126
3533179	1057	1060	CYA	Chemical	D003520
3533179	1095	1119	congestive heart failure	Disease	D006333
3533179	1133	1136	CYA	Chemical	D003520
3533179	1252	1255	CYA	Chemical	D003520
3533179	1271	1274	CYA	Chemical	D003520
3533179	1319	1322	CYA	Chemical	D003520
3533179	1349	1363	Cardiotoxicity	Disease	D066126
3533179	1398	1401	CYA	Chemical	D003520
3533179	1507	1531	Congestive heart failure	Disease	D006333
3533179	1781	1784	CYA	Chemical	D003520
3533179	1785	1799	cardiotoxicity	Disease	D066126
3533179	1816	1819	CYA	Chemical	D003520
3533179	1886	1901	aplastic anemia	Disease	D000741
3533179	1906	1924	immunodeficiencies	Disease	D007153
3533179	1983	1986	CYA	Chemical	D003520
3533179	2047	2061	cardiotoxicity	Disease	D066126
3533179	2082	2085	CYA	Chemical	D003520
3533179	2169	2177	toxicity	Disease	D064420
3533179	CID	D003520	D006333

3538855|t|Studies of risk factors for aminoglycoside nephrotoxicity.
3538855|a|The epidemiology of aminoglycoside-induced nephrotoxicity is not fully understood. Experimental studies in healthy human volunteers indicate aminoglycosides cause proximal tubular damage in most patients, but rarely, if ever, cause glomerular or tubular dysfunction. Clinical trials of aminoglycosides in seriously ill patients indicate that the relative risk for developing acute renal failure during therapy ranges from 8 to 10 and that the attributable risk is 70% to 80%. Further analysis of these data suggests that the duration of therapy, plasma aminoglycoside levels, liver disease, advanced age, high initial estimated creatinine clearance and, possibly, female gender all increase the risk for nephrotoxicity. Other causes of acute renal failure, such as shock, appear to have an additive effect. Predictive models have been developed from these analyses that should be useful for identifying patients at high risk. These models may also be useful in developing insights into the pathophysiology of aminoglycoside-induced nephrotoxicity.
3538855	28	42	aminoglycoside	Chemical	D000617
3538855	43	57	nephrotoxicity	Disease	D007674
3538855	79	93	aminoglycoside	Chemical	D000617
3538855	102	116	nephrotoxicity	Disease	D007674
3538855	200	215	aminoglycosides	Chemical	D000617
3538855	291	324	glomerular or tubular dysfunction	Disease	D007674
3538855	345	360	aminoglycosides	Chemical	D000617
3538855	434	453	acute renal failure	Disease	D058186
3538855	612	626	aminoglycoside	Chemical	D000617
3538855	635	648	liver disease	Disease	D008107
3538855	687	697	creatinine	Chemical	D003404
3538855	763	777	nephrotoxicity	Disease	D007674
3538855	795	814	acute renal failure	Disease	D058186
3538855	824	829	shock	Disease	D012769
3538855	1068	1082	aminoglycoside	Chemical	D000617
3538855	1091	1105	nephrotoxicity	Disease	D007674
3538855	CID	D000617	D007674

3685052|t|Flurothyl seizure thresholds in mice treated neonatally with a single injection of monosodium glutamate (MSG): evaluation of experimental parameters in flurothyl seizure testing.
3685052|a|Monosodium glutamate (MSG) administration to neonatal rodents produces convulsions and results in numerous biochemical and behavioral deficits. These studies were undertaken to determine if neonatal administration of MSG produced permanent alterations in seizure susceptibility, since previous investigations were inconclusive. A flurothyl ether seizure screening technique was used to evaluate seizure susceptibility in adult mice that received neonatal injections of MSG (4 mg/g and 1 mg/g). MSG treatment resulted in significant reductions in whole brain weight but did not alter seizure threshold. A naloxone (5 mg/kg) challenge was also ineffective in altering the seizure thresholds of either control of MSG-treated mice. Flurothyl ether produced hypothermia which was correlated with the duration of flurothyl exposure; however, the relationship of hypothermia to seizure induction was unclear. Flurothyl seizure testing proved to be a rapid and reliable technique with which to evaluate seizure susceptibility.
3685052	0	9	Flurothyl	Chemical	D005481
3685052	10	17	seizure	Disease	D012640
3685052	83	103	monosodium glutamate	Chemical	D012970
3685052	105	108	MSG	Chemical	D012970
3685052	152	161	flurothyl	Chemical	D005481
3685052	162	169	seizure	Disease	D012640
3685052	179	199	Monosodium glutamate	Chemical	D012970
3685052	201	204	MSG	Chemical	D012970
3685052	250	261	convulsions	Disease	D012640
3685052	396	399	MSG	Chemical	D012970
3685052	434	441	seizure	Disease	D012640
3685052	509	518	flurothyl	Chemical	D005481
3685052	519	524	ether	Chemical	D004986
3685052	525	532	seizure	Disease	D012640
3685052	574	581	seizure	Disease	D012640
3685052	648	651	MSG	Chemical	D012970
3685052	673	676	MSG	Chemical	D012970
3685052	762	769	seizure	Disease	D012640
3685052	783	791	naloxone	Chemical	D009270
3685052	849	856	seizure	Disease	D012640
3685052	889	892	MSG	Chemical	D012970
3685052	907	916	Flurothyl	Chemical	D005481
3685052	917	922	ether	Chemical	D004986
3685052	932	943	hypothermia	Disease	D007035
3685052	986	995	flurothyl	Chemical	D005481
3685052	1035	1046	hypothermia	Disease	D007035
3685052	1050	1057	seizure	Disease	D012640
3685052	1081	1090	Flurothyl	Chemical	D005481
3685052	1091	1098	seizure	Disease	D012640
3685052	1174	1181	seizure	Disease	D012640
3685052	CID	D005481	D007035

3708328|t|Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or gamma-vinyl-GABA into the substantia nigra.
3708328|a|Pilocarpine, given intraperitoneally to rats, reproduces the neuropathological sequelae of temporal lobe epilepsy and provides a relevant animal model for studying mechanisms of buildup of convulsive activity and pathways operative in the generalization and propagation of seizures within the forebrain. In the present study, the effects of manipulating the activity of the gamma-aminobutyric acid (GABA)-mediated synaptic inhibition within the substantia nigra on seizures produced by pilocarpine in rats, were investigated. In animals pretreated with microinjections of isoniazid, 150 micrograms, an inhibitor of activity of the GABA-synthesizing enzyme, L-glutamic acid decarboxylase, into the substantia nigra pars reticulata (SNR), bilaterally, non-convulsant doses of pilocarpine, 100 and 200 mg/kg, resulted in severe motor limbic seizures and status epilepticus. Electroencephalographic and behavioral monitoring revealed a profound reduction of the threshold for pilocarpine-induced convulsions. Morphological analysis of frontal forebrain sections with light microscopy revealed seizure-related damage to the hippocampal formation, thalamus, amygdala, olfactory cortex, substantia nigra and neocortex, which is typically observed with pilocarpine in doses exceeding 350 mg/kg. Bilateral intrastriatal injections of isoniazid did not augment seizures produced by pilocarpine, 200 mg/kg. Application of an irreversible inhibitor of GABA transaminase, gamma-vinyl-GABA (D,L-4-amino-hex-5-enoic acid), 5 micrograms, into the SNR, bilaterally, suppressed the appearance of electrographic and behavioral seizures produced by pilocarpine, 380 mg/kg. This treatment was also sufficient to protect animals from the occurrence of brain damage. Microinjections of gamma-vinyl-GABA, 5 micrograms, into the dorsal striatum, bilaterally, failed to prevent the development of convulsions produced by pilocarpine, 380 mg/kg. The results demonstrate that the threshold for pilocarpine-induced seizures in rats is subjected to the regulation of the GABA-mediated synaptic inhibition within the substantia nigra.
3708328	18	26	seizures	Disease	D012640
3708328	39	50	pilocarpine	Chemical	D010862
3708328	83	92	isoniazid	Chemical	D007538
3708328	96	112	gamma-vinyl-GABA	Chemical	D020888
3708328	140	151	Pilocarpine	Chemical	D010862
3708328	231	253	temporal lobe epilepsy	Disease	D004833
3708328	329	339	convulsive	Disease	D012640
3708328	413	421	seizures	Disease	D012640
3708328	514	537	gamma-aminobutyric acid	Chemical	D005680
3708328	539	543	GABA	Chemical	D005680
3708328	605	613	seizures	Disease	D012640
3708328	626	637	pilocarpine	Chemical	D010862
3708328	712	721	isoniazid	Chemical	D007538
3708328	771	775	GABA	Chemical	D005680
3708328	797	812	L-glutamic acid	Chemical	D018698
3708328	914	925	pilocarpine	Chemical	D010862
3708328	978	986	seizures	Disease	D012640
3708328	991	1009	status epilepticus	Disease	D013226
3708328	1112	1123	pilocarpine	Chemical	D010862
3708328	1132	1143	convulsions	Disease	D012640
3708328	1229	1236	seizure	Disease	D012640
3708328	1385	1396	pilocarpine	Chemical	D010862
3708328	1465	1474	isoniazid	Chemical	D007538
3708328	1491	1499	seizures	Disease	D012640
3708328	1512	1523	pilocarpine	Chemical	D010862
3708328	1580	1584	GABA	Chemical	D005680
3708328	1599	1615	gamma-vinyl-GABA	Chemical	D020888
3708328	1617	1645	D,L-4-amino-hex-5-enoic acid	Chemical	D020888
3708328	1748	1756	seizures	Disease	D012640
3708328	1769	1780	pilocarpine	Chemical	D010862
3708328	1870	1882	brain damage	Disease	D001930
3708328	1903	1919	gamma-vinyl-GABA	Chemical	D020888
3708328	2011	2022	convulsions	Disease	D012640
3708328	2035	2046	pilocarpine	Chemical	D010862
3708328	2106	2117	pilocarpine	Chemical	D010862
3708328	2126	2134	seizures	Disease	D012640
3708328	2181	2185	GABA	Chemical	D005680
3708328	CID	D010862	D012640

3746148|t|Non-invasive detection of coronary artery disease by body surface electrocardiographic mapping after dipyridamole infusion.
3746148|a|Electrocardiographic changes after dipyridamole infusion (0.568 mg/kg/4 min) were studied in 41 patients with coronary artery disease and compared with those after submaximal treadmill exercise by use of the body surface mapping technique. Patients were divided into three groups; 19 patients without myocardial infarction (non-MI group), 14 with anterior infarction (ANT-MI) and eight with inferior infarction (INF-MI). Eighty-seven unipolar electrocardiograms (ECGs) distributed over the entire thoracic surface were simultaneously recorded. After dipyridamole, ischemic ST-segment depression (0.05 mV or more) was observed in 84% of the non-MI group, 29% of the ANT-MI group, 63% of the INF-MI group and 61% of the total population. Exercise-induced ST depression was observed in 84% of the non-MI group, 43% of the ANT-MI group, 38% of the INF-MI group and 61% of the total. For individual patients, there were no obvious differences between the body surface distribution of ST depression in both tests. The increase in pressure rate product after dipyridamole was significantly less than that during the treadmill exercise. The data suggest that the dipyridamole-induced myocardial ischemia is caused by the inhomogenous distribution of myocardial blood flow. We conclude that the dipyridamole ECG test is as useful as the exercise ECG test for the assessment of coronary artery disease.
3746148	26	49	coronary artery disease	Disease	D003324
3746148	101	113	dipyridamole	Chemical	D004176
3746148	159	171	dipyridamole	Chemical	D004176
3746148	234	257	coronary artery disease	Disease	D003324
3746148	425	446	myocardial infarction	Disease	D009203
3746148	452	454	MI	Disease	D009203
3746148	471	490	anterior infarction	Disease	D056988
3746148	492	498	ANT-MI	Disease	D056988
3746148	515	534	inferior infarction	Disease	D056989
3746148	536	542	INF-MI	Disease	D056989
3746148	674	686	dipyridamole	Chemical	D004176
3746148	688	696	ischemic	Disease	D007511
3746148	708	718	depression	Disease	D003866
3746148	768	770	MI	Disease	D009203
3746148	789	795	ANT-MI	Disease	D056988
3746148	814	820	INF-MI	Disease	D056989
3746148	880	890	depression	Disease	D003866
3746148	922	924	MI	Disease	D009203
3746148	943	949	ANT-MI	Disease	D056988
3746148	968	974	INF-MI	Disease	D056989
3746148	1106	1116	depression	Disease	D003866
3746148	1176	1188	dipyridamole	Chemical	D004176
3746148	1279	1291	dipyridamole	Chemical	D004176
3746148	1300	1319	myocardial ischemia	Disease	D017202
3746148	1410	1422	dipyridamole	Chemical	D004176
3746148	1492	1515	coronary artery disease	Disease	D003324
3746148	CID	D004176	D017202

3798047|t|Bradycardia after high-dose intravenous methylprednisolone therapy.
3798047|a|In 5 consecutive patients with rheumatoid arthritis who received intravenous high-dose methylprednisolone (MP) therapy (1 g daily for 2 or 3 consecutive days), a decline in pulse rate was observed, most pronounced on day 4. In one of the 5 patients the bradycardia was associated with complaints of substernal pressure. Reversal to normal heart rate was found on day 7. Electrocardiographic registrations showed sinus bradycardia in all cases. No significant changes in plasma concentrations of electrolytes were found. Careful observation of patients receiving high-dose MP is recommended. High-dose MP may be contraindicated in patients with known heart disease.
3798047	0	11	Bradycardia	Disease	D001919
3798047	40	58	methylprednisolone	Chemical	D008775
3798047	99	119	rheumatoid arthritis	Disease	D001172
3798047	155	173	methylprednisolone	Chemical	D008775
3798047	175	177	MP	Chemical	D008775
3798047	321	332	bradycardia	Disease	D001919
3798047	480	497	sinus bradycardia	Disease	D012804
3798047	640	642	MP	Chemical	D008775
3798047	669	671	MP	Chemical	D008775
3798047	718	731	heart disease	Disease	D006331
3798047	CID	D008775	D001919

3812624|t|Two cases of downbeat nystagmus and oscillopsia associated with carbamazepine.
3812624|a|Downbeat nystagmus is often associated with structural lesions at the craniocervical junction, but has occasionally been reported as a manifestation of metabolic imbalance or drug intoxication. We recorded the eye movements of two patients with reversible downbeat nystagmus related to carbamazepine therapy. The nystagmus of both patients resolved after reduction of the serum carbamazepine levels. Neuroradiologic investigations including magnetic resonance imaging scans in both patients showed no evidence of intracranial abnormality. In patients with downbeat nystagmus who are taking anticonvulsant medications, consideration should be given to reduction in dose before further investigation is undertaken.
3812624	13	31	downbeat nystagmus	Disease	D009759
3812624	36	47	oscillopsia	Disease	D015835
3812624	64	77	carbamazepine	Chemical	D002220
3812624	79	97	Downbeat nystagmus	Disease	D009759
3812624	335	353	downbeat nystagmus	Disease	D009759
3812624	365	378	carbamazepine	Chemical	D002220
3812624	392	401	nystagmus	Disease	D009759
3812624	457	470	carbamazepine	Chemical	D002220
3812624	635	653	downbeat nystagmus	Disease	D009759
3812624	CID	D002220	D015835

3831029|t|Improvement by denopamine (TA-064) of pentobarbital-induced cardiac failure in the dog heart-lung preparation.
3831029|a|The efficacy of denopamine, an orally active beta 1-adrenoceptor agonist, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital (118 +/- 28 mg; mean value +/- SD) such that cardiac output and maximum rate of rise of left ventricular pressure (LV dP/dt max) had been reduced by about 35% and 26% of the respective controls were improved by denopamine (10-300 micrograms) in a dose-dependent manner. With 100 micrograms denopamine, almost complete restoration of cardiac performance was attained, associated with a slight increase in heart rate. No arrhythmias were induced by these doses of denopamine. The results warrant clinical trials of denopamine in the treatment of cardiac failure.
3831029	15	25	denopamine	Chemical	C037293
3831029	27	33	TA-064	Chemical	C037293
3831029	38	51	pentobarbital	Chemical	D010424
3831029	60	75	cardiac failure	Disease	D006333
3831029	127	137	denopamine	Chemical	C037293
3831029	198	213	cardiac failure	Disease	D006333
3831029	290	303	pentobarbital	Chemical	D010424
3831029	515	525	denopamine	Chemical	C037293
3831029	594	604	denopamine	Chemical	C037293
3831029	723	734	arrhythmias	Disease	D001145
3831029	766	776	denopamine	Chemical	C037293
3831029	817	827	denopamine	Chemical	C037293
3831029	848	863	cardiac failure	Disease	D006333
3831029	CID	D010424	D006333

3832950|t|Clonazepam monotherapy for epilepsy in childhood.
3832950|a|Sixty patients (age-range one month to 14 years) with other types of epilepsy than infantile spasms were treated with clonazepam. Disappearance of seizures and normalization of abnormal EEG with disappearance of seizures were recognized in 77% and 50%, respectively. Seizures disappeared in 71% of the patients with generalized seizures and 89% of partial seizures. Improvement of abnormal EEG was noticed in 76% of diffuse paroxysms and in 67% of focal paroxysms. In excellent cases, mean effective dosages were 0.086 +/- 0.021 mg/kg/day in infants and 0.057 +/- 0.022 mg/kg/day in schoolchildren, this difference was statistically significant (p less than 0.005). The incidence of side effects such as drowsiness and ataxia was only 5%.
3832950	0	10	Clonazepam	Chemical	D002998
3832950	27	35	epilepsy	Disease	D004827
3832950	119	127	epilepsy	Disease	D004827
3832950	133	149	infantile spasms	Disease	D013036
3832950	168	178	clonazepam	Chemical	D002998
3832950	197	205	seizures	Disease	D012640
3832950	262	270	seizures	Disease	D012640
3832950	317	325	Seizures	Disease	D012640
3832950	378	386	seizures	Disease	D012640
3832950	406	414	seizures	Disease	D012640
3832950	754	764	drowsiness	Disease	D006970
3832950	769	775	ataxia	Disease	D001259
3832950	CID	D002998	D006970
3832950	CID	D002998	D001259

3833372|t|Postmarketing study of timolol-hydrochlorothiazide antihypertensive therapy.
3833372|a|A postmarketing surveillance study was conducted to determine the safety and efficacy of a fixed-ratio combination containing 10 mg of timolol maleate and 25 mg of hydrochlorothiazide, administered twice daily for one month to hypertensive patients. Data on 9,037 patients were collected by 1,455 participating physicians. Mean systolic blood pressure decreased 25 mmHg and mean diastolic blood pressure declined 15 mmHg after one month of timolol-hydrochlorothiazide therapy (P less than 0.01, both comparisons). Age, race, and sex appeared to have no influence on the decrease in blood pressure. The antihypertensive effect of the drug was greater in patients with more severe hypertension. Overall, 1,453 patients experienced a total of 2,658 adverse events, the most common being fatigue, dizziness, and weakness. Treatment in 590 patients was discontinued because of adverse events.
3833372	23	30	timolol	Chemical	D013999
3833372	31	50	hydrochlorothiazide	Chemical	D006852
3833372	212	227	timolol maleate	Chemical	D013999
3833372	241	260	hydrochlorothiazide	Chemical	D006852
3833372	304	316	hypertensive	Disease	D006973
3833372	517	524	timolol	Chemical	D013999
3833372	525	544	hydrochlorothiazide	Chemical	D006852
3833372	756	768	hypertension	Disease	D006973
3833372	861	868	fatigue	Disease	D005221
3833372	870	879	dizziness	Disease	D004244
3833372	885	893	weakness	Disease	D018908
3833372	CID	D013999	D005221
3833372	CID	D013999	D004244
3833372	CID	D006852	D005221
3833372	CID	D006852	D004244
3833372	CID	D006852	D018908
3833372	CID	D013999	D018908

3864191|t|Salicylate nephropathy in the Gunn rat: potential role of prostaglandins.
3864191|a|We examined the potential role of prostaglandins in the development of analgesic nephropathy in the Gunn strain of rat. The homozygous Gunn rats have unconjugated hyperbilirubinemia due to the absence of glucuronyl transferase, leading to marked bilirubin deposition in renal medulla and papilla. These rats are also highly susceptible to develop papillary necrosis with analgesic administration. We used homozygous (jj) and phenotypically normal heterozygous (jJ) animals. Four groups of rats (n = 7) were studied: jj and jJ rats treated either with aspirin 300 mg/kg every other day or sham-treated. After one week, slices of cortex, outer and inner medulla from one kidney were incubated in buffer and prostaglandin synthesis was determined by radioimmunoassay. The other kidney was examined histologically. A marked corticomedullary gradient of prostaglandin synthesis was observed in all groups. PGE2 synthesis was significantly higher in outer medulla, but not cortex or inner medulla, of jj (38 +/- 6 ng/mg prot) than jJ rats (15 +/- 3) (p less than 0.01). Aspirin treatment reduced PGE2 synthesis in all regions, but outer medullary PGE2 remained higher in jj (18 +/- 3) than jJ rats (9 +/- 2) (p less than 0.05). PGF2 alpha was also significantly higher in the outer medulla of jj rats with and without aspirin administration (p less than 0.05). The changes in renal prostaglandin synthesis were accompanied by evidence of renal damage in aspirin-treated jj but not jJ rats as evidenced by: increased incidence and severity of hematuria (p less than 0.01); increased serum creatinine (p less than 0.05); and increase in outer medullary histopathologic lesions (p less than 0.005 compared to either sham-treated jj or aspirin-treated jJ). These results suggest that enhanced prostaglandin synthesis contributes to maintenance of renal function and morphological integrity, and that inhibition of prostaglandin synthesis may lead to pathological renal medullary lesions and deterioration of renal function.
3864191	0	10	Salicylate	Chemical	D012459
3864191	11	22	nephropathy	Disease	D007674
3864191	58	72	prostaglandins	Chemical	D011453
3864191	108	122	prostaglandins	Chemical	D011453
3864191	155	166	nephropathy	Disease	D007674
3864191	237	255	hyperbilirubinemia	Disease	D006932
3864191	278	288	glucuronyl	Chemical	-1
3864191	320	329	bilirubin	Chemical	D001663
3864191	421	439	papillary necrosis	Disease	D007681
3864191	625	632	aspirin	Chemical	D001241
3864191	779	792	prostaglandin	Chemical	D011453
3864191	923	936	prostaglandin	Chemical	D011453
3864191	975	979	PGE2	Chemical	D015232
3864191	1138	1145	Aspirin	Chemical	D001241
3864191	1164	1168	PGE2	Chemical	D015232
3864191	1215	1219	PGE2	Chemical	D015232
3864191	1296	1306	PGF2 alpha	Chemical	D015237
3864191	1386	1393	aspirin	Chemical	D001241
3864191	1450	1463	prostaglandin	Chemical	D011453
3864191	1506	1518	renal damage	Disease	D007674
3864191	1522	1529	aspirin	Chemical	D001241
3864191	1610	1619	hematuria	Disease	D006417
3864191	1656	1666	creatinine	Chemical	D003404
3864191	1800	1807	aspirin	Chemical	D001241
3864191	1857	1870	prostaglandin	Chemical	D011453
3864191	1978	1991	prostaglandin	Chemical	D011453
3864191	2014	2050	pathological renal medullary lesions	Disease	D058186
3864191	2055	2086	deterioration of renal function	Disease	D007674
3864191	CID	D001241	D007674

3895875|t|Prophylactic lidocaine in the early phase of suspected myocardial infarction.
3895875|a|Four hundred two patients with suspected myocardial infarction seen within 6 hours of the onset of symptoms entered a double-blind randomized trial of lidocaine vs placebo. During the 1 hour after administration of the drug the incidence of ventricular fibrillation or sustained ventricular tachycardia among the 204 patients with acute myocardial infarction was low, 1.5%. Lidocaine, given in a 300 mg dose intramuscularly followed by 100 mg intravenously, did not prevent sustained ventricular tachycardia, although there was a significant reduction in the number of patients with warning arrhythmias between 15 and 45 minutes after the administration of lidocaine (p less than 0.05). The average plasma lidocaine level 10 minutes after administration for patients without a myocardial infarction was significantly higher than that for patients with an acute infarction. The mean plasma lidocaine level of patients on beta-blocking agents was no different from that in patients not on beta blocking agents. During the 1-hour study period, the incidence of central nervous system side effects was significantly greater in the lidocaine group, hypotension occurred in 11 patients, nine of whom had received lidocaine, and four patients died from asystole, three of whom had had lidocaine. We cannot advocate the administration of lidocaine prophylactically in the early hours of suspected myocardial infarction.
3895875	13	22	lidocaine	Chemical	D008012
3895875	55	76	myocardial infarction	Disease	D009203
3895875	119	140	myocardial infarction	Disease	D009203
3895875	229	238	lidocaine	Chemical	D008012
3895875	319	343	ventricular fibrillation	Disease	D014693
3895875	357	380	ventricular tachycardia	Disease	D017180
3895875	415	436	myocardial infarction	Disease	D009203
3895875	452	461	Lidocaine	Chemical	D008012
3895875	562	585	ventricular tachycardia	Disease	D017180
3895875	669	680	arrhythmias	Disease	D001145
3895875	735	744	lidocaine	Chemical	D008012
3895875	784	793	lidocaine	Chemical	D008012
3895875	855	876	myocardial infarction	Disease	D009203
3895875	939	949	infarction	Disease	D007238
3895875	967	976	lidocaine	Chemical	D008012
3895875	1205	1214	lidocaine	Chemical	D008012
3895875	1222	1233	hypotension	Disease	D007022
3895875	1285	1294	lidocaine	Chemical	D008012
3895875	1324	1332	asystole	Disease	D006323
3895875	1356	1365	lidocaine	Chemical	D008012
3895875	1408	1417	lidocaine	Chemical	D008012
3895875	1467	1488	myocardial infarction	Disease	D009203
3895875	CID	D008012	D007022

3925479|t|Evidence for a cholinergic role in haloperidol-induced catalepsy.
3925479|a|Experiments in mice tested previous evidence that activation of cholinergic systems promotes catalepsy and that cholinergic mechanisms need to be intact for full expression of neuroleptic-induced catalepsy. Large doses of the cholinomimetic, pilocarpine, could induce catalepsy when peripheral cholinergic receptors were blocked. Low doses of pilocarpine caused a pronounced enhancement of the catalepsy that was induced by the dopaminergic blocker, haloperidol. A muscarinic receptor blocker, atropine, disrupted haloperidol-induced catalepsy. Intracranial injection of an acetylcholine-synthesis inhibitor, hemicholinium, prevented the catalepsy that is usually induced by haloperidol. These findings suggest the hypothesis that the catalepsy that is produced by neuroleptics such as haloperidol is actually mediated by intrinsic central cholinergic systems. Alternatively, activation of central cholinergic systems could promote catalepsy by suppression of dopaminergic systems.
3925479	35	46	haloperidol	Chemical	D006220
3925479	55	64	catalepsy	Disease	D002375
3925479	159	168	catalepsy	Disease	D002375
3925479	242	253	neuroleptic	Chemical	D014150
3925479	262	271	catalepsy	Disease	D002375
3925479	308	319	pilocarpine	Chemical	D010862
3925479	334	343	catalepsy	Disease	D002375
3925479	409	420	pilocarpine	Chemical	D010862
3925479	460	469	catalepsy	Disease	D002375
3925479	516	527	haloperidol	Chemical	D006220
3925479	560	568	atropine	Chemical	D001285
3925479	580	591	haloperidol	Chemical	D006220
3925479	600	609	catalepsy	Disease	D002375
3925479	640	653	acetylcholine	Chemical	D000109
3925479	675	688	hemicholinium	Chemical	D006426
3925479	704	713	catalepsy	Disease	D002375
3925479	741	752	haloperidol	Chemical	D006220
3925479	801	810	catalepsy	Disease	D002375
3925479	831	843	neuroleptics	Chemical	D014150
3925479	852	863	haloperidol	Chemical	D006220
3925479	998	1007	catalepsy	Disease	D002375
3925479	CID	D010862	D002375
3925479	CID	D006220	D002375

3975902|t|Cardiovascular dysfunction and hypersensitivity to sodium pentobarbital induced by chronic barium chloride ingestion.
3975902|a|Barium-supplemented Long-Evans hooded rats were characterized by a persistent hypertension that was evident after 1 month of barium (100 micrograms/ml mineral fortified water) treatment. Analysis of in vivo myocardial excitability, contractility, and metabolic characteristics at 16 months revealed other significant barium-induced disturbances within the cardiovascular system. The most distinctive aspect of the barium effect was a demonstrated hypersensitivity of the cardiovascular system to sodium pentobarbital. Under barbiturate anesthesia, virtually all of the myocardial contractile indices were depressed significantly in barium-exposed rats relative to the corresponding control-fed rats. The lack of a similar response to ketamine and xylazine anesthesia revealed that the cardiovascular actions of sodium pentobarbital in barium-treated rats were linked specifically to this anesthetic, and were not representative of a generalized anesthetic response. Other myocardial pathophysiologic and metabolic changes induced by barium were manifest, irrespective of the anesthetic employed. The contractile element shortening velocity of the cardiac muscle fibers was significantly slower in both groups of barium-treated rats relative to the control groups, irrespective of the anesthetic regimen. Similarly, significant disturbances in myocardial energy metabolism were detected in the barium-exposed rats which were consistent with the reduced contractile element shortening velocity. In addition, the excitability of the cardiac conduction system was depressed preferentially in the atrioventricular nodal region of hearts from barium-exposed rats. Overall, the altered cardiac contractility and excitability characteristics, the myocardial metabolic disturbances, and the hypersensitivity of the cardiovascular system to sodium pentobarbital suggest the existence of a heretofore undescribed cardiomyopathic disorder induced by chronic barium exposure. These experimental findings represent the first indication that life-long barium ingestion may have significant adverse effects on the mammalian cardiovascular system.
3975902	0	26	Cardiovascular dysfunction	Disease	D002318
3975902	31	47	hypersensitivity	Disease	D004342
3975902	51	71	sodium pentobarbital	Chemical	D010424
3975902	91	106	barium chloride	Chemical	C024986
3975902	118	124	Barium	Chemical	D001464
3975902	196	208	hypertension	Disease	D006973
3975902	243	249	barium	Chemical	D001464
3975902	435	441	barium	Chemical	D001464
3975902	450	495	disturbances within the cardiovascular system	Disease	D002318
3975902	532	538	barium	Chemical	D001464
3975902	565	581	hypersensitivity	Disease	D004342
3975902	614	634	sodium pentobarbital	Chemical	D010424
3975902	642	653	barbiturate	Chemical	C032232
3975902	750	756	barium	Chemical	D001464
3975902	852	860	ketamine	Chemical	D007649
3975902	865	873	xylazine	Chemical	D014991
3975902	929	949	sodium pentobarbital	Chemical	D010424
3975902	953	959	barium	Chemical	D001464
3975902	1151	1157	barium	Chemical	D001464
3975902	1330	1336	barium	Chemical	D001464
3975902	1511	1517	barium	Chemical	D001464
3975902	1755	1761	barium	Chemical	D001464
3975902	1868	1890	metabolic disturbances	Disease	D008659
3975902	1900	1916	hypersensitivity	Disease	D004342
3975902	1949	1969	sodium pentobarbital	Chemical	D010424
3975902	2020	2044	cardiomyopathic disorder	Disease	D009202
3975902	2064	2070	barium	Chemical	D001464
3975902	2155	2161	barium	Chemical	D001464
3975902	CID	C024986	D009202
3975902	CID	C024986	D006973

3987172|t|Propranolol antagonism of phenylpropanolamine-induced hypertension.
3987172|a|Phenylpropanolamine (PPA) overdose can cause severe hypertension, intracerebral hemorrhage, and death. We studied the efficacy and safety of propranolol in the treatment of PPA-induced hypertension. Subjects received propranolol either by mouth for 48 hours before PPA or as a rapid intravenous infusion after PPA. PPA, 75 mg alone, increased blood pressure (31 +/- 14 mm Hg systolic, 20 +/- 5 mm Hg diastolic), and propranolol pretreatment antagonized this increase (12 +/- 10 mm Hg systolic, 10 +/- 7 mm Hg diastolic). Intravenous propranolol after PPA also decreased blood pressure. Left ventricular function (assessed by echocardiography) showed that PPA increased the stroke volume 30% (from 62.5 +/- 20.9 to 80.8 +/- 22.4 ml), the ejection fraction 9% (from 64% +/- 10% to 70% +/- 7%), and cardiac output 14% (from 3.6 +/- 0.6 to 4.1 +/- 1.0 L/min). Intravenous propranolol reversed these effects. Systemic vascular resistance was increased by PPA 28% (from 1710 +/- 200 to 2190 +/- 700 dyne X sec/cm5) and was further increased by propranolol 22% (to 2660 +/- 1200 dyne X sec/cm5). We conclude that PPA increases blood pressure by increasing systemic vascular resistance and cardiac output, and that propranolol antagonizes this increase by reversing the effect of PPA on cardiac output. That propranolol antagonizes the pressor effect of PPA is in contrast to the interaction in which propranolol enhances the pressor effect of norepinephrine. This is probably because PPA has less beta 2 activity than does norepinephrine.
3987172	0	11	Propranolol	Chemical	D011433
3987172	26	45	phenylpropanolamine	Chemical	D010665
3987172	54	66	hypertension	Disease	D006973
3987172	68	87	Phenylpropanolamine	Chemical	D010665
3987172	89	92	PPA	Chemical	D010665
3987172	94	102	overdose	Disease	D062787
3987172	120	132	hypertension	Disease	D006973
3987172	134	158	intracerebral hemorrhage	Disease	D002543
3987172	209	220	propranolol	Chemical	D011433
3987172	241	244	PPA	Chemical	D010665
3987172	253	265	hypertension	Disease	D006973
3987172	285	296	propranolol	Chemical	D011433
3987172	333	336	PPA	Chemical	D010665
3987172	378	381	PPA	Chemical	D010665
3987172	383	386	PPA	Chemical	D010665
3987172	484	495	propranolol	Chemical	D011433
3987172	601	612	propranolol	Chemical	D011433
3987172	619	622	PPA	Chemical	D010665
3987172	723	726	PPA	Chemical	D010665
3987172	741	747	stroke	Disease	D020521
3987172	936	947	propranolol	Chemical	D011433
3987172	1018	1021	PPA	Chemical	D010665
3987172	1106	1117	propranolol	Chemical	D011433
3987172	1174	1177	PPA	Chemical	D010665
3987172	1275	1286	propranolol	Chemical	D011433
3987172	1340	1343	PPA	Chemical	D010665
3987172	1368	1379	propranolol	Chemical	D011433
3987172	1414	1417	PPA	Chemical	D010665
3987172	1461	1472	propranolol	Chemical	D011433
3987172	1504	1518	norepinephrine	Chemical	D009638
3987172	1545	1548	PPA	Chemical	D010665
3987172	1584	1598	norepinephrine	Chemical	D009638
3987172	CID	D010665	D006973

3990093|t|Mesangial function and glomerular sclerosis in rats with aminonucleoside nephrosis.
3990093|a|The possible relationship between mesangial dysfunction and development of glomerular sclerosis was studied in the puromycin aminonucleoside (PAN) model. Five male Wistar rats received repeated subcutaneous PAN injections; five controls received saline only. After 4 weeks the PAN rats were severely proteinuric (190 +/- 80 mg/24 hr), and all rats were given colloidal carbon (CC) intravenously. At 5 months glomerular sclerosis was found in 7.6 +/- 3.4% of the glomeruli of PAN rats; glomeruli of the controls were normal. Glomeruli of PAN rats contained significantly more CC than glomeruli of controls. Glomeruli with sclerosis contained significantly more CC than non-sclerotic glomeruli in the same kidneys. CC was preferentially localized within the sclerotic areas of the affected glomeruli. Since mesangial CC clearance from the mesangium did not change during chronic PAN treatment, we conclude that this preferential CC localization within the lesions is caused by an increased CC uptake shortly after injection in apparent vulnerable areas where sclerosis will develop subsequently. Cluster analysis showed a random distribution of lesions in the PAN glomeruli in concordance with the random localization of mesangial areas with dysfunction in this model. Similar to the remnant kidney model in PAN nephrosis the development of glomerular sclerosis may be related to "mesangial overloading."
3990093	23	43	glomerular sclerosis	Disease	D007674
3990093	57	72	aminonucleoside	Chemical	D011692
3990093	73	82	nephrosis	Disease	D009401
3990093	118	139	mesangial dysfunction	Disease	D007674
3990093	159	179	glomerular sclerosis	Disease	D007674
3990093	199	224	puromycin aminonucleoside	Chemical	D011692
3990093	226	229	PAN	Chemical	D011692
3990093	291	294	PAN	Chemical	D011692
3990093	361	364	PAN	Chemical	D011692
3990093	384	395	proteinuric	Disease	D011507
3990093	453	459	carbon	Chemical	D002244
3990093	492	512	glomerular sclerosis	Disease	D007674
3990093	559	562	PAN	Chemical	D011692
3990093	621	624	PAN	Chemical	D011692
3990093	705	714	sclerosis	Disease	D012598
3990093	961	964	PAN	Chemical	D011692
3990093	1141	1150	sclerosis	Disease	D012598
3990093	1242	1245	PAN	Chemical	D011692
3990093	1390	1393	PAN	Chemical	D011692
3990093	1394	1403	nephrosis	Disease	D009401
3990093	1423	1443	glomerular sclerosis	Disease	D007674
3990093	CID	D011692	D011507

4010471|t|Relationship between nicotine-induced seizures and hippocampal nicotinic receptors.
4010471|a|A controversy has existed for several years concerning the physiological relevance of the nicotinic receptor measured by alpha-bungarotoxin binding. Using mice derived from a classical F2 and backcross genetic design, a relationship between nicotine-induced seizures and alpha-bungarotoxin nicotinic receptor concentration was found. Mice sensitive to the convulsant effects of nicotine had greater alpha-bungarotoxin binding in the hippocampus than seizure insensitive mice. The binding sites from seizure sensitive and resistant mice were equally affected by treatment with dithiothreitol, trypsin or heat. Thus it appears that the difference between seizure sensitive and insensitive animals may be due to a difference in hippocampal nicotinic receptor concentration as measured with alpha-bungarotoxin binding.
4010471	21	29	nicotine	Chemical	D009538
4010471	38	46	seizures	Disease	D012640
4010471	325	333	nicotine	Chemical	D009538
4010471	342	350	seizures	Disease	D012640
4010471	462	470	nicotine	Chemical	D009538
4010471	534	541	seizure	Disease	D012640
4010471	583	590	seizure	Disease	D012640
4010471	660	674	dithiothreitol	Chemical	D004229
4010471	737	744	seizure	Disease	D012640
4010471	CID	D009538	D012640

4082192|t|The role of p-aminophenol in acetaminophen-induced nephrotoxicity: effect of bis(p-nitrophenyl) phosphate on acetaminophen and p-aminophenol nephrotoxicity and metabolism in Fischer 344 rats.
4082192|a|Acetaminophen (APAP) produces proximal tubular necrosis in Fischer 344 (F344) rats. Recently, p-aminophenol (PAP), a known potent nephrotoxicant, was identified as a metabolite of APAP in F344 rats. The purpose of this study was to determine if PAP formation is a requisite step in APAP-induced nephrotoxicity. Therefore, the effect of bis(p-nitrophenyl) phosphate (BNPP), an acylamidase inhibitor, on APAP and PAP nephrotoxicity and metabolism was determined. BNPP (1 to 8 mM) reduced APAP deacetylation and covalent binding in F344 renal cortical homogenates in a concentration-dependent manner. Pretreatment of animals with BNPP prior to APAP or PAP administration resulted in marked reduction of APAP (900 mg/kg) nephrotoxicity but not PAP nephrotoxicity. This result was not due to altered disposition of either APAP or acetylated metabolites in plasma or renal cortical and hepatic tissue. Rather, BNPP pretreatment reduced the fraction of APAP excreted as PAP by 64 and 75% after APAP doses of 750 and 900 mg/kg. BNPP did not alter the excretion of APAP or any of its non-deacetylated metabolites nor did BNPP alter excretion of PAP or its metabolites after PAP doses of 150 and 300 mg/kg. Therefore, the BNPP-induced reduction in APAP-induced nephrotoxicity appears to be due to inhibition of APAP deacetylation. It is concluded that PAP formation, in vivo, accounts, at least in part, for APAP-induced renal tubular necrosis.
4082192	12	25	p-aminophenol	Chemical	C026729
4082192	29	42	acetaminophen	Chemical	D000082
4082192	51	65	nephrotoxicity	Disease	D007674
4082192	77	105	bis(p-nitrophenyl) phosphate	Chemical	C002887
4082192	109	122	acetaminophen	Chemical	D000082
4082192	127	140	p-aminophenol	Chemical	C026729
4082192	141	155	nephrotoxicity	Disease	D007674
4082192	192	205	Acetaminophen	Chemical	D000082
4082192	207	211	APAP	Chemical	D000082
4082192	231	247	tubular necrosis	Disease	D007683
4082192	286	299	p-aminophenol	Chemical	C026729
4082192	301	304	PAP	Chemical	C026729
4082192	372	376	APAP	Chemical	D000082
4082192	437	440	PAP	Chemical	C026729
4082192	474	478	APAP	Chemical	D000082
4082192	487	501	nephrotoxicity	Disease	D007674
4082192	528	556	bis(p-nitrophenyl) phosphate	Chemical	C002887
4082192	558	562	BNPP	Chemical	C002887
4082192	594	598	APAP	Chemical	D000082
4082192	603	606	PAP	Chemical	C026729
4082192	607	621	nephrotoxicity	Disease	D007674
4082192	653	657	BNPP	Chemical	C002887
4082192	678	682	APAP	Chemical	D000082
4082192	819	823	BNPP	Chemical	C002887
4082192	833	837	APAP	Chemical	D000082
4082192	841	844	PAP	Chemical	C026729
4082192	892	896	APAP	Chemical	D000082
4082192	909	923	nephrotoxicity	Disease	D007674
4082192	932	935	PAP	Chemical	C026729
4082192	936	950	nephrotoxicity	Disease	D007674
4082192	1009	1013	APAP	Chemical	D000082
4082192	1096	1100	BNPP	Chemical	C002887
4082192	1138	1142	APAP	Chemical	D000082
4082192	1155	1158	PAP	Chemical	C026729
4082192	1179	1183	APAP	Chemical	D000082
4082192	1212	1216	BNPP	Chemical	C002887
4082192	1248	1252	APAP	Chemical	D000082
4082192	1304	1308	BNPP	Chemical	C002887
4082192	1328	1331	PAP	Chemical	C026729
4082192	1357	1360	PAP	Chemical	C026729
4082192	1404	1408	BNPP	Chemical	C002887
4082192	1430	1434	APAP	Chemical	D000082
4082192	1443	1457	nephrotoxicity	Disease	D007674
4082192	1493	1497	APAP	Chemical	D000082
4082192	1534	1537	PAP	Chemical	C026729
4082192	1590	1594	APAP	Chemical	D000082
4082192	1603	1625	renal tubular necrosis	Disease	D007683
4082192	CID	C026729	D007683
4082192	CID	D000082	D007683

4082466|t|Morphine-induced seizures in newborn infants.
4082466|a|Two neonates suffered from generalized seizures during the course of intravenous morphine sulfate for post-operative analgesia. They received morphine in doses of 32 micrograms/kg/hr and 40 micrograms/kg/hr larger than a group of 10 neonates who received 6-24 micrograms/kg/hr and had no seizures. Plasma concentrations of morphine in these neonates was excessive (60 and 90 mg/ml). Other known reasons for seizures were ruled out and the convulsions stopped a few hours after cessation of morphine and did not reoccur in the subsequent 8 months. It is suggested that post-operative intravenous morphine should not exceed 20 micrograms/kg/ml in neonates.
4082466	0	8	Morphine	Chemical	D009020
4082466	17	25	seizures	Disease	D012640
4082466	85	93	seizures	Disease	D012640
4082466	127	143	morphine sulfate	Chemical	D009020
4082466	188	196	morphine	Chemical	D009020
4082466	334	342	seizures	Disease	D012640
4082466	369	377	morphine	Chemical	D009020
4082466	453	461	seizures	Disease	D012640
4082466	485	496	convulsions	Disease	D012640
4082466	536	544	morphine	Chemical	D009020
4082466	641	649	morphine	Chemical	D009020
4082466	CID	D009020	D012640

4631913|t|Effect of vincristine sulfate on Pseudomonas infections in monkeys.
4631913|a|In rhesus monkeys, intravenous challenge with 0.6 x 10(10) to 2.2 x 10(10)Pseudomonas aeruginosa organisms caused acute illness of 4 to 5 days' duration with spontaneous recovery in 13 of 15 monkeys; blood cultures became negative 3 to 17 days after challenge. Leukocytosis was observed in all monkeys. Intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate was followed by leukopenia in 4 to 5 days. Intravenous inoculation of 4.2 x 10(10) to 7.8 x 10(10) pyocin type 6 Pseudomonas organisms in monkeys given vincristine sulfate 4 days previously resulted in fatal infection in 11 of 14 monkeys, whereas none of four receiving Pseudomonas alone died. These studies suggest that an antimetabolite-induced leukopenia predisposes to severe Pseudomonas sepsis and that such monkeys may serve as a biological model for study of comparative efficacy of antimicrobial agents.
4631913	10	29	vincristine sulfate	Chemical	D014750
4631913	33	55	Pseudomonas infections	Disease	D011552
4631913	329	341	Leukocytosis	Disease	D007964
4631913	432	451	vincristine sulfate	Chemical	D014750
4631913	468	478	leukopenia	Disease	D007970
4631913	604	623	vincristine sulfate	Chemical	D014750
4631913	660	669	infection	Disease	D007239
4631913	799	809	leukopenia	Disease	D007970
4631913	844	850	sepsis	Disease	D018805
4631913	CID	D014750	D018805
4631913	CID	D014750	D007970
4631913	CID	D014750	D011552

6106951|t|Central excitatory actions of flurazepam.
6106951|a|Toxic actions of flurazepam (FZP) were studied in cats, mice and rats. High doses caused an apparent central excitation, most clearly seen as clonic convulsions, superimposed on general depression. Following a lethal dose, death was always associated with convulsions. Comparing the relative sensitivity to central depression and excitation revealed that rats were least likely to have convulsions at doses that did not first cause loss of consciousness, while cats most clearly showed marked central excitatory actions. Signs of FZP toxocity in cats included excessive salivation, extreme apprehensive behavior, retching, muscle tremors and convulsions. An interaction between FZP and pentylenetetrazol (PTZ) was shown by pretreating mice with FZP before PTZ challenge. As a function of dose, FZP first protected against convulsions and death. At higher doses, however, convulsions again emerged. These doses of FZP were lower than those that would alone cause convulsions. These results may be relevant to the use of FZP in clinical situations in which there is increased neural excitability, such as epilepsy or sedative-hypnotic drug withdrawal.
6106951	30	40	flurazepam	Chemical	D005479
6106951	59	69	flurazepam	Chemical	D005479
6106951	71	74	FZP	Chemical	D005479
6106951	191	202	convulsions	Disease	D012640
6106951	228	238	depression	Disease	D003866
6106951	298	309	convulsions	Disease	D012640
6106951	357	367	depression	Disease	D003866
6106951	428	439	convulsions	Disease	D012640
6106951	474	495	loss of consciousness	Disease	D014474
6106951	572	575	FZP	Chemical	D005479
6106951	576	584	toxocity	Disease	D064420
6106951	612	622	salivation	Disease	D012798
6106951	665	679	muscle tremors	Disease	D014202
6106951	684	695	convulsions	Disease	D012640
6106951	720	723	FZP	Chemical	D005479
6106951	728	745	pentylenetetrazol	Chemical	D010433
6106951	747	750	PTZ	Chemical	D010433
6106951	787	790	FZP	Chemical	D005479
6106951	798	801	PTZ	Chemical	D010433
6106951	836	839	FZP	Chemical	D005479
6106951	864	875	convulsions	Disease	D012640
6106951	913	924	convulsions	Disease	D012640
6106951	955	958	FZP	Chemical	D005479
6106951	1004	1015	convulsions	Disease	D012640
6106951	1061	1064	FZP	Chemical	D005479
6106951	1145	1153	epilepsy	Disease	D004827
6106951	CID	D005479	D012640
6106951	CID	D010433	D012640

6299641|t|Evidence for cardiac beta 2-adrenoceptors in man.
6299641|a|We compared the effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective), and placebo on both exercise- and isoproterenol-induced tachycardia in two experiments involving nine normal subjects. Maximal exercise heart rate was reduced from 187 +/- 4(SEM) after placebo to 146 +/- 7 bpm after atenolol and 138 +/- 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0.04 mg/kg IV). Isoproterenol sensitivity was determined as the intravenous dose that increased heart rate by 25 bpm (CD25) and this was increased from 1.8 +/- 0.3 micrograms after placebo to 38.9 +/- 8.3 micrograms after propranolol and 8.3 +/- 1.7 micrograms after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2.3 +/- 0.3 micrograms) and atenolol (7.7 +/- 1.3 micrograms); it was reduced after propranolol (24.8 +/- 5.0 micrograms), but remained different from atenolol. This change with propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11.7 +/- 2.1 and 10.1 +/- 2.5 ml/ng). These data are consistent with the hypothesis that exercise-induced tachycardia results largely from beta 1-receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both beta 1- and beta 2-receptors so that after cardioselective blockade there remains a beta 2-component that can be blocked with a nonselective drug. While there appear to be beta 2-receptors in the human heart, their physiologic or pathologic roles remain to be defined.
6299641	99	107	atenolol	Chemical	D001262
6299641	133	144	propranolol	Chemical	D011433
6299641	195	208	isoproterenol	Chemical	D007545
6299641	217	228	tachycardia	Disease	D013610
6299641	377	385	atenolol	Chemical	D001262
6299641	410	421	propranolol	Chemical	D011433
6299641	487	500	isoproterenol	Chemical	D007545
6299641	501	512	tachycardia	Disease	D013610
6299641	546	554	atropine	Chemical	D001285
6299641	572	585	Isoproterenol	Chemical	D007545
6299641	778	789	propranolol	Chemical	D011433
6299641	823	831	atenolol	Chemical	D001262
6299641	897	905	atropine	Chemical	D001285
6299641	972	980	atenolol	Chemical	D001262
6299641	1028	1039	propranolol	Chemical	D011433
6299641	1095	1103	atenolol	Chemical	D001262
6299641	1122	1133	propranolol	Chemical	D011433
6299641	1203	1211	atropine	Chemical	D001285
6299641	1319	1330	tachycardia	Disease	D013610
6299641	1451	1464	isoproterenol	Chemical	D007545
6299641	CID	D007545	D013610

6305660|t|Hormones and risk of breast cancer.
6305660|a|This paper reports the results of a study of 50 menopausal women receiving hormonal replacement therapy. The majority (29) had surgical menopause; their mean age was 45.7 years. It was hypothesized that progestins could equilibrate the effects of the estrogenic stimulation on the mammary and endometrial target tissues of women on hormonal replacement therapy. The treatment schedule consisted of conjugated estrogens (Premarin) 1.25 mg/day for 21 days and Medroxyprogesterone acetate 10 mg/day for 10 days in each month. The mean treatment period was 18 months. During the follow-up period, attention was paid to breast modifications as evidenced by symptomatology, physical examination, and plate thermography. Mastodynia was reported by 21 patients, and physical examination revealed a light increase in breast firmness in 12 women and a moderate increase in breast nodularity in 2 women. Themography confirmed the existence of an excessive breast stimulation in 1 women who complained of moderate mastodynia and in 5 of the 7 women who complained of severe mastodynia. Normalization was obtained by halving the estrogen dose. These results suggest that hormonal replacement therapy can be safely prescribed if the following criteria are satisfied: 1) preliminary evaluation of patients from a clinical, metabolic, cytologic, and mammographic perspective; 2) cyclic treatment schedule, with a progestative phase of 10 days; and 3) periodic complete follow-up, with accurate thermographic evaluation of the breast target tissues.
6305660	21	34	breast cancer	Disease	D001943
6305660	239	249	progestins	Chemical	D011372
6305660	434	454	conjugated estrogens	Chemical	D004966
6305660	456	464	Premarin	Chemical	D004966
6305660	494	521	Medroxyprogesterone acetate	Chemical	D017258
6305660	750	760	Mastodynia	Disease	D059373
6305660	1038	1048	mastodynia	Disease	D059373
6305660	1098	1108	mastodynia	Disease	D059373
6305660	1152	1160	estrogen	Chemical	D004967
6305660	CID	D004966	D059373
6305660	CID	D017258	D059373

6310832|t|Early infections in kidney, heart, and liver transplant recipients on cyclosporine.
6310832|a|Eighty-one renal, seventeen heart, and twenty-four liver transplant patients were followed for infection. Seventeen renal patients received azathioprine (Aza) and prednisone as part of a randomized trial of immunosuppression with 21 cyclosporine-and-prednisone-treated renal transplant patients. All others received cyclosporine and prednisone. The randomized Aza patients had more overall infections (P less than 0.05) and more nonviral infections (P less than 0.02) than the randomized cyclosporine patients. Heart and liver patients had more infections than cyclosporine renal patients but fewer infections than the Aza renal patients. There were no infectious deaths in renal transplant patients on cyclosporine or Aza, but infection played a major role in 3 out of 6 cardiac transplant deaths and in 8 out of 9 liver transplant deaths. Renal patients on cyclosporine had the fewest bacteremias. Analysis of site of infection showed a preponderance of abdominal infections in liver patients, intrathoracic infections in heart patients, and urinary tract infections in renal patients. Pulmonary infections were less common in cyclosporine-treated renal patients than in Aza-treated patients (P less than 0.05). Aza patients had significantly more staphylococcal infections than all other transplant groups (P less than 0.005), and systemic fungal infections occurred only in the liver transplant group. Cytomegalovirus (CMV) shedding or serological rises in antibody titer, or both occurred in 78% of cyclosporine patients and 76% of Aza patients. Of the cyclosporine patients, 15% had symptoms related to CMV infection. Serological evidence for Epstein Barr Virus infection was found in 20% of 65 cyclosporine patients studied. Three had associated symptoms, and one developed a lymphoma.
6310832	6	16	infections	Disease	D007239
6310832	70	82	cyclosporine	Chemical	D016572
6310832	179	188	infection	Disease	D007239
6310832	224	236	azathioprine	Chemical	D001379
6310832	238	241	Aza	Chemical	D001379
6310832	247	257	prednisone	Chemical	D011241
6310832	317	329	cyclosporine	Chemical	D016572
6310832	334	344	prednisone	Chemical	D011241
6310832	400	412	cyclosporine	Chemical	D016572
6310832	417	427	prednisone	Chemical	D011241
6310832	444	447	Aza	Chemical	D001379
6310832	474	484	infections	Disease	D007239
6310832	522	532	infections	Disease	D007239
6310832	572	584	cyclosporine	Chemical	D016572
6310832	629	639	infections	Disease	D007239
6310832	645	657	cyclosporine	Chemical	D016572
6310832	683	693	infections	Disease	D007239
6310832	703	706	Aza	Chemical	D001379
6310832	787	799	cyclosporine	Chemical	D016572
6310832	803	806	Aza	Chemical	D001379
6310832	812	821	infection	Disease	D007239
6310832	943	955	cyclosporine	Chemical	D016572
6310832	971	982	bacteremias	Disease	D016470
6310832	1004	1013	infection	Disease	D007239
6310832	1040	1060	abdominal infections	Disease	D059413
6310832	1094	1104	infections	Disease	D007239
6310832	1128	1152	urinary tract infections	Disease	D014552
6310832	1182	1192	infections	Disease	D007239
6310832	1213	1225	cyclosporine	Chemical	D016572
6310832	1257	1260	Aza	Chemical	D001379
6310832	1298	1301	Aza	Chemical	D001379
6310832	1334	1359	staphylococcal infections	Disease	D013203
6310832	1427	1444	fungal infections	Disease	D009181
6310832	1588	1600	cyclosporine	Chemical	D016572
6310832	1621	1624	Aza	Chemical	D001379
6310832	1642	1654	cyclosporine	Chemical	D016572
6310832	1693	1706	CMV infection	Disease	D003586
6310832	1733	1761	Epstein Barr Virus infection	Disease	D020031
6310832	1785	1797	cyclosporine	Chemical	D016572
6310832	1867	1875	lymphoma	Disease	D008223
6310832	CID	D016572	D007239
6310832	CID	D001379	D007239

6316193|t|Structure-activity and dose-effect relationships of the antagonism of picrotoxin-induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice.
6316193|a|Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N- and C-terminal fragments revealed that the C-terminal tetrapeptide (CCK-5-8) was the active centre of the CCK octapeptide molecule. The analogues CCK-8-SE and CCK-8-NS (dose range 0.2-6.4 mumol/kg) and caerulein dose range 0.1-0.8 mumol/kg) showed bell-shaped dose-effect curves, with the greatest maximum inhibition for CCK-8-NS. The peptide CCK-5-8 had weak anticonvulsant activity in comparison to the octapeptides, 3.2 mumol/kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin-induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK-5-8 demonstrated that the effectiveness of the beta-alanyl derivatives of CCK-5-8 were enhanced and that they were equipotent with CCK-8-SE. Of the CCK-2-8 analogues, Ser(SO3H)7-Ac-CCK-2-8-SE and Thr(SO3H)7-Ac-CCK-2-8-SE and Hyp(SO3H)-Ac-CCK-2-8-SE were slightly more active than CCK-8-SE.
6316193	70	80	picrotoxin	Chemical	D010852
6316193	89	97	seizures	Disease	D012640
6316193	101	116	cholecystokinin	Chemical	D002766
6316193	145	160	cholecystokinin	Chemical	D002766
6316193	204	231	cholecystokinin octapeptide	Chemical	D012844
6316193	248	253	CCK-8	Chemical	D012844
6316193	275	302	cholecystokinin octapeptide	Chemical	D012844
6316193	304	309	CCK-8	Chemical	D012844
6316193	338	346	seizures	Disease	D012640
6316193	358	368	picrotoxin	Chemical	D010852
6316193	544	549	CCK-8	Chemical	D012844
6316193	557	562	CCK-8	Chemical	D012844
6316193	600	609	caerulein	Chemical	D002108
6316193	719	724	CCK-8	Chemical	D012844
6316193	870	878	diazepam	Chemical	D003975
6316193	898	908	picrotoxin	Chemical	D010852
6316193	917	925	seizures	Disease	D012640
6316193	1005	1013	diazepam	Chemical	D003975
6316193	1196	1201	CCK-8	Chemical	D012844
6316193	1345	1350	CCK-8	Chemical	D012844
6316193	CID	D010852	D012640

6321816|t|Vasopressin as a possible contributor to hypertension.
6321816|a|The role of vasopressin as a pressor agent to the hypertensive process was examined. Vasopressin plays a major role in the pathogenesis of DOCA-salt hypertension, since the elevation of blood pressure was not substantial in the rats with lithium-treated diabetes insipidus after DOCA-salt treatment. Administration of DDAVP which has antidiuretic action but minimal vasopressor effect failed to increase blood pressure to the levels observed after administration of AVP. Furthermore, the pressor action of vasopressin appears to be important in the development of this model of hypertension, since the enhanced pressor responsiveness to the hormone was observed in the initial stage of hypertension. Increased secretion of vasopressin from neurohypophysis also promotes the function of the hormone as a pathogenetic factor in hypertension. An unproportional release of vasopressin compared to plasma osmolality may be induced by the absence of an adjusting control of angiotensin II forming and receptor binding capacity for sodium balance in the brain. However, the role of vasopressin remains to be determined in human essential hypertension.
6321816	0	11	Vasopressin	Chemical	D014667
6321816	41	53	hypertension	Disease	D006973
6321816	67	78	vasopressin	Chemical	D014667
6321816	105	117	hypertensive	Disease	D006973
6321816	140	151	Vasopressin	Chemical	D014667
6321816	194	198	DOCA	Chemical	D003900
6321816	204	216	hypertension	Disease	D006973
6321816	293	300	lithium	Chemical	D008094
6321816	309	327	diabetes insipidus	Disease	D003919
6321816	334	338	DOCA	Chemical	D003900
6321816	373	378	DDAVP	Chemical	D003894
6321816	561	572	vasopressin	Chemical	D014667
6321816	633	645	hypertension	Disease	D006973
6321816	741	753	hypertension	Disease	D006973
6321816	778	789	vasopressin	Chemical	D014667
6321816	881	893	hypertension	Disease	D006973
6321816	924	935	vasopressin	Chemical	D014667
6321816	1023	1034	angiotensin	Chemical	D000809
6321816	1080	1086	sodium	Chemical	D012964
6321816	1130	1141	vasopressin	Chemical	D014667
6321816	1186	1198	hypertension	Disease	D006973
6321816	CID	D003900	D006973
6321816	CID	D008094	D003919

6453500|t|Toxic hepatitis induced by disulfiram in a non-alcoholic.
6453500|a|A reversible toxic liver damage was observed in a non-alcoholic woman treated with disulfiram. The causative relationship was proven by challenge.
6453500	0	15	Toxic hepatitis	Disease	D056486
6453500	27	37	disulfiram	Chemical	D004221
6453500	71	89	toxic liver damage	Disease	D056486
6453500	141	151	disulfiram	Chemical	D004221
6453500	CID	D004221	D056486

6517710|t|Atrial thrombosis involving the heart of F-344 rats ingesting quinacrine hydrochloride.
6517710|a|Quinacrine hydrochloride is toxic for the heart of F-344 rats. Rats treated with 500 ppm quinacrine hydrochloride in the diet all developed a high incidence of left atrial thrombosis. The lesion was associated with cardiac hypertrophy and dilatation and focal myocardial degeneration. Rats died from cardiac hypertrophy with severe acute and chronic congestion of the lungs, liver, and other organs. Seventy percent of rats given 250 ppm quinacrine hydrochloride and 1,000 ppm sodium nitrite simultaneously in the diet had thrombosis of the atria of the heart, while untreated control rats in this laboratory did not have atrial thrombosis. Sodium nitrite in combination with quinacrine hydrochloride appeared to have no additional effect.
6517710	0	17	Atrial thrombosis	Disease	D003328
6517710	62	86	quinacrine hydrochloride	Chemical	D011796
6517710	88	112	Quinacrine hydrochloride	Chemical	D011796
6517710	177	201	quinacrine hydrochloride	Chemical	D011796
6517710	253	270	atrial thrombosis	Disease	D003328
6517710	303	322	cardiac hypertrophy	Disease	D006332
6517710	348	371	myocardial degeneration	Disease	D009202
6517710	388	407	cardiac hypertrophy	Disease	D006332
6517710	526	550	quinacrine hydrochloride	Chemical	D011796
6517710	565	579	sodium nitrite	Chemical	D012977
6517710	611	621	thrombosis	Disease	D013927
6517710	710	727	atrial thrombosis	Disease	D003328
6517710	729	743	Sodium nitrite	Chemical	D012977
6517710	764	788	quinacrine hydrochloride	Chemical	D011796
6517710	CID	D011796	D006332
6517710	CID	D011796	D003328

6529939|t|Alternating sinus rhythm and intermittent sinoatrial block induced by propranolol.
6529939|a|Alternating sinus rhythm and intermittent sinoatrial (S-A) block was observed in a 57-year-old woman, under treatment for angina with 80 mg propranolol daily. The electrocardiogram showed alternation of long and short P-P intervals and occasional pauses. These pauses were always preceded by the short P-P intervals and were usually followed by one or two P-P intervals of 0.92-0.95 s representing the basic sinus cycle. Following these basic sinus cycles, alternating rhythm started with the longer P-P interval. The long P-P intervals ranged between 1.04-1.12 s and the short P-P intervals between 0.80-0.84 s, respectively. The duration of the pauses were equal or almost equal to one short plus one long P-P interval or to twice the basic sinus cycle. In one recording a short period of regular sinus rhythm with intermittent 2/1 S-A block was observed. This short period of sinus rhythm was interrupted by sudden prolongation of the P-P interval starting the alternative rhythm. There were small changes in the shape of the P waves and P-R intervals. S-A conduction through two pathways, the first with 2/1 block the second having 0.12-0.14 s longer conduction time and with occasional 2/1 block was proposed for the explanation of the alternating P-P interval and other electrocardiographic features seen. Atropine 1 mg given intravenously resulted in shortening of all P-P intervals without changing the rhythm. The abnormal rhythm disappeared with the withdrawal of propranolol and when the drug was restarted a 2/1 S-A block was seen. This was accepted as evidence for propranolol being the cause of this conduction disorder.
6529939	0	24	Alternating sinus rhythm	Disease	D001146
6529939	42	58	sinoatrial block	Disease	D012848
6529939	70	81	propranolol	Chemical	D011433
6529939	83	107	Alternating sinus rhythm	Disease	D001146
6529939	125	147	sinoatrial (S-A) block	Disease	D012848
6529939	205	211	angina	Disease	D000787
6529939	223	234	propranolol	Chemical	D011433
6529939	540	558	alternating rhythm	Disease	D001146
6529939	917	926	S-A block	Disease	D012848
6529939	1395	1403	Atropine	Chemical	D001285
6529939	1557	1568	propranolol	Chemical	D011433
6529939	1607	1616	S-A block	Disease	D012848
6529939	1661	1672	propranolol	Chemical	D011433
6529939	1697	1716	conduction disorder	Disease	D019955
6529939	CID	D011433	D012848
6529939	CID	D011433	D001146

6585590|t|Antitumor effect, cardiotoxicity, and nephrotoxicity of doxorubicin in the IgM solid immunocytoma-bearing LOU/M/WSL rat.
6585590|a|Antitumor activity, cardiotoxicity, and nephrotoxicity induced by doxorubicin were studied in LOU/M/WSL inbred rats each bearing a transplantable solid IgM immunocytoma. Animals with a tumor (diameter, 15.8 +/- 3.3 mm) were treated with iv injections of doxorubicin on 5 consecutive days, followed by 1 weekly injection for 7 weeks (dose range, 0.015-4.0 mg/kg body wt). Tumor regression was observed with 0.5 mg doxorubicin/kg. Complete disappearance of the tumor was induced with 1.0 mg doxorubicin/kg. Histologic evidence of cardiotoxicity scored as grade III was only observed at a dose of 1.0 mg doxorubicin/kg. Light microscopic evidence of renal damage was seen above a dose of 0.5 mg doxorubicin/kg, which resulted in albuminuria and very low serum albumin levels. In the group that received 1.0 mg doxorubicin/kg, the serum albumin level decreased from 33.6 +/- 4.1 to 1.5 +/- 0.5 g/liter. Ascites and hydrothorax were observed simultaneously. The same experiments were performed with non-tumor-bearing rats, in which no major differences were observed. In conclusion, antitumor activity, cardiotoxicity, and nephrotoxicity were studied simultaneously in the same LOU/M/WSL rat. Albuminuria due to renal damage led to extremely low serum albumin levels, so ascites and hydrothorax were not necessarily a consequence of the observed cardiomyopathy.
6585590	18	32	cardiotoxicity	Disease	D066126
6585590	38	52	nephrotoxicity	Disease	D007674
6585590	56	67	doxorubicin	Chemical	D004317
6585590	85	97	immunocytoma	Disease	-1
6585590	141	155	cardiotoxicity	Disease	D066126
6585590	161	175	nephrotoxicity	Disease	D007674
6585590	187	198	doxorubicin	Chemical	D004317
6585590	277	289	immunocytoma	Disease	-1
6585590	306	311	tumor	Disease	D009369
6585590	375	386	doxorubicin	Chemical	D004317
6585590	492	497	Tumor	Disease	D009369
6585590	534	545	doxorubicin	Chemical	D004317
6585590	580	585	tumor	Disease	D009369
6585590	610	621	doxorubicin	Chemical	D004317
6585590	649	663	cardiotoxicity	Disease	D066126
6585590	722	733	doxorubicin	Chemical	D004317
6585590	768	780	renal damage	Disease	D007674
6585590	813	824	doxorubicin	Chemical	D004317
6585590	847	858	albuminuria	Disease	D000419
6585590	928	939	doxorubicin	Chemical	D004317
6585590	1020	1027	Ascites	Disease	D001201
6585590	1032	1043	hydrothorax	Disease	D006876
6585590	1119	1124	tumor	Disease	D009369
6585590	1219	1233	cardiotoxicity	Disease	D066126
6585590	1239	1253	nephrotoxicity	Disease	D007674
6585590	1309	1320	Albuminuria	Disease	D000419
6585590	1328	1340	renal damage	Disease	D007674
6585590	1387	1394	ascites	Disease	D001201
6585590	1399	1410	hydrothorax	Disease	D006876
6585590	1462	1476	cardiomyopathy	Disease	D009202
6585590	CID	D004317	D006876
6585590	CID	D004317	D001201
6585590	CID	D004317	D000419

6615679|t|Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops.
6615679|a|A 69-yr-old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24-h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2.6 ng ml-1) was consistent with partial beta-adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect.
6615679	15	26	bradycardia	Disease	D001919
6615679	31	42	hypotension	Disease	D007022
6615679	59	66	timolol	Chemical	D013999
6615679	71	82	pilocarpine	Chemical	D010862
6615679	151	170	pilocarpine nitrate	Chemical	D010862
6615679	175	190	timolol maleate	Chemical	D013999
6615679	214	225	bradycardia	Disease	D001919
6615679	237	248	hypotensive	Disease	D007022
6615679	256	265	halothane	Chemical	D006221
6615679	284	291	timolol	Chemical	D013999
6615679	296	307	pilocarpine	Chemical	D010862
6615679	368	375	Timolol	Chemical	D013999
6615679	385	396	pilocarpine	Chemical	D010862
6615679	485	492	timolol	Chemical	D013999
6615679	627	636	halothane	Chemical	D006221
6615679	664	675	bradycardia	Disease	D001919
6615679	680	691	hypotension	Disease	D007022
6615679	693	704	Pilocarpine	Chemical	D010862
6615679	CID	D013999	D007022
6615679	CID	D010862	D001919
6615679	CID	D010862	D007022
6615679	CID	D013999	D001919

6627074|t|Succinylcholine apnoea: attempted reversal with anticholinesterases.
6627074|a|Anticholinesterases were administered in an attempt to antagonize prolonged neuromuscular blockade following the administration of succinylcholine in a patient later found to be homozygous for atypical plasma cholinesterase. Edrophonium 10 mg, given 74 min after succinylcholine, when train-of-four stimulation was characteristic of phase II block, produced partial antagonism which was not sustained. Repeated doses of edrophonium to 70 mg and neostigmine to 2.5 mg did not antagonize or augment the block. Spontaneous respiration recommenced 200 min after succinylcholine administration. It is concluded that anticholinesterases are only partially effective in restoring neuromuscular function in succinylcholine apnoea despite muscle twitch activity typical of phase II block.
6627074	0	15	Succinylcholine	Chemical	D013390
6627074	16	22	apnoea	Disease	D001049
6627074	145	167	neuromuscular blockade	Disease	D020879
6627074	200	215	succinylcholine	Chemical	D013390
6627074	294	305	Edrophonium	Chemical	D004491
6627074	332	347	succinylcholine	Chemical	D013390
6627074	489	500	edrophonium	Chemical	D004491
6627074	514	525	neostigmine	Chemical	D009388
6627074	627	642	succinylcholine	Chemical	D013390
6627074	768	783	succinylcholine	Chemical	D013390
6627074	784	790	apnoea	Disease	D001049
6627074	CID	D013390	D001049

6631522|t|Effect of doxorubicin on [omega-I-131]heptadecanoic acid myocardial scintigraphy and echocardiography in dogs.
6631522|a|The effects of serial treatment with doxorubicin on dynamic myocardial scintigraphy with [omega-I-131]heptadecanoic acid (I-131 HA), and on global left-ventricular function determined echocardiographically, were studied in a group of nine mongrel dogs. Total extractable myocardial lipid was compared postmortem between a group of control dogs and doxorubicin-treated dogs. A significant and then progressive fall in global LV function was observed at a cumulative doxorubicin dose of 4 mg/kg. A significant increase in the myocardial t1/2 of the I-131 HA was observed only at a higher cumulative dose, 10 mg/kg. No significant alteration in total extractable myocardial lipids was observed between control dogs and those treated with doxorubicin. Our findings suggest that the changes leading to an alteration of myocardial dynamic imaging with I-131 HA are not the initiating factor in doxorubicin cardiotoxicity.
6631522	10	21	doxorubicin	Chemical	D004317
6631522	25	56	[omega-I-131]heptadecanoic acid	Chemical	C013102
6631522	148	159	doxorubicin	Chemical	D004317
6631522	200	231	[omega-I-131]heptadecanoic acid	Chemical	C013102
6631522	233	241	I-131 HA	Chemical	C013102
6631522	459	470	doxorubicin	Chemical	D004317
6631522	576	587	doxorubicin	Chemical	D004317
6631522	658	666	I-131 HA	Chemical	C013102
6631522	846	857	doxorubicin	Chemical	D004317
6631522	957	965	I-131 HA	Chemical	C013102
6631522	999	1010	doxorubicin	Chemical	D004317
6631522	1011	1025	cardiotoxicity	Disease	D066126
6631522	CID	D004317	D066126

6673474|t|Hemodynamics and myocardial metabolism under deliberate hypotension. An experimental study in dogs.
6673474|a|Coronary blood flow, cardiac work and metabolism were studied in dogs under sodium nitroprusside (SNP) and trimetaphan (TMP) deliberate hypotension (20% and 40% mean pressure decrease from baseline). Regarding the effects of drug-induced hypotension on coronary blood flow, aortic and coronary sinus metabolic data (pH, pO2, pCO2) we could confirm that nitroprusside hypotension could be safely used to 30% mean blood pressure decrease from control, trimetaphan hypotension to 20% mean blood pressure decrease. Cardiac work was significantly reduced during SNP hypotension. Myocardial O2 consumption and O2 availability were directly dependent on the coronary perfusion. Careful invasive monitoring of the blood pressure, blood gases and of the ECG ST-T segment is mandatory.
6673474	56	67	hypotension	Disease	D007022
6673474	176	196	sodium nitroprusside	Chemical	D009599
6673474	198	201	SNP	Chemical	D009599
6673474	207	218	trimetaphan	Chemical	D014294
6673474	220	223	TMP	Chemical	D014294
6673474	236	247	hypotension	Disease	D007022
6673474	338	349	hypotension	Disease	D007022
6673474	453	466	nitroprusside	Chemical	D009599
6673474	467	478	hypotension	Disease	D007022
6673474	550	561	trimetaphan	Chemical	D014294
6673474	562	573	hypotension	Disease	D007022
6673474	657	660	SNP	Chemical	D009599
6673474	661	672	hypotension	Disease	D007022
6673474	685	687	O2	Chemical	D010100
6673474	704	706	O2	Chemical	D010100
6673474	CID	D014294	D007022
6673474	CID	D009599	D007022

6687006|t|Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat.
6687006|a|Male rats received the noradrenaline neurotoxin DSP4 (50 mg/kg) 7 days prior to injection of D-amphetamine (10 or 40 mumol/kg i.p.). The hyperactivity induced by D-amphetamine (10 mumol/kg) was significantly reduced by DSP4 pretreatment. However, the increased rearings and the amphetamine-induced stereotypies were not blocked by pretreatment with DSP4. The reduction of amphetamine hyperactivity induced by DSP4 was blocked by pretreatment with the noradrenaline-uptake blocking agent, desipramine, which prevents the neurotoxic action of DSP4. The present results suggest a selective involvement of central noradrenergic neurones in the locomotor stimulant effect of amphetamine in the rat.
6687006	95	106	amphetamine	Chemical	D000661
6687006	142	155	noradrenaline	Chemical	D009638
6687006	167	171	DSP4	Chemical	C012102
6687006	212	225	D-amphetamine	Chemical	D003913
6687006	256	269	hyperactivity	Disease	D006948
6687006	281	294	D-amphetamine	Chemical	D003913
6687006	338	342	DSP4	Chemical	C012102
6687006	397	408	amphetamine	Chemical	D000661
6687006	417	429	stereotypies	Disease	D019956
6687006	468	472	DSP4	Chemical	C012102
6687006	491	502	amphetamine	Chemical	D000661
6687006	503	516	hyperactivity	Disease	D006948
6687006	528	532	DSP4	Chemical	C012102
6687006	570	583	noradrenaline	Chemical	D009638
6687006	607	618	desipramine	Chemical	D003891
6687006	639	649	neurotoxic	Disease	D020258
6687006	660	664	DSP4	Chemical	C012102
6687006	789	800	amphetamine	Chemical	D000661
6687006	CID	D003913	D006948

6695685|t|Accelerated junctional rhythms during oral verapamil therapy.
6695685|a|This study examined the frequency of atrioventricular (AV) dissociation and accelerated junctional rhythms in 59 patients receiving oral verapamil. Accelerated junctional rhythms and AV dissociation were frequent in patients with supraventricular tachyarrhythmias, particularly AV nodal reentry. Verapamil administration to these patients led to an asymptomatic increase in activity of these junctional pacemakers. In patients with various chest pain syndromes, verapamil neither increased the frequency of junctional rhythms nor suppressed their role as escape rhythms under physiologically appropriate circumstances.
6695685	0	30	Accelerated junctional rhythms	Disease	D001145
6695685	43	52	verapamil	Chemical	D014700
6695685	138	168	accelerated junctional rhythms	Disease	D001145
6695685	199	208	verapamil	Chemical	D014700
6695685	210	240	Accelerated junctional rhythms	Disease	D001145
6695685	292	325	supraventricular tachyarrhythmias	Disease	D013617
6695685	358	367	Verapamil	Chemical	D014700
6695685	502	512	chest pain	Disease	D002637
6695685	524	533	verapamil	Chemical	D014700
6695685	CID	D014700	D001145

6806735|t|Treatment of ovarian cancer with a combination of cis-platinum, adriamycin, cyclophosphamide and hexamethylmelamine.
6806735|a|During the last 2 1/2 years, 38 patients with ovarian cancer were treated with a combination of cisplatinum (CPDD), 50 mg/m2, adriamycin, 30 mg/m2, cyclophosphamide, 300 mg/m2, on day 1; and hexamethylmelamine (HMM), 6 mg/kg daily, for 14 days. Each course was repeated monthly. 2 patients had stage II, 14 stage III and 22 stage IV disease. 14 of the 38 patients were previously treated with chemotherapy, 1 with radiation, 6 with both chemotherapy and radiation, and 17 did not have any treatment before CPDD combination. 31 of the 38 cases (81.5%) demonstrated objective responses lasting for 2 months or more. These responses were partial in 19 and complete in 12 cases. Hematologic toxicity was moderate and with reversible anemia developing in 71% of patients. Gastrointestinal side effects from CPDD were universal. HMM gastrointestinal toxicity necessitated discontinuation of the drug in 5 patients. Severe nephrotoxicity was observed in 2 patients but was reversible. There were no drug-related deaths.
6806735	13	27	ovarian cancer	Disease	D010051
6806735	50	62	cis-platinum	Chemical	D002945
6806735	64	74	adriamycin	Chemical	D004317
6806735	76	92	cyclophosphamide	Chemical	D003520
6806735	97	115	hexamethylmelamine	Chemical	D006585
6806735	163	177	ovarian cancer	Disease	D010051
6806735	213	224	cisplatinum	Chemical	D002945
6806735	226	230	CPDD	Chemical	C034868
6806735	243	253	adriamycin	Chemical	D004317
6806735	265	281	cyclophosphamide	Chemical	D003520
6806735	308	326	hexamethylmelamine	Chemical	D006585
6806735	328	331	HMM	Chemical	D006585
6806735	623	627	CPDD	Chemical	C034868
6806735	792	812	Hematologic toxicity	Disease	D006402
6806735	846	852	anemia	Disease	D000740
6806735	919	923	CPDD	Chemical	C034868
6806735	940	943	HMM	Chemical	D006585
6806735	944	969	gastrointestinal toxicity	Disease	D005767
6806735	1033	1047	nephrotoxicity	Disease	D007674
6806735	CID	C034868	D000740
6806735	CID	C034868	D007674
6806735	CID	C034868	D005767

6884395|t|Nontraumatic dissecting aneurysm of the basilar artery.
6884395|a|A case of nontraumatic dissecting aneurysm of the basilar artery in association with hypertension, smoke, and oral contraceptives is reported in a young female patient with a locked-in syndrome.
6884395	13	32	dissecting aneurysm	Disease	D000784
6884395	79	98	dissecting aneurysm	Disease	D000784
6884395	141	153	hypertension	Disease	D006973
6884395	166	185	oral contraceptives	Chemical	D003276
6884395	231	249	locked-in syndrome	Disease	D011782
6884395	CID	D003276	D000784

6893265|t|Propylthiouracil-induced hepatic damage.
6893265|a|Two cases of propylthiouracil-induced liver damage have been observed. The first case is of an acute type of damage, proven by rechallenge; the second presents a clinical and histologic picture resembling chronic active hepatitis, with spontaneous remission.
6893265	0	16	Propylthiouracil	Chemical	D011441
6893265	25	39	hepatic damage	Disease	D056486
6893265	54	70	propylthiouracil	Chemical	D011441
6893265	79	91	liver damage	Disease	D056486
6893265	246	270	chronic active hepatitis	Disease	D006521
6893265	CID	D011441	D006521
6893265	CID	D011441	D056486

6985297|t|Studies on the bradycardia induced by bepridil.
6985297|a|Bepridil, a novel active compound for prophylactic treatment of anginal attacks, induced persistent bradycardia and a non-specific anti-tachycardial effect, the mechanisms of which were investigated in vitro and in vivo. In vitro perfusion of bepridil in the life-support medium for isolated sino-atrial tissue from rabbit heart, caused a reduction in action potential (AP) spike frequency (recorded by KCl microelectrodes) starting at doses of 5 X 10(-6) M. This effect was dose-dependent up to concentrations of 5 X 10(-5) M, whereupon blockade of sinus activity set in. Bepridil at a dose of 5 X 10(-6) M, induced a concomitant reduction in AP amplitude (falling from 71 +/- 8 mV to 47 +/- 6 mV), maximum systolic depolarization velocity (phase 0) which fell from 1.85 +/- 0.35 V/s to 0.84 +/- 0.28 V/s, together with maximum diastolic depolarization velocity (phase 4) which fell from 38 +/- 3 mV/s to 24 +/- 5 mV/s. In vivo injection of bepridil at a dose of 5 mg/kg (i.v.) into 6 anaesthetized dogs which had undergone ablation of all the extrinsic cardiac afferent nerve supply, together with a bilateral medullo-adrenalectomy, caused a marked reduction in heart rate which fell from 98.7 +/- 4.2 beats/min to 76 +/- 5.3 beats/min sustained for more than 45 min. It is concluded that bepridil reduces heart rate by acting directly on the sinus node. This effect, which results in a flattening of the phase 0 and phase 4 slope, together with a longer AP duration, may be due to an increase in the time constants of slow inward ionic currents (already demonstrated elsewhere), but also to an increased time constant for deactivation of the outward potassium current (Ip).
6985297	15	26	bradycardia	Disease	D001919
6985297	38	46	bepridil	Chemical	D015764
6985297	48	56	Bepridil	Chemical	D015764
6985297	112	127	anginal attacks	Disease	D000787
6985297	148	159	bradycardia	Disease	D001919
6985297	184	196	tachycardial	Disease	D013610
6985297	291	299	bepridil	Chemical	D015764
6985297	451	454	KCl	Chemical	D011189
6985297	621	629	Bepridil	Chemical	D015764
6985297	990	998	bepridil	Chemical	D015764
6985297	1339	1347	bepridil	Chemical	D015764
6985297	1701	1710	potassium	Chemical	D011188
6985297	CID	D015764	D001919

6985498|t|Hepatitis and renal tubular acidosis after anesthesia with methoxyflurane.
6985498|a|A 69-year-old man operated for acute cholecystitis under methoxyflurane anesthesia developed postoperatively a hepatic insufficiency syndrome and renal tubular acidosis. Massive bleeding appeared during surgery which lasted for six hours. Postoperative evolution under supportive therapy was favourable. Complete recovery was confirmed by repeated controls performed over a period of one year after surgery.
6985498	0	9	Hepatitis	Disease	D056486
6985498	14	36	renal tubular acidosis	Disease	D000141
6985498	59	73	methoxyflurane	Chemical	D008733
6985498	106	125	acute cholecystitis	Disease	D041881
6985498	132	146	methoxyflurane	Chemical	D008733
6985498	186	216	hepatic insufficiency syndrome	Disease	D048550
6985498	221	243	renal tubular acidosis	Disease	D000141
6985498	253	261	bleeding	Disease	D006470
6985498	CID	D008733	D000141
6985498	CID	D008733	D056486

7018927|t|Pituitary response to luteinizing hormone-releasing hormone during haloperidol-induced hyperprolactinemia.
7018927|a|The effects of a 6-hour infusion with haloperidol on serum prolactin and luteinizing hormone (LH) levels was studied in a group of male subjects. Five hours after starting the infusions, a study of the pituitary responses to LH-releasing hormone (LH-RH) was carried out. Control patients received infusions of 0.9% NaCl solution. During the course of haloperidol infusions, significant hyperprolactinemia was found, together with an abolished pituitary response to LH-RH, as compared with responses of control subjects.
7018927	67	78	haloperidol	Chemical	D006220
7018927	87	105	hyperprolactinemia	Disease	D006966
7018927	145	156	haloperidol	Chemical	D006220
7018927	422	426	NaCl	Chemical	D012965
7018927	458	469	haloperidol	Chemical	D006220
7018927	493	511	hyperprolactinemia	Disease	D006966
7018927	CID	D006220	D006966

7121659|t|Antirifampicin antibodies in acute rifampicin-associated renal failure.
7121659|a|5 patients with acute renal failure (3 with thrombopenia and hemolysis) induced by the reintroduction of rifampicin are described. No correlation was found between the severity of clinical manifestations and the total dose taken by the patients. In all but 1 patient, antirifampicin antibodies were detected. Antibodies suggested to be of the IgM class were detected in all 3 patients with hematological disorders. The pattern of non-specific acute tubular necrosis found in the 2 biopsied patients, indistinguishable from that of ischemic origin, raised the possibility of a vascular-mediated damage. In 3 patients, the possibility of a triggering immunoallergic mechanism is discussed.
7121659	35	45	rifampicin	Chemical	D012293
7121659	57	70	renal failure	Disease	D051437
7121659	88	107	acute renal failure	Disease	D058186
7121659	116	128	thrombopenia	Disease	D013921
7121659	133	142	hemolysis	Disease	D006461
7121659	177	187	rifampicin	Chemical	D012293
7121659	462	485	hematological disorders	Disease	D006402
7121659	515	537	acute tubular necrosis	Disease	D007683
7121659	CID	D012293	D006461
7121659	CID	D012293	D013921
7121659	CID	D012293	D007683

7147232|t|Cardiovascular effects of hypotension induced by adenosine triphosphate and sodium nitroprusside on dogs with denervated hearts.
7147232|a|Adenosine triphosphate (ATP) and sodium nitroprusside (SNP) are administered to patients to induce and control hypotension during anesthesia. SNP is authorized for clinical use in USA and UK, and ATP is clinically used in other countries such as Japan. We investigated how these two drugs act on the cardiovascular systems of 20 dogs whose hearts had been denervated by a procedure we had devised. ATP (10 dogs) or SNP (10 dogs) was administered to reduce mean arterial pressure by 30% to 70% of control. Before, during and after induced hypotension, we measured major cardiovascular parameters. Hypotension induced by ATP was accompanied by significant decreases in mean pulmonary arterial pressure (p less than 0.001), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.001), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), total body oxygen consumption (p less than 0.05), and heart rate (p less than 0.001); all these variables returned normal within 30 min after ATP was stopped. Cardiac output did not change. During hypotension produced by SNP similar decreases were observed in mean pulmonary arterial pressure (p less than 0.01), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.01), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), and oxygen content difference between arterial and mixed venous blood (p less than 0.05), while heart rate (p less than 0.001) and cardiac output (p less than 0.05) were increased. Recoveries of heart rate and left ventricular end-diastolic pressure were not shown within 60 min after SNP had been stopped. Both ATP and SNP should act on the pacemaker tissue of the heart.
7147232	26	37	hypotension	Disease	D007022
7147232	49	71	adenosine triphosphate	Chemical	D000255
7147232	76	96	sodium nitroprusside	Chemical	D009599
7147232	129	151	Adenosine triphosphate	Chemical	D000255
7147232	153	156	ATP	Chemical	D000255
7147232	162	182	sodium nitroprusside	Chemical	D009599
7147232	184	187	SNP	Chemical	D009599
7147232	240	251	hypotension	Disease	D007022
7147232	271	274	SNP	Chemical	D009599
7147232	325	328	ATP	Chemical	D000255
7147232	527	530	ATP	Chemical	D000255
7147232	544	547	SNP	Chemical	D009599
7147232	667	678	hypotension	Disease	D007022
7147232	725	736	Hypotension	Disease	D007022
7147232	748	751	ATP	Chemical	D000255
7147232	1059	1065	oxygen	Chemical	D010100
7147232	1190	1193	ATP	Chemical	D000255
7147232	1245	1256	hypotension	Disease	D007022
7147232	1269	1272	SNP	Chemical	D009599
7147232	1562	1568	oxygen	Chemical	D010100
7147232	1843	1846	SNP	Chemical	D009599
7147232	1870	1873	ATP	Chemical	D000255
7147232	1878	1881	SNP	Chemical	D009599
7147232	CID	D009599	D007022
7147232	CID	D000255	D007022

7173007|t|Comparative study: Endografine (diatrizoate), Vasurix polyvidone (acetrizoate), Dimer-X (iocarmate) and Hexabrix (ioxaglate) in hysterosalpingography.
7173007|a|Side effects of hysterosalpingography with Dimer-X, Hexabrix, Vasurix polyvidone and Endografine in 142 consecutive patients, receiving one of the four tested media were evaluated from replies to postal questionnaires. The Dimer-X group had a higher incidence of nausea and dizziness. The Endografine group had a higher incidence of abdominal pain. These differences occur especially in the age groups under 30 years. Hexabrix and Vasurix polyvidone are considered the best contrast media for hysterosalpingography and perhaps because of its low toxicity Hexabrix should be preferred.
7173007	19	30	Endografine	Chemical	C006753
7173007	32	43	diatrizoate	Chemical	D003973
7173007	46	64	Vasurix polyvidone	Chemical	D000100
7173007	66	77	acetrizoate	Chemical	D000100
7173007	80	87	Dimer-X	Chemical	C025504
7173007	89	98	iocarmate	Chemical	C025504
7173007	104	112	Hexabrix	Chemical	D007485
7173007	114	123	ioxaglate	Chemical	D007485
7173007	194	201	Dimer-X	Chemical	C025504
7173007	203	211	Hexabrix	Chemical	D007485
7173007	213	231	Vasurix polyvidone	Chemical	D000100
7173007	236	247	Endografine	Chemical	C006753
7173007	374	381	Dimer-X	Chemical	C025504
7173007	414	420	nausea	Disease	D009325
7173007	425	434	dizziness	Disease	D004244
7173007	440	451	Endografine	Chemical	C006753
7173007	484	498	abdominal pain	Disease	D015746
7173007	569	577	Hexabrix	Chemical	D007485
7173007	582	600	Vasurix polyvidone	Chemical	D000100
7173007	625	639	contrast media	Chemical	D003287
7173007	697	705	toxicity	Disease	D064420
7173007	706	714	Hexabrix	Chemical	D007485
7173007	CID	C006753	D015746
7173007	CID	C025504	D004244
7173007	CID	C025504	D009325

7176945|t|Post-suxamethonium pains in Nigerian surgical patients.
7176945|a|Contrary to an earlier report by Coxon, scoline pain occurs in African negroes. Its incidence was determined in a prospective study involving a total of 100 Nigerian patients (50 out-patients and 50 in-patients). About 62% of the out-patients developed scoline pain as compared with about 26% among the in-patients. The abolition of muscle fasciculations (by 0.075mg/kg dose of Fazadinium) did not influence the occurrence of scoline pain. Neither the type of induction agent (Althesin or Thiopentone) nor the salt preparation of suxamethonium used (chloride or bromide), affected the incidence of scoline pain.
7176945	5	18	suxamethonium	Chemical	D013390
7176945	19	24	pains	Disease	D010146
7176945	96	103	scoline	Chemical	D013390
7176945	104	108	pain	Disease	D010146
7176945	309	316	scoline	Chemical	D013390
7176945	317	321	pain	Disease	D010146
7176945	396	410	fasciculations	Disease	D005207
7176945	434	444	Fazadinium	Chemical	C084773
7176945	482	489	scoline	Chemical	D013390
7176945	490	494	pain	Disease	D010146
7176945	533	541	Althesin	Chemical	D000530
7176945	545	556	Thiopentone	Chemical	D013874
7176945	586	599	suxamethonium	Chemical	D013390
7176945	606	614	chloride	Chemical	D002712
7176945	618	625	bromide	Chemical	D001965
7176945	654	661	scoline	Chemical	D013390
7176945	662	666	pain	Disease	D010146
7176945	CID	D013390	D005207
7176945	CID	D013390	D010146

7315949|t|Medial changes in arterial spasm induced by L-norepinephrine.
7315949|a|In normal rats, the media of small arteries (0.4--0.2 mm in diameter) previously was shown to contain intracellular vacuoles, identified ultrastructurally as herniations of one smooth muscle cell into another. The hypothesis that intense vasoconstriction would increase the number of such vacuoles has been tested. In the media of the saphenous artery and its distal branch, vasoconstriction induced by L-norepinephrine produced many cell-to-cell hernias within 15 minutes. At 1 day their number was reduced to about 1/10 of the original number. By 7 days the vessel was almost restored to normal. Triple stimulation over 1 day induced more severe changes in the media. These findings suggest that smooth muscle cells are susceptible to damage in the course of their specific function. The experimental data are discussed in relation to medial changes observed in other instances of arterial spasm. Endothelial changes that developed in the same experimental model were described in a previous paper.
7315949	27	32	spasm	Disease	D013035
7315949	44	60	L-norepinephrine	Chemical	D009638
7315949	465	481	L-norepinephrine	Chemical	D009638
7315949	509	516	hernias	Disease	D006547
7315949	954	959	spasm	Disease	D013035
7315949	CID	D009638	D013035

7369302|t|Abnormalities of the pupil and visual-evoked potential in quinine amblyopia.
7369302|a|Total blindness with a transient tonic pupillary response, denervation supersensitivity, and abnormal visual-evoked potentials developed in a 54-year-old man after the use of quinine sulfate for leg cramps. He later recovered normal visual acuity. A transient tonic pupillary response, denervation supersensitivity, and abnormal visual-evoked potentials in quinine toxicity, to our knowledge, have not been previously reported.
7369302	58	65	quinine	Chemical	D011803
7369302	66	75	amblyopia	Disease	D000550
7369302	83	92	blindness	Disease	D001766
7369302	110	125	tonic pupillary	Disease	D015845
7369302	252	267	quinine sulfate	Chemical	D011803
7369302	272	282	leg cramps	Disease	D009120
7369302	337	352	tonic pupillary	Disease	D015845
7369302	434	441	quinine	Chemical	D011803
7369302	442	450	toxicity	Disease	D064420
7369302	CID	D011803	D015845
7369302	CID	D011803	D000550
7369302	CID	D011803	D001766

7378868|t|Suxamethonium-induced jaw stiffness and myalgia associated with atypical cholinesterase: case report.
7378868|a|An 11-year-old boy was given halothane, nitrous oxide and oxygen, pancuronium 0.4 mg and suxamethonium 100 mg for induction of anaesthesia. In response to this a marked jaw stiffness occurred which lasted for two minutes and the anaesthesia were terminated. Four hours of apnoea ensued and he suffered generalized severe myalgia lasting for one week. He was found to have atypical plasma cholinesterase with a dibucaine number of 12, indicating homozygocity. This was verified by study of the family. The case shows that prolonged jaw rigidity and myalgia may occur after suxamethonium in patients with atypical cholinesterase despite pretreatment with pancuronium.
7378868	0	13	Suxamethonium	Chemical	D013390
7378868	22	35	jaw stiffness	Disease	D014313
7378868	40	47	myalgia	Disease	D063806
7378868	131	140	halothane	Chemical	D006221
7378868	142	155	nitrous oxide	Chemical	D009609
7378868	160	166	oxygen	Chemical	D010100
7378868	168	179	pancuronium	Chemical	D010197
7378868	191	204	suxamethonium	Chemical	D013390
7378868	271	284	jaw stiffness	Disease	D014313
7378868	374	380	apnoea	Disease	D001049
7378868	423	430	myalgia	Disease	D063806
7378868	512	521	dibucaine	Chemical	D003992
7378868	623	645	prolonged jaw rigidity	Disease	D014313
7378868	650	657	myalgia	Disease	D063806
7378868	674	687	suxamethonium	Chemical	D013390
7378868	755	766	pancuronium	Chemical	D010197
7378868	CID	D013390	D014313
7378868	CID	D013390	D001049
7378868	CID	D013390	D063806

7411769|t|Indomethacin-induced hyperkalemia in three patients with gouty arthritis.
7411769|a|We describe three patients in whom severe, life-threatening hyperkalemia and renal insufficiency developed after treatment of acute gouty arthritis with indomethacin. This complication may result from an inhibition of prostaglandin synthesis and consequent hyporeninemic hypoaidosteronism. Careful attention to renal function and potassium balance in patients receiving indomethacin or other nonsteroidal anti-inflammatory agents, particularly in those patients with diabetes mellitus or preexisting renal disease, will help prevent this potentially serious complication.
7411769	0	12	Indomethacin	Chemical	D007213
7411769	21	33	hyperkalemia	Disease	D006947
7411769	57	72	gouty arthritis	Disease	D015210
7411769	134	146	hyperkalemia	Disease	D006947
7411769	151	170	renal insufficiency	Disease	D051437
7411769	206	221	gouty arthritis	Disease	D015210
7411769	227	239	indomethacin	Chemical	D007213
7411769	292	305	prostaglandin	Chemical	D011453
7411769	331	362	hyporeninemic hypoaidosteronism	Disease	D006994
7411769	404	413	potassium	Chemical	D011188
7411769	444	456	indomethacin	Chemical	D007213
7411769	541	558	diabetes mellitus	Disease	D003920
7411769	574	587	renal disease	Disease	D007674
7411769	CID	D007213	D006947
7411769	CID	D007213	D051437

7457821|t|Etomidate: a foreshortened clinical trial.
7457821|a|A clinical evaluation of etomidate for outpatient cystoscopy was embarked upon. Unpremedicated patients were given fentanyl 1 microgram/kg followed by etomidate 0.3 mg/kg. Anaesthesia was maintained with intermittent etomidate in 2-4 mg doses. Patients were interviewed personally later the same day, and by questionnaire three to four weeks later. The trial was discontinued after 20 cases because of an unacceptable incidence of side effects. Venous pain occurred in 68% of patients and 50% had redness, pain or swelling related to the injection site, in some cases lasting up to three weeks after anaesthesia. Skeletal movements occurred in 50% of patients; 30% experienced respiratory upset, one sufficiently severe to necessitate abandoning the technique. Nausea and vomiting occurred in 40% and 25% had disturbing emergence psychoses.
7457821	0	9	Etomidate	Chemical	D005045
7457821	68	77	etomidate	Chemical	D005045
7457821	158	166	fentanyl	Chemical	D005283
7457821	194	203	etomidate	Chemical	D005045
7457821	260	269	etomidate	Chemical	D005045
7457821	495	499	pain	Disease	D010146
7457821	549	553	pain	Disease	D010146
7457821	557	565	swelling	Disease	D004487
7457821	720	737	respiratory upset	Disease	D012140
7457821	804	810	Nausea	Disease	D009325
7457821	815	823	vomiting	Disease	D014839
7457821	873	882	psychoses	Disease	D011605
7457821	CID	D005045	D009325
7457821	CID	D005045	D014839
7457821	CID	D005045	D010146
7457821	CID	D005045	D012140
7457821	CID	D005045	D011605

7477981|t|Levodopa-induced dyskinesias are improved by fluoxetine.
7477981|a|We evaluated the severity of motor disability and dyskinesias in seven levodopa-responsive patients with Parkinson's disease after an acute challenge with the mixed dopamine agonist, apomorphine, before and after the administration of fluoxetine (20 mg twice per day) for 11 +/- 1 days. After fluoxetine treatment, there was a significant 47% improvement (p < 0.05) of apomorphine-induced dyskinesias without modification of parkinsonian motor disability. The dyskinesias were reduced predominantly in the lower limbs during the onset and disappearance of dystonic dyskinesias (onset- and end-of-dose dyskinesias) and in the upper limbs during choreic mid-dose dyskinesias. The results suggest that increased brain serotoninergic transmission with fluoxetine may reduce levodopa- or dopamine agonist-induced dyskinesias without aggravating parkinsonian motor disability.
7477981	0	8	Levodopa	Chemical	D007980
7477981	17	28	dyskinesias	Disease	D004409
7477981	45	55	fluoxetine	Chemical	D005473
7477981	86	102	motor disability	Disease	D009069
7477981	107	118	dyskinesias	Disease	D004409
7477981	128	136	levodopa	Chemical	D007980
7477981	162	181	Parkinson's disease	Disease	D010300
7477981	222	230	dopamine	Chemical	D004298
7477981	240	251	apomorphine	Chemical	D001058
7477981	292	302	fluoxetine	Chemical	D005473
7477981	350	360	fluoxetine	Chemical	D005473
7477981	426	437	apomorphine	Chemical	D001058
7477981	446	457	dyskinesias	Disease	D004409
7477981	482	494	parkinsonian	Disease	D010300
7477981	495	511	motor disability	Disease	D009069
7477981	517	528	dyskinesias	Disease	D004409
7477981	613	633	dystonic dyskinesias	Disease	D020821|D004409	dystonic|dyskinesias
7477981	658	669	dyskinesias	Disease	D004409
7477981	701	729	choreic mid-dose dyskinesias	Disease	D002819|D004409	choreic|mid-dose dyskinesias
7477981	805	815	fluoxetine	Chemical	D005473
7477981	827	835	levodopa	Chemical	D007980
7477981	840	848	dopamine	Chemical	D004298
7477981	865	876	dyskinesias	Disease	D004409
7477981	897	909	parkinsonian	Disease	D010300
7477981	910	926	motor disability	Disease	D009069
7477981	CID	D001058	D004409
7477981	CID	D005473	D004409

7479194|t|A large population-based follow-up study of trimethoprim-sulfamethoxazole, trimethoprim, and cephalexin for uncommon serious drug toxicity.
7479194|a|We conducted a population-based 45-day follow-up study of 232,390 people who were prescribed trimethoprim-sulfamethoxazole (TMP-SMZ), 266,951 prescribed trimethoprim alone, and 196,397 prescribed cephalexin, to estimate the risk of serious liver, blood, skin, and renal disorders resulting in referral or hospitalization associated with these drugs. The results were based on information recorded on office computers by selected general practitioners in the United Kingdom, together with a review of clinical records. The risk of clinically important idiopathic liver disease was similar for persons prescribed TMP-SMZ (5.2/100,000) and those prescribed trimethoprim alone (3.8/100,000). The risk for those prescribed cephalexin was somewhat lower (2.0/100,000). Only five patients experienced blood disorders, one of whom was exposed to TMP-SMZ; of seven with erythema multiforme and Stevens-Johnson syndrome, four were exposed to TMP-SMZ. The one case of toxic epidermal necrolysis occurred in a patient who took cephalexin. Finally, only five cases of acute parenchymal renal disease occurred, none likely to be caused by a study drug. We conclude that the risk of the serious diseases studied is small for the three agents, and compares reasonably with the risk for many other antibiotics.
7479194	44	73	trimethoprim-sulfamethoxazole	Chemical	D015662
7479194	75	87	trimethoprim	Chemical	D014295
7479194	93	103	cephalexin	Chemical	D002506
7479194	125	138	drug toxicity	Disease	D064420
7479194	233	262	trimethoprim-sulfamethoxazole	Chemical	D015662
7479194	264	271	TMP-SMZ	Chemical	D015662
7479194	293	305	trimethoprim	Chemical	D014295
7479194	336	346	cephalexin	Chemical	D002506
7479194	380	419	liver, blood, skin, and renal disorders	Disease	D008107|D006402|D012871|D007674	liver disorders|blood disorders|skin disorders|renal disorders
7479194	702	715	liver disease	Disease	D008107
7479194	751	758	TMP-SMZ	Chemical	D015662
7479194	794	806	trimethoprim	Chemical	D014295
7479194	858	868	cephalexin	Chemical	D002506
7479194	978	985	TMP-SMZ	Chemical	D015662
7479194	1001	1020	erythema multiforme	Disease	D004892
7479194	1025	1049	Stevens-Johnson syndrome	Disease	D013262
7479194	1072	1079	TMP-SMZ	Chemical	D015662
7479194	1097	1123	toxic epidermal necrolysis	Disease	D013262
7479194	1155	1165	cephalexin	Chemical	D002506
7479194	1213	1226	renal disease	Disease	D007674
7479194	CID	D014295	D008107
7479194	CID	D015662	D008107
7479194	CID	D002506	D008107
7479194	CID	D002506	D013262
7479194	CID	D015662	D013262

7492040|t|Clinical safety of lidocaine in patients with cocaine-associated myocardial infarction.
7492040|a|STUDY OBJECTIVE: To evaluate the safety of lidocaine in the setting of cocaine-induced myocardial infarction (MI). DESIGN: A retrospective, multicenter study. SETTING: Twenty-nine university, university-affiliated, or community hospitals during a 6-year period (total of 117 cumulative hospital-years). PARTICIPANTS: Patients with cocaine-associated MI who received lidocaine in the emergency department. RESULTS: Of 29 patients who received lidocaine in the setting of cocaine-associated MI, no patient died; exhibited bradydysrhythmias, ventricular tachycardia, or ventricular fibrillation; or experienced seizures after administration of lidocaine (95% confidence interval, 0% to 11%). CONCLUSION: Despite theoretical concerns that lidocaine may enhance cocaine toxicity, the use of lidocaine in patients with cocaine-associated MI was not associated with significant cardiovascular or central nervous system toxicity.
7492040	19	28	lidocaine	Chemical	D008012
7492040	46	53	cocaine	Chemical	D003042
7492040	65	86	myocardial infarction	Disease	D009203
7492040	131	140	lidocaine	Chemical	D008012
7492040	159	166	cocaine	Chemical	D003042
7492040	175	196	myocardial infarction	Disease	D009203
7492040	198	200	MI	Disease	D009203
7492040	419	426	cocaine	Chemical	D003042
7492040	438	440	MI	Disease	D009203
7492040	454	463	lidocaine	Chemical	D008012
7492040	530	539	lidocaine	Chemical	D008012
7492040	558	565	cocaine	Chemical	D003042
7492040	577	579	MI	Disease	D009203
7492040	608	625	bradydysrhythmias	Disease	D001919
7492040	627	650	ventricular tachycardia	Disease	D017180
7492040	655	679	ventricular fibrillation	Disease	D014693
7492040	696	704	seizures	Disease	D012640
7492040	729	738	lidocaine	Chemical	D008012
7492040	823	832	lidocaine	Chemical	D008012
7492040	845	852	cocaine	Chemical	D003042
7492040	853	861	toxicity	Disease	D064420
7492040	874	883	lidocaine	Chemical	D008012
7492040	901	908	cocaine	Chemical	D003042
7492040	920	922	MI	Disease	D009203
7492040	959	1008	cardiovascular or central nervous system toxicity	Disease	D002318|D002493	cardiovascular toxicity|central nervous system toxicity
7492040	CID	D003042	D009203

7644931|t|Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials.
7644931|a|Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour infusion was combined with carboplatin in a phase I/II study directed to patients with non-small cell lung cancer. Carboplatin was given at a fixed target area under the concentration-time curve of 6.0 by the Calvert formula, whereas paclitaxel was escalated in patient cohorts from 150 mg/m2 (dose level I) to 175, 200, 225, and 250 mg/m2. The 225 mg/m2 level was expanded for the phase II study since the highest level achieved (250 mg/m2) required modification because of nonhematologic toxicities (arthralgia and sensory neuropathy). Therapeutic effects were noted at all dose levels, with objective responses in 17 (two complete and 15 partial regressions) of 41 previously untreated patients. Toxicities were compared with a cohort of patients in a phase I trial of paclitaxel alone at identical dose levels. Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel/carboplatin combination could be dosed every 3 weeks.
7644931	0	10	Paclitaxel	Chemical	D017239
7644931	57	68	carboplatin	Chemical	D016190
7644931	117	127	Paclitaxel	Chemical	D017239
7644931	129	134	Taxol	Chemical	D017239
7644931	218	229	carboplatin	Chemical	D016190
7644931	278	304	non-small cell lung cancer	Disease	D002289
7644931	306	317	Carboplatin	Chemical	D016190
7644931	425	435	paclitaxel	Chemical	D017239
7644931	681	691	toxicities	Disease	D064420
7644931	693	703	arthralgia	Disease	D018771
7644931	708	726	sensory neuropathy	Disease	D012678
7644931	890	900	Toxicities	Disease	D064420
7644931	963	973	paclitaxel	Chemical	D017239
7644931	1006	1017	Carboplatin	Chemical	D016190
7644931	1047	1069	hematologic toxicities	Disease	D006402
7644931	1088	1098	paclitaxel	Chemical	D017239
7644931	1099	1110	carboplatin	Chemical	D016190
7644931	CID	D017239	D012678
7644931	CID	D017239	D006402
7644931	CID	D017239	D018771

7661171|t|The dose-dependent effect of misoprostol on indomethacin-induced renal dysfunction in well compensated cirrhosis.
7661171|a|Misoprostol (200 micrograms) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal hemodynamics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-micrograms dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-micrograms dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 micrograms of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis.
7661171	29	40	misoprostol	Chemical	D016595
7661171	44	56	indomethacin	Chemical	D007213
7661171	65	82	renal dysfunction	Disease	D007674
7661171	103	112	cirrhosis	Disease	D005355
7661171	114	125	Misoprostol	Chemical	D016595
7661171	184	196	indomethacin	Chemical	D007213
7661171	205	222	renal dysfunction	Disease	D007674
7661171	243	252	cirrhotic	Disease	D005355
7661171	331	342	misoprostol	Chemical	D016595
7661171	408	414	sodium	Chemical	D012964
7661171	495	504	cirrhotic	Disease	D005355
7661171	563	575	indomethacin	Chemical	D007213
7661171	597	608	misoprostol	Chemical	D016595
7661171	695	707	indomethacin	Chemical	D007213
7661171	801	807	sodium	Chemical	D012964
7661171	1003	1014	misoprostol	Chemical	D016595
7661171	1092	1103	misoprostol	Chemical	D016595
7661171	1138	1150	indomethacin	Chemical	D007213
7661171	1297	1306	cirrhosis	Disease	D005355
7661171	CID	D007213	D007674

7671401|t|Increased frequency and severity of angio-oedema related to long-term therapy with angiotensin-converting enzyme inhibitor in two patients.
7671401|a|Adverse reactions to drugs are well recognized as a cause of acute or chronic urticaria, and angio-oedema. Angiotensin-converting enzyme (ACE) inhibitors, used to treat hypertension and congestive heart failure, were introduced in Europe in the middle of the eighties, and the use of these drugs has increased progressively. Soon after the introduction of ACE inhibitors, acute bouts of angio-oedema were reported in association with the use of these drugs. We wish to draw attention to the possibility of adverse reactions to ACE inhibitors after long-term use and in patients with pre-existing angio-oedema.
7671401	36	48	angio-oedema	Disease	D000799
7671401	83	122	angiotensin-converting enzyme inhibitor	Chemical	D000806
7671401	218	227	urticaria	Disease	D014581
7671401	233	245	angio-oedema	Disease	D000799
7671401	247	293	Angiotensin-converting enzyme (ACE) inhibitors	Chemical	D000806
7671401	309	321	hypertension	Disease	D006973
7671401	326	350	congestive heart failure	Disease	D006333
7671401	496	510	ACE inhibitors	Chemical	D000806
7671401	527	539	angio-oedema	Disease	D000799
7671401	667	681	ACE inhibitors	Chemical	D000806
7671401	736	748	angio-oedema	Disease	D000799
7671401	CID	D000806	D000799

7727612|t|Myoclonus associated with lorazepam therapy in very-low-birth-weight infants.
7727612|a|Lorazepam is being used with increasing frequency as a sedative in the newborn and the young infant. Concern has been raised with regard to the safety of lorazepam in this age group, especially in very-low-birth-weight (VLBW; < 1,500 g) infants. Three young infants, all of birth weight < 1,500 g, experienced myoclonus following the intravenous administration of lorazepam. The potential neurotoxic effects of the drug (and its vehicle) in this population are discussed. Injectable lorazepam should be used with caution in VLBW infants.
7727612	0	9	Myoclonus	Disease	D009207
7727612	26	35	lorazepam	Chemical	D008140
7727612	78	87	Lorazepam	Chemical	D008140
7727612	232	241	lorazepam	Chemical	D008140
7727612	388	397	myoclonus	Disease	D009207
7727612	442	451	lorazepam	Chemical	D008140
7727612	467	477	neurotoxic	Disease	D020258
7727612	561	570	lorazepam	Chemical	D008140
7727612	CID	D008140	D009207

7739955|t|Transvenous right ventricular pacing during cardiopulmonary resuscitation of pediatric patients with acute cardiomyopathy.
7739955|a|We describe the cardiopulmonary resuscitation efforts on five patients who presented in acute circulatory failure from myocardial dysfunction. Three patients had acute viral myocarditis, one had a carbamazepine-induced acute eosinophilic myocarditis, and one had cardiac hemosiderosis resulting in acute cardiogenic shock. All patients were continuously monitored with central venous and arterial catheters in addition to routine noninvasive monitoring. An introducer sheath, a pacemaker, and sterile pacing wires were made readily available for the patients, should the need arise to terminate resistant cardiac dysrhythmias. All patients developed cardiocirculatory arrest associated with extreme hypotension and dysrhythmias within the first 48 hours of their admission to the pediatric intensive care unit (PICU). Right ventricular pacemaker wires were inserted in all of them during cardiopulmonary resuscitation (CPR). In four patients, cardiac pacing was used, resulting in a temporary captured rhythm and restoration of their cardiac output. These patients had a second event of cardiac arrest, resulting in death, within 10 to 60 minutes. In one patient, cardiac pacing was not used, because he converted to normal sinus rhythm by electrical defibrillation within three minutes of initiating CPR. We conclude that cardiac pacing during resuscitative efforts in pediatric patients suffering from acute myocardial dysfunction may not have long-term value in and of itself; however, if temporary hemodynamic stability is achieved by this procedure, it may provide additional time needed to institute other therapeutic modalities.
7739955	107	121	cardiomyopathy	Disease	D009202
7739955	217	236	circulatory failure	Disease	D012769
7739955	242	264	myocardial dysfunction	Disease	D009202
7739955	297	308	myocarditis	Disease	D009205
7739955	320	333	carbamazepine	Chemical	D002220
7739955	348	372	eosinophilic myocarditis	Disease	D004802|D009205	eosinophilic|myocarditis
7739955	427	444	cardiogenic shock	Disease	D012770
7739955	736	748	dysrhythmias	Disease	D001145
7739955	822	833	hypotension	Disease	D007022
7739955	838	850	dysrhythmias	Disease	D001145
7739955	1210	1224	cardiac arrest	Disease	D006323
7739955	1533	1555	myocardial dysfunction	Disease	D009202
7739955	CID	D002220	D004802
7739955	CID	D002220	D009205

7931490|t|Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin.
7931490|a|PURPOSE: To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. PATIENTS AND METHODS: One hundred eighty-four chemotherapy-naive patients receiving high-dose cisplatin (81 to 120 mg/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 micrograms/kg) administered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experiences and laboratory parameter changes. RESULTS: After granisetron doses of 5, 10, 20, and 40 micrograms/kg, a major response (< or = two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60% of patients, respectively, and a complete response (no vomiting or retching, and no antiemetic rescue) in 18%, 41%, 40%, and 47% of patients, respectively. There was a statistically longer time to first episode of nausea (P = .0015) and vomiting (P = .0001), and fewer patients were administered additional antiemetic medication in the 10-micrograms/kg dosing groups than in the 5-micrograms/kg dosing group. As granisetron dose increased, appetite return increased (P = .040). Headache was the most frequently reported adverse event (20%). CONCLUSION: A single 10-, 20-, or 40-micrograms/kg dose of granisetron was effective in controlling vomiting in 57% to 60% of patients who received cisplatin at doses greater than 81 mg/m2 and totally prevented vomiting in 40% to 47% of patients. There were no statistically significant differences in efficacy between the 10-micrograms/kg dose and the 20- and 40-micrograms/kg doses. Granisetron was well tolerated at all doses.
7931490	23	34	granisetron	Chemical	D017829
7931490	48	67	5-hydroxytryptamine	Chemical	D012701
7931490	112	118	nausea	Disease	D009325
7931490	123	131	vomiting	Disease	D014839
7931490	153	162	cisplatin	Chemical	D002945
7931490	252	263	granisetron	Chemical	D017829
7931490	265	271	Kytril	Chemical	D017829
7931490	398	407	cisplatin	Chemical	D002945
7931490	416	422	nausea	Disease	D009325
7931490	427	435	vomiting	Disease	D014839
7931490	531	540	cisplatin	Chemical	D002945
7931490	598	609	granisetron	Chemical	D017829
7931490	765	771	nausea	Disease	D009325
7931490	773	781	vomiting	Disease	D014839
7931490	928	939	granisetron	Chemical	D017829
7931490	1011	1019	vomiting	Disease	D014839
7931490	1162	1170	vomiting	Disease	D014839
7931490	1321	1327	nausea	Disease	D009325
7931490	1344	1352	vomiting	Disease	D014839
7931490	1519	1530	granisetron	Chemical	D017829
7931490	1585	1593	Headache	Disease	D006261
7931490	1707	1718	granisetron	Chemical	D017829
7931490	1748	1756	vomiting	Disease	D014839
7931490	1796	1805	cisplatin	Chemical	D002945
7931490	1859	1867	vomiting	Disease	D014839
7931490	2033	2044	Granisetron	Chemical	D017829
7931490	CID	D002945	D014839
7931490	CID	D017829	D006261
7931490	CID	D002945	D009325

7949506|t|Adverse interaction between clonidine and verapamil.
7949506|a|OBJECTIVE: To report two cases of a possible adverse interaction between clonidine and verapamil resulting in atrioventricular (AV) block in both patients and severe hypotension in one patient. CASE SUMMARIES: A 54-year-old woman with hyperaldosteronism was treated with verapamil 480 mg/d and spironolactone 100 mg/d. After the addition of a minimal dose of clonidine (0.15 mg bid), she developed complete AV block and severe hypotension, which resolved upon cessation of all medications. A 65-year-old woman was treated with extended-release verapamil 240 mg/d. After the addition of clonidine 0.15 mg bid she developed complete AV block, which resolved after all therapy was stopped. DISCUSSION: An adverse interaction between clonidine and verapamil has not been reported previously. We describe two such cases and discuss the various mechanisms that might cause such an interaction. Clinicians should be acquainted with this possibly fatal interaction between two commonly used antihypertensive drugs. CONCLUSIONS: Caution is recommended in combining clonidine and verapamil therapy, even in patients who do not have sinus or AV node dysfunction. The two drugs may act synergistically on both the AV node and the peripheral circulation.
7949506	28	37	clonidine	Chemical	D003000
7949506	42	51	verapamil	Chemical	D014700
7949506	126	135	clonidine	Chemical	D003000
7949506	140	149	verapamil	Chemical	D014700
7949506	163	190	atrioventricular (AV) block	Disease	D054537
7949506	219	230	hypotension	Disease	D007022
7949506	288	306	hyperaldosteronism	Disease	D006929
7949506	324	333	verapamil	Chemical	D014700
7949506	347	361	spironolactone	Chemical	D013148
7949506	412	421	clonidine	Chemical	D003000
7949506	460	468	AV block	Disease	D054537
7949506	480	491	hypotension	Disease	D007022
7949506	597	606	verapamil	Chemical	D014700
7949506	639	648	clonidine	Chemical	D003000
7949506	684	692	AV block	Disease	D054537
7949506	783	792	clonidine	Chemical	D003000
7949506	797	806	verapamil	Chemical	D014700
7949506	1109	1118	clonidine	Chemical	D003000
7949506	1123	1132	verapamil	Chemical	D014700
7949506	CID	D014700	D007022
7949506	CID	D014700	D054537
7949506	CID	D003000	D054537
7949506	CID	D003000	D007022

7967231|t|Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.
7967231|a|S-312, S-312-d, but not S-312-l, L-type calcium channel antagonists, showed anticonvulsant effects on the audiogenic tonic convulsions in DBA/2 mice; and their ED50 values were 18.4 (12.8-27.1) mg/kg, p.o. and 15.0 (10.2-23.7) mg/kg, p.o., respectively, while that of flunarizine was 34.0 (26.0-44.8) mg/kg, p.o. Although moderate anticonvulsant effects of S-312-d in higher doses were observed against the clonic convulsions induced by pentylenetetrazole (85 mg/kg, s.c.) or bemegride (40 mg/kg, s.c.), no effects were observed in convulsions induced by N-methyl-D-aspartate, picrotoxin, or electroshock in Slc:ddY mice. S-312-d may be useful in the therapy of certain types of human epilepsy.
7967231	33	62	dihydrothienopyridine calcium	Chemical	-1
7967231	75	82	S-312-d	Chemical	C059447
7967231	135	140	S-312	Chemical	C059447
7967231	142	149	S-312-d	Chemical	C059447
7967231	159	166	S-312-l	Chemical	-1
7967231	175	182	calcium	Chemical	D002118
7967231	241	269	audiogenic tonic convulsions	Disease	D020195
7967231	403	414	flunarizine	Chemical	D005444
7967231	492	499	S-312-d	Chemical	C059447
7967231	549	560	convulsions	Disease	D012640
7967231	572	590	pentylenetetrazole	Chemical	D010433
7967231	611	620	bemegride	Chemical	D001534
7967231	667	678	convulsions	Disease	D012640
7967231	690	710	N-methyl-D-aspartate	Chemical	D016202
7967231	712	722	picrotoxin	Chemical	D010852
7967231	757	764	S-312-d	Chemical	C059447
7967231	820	828	epilepsy	Disease	D004827
7967231	CID	D010852	D012640
7967231	CID	D010433	D012640
7967231	CID	D001534	D012640

8096565|t|Transmural myocardial infarction with sumatriptan.
8096565|a|For sumatriptan, tightness in the chest caused by an unknown mechanism has been reported in 3-5% of users. We describe a 47-year-old woman with an acute myocardial infarction after administration of sumatriptan 6 mg subcutaneously for cluster headache. The patient had no history of underlying ischaemic heart disease or Prinzmetal's angina. She recovered without complications.
8096565	11	32	myocardial infarction	Disease	D009203
8096565	38	49	sumatriptan	Chemical	D018170
8096565	55	66	sumatriptan	Chemical	D018170
8096565	204	225	myocardial infarction	Disease	D009203
8096565	250	261	sumatriptan	Chemical	D018170
8096565	286	302	cluster headache	Disease	D003027
8096565	345	368	ischaemic heart disease	Disease	D017202
8096565	372	391	Prinzmetal's angina	Disease	D000788
8096565	CID	D018170	D009203

8135424|t|Flumazenil induces seizures and death in mixed cocaine-diazepam intoxications.
8135424|a|STUDY HYPOTHESIS: Administration of the benzodiazepine antagonist flumazenil may unmask seizures in mixed cocaine-benzodiazepine intoxication. DESIGN: Male Sprague-Dawley rats received 100 mg/kg cocaine IP alone, 5 mg/kg diazepam alone, or a combination of diazepam and cocaine. Three minutes later, groups were challenged with vehicle or flumazenil 5 or 10 mg/kg IP. Animal behavior, seizures (time to and incidence), death (time to and incidence), and cortical EEG tracings were recorded. INTERVENTIONS: Administration of flumazenil to animals after they had received a combination dose of cocaine and diazepam. RESULTS: In group 1, animals received cocaine followed by vehicle. This resulted in 100% developing seizures and death. Group 2 received diazepam alone followed by vehicle. Animals became somnolent and none died. Group 3 received diazepam followed by 5 mg/kg flumazenil. Animals became somnolent after diazepam and then active after flumazenil administration. In group 4, a combination of cocaine and diazepam was administered simultaneously. This resulted in no overt or EEG-detectable seizures and a 50% incidence of death. Group 5 received a similar combination of cocaine and diazepam, followed later by 5 mg/kg flumazenil. This resulted in an increased incidence of seizures, 90% (P < .01), and death, 100% (P < or = .01), compared with group 4. Group 6 received cocaine and diazepam followed by 10 mg/kg flumazenil. This also resulted in an increased incidence of seizures, 90% (P < or = .01), and death, 90% (P < or = .05), compared with group 4. CONCLUSION: Flumazenil can unmask seizures and increase the incidence of death in a model of combined cocaine-diazepam intoxications.
8135424	0	10	Flumazenil	Chemical	D005442
8135424	19	27	seizures	Disease	D012640
8135424	47	54	cocaine	Chemical	D003042
8135424	55	63	diazepam	Chemical	D003975
8135424	119	133	benzodiazepine	Chemical	D001569
8135424	145	155	flumazenil	Chemical	D005442
8135424	167	175	seizures	Disease	D012640
8135424	185	192	cocaine	Chemical	D003042
8135424	193	207	benzodiazepine	Chemical	D001569
8135424	274	281	cocaine	Chemical	D003042
8135424	300	308	diazepam	Chemical	D003975
8135424	336	344	diazepam	Chemical	D003975
8135424	349	356	cocaine	Chemical	D003042
8135424	418	428	flumazenil	Chemical	D005442
8135424	464	472	seizures	Disease	D012640
8135424	603	613	flumazenil	Chemical	D005442
8135424	671	678	cocaine	Chemical	D003042
8135424	683	691	diazepam	Chemical	D003975
8135424	731	738	cocaine	Chemical	D003042
8135424	793	801	seizures	Disease	D012640
8135424	830	838	diazepam	Chemical	D003975
8135424	923	931	diazepam	Chemical	D003975
8135424	952	962	flumazenil	Chemical	D005442
8135424	995	1003	diazepam	Chemical	D003975
8135424	1026	1036	flumazenil	Chemical	D005442
8135424	1082	1089	cocaine	Chemical	D003042
8135424	1094	1102	diazepam	Chemical	D003975
8135424	1180	1188	seizures	Disease	D012640
8135424	1261	1268	cocaine	Chemical	D003042
8135424	1273	1281	diazepam	Chemical	D003975
8135424	1309	1319	flumazenil	Chemical	D005442
8135424	1364	1372	seizures	Disease	D012640
8135424	1461	1468	cocaine	Chemical	D003042
8135424	1473	1481	diazepam	Chemical	D003975
8135424	1503	1513	flumazenil	Chemical	D005442
8135424	1563	1571	seizures	Disease	D012640
8135424	1659	1669	Flumazenil	Chemical	D005442
8135424	1681	1689	seizures	Disease	D012640
8135424	1749	1756	cocaine	Chemical	D003042
8135424	1757	1765	diazepam	Chemical	D003975
8135424	CID	D003975	D012640
8135424	CID	D005442	D012640
8135424	CID	D003042	D012640

8160791|t|Mechanisms for protective effects of free radical scavengers on gentamicin-mediated nephropathy in rats.
8160791|a|Studies were performed to examine the mechanisms for the protective effects of free radical scavengers on gentamicin (GM)-mediated nephropathy. Administration of GM at 40 mg/kg sc for 13 days to rats induced a significant reduction in renal blood flow (RBF) and inulin clearance (CIn) as well as marked tubular damage. A significant reduction in urinary guanosine 3',5'-cyclic monophosphate (cGMP) excretion and a significant increase in renal cortical renin and endothelin-1 contents were also observed in GM-mediated nephropathy. Superoxide dismutase (SOD) or dimethylthiourea (DMTU) significantly lessened the GM-induced decrement in CIn. The SOD-induced increase in glomerular filtration rate was associated with a marked improvement in RBF, an increase in urinary cGMP excretion, and a decrease in renal renin and endothelin-1 content. SOD did not attenuate the tubular damage. In contrast, DMTU significantly reduced the tubular damage and lipid peroxidation, but it did not affect renal hemodynamics and vasoactive substances. Neither SOD nor DMTU affected the renal cortical GM content in GM-treated rats. These results suggest that 1) both SOD and DMTU have protective effects on GM-mediated nephropathy, 2) the mechanisms for the protective effects differ for SOD and DMTU, and 3) superoxide anions play a critical role in GM-induced renal vasoconstriction.
8160791	64	74	gentamicin	Chemical	D005839
8160791	84	95	nephropathy	Disease	D007674
8160791	211	221	gentamicin	Chemical	D005839
8160791	223	225	GM	Chemical	D005839
8160791	236	247	nephropathy	Disease	D007674
8160791	267	269	GM	Chemical	D005839
8160791	408	422	tubular damage	Disease	D007674
8160791	459	495	guanosine 3',5'-cyclic monophosphate	Chemical	D006152
8160791	497	501	cGMP	Chemical	D006152
8160791	612	614	GM	Chemical	D005839
8160791	624	635	nephropathy	Disease	D007674
8160791	637	647	Superoxide	Chemical	D013481
8160791	667	683	dimethylthiourea	Chemical	C038983
8160791	685	689	DMTU	Chemical	C038983
8160791	718	720	GM	Chemical	D005839
8160791	874	878	cGMP	Chemical	D006152
8160791	972	986	tubular damage	Disease	D007674
8160791	1001	1005	DMTU	Chemical	C038983
8160791	1032	1046	tubular damage	Disease	D007674
8160791	1155	1159	DMTU	Chemical	C038983
8160791	1188	1190	GM	Chemical	D005839
8160791	1202	1204	GM	Chemical	D005839
8160791	1262	1266	DMTU	Chemical	C038983
8160791	1294	1296	GM	Chemical	D005839
8160791	1306	1317	nephropathy	Disease	D007674
8160791	1383	1387	DMTU	Chemical	C038983
8160791	1396	1406	superoxide	Chemical	D013481
8160791	1438	1440	GM	Chemical	D005839
8160791	CID	D005839	D007674

8184922|t|Assessment of cardiomyocyte DNA synthesis during hypertrophy in adult mice.
8184922|a|The ability of cardiomyocytes to synthesize DNA in response to experimentally induced cardiac hypertrophy was assessed in adult mice. Isoproterenol delivered by osmotic minipump implantation in adult C3Heb/FeJ mice resulted in a 46% increase in heart weight and a 19.3% increase in cardiomyocyte area. No DNA synthesis, as assessed by autoradiographic analysis of isolated cardiomyocytes, was observed in control or hypertrophic hearts. A survey of 15 independent inbred strains of mice revealed that ventricular cardiomyocyte nuclear number ranged from 3 to 13% mononucleate, suggesting that cardiomyocyte terminal differentiation is influenced directly or indirectly by genetic background. To determine whether the capacity for reactive DNA synthesis was also subject to genetic regulation, cardiac hypertrophy was induced in the strains of mice comprising the extremes of the nuclear number survey. These data indicate that adult mouse atrial and ventricular cardiomyocytes do not synthesize DNA in response to isoproterenol-induced cardiac hypertrophy.
8184922	49	60	hypertrophy	Disease	D006984
8184922	162	181	cardiac hypertrophy	Disease	D006332
8184922	210	223	Isoproterenol	Chemical	D007545
8184922	492	511	hypertrophic hearts	Disease	D006332
8184922	869	888	cardiac hypertrophy	Disease	D006332
8184922	1090	1103	isoproterenol	Chemical	D007545
8184922	1112	1131	cardiac hypertrophy	Disease	D006332
8184922	CID	D007545	D006332

8188982|t|Central cardiovascular effects of AVP and ANP in normotensive and spontaneously hypertensive rats.
8188982|a|The purpose of the present study was to compare influence of central arginine vasopressin (AVP) and of atrial natriuretic peptide (ANP) on control of arterial blood pressure (MAP) and heart rate (HR) in normotensive (WKY) and spontaneously hypertensive (SHR) rats. Three series of experiments were performed on 30 WKY and 30 SHR, chronically instrumented with guide tubes in the lateral ventricle (LV) and arterial and venous catheters. MAP and HR were monitored before and after i.v. injections of either vehicle or 1, 10 and 50 ng of AVP and 25, 125 and 500 ng of ANP. Sensitivity of cardiac component of baroreflex (CCB), expressed as a slope of the regression line was determined from relationships between systolic arterial pressure (SAP) and HR period (HRp) during phenylephrine (Phe)-induced hypertension and sodium nitroprusside (SN)-induced hypotension. CCB was measured before and after administration of either vehicle, AVP, ANP, or both peptides together. Increases of MAP occurred after LV administration of 1, 10 and 50 ng of AVP in WKY and of 10 and 50 ng in SHR. ANP did not cause significant changes in MAP in both strains as compared to vehicle, but it abolished AVP-induced MAP increase in WKY and SHR. CCB was reduced in WKY and SHR after LV administration of AVP during SN-induced hypotension. In SHR but not in WKY administration of ANP, AVP and ANP + AVP decreased CCB during Phe-induced MAP elevation. The results indicate that centrally applied AVP and ANP exert differential effects on blood pressure and baroreflex control of heart rate in WKY and SHR and suggest interaction of these two peptides in blood pressure regulation at the level of central nervous system.
8188982	34	37	AVP	Chemical	D001127
8188982	80	92	hypertensive	Disease	D006973
8188982	168	188	arginine vasopressin	Chemical	D001127
8188982	190	193	AVP	Chemical	D001127
8188982	339	351	hypertensive	Disease	D006973
8188982	635	638	AVP	Chemical	D001127
8188982	870	883	phenylephrine	Chemical	D010656
8188982	885	888	Phe	Chemical	D010656
8188982	898	910	hypertension	Disease	D006973
8188982	915	935	sodium nitroprusside	Chemical	D009599
8188982	937	939	SN	Chemical	D009599
8188982	949	960	hypotension	Disease	D007022
8188982	1030	1033	AVP	Chemical	D001127
8188982	1139	1142	AVP	Chemical	D001127
8188982	1280	1283	AVP	Chemical	D001127
8188982	1379	1382	AVP	Chemical	D001127
8188982	1390	1392	SN	Chemical	D009599
8188982	1401	1412	hypotension	Disease	D007022
8188982	1459	1462	AVP	Chemical	D001127
8188982	1473	1476	AVP	Chemical	D001127
8188982	1498	1501	Phe	Chemical	D010656
8188982	1569	1572	AVP	Chemical	D001127
8188982	CID	D010656	D006973
8188982	CID	D009599	D007022
8188982	CID	D001127	D006973

8308951|t|Cutaneous exposure to warfarin-like anticoagulant causing an intracerebral hemorrhage: a case report.
8308951|a|A case of intercerebral hematoma due to warfarin-induced coagulopathy is presented. The 39-year-old woman had spread a warfarin-type rat poison around her house weekly using her bare hands, with no washing post application. Percutaneous absorption of warfarin causing coagulopathy, reported three times in the past, is a significant risk if protective measures, such as gloves, are not used. An adverse drug interaction with piroxicam, which she took occasionally, may have exacerbated the coagulopathy.
8308951	22	30	warfarin	Chemical	D014859
8308951	61	85	intracerebral hemorrhage	Disease	D002543
8308951	126	134	hematoma	Disease	D006406
8308951	142	150	warfarin	Chemical	D014859
8308951	159	171	coagulopathy	Disease	D001778
8308951	221	229	warfarin	Chemical	D014859
8308951	353	361	warfarin	Chemical	D014859
8308951	370	382	coagulopathy	Disease	D001778
8308951	527	536	piroxicam	Chemical	D010894
8308951	592	604	coagulopathy	Disease	D001778
8308951	CID	D014859	D002543

8312343|t|Pediatric heart transplantation without chronic maintenance steroids.
8312343|a|From 1986 to February 1993, 40 children aged 2 months to 18 years (average age 10.4 +/- 5.8 years) underwent heart transplantation. Indications for transplantation were idiopathic cardiomyopathy (52%), congenital heart disease (35%) with and without prior repair (71% and 29%, respectively), hypertrophic cardiomyopathy (5%), valvular heart disease (3%), and doxorubicin cardiomyopathy (5%). Patients were managed with cyclosporine and azathioprine. No prophylaxis with antilymphocyte globulin was used. Steroids were given to 39% of patients for refractory rejection, but weaning was always attempted and generally successful (64%). Five patients (14%) received maintenance steroids. Four patients died in the perioperative period and one died 4 months later. There have been no deaths related to rejection or infection. Average follow-up was 36 +/- 19 months (range 1 to 65 months). Cumulative survival is 88% at 5 years. In patients less than 7 years of age, rejection was monitored noninvasively. In the first postoperative month, 89% of patients were treated for rejection. Freedom from serious infections was 83% at 1 month and 65% at 1 year. Cytomegalovirus infections were treated successfully with ganciclovir in 11 patients. No impairment of growth was observed in children who underwent transplantation compared with a control population. Twenty-one patients (60%) have undergone annual catheterizations and no sign of graft atherosclerosis has been observed. Seizures occurred in five patients (14%) and hypertension was treated in 10 patients (28%). No patient was disabled and no lymphoproliferative disorder was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
8312343	60	68	steroids	Chemical	D013256
8312343	239	264	idiopathic cardiomyopathy	Disease	D002311
8312343	272	296	congenital heart disease	Disease	D006331
8312343	362	389	hypertrophic cardiomyopathy	Disease	D002312
8312343	396	418	valvular heart disease	Disease	D006349
8312343	429	440	doxorubicin	Chemical	D004317
8312343	441	455	cardiomyopathy	Disease	D009202
8312343	489	501	cyclosporine	Chemical	D016572
8312343	506	518	azathioprine	Chemical	D001379
8312343	574	582	Steroids	Chemical	D013256
8312343	745	753	steroids	Chemical	D013256
8312343	881	890	infection	Disease	D007239
8312343	1170	1180	infections	Disease	D007239
8312343	1219	1245	Cytomegalovirus infections	Disease	D003586
8312343	1277	1288	ganciclovir	Chemical	D015774
8312343	1506	1521	atherosclerosis	Disease	D050197
8312343	1541	1549	Seizures	Disease	D012640
8312343	1586	1598	hypertension	Disease	D006973
8312343	1664	1692	lymphoproliferative disorder	Disease	D008232
8312343	CID	D004317	D009202

8312983|t|Delirium during fluoxetine treatment. A case report.
8312983|a|The correlation between high serum tricyclic antidepressant concentrations and central nervous system side effects has been well established. Only a few reports exist, however, on the relationship between the serum concentrations of selective serotonin reuptake inhibitors (SSRIs) and their toxic effects. In some cases, a high serum concentration of citalopram (> 600 nmol/L) in elderly patients has been associated with increased somnolence and movement difficulties. Widespread cognitive disorders, such as delirium, have not been previously linked with high blood levels of SSRIs. In this report, we describe a patient with acute hyperkinetic delirium connected with a high serum total fluoxetine (fluoxetine plus desmethylfluoxetine) concentration.
8312983	0	8	Delirium	Disease	D003693
8312983	16	26	fluoxetine	Chemical	D005473
8312983	296	305	serotonin	Chemical	D012701
8312983	404	414	citalopram	Chemical	D015283
8312983	485	495	somnolence	Disease	D006970
8312983	500	521	movement difficulties	Disease	D020820
8312983	534	553	cognitive disorders	Disease	D003072
8312983	563	571	delirium	Disease	D003693
8312983	687	699	hyperkinetic	Disease	D006948
8312983	700	708	delirium	Disease	D003693
8312983	743	753	fluoxetine	Chemical	D005473
8312983	755	765	fluoxetine	Chemical	D005473
8312983	771	790	desmethylfluoxetine	Chemical	C036139
8312983	CID	D005473	D006948
8312983	CID	D005473	D003693

8318674|t|Pulmonary edema and shock after high-dose aracytine-C for lymphoma; possible role of TNF-alpha and PAF.
8318674|a|Four out of 23 consecutive patients treated with high-dose Ara-C for lymphomas in our institution developed a strikingly similar syndrome during the perfusion. It was characterized by the onset of fever, diarrhea, shock, pulmonary edema, acute renal failure, metabolic acidosis, weight gain and leukocytosis. Thorough bacteriological screening failed to provide evidence of infection. Sequential biological assays of IL-1, IL-2, TNF and PAF were performed during Ara-C infusion to ten patients, including the four who developed the syndrome. TNF and PAF activity was found in the serum of respectively two and four of the cases, but not in the six controls. As TNF and PAF are thought to be involved in the development of septic shock and adult respiratory distress syndrome, we hypothesize that high-dose Ara-C may be associated with cytokine release.
8318674	0	15	Pulmonary edema	Disease	D011654
8318674	20	25	shock	Disease	D012769
8318674	42	53	aracytine-C	Chemical	D003561
8318674	58	66	lymphoma	Disease	D008223
8318674	163	168	Ara-C	Chemical	D003561
8318674	173	182	lymphomas	Disease	D008223
8318674	301	306	fever	Disease	D005334
8318674	308	316	diarrhea	Disease	D003967
8318674	318	323	shock	Disease	D012769
8318674	325	340	pulmonary edema	Disease	D011654
8318674	342	361	acute renal failure	Disease	D058186
8318674	363	381	metabolic acidosis	Disease	D000138
8318674	383	394	weight gain	Disease	D015430
8318674	399	411	leukocytosis	Disease	D007964
8318674	478	487	infection	Disease	D007239
8318674	567	572	Ara-C	Chemical	D003561
8318674	833	838	shock	Disease	D012769
8318674	843	878	adult respiratory distress syndrome	Disease	D012128
8318674	910	915	Ara-C	Chemical	D003561
8318674	CID	D003561	D003967
8318674	CID	D003561	D005334
8318674	CID	D003561	D011654
8318674	CID	D003561	D058186
8318674	CID	D003561	D015430
8318674	CID	D003561	D012769
8318674	CID	D003561	D007964
8318674	CID	D003561	D000138

8392553|t|Protective effect of clentiazem against epinephrine-induced cardiac injury in rats.
8392553|a|We investigated the effects of clentiazem, a 1,5-benzothiazepine calcium antagonist, on epinephrine-induced cardiomyopathy in rats. With 2-week chronic epinephrine infusion, 16 of 30 rats died within 4 days, and severe ischemic lesions and fibrosis of the left ventricles were observed. In epinephrine-treated rats, left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced, but responses to calcium were normal or enhanced compared to controls. Left ventricular alpha and beta adrenoceptor densities were also reduced compared to controls. Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner. Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol. On the other hand clentiazem did not prevent epinephrine-induced down-regulation of alpha and beta adrenoceptors. Interestingly, clentiazem, infused alone, resulted in decreased adrenergic receptor densities in the left ventricle. Clentiazem also did not prevent the enhanced responses to calcium seen in the epinephrine-treated animals, although the high dose of clentiazem partially attenuated the maximal response to calcium compared to epinephrine-treated animals. In conclusion, clentiazem attenuated epinephrine-induced cardiac injury, possibly through its effect on the adrenergic pathway.
8392553	21	31	clentiazem	Chemical	C056595
8392553	40	51	epinephrine	Chemical	D004837
8392553	60	74	cardiac injury	Disease	D006331
8392553	115	125	clentiazem	Chemical	C056595
8392553	129	148	1,5-benzothiazepine	Chemical	C106746
8392553	149	156	calcium	Chemical	D002118
8392553	172	183	epinephrine	Chemical	D004837
8392553	192	206	cardiomyopathy	Disease	D009202
8392553	236	247	epinephrine	Chemical	D004837
8392553	303	319	ischemic lesions	Disease	D007511
8392553	324	332	fibrosis	Disease	D005355
8392553	374	385	epinephrine	Chemical	D004837
8392553	475	488	isoproterenol	Chemical	D007545
8392553	520	527	calcium	Chemical	D002118
8392553	684	694	clentiazem	Chemical	C056595
8392553	705	716	epinephrine	Chemical	D004837
8392553	773	789	ischemic lesions	Disease	D007511
8392553	794	802	fibrosis	Disease	D005355
8392553	907	920	isoproterenol	Chemical	D007545
8392553	978	988	clentiazem	Chemical	C056595
8392553	1014	1025	epinephrine	Chemical	D004837
8392553	1027	1037	clentiazem	Chemical	C056595
8392553	1122	1135	isoproterenol	Chemical	D007545
8392553	1155	1165	clentiazem	Chemical	C056595
8392553	1182	1193	epinephrine	Chemical	D004837
8392553	1266	1276	clentiazem	Chemical	C056595
8392553	1368	1378	Clentiazem	Chemical	C056595
8392553	1426	1433	calcium	Chemical	D002118
8392553	1446	1457	epinephrine	Chemical	D004837
8392553	1501	1511	clentiazem	Chemical	C056595
8392553	1557	1564	calcium	Chemical	D002118
8392553	1577	1588	epinephrine	Chemical	D004837
8392553	1621	1631	clentiazem	Chemical	C056595
8392553	1643	1654	epinephrine	Chemical	D004837
8392553	1663	1677	cardiac injury	Disease	D006331
8392553	CID	D004837	D009202

8511251|t|Cocaine induced myocardial ischemia.
8511251|a|We report a case of myocardial ischemia induced by cocaine. The ischemia probably induced by coronary artery spasm was reversed by nitroglycerin and calcium blocking agents.
8511251	0	7	Cocaine	Chemical	D003042
8511251	16	35	myocardial ischemia	Disease	D017202
8511251	57	76	myocardial ischemia	Disease	D017202
8511251	88	95	cocaine	Chemical	D003042
8511251	101	109	ischemia	Disease	D007511
8511251	130	151	coronary artery spasm	Disease	D003329
8511251	168	181	nitroglycerin	Chemical	D005996
8511251	186	193	calcium	Chemical	D002118
8511251	CID	D003042	D017202
8511251	CID	D003042	D003329

8603459|t|Doxorubicin-induced cardiotoxicity monitored by ECG in freely moving mice. A new model to test potential protectors.
8603459|a|In laboratory animals, histology is most commonly used to study doxorubicin-induced cardiotoxicity. However, for monitoring during treatment, large numbers of animals are needed. Recently we developed a new method to measure ECG values in freely moving mice by telemetry. With this model we investigated the effect of chronic doxorubicin administration on the ECG of freely moving BALB/c mice and the efficacy of ICRF-187 as a protective agent. The ST interval significantly widened from 15.0 +/- 1.5 to 56.8 +/- 11.8 ms in week 10 (7 weekly doses of 4 mg/kg doxorubicin given i.v. plus 3 weeks of observation). The ECG of the control animals did not change during the entire study. After sacrifice the hearts of doxorubicin-treated animals were enlarged and the atria were hypertrophic. As this schedule exerted more toxicity than needed to investigate protective agents, the protection of ICRF-187 was determined using a dose schedule with lower general toxicity (6 weekly doses of 4 mg/kg doxorubicin given i.v. plus 2 weeks of observation). On this schedule, the animals' hearts appeared normal after sacrifice and ICRF-187 (50 mg/kg given i.p. 1 h before doxorubicin) provided almost full protection. These data were confirmed by histology. The results indicate that this new model is very sensitive and enables monitoring of the development of cardiotoxicity with time. These findings result in a model that allows the testing of protectors against doxorubicin-induced cardiotoxicity as demonstrated by the protection provided by ICRF-187.
8603459	0	11	Doxorubicin	Chemical	D004317
8603459	20	34	cardiotoxicity	Disease	D066126
8603459	181	192	doxorubicin	Chemical	D004317
8603459	201	215	cardiotoxicity	Disease	D066126
8603459	443	454	doxorubicin	Chemical	D004317
8603459	530	538	ICRF-187	Chemical	D064730
8603459	676	687	doxorubicin	Chemical	D004317
8603459	830	841	doxorubicin	Chemical	D004317
8603459	891	903	hypertrophic	Disease	D006984
8603459	935	943	toxicity	Disease	D064420
8603459	1008	1016	ICRF-187	Chemical	D064730
8603459	1073	1081	toxicity	Disease	D064420
8603459	1109	1120	doxorubicin	Chemical	D004317
8603459	1236	1244	ICRF-187	Chemical	D064730
8603459	1277	1288	doxorubicin	Chemical	D004317
8603459	1467	1481	cardiotoxicity	Disease	D066126
8603459	1572	1583	doxorubicin	Chemical	D004317
8603459	1592	1606	cardiotoxicity	Disease	D066126
8603459	1653	1661	ICRF-187	Chemical	D064730
8603459	CID	D004317	D066126

8659767|t|Epinephrine dysrhythmogenicity is not enhanced by subtoxic bupivacaine in dogs.
8659767|a|Since bupivacaine and epinephrine may both precipitate dysrhythmias, circulating bupivacaine during regional anesthesia could potentiate dysrhythmogenic effects of epinephrine. We therefore examined whether bupivacaine alters the dysrhythmogenicity of subsequent administration of epinephrine in conscious, healthy dogs and in anesthetized dogs with myocardial infarction. Forty-one conscious dogs received 10 micrograms.kg-1.min-1 epinephrine. Seventeen animals responded with ventricular tachycardia (VT) within 3 min. After 3 h, these responders randomly received 1 or 2 mg/kg bupivacaine or saline over 5 min, followed by 10 micrograms.kg-1.min-1 epinephrine. In the bupivacaine groups, epinephrine caused fewer prodysrhythmic effects than without bupivacaine. VT appeared in fewer dogs and at a later time, and there were more sinoatrial beats and less ectopies. Epinephrine shortened QT less after bupivacaine than in control animals. One day after experimental myocardial infarction, six additional halothane-anesthetized dogs received 4 micrograms.kg-1.min-1 epinephrine until VT appeared. After 45 min, 1 mg/kg bupivacaine was injected over 5 min, again followed by 4 micrograms.kg-1.min-1 epinephrine. In these dogs, the prodysrhythmic response to epinephrine was also mitigated by preceding bupivacaine. Bupivacaine antagonizes epinephrine dysrhythmogenicity in conscious dogs susceptible to VT and in anesthetized dogs with spontaneous postinfarct dysrhythmias. There is no evidence that systemic subtoxic bupivacaine administration enhances the dysrhythmogenicity of subsequent epinephrine.
8659767	0	11	Epinephrine	Chemical	D004837
8659767	59	70	bupivacaine	Chemical	D002045
8659767	86	97	bupivacaine	Chemical	D002045
8659767	102	113	epinephrine	Chemical	D004837
8659767	135	147	dysrhythmias	Disease	D001145
8659767	161	172	bupivacaine	Chemical	D002045
8659767	244	255	epinephrine	Chemical	D004837
8659767	287	298	bupivacaine	Chemical	D002045
8659767	361	372	epinephrine	Chemical	D004837
8659767	430	451	myocardial infarction	Disease	D009203
8659767	512	523	epinephrine	Chemical	D004837
8659767	558	581	ventricular tachycardia	Disease	D017180
8659767	583	585	VT	Disease	D017180
8659767	660	671	bupivacaine	Chemical	D002045
8659767	731	742	epinephrine	Chemical	D004837
8659767	751	762	bupivacaine	Chemical	D002045
8659767	771	782	epinephrine	Chemical	D004837
8659767	832	843	bupivacaine	Chemical	D002045
8659767	845	847	VT	Disease	D017180
8659767	948	959	Epinephrine	Chemical	D004837
8659767	984	995	bupivacaine	Chemical	D002045
8659767	1048	1069	myocardial infarction	Disease	D009203
8659767	1086	1095	halothane	Chemical	D006221
8659767	1147	1158	epinephrine	Chemical	D004837
8659767	1165	1167	VT	Disease	D017180
8659767	1200	1211	bupivacaine	Chemical	D002045
8659767	1279	1290	epinephrine	Chemical	D004837
8659767	1338	1349	epinephrine	Chemical	D004837
8659767	1382	1393	bupivacaine	Chemical	D002045
8659767	1395	1406	Bupivacaine	Chemical	D002045
8659767	1419	1430	epinephrine	Chemical	D004837
8659767	1483	1485	VT	Disease	D017180
8659767	1540	1552	dysrhythmias	Disease	D001145
8659767	1598	1609	bupivacaine	Chemical	D002045
8659767	1671	1682	epinephrine	Chemical	D004837
8659767	CID	D004837	D017180

8667442|t|Milk-alkali syndrome induced by 1,25(OH)2D in a patient with hypoparathyroidism.
8667442|a|Milk-alkali syndrome was first described 70 years ago in the context of the treatment of peptic ulcer disease with large amounts of calcium and alkali. Although with current ulcer therapy (H-2 blockers, omeprazole, and sucralfate), the frequency of milk-alkali syndrome has decreased significantly, the classic triad of hypercalcemia, alkalosis, and renal impairment remains the hallmark of the syndrome. Milk-alkali syndrome can present serious and occasionally life-threatening illness unless diagnosed and treated appropriately. This article presents a patient with hypoparathyroidism who was treated with calcium carbonate and calcitriol resulting in two admissions to the hospital for milk-alkali syndrome. The patient was successfully treated with intravenous pamidronate on his first admission and with hydrocortisone on the second. This illustrates intravenous pamidronate as a valuable therapeutic tool when milk-alkali syndrome presents as hypercalcemic emergency.
8667442	0	20	Milk-alkali syndrome	Disease	D006934
8667442	32	42	1,25(OH)2D	Chemical	D002117
8667442	61	79	hypoparathyroidism	Disease	D007011
8667442	81	101	Milk-alkali syndrome	Disease	D006934
8667442	170	190	peptic ulcer disease	Disease	D010437
8667442	213	220	calcium	Chemical	D002118
8667442	225	231	alkali	Chemical	D000468
8667442	255	260	ulcer	Disease	D014456
8667442	284	294	omeprazole	Chemical	D009853
8667442	300	310	sucralfate	Chemical	D013392
8667442	330	350	milk-alkali syndrome	Disease	D006934
8667442	401	414	hypercalcemia	Disease	D006934
8667442	416	425	alkalosis	Disease	D000471
8667442	431	447	renal impairment	Disease	D051437
8667442	486	506	Milk-alkali syndrome	Disease	D006934
8667442	650	668	hypoparathyroidism	Disease	D007011
8667442	690	707	calcium carbonate	Chemical	D002119
8667442	712	722	calcitriol	Chemical	D002117
8667442	771	791	milk-alkali syndrome	Disease	D006934
8667442	847	858	pamidronate	Chemical	C019248
8667442	891	905	hydrocortisone	Chemical	D006854
8667442	950	961	pamidronate	Chemical	C019248
8667442	998	1018	milk-alkali syndrome	Disease	D006934
8667442	1031	1054	hypercalcemic emergency	Disease	D006934
8667442	CID	D002117	D051437
8667442	CID	D013392	D010437
8667442	CID	D002118	D000471
8667442	CID	D000468	D051437
8667442	CID	D000468	D000471
8667442	CID	D002119	D000471
8667442	CID	D009853	D010437
8667442	CID	D002117	D006934
8667442	CID	D000468	D006934
8667442	CID	D002117	D000471
8667442	CID	D002118	D006934
8667442	CID	D002119	D006934
8667442	CID	D002119	D051437
8667442	CID	D002118	D051437

8748050|t|Encephalopathy during amitriptyline therapy: are neuroleptic malignant syndrome and serotonin syndrome spectrum disorders?
8748050|a|This report describes a case of encephalopathy developed in the course of amitriptyline therapy, during a remission of unipolar depression. This patient could have been diagnosed as having either neuroleptic malignant syndrome (NMS) or serotonin syndrome (SS). The major determinant of the symptoms may have been dopamine/serotonin imbalance in the central nervous system. The NMS-like encephalopathy that develops in association with the use of antidepressants indicates that NMS and SS are spectrum disorders induced by drugs with both antidopaminergic and serotonergic effects.
8748050	0	14	Encephalopathy	Disease	D001927
8748050	22	35	amitriptyline	Chemical	D000639
8748050	49	79	neuroleptic malignant syndrome	Disease	D009459
8748050	84	102	serotonin syndrome	Disease	D020230
8748050	155	169	encephalopathy	Disease	D001927
8748050	197	210	amitriptyline	Chemical	D000639
8748050	242	261	unipolar depression	Disease	D003866
8748050	319	349	neuroleptic malignant syndrome	Disease	D009459
8748050	351	354	NMS	Disease	D009459
8748050	359	377	serotonin syndrome	Disease	D020230
8748050	379	381	SS	Disease	D020230
8748050	436	444	dopamine	Chemical	D004298
8748050	445	454	serotonin	Chemical	D012701
8748050	500	503	NMS	Disease	D009459
8748050	509	523	encephalopathy	Disease	D001927
8748050	600	603	NMS	Disease	D009459
8748050	608	610	SS	Disease	D020230
8748050	CID	D000639	D001927

8755612|t|Genetic separation of tumor growth and hemorrhagic phenotypes in an estrogen-induced tumor.
8755612|a|Chronic administration of estrogen to the Fischer 344 (F344) rat induces growth of large, hemorrhagic pituitary tumors. Ten weeks of diethylstilbestrol (DES) treatment caused female F344 rat pituitaries to grow to an average of 109.2 +/- 6.3 mg (mean +/- SE) versus 11.3 +/- 1.4 mg for untreated rats, and to become highly hemorrhagic. The same DES treatment produced no significant growth (8.9 +/- 0.5 mg for treated females versus 8.7 +/- 1.1 for untreated females) or morphological changes in Brown Norway (BN) rat pituitaries. An F1 hybrid of F344 and BN exhibited significant pituitary growth after 10 weeks of DES treatment with an average mass of 26.3 +/- 0.7 mg compared with 8.6 +/- 0.9 mg for untreated rats. Surprisingly, the F1 hybrid tumors were not hemorrhagic and had hemoglobin content and outward appearance identical to that of BN. Expression of both growth and morphological changes is due to multiple genes. However, while DES-induced pituitary growth exhibited quantitative, additive inheritance, the hemorrhagic phenotype exhibited recessive, epistatic inheritance. Only 5 of the 160 F2 pituitaries exhibited the hemorrhagic phenotype; 36 of the 160 F2 pituitaries were in the F344 range of mass, but 31 of these were not hemorrhagic, indicating that the hemorrhagic phenotype is not merely a consequence of extensive growth. The hemorrhagic F2 pituitaries were all among the most massive, indicating that some of the genes regulate both phenotypes.
8755612	22	27	tumor	Disease	D009369
8755612	39	50	hemorrhagic	Disease	D006470
8755612	68	76	estrogen	Chemical	D004967
8755612	85	90	tumor	Disease	D009369
8755612	118	126	estrogen	Chemical	D004967
8755612	182	193	hemorrhagic	Disease	D006470
8755612	194	210	pituitary tumors	Disease	D010911
8755612	225	243	diethylstilbestrol	Chemical	D004054
8755612	245	248	DES	Chemical	D004054
8755612	415	426	hemorrhagic	Disease	D006470
8755612	437	440	DES	Chemical	D004054
8755612	708	711	DES	Chemical	D004054
8755612	839	845	tumors	Disease	D009369
8755612	855	866	hemorrhagic	Disease	D006470
8755612	1035	1038	DES	Chemical	D004054
8755612	1114	1125	hemorrhagic	Disease	D006470
8755612	1227	1238	hemorrhagic	Disease	D006470
8755612	1336	1347	hemorrhagic	Disease	D006470
8755612	1369	1380	hemorrhagic	Disease	D006470
8755612	1444	1455	hemorrhagic	Disease	D006470
8755612	CID	D004054	D010911

8808730|t|Increased expression of neuronal nitric oxide synthase in bladder afferent pathways following chronic bladder irritation.
8808730|a|Immunocytochemical techniques were used to examine alterations in the expression of neuronal nitric oxide synthase (NOS) in bladder pathways following acute and chronic irritation of the urinary tract of the rat. Chemical cystitis was induced by cyclophosphamide (CYP) which is metabolized to acrolein, an irritant eliminated in the urine. Injection of CYP (n = 10, 75 mg/kg, i.p.) 2 hours prior to perfusion (acute treatment) of the animals increased Fos-immunoreactivity (IR) in neurons in the dorsal commissure, dorsal horn, and autonomic regions of spinal segments (L1-L2 and L6-S1) which receive afferent inputs from the bladder, urethra, and ureter. Fos-IR in the spinal cord was not changed in rats receiving chronic CYP treatment (n = 15, 75 mg/kg, i.p., every 3rd day for 2 weeks). In control animals and in animals treated acutely with CYP, only small numbers of NOS-IR cells (0.5-0.7 cell profiles/sections) were detected in the L6-S1 dorsal root ganglia (DRG). Chronic CYP administration significantly (P < or = .002) increased bladder weight by 60% and increased (7- to 11-fold) the numbers of NOS-immunoreactive (IR) afferent neurons in the L6-S1 DRG. A small increase (1.5-fold) also occurred in the L1 DRG, but no change was detected in the L2 and L5 DRG. Bladder afferent cells in the L6-S1 DRG labeled by Fluorogold (40 microliters) injected into the bladder wall did not exhibit NOS-IR in control animals; however, following chronic CYP administration, a significant percentage of bladder afferent neurons were NOS-IR: L6 (19.8 +/- 4.6%) and S1 (25.3 +/- 2.9%). These results indicate that neuronal gene expression in visceral sensory pathways can be upregulated by chemical irritation of afferent receptors in the urinary tract and/or that pathological changes in the urinary tract can initiate chemical signals that alter the chemical properties of visceral afferent neurons.
8808730	33	45	nitric oxide	Chemical	D009569
8808730	102	120	bladder irritation	Disease	D001745
8808730	215	227	nitric oxide	Chemical	D009569
8808730	291	322	irritation of the urinary tract	Disease	D014570
8808730	344	352	cystitis	Disease	D003556
8808730	368	384	cyclophosphamide	Chemical	D003520
8808730	386	389	CYP	Chemical	D003520
8808730	415	423	acrolein	Chemical	D000171
8808730	475	478	CYP	Chemical	D003520
8808730	846	849	CYP	Chemical	D003520
8808730	968	971	CYP	Chemical	D003520
8808730	1103	1106	CYP	Chemical	D003520
8808730	1574	1577	CYP	Chemical	D003520
8808730	CID	D003520	D003556

8819482|t|Effects of a new calcium antagonist, CD-832, on isoproterenol-induced myocardial ischemia in dogs with partial coronary stenosis.
8819482|a|Effects of CD-832 on isoproterenol (ISO)-induced myocardial ischemia were studied in dogs with partial coronary stenosis of the left circumflex coronary artery and findings were compared with those for nifedipine or diltiazem. In the presence of coronary artery stenosis, 3-min periods of intracoronary ISO infusion (10 ng/kg/min) increased heart rate and maximal rate of left ventricular pressure rise, which resulted in a decrease in percentage segmental shortening and ST-segment elevation of the epicardial electrocardiogram. After the control ISO infusion with stenosis was performed, equihypotensive doses of CD-832 (3 and 10 micrograms/kg/min, n = 7), nifedipine (1 and 3 micrograms/kg/min, n = 9) or diltiazem (10 and 30 micrograms/kg/min, n = 7) were infused 5 min before and during the second and third ISO infusion. Both CD-832 and diltiazem, but not nifedipine, significantly reduced the increase in heart rate induced by ISO infusion. In contrast to nifedipine, CD-832 (10 micrograms/kg/min) prevented the decrease in percentage segmental shortening from 32 +/- 12% to 115 +/- 26% of the control value (P < .01) and ST-segment elevation from 5.6 +/- 1.0 mV to 1.6 +/- 1.3 mV (P < .01) at 3 min after ISO infusion with stenosis. Diltiazem (30 micrograms/kg/min) also prevented the decrease in percentage segmental shortening from 34 +/- 14% to 63 +/- 18% of the control value (P < .05) and ST-segment elevation from 4.7 +/- 0.7 mV to 2.1 +/- 0.7 mV (P < .01) at 3 min after ISO infusion with stenosis. These data show that CD-832 improves myocardial ischemia during ISO infusion with stenosis and suggest that the negative chronotropic property of CD-832 plays a major role in the beneficial effects of CD-832.
8819482	17	24	calcium	Chemical	D002118
8819482	37	43	CD-832	Chemical	C082828
8819482	48	61	isoproterenol	Chemical	D007545
8819482	70	89	myocardial ischemia	Disease	D017202
8819482	111	128	coronary stenosis	Disease	D023921
8819482	141	147	CD-832	Chemical	C082828
8819482	151	164	isoproterenol	Chemical	D007545
8819482	166	169	ISO	Chemical	D007545
8819482	179	198	myocardial ischemia	Disease	D017202
8819482	233	250	coronary stenosis	Disease	D023921
8819482	332	342	nifedipine	Chemical	D009543
8819482	346	355	diltiazem	Chemical	D004110
8819482	376	400	coronary artery stenosis	Disease	D023921
8819482	433	436	ISO	Chemical	D007545
8819482	678	681	ISO	Chemical	D007545
8819482	696	704	stenosis	Disease	D003251
8819482	745	751	CD-832	Chemical	C082828
8819482	789	799	nifedipine	Chemical	D009543
8819482	838	847	diltiazem	Chemical	D004110
8819482	943	946	ISO	Chemical	D007545
8819482	962	968	CD-832	Chemical	C082828
8819482	973	982	diltiazem	Chemical	D004110
8819482	992	1002	nifedipine	Chemical	D009543
8819482	1064	1067	ISO	Chemical	D007545
8819482	1093	1103	nifedipine	Chemical	D009543
8819482	1105	1111	CD-832	Chemical	C082828
8819482	1343	1346	ISO	Chemical	D007545
8819482	1361	1369	stenosis	Disease	D003251
8819482	1371	1380	Diltiazem	Chemical	D004110
8819482	1616	1619	ISO	Chemical	D007545
8819482	1634	1642	stenosis	Disease	D003251
8819482	1665	1671	CD-832	Chemical	C082828
8819482	1681	1700	myocardial ischemia	Disease	D017202
8819482	1708	1711	ISO	Chemical	D007545
8819482	1726	1734	stenosis	Disease	D003251
8819482	1790	1796	CD-832	Chemical	C082828
8819482	1845	1851	CD-832	Chemical	C082828
8819482	CID	D007545	D017202

8825380|t|The effect of recombinant human insulin-like growth factor-I on chronic puromycin aminonucleoside nephropathy in rats.
8825380|a|We recently demonstrated that recombinant hGH exacerbates renal functional and structural injury in chronic puromycin aminonucleoside (PAN) nephropathy, an experimental model of glomerular disease. Therefore, we examined whether recombinant human (rh) IGF-I is a safer alternative for the treatment of growth failure in rats with chronic PAN nephropathy. The glomerulopathy was induced by seven serial injections of PAN over 12 wk. Experimental animals (n = 6) received rhIGF-I, 400 micrograms/d, whereas control rats (n = 6) received the vehicle. rhIGF-I improved weight gain by 14% (p < 0.05), without altering hematocrit or blood pressure in rats with renal disease. Urinary protein excretion was unaltered by rhIGF-I treatment in rats with chronic PAN nephropathy. After 12 wk, the inulin clearance was higher in rhIGF-I-treated rats, 0.48 +/- 0.08 versus 0.24 +/- 0.06 mL/min/100 g of body weight in untreated PAN nephropathy animals, p < 0.05. The improvement in GFR was not associated with enhanced glomerular hypertrophy or increased segmental glomerulosclerosis, tubulointerstitial injury, or renal cortical malondialdehyde content. In rats with PAN nephropathy, administration of rhIGF-I increased IGF-I and GH receptor gene expression, without altering the steady state level of IGF-I receptor mRNA. In normal rats with intact kidneys, rhIGF-I administration (n = 4) did not alter weight gain, blood pressure, proteinuria, GFR, glomerular planar area, renal cortical malondialdehyde content, or glomerular or tubulointerstitial damage, compared with untreated animals (n = 4). rhIGF-I treatment reduced the steady state renal IGF-I mRNA level but did not modify gene expression of the IGF-I or GH receptors. We conclude that: 1) administration of rhIGF-I improves growth and GFR in rats with chronic PAN nephropathy and 2) unlike rhGH, long-term use of rhIGF-I does not worsen renal functional and structural injury in this disease model.
8825380	72	97	puromycin aminonucleoside	Chemical	D011692
8825380	98	109	nephropathy	Disease	D007674
8825380	227	252	puromycin aminonucleoside	Chemical	D011692
8825380	254	257	PAN	Chemical	D011692
8825380	259	270	nephropathy	Disease	D007674
8825380	297	315	glomerular disease	Disease	D007674
8825380	421	435	growth failure	Disease	D006130
8825380	457	460	PAN	Chemical	D011692
8825380	461	472	nephropathy	Disease	D007674
8825380	478	492	glomerulopathy	Disease	D007674
8825380	535	538	PAN	Chemical	D011692
8825380	774	787	renal disease	Disease	D007674
8825380	871	874	PAN	Chemical	D011692
8825380	875	886	nephropathy	Disease	D007674
8825380	1034	1037	PAN	Chemical	D011692
8825380	1038	1049	nephropathy	Disease	D007674
8825380	1125	1147	glomerular hypertrophy	Disease	D007674
8825380	1171	1189	glomerulosclerosis	Disease	D005921
8825380	1191	1216	tubulointerstitial injury	Disease	-1
8825380	1236	1251	malondialdehyde	Chemical	D008315
8825380	1274	1277	PAN	Chemical	D011692
8825380	1278	1289	nephropathy	Disease	D007674
8825380	1540	1551	proteinuria	Disease	D011507
8825380	1597	1612	malondialdehyde	Chemical	D008315
8825380	1639	1664	tubulointerstitial damage	Disease	D007674
8825380	1930	1933	PAN	Chemical	D011692
8825380	1934	1945	nephropathy	Disease	D007674
8825380	CID	D011692	D007674

8829135|t|Nefiracetam (DM-9384) reverses apomorphine-induced amnesia of a passive avoidance response: delayed emergence of the memory retention effects.
8829135|a|Nefiracetam is a novel pyrrolidone derivative which attenuates scopolamine-induced learning and post-training consolidation deficits. Given that apomorphine inhibits passive avoidance retention when given during training or in a defined 10-12h post-training period, we evaluated the ability of nefiracetam to attenuate amnesia induced by dopaminergic agonism. A step-down passive avoidance paradigm was employed and nefiracetam (3 mg/kg) and apomorphine (0.5 mg/kg) were given alone or in combination during training and at the 10-12h post-training period of consolidation. Co-administration of nefiracetam and apomorphine during training or 10h thereafter produced no significant anti-amnesic effect. However, administration of nefiracetam during training completely reversed the amnesia induced by apomorphine at the 10h post-training time and the converse was also true. These effects were not mediated by a dopaminergic mechanism as nefiracetam, at millimolar concentrations, failed to displace either [3H]SCH 23390 or [3H]spiperone binding from D1 or D2 dopamine receptor subtypes, respectively. It is suggested that nefiracetam augments molecular processes in the early stages of events which ultimately lead to consolidation of memory.
8829135	0	11	Nefiracetam	Chemical	C058876
8829135	13	20	DM-9384	Chemical	C058876
8829135	31	42	apomorphine	Chemical	D001058
8829135	51	58	amnesia	Disease	D000647
8829135	143	154	Nefiracetam	Chemical	C058876
8829135	166	177	pyrrolidone	Chemical	D011760
8829135	206	217	scopolamine	Chemical	D012601
8829135	226	275	learning and post-training consolidation deficits	Disease	D007859
8829135	288	299	apomorphine	Chemical	D001058
8829135	437	448	nefiracetam	Chemical	C058876
8829135	462	469	amnesia	Disease	D000647
8829135	559	570	nefiracetam	Chemical	C058876
8829135	585	596	apomorphine	Chemical	D001058
8829135	738	749	nefiracetam	Chemical	C058876
8829135	754	765	apomorphine	Chemical	D001058
8829135	872	883	nefiracetam	Chemical	C058876
8829135	924	931	amnesia	Disease	D000647
8829135	943	954	apomorphine	Chemical	D001058
8829135	1080	1091	nefiracetam	Chemical	C058876
8829135	1153	1162	SCH 23390	Chemical	C534628
8829135	1170	1179	spiperone	Chemical	D013134
8829135	1202	1210	dopamine	Chemical	D004298
8829135	1265	1276	nefiracetam	Chemical	C058876
8829135	CID	D012601	D007859
8829135	CID	D001058	D000647

8957205|t|Human corticotropin-releasing hormone and thyrotropin-releasing hormone modulate the hypercapnic ventilatory response in humans.
8957205|a|Human corticotropin-releasing hormone (hCRH) and thyrotropin-releasing hormone (TRH) are known to stimulate ventilation after i.v. administration in humans. In a placebo-controlled, single-blind study we aimed to clarify if both peptides act by altering central chemosensitivity. Two subsequent CO2-rebreathing tests were performed in healthy young volunteers. During the first test 0.9% NaCl was given i.v.; during the second test 200 micrograms of hCRH (n = 12) or 400 micrograms of TRH (n = 6) was administered i.v. Nine subjects received 0.9% NaCl i.v. during both rebreathing manoeuvres. The CO2-response curves for the two tests were compared within the same subject. In the hCRH group a marked parallel shift of the CO2-response curve to the left was observed after hCRH (P < 0.01). The same effect occurred following TRH but was less striking (P = 0.05). hCRH and TRH caused a reduction in the CO2 threshold. The CO2-response curves in the control group were nearly identical. The results indicate an additive effect of both releasing hormones on the hypercapnic ventilatory response in humans, presumably independent of central chemosensitivity.
8957205	6	19	corticotropin	Chemical	D000324
8957205	42	53	thyrotropin	Chemical	D013972
8957205	85	96	hypercapnic	Disease	D006935
8957205	135	148	corticotropin	Chemical	D000324
8957205	178	189	thyrotropin	Chemical	D013972
8957205	424	427	CO2	Chemical	D002245
8957205	517	521	NaCl	Chemical	D012965
8957205	676	680	NaCl	Chemical	D012965
8957205	726	729	CO2	Chemical	D002245
8957205	852	855	CO2	Chemical	D002245
8957205	1031	1034	CO2	Chemical	D002245
8957205	1050	1053	CO2	Chemical	D002245
8957205	1188	1199	hypercapnic	Disease	D006935
8957205	CID	D002245	D006935

8985298|t|Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial.
8985298|a|Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved.
8985298	0	10	Lamivudine	Chemical	D019259
8985298	39	50	hepatitis B	Disease	D006509
8985298	72	99	hepatitis B surface antigen	Chemical	D006514
8985298	138	148	Lamivudine	Chemical	D019259
8985298	160	182	2',3'-dideoxy cytosine	Chemical	D019259
8985298	230	241	hepatitis B	Disease	D006509
8985298	386	413	hepatitis B surface antigen	Chemical	D006514
8985298	415	420	HBsAg	Chemical	D006514
8985298	450	455	HBsAg	Chemical	D006514
8985298	516	526	lamivudine	Chemical	D019259
8985298	785	795	lamivudine	Chemical	D019259
8985298	814	825	hepatitis B	Disease	D006509
8985298	909	919	lamivudine	Chemical	D019259
8985298	1186	1197	hepatitis B	Disease	D006509
8985298	1321	1331	lamivudine	Chemical	D019259
8985298	1392	1397	HBsAg	Chemical	D006514
8985298	1472	1482	lamivudine	Chemical	D019259
8985298	CID	D006514	D006509

8996419|t|Population-based study of risk of venous thromboembolism associated with various oral contraceptives.
8996419|a|BACKGROUND: Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies. METHODS: We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540,000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease. FINDINGS: 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens. INTERPRETATION: The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 micrograms ethinyloestradiol and desogestrel compared with the 30 micrograms product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding.
8996419	34	56	venous thromboembolism	Disease	D054556
8996419	81	100	oral contraceptives	Chemical	D003276
8996419	190	212	venous thromboembolism	Disease	D054556
8996419	214	217	VTE	Disease	D054556
8996419	248	267	oral contraceptives	Chemical	D003276
8996419	269	272	OCs	Chemical	D003276
8996419	306	318	progestagens	Chemical	D011374
8996419	319	328	gestodene	Chemical	C033273
8996419	332	343	desogestrel	Chemical	D017135
8996419	361	364	OCs	Chemical	D003276
8996419	394	406	progestagens	Chemical	D011374
8996419	572	575	VTE	Disease	D054556
8996419	580	582	OC	Chemical	D003276
8996419	916	936	deep-vein thrombosis	Disease	D020246
8996419	938	955	venous thrombosis	Disease	D020246
8996419	1112	1115	VTE	Disease	D054556
8996419	1179	1182	VTE	Disease	D054556
8996419	1204	1206	OC	Chemical	D003276
8996419	1285	1288	VTE	Disease	D054556
8996419	1331	1333	OC	Chemical	D003276
8996419	1496	1499	OCs	Chemical	D003276
8996419	1613	1615	OC	Chemical	D003276
8996419	1751	1754	VTE	Disease	D054556
8996419	1782	1793	progestagen	Chemical	D011372
8996419	1799	1802	OCs	Chemical	D003276
8996419	1823	1826	VTE	Disease	D054556
8996419	1859	1862	OCs	Chemical	D003276
8996419	1884	1904	deep-vein thrombosis	Disease	D020246
8996419	1922	1932	thrombosis	Disease	D013927
8996419	1946	1963	venous thrombosis	Disease	D020246
8996419	2007	2010	VTE	Disease	D054556
8996419	2067	2069	OC	Chemical	D003276
8996419	2106	2109	OCs	Chemical	D003276
8996419	2207	2210	VTE	Disease	D054556
8996419	2270	2273	OCs	Chemical	D003276
8996419	2371	2374	VTE	Disease	D054556
8996419	2431	2434	OCs	Chemical	D003276
8996419	2468	2480	progestagens	Chemical	D011374
8996419	2494	2497	VTE	Disease	D054556
8996419	2521	2532	desogestrel	Chemical	D017135
8996419	2543	2560	ethinyloestradiol	Chemical	D004997
8996419	2578	2587	gestodene	Chemical	C033273
8996419	2591	2602	desogestrel	Chemical	D017135
8996419	2613	2630	ethinyloestradiol	Chemical	D004997
8996419	2659	2662	OCs	Chemical	D003276
8996419	2701	2704	VTE	Disease	D054556
8996419	2732	2743	desogestrel	Chemical	D017135
8996419	2754	2771	ethinyloestradiol	Chemical	D004997
8996419	2824	2836	progestagens	Chemical	D011374
8996419	2934	2937	OCs	Chemical	D003276
8996419	3125	3142	ethinyloestradiol	Chemical	D004997
8996419	3147	3158	desogestrel	Chemical	D017135
8996419	CID	D003276	D054556

9061777|t|MK-801 augments pilocarpine-induced electrographic seizure but protects against brain damage in rats.
9061777|a|1. The authors examined the anticonvulsant effects of MK-801 on the pilocarpine-induced seizure model. Intraperitoneal injection of pilocarpine (400 mg/kg) induced tonic and clonic seizure. Scopolamine (10 mg/kg) and pentobarbital (5 mg/kg) prevented development of pilocarpine-induced behavioral seizure but MK-801 (0.5 mg/kg) did not. 2. An electrical seizure measured with hippocampal EEG appeared in the pilocarpine-treated group. Scopolamine and pentobarbital blocked the pilocarpine-induced electrographic seizure, MK-801 treatment augmented the electrographic seizure induced by pilocarpine. 3. Brain damage was assessed by examining the hippocampus microscopically. Pilocarpine produced neuronal death in the hippocampus, which showed pyknotic changes. Pentobarbital, scopolamine and MK-801 protected the brain damage by pilocarpine, though in the MK-801-treated group, the pyramidal cells of hippocampus appeared darker than normal. In all treatments, granule cells of the dentate gyrus were not affected. 4. These results indicate that status epilepticus induced by pilocarpine is initiated by cholinergic overstimulation and propagated by glutamatergic transmission, the elevation of which may cause brain damage through an excitatory NMDA receptor-mediated mechanism.
9061777	0	6	MK-801	Chemical	D016291
9061777	16	27	pilocarpine	Chemical	D010862
9061777	51	58	seizure	Disease	D012640
9061777	80	92	brain damage	Disease	D001930
9061777	156	162	MK-801	Chemical	D016291
9061777	170	181	pilocarpine	Chemical	D010862
9061777	190	197	seizure	Disease	D012640
9061777	234	245	pilocarpine	Chemical	D010862
9061777	266	290	tonic and clonic seizure	Disease	D012640
9061777	292	303	Scopolamine	Chemical	D012601
9061777	319	332	pentobarbital	Chemical	D010424
9061777	368	379	pilocarpine	Chemical	D010862
9061777	399	406	seizure	Disease	D012640
9061777	411	417	MK-801	Chemical	D016291
9061777	456	463	seizure	Disease	D012640
9061777	510	521	pilocarpine	Chemical	D010862
9061777	537	548	Scopolamine	Chemical	D012601
9061777	553	566	pentobarbital	Chemical	D010424
9061777	579	590	pilocarpine	Chemical	D010862
9061777	614	621	seizure	Disease	D012640
9061777	623	629	MK-801	Chemical	D016291
9061777	669	676	seizure	Disease	D012640
9061777	688	699	pilocarpine	Chemical	D010862
9061777	704	716	Brain damage	Disease	D001930
9061777	776	787	Pilocarpine	Chemical	D010862
9061777	797	811	neuronal death	Disease	D009410
9061777	863	876	Pentobarbital	Chemical	D010424
9061777	878	889	scopolamine	Chemical	D012601
9061777	894	900	MK-801	Chemical	D016291
9061777	915	927	brain damage	Disease	D001930
9061777	931	942	pilocarpine	Chemical	D010862
9061777	958	964	MK-801	Chemical	D016291
9061777	1148	1166	status epilepticus	Disease	D013226
9061777	1178	1189	pilocarpine	Chemical	D010862
9061777	1313	1325	brain damage	Disease	D001930
9061777	1348	1352	NMDA	Chemical	D016202
9061777	CID	D010862	D009410
9061777	CID	D010862	D013226
9061777	CID	D010862	D012640
9061777	CID	D016291	D012640

9071336|t|Paclitaxel, 5-fluorouracil, and folinic acid in metastatic breast cancer: BRE-26, a phase II trial.
9071336|a|5-Fluorouracil plus folinic acid and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are effective salvage therapies for metastatic breast cancer patients. Paclitaxel and 5-fluorouracil have additive cytotoxicity in MCF-7 cell lines. We performed a phase II trial of paclitaxel 175 mg/m2 over 3 hours on day I followed by folinic acid 300 mg over 1 hour before 5-fluorouracil 350 mg/m2 on days 1 to 3 every 28 days (TFL) in women with metastatic breast cancer. Analysis is reported on 37 patients with a minimum of 6 months follow-up who received a total of 192 cycles of TFL: nine cycles (5%) were associated with grade 3/4 neutropenia requiring hospitalization; seven (4%) cycles in two patients required granulocyte colony-stimulating factor due to neutropenia; no patient required platelet transfusions. Grade 3/4 nonhematologic toxicities were uncommon. Among the 34 patients evaluable for response, there were three complete responses (9%) and 18 partial responses (53%) for an overall response rate of 62%. Of the 19 evaluable patients with prior doxorubicin exposure, 11 (58%) responded compared with nine of 15 (60%) without prior doxorubicin. Plasma paclitaxel concentrations were measured at the completion of paclitaxel infusion and at 24 hours in 19 patients. TFL is an active, well-tolerated regimen in metastatic breast cancer.
9071336	0	10	Paclitaxel	Chemical	D017239
9071336	12	26	5-fluorouracil	Chemical	D005472
9071336	32	44	folinic acid	Chemical	D002955
9071336	59	72	breast cancer	Disease	D001943
9071336	100	114	5-Fluorouracil	Chemical	D005472
9071336	120	132	folinic acid	Chemical	D002955
9071336	137	147	paclitaxel	Chemical	D017239
9071336	149	154	Taxol	Chemical	D017239
9071336	248	261	breast cancer	Disease	D001943
9071336	272	282	Paclitaxel	Chemical	D017239
9071336	287	301	5-fluorouracil	Chemical	D005472
9071336	316	328	cytotoxicity	Disease	D064420
9071336	383	393	paclitaxel	Chemical	D017239
9071336	438	450	folinic acid	Chemical	D002955
9071336	477	491	5-fluorouracil	Chemical	D005472
9071336	562	575	breast cancer	Disease	D001943
9071336	741	752	neutropenia	Disease	D009503
9071336	823	860	granulocyte colony-stimulating factor	Chemical	D016179
9071336	868	879	neutropenia	Disease	D009503
9071336	949	959	toxicities	Disease	D064420
9071336	1170	1181	doxorubicin	Chemical	D004317
9071336	1256	1267	doxorubicin	Chemical	D004317
9071336	1276	1286	paclitaxel	Chemical	D017239
9071336	1337	1347	paclitaxel	Chemical	D017239
9071336	1444	1457	breast cancer	Disease	D001943
9071336	CID	D002955	D009503
9071336	CID	D017239	D009503
9071336	CID	D005472	D009503

9125676|t|Efficacy and proarrhythmia with the use of d,l-sotalol for sustained ventricular tachyarrhythmias.
9125676|a|This study prospectively evaluated the clinical efficacy, the incidence of torsades de pointes, and the presumable risk factors for torsades de pointes in patients treated with d,l-sotalol for sustained ventricular tachyarrhythmias. Eighty-one consecutive patients (54 with coronary artery disease, and 20 with dilated cardiomyopathy) with inducible sustained ventricular tachycardia or ventricular fibrillation received oral d,l-sotalol to prevent induction of the ventricular tachyarrhythmia. During oral loading with d,l-sotalol, continuous electrocardiographic (ECG) monitoring was performed. Those patients in whom d,l-sotalol prevented induction of ventricular tachycardia or ventricular fibrillation were discharged with the drug and followed up on an outpatient basis for 21 +/- 18 months. Induction of the ventricular tachyarrhythmia was prevented by oral d,l-sotalol in 35 (43%) patients; the ventricular tachyarrhythmia remained inducible in 40 (49%) patients; and two (2.5%) patients did not tolerate even 40 mg of d,l-sotalol once daily. Four (5%) patients had from torsades de pointes during the initial oral treatment with d,l-sotalol. Neither ECG [sinus-cycle length (SCL), QT or QTc interval, or U wave] nor clinical parameters identified patients at risk for torsades de pointes. However, the oral dose of d,l-sotalol was significantly lower in patients with torsades de pointes (200 +/- 46 vs. 328 +/- 53 mg/day; p = 0.0017). Risk factors associated with the development of torsades de pointes were the appearance of an U wave (p = 0.049), female gender (p = 0.015), and significant dose-corrected changes of SCL, QT interval, and QTc interval (p < 0.05). During follow-up, seven (20%) patients had a nonfatal ventricular tachycardia recurrence, and two (6%) patients died suddenly. One female patient with stable cardiac disease had recurrent torsades de pointes after 2 years of successful treatment with d,l-sotalol. Torsades de pointes occurred early during treatment even with low doses of oral d,l-sotalol. Pronounced changes in the surface ECG (cycle length, QT, and QTc) in relation to the dose of oral d,l-sotalol might identify a subgroup of patients with an increased risk for torsades de pointes. Other ECG parameters before the application of d,l-sotalol did not identify patients at increased risk for torsades de pointes. Recurrence rates of ventricular tachyarrhythmias are high despite complete suppression of the arrhythmia during programmed stimulation. Therefore programmed electrical stimulation in the case of d,l-sotalol seems to be of limited prognostic value.
9125676	13	26	proarrhythmia	Disease	-1
9125676	43	54	d,l-sotalol	Chemical	D013015
9125676	69	97	ventricular tachyarrhythmias	Disease	D017180
9125676	174	193	torsades de pointes	Disease	D016171
9125676	231	250	torsades de pointes	Disease	D016171
9125676	276	287	d,l-sotalol	Chemical	D013015
9125676	302	330	ventricular tachyarrhythmias	Disease	D017180
9125676	373	396	coronary artery disease	Disease	D003324
9125676	410	432	dilated cardiomyopathy	Disease	D002311
9125676	459	482	ventricular tachycardia	Disease	D017180
9125676	486	510	ventricular fibrillation	Disease	D014693
9125676	525	536	d,l-sotalol	Chemical	D013015
9125676	565	592	ventricular tachyarrhythmia	Disease	D017180
9125676	619	630	d,l-sotalol	Chemical	D013015
9125676	719	730	d,l-sotalol	Chemical	D013015
9125676	754	777	ventricular tachycardia	Disease	D017180
9125676	781	805	ventricular fibrillation	Disease	D014693
9125676	914	941	ventricular tachyarrhythmia	Disease	D017180
9125676	964	975	d,l-sotalol	Chemical	D013015
9125676	1002	1029	ventricular tachyarrhythmia	Disease	D017180
9125676	1126	1137	d,l-sotalol	Chemical	D013015
9125676	1178	1197	torsades de pointes	Disease	D016171
9125676	1237	1248	d,l-sotalol	Chemical	D013015
9125676	1376	1395	torsades de pointes	Disease	D016171
9125676	1423	1434	d,l-sotalol	Chemical	D013015
9125676	1476	1495	torsades de pointes	Disease	D016171
9125676	1592	1611	torsades de pointes	Disease	D016171
9125676	1828	1851	ventricular tachycardia	Disease	D017180
9125676	1932	1947	cardiac disease	Disease	D006331
9125676	1962	1981	torsades de pointes	Disease	D016171
9125676	2025	2036	d,l-sotalol	Chemical	D013015
9125676	2038	2057	Torsades de pointes	Disease	D016171
9125676	2118	2129	d,l-sotalol	Chemical	D013015
9125676	2229	2240	d,l-sotalol	Chemical	D013015
9125676	2306	2325	torsades de pointes	Disease	D016171
9125676	2374	2385	d,l-sotalol	Chemical	D013015
9125676	2434	2453	torsades de pointes	Disease	D016171
9125676	2475	2503	ventricular tachyarrhythmias	Disease	D017180
9125676	2549	2559	arrhythmia	Disease	D001145
9125676	2650	2661	d,l-sotalol	Chemical	D013015
9125676	CID	D013015	D016171

9128918|t|Chronic hyperprolactinemia and changes in dopamine neurons.
9128918|a|The tuberoinfundibular dopaminergic (TIDA) system is known to inhibit prolactin (PRL) secretion. In young animals this system responds to acute elevations in serum PRL by increasing its activity. However, this responsiveness is lost in aging rats with chronically high serum PRL levels. The purpose of this study was to induce hyperprolactinemia in rats for extended periods of time and examine its effects on dopaminergic systems in the brain. Hyperprolactinemia was induced by treatment with haloperidol, a dopamine receptor antagonist, and Palkovits' microdissection technique in combination with high-performance liquid chromatography was used to measure neurotransmitter concentrations in several areas of the brain. After 6 months of hyperprolactinemia, dopamine (DA) concentrations in the median eminence (ME) increased by 84% over the control group. Nine months of hyperprolactinemia produced a 50% increase in DA concentrations in the ME over the control group. However, DA response was lost if a 9-month long haloperidol-induced hyperprolactinemia was followed by a 1 1/2 month-long extremely high increase in serum PRL levels produced by implantation of MMQ cells under the kidney capsule. There was no change in the levels of DA, norepinephrine (NE), serotonin (5-HT), or their metabolites in the arcuate nucleus (AN), medial preoptic area (MPA), caudate putamen (CP), substantia nigra (SN), and zona incerta (ZI), except for a decrease in 5-hydroxyindoleacetic acid (5-HIAA) in the AN after 6-months of hyperprolactinemia and an increase in DA concentrations in the AN after 9-months of hyperprolactinemia. These results demonstrate that hyperprolactinemia specifically affects TIDA neurons and these effects vary, depending on the duration and intensity of hyperprolactinemia. The age-related decrease in hypothalamic dopamine function may be associated with increases in PRL secretion.
9128918	8	26	hyperprolactinemia	Disease	D006966
9128918	42	50	dopamine	Chemical	D004298
9128918	387	405	hyperprolactinemia	Disease	D006966
9128918	505	523	Hyperprolactinemia	Disease	D006966
9128918	554	565	haloperidol	Chemical	D006220
9128918	569	577	dopamine	Chemical	D004298
9128918	800	818	hyperprolactinemia	Disease	D006966
9128918	820	828	dopamine	Chemical	D004298
9128918	830	832	DA	Chemical	D004298
9128918	933	951	hyperprolactinemia	Disease	D006966
9128918	979	981	DA	Chemical	D004298
9128918	1040	1042	DA	Chemical	D004298
9128918	1079	1090	haloperidol	Chemical	D006220
9128918	1099	1117	hyperprolactinemia	Disease	D006966
9128918	1298	1300	DA	Chemical	D004298
9128918	1302	1316	norepinephrine	Chemical	D009638
9128918	1318	1320	NE	Chemical	D009638
9128918	1323	1332	serotonin	Chemical	D012701
9128918	1334	1338	5-HT	Chemical	D012701
9128918	1512	1538	5-hydroxyindoleacetic acid	Chemical	D006897
9128918	1540	1546	5-HIAA	Chemical	D006897
9128918	1576	1594	hyperprolactinemia	Disease	D006966
9128918	1614	1616	DA	Chemical	D004298
9128918	1660	1678	hyperprolactinemia	Disease	D006966
9128918	1711	1729	hyperprolactinemia	Disease	D006966
9128918	1831	1849	hyperprolactinemia	Disease	D006966
9128918	1892	1900	dopamine	Chemical	D004298
9128918	CID	D006220	D006966

9132810|t|Treatment-related disseminated necrotizing leukoencephalopathy with characteristic contrast enhancement of the white matter.
9132810|a|This report describes unique contrast enhancement of the white matter on T1-weighted magnetic resonance images of two patients with disseminated necrotizing leukoencephalopathy, which developed from acute lymphoblastic leukemia treated with high-dose methotrexate. In both patients, the enhancement was more pronounced near the base of the brain than at the vertex. Necropsy of the first case revealed loss of myelination and necrosis of the white matter. Possible mechanisms causing such a leukoencephalopathy are discussed.
9132810	43	62	leukoencephalopathy	Disease	D056784
9132810	282	301	leukoencephalopathy	Disease	D056784
9132810	324	352	acute lymphoblastic leukemia	Disease	D054198
9132810	376	388	methotrexate	Chemical	D008727
9132810	527	546	loss of myelination	Disease	D003711
9132810	551	559	necrosis	Disease	D009336
9132810	616	635	leukoencephalopathy	Disease	D056784
9132810	CID	D008727	D003711
9132810	CID	D008727	D056784
9132810	CID	D008727	D009336

9158667|t|Thrombotic complications in acute promyelocytic leukemia during all-trans-retinoic acid therapy.
9158667|a|A case of acute renal failure, due to occlusion of renal vessels in a patient with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and tranexamic acid has been described recently. We report a case of acute renal failure in an APL patient treated with ATRA alone. This case further supports the concern about thromboembolic complications associated with ATRA therapy in APL patients. The patients, a 43-year-old man, presented all the signs and symptoms of APL and was included in a treatment protocol with ATRA. After 10 days of treatment, he developed acute renal failure that was completely reversible after complete remission of APL was achieved and therapy discontinued. We conclude that ATRA is a valid therapeutic choice for patients with APL, although the procoagulant tendency is not completely corrected. Thrombotic events, however, could be avoided by using low-dose heparin.
9158667	0	10	Thrombotic	Disease	D013927
9158667	28	56	acute promyelocytic leukemia	Disease	D015473
9158667	64	87	all-trans-retinoic acid	Chemical	D014212
9158667	107	126	acute renal failure	Disease	D058186
9158667	135	161	occlusion of renal vessels	Disease	-1
9158667	180	208	acute promyelocytic leukemia	Disease	D015473
9158667	210	213	APL	Disease	D015473
9158667	228	251	all-trans-retinoic acid	Chemical	D014212
9158667	253	257	ATRA	Chemical	D014212
9158667	263	278	tranexamic acid	Chemical	D014148
9158667	328	347	acute renal failure	Disease	D058186
9158667	354	357	APL	Disease	D015473
9158667	379	383	ATRA	Chemical	D014212
9158667	436	450	thromboembolic	Disease	D013923
9158667	481	485	ATRA	Chemical	D014212
9158667	497	500	APL	Disease	D015473
9158667	584	587	APL	Disease	D015473
9158667	634	638	ATRA	Chemical	D014212
9158667	681	700	acute renal failure	Disease	D058186
9158667	760	763	APL	Disease	D015473
9158667	820	824	ATRA	Chemical	D014212
9158667	873	876	APL	Disease	D015473
9158667	942	952	Thrombotic	Disease	D013927
9158667	1005	1012	heparin	Chemical	D006493
9158667	CID	D014212	D013927
9158667	CID	D014212	D058186

9197951|t|Pupillary changes associated with the development of stimulant-induced mania: a case report.
9197951|a|A 30-year-old cocaine-dependent man who was a subject in a study evaluating the anticraving efficacy of the stimulant medication diethylpropion (DEP) became manic during his second week on the study drug. Pupillometric changes while on DEP, especially changes in the total power of pupillary oscillation, were dramatically different than those observed in the eight other study subjects who did not become manic. The large changes in total power of pupillary oscillation occurred a few days before the patient became fully manic. Such medication-associated changes in the total power of pupillary oscillation might be of utility in identifying persons at risk for manic-like adverse effects during the medical use of psychomotor stimulants or sympathomimetic agents.
9197951	71	76	mania	Disease	D001714
9197951	107	114	cocaine	Chemical	D003042
9197951	222	236	diethylpropion	Chemical	D004053
9197951	238	241	DEP	Chemical	D004053
9197951	250	255	manic	Disease	D001714
9197951	329	332	DEP	Chemical	D004053
9197951	375	396	pupillary oscillation	Disease	D011681
9197951	499	504	manic	Disease	D001714
9197951	542	563	pupillary oscillation	Disease	D011681
9197951	616	621	manic	Disease	D001714
9197951	680	701	pupillary oscillation	Disease	D011681
9197951	757	762	manic	Disease	D001714
9197951	CID	D004053	D001714

9272404|t|The negative mucosal potential: separating central and peripheral effects of NSAIDs in man.
9272404|a|OBJECTIVE: We wanted to test whether assessment of both a central pain-related signal (chemo-somatosensory evoked potential, CSSEP) and a concomitantly recorded peripheral signal (negative mucosal potential, NMP) allows for separation of central and peripheral effects of NSAIDs. For this purpose, experimental conditions were created in which NSAIDs had previously been observed to produce effects on phasic and tonic pain by either central or peripheral mechanisms. METHODS: According to a double-blind, randomised, controlled, threefold cross-over design, 18 healthy subjects (11 males, 7 females; mean age 26 years) received either placebo, 400 mg ibuprofen, or 800 mg ibuprofen. Phasic pain was applied by means of short pulses of CO2 to the nasal mucosa (stimulus duration 500 ms, interval approximately 60 s), and tonic pain was induced in the nasal cavity by means of dry air of controlled temperature, humidity and flow rate (22 degrees C, 0% relative humidity, 145 ml.s-1). Both CSSEPs as central and NMPs as peripheral correlates of pain were obtained in response to the CO2 stimuli. Additionally, the subjects rated the intensity of both phasic and tonic pain by means of visual analogue scales. RESULTS: As described earlier, administration of ibuprofen was followed by a decrease in tonic pain but-relative to placebo-an increase in correlates of phasic pain, indicating a specific effect of ibuprofen on the interaction between the pain stimuli under these special experimental conditions. Based on the similar behaviour of CSSEP and NMP, it was concluded that the pharmacological process underlying this phenomenon was localised in the periphery. By means of the simultaneous recording of interrelated peripheral and central electrophysiologic correlates of nociception, it was possible to separate central and peripheral effects of an NSAID. The major advantage of this pain model is the possibility of obtaining peripheral pain-related activity directly using a non-invasive technique in humans.
9272404	158	162	pain	Disease	D010146
9272404	511	515	pain	Disease	D010146
9272404	744	753	ibuprofen	Chemical	D007052
9272404	765	774	ibuprofen	Chemical	D007052
9272404	783	787	pain	Disease	D010146
9272404	828	831	CO2	Chemical	D002245
9272404	919	923	pain	Disease	D010146
9272404	1136	1140	pain	Disease	D010146
9272404	1174	1177	CO2	Chemical	D002245
9272404	1259	1263	pain	Disease	D010146
9272404	1349	1358	ibuprofen	Chemical	D007052
9272404	1395	1399	pain	Disease	D010146
9272404	1460	1464	pain	Disease	D010146
9272404	1498	1507	ibuprofen	Chemical	D007052
9272404	1539	1543	pain	Disease	D010146
9272404	1979	1983	pain	Disease	D010146
9272404	2033	2037	pain	Disease	D010146
9272404	CID	D007052	D010146

9323412|t|Acute severe depression following peri-operative ondansetron.
9323412|a|A 41-year-old woman with a strong history of postoperative nausea and vomiting presented for abdominal hysterectomy 3 months after a previous anaesthetic where ondansetron prophylaxis had been used. She had developed a severe acute major depression disorder almost immediately thereafter, possibly related to the use of a serotonin antagonist. Nine years before she had experienced a self-limited puerperal depressive episode. Anaesthesia with a propofol infusion and avoidance of serotonin antagonists provided a nausea-free postoperative course without exacerbation of the depression disorder.
9323412	13	23	depression	Disease	D003866
9323412	49	60	ondansetron	Chemical	D017294
9323412	107	140	postoperative nausea and vomiting	Disease	D020250
9323412	222	233	ondansetron	Chemical	D017294
9323412	294	319	major depression disorder	Disease	D003865
9323412	384	393	serotonin	Chemical	D012701
9323412	469	487	depressive episode	Disease	D003866
9323412	508	516	propofol	Chemical	D015742
9323412	543	552	serotonin	Chemical	D012701
9323412	576	582	nausea	Disease	D009325
9323412	637	656	depression disorder	Disease	D003866
9323412	CID	D017294	D003865

9382023|t|Hypertensive response during dobutamine stress echocardiography.
9382023|a|Among 3,129 dobutamine stress echocardiographic studies, a hypertensive response, defined as systolic blood pressure (BP) > or = 220 mm Hg and/or diastolic BP > or = 110 mm Hg, occurred in 30 patients (1%). Patients with this response more often had a history of hypertension and had higher resting systolic and diastolic BP before dobutamine infusion.
9382023	0	12	Hypertensive	Disease	D006973
9382023	29	39	dobutamine	Chemical	D004280
9382023	77	87	dobutamine	Chemical	D004280
9382023	124	136	hypertensive	Disease	D006973
9382023	328	340	hypertension	Disease	D006973
9382023	397	407	dobutamine	Chemical	D004280
9382023	CID	D004280	D006973

9428298|t|Continuously nebulized albuterol in severe exacerbations of asthma in adults: a case-controlled study.
9428298|a|A retrospective, case-controlled analysis comparing patients admitted to a medical intensive care unit with severe exacerbations of asthma who received continuously nebulized albuterol (CNA) versus intermittent albuterol (INA) treatments is reported. Forty matched pairs of patients with asthma are compared. CNA was administered for a mean of 11 +/- 10 hr. The incidence of cardiac dysrhythmias was similar between groups. Symptomatic hypokalemia did not occur. CNA patients had higher heart rates during treatment, which may reflect severity of illness. The incidence of intubation was similar. We conclude that CNA and INA demonstrated similar profiles with regard to safety, morbidity, and mortality.
9428298	23	32	albuterol	Chemical	D000420
9428298	60	66	asthma	Disease	D001249
9428298	235	241	asthma	Disease	D001249
9428298	278	287	albuterol	Chemical	D000420
9428298	314	323	albuterol	Chemical	D000420
9428298	391	397	asthma	Disease	D001249
9428298	478	498	cardiac dysrhythmias	Disease	D001145
9428298	539	550	hypokalemia	Disease	D007008
9428298	CID	D000420	D001145

9538487|t|Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus.
9538487|a|A 45-year-old man, with a 10-year history of manic depression treated with lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year history of polyuria and polydipsia, during which time urinalysis had been negative for glucose. After recovery from hyperglycaemia, he remained polyuric despite normal blood glucose concentrations; water deprivation testing indicated nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that when this man developed type 2 diabetes, chronic polyuria due to nephrogenic diabetes insipidus was sufficient to precipitate hyperosmolar dehydration.
9538487	0	28	Hyperosmolar nonketotic coma	Disease	D006944
9538487	45	52	lithium	Chemical	D008094
9538487	61	91	nephrogenic diabetes insipidus	Disease	D018500
9538487	138	154	manic depression	Disease	D001714
9538487	168	175	lithium	Chemical	D008094
9538487	195	224	hyperosmolar, nonketotic coma	Disease	D006944
9538487	257	265	polyuria	Disease	D011141
9538487	270	280	polydipsia	Disease	D059606
9538487	333	340	glucose	Chemical	D005947
9538487	362	376	hyperglycaemia	Disease	-1
9538487	390	398	polyuric	Disease	D011141
9538487	420	427	glucose	Chemical	D005947
9538487	480	510	nephrogenic diabetes insipidus	Disease	D018500
9538487	525	532	lithium	Chemical	D008094
9538487	586	601	type 2 diabetes	Disease	D003924
9538487	611	619	polyuria	Disease	D011141
9538487	627	657	nephrogenic diabetes insipidus	Disease	D018500
9538487	701	712	dehydration	Disease	D003681
9538487	CID	D008094	D011141
9538487	CID	D008094	D018500
9538487	CID	D008094	D006944

9570197|t|Effects of the intracoronary infusion of cocaine on left ventricular systolic and diastolic function in humans.
9570197|a|BACKGROUND: In dogs, a large amount of intravenous cocaine causes a profound deterioration of left ventricular (LV) systolic function and an increase in LV end-diastolic pressure. This study was done to assess the influence of a high intracoronary cocaine concentration on LV systolic and diastolic function in humans. METHODS AND RESULTS: In 20 patients (14 men and 6 women aged 39 to 72 years) referred for cardiac catheterization for the evaluation of chest pain, we measured heart rate, systemic arterial pressure, LV pressure and its first derivative (dP/dt), and LV volumes and ejection fraction before and during the final 2 to 3 minutes of a 15-minute intracoronary infusion of saline (n=10, control subjects) or cocaine hydrochloride 1 mg/min (n=10). No variable changed with saline. With cocaine, the drug concentration in blood obtained from the coronary sinus was 3.0+/-0.4 (mean+/-SD) mg/L, similar in magnitude to the blood cocaine concentration reported in abusers dying of cocaine intoxication. Cocaine induced no significant change in heart rate, LV dP/dt (positive or negative), or LV end-diastolic volume, but it caused an increase in systolic and mean arterial pressures, LV end-diastolic pressure, and LV end-systolic volume, as well as a decrease in LV ejection fraction. CONCLUSIONS: In humans, the intracoronary infusion of cocaine sufficient in amount to achieve a high drug concentration in coronary sinus blood causes a deterioration of LV systolic and diastolic performance.
9570197	41	48	cocaine	Chemical	D003042
9570197	163	170	cocaine	Chemical	D003042
9570197	189	245	deterioration of left ventricular (LV) systolic function	Disease	D018487
9570197	360	367	cocaine	Chemical	D003042
9570197	567	577	chest pain	Disease	D002637
9570197	833	854	cocaine hydrochloride	Chemical	D003042
9570197	910	917	cocaine	Chemical	D003042
9570197	1050	1057	cocaine	Chemical	D003042
9570197	1101	1108	cocaine	Chemical	D003042
9570197	1123	1130	Cocaine	Chemical	D003042
9570197	1460	1467	cocaine	Chemical	D003042
9570197	1559	1613	deterioration of LV systolic and diastolic performance	Disease	D018487
9570197	CID	D003042	D018487

9646784|t|Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy.
9646784|a|Although several new anticoagulant drugs are in development, heparin remains the drug of choice for most anticoagulation needs. The clinical effects of heparin are meritorious, but side effects do exist. Important untoward effects of heparin therapy including heparin-induced thrombocytopenia, heparin-associated osteoporosis, eosinophilia, skin reactions, allergic reactions other than thrombocytopenia and alopecia will be discussed in this article.
9646784	0	7	Heparin	Chemical	D006493
9646784	16	32	thrombocytopenia	Disease	D013921
9646784	46	61	thromboembolism	Disease	D013923
9646784	89	96	heparin	Chemical	D006493
9646784	167	174	heparin	Chemical	D006493
9646784	258	265	heparin	Chemical	D006493
9646784	340	347	heparin	Chemical	D006493
9646784	366	373	heparin	Chemical	D006493
9646784	382	398	thrombocytopenia	Disease	D013921
9646784	400	407	heparin	Chemical	D006493
9646784	419	431	osteoporosis	Disease	D010024
9646784	433	445	eosinophilia	Disease	D004802
9646784	447	461	skin reactions	Disease	D012871
9646784	463	481	allergic reactions	Disease	D004342
9646784	493	509	thrombocytopenia	Disease	D013921
9646784	514	522	alopecia	Disease	D000505
9646784	CID	D006493	D000505
9646784	CID	D006493	D010024
9646784	CID	D006493	D013923
9646784	CID	D006493	D013921
9646784	CID	D006493	D004342
9646784	CID	D006493	D004802
9646784	CID	D006493	D012871

9725303|t|Nonopaque crystal deposition causing ureteric obstruction in patients with HIV undergoing indinavir therapy.
9725303|a|OBJECTIVE: We describe the unique CT features of ureteric calculi in six HIV-infected patients receiving indinavir, the most commonly used HIV protease inhibitor, which is associated with an increased incidence of urolithiasis. CONCLUSION: Ureteric obstruction caused by precipitated indinavir crystals may be difficult to diagnose with unenhanced CT. The calculi are not opaque, and secondary signs of obstruction may be absent or minimal and should be sought carefully. Images may need to be obtained using i.v. contrast material to enable diagnosis of ureteric stones or obstruction in patients with HIV infection who receive indinavir therapy.
9725303	37	57	ureteric obstruction	Disease	D014517
9725303	90	99	indinavir	Chemical	D019469
9725303	158	174	ureteric calculi	Disease	D014514
9725303	182	194	HIV-infected	Disease	D015658
9725303	214	223	indinavir	Chemical	D019469
9725303	323	335	urolithiasis	Disease	D052878
9725303	349	369	Ureteric obstruction	Disease	D014517
9725303	393	402	indinavir	Chemical	D019469
9725303	664	694	ureteric stones or obstruction	Disease	D014514|D014517	ureteric stones|ureteric obstruction
9725303	712	725	HIV infection	Disease	D015658
9725303	738	747	indinavir	Chemical	D019469
9725303	CID	D019469	D014514

9759693|t|Ischemic colitis and sumatriptan use.
9759693|a|Sumatriptan succinate, a serotonin-1 (5-hydroxytryptamine-1) receptor agonist, is an antimigraine drug that is reported to act by selectively constricting intracranial arteries. Recently, vasopressor responses that are distinct from the cranial circulation have been demonstrated to occur in the systemic, pulmonary, and coronary circulations. Cases have been published of coronary vasospasm, myocardial ischemia, and myocardial infarction occurring after sumatriptan use. We report on the development of 8 serious cases of ischemic colitis in patients with migraine treated with sumatriptan.
9759693	0	16	Ischemic colitis	Disease	D017091
9759693	21	32	sumatriptan	Chemical	D018170
9759693	38	59	Sumatriptan succinate	Chemical	D018170
9759693	63	72	serotonin	Chemical	D012701
9759693	76	95	5-hydroxytryptamine	Chemical	D012701
9759693	411	429	coronary vasospasm	Disease	D003329
9759693	431	450	myocardial ischemia	Disease	D017202
9759693	456	477	myocardial infarction	Disease	D009203
9759693	494	505	sumatriptan	Chemical	D018170
9759693	562	578	ischemic colitis	Disease	D017091
9759693	596	604	migraine	Disease	D008881
9759693	618	629	sumatriptan	Chemical	D018170
9759693	CID	D018170	D017091

9782254|t|Pallidotomy with the gamma knife: a positive experience.
9782254|a|51 patients with medically refractory Parkinson's disease underwent stereotactic posteromedial pallidotomy between August 1993 and February 1997 for treatment of bradykinesia, rigidity, and L-DOPA-induced dyskinesias. In 29 patients, the pallidotomies were performed with the Leksell Gamma Knife and in 22 they were performed with the standard radiofrequency (RF) method. Clinical assessment as well as blinded ratings of Unified Parkinson's Disease Rating Scale (UPDRS) scores were carried out pre- and postoperatively. Mean follow-up time is 20.6 months (range 6-48) and all except 4 patients have been followed more than one year. 85 percent of patients with dyskinesias were relieved of symptoms, regardless of whether the pallidotomies were performed with the Gamma Knife or radiofrequency methods. About 2/3 of the patients in both Gamma Knife and radiofrequency groups showed improvements in bradykinesia and rigidity, although when considered as a group neither the Gamma Knife nor the radiofrequency group showed statistically significant improvements in UPDRS scores. One patient in the Gamma Knife group (3.4%) developed a homonymous hemianopsia 9 months following treatment and 5 patients (27.7%) in the radiofrequency group became transiently confused postoperatively. No other complications were seen. Gamma Knife pallidotomy is as effective as radiofrequency pallidotomy in controlling certain of the symptoms of Parkinson's disease. It may be the only practical technique available in certain patients, such as those who take anticoagulants, have bleeding diatheses or serious systemic medical illnesses. It is a viable option for other patients as well.
9782254	95	114	Parkinson's disease	Disease	D010300
9782254	219	231	bradykinesia	Disease	D018476
9782254	233	241	rigidity	Disease	D009127
9782254	247	253	L-DOPA	Chemical	D007980
9782254	262	273	dyskinesias	Disease	D004409
9782254	487	506	Parkinson's Disease	Disease	D010300
9782254	719	730	dyskinesias	Disease	D004409
9782254	956	968	bradykinesia	Disease	D018476
9782254	973	981	rigidity	Disease	D009127
9782254	1191	1213	homonymous hemianopsia	Disease	D006423
9782254	1485	1504	Parkinson's disease	Disease	D010300
9782254	1620	1628	bleeding	Disease	D006470
9782254	CID	D007980	D004409

9831002|t|Neuroleptic malignant syndrome and methylphenidate.
9831002|a|A 1-year-old female presented with neuroleptic malignant syndrome probably caused by methylphenidate. She had defects in the supratentorial brain including the basal ganglia and the striatum (multicystic encephalomalacia) due to severe perinatal hypoxic-ischemic encephalopathy, which was considered to be a possible predisposing factor causing neuroleptic malignant syndrome. A dopaminergic blockade mechanism generally is accepted as the pathogenesis of this syndrome. However, methylphenidate is a dopamine agonist via the inhibition of uptake of dopamine, and therefore dopaminergic systems in the brainstem (mainly the midbrain) and the spinal cord were unlikely to participate in the onset of this syndrome. A relative gamma-aminobutyric acid-ergic deficiency might occur because diazepam, a gamma-aminobutyric acid-mimetic agent, was strikingly effective. This is the first reported patient with neuroleptic malignant syndrome probably caused by methylphenidate.
9831002	0	30	Neuroleptic malignant syndrome	Disease	D009459
9831002	35	50	methylphenidate	Chemical	D008774
9831002	87	117	neuroleptic malignant syndrome	Disease	D009459
9831002	137	152	methylphenidate	Chemical	D008774
9831002	244	272	multicystic encephalomalacia	Disease	D004678
9831002	298	329	hypoxic-ischemic encephalopathy	Disease	D020925
9831002	397	427	neuroleptic malignant syndrome	Disease	D009459
9831002	532	547	methylphenidate	Chemical	D008774
9831002	553	561	dopamine	Chemical	D004298
9831002	602	610	dopamine	Chemical	D004298
9831002	777	800	gamma-aminobutyric acid	Chemical	D005680
9831002	838	846	diazepam	Chemical	D003975
9831002	850	873	gamma-aminobutyric acid	Chemical	D005680
9831002	955	985	neuroleptic malignant syndrome	Disease	D009459
9831002	1005	1020	methylphenidate	Chemical	D008774
9831002	CID	D008774	D009459

9869655|t|Differential effects of 17alpha-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat.
9869655|a|Effects of 17alpha-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis. For this purpose, bile salt pool composition, synthesis of individual BS in vivo, hepatic activities, and expression levels of cholesterol 7alpha-hydroxylase (CYP7A), and sterol 27-hydroxylase (CYP27), as well as of other enzymes involved in BS synthesis, were analyzed in rats treated with EE (5 mg/kg, 3 days) or its vehicle. BS pool size was decreased by 27% but total BS synthesis was not affected by EE in intact rats. Synthesis of cholate was reduced by 68% in EE-treated rats, while that of chenodeoxycholate was increased by 60%. The recently identified Delta22-isomer of beta-muricholate contributed for 5.4% and 18.3 % (P < 0.01) to the pool in control and EE-treated rats, respectively, but could not be detected in bile after exhaustion of the pool. A clear reduction of BS synthesis was found in bile-diverted rats treated with EE, yet biliary BS composition was only minimally affected. Activity of CYP7A was decreased by EE in both intact and bile-diverted rats, whereas the activity of the CYP27 was not affected. Hepatic mRNA levels of CYP7A were significantly reduced by EE in bile-diverted rats only; CYP27 mRNA levels were not affected by EE. In addition, mRNA levels of sterol 12alpha-hydroxylase and lithocholate 6beta-hydroxylase were increased by bile diversion and suppressed by EE. This study shows that 17alpha-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats is associated with selective inhibition of the neutral pathway of bile salt (BS) synthesis. Simultaneous impairment of other enzymes in the BS biosynthetic pathways may contribute to overall effects of EE on BS synthesis.
9869655	24	48	17alpha-ethinylestradiol	Chemical	D004997
9869655	87	96	bile salt	Chemical	D001647
9869655	130	154	17alpha-ethinylestradiol	Chemical	D004997
9869655	156	158	EE	Chemical	D004997
9869655	211	220	bile salt	Chemical	D001647
9869655	222	224	BS	Chemical	D001647
9869655	352	354	BS	Chemical	D001647
9869655	384	393	bile salt	Chemical	D001647
9869655	436	438	BS	Chemical	D001647
9869655	493	504	cholesterol	Chemical	D002784
9869655	537	543	sterol	Chemical	D013261
9869655	608	610	BS	Chemical	D001647
9869655	657	659	EE	Chemical	D004997
9869655	694	696	BS	Chemical	D001647
9869655	738	740	BS	Chemical	D001647
9869655	771	773	EE	Chemical	D004997
9869655	803	810	cholate	Chemical	D020355
9869655	833	835	EE	Chemical	D004997
9869655	864	881	chenodeoxycholate	Chemical	D002635
9869655	1033	1035	EE	Chemical	D004997
9869655	1149	1151	BS	Chemical	D001647
9869655	1207	1209	EE	Chemical	D004997
9869655	1223	1225	BS	Chemical	D001647
9869655	1302	1304	EE	Chemical	D004997
9869655	1455	1457	EE	Chemical	D004997
9869655	1525	1527	EE	Chemical	D004997
9869655	1557	1563	sterol	Chemical	D013261
9869655	1670	1672	EE	Chemical	D004997
9869655	1696	1720	17alpha-ethinylestradiol	Chemical	D004997
9869655	1722	1724	EE	Chemical	D004997
9869655	1734	1758	intrahepatic cholestasis	Disease	D002780
9869655	1833	1842	bile salt	Chemical	D001647
9869655	1844	1846	BS	Chemical	D001647
9869655	1907	1909	BS	Chemical	D001647
9869655	1969	1971	EE	Chemical	D004997
9869655	1975	1977	BS	Chemical	D001647
9869655	CID	D004997	D002780

9881641|t|Glibenclamide-sensitive hypotension produced by helodermin assessed in the rat.
9881641|a|The effects of helodermin, a basic 35-amino acid peptide isolated from the venom of a lizard salivary gland, on arterial blood pressure and heart rate were examined in the rat, focusing on the possibility that activation of ATP sensitive K+ (K(ATP)) channels is involved in the responses. The results were also compared with those of vasoactive intestinal polypeptide (VIP). Helodermin produced hypotension in a dose-dependent manner with approximately similar potency and duration to VIP. Hypotension induced by both peptides was significantly attenuated by glibenclamide, which abolished a levcromakalim-produced decrease in arterial blood pressure. Oxyhemoglobin did not affect helodermin-induced hypotension, whereas it shortened the duration of acetylcholine (ACh)-produced hypotension. These findings suggest that helodermin-produced hypotension is partly attributable to the activation of glibenclamide-sensitive K+ channels (K(ATP) channels), which presumably exist on arterial smooth muscle cells. EDRF (endothelium-derived relaxing factor)/nitric oxide does not seem to play an important role in the peptide-produced hypotension.
9881641	0	13	Glibenclamide	Chemical	D005905
9881641	24	35	hypotension	Disease	D007022
9881641	48	58	helodermin	Chemical	C040442
9881641	95	105	helodermin	Chemical	C040442
9881641	118	128	amino acid	Chemical	D000596
9881641	304	307	ATP	Chemical	D000255
9881641	318	319	K	Chemical	D011188
9881641	322	323	K	Chemical	D011188
9881641	324	327	ATP	Chemical	D000255
9881641	455	465	Helodermin	Chemical	C040442
9881641	475	486	hypotension	Disease	D007022
9881641	570	581	Hypotension	Disease	D007022
9881641	639	652	glibenclamide	Chemical	D005905
9881641	672	685	levcromakalim	Chemical	D019806
9881641	761	771	helodermin	Chemical	C040442
9881641	780	791	hypotension	Disease	D007022
9881641	830	843	acetylcholine	Chemical	D000109
9881641	845	848	ACh	Chemical	D000109
9881641	859	870	hypotension	Disease	D007022
9881641	900	910	helodermin	Chemical	C040442
9881641	920	931	hypotension	Disease	D007022
9881641	976	989	glibenclamide	Chemical	D005905
9881641	1000	1001	K	Chemical	D011188
9881641	1013	1014	K	Chemical	D011188
9881641	1015	1018	ATP	Chemical	D000255
9881641	1130	1142	nitric oxide	Chemical	D009569
9881641	1207	1218	hypotension	Disease	D007022
9881641	CID	D000109	D007022
9881641	CID	D019806	D007022
9881641	CID	C040442	D007022

9889429|t|Long-term efficacy and adverse event of nifedipine sustained-release tablets for cyclosporin A-induced hypertension in patients with psoriasis.
9889429|a|Thirteen psoriatic patients with hypertension during the course of cyclosporin A therapy were treated for 25 months with a calcium channel blocker, sustained-release nifedipine, to study the clinical antihypertensive effects and adverse events during treatment with both drugs. Seven of the 13 patients had exhibited a subclinical hypertensive state before cyclosporin A therapy. Both systolic and diastolic blood pressures of these 13 patients were decreased significantly after 4 weeks of nifedipine therapy, and blood pressure was maintained within the normal range thereafter for 25 months. The adverse events during combined therapy with cyclosporin A and nifedipine included an increase in blood urea nitrogen levels in 9 of the 13 patients and development of gingival hyperplasia in 2 of the 13 patients. Our findings indicate that sustained-release nifedipine is useful for hypertensive psoriatic patients under long-term treatment with cyclosporin A, but that these patients should be monitored for gingival hyperplasia.
9889429	40	50	nifedipine	Chemical	D009543
9889429	81	94	cyclosporin A	Chemical	D016572
9889429	103	115	hypertension	Disease	D006973
9889429	133	142	psoriasis	Disease	D011565
9889429	153	162	psoriatic	Disease	D011565
9889429	177	189	hypertension	Disease	D006973
9889429	211	224	cyclosporin A	Chemical	D016572
9889429	267	274	calcium	Chemical	D002118
9889429	310	320	nifedipine	Chemical	D009543
9889429	475	487	hypertensive	Disease	D006973
9889429	501	514	cyclosporin A	Chemical	D016572
9889429	635	645	nifedipine	Chemical	D009543
9889429	787	800	cyclosporin A	Chemical	D016572
9889429	805	815	nifedipine	Chemical	D009543
9889429	840	859	blood urea nitrogen	Chemical	D001806
9889429	910	930	gingival hyperplasia	Disease	D005885
9889429	1001	1011	nifedipine	Chemical	D009543
9889429	1026	1038	hypertensive	Disease	D006973
9889429	1039	1048	psoriatic	Disease	D011565
9889429	1089	1102	cyclosporin A	Chemical	D016572
9889429	1152	1172	gingival hyperplasia	Disease	D005885
9889429	CID	D016572	D005885
9889429	CID	D016572	D006973
9889429	CID	D009543	D005885

10087562|t|Torsade de pointes ventricular tachycardia during low dose intermittent dobutamine treatment in a patient with dilated cardiomyopathy and congestive heart failure.
10087562|a|The authors describe the case of a 56-year-old woman with chronic, severe heart failure secondary to dilated cardiomyopathy and absence of significant ventricular arrhythmias who developed QT prolongation and torsade de pointes ventricular tachycardia during one cycle of intermittent low dose (2.5 mcg/kg per min) dobutamine. This report of torsade de pointes ventricular tachycardia during intermittent dobutamine supports the hypothesis that unpredictable fatal arrhythmias may occur even with low doses and in patients with no history of significant rhythm disturbances. The mechanisms of proarrhythmic effects of Dubutamine are discussed.
10087562	0	18	Torsade de pointes	Disease	D016171
10087562	19	42	ventricular tachycardia	Disease	D017180
10087562	72	82	dobutamine	Chemical	D004280
10087562	111	133	dilated cardiomyopathy	Disease	D002311
10087562	138	162	congestive heart failure	Disease	D006333
10087562	238	251	heart failure	Disease	D006333
10087562	265	287	dilated cardiomyopathy	Disease	D002311
10087562	315	338	ventricular arrhythmias	Disease	D001145
10087562	353	368	QT prolongation	Disease	D008133
10087562	373	391	torsade de pointes	Disease	D016171
10087562	392	415	ventricular tachycardia	Disease	D017180
10087562	479	489	dobutamine	Chemical	D004280
10087562	506	524	torsade de pointes	Disease	D016171
10087562	525	548	ventricular tachycardia	Disease	D017180
10087562	569	579	dobutamine	Chemical	D004280
10087562	629	640	arrhythmias	Disease	D001145
10087562	782	792	Dubutamine	Chemical	D004280
10087562	CID	D004280	D016171

10219427|t|Positive skin tests in late reactions to radiographic contrast media.
10219427|a|In the last few years delayed reactions several hours after the injection of radiographic and contrast materials (PRC) have been described with increasing frequency. The authors report two observations on patients with delayed reactions in whom intradermoreactions (IDR) and patch tests to a series of ionic and non ionic PRC were studied. After angiography by the venous route in patient n degree 1 a biphasic reaction with an immediate reaction (dyspnea, loss of consciousness) and delayed macro-papular rash appeared, whilst patient n degree 2 developed a generalised sensation of heat, persistent pain at the site of injection immediately and a generalised macro-papular reaction after 24 hours. The skin tests revealed positive delayed reactions of 24 hours and 48 hours by IDR and patch tests to only some PRC with common chains in their structures. The positive skin tests are in favour of immunological reactions and may help in diagnosis of allergy in the patients.
10219427	54	68	contrast media	Chemical	D003287
10219427	164	182	contrast materials	Chemical	D003287
10219427	184	187	PRC	Chemical	D003287
10219427	392	395	PRC	Chemical	D003287
10219427	518	525	dyspnea	Disease	D004417
10219427	527	548	loss of consciousness	Disease	D014474
10219427	562	580	macro-papular rash	Disease	D003875
10219427	671	675	pain	Disease	D010146
10219427	882	885	PRC	Chemical	D003287
10219427	1020	1027	allergy	Disease	D004342
10219427	CID	D003287	D010146
10219427	CID	D003287	D003875
10219427	CID	D003287	D004417
10219427	CID	D003287	D014474

10327032|t|Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection.
10327032|a|From 1986 to 1998, 29 cancer patients who had 32 episodes of transient hyperammonemic encephalopathy related to continuous infusion of 5-fluorouracil (5-FU) were identified. None of the patients had decompensated liver disease. Onset of hyperammonemic encephalopathy varied from 0.5 to 5 days (mean: 2.6 +/- 1.3 days) after the initiation of chemotherapy. Plasma ammonium level ranged from 248 to 2387 microg% (mean: 626 +/- 431 microg%). Among the 32 episodes, 26 (81%) had various degrees of azotemia, 18 (56%) occurred during bacterial infections and 14 (44%) without infection occurred during periods of dehydration. Higher plasma ammonium levels and more rapid onset of hyperammonemia were seen in 18 patients with bacterial infections (p=0.003 and 0.0006, respectively) and in nine patients receiving high daily doses (2600 or 1800 mg/m2) of 5-FU (p=0.0001 and < 0.0001, respectively). In 25 out of 32 episodes (78%), plasma ammonium levels and mental status returned to normal within 2 days after adequate management. In conclusion, hyperammonemic encephalopathy can occur in patients receiving continuous infusion of 5-FU. Azotemia, body fluid insufficiency and bacterial infections were frequently found in these patients. It is therefore important to recognize this condition in patients receiving continuous infusion of 5-FU.
10327032	18	47	hyperammonemic encephalopathy	Disease	D022124|D001927	hyperammonemic|encephalopathy
10327032	51	57	cancer	Disease	D009369
10327032	103	117	5-fluorouracil	Chemical	D005472
10327032	143	154	dehydration	Disease	D003681
10327032	159	168	infection	Disease	D007239
10327032	192	198	cancer	Disease	D009369
10327032	241	270	hyperammonemic encephalopathy	Disease	D022124|D001927	hyperammonemic|encephalopathy
10327032	305	319	5-fluorouracil	Chemical	D005472
10327032	321	325	5-FU	Chemical	D005472
10327032	383	396	liver disease	Disease	D008107
10327032	407	436	hyperammonemic encephalopathy	Disease	D022124|D001927	hyperammonemic|encephalopathy
10327032	533	541	ammonium	Chemical	D000644
10327032	664	672	azotemia	Disease	D053099
10327032	699	719	bacterial infections	Disease	D001424
10327032	741	750	infection	Disease	D007239
10327032	778	789	dehydration	Disease	D003681
10327032	805	813	ammonium	Chemical	D000644
10327032	845	859	hyperammonemia	Disease	D022124
10327032	890	910	bacterial infections	Disease	D001424
10327032	1018	1022	5-FU	Chemical	D005472
10327032	1101	1109	ammonium	Chemical	D000644
10327032	1210	1239	hyperammonemic encephalopathy	Disease	D022124|D001927	hyperammonemic|encephalopathy
10327032	1295	1299	5-FU	Chemical	D005472
10327032	1301	1309	Azotemia	Disease	D053099
10327032	1340	1360	bacterial infections	Disease	D001424
10327032	1501	1505	5-FU	Chemical	D005472
10327032	CID	D005472	D022124
10327032	CID	D005472	D001927

10390729|t|The effects of quinine and 4-aminopyridine on conditioned place preference and changes in motor activity induced by morphine in rats.
10390729|a|1. The effects of two unselective potassium (K(+)-) channel blockers, quinine (12.5, 25 and 50 mg/kg) and 4-aminopyridine (1 and 2 mg/kg), on conditioned place preference and biphasic changes in motor activity induced by morphine (10 mg/kg) were tested in Wistar rats. Quinine is known to block voltage-, calcium- and ATP-sensitive K(+)-channels while 4-aminopyridine is known to block voltage-sensitive K(+)-channels. 2. In the counterbalanced method, quinine attenuated morphine-induced place preference, whereas 4-aminopyridine was ineffective. In the motor activity test measured with an Animex-activity meter neither of the K(+)-channel blockers affected morphine-induced hypoactivity, but both K(+)-channel blockers prevented morphine-induced secondary hyperactivity. 3. These results suggest the involvement of quinine-sensitive but not 4-aminopyridine-sensitive K(+)-channels in morphine reward. It is also suggested that the blockade of K(+)-channels sensitive to these blockers is not sufficient to prevent morphine-induced hypoactivity whereas morphine-induced hyperactivity seems to be connected to both quinine- and 4-aminopyridine-sensitive K(+)-channels.
10390729	15	22	quinine	Chemical	D011803
10390729	27	42	4-aminopyridine	Chemical	D015761
10390729	116	124	morphine	Chemical	D009020
10390729	168	177	potassium	Chemical	D011188
10390729	179	180	K	Chemical	D011188
10390729	204	211	quinine	Chemical	D011803
10390729	240	255	4-aminopyridine	Chemical	D015761
10390729	355	363	morphine	Chemical	D009020
10390729	403	410	Quinine	Chemical	D011803
10390729	439	446	calcium	Chemical	D002118
10390729	452	455	ATP	Chemical	D000255
10390729	466	467	K	Chemical	D011188
10390729	486	501	4-aminopyridine	Chemical	D015761
10390729	538	539	K	Chemical	D011188
10390729	587	594	quinine	Chemical	D011803
10390729	606	614	morphine	Chemical	D009020
10390729	649	664	4-aminopyridine	Chemical	D015761
10390729	763	764	K	Chemical	D011188
10390729	794	802	morphine	Chemical	D009020
10390729	811	823	hypoactivity	Disease	D009069
10390729	834	835	K	Chemical	D011188
10390729	866	874	morphine	Chemical	D009020
10390729	893	906	hyperactivity	Disease	D006948
10390729	952	959	quinine	Chemical	D011803
10390729	978	993	4-aminopyridine	Chemical	D015761
10390729	1004	1005	K	Chemical	D011188
10390729	1021	1029	morphine	Chemical	D009020
10390729	1080	1081	K	Chemical	D011188
10390729	1151	1159	morphine	Chemical	D009020
10390729	1168	1180	hypoactivity	Disease	D009069
10390729	1189	1197	morphine	Chemical	D009020
10390729	1206	1219	hyperactivity	Disease	D006948
10390729	1250	1257	quinine	Chemical	D011803
10390729	1263	1278	4-aminopyridine	Chemical	D015761
10390729	1289	1290	K	Chemical	D011188
10390729	CID	D009020	D006948

10401555|t|Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice.
10401555|a|1. Nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid receptor-like receptor 1 (ORL1) and involves in various functions in the central nervous system (CNS). On the other hand, nocistatin is recently isolated from the same precursor as nociceptin and blocks nociceptin-induced allodynia and hyperalgesia. 2. Although ORL1 receptors which display a high degree of sequence homology with classical opioid receptors are abundant in the hippocampus, little is known regarding their role in learning and memory. 3. The present study was designed to investigate whether nociceptin/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory.
10401555	0	10	Nociceptin	Chemical	C096012
10401555	11	22	orphanin FQ	Chemical	C096012
10401555	27	37	nocistatin	Chemical	C111148
10401555	41	71	learning and memory impairment	Disease	D007859|D008569	learning impairment|memory impairment
10401555	83	94	scopolamine	Chemical	D012601
10401555	107	117	Nociceptin	Chemical	C096012
10401555	133	144	orphanin FQ	Chemical	C096012
10401555	314	324	nocistatin	Chemical	C111148
10401555	373	383	nociceptin	Chemical	C096012
10401555	395	405	nociceptin	Chemical	C096012
10401555	414	423	allodynia	Disease	D006930
10401555	428	440	hyperalgesia	Disease	D006930
10401555	701	711	nociceptin	Chemical	C096012
10401555	712	723	orphanin FQ	Chemical	C096012
10401555	728	738	nocistatin	Chemical	C111148
10401555	754	787	impairment of learning and memory	Disease	D007859|D008569	impairment of learning|impairment of memory
10401555	799	810	scopolamine	Chemical	D012601
10401555	959	969	nocistatin	Chemical	C111148
10401555	1298	1308	nociceptin	Chemical	C096012
10401555	1389	1399	nocistatin	Chemical	C111148
10401555	1558	1569	scopolamine	Chemical	D012601
10401555	1682	1692	nocistatin	Chemical	C111148
10401555	1813	1824	scopolamine	Chemical	D012601
10401555	CID	D012601	D008569
10401555	CID	D012601	D007859

10427794|t|Meloxicam-induced liver toxicity.
10427794|a|We report the case of a female patient with rheumatoid arthritis who developed acute cytolytic hepatitis due to meloxicam. Recently introduced in Belgium, meloxicam is the first nonsteroidal antiinflammatory drug with selective action on the inducible form of cyclooxygenase 2. The acute cytolytic hepatitis occurred rapidly after meloxicam administration and was associated with the development of antinuclear antibodies suggesting a hypersensitivity mechanism. This first case of meloxicam related liver toxicity demonstrates the potential of this drug to induce hepatic damage.
10427794	0	9	Meloxicam	Chemical	C065757
10427794	18	32	liver toxicity	Disease	D056486
10427794	78	98	rheumatoid arthritis	Disease	D001172
10427794	129	138	hepatitis	Disease	D056486
10427794	146	155	meloxicam	Chemical	C065757
10427794	189	198	meloxicam	Chemical	C065757
10427794	332	341	hepatitis	Disease	D056486
10427794	365	374	meloxicam	Chemical	C065757
10427794	469	485	hypersensitivity	Disease	D004342
10427794	516	525	meloxicam	Chemical	C065757
10427794	534	548	liver toxicity	Disease	D056486
10427794	599	613	hepatic damage	Disease	D056486
10427794	CID	C065757	D004342
10427794	CID	C065757	D056486

10462057|t|Induction of apoptosis by remoxipride metabolites in HL60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia.
10462057|a|The antipsychotic agent, remoxipride [(S)-(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenz amide] has been associated with acquired aplastic anemia. We have examined the ability of remoxipride, three pyrrolidine ring metabolites and five aromatic ring metabolites of the parent compound to induce apoptosis in HL60 cells and human bone marrow progenitor (HBMP) cells. Cells were treated for 0-24 h with each compound (0-200 microM). Apoptosis was assessed by fluorescence microscopy in Hoechst 33342- and propidium iodide stained cell samples. Results were confirmed by determination of internucleosomal DNA fragmentation using gel electrophoresis for HL60 cell samples and terminal deoxynucleotidyl transferase assay in HBMP cells. The catechol and hydroquinone metabolites, NCQ436 and NCQ344, induced apoptosis in HL60 and HBMP cells in a time- and concentration dependent manner, while the phenols, NCR181, FLA873, and FLA797, and the derivatives formed by oxidation of the pyrrolidine ring, FLA838, NCM001, and NCL118, had no effect. No necrosis was observed in cells treated with NCQ436 but NCQ344 had a biphasic effect in both cell types, inducing apoptosis at lower concentrations and necrosis at higher concentrations. These data show that the catechol and hydroquinone metabolites of remoxipride have direct toxic effects in HL60 and HBMP cells, leading to apoptosis, while the phenol metabolites were inactive. Similarly, benzene-derived catechol and hydroquinone, but not phenol, induce apoptosis in HBMP cells [Moran et al., Mol. Pharmacol., 50 (1996) 610-615]. We propose that remoxipride and benzene may induce aplastic anemia via production of similar reactive metabolites and that the ability of NCQ436 and NCQ344 to induce apoptosis in HBMP cells may contribute to the mechanism underlying acquired aplastic anemia that has been associated with remoxipride.
10462057	26	37	remoxipride	Chemical	D017330
10462057	133	144	remoxipride	Chemical	D017330
10462057	153	168	aplastic anemia	Disease	D000741
10462057	195	206	remoxipride	Chemical	D017330
10462057	208	282	(S)-(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenz amide	Chemical	D017330
10462057	318	333	aplastic anemia	Disease	D000741
10462057	367	378	remoxipride	Chemical	D017330
10462057	386	397	pyrrolidine	Chemical	C032519
10462057	672	685	Hoechst 33342	Chemical	C017807
10462057	691	707	propidium iodide	Chemical	D011419
10462057	923	931	catechol	Chemical	C034221
10462057	936	948	hydroquinone	Chemical	C031927
10462057	962	968	NCQ436	Chemical	C084325
10462057	973	979	NCQ344	Chemical	C112341
10462057	1079	1086	phenols	Chemical	D010636
10462057	1108	1114	FLA797	Chemical	C050313
10462057	1163	1174	pyrrolidine	Chemical	C032519
10462057	1227	1235	necrosis	Disease	D009336
10462057	1271	1277	NCQ436	Chemical	C084325
10462057	1282	1288	NCQ344	Chemical	C112341
10462057	1378	1386	necrosis	Disease	D009336
10462057	1438	1446	catechol	Chemical	C034221
10462057	1451	1463	hydroquinone	Chemical	C031927
10462057	1479	1490	remoxipride	Chemical	D017330
10462057	1573	1579	phenol	Chemical	D019800
10462057	1618	1625	benzene	Chemical	D001554
10462057	1634	1642	catechol	Chemical	C034221
10462057	1647	1659	hydroquinone	Chemical	C031927
10462057	1669	1675	phenol	Chemical	D019800
10462057	1776	1787	remoxipride	Chemical	D017330
10462057	1792	1799	benzene	Chemical	D001554
10462057	1811	1826	aplastic anemia	Disease	D000741
10462057	1898	1904	NCQ436	Chemical	C084325
10462057	1909	1915	NCQ344	Chemical	C112341
10462057	2002	2017	aplastic anemia	Disease	D000741
10462057	2048	2059	remoxipride	Chemical	D017330
10462057	CID	D017330	D000741
10462057	CID	D001554	D000741

10510854|t|Synthesis and preliminary pharmacological investigations of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine derivatives as potential atypical antipsychotic agents in mice.
10510854|a|In research towards the development of new atypical antipsychotic agents, one strategy is that the dopaminergic system can be modulated through manipulation of the serotonergic system. The synthesis and preliminary pharmacological evaluation of a series of potential atypical antipsychotic agents based on the structure of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine (7) is described. Compound 7e, 5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]ethyl}-2,3-dihy dro-1H- indol-2-one, from this series showed significant affinities at the 5-HT1A and 5-HT2A receptors and moderate affinity at the D2 receptor. 7e exhibits a high reversal of catalepsy induced by haloperidol indicating its atypical antipsychotic nature.
10510854	60	103	1-(1,2-dihydro-2-acenaphthylenyl)piperazine	Chemical	-1
10510854	491	534	1-(1,2-dihydro-2-acenaphthylenyl)piperazine	Chemical	-1
10510854	566	652	5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]ethyl}-2,3-dihy dro-1H- indol-2-one	Chemical	-1
10510854	809	818	catalepsy	Disease	D002375
10510854	830	841	haloperidol	Chemical	D006220
10510854	CID	D006220	D002375

10672628|t|Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice.
10672628|a|RATIONALE: NG-nitro-L-arginine (L-NOARG), an inhibitor of nitric-oxide synthase (NOS), induces catalepsy in mice. This effect undergoes rapid tolerance, showing a significant decrease after 2 days of sub-chronic L-NOARG treatment. Nitric oxide (NO) has been shown to influence dopaminergic neurotransmission in the striatum. Neuroleptic drugs such as haloperidol, which block dopamine receptors, also cause catalepsy in rodents. OBJECTIVES: To investigate the effects of subchronic L-NOARG treatment in haloperidol-induced catalepsy and the number of NOS neurons in areas related to motor control. METHODS: Male albino Swiss mice were treated sub-chronically (twice a day for 4 days) with L-NOARG (40 mg/kg i.p.) or haloperidol (1 mg/kg i.p.). Catalepsy was evaluated at the beginning and the end of the treatments. Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was also employed to visualize NOS as an index of enzyme expression in mice brain regions related to motor control. RESULTS: L-NOARG sub-chronic administration produced tolerance of L-NOARG and of haloperidol-induced catalepsy. It also induced an increase in the number of NADPH-d-positive cells in the dorsal part of the caudate and accumbens nuclei compared with haloperidol and in the pedunculopontine tegmental nucleus compared with saline. In contrast, there was a decrease in NADPH-d neuron number in the substantia nigra, pars compacta in both haloperidol-treated and L-NOARG-treated animals. CONCLUSIONS: The results give further support to the hypothesis that NO plays a role in motor behavior control and suggest that it may take part in the synaptic changes produced by antipsychotic treatment.
10672628	26	38	nitric-oxide	Chemical	D009569
10672628	58	69	haloperidol	Chemical	D006220
10672628	78	87	catalepsy	Disease	D002375
10672628	106	111	NADPH	Chemical	D009249
10672628	151	170	NG-nitro-L-arginine	Chemical	D019335
10672628	172	179	L-NOARG	Chemical	D019335
10672628	198	210	nitric-oxide	Chemical	D009569
10672628	235	244	catalepsy	Disease	D002375
10672628	352	359	L-NOARG	Chemical	D019335
10672628	371	383	Nitric oxide	Chemical	D009569
10672628	385	387	NO	Chemical	D009569
10672628	491	502	haloperidol	Chemical	D006220
10672628	516	524	dopamine	Chemical	D004298
10672628	547	556	catalepsy	Disease	D002375
10672628	622	629	L-NOARG	Chemical	D019335
10672628	643	654	haloperidol	Chemical	D006220
10672628	663	672	catalepsy	Disease	D002375
10672628	829	836	L-NOARG	Chemical	D019335
10672628	856	867	haloperidol	Chemical	D006220
10672628	884	893	Catalepsy	Disease	D002375
10672628	964	1007	nicotinamide adenine dinucleotide phosphate	Chemical	D009249
10672628	1020	1025	NADPH	Chemical	D009249
10672628	1169	1176	L-NOARG	Chemical	D019335
10672628	1226	1233	L-NOARG	Chemical	D019335
10672628	1241	1252	haloperidol	Chemical	D006220
10672628	1261	1270	catalepsy	Disease	D002375
10672628	1317	1322	NADPH	Chemical	D009249
10672628	1409	1420	haloperidol	Chemical	D006220
10672628	1526	1531	NADPH	Chemical	D009249
10672628	1595	1606	haloperidol	Chemical	D006220
10672628	1619	1626	L-NOARG	Chemical	D019335
10672628	1713	1715	NO	Chemical	D009569
10672628	CID	D006220	D002375

10677406|t|Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia.
10677406|a|OBJECTIVE: To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. DESIGN: A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. SUBJECTS: 10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. INTERVENTIONS: Treadmill exercise and dobutamine stress were performed on different days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. RESULTS: Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no difference in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), -5.6 (1.5)%, p < 0.05; and -6.1 (2.2)%, p < 0. 01), and at 30 and 45 minutes after dobutamine (-10.8 (1.8)% and -5. 5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst affected segment 15 and 30 minutes after exercise (-27.9 (7.2)% and -28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (-32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). CONCLUSIONS: In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease.
10677406	10	38	left ventricular dysfunction	Disease	D018487
10677406	63	86	coronary artery disease	Disease	D003324
10677406	98	108	dobutamine	Chemical	D004280
10677406	130	150	myocardial ischaemia	Disease	D017202
10677406	241	269	left ventricular dysfunction	Disease	D018487
10677406	287	310	coronary artery disease	Disease	D003324
10677406	474	484	dobutamine	Chemical	D004280
10677406	493	502	ischaemia	Disease	D007511
10677406	531	544	stable angina	Disease	D060050
10677406	570	593	coronary artery disease	Disease	D003324
10677406	671	681	dobutamine	Chemical	D004280
10677406	1073	1083	depression	Disease	D003866
10677406	1309	1319	dobutamine	Chemical	D004280
10677406	1540	1550	dobutamine	Chemical	D004280
10677406	1701	1724	coronary artery disease	Disease	D003324
10677406	1726	1736	dobutamine	Chemical	D004280
10677406	1745	1754	ischaemia	Disease	D007511
10677406	1787	1815	left ventricular dysfunction	Disease	D018487
10677406	1832	1851	myocardial stunning	Disease	D017682
10677406	1890	1900	Dobutamine	Chemical	D004280
10677406	1909	1918	ischaemia	Disease	D007511
10677406	2016	2039	coronary artery disease	Disease	D003324
10677406	CID	D004280	D018487
10677406	CID	D004280	D017682

10713017|t|Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension.
10713017|a|BACKGROUND: The use of appetite suppressants in Europe has been associated with the development of primary pulmonary hypertension (PPH). Recently, fenfluramine appetite suppressants became widely used in the United States but were withdrawn in September 1997 because of concerns over adverse effects. MATERIALS AND METHODS: We conducted a prospective surveillance study on patients diagnosed with pulmonary hypertension at 12 large referral centers in North America. Data collected on patients seen from September 1, 1996, to December 31, 1997, included the cause of the pulmonary hypertension and its severity. Patients with no identifiable cause of pulmonary hypertension were classed as PPH. A history of drug exposure also was taken with special attention on the use of antidepressants, anorexigens, and amphetamines. RESULTS: Five hundred seventy-nine patients were studied, 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension [SPH]). The use of anorexigens was common in both groups. However, of the medications surveyed, only the fenfluramines had a significant preferential association with PPH as compared with SPH (adjusted odds ratio for use > 6 months, 7.5; 95% confidence interval, 1.7 to 32.4). The association was stronger with longer duration of use when compared to shorter duration of use and was more pronounced in recent users than in remote users. An unexpectedly high (11.4%) number of patients with SPH had used anorexigens. CONCLUSION: The magnitude of the association with PPH, the increase of association with increasing duration of use, and the specificity for fenfluramines are consistent with previous studies indicating that fenfluramines are causally related to PPH. The high prevalence of anorexigen use in patients with SPH also raises the possibility that these drugs precipitate pulmonary hypertension in patients with underlying conditions associated with SPH.
10713017	16	38	pulmonary hypertension	Disease	D006976
10713017	109	131	pulmonary hypertension	Disease	D006976
10713017	232	262	primary pulmonary hypertension	Disease	D006976
10713017	264	267	PPH	Disease	D006976
10713017	280	292	fenfluramine	Chemical	D005277
10713017	530	552	pulmonary hypertension	Disease	D006976
10713017	704	726	pulmonary hypertension	Disease	D006976
10713017	784	806	pulmonary hypertension	Disease	D006976
10713017	823	826	PPH	Disease	D006976
10713017	941	953	amphetamines	Chemical	D000662
10713017	1022	1025	PPH	Disease	D006976
10713017	1039	1061	pulmonary hypertension	Disease	D006976
10713017	1091	1113	pulmonary hypertension	Disease	D006976
10713017	1219	1232	fenfluramines	Chemical	D005277
10713017	1281	1284	PPH	Disease	D006976
10713017	1680	1683	PPH	Disease	D006976
10713017	1770	1783	fenfluramines	Chemical	D005277
10713017	1837	1850	fenfluramines	Chemical	D005277
10713017	1875	1878	PPH	Disease	D006976
10713017	1996	2018	pulmonary hypertension	Disease	D006976
10713017	CID	D005277	D006976

10726030|t|Clinical aspects of heparin-induced thrombocytopenia and thrombosis and other side effects of heparin therapy.
10726030|a|Heparin, first used to prevent the clotting of blood in vitro, has been clinically used to treat thrombosis for more than 50 years. Although several new anticoagulant drugs are in development, heparin remains the anticoagulant of choice to treat acute thrombotic episodes. The clinical effects of heparin are meritorious, but side effects do exist. Bleeding is the primary untoward effect of heparin. Major bleeding is of primary concern in patients receiving heparin therapy. However, additional important untoward effects of heparin therapy include heparin-induced thrombocytopenia, heparin-associated osteoporosis, eosinophilia, skin reactions, allergic reactions other than thrombocytopenia, alopecia, transaminasemia, hyperkalemia, hypoaldosteronism, and priapism. These side effects are relatively rare in a given individual, but given the extremely widespread use of heparin, some are quite common, particularly HITT and osteoporosis. Although reasonable incidences of many of these side effects can be "softly" deduced from current reports dealing with unfractionated heparin, at present the incidences of these side effects with newer low molecular weight heparins appear to be much less common. However, only longer experience will more clearly define the incidence of each side effect with low molecular weight preparations.
10726030	20	27	heparin	Chemical	D006493
10726030	36	52	thrombocytopenia	Disease	D013921
10726030	57	67	thrombosis	Disease	D013927
10726030	94	101	heparin	Chemical	D006493
10726030	111	118	Heparin	Chemical	D006493
10726030	208	218	thrombosis	Disease	D013927
10726030	304	311	heparin	Chemical	D006493
10726030	363	373	thrombotic	Disease	D013927
10726030	408	415	heparin	Chemical	D006493
10726030	460	468	Bleeding	Disease	D006470
10726030	503	510	heparin	Chemical	D006493
10726030	518	526	bleeding	Disease	D006470
10726030	571	578	heparin	Chemical	D006493
10726030	638	645	heparin	Chemical	D006493
10726030	662	669	heparin	Chemical	D006493
10726030	678	694	thrombocytopenia	Disease	D013921
10726030	696	703	heparin	Chemical	D006493
10726030	715	727	osteoporosis	Disease	D010024
10726030	729	741	eosinophilia	Disease	D004802
10726030	743	757	skin reactions	Disease	D012871
10726030	759	777	allergic reactions	Disease	D004342
10726030	789	805	thrombocytopenia	Disease	D013921
10726030	807	815	alopecia	Disease	D000505
10726030	834	846	hyperkalemia	Disease	D006947
10726030	848	865	hypoaldosteronism	Disease	D006994
10726030	871	879	priapism	Disease	D011317
10726030	985	992	heparin	Chemical	D006493
10726030	1030	1034	HITT	Disease	D013921|D013927
10726030	1039	1051	osteoporosis	Disease	D010024
10726030	1187	1194	heparin	Chemical	D006493
10726030	1276	1284	heparins	Chemical	D006493
10726030	CID	D006493	D012871
10726030	CID	D006493	D004342
10726030	CID	D006493	D013921
10726030	CID	D006493	D006947
10726030	CID	D006493	D010024
10726030	CID	D006493	D011317
10726030	CID	D006493	D006994
10726030	CID	D006493	D004802
10726030	CID	D006493	D000505

10764869|t|A case of bilateral optic neuropathy in a patient on tacrolimus (FK506) therapy after liver transplantation.
10764869|a|PURPOSE: To report a case of bilateral optic neuropathy in a patient receiving tacrolimus (FK 506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) for immunosuppression after orthotropic liver transplantation. METHOD: Case report. In a 58-year-old man receiving tacrolimus after orthotropic liver transplantation, serial neuro-ophthalmologic examinations and laboratory studies were performed. RESULTS: The patient had episodic deterioration of vision in both eyes, with clinical features resembling ischemic optic neuropathies. Deterioration of vision occurred despite discontinuation of the tacrolimus. CONCLUSION: Tacrolimus and other immunosuppressive agents may be associated with optic nerve toxicity.
10764869	20	36	optic neuropathy	Disease	D009901
10764869	53	63	tacrolimus	Chemical	D016559
10764869	65	70	FK506	Chemical	D016559
10764869	148	164	optic neuropathy	Disease	D009901
10764869	188	198	tacrolimus	Chemical	D016559
10764869	200	206	FK 506	Chemical	D016559
10764869	372	382	tacrolimus	Chemical	D016559
10764869	610	637	ischemic optic neuropathies	Disease	D018917
10764869	639	662	Deterioration of vision	Disease	D015354
10764869	703	713	tacrolimus	Chemical	D016559
10764869	727	737	Tacrolimus	Chemical	D016559
10764869	796	816	optic nerve toxicity	Disease	D009901
10764869	CID	D016559	D009901

10770468|t|Hypercalcemia, arrhythmia, and mood stabilizers.
10770468|a|Recent findings in a bipolar patient receiving maintenance lithium therapy who developed hypercalcemia and severe bradyarrhythmia prompted the authors to conduct a retrospective study of bipolar patients with lithium-associated hypercalcemia. A printout of all cases of hypercalcemia that presented during a 1-year period was generated. After eliminating spurious hypercalcemias or those associated with intravenous fluids, the authors identified 18 non-lithium-treated patients with hypercalcemias related to malignancies and other medical conditions (group A) and 12 patients with lithium-associated hypercalcemia (group B). Patients in group B were not comparable to those in group A, as the latter were medically compromised and were receiving multiple pharmacotherapies. Thus, two control groups were generated: group C1, which included age- and sex-comparable lithium-treated bipolar normocalcemic patients, and group C2, which included bipolar normocalcemic patients treated with anticonvulsant mood stabilizers. The electrocardiographic (ECG) findings for patients in group B were compared with those of patients in groups C1 and C2. It was found that these groups did not differ in their overall frequency of ECG abnormalities; however, there were significant differences in the frequency of conduction defects. Patients with hypercalcemia resulting from medical diseases and bipolar patients with lithium-associated hypercalcemia had significantly higher frequencies of conduction defects. Patients in group A had significant mortality at 2-year follow-up (28%), in contrast to zero mortality in the other three groups. The clinical implications of these findings are discussed.
10770468	0	13	Hypercalcemia	Disease	D006934
10770468	15	25	arrhythmia	Disease	D001145
10770468	70	77	bipolar	Disease	D001714
10770468	108	115	lithium	Chemical	D008094
10770468	138	151	hypercalcemia	Disease	D006934
10770468	163	178	bradyarrhythmia	Disease	D001919
10770468	236	243	bipolar	Disease	D001714
10770468	258	265	lithium	Chemical	D008094
10770468	277	290	hypercalcemia	Disease	D006934
10770468	319	332	hypercalcemia	Disease	D006934
10770468	413	427	hypercalcemias	Disease	D006934
10770468	503	510	lithium	Chemical	D008094
10770468	533	547	hypercalcemias	Disease	D006934
10770468	559	571	malignancies	Disease	D009369
10770468	632	639	lithium	Chemical	D008094
10770468	651	664	hypercalcemia	Disease	D006934
10770468	915	922	lithium	Chemical	D008094
10770468	931	938	bipolar	Disease	D001714
10770468	992	999	bipolar	Disease	D001714
10770468	1384	1397	hypercalcemia	Disease	D006934
10770468	1434	1441	bipolar	Disease	D001714
10770468	1456	1463	lithium	Chemical	D008094
10770468	1475	1488	hypercalcemia	Disease	D006934
10770468	CID	D008094	D006934

10933650|t|Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating amphotericin B.
10933650|a|NS-718, a lipid nanosphere incorporating amphotericin B, is effective against pathogenic fungi and has low toxicity. We compared the toxicity of NS-718 with that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vitro using renal cell cultures and in vivo by biochemical analysis, histopathological study of the kidney and pharmacokinetic study of amphotericin B following intravenous infusion of the formulation in rats. Incubation with NS-718 resulted in significantly less damage of cultured human renal proximal tubular epithelial cells compared with D-AmB. Serum blood urea and creatinine concentrations increased significantly in rats given an iv infusion of D-AmB 3 mg/kg but not in those given the same dose of NS-718. Histopathological examination of the kidney showed tubular necrosis in D-AmB-treated rats but no change in NS-718-treated rats. Amphotericin B concentrations in the kidney in NS-718-treated rats were higher than those in D-AmB-treated rats. Our in vitro and in vivo results suggest that incorporation of amphotericin B into lipid nanospheres of NS-718 attenuates the nephrotoxicity of amphotericin B.
10933650	15	29	nephrotoxicity	Disease	D007674
10933650	81	95	amphotericin B	Chemical	D000666
10933650	138	152	amphotericin B	Chemical	D000666
10933650	204	212	toxicity	Disease	D064420
10933650	230	238	toxicity	Disease	D064420
10933650	262	271	Fungizone	Chemical	D000666
10933650	273	307	amphotericin B-sodium deoxycholate	Chemical	C059765
10933650	309	314	D-AmB	Chemical	C059765
10933650	455	469	amphotericin B	Chemical	D000666
10933650	662	667	D-AmB	Chemical	C059765
10933650	681	685	urea	Chemical	D014508
10933650	690	700	creatinine	Chemical	D003404
10933650	772	777	D-AmB	Chemical	C059765
10933650	885	901	tubular necrosis	Disease	D007683
10933650	905	910	D-AmB	Chemical	C059765
10933650	962	976	Amphotericin B	Chemical	D000666
10933650	1055	1060	D-AmB	Chemical	C059765
10933650	1138	1152	amphotericin B	Chemical	D000666
10933650	1201	1215	nephrotoxicity	Disease	D007674
10933650	1219	1233	amphotericin B	Chemical	D000666
10933650	CID	C059765	D007683

10939760|t|Patterns of sulfadiazine acute nephrotoxicity.
10939760|a|Sulfadiazine acute nephrotoxicity is reviving specially because of its use in toxoplasmosis in HIV-positive patients. We report 4 cases, one of them in a previously healthy person. Under treatment with sulfadiazine they developed oliguria, abdominal pain, renal failure and showed multiple radiolucent renal calculi in echography. All patients recovered their previous normal renal function after adequate hydration and alcalinization. A nephrostomy tube had to be placed in one of the patients for ureteral lithiasis in a single functional kidney. None of them needed dialysis or a renal biopsy because of a typical benign course. Treatment with sulfadiazine requires exquisite control of renal function, an increase in water ingestion and possibly the alcalinization of the urine. We communicate a case in a previously healthy person, a fact not found in the recent literature. Probably many more cases are not detected. We think that a prospective study would be useful.
10939760	12	24	sulfadiazine	Chemical	D013411
10939760	25	45	acute nephrotoxicity	Disease	D058186
10939760	47	59	Sulfadiazine	Chemical	D013411
10939760	60	80	acute nephrotoxicity	Disease	D058186
10939760	125	138	toxoplasmosis	Disease	D014123
10939760	249	261	sulfadiazine	Chemical	D013411
10939760	277	285	oliguria	Disease	D009846
10939760	287	301	abdominal pain	Disease	D015746
10939760	303	316	renal failure	Disease	D051437
10939760	349	362	renal calculi	Disease	D007669
10939760	546	564	ureteral lithiasis	Disease	D052878
10939760	694	706	sulfadiazine	Chemical	D013411
10939760	CID	D013411	D007669
10939760	CID	D013411	D058186

10960401|t|Downbeat nystagmus associated with intravenous patient-controlled administration of morphine.
10960401|a|IMPLICATIONS: This case documents a patient who developed dizziness with downbeating nystagmus while receiving a relatively large dose of IV patient-controlled analgesia morphine. Although there have been case reports of epidural morphine with these symptoms and signs, this has not been previously documented with IV or patient-controlled analgesia morphine.
10960401	0	18	Downbeat nystagmus	Disease	D009759
10960401	84	92	morphine	Chemical	D009020
10960401	152	161	dizziness	Disease	D004244
10960401	167	188	downbeating nystagmus	Disease	D009759
10960401	264	272	morphine	Chemical	D009020
10960401	324	332	morphine	Chemical	D009020
10960401	444	452	morphine	Chemical	D009020
10960401	CID	D009020	D004244
10960401	CID	D009020	D009759

10975596|t|Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction.
10975596|a|The hemodynamic and antiadrenergic effects of dronedarone, a noniodinated compound structurally related to amiodarone, were compared with those of amiodarone after prolonged oral administration, both at rest and during sympathetic stimulation in conscious dogs with a healed myocardial infarction. All dogs (n = 6) randomly received orally dronedarone (10 and 30 mg/kg), amiodarone (10 and 30 mg/kg), and placebo twice daily for 7 days, with a 3-week washout between consecutive treatments. Heart rate (HR), mean arterial pressure (MBP), positive rate of increase of left ventricular pressure (+LVdP/dt), echocardiographically assessed left ventricular ejection fraction (LVEF), and fractional shortening (FS), as well as chronotropic response to isoproterenol and exercise-induced sympathetic stimulation were evaluated under baseline and posttreatment conditions. Resting values of LVEF, FS, +LVdP/dt, and MBP remained unchanged whatever the drug and the dosing regimen, whereas resting HR was significantly and dose-dependently lowered after dronedarone and to a lesser extent after amiodarone. Both dronedarone and amiodarone significantly reduced the exercise-induced tachycardia and, at the highest dose, decreased the isoproterenol-induced tachycardia. Thus, dronedarone and amiodarone displayed a similar level of antiadrenergic effect and did not impair the resting left ventricular function. Consequently, dronedarone might be particularly suitable for the treatment and prevention of various clinical arrhythmias, without compromising the left ventricular function.
10975596	42	53	dronedarone	Chemical	C118667
10975596	58	68	amiodarone	Chemical	D000638
10975596	94	115	myocardial infarction	Disease	D009203
10975596	163	174	dronedarone	Chemical	C118667
10975596	224	234	amiodarone	Chemical	D000638
10975596	264	274	amiodarone	Chemical	D000638
10975596	392	413	myocardial infarction	Disease	D009203
10975596	457	468	dronedarone	Chemical	C118667
10975596	488	498	amiodarone	Chemical	D000638
10975596	864	877	isoproterenol	Chemical	D007545
10975596	1162	1173	dronedarone	Chemical	C118667
10975596	1203	1213	amiodarone	Chemical	D000638
10975596	1220	1231	dronedarone	Chemical	C118667
10975596	1236	1246	amiodarone	Chemical	D000638
10975596	1290	1301	tachycardia	Disease	D013610
10975596	1342	1355	isoproterenol	Chemical	D007545
10975596	1364	1375	tachycardia	Disease	D013610
10975596	1383	1394	dronedarone	Chemical	C118667
10975596	1399	1409	amiodarone	Chemical	D000638
10975596	1533	1544	dronedarone	Chemical	C118667
10975596	1629	1640	arrhythmias	Disease	D001145
10975596	CID	D007545	D013610

10985896|t|Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum.
10985896|a|BACKGROUND: Several studies have demonstrated liposomal doxorubicin (Doxil) to be an active antineoplastic agent in platinum-resistant ovarian cancer, with dose limiting toxicity of the standard dosing regimen (50 mg/m(2) q 4 weeks) being severe erythrodysesthesia ("hand-foot syndrome") and stomatitis. We wished to develop a more tolerable liposomal doxorubicin treatment regimen and document its level of activity in a well-defined patient population with platinum/paclitaxel-refractory disease. METHODS AND MATERIALS: Patients with ovarian or fallopian tube cancers or primary peritoneal carcinoma with platinum/paclitaxel-refractory disease (stable or progressive disease following treatment with these agents or previous objective response <3 months in duration) were treated with liposomal doxorubicin at a dose of 40 mg/m(2) q 4 weeks. RESULTS: A total of 49 patients (median age: 60; range 41-81) entered this phase 2 trial. The median number of prior regimens was 2 (range: 1-6). Six (12%) and 4 (8%) patients experienced grade 2 hand-foot syndrome and stomatitis, respectively (no episodes of grade 3). One patient developed grade 3 diarrhea requiring hospitalization for hydration. Six (12%) individuals required dose reductions. The median number of courses of liposomal doxorubicin administered on this protocol was 2 (range: 1-12). Four of 44 patients (9%) evaluable for response exhibited objective and subjective evidence of an antineoplastic effect of therapy. CONCLUSION: This modified liposomal doxorubicin regimen results in less toxicity (stomatitis, hand-foot syndrome) than the standard FDA-approved dose schedule. Definite, although limited, antineoplastic activity is observed in patients with well-defined platinum- and paclitaxel-refractory ovarian cancer.
10985896	27	38	doxorubicin	Chemical	D004317
10985896	55	63	platinum	Chemical	D010984
10985896	64	74	paclitaxel	Chemical	D017239
10985896	86	120	ovarian and fallopian tube cancers	Disease	D010051|D005185	ovarian cancers|fallopian tube cancers
10985896	133	160	carcinoma of the peritoneum	Disease	D010534
10985896	218	229	doxorubicin	Chemical	D004317
10985896	231	236	Doxil	Chemical	D004317
10985896	278	286	platinum	Chemical	D010984
10985896	297	311	ovarian cancer	Disease	D010051
10985896	332	340	toxicity	Disease	D064420
10985896	408	426	erythrodysesthesia	Disease	D060831
10985896	429	447	hand-foot syndrome	Disease	D060831
10985896	454	464	stomatitis	Disease	D013280
10985896	514	525	doxorubicin	Chemical	D004317
10985896	621	629	platinum	Chemical	D010984
10985896	630	640	paclitaxel	Chemical	D017239
10985896	698	731	ovarian or fallopian tube cancers	Disease	D010051|D005185	ovarian cancers|fallopian tube cancers
10985896	743	763	peritoneal carcinoma	Disease	D010534
10985896	769	777	platinum	Chemical	D010984
10985896	778	788	paclitaxel	Chemical	D017239
10985896	959	970	doxorubicin	Chemical	D004317
10985896	1202	1220	hand-foot syndrome	Disease	D060831
10985896	1225	1235	stomatitis	Disease	D013280
10985896	1306	1314	diarrhea	Disease	D003967
10985896	1446	1457	doxorubicin	Chemical	D004317
10985896	1677	1688	doxorubicin	Chemical	D004317
10985896	1713	1721	toxicity	Disease	D064420
10985896	1723	1733	stomatitis	Disease	D013280
10985896	1735	1753	hand-foot syndrome	Disease	D060831
10985896	1895	1903	platinum	Chemical	D010984
10985896	1909	1919	paclitaxel	Chemical	D017239
10985896	1931	1945	ovarian cancer	Disease	D010051
10985896	CID	D004317	D013280
10985896	CID	D004317	D003967
10985896	CID	D004317	D060831

10986547|t|Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group.
10986547|a|BACKGROUND: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania. METHODS: Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. RESULTS: Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively). CONCLUSION: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.
10986547	12	22	olanzapine	Chemical	C076029
10986547	32	45	bipolar mania	Disease	D001714
10986547	93	103	Olanzipine	Chemical	C076029
10986547	173	183	olanzapine	Chemical	C076029
10986547	222	235	bipolar mania	Disease	D001714
10986547	350	366	bipolar disorder	Disease	D001714
10986547	368	373	manic	Disease	D001714
10986547	403	413	olanzapine	Chemical	C076029
10986547	502	507	Mania	Disease	D001714
10986547	774	796	Extrapyramidal Symptom	Disease	D001480
10986547	798	801	EPS	Disease	D001480
10986547	898	908	Olanzapine	Chemical	C076029
10986547	1269	1279	Olanzapine	Chemical	C076029
10986547	1506	1510	EPSs	Disease	D001480
10986547	1536	1546	olanzapine	Chemical	C076029
10986547	1618	1629	weight gain	Disease	D015430
10986547	1752	1762	somnolence	Disease	D006970
10986547	1825	1835	Olanzapine	Chemical	C076029
10986547	1905	1918	bipolar mania	Disease	D001714
10986547	CID	C076029	D006970
10986547	CID	C076029	D015430

11026989|t|The effect of pupil dilation with tropicamide on vision and driving simulator performance.
11026989|a|PURPOSE: To assess the effect of pupil dilation on vision and driving ability. METHODS: A series of tests on various parameters of visual function and driving simulator performance were performed on 12 healthy drivers, before and after pupil dilation using guttae tropicamide 1%. A driving simulator (Transport Research Laboratory) was used to measure reaction time (RT), speed maintenance and steering accuracy. Tests of basic visual function included high- and low-contrast visual acuity (HCVA and LCVA), Pelli-Robson contrast threshold (CT) and Goldmann perimetry (FIELDS). Useful Field of View (UFOV--a test of visual attention) was also undertaken. The mean differences in the pre- and post-dilatation measurements were tested for statistical significance at the 95% level using one-tail paired t-tests. RESULTS: Pupillary dilation resulted in a statistically significant deterioration in CT and HCVA only. Five of 12 drivers also exhibited deterioration in LCVA, CT and RT. Little evidence emerged for deterioration in FIELDS and UFOV. Also, 7 of 12 drivers appeared to adjust their driving behaviour by reducing their speed on the driving simulator, leading to improved steering accuracy. CONCLUSIONS: Pupillary dilation may lead to a decrease in vision and daylight driving performance in young people. A larger study, including a broader spectrum of subjects, is warranted before guidelines can be recommended.
11026989	14	28	pupil dilation	Disease	D015878
11026989	34	45	tropicamide	Chemical	D014331
11026989	124	138	pupil dilation	Disease	D015878
11026989	327	341	pupil dilation	Disease	D015878
11026989	355	366	tropicamide	Chemical	D014331
11026989	909	927	Pupillary dilation	Disease	D015878
11026989	1300	1318	Pupillary dilation	Disease	D015878
11026989	CID	D014331	D015878

11105626|t|A case of isotretinoin embryopathy with bilateral anotia and Taussig-Bing malformation.
11105626|a|We report a newborn infant with multiple congenital anomalies (anotia and Taussig-Bing malformation) due to exposure to isotretinoin within the first trimester. In this paper we aim to draw to the fact that caution is needed when prescribing vitamin A-containing drugs to women of childbearing years.
11105626	10	34	isotretinoin embryopathy	Disease	C535670
11105626	50	56	anotia	Disease	D065817
11105626	61	86	Taussig-Bing malformation	Disease	D004310
11105626	151	157	anotia	Disease	D065817
11105626	162	187	Taussig-Bing malformation	Disease	D004310
11105626	208	220	isotretinoin	Chemical	D015474
11105626	330	339	vitamin A	Chemical	D014801
11105626	CID	D015474	D004310
11105626	CID	D015474	D065817
11105626	CID	D015474	C535670

11135381|t|Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo-controlled, double-blind crossover study.
11135381|a|The aim of the study was to evaluate the potential role for a selective alpha1-adrenoceptor agonist in the treatment of urinary stress incontinence. A randomised, double-blind, placebo-controlled, crossover study design was employed. Half log incremental doses of intravenous methoxamine or placebo (saline) were administered to a group of women with genuine stress incontinence while measuring maximum urethral pressure (MUP), blood pressure, heart rate, and symptomatic side effects. Methoxamine evoked non-significant increases in MUP and diastolic blood pressure but caused a significant rise in systolic blood pressure and significant fall in heart rate at maximum dosage. Systemic side effects including piloerection, headache, and cold extremities were experienced in all subjects. The results indicate that the clinical usefulness of direct, peripherally acting sub-type-selective alpha1-adrenoceptor agonists in the medical treatment of stress incontinence may be limited by associated piloerection and cardiovascular side effects.
11135381	10	21	methoxamine	Chemical	D008729
11135381	73	92	stress incontinence	Disease	D014550
11135381	266	293	urinary stress incontinence	Disease	D014550
11135381	422	433	methoxamine	Chemical	D008729
11135381	505	524	stress incontinence	Disease	D014550
11135381	632	643	Methoxamine	Chemical	D008729
11135381	724	769	a significant rise in systolic blood pressure	Disease	D006973
11135381	870	878	headache	Disease	D006261
11135381	1092	1111	stress incontinence	Disease	D014550
11135381	CID	D008729	D006973
11135381	CID	D008729	D006261

11176729|t|Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival.
11176729|a|BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.
11176729	28	68	angiotensin-converting enzyme inhibitors	Chemical	D000806
11176729	94	107	heart failure	Disease	D006333
11176729	172	182	Lisinopril	Chemical	D017706
11176729	224	270	angiotensin-converting enzyme (ACE) inhibitors	Chemical	D000806
11176729	328	341	heart failure	Disease	D006333
11176729	343	346	CHF	Disease	D006333
11176729	696	706	lisinopril	Chemical	D017706
11176729	710	713	CHF	Disease	D006333
11176729	742	752	Lisinopril	Chemical	D017706
11176729	865	878	ACE inhibitor	Chemical	D000806
11176729	927	937	lisinopril	Chemical	D017706
11176729	1136	1139	CHF	Disease	D006333
11176729	1405	1416	hypotension	Disease	D007022
11176729	1421	1438	renal dysfunction	Disease	D007674
11176729	1493	1506	ACE inhibitor	Chemical	D000806
11176729	1636	1647	hypotension	Disease	D007022
11176729	1669	1686	renal dysfunction	Disease	D007674
11176729	1690	1702	hyperkalemia	Disease	D006947
11176729	2046	2059	ACE inhibitor	Chemical	D000806
11176729	2101	2111	creatinine	Chemical	D003404
11176729	2194	2202	diabetes	Disease	D003920
11176729	2293	2306	ACE inhibitor	Chemical	D000806
11176729	2337	2340	CHF	Disease	D006333
11176729	CID	D017706	D007674
11176729	CID	D017706	D006947
11176729	CID	D017706	D007022

11229942|t|Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse.
11229942|a|OBJECTIVES: Simultaneous abuse of cocaine and ethanol affects 12 million Americans annually. In combination, these substances are substantially more toxic than either drug alone. Their combined cardiac toxicity may be due to independent effects of each drug; however, they may also be due to cocaethylene (CE), a cocaine metabolite formed only in the presence of ethanol. The purpose of this study was to delineate the role of CE in the combined cardiotoxicity of cocaine and ethanol in a model simulating their abuse. METHODS: Twenty-three dogs were randomized to receive either 1) three intravenous (IV) boluses of cocaine 7.5 mg/kg with ethanol (1 g/kg) as an IV infusion (C+E, n = 8), 2) three cocaine boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo boluses and infusion (n = 4). Hemodynamic measurements, electrocardiograms, and serum drug concentrations were obtained at baseline, and then at fixed time intervals after each drug was administered. RESULTS: Two of eight dogs in the C+E group experienced cardiovascular collapse. The most dramatic hemodynamic changes occurred after each cocaine bolus in the C+E and C only groups; however, persistent hemodynamic changes occurred in the C+E group. Peak CE levels were associated with a 45% (SD +/- 22%, 95% CI = 22% to 69%) decrease in cardiac output (p < 0.05), a 56% (SD +/- 23%, 95% CI = 32% to 80%) decrease in dP/dt(max) (p <.006), and a 23% (SD +/- 15%, 95% CI = 7% to 49%) decrease in SVO(2) (p < 0.025). Ventricular arrhythmias were primarily observed in the C+E group, in which four of eight dogs experienced ventricular tachycardia. CONCLUSIONS: Cocaine and ethanol in combination were more toxic than either substance alone. Co-administration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myocardial depression.
11229942	0	7	Cocaine	Chemical	D003042
11229942	9	16	ethanol	Chemical	D000431
11229942	22	34	cocaethylene	Chemical	C066444
11229942	35	47	cardiotoxity	Disease	D066126
11229942	70	95	cocaine and ethanol abuse	Disease	D019970|D000437	cocaine abuse|ethanol abuse
11229942	122	150	abuse of cocaine and ethanol	Disease	D019970|D000437	abuse of cocaine|abuse of ethanol
11229942	291	307	cardiac toxicity	Disease	D066126
11229942	389	401	cocaethylene	Chemical	C066444
11229942	403	405	CE	Chemical	C066444
11229942	410	417	cocaine	Chemical	D003042
11229942	460	467	ethanol	Chemical	D000431
11229942	524	526	CE	Chemical	C066444
11229942	543	557	cardiotoxicity	Disease	D066126
11229942	561	568	cocaine	Chemical	D003042
11229942	573	580	ethanol	Chemical	D000431
11229942	714	721	cocaine	Chemical	D003042
11229942	737	744	ethanol	Chemical	D000431
11229942	795	802	cocaine	Chemical	D003042
11229942	831	838	ethanol	Chemical	D000431
11229942	1135	1158	cardiovascular collapse	Disease	-1
11229942	1218	1225	cocaine	Chemical	D003042
11229942	1334	1336	CE	Chemical	C066444
11229942	1405	1431	decrease in cardiac output	Disease	D002303
11229942	1593	1616	Ventricular arrhythmias	Disease	D001145
11229942	1699	1722	ventricular tachycardia	Disease	D017180
11229942	1737	1744	Cocaine	Chemical	D003042
11229942	1749	1756	ethanol	Chemical	D000431
11229942	1857	1873	cardiac toxicity	Disease	D066126
11229942	1910	1922	cocaethylene	Chemical	C066444
11229942	1969	1990	myocardial depression	Disease	D009202
11229942	CID	D000431	D017180
11229942	CID	D003042	D017180
11229942	CID	C066444	D002303

11299446|t|Worsening of Parkinsonism after the use of veralipride for treatment of menopause: case report.
11299446|a|We describe a female patient with stable Parkinson's disease who has shown a marked worsening of her motor functions following therapy of menopause related symptoms with veralipride, as well as the improvement of her symptoms back to baseline after discontinuation of the drug. We emphasize the anti-dopaminergic effect of veralipride.
11299446	13	25	Parkinsonism	Disease	D010302
11299446	43	54	veralipride	Chemical	C027429
11299446	137	156	Parkinson's disease	Disease	D010302
11299446	266	277	veralipride	Chemical	C027429
11299446	419	430	veralipride	Chemical	C027429
11299446	CID	C027429	D010302

11366874|t|Viracept and irregular heartbeat warning.
11366874|a|A group of doctors in Boston warn that the protease inhibitor Viracept may cause an irregular heart beat, known as bradycardia, in people with HIV. Bradycardia occurred in a 45-year-old male patient who was Viracept in combination with other anti-HIV drugs. The symptoms ceased after switching to another drug combination.
11366874	0	8	Viracept	Chemical	D019888
11366874	13	32	irregular heartbeat	Disease	D001145
11366874	104	112	Viracept	Chemical	D019888
11366874	126	146	irregular heart beat	Disease	D001145
11366874	157	168	bradycardia	Disease	D001919
11366874	190	201	Bradycardia	Disease	D001919
11366874	249	257	Viracept	Chemical	D019888
11366874	CID	D019888	D001919

11380496|t|Frequency of appearance of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO-ANCA and clinical manifestations.
11380496|a|OBJECTIVE: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO-ANCA in these cases was suspected of being related to PTU because the titres of MPO-ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO-ANCA and vasculitis during PTU therapy, or on the incidence of MPO-ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease. PATIENTS: We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO-ANCA, and for the development vasculitis after starting PTU therapy. Twenty-nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23.6 months (range: 3-37 months). MEASUREMENTS: MPO-ANCA was measured at intervals of 2-6 months. RESULTS: Before treatment, the MPO-ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U/ml). Three (4.1%) of the 73 patients were positive for MPO-ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO-ANCA titres transiently increased to 12.8 and 15.0 U/ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO-ANCA titre increased to 204 U/ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO-ANCA titre decreased to 20.7 U/ml by 4 months after discontinuing PTU. CONCLUSIONS: PTU therapy may be related to the appearance of MPO-ANCA, but MPO-ANCA does not appear to be closely related to vasculitis.
11380496	93	108	Graves' disease	Disease	D006111
11380496	131	147	propylthiouracil	Chemical	D011441
11380496	298	308	vasculitis	Disease	D014657
11380496	344	359	Graves' disease	Disease	D006111
11380496	382	398	propylthiouracil	Chemical	D011441
11380496	400	403	PTU	Chemical	D011441
11380496	482	485	PTU	Chemical	D011441
11380496	532	535	PTU	Chemical	D011441
11380496	658	668	vasculitis	Disease	D014657
11380496	676	679	PTU	Chemical	D011441
11380496	734	749	Graves' disease	Disease	D006111
11380496	826	841	Graves' disease	Disease	D006111
11380496	897	912	hyperthyroidism	Disease	D006980
11380496	920	935	Graves' disease	Disease	D006111
11380496	990	1000	vasculitis	Disease	D014657
11380496	1016	1019	PTU	Chemical	D011441
11380496	1099	1102	PTU	Chemical	D011441
11380496	1511	1526	Graves' disease	Disease	D006111
11380496	1702	1705	PTU	Chemical	D011441
11380496	1828	1831	PTU	Chemical	D011441
11380496	1848	1868	vasculitic disorders	Disease	D014652
11380496	1970	1975	fever	Disease	D005334
11380496	1977	1988	oral ulcers	Disease	D019226
11380496	1993	2007	polyarthralgia	Disease	D018771
11380496	2058	2061	PTU	Chemical	D011441
11380496	2149	2152	PTU	Chemical	D011441
11380496	2167	2170	PTU	Chemical	D011441
11380496	2279	2289	vasculitis	Disease	D014657
11380496	CID	D011441	D005334
11380496	CID	D011441	D018771
11380496	CID	D011441	D019226

11385188|t|Prevalence of heart disease in asymptomatic chronic cocaine users.
11385188|a|To determine the prevalence of heart disease in outpatient young asymptomatic chronic cocaine users, 35 cocaine users and 32 age-matched controls underwent resting and exercise electrocardiography (ECG) and Doppler echocardiography. Findings consistent with coronary artery disease were detected in 12 (34%) patients and 3 (9%) controls (p = 0.01). Decreased left ventricular systolic function was demonstrated in 5 (14%) patients, but in none of the controls (p = 0.055). Finally, resting and peak exercise abnormal left ventricular filling was detected in 38 and 35% of patients as compared to 19 and 9% of controls, respectively (p = 0.11 and 0.02, respectively). We conclude that coronary artery or myocardial disease is common (38%) in young asymptomatic chronic cocaine users. Therefore, screening ECG and echocardiography may be warranted in these patients.
11385188	14	27	heart disease	Disease	D006331
11385188	52	59	cocaine	Chemical	D003042
11385188	98	111	heart disease	Disease	D006331
11385188	153	160	cocaine	Chemical	D003042
11385188	171	178	cocaine	Chemical	D003042
11385188	325	348	coronary artery disease	Disease	D003324
11385188	575	608	abnormal left ventricular filling	Disease	D018487
11385188	751	788	coronary artery or myocardial disease	Disease	D003324|D009202	coronary artery disease|myocardial disease
11385188	835	842	cocaine	Chemical	D003042
11385188	CID	D003042	D003324
11385188	CID	D003042	D009202

11395263|t|Cardioprotective effects of Picrorrhiza kurroa against isoproterenol-induced myocardial stress in rats.
11395263|a|The cardioprotective effect of the ethanol extract of Picrorrhiza kurroa rhizomes and roots (PK) on isoproterenol-induced myocardial infarction in rats with respect to lipid metabolism in serum and heart tissue has been investigated. Oral pre-treatment with PK (80 mg kg(-1) day(-1) for 15 days) significantly prevented the isoproterenol-induced myocardial infarction and maintained the rats at near normal status.
11395263	55	68	isoproterenol	Chemical	D007545
11395263	139	146	ethanol	Chemical	D000431
11395263	204	217	isoproterenol	Chemical	D007545
11395263	226	247	myocardial infarction	Disease	D009203
11395263	428	441	isoproterenol	Chemical	D007545
11395263	450	471	myocardial infarction	Disease	D009203
11395263	CID	D007545	D009203

11401944|t|Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome : direct evidence from intracellular recordings in the intact left ventricular wall.
11401944|a|BACKGROUND: This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl-sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. METHODS AND RESULTS: Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl-Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 micromol/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 micromol/L but shortened them at 30 micromol/L. Unlike dl-sotalol, azimilide (>3 micromol/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl-sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl-sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 micromol/L) increased APD more than dl-sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. CONCLUSIONS: This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation.
11401944	62	85	ventricular tachycardia	Disease	D017180
11401944	98	114	long-QT syndrome	Disease	D008133
11401944	319	337	torsade de pointes	Disease	D016171
11401944	339	342	TdP	Disease	D016171
11401944	349	364	QT prolongation	Disease	D008133
11401944	379	386	sotalol	Chemical	D013015
11401944	391	400	azimilide	Chemical	C086123
11401944	524	527	TdP	Disease	D016171
11401944	786	793	Sotalol	Chemical	D013015
11401944	913	928	QT prolongation	Disease	D008133
11401944	953	962	Azimilide	Chemical	C086123
11401944	1108	1115	sotalol	Chemical	D013015
11401944	1117	1126	azimilide	Chemical	C086123
11401944	1221	1228	sotalol	Chemical	D013015
11401944	1233	1242	azimilide	Chemical	C086123
11401944	1355	1370	QT prolongation	Disease	D008133
11401944	1406	1413	sotalol	Chemical	D013015
11401944	1505	1508	TdP	Disease	D016171
11401944	1561	1570	azimilide	Chemical	C086123
11401944	1619	1626	sotalol	Chemical	D013015
11401944	1931	1934	TdP	Disease	D016171
11401944	1941	1956	QT prolongation	Disease	D008133
11401944	CID	D013015	D008133
11401944	CID	D013015	D016171

11425091|t|Prenatal cocaine exposure and cranial sonographic findings in preterm infants.
11425091|a|PURPOSE: Prenatal cocaine exposure has been linked with subependymal hemorrhage and the formation of cysts that are detectable on cranial sonography in neonates born at term. We sought to determine if prenatal cocaine exposure increases the incidence of subependymal cysts in preterm infants. METHODS: We retrospectively reviewed the medical records and cranial sonograms obtained during a 1-year period on 122 premature (< 36 weeks of gestation) infants. Infants were categorized into 1 of 2 groups: those exposed to cocaine and those not exposed to cocaine. Infants were assigned to the cocaine-exposed group if there was a maternal history of cocaine abuse during pregnancy or if maternal or neonatal urine toxicology results were positive at the time of delivery. RESULTS: Five of the 122 infants were excluded from the study because of insufficient medical and drug histories. The incidence of subependymal cysts in the 117 remaining infants was 14% (16 of 117). The incidence of subependymal cysts in infants exposed to cocaine prenatally was 44% (8 of 18) compared with 8% (8 of 99) in the unexposed group (p < 0.01). CONCLUSIONS: We found an increased incidence of subependymal cyst formation in preterm infants who were exposed to cocaine prenatally. This result is consistent with results of similar studies in term infants.
11425091	9	16	cocaine	Chemical	D003042
11425091	62	77	preterm infants	Disease	D007235
11425091	97	104	cocaine	Chemical	D003042
11425091	148	158	hemorrhage	Disease	D006470
11425091	180	185	cysts	Disease	D003560
11425091	289	296	cocaine	Chemical	D003042
11425091	333	351	subependymal cysts	Disease	D001927|D003560	subependymal cysts|cysts
11425091	355	370	preterm infants	Disease	D007235
11425091	490	533	premature (< 36 weeks of gestation) infants	Disease	D007235
11425091	597	604	cocaine	Chemical	D003042
11425091	630	637	cocaine	Chemical	D003042
11425091	668	675	cocaine	Chemical	D003042
11425091	725	738	cocaine abuse	Disease	D019970
11425091	978	996	subependymal cysts	Disease	D001927|D003560	subependymal cysts|cysts
11425091	1064	1082	subependymal cysts	Disease	D001927|D003560	subependymal cysts|cysts
11425091	1105	1112	cocaine	Chemical	D003042
11425091	1252	1269	subependymal cyst	Disease	D001927|D003560	subependymal cyst|cyst
11425091	1283	1298	preterm infants	Disease	D007235
11425091	1319	1326	cocaine	Chemical	D003042
11425091	CID	D003042	D003560
11425091	CID	D003042	D001927
11425091	CID	D003042	D007235

11439380|t|Thalidomide neuropathy in patients treated for metastatic prostate cancer.
11439380|a|We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection.
11439380	0	11	Thalidomide	Chemical	D013792
11439380	12	22	neuropathy	Disease	D009422
11439380	58	73	prostate cancer	Disease	D011471
11439380	102	113	thalidomide	Chemical	D013792
11439380	122	132	neuropathy	Disease	D009422
11439380	198	206	androgen	Chemical	D000728
11439380	219	234	prostate cancer	Disease	D011471
11439380	266	277	thalidomide	Chemical	D013792
11439380	715	726	Thalidomide	Chemical	D013792
11439380	843	854	thalidomide	Chemical	D013792
11439380	944	954	neuropathy	Disease	D009422
11439380	1095	1105	Neuropathy	Disease	D009422
11439380	1143	1154	thalidomide	Chemical	D013792
11439380	1212	1233	peripheral neuropathy	Disease	D010523
11439380	CID	D013792	D010523

11474137|t|Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss.
11474137|a|The participation of reactive oxygen species in aminoglycoside-induced ototoxicity has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg/kg body weight/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45-50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention.
11474137	18	24	copper	Chemical	D003300
11474137	25	29	zinc	Chemical	D015032
11474137	30	40	superoxide	Chemical	D013481
11474137	65	74	kanamycin	Chemical	D007612
11474137	83	95	hearing loss	Disease	D034381
11474137	127	133	oxygen	Chemical	D010100
11474137	145	159	aminoglycoside	Chemical	D000617
11474137	168	179	ototoxicity	Disease	D006311
11474137	220	234	aminoglycoside	Chemical	D000617
11474137	235	239	iron	Chemical	D007501
11474137	276	286	superoxide	Chemical	D013481
11474137	337	348	ototoxicity	Disease	D006311
11474137	407	409	Cu	Chemical	D003300
11474137	410	412	Zn	Chemical	D015032
11474137	413	423	superoxide	Chemical	D013481
11474137	479	490	ototoxicity	Disease	D006311
11474137	656	665	kanamycin	Chemical	D007612
11474137	882	891	kanamycin	Chemical	D007612
11474137	985	994	kanamycin	Chemical	D007612
11474137	1142	1152	superoxide	Chemical	D013481
11474137	1235	1249	aminoglycoside	Chemical	D000617
11474137	1258	1269	ototoxicity	Disease	D006311
11474137	CID	D007612	D034381

11708428|t|Prednisone induces anxiety and glial cerebral changes in rats.
11708428|a|OBJECTIVE: To assess whether prednisone (PDN) produces anxiety and/or cerebral glial changes in rats. METHODS: Male Wistar rats were studied and 3 groups were formed (8 rats per group). The moderate-dose group received 5 mg/kg/day PDN released from a subcutaneous implant. In the high-dose group, implants containing PDN equivalent to 60 mg/kg/day were applied. In the control group implants contained no PDN. Anxiety was assessed using an open field and elevated plus-maze devices. The number of cells and cytoplasmic transformation of astrocytes and microglia cells were assessed by immunohistochemical analyses. RESULTS: Anxiety was documented in both groups of PDN treated rats compared with controls. The magnitude of transformation of the microglia assessed by the number of intersections was significantly higher in the PDN groups than in controls in the prefrontal cortex (moderate-dose, 24.1; high-dose, 23.6; controls 18.7; p < 0.01) and striatum (moderate-dose 25.6; high-dose 26.3; controls 18.9; p < 0.01), but not in hippocampus. The number of stained microglia cells was significantly higher in the PDN treated groups in the prefrontal cortex than in controls (moderate-dose, 29.1; high-dose, 28.4; control, 17.7 cells per field; p < 0.01). Stained microglia cells were significantly more numerous striatum and hippocampus in the high-dose group compared to controls. CONCLUSION: Subacute exposure to PDN induced anxiety and reactivity of microglia. The relevance of these features for patients using PDN remains to be elucidated.
11708428	0	10	Prednisone	Chemical	D011241
11708428	19	26	anxiety	Disease	D001008
11708428	92	102	prednisone	Chemical	D011241
11708428	104	107	PDN	Chemical	D011241
11708428	118	125	anxiety	Disease	D001008
11708428	294	297	PDN	Chemical	D011241
11708428	380	383	PDN	Chemical	D011241
11708428	468	471	PDN	Chemical	D011241
11708428	473	480	Anxiety	Disease	D001008
11708428	687	694	Anxiety	Disease	D001008
11708428	728	731	PDN	Chemical	D011241
11708428	890	893	PDN	Chemical	D011241
11708428	1177	1180	PDN	Chemical	D011241
11708428	1479	1482	PDN	Chemical	D011241
11708428	1491	1498	anxiety	Disease	D001008
11708428	1579	1582	PDN	Chemical	D011241
11708428	CID	D011241	D001008

11745287|t|Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.
11745287|a|BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.
11745287	18	29	carboplatin	Chemical	D016190
11745287	44	55	doxorubicin	Chemical	D004317
11745287	83	120	squamous cell carcinoma of the cervix	Disease	D002294|D002583	squamous cell carcinoma|carcinoma of the cervix
11745287	169	180	carboplatin	Chemical	D016190
11745287	195	206	doxorubicin	Chemical	D004317
11745287	265	283	cervical carcinoma	Disease	D002583
11745287	313	324	carboplatin	Chemical	D016190
11745287	385	396	doxorubicin	Chemical	D004317
11745287	398	403	Doxil	Chemical	D004317
11745287	507	539	squamous cell cervical carcinoma	Disease	D002294|D002583	squamous cell carcinoma|cervical carcinoma
11745287	576	584	toxicity	Disease	D064420
11745287	690	698	toxicity	Disease	D064420
11745287	887	903	myelosuppression	Disease	D001855
11745287	924	935	neutropenia	Disease	D009503
11745287	952	958	anemia	Disease	D000740
11745287	975	991	thrombocytopenia	Disease	D013921
11745287	1012	1029	neutropenic fever	Disease	D009503|D005334	neutropenic|fever
11745287	1128	1139	doxorubicin	Chemical	D004317
11745287	1227	1235	toxicity	Disease	D064420
11745287	1245	1251	nausea	Disease	D009325
11745287	1268	1274	emesis	Disease	D014839
11745287	1291	1298	fatigue	Disease	D005221
11745287	1314	1323	mucositis	Disease	D052016
11745287	1331	1341	stomatitis	Disease	D013280
11745287	1357	1369	constipation	Disease	D003248
11745287	1385	1396	weight loss	Disease	D015431
11745287	1412	1430	hand-foot syndrome	Disease	D060831
11745287	1450	1464	skin reactions	Disease	D012871
11745287	1512	1523	carboplatin	Chemical	D016190
11745287	1538	1549	doxorubicin	Chemical	D004317
11745287	1597	1615	cervical carcinoma	Disease	D002583
11745287	CID	D004317	D009503
11745287	CID	D004317	D003248
11745287	CID	D016190	D009503
11745287	CID	D016190	D013921
11745287	CID	D004317	D052016
11745287	CID	D016190	D014839
11745287	CID	D004317	D015431
11745287	CID	D016190	D005221
11745287	CID	D004317	D012871
11745287	CID	D004317	D000740
11745287	CID	D004317	D009325
11745287	CID	D016190	D012871
11745287	CID	D016190	D003248
11745287	CID	D004317	D005221
11745287	CID	D016190	D009325
11745287	CID	D004317	D014839
11745287	CID	D016190	D052016
11745287	CID	D016190	D015431
11745287	CID	D004317	D013921
11745287	CID	D016190	D000740

11799346|t|Antimicrobial-induced mania (antibiomania): a review of spontaneous reports.
11799346|a|The authors reviewed reported cases of antibiotic-induced manic episodes by means of a MEDLINE and PsychLit search for reports of antibiotic-induced mania. Unpublished reports were requested from the World Health Organization (WHO) and the Food and Drug Administration (FDA). Twenty-one reports of antimicrobial-induced mania were found in the literature. There were 6 cases implicating clarithromycin, 13 implicating isoniazid, and 1 case each implicating erythromycin and amoxicillin. The WHO reported 82 cases. Of these, clarithromycin was implicated in 23 (27.6%) cases, ciprofloxacin in 12 (14.4%) cases, and ofloxacin in 10 (12%) cases. Cotrimoxazole, metronidazole, and erythromycin were involved in 15 reported manic episodes. Cases reported by the FDA showed clarithromycin and ciprofloxacin to be the most frequently associated with the development of mania. Statistical analysis of the data would not have demonstrated a significant statistical correlative risk and was therefore not undertaken. Patients have an increased risk of developing mania while being treated with antimicrobials. Although this is not a statistically significant risk, physicians must be aware of the effect and reversibility. Further research clearly is required to determine the incidence of antimicrobial-induced mania, the relative risk factors of developing an antimicrobial-induced manic episode among various demographic populations, and the incidence of patients who continue to have persistent affective disorders once the initial episode, which occurs while the patient is taking antibiotics, subsides. The authors elected to name this syndrome "antibiomania."
11799346	22	27	mania	Disease	D001714
11799346	29	41	antibiomania	Disease	D001714
11799346	135	140	manic	Disease	D001714
11799346	226	231	mania	Disease	D001714
11799346	397	402	mania	Disease	D001714
11799346	464	478	clarithromycin	Chemical	D017291
11799346	495	504	isoniazid	Chemical	D007538
11799346	534	546	erythromycin	Chemical	D004917
11799346	551	562	amoxicillin	Chemical	D000658
11799346	601	615	clarithromycin	Chemical	D017291
11799346	652	665	ciprofloxacin	Chemical	D002939
11799346	691	700	ofloxacin	Chemical	D015242
11799346	720	733	Cotrimoxazole	Chemical	D015662
11799346	735	748	metronidazole	Chemical	D008795
11799346	754	766	erythromycin	Chemical	D004917
11799346	796	801	manic	Disease	D001714
11799346	845	859	clarithromycin	Chemical	D017291
11799346	864	877	ciprofloxacin	Chemical	D002939
11799346	939	944	mania	Disease	D001714
11799346	1130	1135	mania	Disease	D001714
11799346	1379	1384	mania	Disease	D001714
11799346	1451	1456	manic	Disease	D001714
11799346	1719	1731	antibiomania	Disease	D001714
11799346	CID	D002939	D001714
11799346	CID	D015662	D001714
11799346	CID	D008795	D001714
11799346	CID	D007538	D001714
11799346	CID	D015242	D001714
11799346	CID	D000658	D001714
11799346	CID	D017291	D001714
11799346	CID	D004917	D001714

11835460|t|Levodopa-induced ocular dyskinesias in Parkinson's disease.
11835460|a|Levodopa-induced ocular dyskinesias are very uncommon. Usually they occur simultaneously with limb peak-dose choreatic dyskinesias. We report on a patient with leftward and upward deviations of gaze during the peak effect of levodopa, and hypothesize that a severe dopaminergic denervation in the caudate nucleus is needed for the appearance of these levodopa-induce ocular dyskinesias.
11835460	0	8	Levodopa	Chemical	D007980
11835460	17	35	ocular dyskinesias	Disease	D015835
11835460	39	58	Parkinson's disease	Disease	D010300
11835460	60	68	Levodopa	Chemical	D007980
11835460	77	95	ocular dyskinesias	Disease	D015835
11835460	169	190	choreatic dyskinesias	Disease	D002819
11835460	285	293	levodopa	Chemical	D007980
11835460	411	419	levodopa	Chemical	D007980
11835460	427	445	ocular dyskinesias	Disease	D015835
11835460	CID	D007980	D015835

11915580|t|A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.
11915580|a|Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.
11915580	16	35	glyceryl trinitrate	Chemical	D005996
11915580	41	51	diclofenac	Chemical	D004008
11915580	81	93	dysmenorrhea	Disease	D004412
11915580	142	154	dysmenorrhea	Disease	D004412
11915580	258	272	prostaglandins	Chemical	D011453
11915580	474	486	nitric oxide	Chemical	D009569
11915580	488	490	NO	Chemical	D009569
11915580	555	574	glyceryl trinitrate	Chemical	D005996
11915580	576	579	GTN	Chemical	D005996
11915580	585	587	NO	Chemical	D009569
11915580	624	636	dysmenorrhea	Disease	D004412
11915580	656	666	diclofenac	Chemical	D004008
11915580	668	671	DCF	Chemical	D004008
11915580	734	746	dysmenorrhea	Disease	D004412
11915580	887	890	DCF	Chemical	D004008
11915580	901	904	GTN	Chemical	D005996
11915580	1080	1083	DCF	Chemical	D004008
11915580	1111	1114	GTN	Chemical	D005996
11915580	1392	1396	pain	Disease	D010146
11915580	1512	1515	GTN	Chemical	D005996
11915580	1533	1536	DCF	Chemical	D004008
11915580	1564	1567	DCF	Chemical	D004008
11915580	1606	1617	pelvic pain	Disease	D017699
11915580	1641	1644	GTN	Chemical	D005996
11915580	1755	1758	GTN	Chemical	D005996
11915580	1817	1820	GTN	Chemical	D005996
11915580	1872	1885	Low back pain	Disease	D017116
11915580	1919	1927	Headache	Disease	D006261
11915580	1959	1962	GTN	Chemical	D005996
11915580	1974	1977	DCF	Chemical	D004008
11915580	2008	2011	GTN	Chemical	D005996
11915580	2020	2028	headache	Disease	D006261
11915580	2102	2105	GTN	Chemical	D005996
11915580	2165	2168	DCF	Chemical	D004008
11915580	2197	2209	dysmenorrhea	Disease	D004412
11915580	CID	D005996	D006261

11936424|t|Temocapril, a long-acting non-SH group angiotensin converting enzyme inhibitor, modulates glomerular injury in chronic puromycin aminonucleoside nephrosis.
11936424|a|The purpose of the present study was to determine whether chronic administration of temocapril, a long-acting non-SH group angiotensin converting enzyme (ACE) inhibitor, reduced proteinuria, inhibited glomerular hypertrophy and prevented glomerulosclerosis in chronic puromycin aminonucleoside (PAN) - induced nephrotic rats. Nephrosis was induced by injection of PAN (15mg/100g body weight) in male Sprague-Dawley (SD) rats. Four groups were used, i) the PAN group (14), ii) PAN/temocapril (13), iii) temocapril (14) and iv) untreated controls (15). Temocapril (8 mg/kg/day) was administered to the rats which were killed at weeks 4, 14 or 20. At each time point, systolic blood pressure (BP), urinary protein excretion and renal histopathological findings were evaluated, and morphometric image analysis was done. Systolic BP in the PAN group was significantly high at 4, 14 and 20 weeks, but was normal in the PAN/temocapril group. Urinary protein excretion in the PAN group increased significantly, peaking at 8 days, then decreased at 4 weeks, but rose again significantly at 14 and 20 weeks. Temocapril did not attenuate proteinuria at 8 days, but it did markedly lower it from weeks 4 to 20. The glomerulosclerosis index (GSI) was 6.21 % at 4 weeks and respectively 25.35 % and 30.49 % at 14 and 20 weeks in the PAN group. There was a significant correlation between urinary protein excretion and GSI (r = 0.808, p < 0.0001). The ratio of glomerular tuft area to the area of Bowman's capsules (GT/BC) in the PAN group was significantly increased, but it was significantly lower in the PAN/temocapril group. It appears that temocapril was effective in retarding renal progression and protected renal function in PAN neprotic rats.
11936424	0	10	Temocapril	Chemical	C055603
11936424	39	50	angiotensin	Chemical	D000809
11936424	90	107	glomerular injury	Disease	D007674
11936424	119	144	puromycin aminonucleoside	Chemical	D011692
11936424	145	154	nephrosis	Disease	D009401
11936424	240	250	temocapril	Chemical	C055603
11936424	279	290	angiotensin	Chemical	D000809
11936424	334	345	proteinuria	Disease	D011507
11936424	368	379	hypertrophy	Disease	D006984
11936424	394	412	glomerulosclerosis	Disease	D005921
11936424	424	449	puromycin aminonucleoside	Chemical	D011692
11936424	451	454	PAN	Chemical	D011692
11936424	466	475	nephrotic	Disease	D009404
11936424	482	491	Nephrosis	Disease	D009401
11936424	520	523	PAN	Chemical	D011692
11936424	612	615	PAN	Chemical	D011692
11936424	632	635	PAN	Chemical	D011692
11936424	636	646	temocapril	Chemical	C055603
11936424	658	668	temocapril	Chemical	C055603
11936424	707	717	Temocapril	Chemical	C055603
11936424	991	994	PAN	Chemical	D011692
11936424	1069	1072	PAN	Chemical	D011692
11936424	1073	1083	temocapril	Chemical	C055603
11936424	1124	1127	PAN	Chemical	D011692
11936424	1254	1264	Temocapril	Chemical	C055603
11936424	1283	1294	proteinuria	Disease	D011507
11936424	1359	1377	glomerulosclerosis	Disease	D005921
11936424	1475	1478	PAN	Chemical	D011692
11936424	1671	1674	PAN	Chemical	D011692
11936424	1748	1751	PAN	Chemical	D011692
11936424	1752	1762	temocapril	Chemical	C055603
11936424	1786	1796	temocapril	Chemical	C055603
11936424	1874	1877	PAN	Chemical	D011692
11936424	1878	1886	neprotic	Disease	D009401
11936424	CID	D011692	D011507
11936424	CID	D011692	D009401

11988250|t|Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants.
11988250|a|We report three cases of severe hypoxaemia after ibuprofen administration during a randomised controlled trial of prophylactic treatment of patent ductus arteriosus with ibuprofen in premature infants born at less than 28 weeks of gestation. Echocardiography showed severely decreased pulmonary blood flow. Hypoxaemia resolved quickly on inhaled nitric oxide therapy. We suggest that investigators involved in similar trials pay close attention to pulmonary pressure if hypoxaemia occurs after prophylactic administration of ibuprofen.
11988250	0	22	Pulmonary hypertension	Disease	D006976
11988250	29	38	ibuprofen	Chemical	D007052
11988250	108	118	hypoxaemia	Disease	D000860
11988250	125	134	ibuprofen	Chemical	D007052
11988250	216	240	patent ductus arteriosus	Disease	D004374
11988250	246	255	ibuprofen	Chemical	D007052
11988250	383	393	Hypoxaemia	Disease	D000860
11988250	422	434	nitric oxide	Chemical	D009569
11988250	546	556	hypoxaemia	Disease	D000860
11988250	601	610	ibuprofen	Chemical	D007052
11988250	CID	D007052	D006976
11988250	CID	D007052	D000860

12051122|t|Hyponatremia and syndrome of inappropriate anti-diuretic hormone reported with the use of Vincristine: an over-representation of Asians?
12051122|a|PURPOSE: This retrospective study used a pharmaceutical company's global safety database to determine the reporting rate of hyponatremia and/or syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) among vincristine-treated patients and to explore the possibility of at-risk population subgroups. METHOD: We searched the Eli Lilly and Company's computerized adverse event database for all reported cases of hyponatremia and/or SIADH as of 1 November 1999 that had been reported during the use of vincristine. RESULTS: A total of 76 cases of hyponatremia and/or SIADH associated with vincristine use were identified. The overall reporting rate was estimated to be 1.3/100,000 treated patients. The average age of patients was 35.6 +/- 28.3 years, and 62% were males. Approximately 75% of the patients were receiving treatment for leukemia or lymphoma. Among the 39 reports that included information on race, the racial distribution was: 1 Black, 3 Caucasian, and 35 Asian. CONCLUSION: Our data suggest that Asian patients may be at increased risk of hyponatremia and/or SIADH associated with vincristine use. Although the overall reported rate of SIADH associated with vincristine is very low, physicians caring for Asian oncology patients should be aware of this potential serious but reversible adverse event.
12051122	0	12	Hyponatremia	Disease	D007010
12051122	17	64	syndrome of inappropriate anti-diuretic hormone	Disease	D007177
12051122	90	101	Vincristine	Chemical	D014750
12051122	261	273	hyponatremia	Disease	D007010
12051122	281	341	syndrome of inappropriate secretion of anti-diuretic hormone	Disease	D007177
12051122	343	348	SIADH	Disease	D007177
12051122	356	367	vincristine	Chemical	D014750
12051122	559	571	hyponatremia	Disease	D007010
12051122	579	584	SIADH	Disease	D007177
12051122	648	659	vincristine	Chemical	D014750
12051122	693	705	hyponatremia	Disease	D007010
12051122	713	718	SIADH	Disease	D007177
12051122	735	746	vincristine	Chemical	D014750
12051122	981	989	leukemia	Disease	D007938
12051122	993	1001	lymphoma	Disease	D008223
12051122	1201	1213	hyponatremia	Disease	D007010
12051122	1221	1226	SIADH	Disease	D007177
12051122	1243	1254	vincristine	Chemical	D014750
12051122	1298	1303	SIADH	Disease	D007177
12051122	1320	1331	vincristine	Chemical	D014750
12051122	CID	D014750	D007177
12051122	CID	D014750	D007010

12059909|t|Delayed toxicity of cyclophosphamide on the bladder of DBA/2 and C57BL/6 female mouse.
12059909|a|The present study describes the delayed development of a severe bladder pathology in a susceptible strain of mice (DBA/2) but not in a resistant strain (C57BL/6) when both were treated with a single 300 mg/kg dose of cyclophosphamide (CY). Inbred DBA/2 and C57BL/6 female mice were injected with CY, and the effect of the drug on the bladder was assessed during 100 days by light microscopy using different staining procedures, and after 30 days by conventional electron microscopy. Early CY toxicity caused a typical haemorrhagic cystitis in both strains that was completely repaired in about 7-10 days. After 30 days of CY injection ulcerous and non-ulcerous forms of chronic cystitis appeared in 86% of DBA/2 mice but only in 4% of C57BL/6 mice. Delayed cystitis was characterized by infiltration and transepithelial passage into the lumen of inflammatory cells and by frequent exfoliation of the urothelium. Mast cells appeared in the connective and muscular layers of the bladder at a much higher number in DBA/2 mice than in C57BL/6 mice or untreated controls. Electron microscopy disclosed the absence of the typical discoidal vesicles normally present in the cytoplasm of surface cells. Instead, numerous abnormal vesicles containing one or several dark granules were observed in the cytoplasm of cells from all the epithelial layers. Delayed cystitis still persisted in DBA/2 mice 100 days after treatment. These results indicate that delayed toxicity of CY in female DBA/2 mice causes a bladder pathology that is not observed in C57BL/6 mice. This pathology resembles interstitial cystitis in humans and could perhaps be used as an animal model for studies on the disease.
12059909	8	16	toxicity	Disease	D064420
12059909	20	36	cyclophosphamide	Chemical	D003520
12059909	304	320	cyclophosphamide	Chemical	D003520
12059909	322	324	CY	Chemical	D003520
12059909	383	385	CY	Chemical	D003520
12059909	576	578	CY	Chemical	D003520
12059909	579	587	toxicity	Disease	D064420
12059909	605	617	haemorrhagic	Disease	D006470
12059909	618	626	cystitis	Disease	D003556
12059909	709	711	CY	Chemical	D003520
12059909	765	773	cystitis	Disease	D003556
12059909	844	852	cystitis	Disease	D003556
12059909	1438	1446	cystitis	Disease	D003556
12059909	1539	1547	toxicity	Disease	D064420
12059909	1551	1553	CY	Chemical	D003520
12059909	1665	1686	interstitial cystitis	Disease	D018856
12059909	CID	D003520	D006470
12059909	CID	D003520	D003556

12119460|t|High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer. A phase II study.
12119460|a|BACKGROUND: The 24-hour continuous infusion of 5-fluorouracil (5-FU) and folinic acid (FA) as part of several new multidrug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective, with low toxicity. In a previous phase II study with 3-weekly bolus 5-FU, FA and mitomycin C (MMC) we found a low toxicity rate and response rates comparable to those of regimens such as ELF, FAM or FAMTX, and a promising median overall survival. In order to improve this MMC-dependent schedule we initiated a phase II study with high-dose 5-FU/FA and 3-weekly bolus MMC. PATIENTS AND METHODS: From February, 1998 to September, 2000 we recruited 33 patients with AGC to receive weekly 24-hour 5-FU 2,600 mg/m(2) preceded by 2-hour FA 500 mg/m(2) for 6 weeks, followed by a 2-week rest period. Bolus MMC 10 mg/m(2) was added in 3-weekly intervals. Treatment given on an outpatient basis, using portable pump systems, was repeated on day 57. Patients' characteristics were: male/female ratio 20/13; median age 57 (27-75) years; median WHO status 1 (0-2). 18 patients had a primary AGC, and 15 showed a relapsed AGC. Median follow-up was 11.8 months (range of those surviving: 2.7-11.8 months). RESULTS: 32 patients were evaluable for response - complete remission 9.1% (n = 3), partial remission 45.5% (n = 15), no change 27.3% (n = 9), progressive disease 15.1% (n = 5). Median overall survival time was 10.2 months [95% confidence interval (CI): 8.7-11.6], and median progression-free survival time was 7.6 months (95% CI: 4.4-10.9). The worst toxicities (%) observed were (CTC-NCI 1/2/3): leukopenia 45.5/18.2/6.1, thrombocytopenia 33.3/9.1/6.1, vomitus 24.2/9.1/0, diarrhea 36.4/6.1/3.0, stomatitis 18.2/9.1/0, hand-foot syndrome 12.1/0/0. Two patients developed hemolytic-uremic syndrome (HUS). CONCLUSIONS: High-dose 5-FU/FA/MMC is an effective and well-tolerated outpatient regimen for AGC (objective response rate 54.6%). It may serve as an alternative to cisplatin-containing regimens; however, it has to be considered that possibly HUS may occur.
12119460	10	24	5-fluorouracil	Chemical	D005472
12119460	27	39	folinic acid	Chemical	D002955
12119460	73	84	mitomycin C	Chemical	D016685
12119460	114	128	gastric cancer	Disease	D013274
12119460	195	209	5-fluorouracil	Chemical	D005472
12119460	211	215	5-FU	Chemical	D005472
12119460	221	233	folinic acid	Chemical	D002955
12119460	235	237	FA	Chemical	D002955
12119460	306	320	gastric cancer	Disease	D013274
12119460	322	325	AGC	Disease	D013274
12119460	363	371	toxicity	Disease	D064420
12119460	422	426	5-FU	Chemical	D005472
12119460	428	430	FA	Chemical	D002955
12119460	435	446	mitomycin C	Chemical	D016685
12119460	448	451	MMC	Chemical	D016685
12119460	468	476	toxicity	Disease	D064420
12119460	626	629	MMC	Chemical	D016685
12119460	694	698	5-FU	Chemical	D005472
12119460	699	701	FA	Chemical	D002955
12119460	721	724	MMC	Chemical	D016685
12119460	817	820	AGC	Disease	D013274
12119460	847	851	5-FU	Chemical	D005472
12119460	885	887	FA	Chemical	D002955
12119460	953	956	MMC	Chemical	D016685
12119460	1233	1236	AGC	Disease	D013274
12119460	1263	1266	AGC	Disease	D013274
12119460	1698	1708	toxicities	Disease	D064420
12119460	1744	1754	leukopenia	Disease	D007970
12119460	1770	1786	thrombocytopenia	Disease	D013921
12119460	1801	1808	vomitus	Disease	D014839
12119460	1821	1829	diarrhea	Disease	D003967
12119460	1844	1854	stomatitis	Disease	D013280
12119460	1867	1885	hand-foot syndrome	Disease	D060831
12119460	1919	1944	hemolytic-uremic syndrome	Disease	D006463
12119460	1946	1949	HUS	Disease	D006463
12119460	1975	1979	5-FU	Chemical	D005472
12119460	1980	1982	FA	Chemical	D002955
12119460	1983	1986	MMC	Chemical	D016685
12119460	2045	2048	AGC	Disease	D013274
12119460	2116	2125	cisplatin	Chemical	D002945
12119460	2194	2197	HUS	Disease	D006463
12119460	CID	D002955	D014839
12119460	CID	D002955	D013921
12119460	CID	D016685	D003967
12119460	CID	D002955	D013280
12119460	CID	D016685	D013921
12119460	CID	D005472	D014839
12119460	CID	D016685	D007970
12119460	CID	D016685	D006463
12119460	CID	D005472	D003967
12119460	CID	D002955	D003967
12119460	CID	D005472	D006463
12119460	CID	D005472	D013280
12119460	CID	D005472	D007970
12119460	CID	D005472	D013921
12119460	CID	D002955	D007970
12119460	CID	D016685	D014839
12119460	CID	D016685	D013280
12119460	CID	D002955	D006463
12119460	CID	D005472	D060831
12119460	CID	D002955	D060831
12119460	CID	D016685	D060831

12165618|t|Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir.
12165618|a|BACKGROUND: Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children. DESIGN: A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir. METHODS: Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-state pharmacokinetics of indinavir were done at week 4 after the initiation of indinavir. RESULTS: The cumulative incidence of persistent sterile leukocyturia (> or =75 cells/ micro L in at least 2 consecutive visits) after 96 weeks was 53%. Persistent sterile leukocyturia was frequently associated with a mild increase in the urine albumin/creatinine ratio and by microscopic hematuria. The cumulative incidence of serum creatinine levels >50% above normal was 33% after 96 weeks. Children with persistent sterile leukocyturia more frequently had serum creatinine levels of 50% above normal than those children without persistent sterile leukocyturia. In children younger than 5.6 years, persistent sterile leukocyturia was significantly more frequent than in older children. A higher cumulative incidence of persistent leukocyturia was found in children with an area under the curve >19 mg/L x h or a peak serum level of indinavir >12 mg/L. In 4 children, indinavir was discontinued because of nephrotoxicity. Subsequently, the serum creatinine levels decreased, the urine albumin/creatinine ratios returned to zero, and the leukocyturia disappeared within 3 months. CONCLUSIONS: Children treated with indinavir have a high cumulative incidence of persistent sterile leukocyturia. Children with persistent sterile leukocyturia more frequently had an increase in serum creatinine levels of >50% above normal. Younger children have an additional risk for renal complications. The impairment of the renal function in these children occurred in the absence of clinical symptoms of nephrolithiasis. Indinavir-associated nephrotoxicity must be monitored closely, especially in children with risk factors such as persistent sterile leukocyturia, age <5.6 years, an area under the curve of indinavir >19 mg/L x h, and a C(max) >12 mg/L.
12165618	19	31	leukocyturia	Disease	-1
12165618	51	74	impaired renal function	Disease	D007674
12165618	78	122	human immunodeficiency virus type 1-infected	Disease	D015658
12165618	145	154	indinavir	Chemical	D019469
12165618	196	205	indinavir	Chemical	D019469
12165618	432	441	indinavir	Chemical	D019469
12165618	450	464	nephrotoxicity	Disease	D007674
12165618	483	527	human immunodeficiency virus type 1-infected	Disease	D015658
12165618	550	559	indinavir	Chemical	D019469
12165618	591	601	creatinine	Chemical	D003404
12165618	729	739	creatinine	Chemical	D003404
12165618	831	840	indinavir	Chemical	D019469
12165618	885	894	indinavir	Chemical	D019469
12165618	952	964	leukocyturia	Disease	-1
12165618	1067	1079	leukocyturia	Disease	-1
12165618	1148	1158	creatinine	Chemical	D003404
12165618	1184	1193	hematuria	Disease	D006417
12165618	1229	1239	creatinine	Chemical	D003404
12165618	1322	1334	leukocyturia	Disease	-1
12165618	1361	1371	creatinine	Chemical	D003404
12165618	1446	1458	leukocyturia	Disease	-1
12165618	1515	1527	leukocyturia	Disease	-1
12165618	1628	1640	leukocyturia	Disease	-1
12165618	1730	1739	indinavir	Chemical	D019469
12165618	1765	1774	indinavir	Chemical	D019469
12165618	1803	1817	nephrotoxicity	Disease	D007674
12165618	1843	1853	creatinine	Chemical	D003404
12165618	1890	1900	creatinine	Chemical	D003404
12165618	1934	1946	leukocyturia	Disease	-1
12165618	2011	2020	indinavir	Chemical	D019469
12165618	2076	2088	leukocyturia	Disease	-1
12165618	2123	2135	leukocyturia	Disease	-1
12165618	2177	2187	creatinine	Chemical	D003404
12165618	2287	2319	impairment of the renal function	Disease	D007674
12165618	2386	2401	nephrolithiasis	Disease	D053040
12165618	2403	2412	Indinavir	Chemical	D019469
12165618	2424	2438	nephrotoxicity	Disease	D007674
12165618	2534	2546	leukocyturia	Disease	-1
12165618	2591	2600	indinavir	Chemical	D019469
12165618	CID	D019469	D007674
12165618	CID	D019469	D006417

12359538|t|Utility of troponin I in patients with cocaine-associated chest pain.
12359538|a|Baseline electrocardiogram abnormalities and market elevations not associated with myocardial necrosis make accurate diagnosis of myocardial infarction (MI) difficult in patients with cocaine-associated chest pain. Troponin sampling may offer greater diagnostic utility in these patients. OBJECTIVE: To assess outcomes based on troponin positivity in patients with cocaine chest pain admitted for exclusion of MI. METHODS: Outcomes were examined in patients admitted for possible MI after cocaine use. All patients underwent a rapid rule-in protocol that included serial sampling of creatine kinase (CK), CK-MB, and cardiac troponin I (cTnI) over eight hours. Outcomes included CK-MB MI (CK-MB >or= 8 ng/mL with a relative index [(CK-MB x 100)/total CK] >or= 4, cardiac death, and significant coronary disease (>or=50%). RESULTS: Of the 246 admitted patients, 34 (14%) met CK-MB criteria for MI and 38 (16%) had cTnI elevations. Angiography was performed in 29 of 38 patients who were cTnI-positive, with significant disease present in 25 (86%). Three of the four patients without significant disease who had cTnI elevations met CK-MB criteria for MI, and the other had a peak CK-MB level of 13 ng/mL. Sensitivities, specificities, and positive and negative likelihood ratios for predicting cardiac death or significant disease were high for both CK-MB MI and cTnI and were not significantly different. CONCLUSIONS: Most patients with cTnI elevations meet CK-MB criteria for MI, as well as have a high incidence of underlying significant disease. Troponin appears to have an equivalent diagnostic accuracy compared with CK-MB for diagnosing necrosis in patients with cocaine-associated chest pain and suspected MI.
12359538	39	46	cocaine	Chemical	D003042
12359538	58	68	chest pain	Disease	D002637
12359538	153	172	myocardial necrosis	Disease	D009202
12359538	200	221	myocardial infarction	Disease	D009203
12359538	223	225	MI	Disease	D009203
12359538	254	261	cocaine	Chemical	D003042
12359538	273	283	chest pain	Disease	D002637
12359538	435	442	cocaine	Chemical	D003042
12359538	443	453	chest pain	Disease	D002637
12359538	480	482	MI	Disease	D009203
12359538	550	552	MI	Disease	D009203
12359538	559	566	cocaine	Chemical	D003042
12359538	653	661	creatine	Chemical	D003401
12359538	754	756	MI	Disease	D009203
12359538	832	845	cardiac death	Disease	D003643
12359538	863	879	coronary disease	Disease	D003327
12359538	962	964	MI	Disease	D009203
12359538	1218	1220	MI	Disease	D009203
12359538	1361	1374	cardiac death	Disease	D003643
12359538	1423	1425	MI	Disease	D009203
12359538	1545	1547	MI	Disease	D009203
12359538	1711	1719	necrosis	Disease	D009336
12359538	1737	1744	cocaine	Chemical	D003042
12359538	1756	1766	chest pain	Disease	D002637
12359538	1781	1783	MI	Disease	D009203
12359538	CID	D003042	D009203

12372954|t|Acute interstitial nephritis due to nicergoline (Sermion).
12372954|a|We report a case of acute interstitial nephritis (AIN) due to nicergoline (Sermion). A 50-year-old patient admitted to our hospital for fever and acute renal failure. Before admission, he had been taking nicergoline and bendazac lysine due to retinal vein occlusion at ophthalmologic department. Thereafter, he experienced intermittent fever and skin rash. On admission, clinical symptoms (i.e. arthralgia and fever) and laboratory findings (i.e. eosinophilia and renal failure) suggested AIN, and which was confirmed by pathologic findings on renal biopsy. A lymphocyte transformation test demonstrated a positive result against nicergoline. Treatment was consisted of withdrawal of nicergoline and intravenous methylprednisolone, and his renal function was completely recovered. To our knowledge, this is the first report of nicergoline-associated AIN.
12372954	6	28	interstitial nephritis	Disease	D009395
12372954	36	47	nicergoline	Chemical	D009530
12372954	49	56	Sermion	Chemical	D009530
12372954	85	107	interstitial nephritis	Disease	D009395
12372954	109	112	AIN	Disease	D009395
12372954	121	132	nicergoline	Chemical	D009530
12372954	134	141	Sermion	Chemical	D009530
12372954	195	200	fever	Disease	D005334
12372954	205	224	acute renal failure	Disease	D058186
12372954	263	274	nicergoline	Chemical	D009530
12372954	279	294	bendazac lysine	Chemical	C036067
12372954	302	324	retinal vein occlusion	Disease	D012170
12372954	395	400	fever	Disease	D005334
12372954	405	414	skin rash	Disease	D005076
12372954	454	464	arthralgia	Disease	D018771
12372954	469	474	fever	Disease	D005334
12372954	506	518	eosinophilia	Disease	D004802
12372954	523	536	renal failure	Disease	D051437
12372954	548	551	AIN	Disease	D009395
12372954	689	700	nicergoline	Chemical	D009530
12372954	743	754	nicergoline	Chemical	D009530
12372954	771	789	methylprednisolone	Chemical	D008775
12372954	886	897	nicergoline	Chemical	D009530
12372954	909	912	AIN	Disease	D009395
12372954	CID	D009530	D004802
12372954	CID	D009530	D051437
12372954	CID	D009530	D009395
12372954	CID	D009530	D005334
12372954	CID	D009530	D018771

12452552|t|Neuroleptic malignant syndrome complicated by massive intestinal bleeding in a patient with chronic renal failure.
12452552|a|A patient with chronic renal failure (CRF) developed neuroleptic malignant syndrome (NMS) after administration of risperidone and levomepromazine. In addition to the typical symptoms of NMS, massive intestinal bleeding was observed during the episode. This report suggests that NMS in a patient with CRF may be complicated by intestinal bleeding and needs special caution for this complication.
12452552	0	30	Neuroleptic malignant syndrome	Disease	D009459
12452552	65	73	bleeding	Disease	D006470
12452552	92	113	chronic renal failure	Disease	D007676
12452552	130	151	chronic renal failure	Disease	D007676
12452552	153	156	CRF	Disease	D007676
12452552	168	198	neuroleptic malignant syndrome	Disease	D009459
12452552	200	203	NMS	Disease	D009459
12452552	229	240	risperidone	Chemical	D018967
12452552	245	260	levomepromazine	Chemical	D008728
12452552	301	304	NMS	Disease	D009459
12452552	325	333	bleeding	Disease	D006470
12452552	393	396	NMS	Disease	D009459
12452552	415	418	CRF	Disease	D007676
12452552	452	460	bleeding	Disease	D006470
12452552	CID	D018967	D009459
12452552	CID	D008728	D009459

12487093|t|Blood brain barrier in right- and left-pawed female rats assessed by a new staining method.
12487093|a|The asymmetrical breakdown of the blood-brain barrier (BBB) was studied in female rats. Paw preference was assessed by a food reaching test. Adrenaline-induced hypertension was used to destroy the BBB, which was evaluated using triphenyltetrazolium (TTC) staining of the brain slices just after giving adrenaline for 30 s. In normal rats, the whole brain sections exhibited complete staining with TTC. After adrenaline infusion for 30 s, there were large unstained areas in the left brain in right-pawed animals, and vice versa in left-pawed animals. Similar results were obtained in seizure-induced breakdown of BBB. These results were explained by an asymmetric cerebral blood flow depending upon the paw preference in rats. It was suggested that this new method and the results are consistent with contralateral motor control that may be important in determining the dominant cerebral hemisphere in animals.
12487093	233	243	Adrenaline	Chemical	D004837
12487093	252	264	hypertension	Disease	D006973
12487093	320	340	triphenyltetrazolium	Chemical	C009591
12487093	342	345	TTC	Chemical	C009591
12487093	394	404	adrenaline	Chemical	D004837
12487093	489	492	TTC	Chemical	C009591
12487093	500	510	adrenaline	Chemical	D004837
12487093	676	683	seizure	Disease	D012640
12487093	CID	D004837	D006973

12498738|t|Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy.
12498738|a|Several cytopathic mechanisms have been suggested to mediate the dose-limiting cumulative and irreversible cardiomyopathy caused by doxorubicin. Recent evidence indicates that oxidative stress and mitochondrial dysfunction are key factors in the pathogenic process. The objective of this investigation was to test the hypothesis that carvedilol, a nonselective beta-adrenergic receptor antagonist with potent antioxidant properties, protects against the cardiac and hepatic mitochondrial bioenergetic dysfunction associated with subchronic doxorubicin toxicity. Heart and liver mitochondria were isolated from rats treated for 7 weeks with doxorubicin (2 mg/kg sc/week), carvedilol (1 mg/kg ip/week), or the combination of the two drugs. Heart mitochondria isolated from doxorubicin-treated rats exhibited depressed rates for state 3 respiration (336 +/- 26 versus 425 +/- 53 natom O/min/mg protein) and a lower respiratory control ratio (RCR) (4.3 +/- 0.6 versus 5.8 +/- 0.4) compared with cardiac mitochondria isolated from saline-treated rats. Mitochondrial calcium-loading capacity and the activity of NADH-dehydrogenase were also suppressed in cardiac mitochondria from doxorubicin-treated rats. Doxorubicin treatment also caused a decrease in RCR for liver mitochondria (3.9 +/- 0.9 versus 5.6 +/- 0.7 for control rats) and inhibition of hepatic cytochrome oxidase activity. Coadministration of carvedilol decreased the extent of cellular vacuolization in cardiac myocytes and prevented the inhibitory effect of doxorubicin on mitochondrial respiration in both heart and liver. Carvedilol also prevented the decrease in mitochondrial Ca(2+) loading capacity and the inhibition of the respiratory complexes of heart mitochondria caused by doxorubicin. Carvedilol by itself did not affect any of the parameters measured for heart or liver mitochondria. It is concluded that this protection by carvedilol against both the structural and functional cardiac tissue damage may afford significant clinical advantage in minimizing the dose-limiting mitochondrial dysfunction and cardiomyopathy that accompanies long-term doxorubicin therapy in cancer patients.
12498738	0	10	Carvedilol	Chemical	C043211
12498738	28	39	doxorubicin	Chemical	D004317
12498738	62	76	cardiomyopathy	Disease	D009202
12498738	185	199	cardiomyopathy	Disease	D009202
12498738	210	221	doxorubicin	Chemical	D004317
12498738	275	300	mitochondrial dysfunction	Disease	D028361
12498738	412	422	carvedilol	Chemical	C043211
12498738	618	629	doxorubicin	Chemical	D004317
12498738	630	638	toxicity	Disease	D064420
12498738	718	729	doxorubicin	Chemical	D004317
12498738	749	759	carvedilol	Chemical	C043211
12498738	849	860	doxorubicin	Chemical	D004317
12498738	1139	1146	calcium	Chemical	D002118
12498738	1253	1264	doxorubicin	Chemical	D004317
12498738	1279	1290	Doxorubicin	Chemical	D004317
12498738	1479	1489	carvedilol	Chemical	C043211
12498738	1596	1607	doxorubicin	Chemical	D004317
12498738	1662	1672	Carvedilol	Chemical	C043211
12498738	1718	1720	Ca	Chemical	D002118
12498738	1822	1833	doxorubicin	Chemical	D004317
12498738	1835	1845	Carvedilol	Chemical	C043211
12498738	1975	1985	carvedilol	Chemical	C043211
12498738	2125	2150	mitochondrial dysfunction	Disease	D028361
12498738	2155	2169	cardiomyopathy	Disease	D009202
12498738	2197	2208	doxorubicin	Chemical	D004317
12498738	2220	2226	cancer	Disease	D009369
12498738	CID	D004317	D009202

12523489|t|Cocaine-induced hyperactivity is more influenced by adenosine receptor agonists than amphetamine-induced hyperactivity.
12523489|a|The influence of adenosine receptor agonists and antagonists on cocaine-and amphetamine-induced hyperactivity was examined in mice. All adenosine receptor agonists significantly decreased the locomotor activity in mice, and the effects were dose-dependent. It seems that adenosine A1 and A2 receptors might be involved in this reaction. Moreover, all adenosine receptor agonists: 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), A2A receptor agonist, N6-cyclopentyladenosine (CPA), A1 receptor agonist, and 5'-N-ethylcarboxamidoadenosine (NECA), A2/A1 receptor agonist significantly and dose-dependently decreased cocaine-induced locomotor activity. CPA reduced cocaine action at the doses which, given alone, did not influence motility, while CGS 21680 and NECA decreased the action of cocaine at the doses which, given alone, decreased locomotor activity in animals. These results suggest the involvement of both adenosine receptors in the action of cocaine although agonists of A1 receptors seem to have stronger influence on it. The selective blockade of A2 adenosine receptor by DMPX (3,7-dimethyl-1-propargylxanthine) significantly enhanced cocaine-induced locomotor activity of animals. Caffeine had similar action but the effect was not significant. CPT (8-cyclopentyltheophylline)--A1 receptor antagonist, did not show any influence in this test. Similarly, all adenosine receptor agonists decreased amphetamine-induced hyperactivity, but at the higher doses than those which were active in cocaine-induced hyperactivity. The selective blockade of A2 adenosine receptors (DMPX) and non-selective blockade of adenosine receptors (caffeine) significantly increased the action of amphetamine in the locomotor activity test. Our results have shown that all adenosine receptor agonists (A1 and A2) reduce cocaine- and amphetamine-induced locomotor activity and indicate that cocaine-induced hyperactivity is more influenced by adenosine receptor agonists (particularly A1 receptors) than amphetamine-induced hyperactivity.
12523489	0	7	Cocaine	Chemical	D003042
12523489	16	29	hyperactivity	Disease	D006948
12523489	52	61	adenosine	Chemical	D000241
12523489	85	96	amphetamine	Chemical	D000661
12523489	105	118	hyperactivity	Disease	D006948
12523489	137	146	adenosine	Chemical	D000241
12523489	184	191	cocaine	Chemical	D003042
12523489	196	207	amphetamine	Chemical	D000661
12523489	216	229	hyperactivity	Disease	D006948
12523489	256	265	adenosine	Chemical	D000241
12523489	298	330	decreased the locomotor activity	Disease	D004409
12523489	391	400	adenosine	Chemical	D000241
12523489	471	480	adenosine	Chemical	D000241
12523489	500	565	2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine	Chemical	C061282
12523489	567	576	CGS 21680	Chemical	C061282
12523489	601	624	N6-cyclopentyladenosine	Chemical	C048599
12523489	626	629	CPA	Chemical	C048599
12523489	657	687	5'-N-ethylcarboxamidoadenosine	Chemical	D019830
12523489	689	693	NECA	Chemical	D019830
12523489	764	771	cocaine	Chemical	D003042
12523489	800	803	CPA	Chemical	C048599
12523489	812	819	cocaine	Chemical	D003042
12523489	894	903	CGS 21680	Chemical	C061282
12523489	908	912	NECA	Chemical	D019830
12523489	937	944	cocaine	Chemical	D003042
12523489	1065	1074	adenosine	Chemical	D000241
12523489	1102	1109	cocaine	Chemical	D003042
12523489	1212	1221	adenosine	Chemical	D000241
12523489	1234	1238	DMPX	Chemical	C057837
12523489	1240	1272	3,7-dimethyl-1-propargylxanthine	Chemical	C057837
12523489	1297	1304	cocaine	Chemical	D003042
12523489	1344	1352	Caffeine	Chemical	D002110
12523489	1408	1411	CPT	Chemical	C053907
12523489	1413	1438	8-cyclopentyltheophylline	Chemical	C053907
12523489	1521	1530	adenosine	Chemical	D000241
12523489	1559	1570	amphetamine	Chemical	D000661
12523489	1579	1592	hyperactivity	Disease	D006948
12523489	1650	1657	cocaine	Chemical	D003042
12523489	1666	1679	hyperactivity	Disease	D006948
12523489	1710	1719	adenosine	Chemical	D000241
12523489	1731	1735	DMPX	Chemical	C057837
12523489	1767	1776	adenosine	Chemical	D000241
12523489	1788	1796	caffeine	Chemical	D002110
12523489	1836	1847	amphetamine	Chemical	D000661
12523489	1912	1921	adenosine	Chemical	D000241
12523489	1959	1966	cocaine	Chemical	D003042
12523489	1972	1983	amphetamine	Chemical	D000661
12523489	2029	2036	cocaine	Chemical	D003042
12523489	2045	2058	hyperactivity	Disease	D006948
12523489	2081	2090	adenosine	Chemical	D000241
12523489	2142	2153	amphetamine	Chemical	D000661
12523489	2162	2175	hyperactivity	Disease	D006948
12523489	CID	D000661	D004409
12523489	CID	D003042	D004409
12523489	CID	C057837	D004409

12535818|t|Amiodarone and the risk of bradyarrhythmia requiring permanent pacemaker in elderly patients with atrial fibrillation and prior myocardial infarction.
12535818|a|OBJECTIVES: The aim of this study was to determine whether the use of amiodarone in patients with atrial fibrillation (AF) increases the risk of bradyarrhythmia requiring a permanent pacemaker. BACKGROUND: Reports of severe bradyarrhythmia during amiodarone therapy are infrequent and limited to studies assessing the therapy's use in the management of patients with ventricular arrhythmias. METHODS: A study cohort of 8,770 patients age > or =65 years with a new diagnosis of AF was identified from a provincewide database of Quebec residents with a myocardial infarction (MI) between 1991 and 1999. Using a nested case-control design, 477 cases of bradyarrhythmia requiring a permanent pacemaker were matched (1:4) to 1,908 controls. Multivariable logistic regression was used to estimate the odds ratio (OR) of pacemaker insertion associated with amiodarone use, controlling for baseline risk factors and exposure to sotalol, Class I antiarrhythmic agents, beta-blockers, calcium channel blockers, and digoxin. RESULTS: amiodarone use was associated with an increased risk of pacemaker insertion (OR: 2.14, 95% confidence interval [CI]: 1.30 to 3.54). This effect was modified by gender, with a greater risk in women versus men (OR: 3.86, 95% CI: 1.70 to 8.75 vs. OR: 1.52, 95% CI: 0.80 to 2.89). Digoxin was the only other medication associated with an increased risk of pacemaker insertion (OR: 1.78, 95% CI: 1.37 to 2.31). CONCLUSIONS: This study suggests that the use of amiodarone in elderly patients with AF and a previous MI increases the risk of bradyarrhythmia requiring a permanent pacemaker. The finding of an augmented risk of pacemaker insertion in elderly women receiving amiodarone requires further investigation.
12535818	0	10	Amiodarone	Chemical	D000638
12535818	27	42	bradyarrhythmia	Disease	D001919
12535818	98	117	atrial fibrillation	Disease	D001281
12535818	128	149	myocardial infarction	Disease	D009203
12535818	221	231	amiodarone	Chemical	D000638
12535818	249	268	atrial fibrillation	Disease	D001281
12535818	270	272	AF	Disease	D001281
12535818	296	311	bradyarrhythmia	Disease	D001919
12535818	375	390	bradyarrhythmia	Disease	D001919
12535818	398	408	amiodarone	Chemical	D000638
12535818	518	541	ventricular arrhythmias	Disease	D001145
12535818	628	630	AF	Disease	D001281
12535818	702	723	myocardial infarction	Disease	D009203
12535818	725	727	MI	Disease	D009203
12535818	801	816	bradyarrhythmia	Disease	D001919
12535818	1001	1011	amiodarone	Chemical	D000638
12535818	1071	1078	sotalol	Chemical	D013015
12535818	1126	1133	calcium	Chemical	D002118
12535818	1156	1163	digoxin	Chemical	D004077
12535818	1174	1184	amiodarone	Chemical	D000638
12535818	1451	1458	Digoxin	Chemical	D004077
12535818	1629	1639	amiodarone	Chemical	D000638
12535818	1665	1667	AF	Disease	D001281
12535818	1683	1685	MI	Disease	D009203
12535818	1708	1723	bradyarrhythmia	Disease	D001919
12535818	1840	1850	amiodarone	Chemical	D000638
12535818	CID	D000638	D001919

12559315|t|Indomethacin-induced morphologic changes in the rat urinary bladder epithelium.
12559315|a|OBJECTIVES: To evaluate the morphologic changes in rat urothelium induced by indomethacin. Nonsteroidal anti-inflammatory drug-induced cystitis is a poorly recognized and under-reported condition. In addition to tiaprofenic acid, indomethacin has been reported to be associated with this condition. METHODS: Three groups were established: a control group (n = 10), a high-dose group (n = 10), treated with one intraperitoneal injection of indomethacin 20 mg/kg, and a therapeutic dose group (n = 10) in which oral indomethacin was administered 3.25 mg/kg body weight daily for 3 weeks. The animals were then killed and the bladders removed for light and electron microscopic studies. RESULTS: The light microscopic findings showed some focal epithelial degeneration that was more prominent in the high-dose group. When compared with the control group, both indomethacin groups revealed statistically increased numbers of mast cells in the mucosa (P <0.0001) and penetration of lanthanum nitrate through intercellular areas of the epithelium. Furthermore, the difference in mast cell counts between the high and therapeutic dose groups was also statistically significant (P <0.0001). CONCLUSIONS: Indomethacin resulted in histopathologic findings typical of interstitial cystitis, such as leaky bladder epithelium and mucosal mastocytosis. The true incidence of nonsteroidal anti-inflammatory drug-induced cystitis in humans must be clarified by prospective clinical trials.
12559315	0	12	Indomethacin	Chemical	D007213
12559315	157	169	indomethacin	Chemical	D007213
12559315	215	223	cystitis	Disease	D003556
12559315	292	308	tiaprofenic acid	Chemical	C021270
12559315	310	322	indomethacin	Chemical	D007213
12559315	519	531	indomethacin	Chemical	D007213
12559315	594	606	indomethacin	Chemical	D007213
12559315	937	949	indomethacin	Chemical	D007213
12559315	1057	1074	lanthanum nitrate	Chemical	C016534
12559315	1276	1288	Indomethacin	Chemical	D007213
12559315	1337	1358	interstitial cystitis	Disease	D018856
12559315	1405	1417	mastocytosis	Disease	D008415
12559315	1485	1493	cystitis	Disease	D003556
12559315	CID	D007213	D008415
12559315	CID	D007213	D018856

12644816|t|An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer.
12644816|a|The antiangiogenic effects of thalidomide have been assessed in clinical trials in patients with various solid and haematological malignancies. Thalidomide blocks the activity of angiogenic agents including bFGF, VEGF and IL-6. We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with androgen-independent prostate cancer. The mean time of study was 109 days (median 107, range 4-184 days). Patients underwent regular measurement of prostate-specific antigen (PSA), urea and electrolytes, serum bFGF and VEGF. Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. Increasing levels of serum bFGF and VEGF were associated with progressive disease; five of six men who demonstrated a fall in PSA also showed a decline in bFGF and VEGF levels, and three of four men with a rising PSA showed an increase in both growth factors. Adverse effects included constipation, morning drowsiness, dizziness and rash, and resulted in withdrawal from the study by three men. Evidence of peripheral sensory neuropathy was found in nine of 13 men before treatment. In the seven men who completed six months on thalidomide, subclinical evidence of peripheral neuropathy was found in four before treatment, but in all seven at repeat testing. The findings indicate that thalidomide may be an option for patients who have failed other forms of therapy, provided close follow-up is maintained for development of peripheral neuropathy.
12644816	41	52	thalidomide	Chemical	D013792
12644816	56	64	androgen	Chemical	D000728
12644816	77	92	prostate cancer	Disease	D011471
12644816	124	135	thalidomide	Chemical	D013792
12644816	209	236	haematological malignancies	Disease	D019337
12644816	238	249	Thalidomide	Chemical	D013792
12644816	361	372	thalidomide	Chemical	D013792
12644816	425	433	androgen	Chemical	D000728
12644816	446	461	prostate cancer	Disease	D011471
12644816	606	610	urea	Chemical	D014508
12644816	1133	1145	constipation	Disease	D003248
12644816	1155	1165	drowsiness	Disease	D006970
12644816	1167	1176	dizziness	Disease	D004244
12644816	1181	1185	rash	Disease	D005076
12644816	1255	1284	peripheral sensory neuropathy	Disease	D010523
12644816	1376	1387	thalidomide	Chemical	D013792
12644816	1413	1434	peripheral neuropathy	Disease	D010523
12644816	1534	1545	thalidomide	Chemical	D013792
12644816	1674	1695	peripheral neuropathy	Disease	D010523
12644816	CID	D013792	D004244
12644816	CID	D013792	D003248
12644816	CID	D013792	D005076
12644816	CID	D013792	D006970
12644816	CID	D013792	D010523

12677626|t|Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases.
12677626|a|BACKGROUND AND OBJECTIVES: Central nervous system and cardiac toxicity following the administration of local anesthetics is a recognized complication of regional anesthesia. Levobupivacaine, the pure S(-) enantiomer of bupivacaine, was developed to improve the cardiac safety profile of bupivacaine. We describe 2 cases of grand mal seizures following accidental intravascular injection of levobupivacaine. CASE REPORT: Two patients presenting for elective orthopedic surgery of the lower limb underwent blockade of the lumbar plexus via the posterior approach. Immediately after the administration of levobupivacaine 0.5% with epinephrine 2.5 microgram/mL, the patients developed grand mal seizures, despite negative aspiration for blood and no clinical signs of intravenous epinephrine administration. The seizures were successfully treated with sodium thiopental in addition to succinylcholine in 1 patient. Neither patient developed signs of cardiovascular toxicity. Both patients were treated preoperatively with beta-adrenergic antagonist medications, which may have masked the cardiovascular signs of the unintentional intravascular administration of levobupivacaine with epinephrine. CONCLUSIONS: Although levobupivacaine may have a safer cardiac toxicity profile than racemic bupivacaine, if adequate amounts of levobupivacaine reach the circulation, it will result in convulsions. Plasma concentrations sufficient to result in central nervous system toxicity did not produce manifestations of cardiac toxicity in these 2 patients.
12677626	0	31	Central nervous system toxicity	Disease	D020258
12677626	64	79	levobupivacaine	Chemical	C476513
12677626	155	198	Central nervous system and cardiac toxicity	Disease	D020258|D066126	Central nervous system toxicity|cardiac toxicity
12677626	302	317	Levobupivacaine	Chemical	C476513
12677626	347	358	bupivacaine	Chemical	D002045
12677626	415	426	bupivacaine	Chemical	D002045
12677626	451	469	grand mal seizures	Disease	D004830
12677626	518	533	levobupivacaine	Chemical	C476513
12677626	730	745	levobupivacaine	Chemical	C476513
12677626	756	767	epinephrine	Chemical	D004837
12677626	809	827	grand mal seizures	Disease	D004830
12677626	904	915	epinephrine	Chemical	D004837
12677626	936	944	seizures	Disease	D012640
12677626	976	993	sodium thiopental	Chemical	D013874
12677626	1009	1024	succinylcholine	Chemical	D013390
12677626	1074	1097	cardiovascular toxicity	Disease	D002318
12677626	1286	1301	levobupivacaine	Chemical	C476513
12677626	1307	1318	epinephrine	Chemical	D004837
12677626	1342	1357	levobupivacaine	Chemical	C476513
12677626	1375	1391	cardiac toxicity	Disease	D066126
12677626	1413	1424	bupivacaine	Chemical	D002045
12677626	1449	1464	levobupivacaine	Chemical	C476513
12677626	1506	1517	convulsions	Disease	D012640
12677626	1565	1596	central nervous system toxicity	Disease	D020258
12677626	1631	1647	cardiac toxicity	Disease	D066126
12677626	CID	C476513	D004830

12699527|t|Anaesthetic complications associated with myotonia congenita: case study and comparison with other myotonic disorders.
12699527|a|Myotonia congenita (MC) is caused by a defect in the skeletal muscle chloride channel function, which may cause sustained membrane depolarisation. We describe a previously healthy 32-year-old woman who developed a life-threatening muscle spasm and secondary ventilation difficulties following a preoperative injection of suxamethonium. The muscle spasms disappeared spontaneously and the surgery proceeded without further problems. When subsequently questioned, she reported minor symptoms suggesting a myotonic condition. Myotonia was found on clinical examination and EMG. The diagnosis MC was confirmed genetically. Neither the patient nor the anaesthetist were aware of the diagnosis before this potentially lethal complication occurred. We give a brief overview of ion channel disorders including malignant hyperthermia and their anaesthetic considerations.
12699527	42	60	myotonia congenita	Disease	D009224
12699527	99	117	myotonic disorders	Disease	D020967
12699527	119	137	Myotonia congenita	Disease	D009224
12699527	139	141	MC	Disease	D009224
12699527	188	196	chloride	Chemical	D002712
12699527	231	264	sustained membrane depolarisation	Disease	-1
12699527	350	362	muscle spasm	Disease	D013035
12699527	440	453	suxamethonium	Chemical	D013390
12699527	459	472	muscle spasms	Disease	D013035
12699527	622	640	myotonic condition	Disease	D020967
12699527	642	650	Myotonia	Disease	D009222
12699527	708	710	MC	Disease	D009224
12699527	889	910	ion channel disorders	Disease	-1
12699527	921	943	malignant hyperthermia	Disease	D008305
12699527	CID	D013390	D013035

12752472|t|Respiratory pattern in a rat model of epilepsy.
12752472|a|PURPOSE: Apnea is known to occur during seizures, but systematic studies of ictal respiratory changes in adults are few. Data regarding respiratory pattern defects during interictal periods also are scarce. Here we sought to generate information with regard to the interictal period in animals with pilocarpine-induced epilepsy. METHODS: Twelve rats (six chronically epileptic animals and six controls) were anesthetized, given tracheotomies, and subjected to hyperventilation or hypoventilation conditions. Breathing movements caused changes in thoracic volume and forced air to flow tidally through a pneumotachograph. This flow was measured by using a differential pressure transducer, passed through a polygraph, and from this to a computer with custom software that derived ventilation (VE), tidal volume (VT), inspiratory time (TI), expiratory time (TE), breathing frequency (f), and mean inspiratory flow (VT/TI) on a breath-by-breath basis. RESULTS: The hyperventilation maneuver caused a decrease in spontaneous ventilation in pilocarpine-treated and control rats. Although VE had a similar decrease in both groups, in the epileptic group, the decrease in VE was due to a significant (p < 0.05) increase in TE peak in relation to that of the control animals. The hypoventilation maneuver led to an increase in the arterial Paco2, followed by an increase in VE. In the epileptic group, the increase in VE was mediated by a significant (p < 0.05) decrease in TE peak compared with the control group. Systemic application of KCN, to evaluate the effects of peripheral chemoreception activation on ventilation, led to a similar increase in VE for both groups. CONCLUSIONS: The data indicate that pilocarpine-treated animals have an altered ability to react to (or compensate for) blood gas changes with changes in ventilation and suggest that it is centrally determined. We speculate on the possible relation of the current findings on treating different epilepsy-associated conditions.
12752472	38	46	epilepsy	Disease	D004827
12752472	57	62	Apnea	Disease	D001049
12752472	88	96	seizures	Disease	D012640
12752472	347	358	pilocarpine	Chemical	D010862
12752472	367	375	epilepsy	Disease	D004827
12752472	415	424	epileptic	Disease	D004827
12752472	508	524	hyperventilation	Disease	D006985
12752472	1010	1026	hyperventilation	Disease	D006985
12752472	1084	1095	pilocarpine	Chemical	D010862
12752472	1180	1189	epileptic	Disease	D004827
12752472	1425	1434	epileptic	Disease	D004827
12752472	1749	1760	pilocarpine	Chemical	D010862
12752472	2008	2016	epilepsy	Disease	D004827
12752472	CID	D010862	D004827

12828076|t|Increased serum soluble Fas in patients with acute liver failure due to paracetamol overdose.
12828076|a|BACKGROUND/AIMS: Experimental studies have suggested that apoptosis via the Fas/Fas Ligand signaling system may play an important role in the development of acute liver failure. The aim of the study was to investigate the soluble form of Fas in patients with acute liver failure. METHODOLOGY: Serum levels of sFas (soluble Fas) were measured by ELISA in 24 patients with acute liver failure and 10 normal control subjects. Serum levels of tumor necrosis factor-alpha and interferon-gamma were also determined by ELISA. RESULTS: Serum sFas was significantly increased in patients with acute liver failure (median, 26.8 U/mL; range, 6.9-52.7 U/mL) compared to the normal controls (median, 8.6 U/mL; range, 6.5-12.0 U/mL, P < 0.0001). Levels were significantly greater in patients with acute liver failure due to paracetamol overdose (median, 28.7 U/mL; range, 12.8-52.7 U/mL, n = 17) than those due to non-A to E hepatitis (median, 12.5 U/mL; range, 6.9-46.0 U/mL, n = 7, P < 0.01). There was no relationship of sFas to eventual outcome in the patients. A significant correlation was observed between serum sFas levels and aspartate aminotransferase (r = 0.613, P < 0.01). CONCLUSIONS: The increased concentration of sFas in serum of patients with acute liver failure may reflect activation of Fas-mediated apoptosis in the liver and this together with increased tumor necrosis factor-alpha may be an important factor in liver cell loss.
12828076	45	64	acute liver failure	Disease	D017114
12828076	72	83	paracetamol	Chemical	D000082
12828076	84	92	overdose	Disease	D062787
12828076	251	270	acute liver failure	Disease	D017114
12828076	353	372	acute liver failure	Disease	D017114
12828076	465	484	acute liver failure	Disease	D017114
12828076	533	538	tumor	Disease	D009369
12828076	539	547	necrosis	Disease	D009336
12828076	678	697	acute liver failure	Disease	D017114
12828076	877	896	acute liver failure	Disease	D017114
12828076	904	915	paracetamol	Chemical	D000082
12828076	916	924	overdose	Disease	D062787
12828076	1005	1014	hepatitis	Disease	D056486
12828076	1215	1224	aspartate	Chemical	D001224
12828076	1340	1359	acute liver failure	Disease	D017114
12828076	1455	1460	tumor	Disease	D009369
12828076	1461	1469	necrosis	Disease	D009336
12828076	CID	D000082	D017114

12865514|t|Bilateral subthalamic nucleus stimulation for Parkinson's disease.
12865514|a|High frequency stimulation of the subthalamic nucleus (STN) is known to ameliorate the signs and symptoms of advanced Parkinson's disease. AIM: We studied the effect of high frequency STN stimulation in 23 patients. METHOD: Twenty-three patients suffering from severe Parkinson's disease (Stages III-V on Hoehn and Yahr scale) and, particularly bradykinesia, rigidity, and levodopa-induced dyskinesias underwent bilateral implantation of electrodes in the STN. Preoperative and postoperative assessments of these patients at 1, 3, 6 and 12 months follow-up, in "on" and "off" drug conditions, was carried out using Unified Parkinson's Disease Rating Scale, Hoehn and Yahr staging, England activities of daily living score and video recordings. RESULTS: After one year of electrical stimulation of the STN, the patients' scores for activities of daily living and motor examination scores (Unified Parkinson's Disease Rating Scale parts II and III) off medication improved by 62% and 61% respectively (p<0.0005). The subscores for the akinesia, rigidity, tremor and gait also improved. (p<0.0005). The average levodopa dose decreased from 813 mg to 359 mg. The cognitive functions remained unchanged. Two patients developed device-related complications and two patients experienced abnormal weight gain. CONCLUSION: Bilateral subthalamic nucleus stimulation is an effective treatment for advanced Parkinson's disease. It reduces the severity of "off" phase symptoms, improves the axial symptoms and reduces levodopa requirements. The reduction in the levodopa dose is useful in controlling drug-induced dyskinesias.
12865514	46	65	Parkinson's disease	Disease	D010300
12865514	185	204	Parkinson's disease	Disease	D010300
12865514	335	354	Parkinson's disease	Disease	D010300
12865514	412	424	bradykinesia	Disease	D018476
12865514	426	434	rigidity	Disease	D009127
12865514	440	448	levodopa	Chemical	D007980
12865514	457	468	dyskinesias	Disease	D004409
12865514	690	709	Parkinson's Disease	Disease	D010300
12865514	963	982	Parkinson's Disease	Disease	D010300
12865514	1100	1108	akinesia	Disease	D004409
12865514	1110	1118	rigidity	Disease	D009127
12865514	1120	1126	tremor	Disease	D014202
12865514	1175	1183	levodopa	Chemical	D007980
12865514	1462	1481	Parkinson's disease	Disease	D010300
12865514	1572	1580	levodopa	Chemical	D007980
12865514	1616	1624	levodopa	Chemical	D007980
12865514	1655	1679	drug-induced dyskinesias	Disease	D004409
12865514	CID	D007980	D004409

12912689|t|Ocular motility changes after subtenon carboplatin chemotherapy for retinoblastoma.
12912689|a|BACKGROUND: Focal subtenon carboplatin injections have recently been used as a presumably toxicity-free adjunct to systemic chemotherapy for intraocular retinoblastoma. OBJECTIVE: To report our clinical experience with abnormal ocular motility in patients treated with subtenon carboplatin chemotherapy. METHODS: We noted abnormal ocular motility in 10 consecutive patients with retinoblastoma who had received subtenon carboplatin. During ocular manipulation under general anesthesia, we assessed their eyes by forced duction testing, comparing ocular motility after tumor control with ocular motility at diagnosis. Eyes subsequently enucleated because of treatment failure (n = 4) were examined histologically. RESULTS: Limitation of ocular motility was detected in all 12 eyes of 10 patients treated for intraocular retinoblastoma with 1 to 6 injections of subtenon carboplatin as part of multimodality therapy. Histopathological examination revealed many lipophages in the periorbital fat surrounding the optic nerve in 1 eye, indicative of phagocytosis of previously existing fat cells and suggesting prior fat necrosis. The enucleations were technically difficult and hazardous for globe rupture because of extensive orbital soft tissue adhesions. CONCLUSIONS: Subtenon carboplatin chemotherapy is associated with significant fibrosis of orbital soft tissues, leading to mechanical restriction of eye movements and making subsequent enucleation difficult. Subtenon carboplatin is not free of toxicity, and its use is best restricted to specific indications.
12912689	39	50	carboplatin	Chemical	D016190
12912689	68	82	retinoblastoma	Disease	D012175
12912689	111	122	carboplatin	Chemical	D016190
12912689	174	182	toxicity	Disease	D064420
12912689	237	251	retinoblastoma	Disease	D012175
12912689	303	327	abnormal ocular motility	Disease	D015835
12912689	362	373	carboplatin	Chemical	D016190
12912689	406	430	abnormal ocular motility	Disease	D015835
12912689	463	477	retinoblastoma	Disease	D012175
12912689	504	515	carboplatin	Chemical	D016190
12912689	652	657	tumor	Disease	D009369
12912689	903	917	retinoblastoma	Disease	D012175
12912689	953	964	carboplatin	Chemical	D016190
12912689	1200	1208	necrosis	Disease	D009336
12912689	1278	1285	rupture	Disease	D012421
12912689	1360	1371	carboplatin	Chemical	D016190
12912689	1416	1424	fibrosis	Disease	D005355
12912689	1555	1566	carboplatin	Chemical	D016190
12912689	1582	1590	toxicity	Disease	D064420
12912689	CID	D016190	D015835
12912689	CID	D016190	D005355

12948256|t|Ethambutol and optic neuropathy.
12948256|a|PURPOSE: To demonstrate the association between ethambutol and optic neuropathy. METHOD: Thirteen patients who developed optic neuropathy after being treated with ethambutol for tuberculosis of the lung or lymph node at Siriraj Hospital between 1997 and 2001 were retrospectively reviewed. The clinical characteristics and initial and final visual acuity were analyzed to determine visual outcome. RESULTS: All patients had optic neuropathy between 1 to 6 months (mean = 2.9 months) after starting ethambutol therapy at a dosage ranging from 13 to 20 mg/kg/day (mean = 17 mg/kg/day). Seven (54%) of the 13 patients experienced visual recovery after stopping the drug. Of 6 patients with irreversible visual impairment, 4 patients had diabetes mellitus, glaucoma and a history of heavy smoking. CONCLUSION: Early recognition of optic neuropathy should be considered in patients with ethambutol therapy. A low dose and prompt discontinuation of the drug is recommended particularly in individuals with diabetes mellitus, glaucoma or who are heavy smokers.
12948256	0	10	Ethambutol	Chemical	D004977
12948256	15	31	optic neuropathy	Disease	D009901
12948256	81	91	ethambutol	Chemical	D004977
12948256	96	112	optic neuropathy	Disease	D009901
12948256	154	170	optic neuropathy	Disease	D009901
12948256	196	206	ethambutol	Chemical	D004977
12948256	211	249	tuberculosis of the lung or lymph node	Disease	D014397|D014388	tuberculosis of the lung|tuberculosis of lymph node
12948256	457	473	optic neuropathy	Disease	D009901
12948256	531	541	ethambutol	Chemical	D004977
12948256	733	750	visual impairment	Disease	D014786
12948256	767	784	diabetes mellitus	Disease	D003920
12948256	786	794	glaucoma	Disease	D005901
12948256	860	876	optic neuropathy	Disease	D009901
12948256	915	925	ethambutol	Chemical	D004977
12948256	1033	1050	diabetes mellitus	Disease	D003920
12948256	1052	1060	glaucoma	Disease	D005901
12948256	CID	D004977	D009901

12950111|t|Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate.
12950111|a|Gustatory hyperhidrosis is facial sweating usually associated with the eating of hot spicy food or even smelling this food. Current options of treatment include oral anticholinergic drugs, the topical application of anticholinergics or aluminum chloride, and the injection of botulinum toxin. Thirteen patients have been treated to date with 1.5% or 2% topical glycopyrrolate. All patients had gustatory hyperhidrosis, which interfered with their social activities, after transthroacic endoscopic sympathectomy, and which was associated with compensatory focal hyperhidrosis. After applying topical glycopyrrolate, the subjective effect was excellent (no sweating after eating hot spicy food) in 10 patients (77%), and fair (clearly reduced sweating) in 3 patients (23%). All had reported incidents of being very embarrassed whilst eating hot spicy foods. Adverse effects included a mildly dry mouth and a sore throat in 2 patients (2% glycopyrrolate), a light headache in 1 patient (1.5% glycopyrrolate). The topical application of a glycopyrrolate pad appeared to be safe, efficacious, well tolerated, and a convenient method of treatment for moderate to severe symptoms of gustatory hyperhidrosis in post transthoracic endoscopic sympathectomy or sympathicotomy patients, with few side effects.
12950111	26	49	gustatory hyperhidrosis	Disease	D013547
12950111	63	77	glycopyrrolate	Chemical	D006024
12950111	79	102	Gustatory hyperhidrosis	Disease	D013547
12950111	113	121	sweating	Disease	D013547
12950111	315	332	aluminum chloride	Chemical	C010845
12950111	440	454	glycopyrrolate	Chemical	D006024
12950111	473	496	gustatory hyperhidrosis	Disease	D013547
12950111	640	653	hyperhidrosis	Disease	D006945
12950111	678	692	glycopyrrolate	Chemical	D006024
12950111	734	742	sweating	Disease	D013547
12950111	820	828	sweating	Disease	D013547
12950111	969	978	dry mouth	Disease	D014987
12950111	985	996	sore throat	Disease	D010612
12950111	1015	1029	glycopyrrolate	Chemical	D006024
12950111	1040	1048	headache	Disease	D006261
12950111	1068	1082	glycopyrrolate	Chemical	D006024
12950111	1114	1128	glycopyrrolate	Chemical	D006024
12950111	1255	1278	gustatory hyperhidrosis	Disease	D013547
12950111	CID	D006024	D006261
12950111	CID	D006024	D010612

14616590|t|Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil.
14616590|a|We compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan 1%). In a randomised, double-blind, cross-over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg-1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three-compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p < 0.01) and thrombophlebitis (93.3 vs. 6.6%, p < 0.001) occurred more frequently with AM149 than with Disoprivan. Although both formulations had similar pharmacokinetic and pharmacodynamic profiles the new formulation is not suitable for clinical use due to the high incidence of thrombophlebitis produced.
14616590	81	89	propofol	Chemical	D015742
14616590	214	222	propofol	Chemical	D015742
14616590	303	311	propofol	Chemical	D015742
14616590	313	323	Disoprivan	Chemical	D015742
14616590	461	469	propofol	Chemical	D015742
14616590	478	486	propofol	Chemical	D015742
14616590	725	729	pain	Disease	D010146
14616590	825	841	thrombophlebitis	Disease	D013924
14616590	1211	1215	Pain	Disease	D010146
14616590	1256	1272	thrombophlebitis	Disease	D013924
14616590	1346	1356	Disoprivan	Chemical	D015742
14616590	1524	1540	thrombophlebitis	Disease	D013924
14616590	CID	D015742	D013924
14616590	CID	D015742	D010146

14748761|t|Vinorelbine-related cardiac events: a meta-analysis of randomized clinical trials.
14748761|a|Several cases of cardiac adverse reactions related to vinorelbine (VNR) have been reported in the literature. In order to quantify the incidence of these cardiac events, we performed a meta-analysis of clinical trials comparing VNR with other chemotherapeutic agents in the treatment of various malignancies. Randomized clinical trials comparing VNR with other drugs in the treatment of cancer were searched in Medline, Embase, Evidence-based Medicine Reviews databases and the Cochrane library from 1987 to 2002. Outcomes of interest were severe cardiac events, toxic deaths and cardiac event-related deaths reported in each publication. We found 19 trials, involving 2441 patients treated by VNR and 2050 control patients. The incidence of cardiac events with VNR was 1.19% [95% confidence interval (CI) (0.75; 1.67)]. There was no difference in the risk of cardiac events between VNR and other drugs [odds ratio: 0.92, 95% CI (0.54; 1.55)]. The risk of VNR cardiac events was similar to vindesine (VDS) and other cardiotoxic drugs [fluorouracil, anthracyclines, gemcitabine (GEM) em leader ]. Even if it did not reach statistical significance because of a few number of cases, the risk was lower in trials excluding patients with cardiac history, and seemed to be higher in trials including patients with pre-existing cardiac diseases. Vinorelbine-related cardiac events concern about 1% of treated patients in clinical trials. However, the risk associated with VNR seems to be similar to that of other chemotherapeutic agents in the same indications.
14748761	0	11	Vinorelbine	Chemical	C030852
14748761	137	148	vinorelbine	Chemical	C030852
14748761	150	153	VNR	Chemical	C030852
14748761	311	314	VNR	Chemical	C030852
14748761	378	390	malignancies	Disease	D009369
14748761	429	432	VNR	Chemical	C030852
14748761	470	476	cancer	Disease	D009369
14748761	777	780	VNR	Chemical	C030852
14748761	845	848	VNR	Chemical	C030852
14748761	966	969	VNR	Chemical	C030852
14748761	1039	1042	VNR	Chemical	C030852
14748761	1073	1082	vindesine	Chemical	D014751
14748761	1084	1087	VDS	Chemical	D014751
14748761	1099	1110	cardiotoxic	Disease	D066126
14748761	1118	1130	fluorouracil	Chemical	D005472
14748761	1132	1146	anthracyclines	Chemical	D018943
14748761	1148	1159	gemcitabine	Chemical	C056507
14748761	1161	1164	GEM	Chemical	C056507
14748761	1404	1420	cardiac diseases	Disease	D006331
14748761	1422	1433	Vinorelbine	Chemical	C030852
14748761	1548	1551	VNR	Chemical	C030852
14748761	CID	C030852	D066126

15018178|t|MRI findings of hypoxic cortical laminar necrosis in a child with hemolytic anemia crisis.
15018178|a|We present magnetic resonance imaging findings of a 5-year-old girl who had a rapidly installing hemolytic anemia crisis induced by trimethoprim-sulfomethoxazole, resulting in cerebral anoxia leading to permanent damage. Magnetic Resonance imaging revealed cortical laminar necrosis in arterial border zones in both cerebral hemispheres, ischemic changes in subcortical white matter of left cerebral hemisphere, and in the left putamen. Although cortical laminar necrosis is a classic entity in adulthood related to conditions of energy depletions, there are few reports available in children. A wide review of the literature is also presented.
15018178	41	49	necrosis	Disease	D009336
15018178	66	82	hemolytic anemia	Disease	D000743
15018178	188	204	hemolytic anemia	Disease	D000743
15018178	223	252	trimethoprim-sulfomethoxazole	Chemical	D015662
15018178	267	282	cerebral anoxia	Disease	D002534
15018178	365	373	necrosis	Disease	D009336
15018178	554	562	necrosis	Disease	D009336
15018178	CID	D015662	D000743

15094729|t|The natural history of Vigabatrin associated visual field defects in patients electing to continue their medication.
15094729|a|PURPOSE: To determine the natural history of visual field defects in a group of patients known to have Vigabatrin-associated changes who elected to continue the medication because of good seizure control. METHODS: All patients taking Vigabatrin alone or in combination with other antiepileptic drugs for at least 5 years (range 5-12 years) were entered into a visual surveillance programme. Patients were followed up at 6-monthly intervals for not less than 18 months (range 18-43 months). In all, 16 patients with unequivocal defects continued the medication. Following already published methodology (Eye 2002; 16;567-571) monocular mean radial degrees (MRDs) to the I/4e isopter on Goldmann perimetry was calculated for the right eye at the time of discovery of a visual field defect and again after not less than 18 months follow-up. RESULTS: Mean right eye MRD at presentation was 36.98 degrees (range 22.25-51.0), compared to 38.40 degrees (range 22.5-49.75) after follow-up; P=0.338 unpaired t-test. Only one patient demonstrated a deterioration in visual field during the study period and discontinued treatment. CONCLUSION: Established visual field defects presumed to be due to Vigabatrin therapy did not usually progress in spite of continuing use of the medication. These data give support to the hypothesis that the pathogenesis of Vigabatrin-associated visual field defects may be an idiosyncratic adverse drug reaction rather than dose-dependent toxicity.
15094729	23	33	Vigabatrin	Chemical	D020888
15094729	45	65	visual field defects	Disease	D014786
15094729	162	182	visual field defects	Disease	D014786
15094729	220	230	Vigabatrin	Chemical	D020888
15094729	305	312	seizure	Disease	D012640
15094729	351	361	Vigabatrin	Chemical	D020888
15094729	883	902	visual field defect	Disease	D014786
15094729	1155	1184	deterioration in visual field	Disease	D014786
15094729	1261	1281	visual field defects	Disease	D014786
15094729	1304	1314	Vigabatrin	Chemical	D020888
15094729	1461	1471	Vigabatrin	Chemical	D020888
15094729	1483	1503	visual field defects	Disease	D014786
15094729	1577	1585	toxicity	Disease	D064420
15094729	CID	D020888	D014786

15096374|t|Induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment.
15096374|a|BACKGROUND: Tacrolimus ointment is increasingly used for anti-inflammatory treatment of sensitive areas such as the face, and recent observations indicate that the treatment is effective in steroid-aggravated rosacea and perioral dermatitis. We report on rosaceiform dermatitis as a complication of treatment with tacrolimus ointment. OBSERVATIONS: Six adult patients with inflammatory facial dermatoses were treated with tacrolimus ointment because of the ineffectiveness of standard treatments. Within 2 to 3 weeks of initially effective and well-tolerated treatment, 3 patients with a history of rosacea and 1 with a history of acne experienced sudden worsening with pustular rosaceiform lesions. Biopsy revealed an abundance of Demodex mites in 2 of these patients. In 1 patient with eyelid eczema, rosaceiform periocular dermatitis gradually appeared after 3 weeks of treatment. In 1 patient with atopic dermatitis, telangiectatic and papular rosacea insidiously appeared after 5 months of treatment. CONCLUSIONS: Our observations suggest that the spectrum of rosaceiform dermatitis as a complication of treatment with tacrolimus ointment is heterogeneous. A variety of factors, such as vasoactive properties of tacrolimus, proliferation of Demodex due to local immunosuppression, and the occlusive properties of the ointment, may be involved in the observed phenomena. Future studies are needed to identify individual risk factors.
15096374	25	35	dermatitis	Disease	D003872
15096374	56	86	facial inflammatory dermatoses	Disease	D005148
15096374	92	102	tacrolimus	Chemical	D016559
15096374	125	135	Tacrolimus	Chemical	D016559
15096374	303	310	steroid	Chemical	D013256
15096374	322	329	rosacea	Disease	D012393
15096374	334	353	perioral dermatitis	Disease	D019557
15096374	380	390	dermatitis	Disease	D003872
15096374	427	437	tacrolimus	Chemical	D016559
15096374	486	516	inflammatory facial dermatoses	Disease	D005148
15096374	535	545	tacrolimus	Chemical	D016559
15096374	712	719	rosacea	Disease	D012393
15096374	744	748	acne	Disease	D000152
15096374	908	914	eczema	Disease	D004485
15096374	928	949	periocular dermatitis	Disease	D019557
15096374	1015	1032	atopic dermatitis	Disease	D003876
15096374	1053	1068	papular rosacea	Disease	D012393
15096374	1190	1200	dermatitis	Disease	D003872
15096374	1237	1247	tacrolimus	Chemical	D016559
15096374	1330	1340	tacrolimus	Chemical	D016559
15096374	CID	D016559	D012393

15229250|t|Structural abnormalities in the brains of human subjects who use methamphetamine.
15229250|a|We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.
15229250	65	80	methamphetamine	Chemical	D008694
15229250	131	169	structural deficits in the human brain	Disease	D001930
15229250	194	209	methamphetamine	Chemical	D008694
15229250	211	213	MA	Chemical	D008694
15229250	262	264	MA	Chemical	D008694
15229250	354	377	metabolic abnormalities	Disease	D008659
15229250	548	550	MA	Chemical	D008694
15229250	605	625	cognitive impairment	Disease	D003072
15229250	718	788	abnormalities in the cortex, hippocampus, white matter, and ventricles	Disease	D001930
15229250	819	821	MA	Chemical	D008694
15229250	964	966	MA	Chemical	D008694
15229250	1030	1032	MA	Chemical	D008694
15229250	1173	1184	hypertrophy	Disease	D006984
15229250	1345	1360	methamphetamine	Chemical	D008694
15229250	1440	1467	impaired memory performance	Disease	D008569
15229250	1469	1471	MA	Chemical	D008694
15229250	1673	1684	hypertrophy	Disease	D006984
15229250	1759	1766	gliosis	Disease	D005911
15229250	1780	1795	neuronal damage	Disease	D009422
15229250	1857	1859	MA	Chemical	D008694
15229250	1914	1926	brain injury	Disease	D001930
15229250	CID	D008694	D008569
15229250	CID	D008694	D001930

15265979|t|Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is associated with peroxisome proliferator-activated receptor-alpha target gene activation.
15265979|a|Amiodarone, an efficacious and widely used antiarrhythmic agent, has been reported to cause hepatotoxicity in some patients. To gain insight into the mechanism of this unwanted effect, mice were administered various doses of amiodarone and examined for changes in hepatic histology and gene regulation. Amiodarone induced hepatomegaly, hepatocyte microvesicular lipid accumulation, and a significant decrease in serum triglycerides and glucose. Northern blot analysis of hepatic RNA revealed a dose-dependent increase in the expression of a number of genes critical for fatty acid oxidation, lipoprotein assembly, and lipid transport. Many of these genes are regulated by the peroxisome proliferator-activated receptor-alpha (PPARalpha), a ligand-activated nuclear hormone receptor transcription factor. The absence of induction of these genes as well as hepatomegaly in PPARalpha knockout [PPARalpha-/-] mice indicated that the effects of amiodarone were dependent upon the presence of a functional PPARalpha gene. Compared to wild-type mice, treatment of PPARalpha-/- mice with amiodarone resulted in an increased rate and extent of total body weight loss. The inability of amiodarone to directly activate either human or mouse PPARalpha transiently expressed in human HepG2 hepatoma cells indicates that the effects of amiodarone on the function of this receptor were indirect. Based upon these results, we conclude that amiodarone disrupts hepatic lipid homeostasis and that the increased expression of PPARalpha target genes is secondary to this toxic effect. These results provide important new mechanistic information regarding the hepatotoxic effects of amiodarone and indicate that PPARalpha protects against amiodarone-induced hepatotoxicity.
15265979	54	64	amiodarone	Chemical	D000638
15265979	167	177	Amiodarone	Chemical	D000638
15265979	259	273	hepatotoxicity	Disease	D056486
15265979	392	402	amiodarone	Chemical	D000638
15265979	470	480	Amiodarone	Chemical	D000638
15265979	489	501	hepatomegaly	Disease	D006529
15265979	585	598	triglycerides	Chemical	D014280
15265979	603	610	glucose	Chemical	D005947
15265979	737	747	fatty acid	Chemical	D005227
15265979	1022	1034	hepatomegaly	Disease	D006529
15265979	1107	1117	amiodarone	Chemical	D000638
15265979	1247	1257	amiodarone	Chemical	D000638
15265979	1313	1324	weight loss	Disease	D015431
15265979	1343	1353	amiodarone	Chemical	D000638
15265979	1444	1452	hepatoma	Disease	D006528
15265979	1489	1499	amiodarone	Chemical	D000638
15265979	1591	1601	amiodarone	Chemical	D000638
15265979	1806	1817	hepatotoxic	Disease	D056486
15265979	1829	1839	amiodarone	Chemical	D000638
15265979	1885	1895	amiodarone	Chemical	D000638
15265979	1904	1918	hepatotoxicity	Disease	D056486
15265979	CID	D000638	D006529
15265979	CID	D000638	D056486

15276093|t|Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study.
15276093|a|Niacin extended-release/lovastatin is a new combination product approved for treatment of primary hypercholesterolemia and mixed dyslipidemia. This open-labeled, multicenter study evaluated the safety of bedtime niacin extended-release/lovastatin when dosed as initial therapy and patient compliance to treatment in various clinical practice settings. A total of 4,499 patients with dyslipidemia requiring drug intervention was enrolled at 1,081 sites. Patients were treated with 1 tablet (500 mg of niacin extended-release/20 mg of lovastatin) once nightly for 4 weeks and then 2 tablets for 8 weeks. Patients also received dietary counseling, educational materials, and reminders to call a toll-free number that provided further education about dyslipidemia and niacin extended-release/lovastatin. Primary end points were study compliance, increases in liver transaminases to >3 times the upper limit of normal, and clinical myopathy. Final study status was available for 4,217 patients (94%). Compliance to niacin extended-release/lovastatin was 77%, with 3,245 patients completing the study. Patients in the southeast and those enrolled by endocrinologists had the lowest compliance and highest adverse event rates. Flushing was the most common adverse event, reported by 18% of patients and leading to discontinuation by 6%. Incidence of increased aspartate aminotransferase and/or alanine aminotransferase >3 times the upper limit of normal was <0.3%. An increase of creatine phosphokinase to >5 times the upper limit of normal occurred in 0.24% of patients, and no cases of drug-induced myopathy were observed. Niacin extended-release/lovastatin 1,000/40 mg, dosed as initial therapy, was associated with good compliance and safety and had very low incidences of increased liver and muscle enzymes.
15276093	38	72	niacin extended-release/lovastatin	Chemical	C451780
15276093	181	215	Niacin extended-release/lovastatin	Chemical	C451780
15276093	279	299	hypercholesterolemia	Disease	D006937
15276093	310	322	dyslipidemia	Disease	D050171
15276093	393	427	niacin extended-release/lovastatin	Chemical	C451780
15276093	564	576	dyslipidemia	Disease	D050171
15276093	681	687	niacin	Chemical	D009525
15276093	714	724	lovastatin	Chemical	D008148
15276093	928	940	dyslipidemia	Disease	D050171
15276093	945	979	niacin extended-release/lovastatin	Chemical	C451780
15276093	1108	1116	myopathy	Disease	D009135
15276093	1191	1225	niacin extended-release/lovastatin	Chemical	C451780
15276093	1401	1409	Flushing	Disease	D005483
15276093	1534	1543	aspartate	Chemical	D001224
15276093	1568	1575	alanine	Chemical	D000409
15276093	1654	1662	creatine	Chemical	D003401
15276093	1775	1783	myopathy	Disease	D009135
15276093	1799	1833	Niacin extended-release/lovastatin	Chemical	C451780
15276093	CID	C451780	D005483

15282950|t|Protective effect of Terminalia chebula against experimental myocardial injury induced by isoproterenol.
15282950|a|Cardioprotective effect of ethanolic extract of Terminalia chebula fruits (500 mg/kg body wt) was examined in isoproterenol (200 mg/kg body wt) induced myocardial damage in rats. In isoproterenol administered rats, the level of lipid peroxides increased significantly in the serum and heart. A significant decrease was observed in the activity of the myocardial marker enzymes with a concomitant increase in their activity in serum. Histopathological examination was carried out to confirm the myocardial necrosis. T. chebula extract pretreatment was found to ameliorate the effect of isoproterenol on lipid peroxide formation and retained the activities of the diagnostic marker enzymes.
15282950	21	39	Terminalia chebula	Chemical	D010936
15282950	61	78	myocardial injury	Disease	D009202
15282950	90	103	isoproterenol	Chemical	D007545
15282950	132	178	ethanolic extract of Terminalia chebula fruits	Chemical	D010936
15282950	215	228	isoproterenol	Chemical	D007545
15282950	257	274	myocardial damage	Disease	D009202
15282950	287	300	isoproterenol	Chemical	D007545
15282950	339	348	peroxides	Chemical	D010545
15282950	610	618	necrosis	Disease	D009336
15282950	620	638	T. chebula extract	Chemical	D010936
15282950	690	703	isoproterenol	Chemical	D007545
15282950	713	721	peroxide	Chemical	D010545
15282950	CID	D007545	D009336
15282950	CID	D007545	D009202

15321332|t|A case of postoperative anxiety due to low dose droperidol used with patient-controlled analgesia.
15321332|a|A multiparous woman in good psychological health underwent urgent caesarean section in labour. Postoperatively, she was given a patient-controlled analgesia device delivering boluses of diamorphine 0.5 mg and droperidol 0.025 mg. Whilst using the device she gradually became anxious, the feeling worsening after each bolus. The diagnosis of droperidol-induced psychological disturbance was not made straight away although on subsequent close questioning the patient gave a very clear history. After she had received a total of only 0.9 mg droperidol, a syringe containing diamorphine only was substituted and her unease resolved completely. We feel that, although the dramatic extrapyramidal side effects of dopaminergic antiemetics are well known, more subtle manifestations may easily be overlooked.
15321332	24	31	anxiety	Disease	D001008
15321332	48	58	droperidol	Chemical	D004329
15321332	285	296	diamorphine	Chemical	D003932
15321332	308	318	droperidol	Chemical	D004329
15321332	440	450	droperidol	Chemical	D004329
15321332	459	484	psychological disturbance	Disease	D001008
15321332	638	648	droperidol	Chemical	D004329
15321332	671	682	diamorphine	Chemical	D003932
15321332	CID	D004329	D001008

15366550|t|Accurate patient history contributes to differentiating diabetes insipidus: a case study.
15366550|a|This case study highlights the important contribution of nursing in obtaining an accurate health history. The case discussed herein initially appeared to be neurogenic diabetes insipidus (DI) secondary to a traumatic brain injury. The nursing staff, by reviewing the patient's health history with his family, discovered a history of polydipsia and long-standing lithium use. Lithium is implicated in drug-induced nephrogenic DI, and because the patient had not received lithium since being admitted to the hospital, his treatment changed to focus on nephrogenic DI. By combining information from the patient history, the physical examination, and radiologic and laboratory studies, the critical care team demonstrated that the patient had been self-treating his lithium-induced nephrogenic DI and developed neurogenic DI secondary to brain trauma. Thus successful treatment required that nephrogenic and neurogenic DI be treated concomitantly.
15366550	56	74	diabetes insipidus	Disease	D003919
15366550	247	276	neurogenic diabetes insipidus	Disease	D018500
15366550	278	280	DI	Disease	D003919
15366550	297	319	traumatic brain injury	Disease	D001930
15366550	423	433	polydipsia	Disease	D059606
15366550	452	459	lithium	Chemical	D008094
15366550	465	472	Lithium	Chemical	D008094
15366550	503	517	nephrogenic DI	Disease	D018500
15366550	560	567	lithium	Chemical	D008094
15366550	640	654	nephrogenic DI	Disease	D018500
15366550	852	859	lithium	Chemical	D008094
15366550	868	882	nephrogenic DI	Disease	D018500
15366550	897	910	neurogenic DI	Disease	D018500
15366550	924	936	brain trauma	Disease	D001930
15366550	994	1007	neurogenic DI	Disease	D018500
15366550	CID	D008094	D018500

15482540|t|Factors contributing to ribavirin-induced anemia.
15482540|a|BACKGROUND AND AIM: Interferon and ribavirin combination therapy for chronic hepatitis C produces hemolytic anemia. This study was conducted to identify the factors contributing to ribavirin-induced anemia. METHODS: Eighty-eight patients with chronic hepatitis C who received interferon-alpha-2b at a dose of 6 MU administered intramuscularly for 24 weeks in combination with ribavirin administered orally at a dose of 600 mg or 800 mg participated in the study. A hemoglobin concentration of <10 g/dL was defined as ribavirin-induced anemia. RESULTS: Ribavirin-induced anemia occurred in 18 (20.5%) patients during treatment. A 2 g/dL decrease in hemoglobin concentrations in patients with anemia was observed at week 2 after the start of treatment. The hemoglobin concentration in patients with > or =2 g/dL decrease at week 2 was observed to be significantly lower even after week 2 than in patients with <2 g/dL decrease (P < 0.01). A significant relationship was observed between the rate of reduction of hemoglobin concentrations at week 2 and the severity of anemia (P < 0.01). Such factors as sex (female), age (> or =60 years old), and the ribavirin dose by body weight (12 mg/kg or more) were significant by univariate analysis. CONCLUSIONS: Careful administration is necessary in patients > or =60 years old, in female patients, and in patients receiving a ribavirin dose of 12 mg/kg or more. Patients who experience a fall in hemoglobin concentrations of 2 g/dL or more at week 2 after the start of treatment should be monitored with particular care.
15482540	24	33	ribavirin	Chemical	D012254
15482540	42	48	anemia	Disease	D000740
15482540	70	80	Interferon	Chemical	D016898
15482540	85	94	ribavirin	Chemical	D012254
15482540	119	138	chronic hepatitis C	Disease	D019698
15482540	148	164	hemolytic anemia	Disease	D000743
15482540	231	240	ribavirin	Chemical	D012254
15482540	249	255	anemia	Disease	D000740
15482540	293	312	chronic hepatitis C	Disease	D019698
15482540	326	345	interferon-alpha-2b	Chemical	D016898
15482540	426	435	ribavirin	Chemical	D012254
15482540	567	576	ribavirin	Chemical	D012254
15482540	585	591	anemia	Disease	D000740
15482540	602	611	Ribavirin	Chemical	D012254
15482540	620	626	anemia	Disease	D000740
15482540	741	747	anemia	Disease	D000740
15482540	1116	1122	anemia	Disease	D000740
15482540	1199	1208	ribavirin	Chemical	D012254
15482540	1418	1427	ribavirin	Chemical	D012254
15482540	CID	D012254	D000743
15482540	CID	D016898	D000743

15605432|t|Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury.
15605432|a|The purpose of the present study was to determine if elevated reactive oxygen (ROS)/nitrogen species (RNS) reported to be present in adriamycin (ADR)-induced cardiotoxicity actually resulted in cardiomyocyte oxidative/nitrative damage, and to quantitatively determine the time course and subcellular localization of these postulated damage products using an in vivo approach. B6C3 mice were treated with a single dose of 20 mg/kg ADR. Ultrastructural damage and levels of 4-hydroxy-2-nonenal (4HNE)-protein adducts and 3-nitrotyrosine (3NT) were analyzed. Quantitative ultrastructural damage using computerized image techniques showed cardiomyocyte injury as early as 3 hours, with mitochondria being the most extensively and progressively injured subcellular organelle. Analysis of 4HNE protein adducts by immunogold electron microscopy showed appearance of 4HNE protein adducts in mitochondria as early as 3 hours, with a peak at 6 hours and subsequent decline at 24 hours. 3NT levels were significantly increased in all subcellular compartments at 6 hours and subsequently declined at 24 hours. Our data showed ADR induced 4HNE-protein adducts in mitochondria at the same time point as when mitochondrial injury initially appeared. These results document for the first time in vivo that mitochondrial oxidative damage precedes nitrative damage. The progressive nature of mitochondrial injury suggests that mitochondria, not other subcellular organelles, are the major site of intracellular injury.
15605432	46	56	adriamycin	Chemical	D004317
15605432	73	93	mitochondrial injury	Disease	D028361
15605432	166	172	oxygen	Chemical	D010100
15605432	179	187	nitrogen	Chemical	D009584
15605432	228	238	adriamycin	Chemical	D004317
15605432	240	243	ADR	Chemical	D004317
15605432	253	267	cardiotoxicity	Disease	D066126
15605432	525	528	ADR	Chemical	D004317
15605432	567	586	4-hydroxy-2-nonenal	Chemical	C027576
15605432	588	592	4HNE	Chemical	C027576
15605432	614	629	3-nitrotyrosine	Chemical	C002744
15605432	631	634	3NT	Chemical	C002744
15605432	878	882	4HNE	Chemical	C027576
15605432	954	958	4HNE	Chemical	C027576
15605432	1071	1074	3NT	Chemical	C002744
15605432	1209	1212	ADR	Chemical	D004317
15605432	1221	1225	4HNE	Chemical	C027576
15605432	1289	1309	mitochondrial injury	Disease	D028361
15605432	1385	1415	mitochondrial oxidative damage	Disease	D028361
15605432	1469	1489	mitochondrial injury	Disease	D028361
15605432	CID	D004317	D028361

15609701|t|Sotalol-induced coronary spasm in a patient with dilated cardiomyopathy associated with sustained ventricular tachycardia.
15609701|a|A 54-year-old man with severe left ventricular dysfunction due to dilated cardiomyopathy was referred to our hospital for symptomatic incessant sustained ventricular tachycardia (VT). After the administration of nifekalant hydrochloride, sustained VT was terminated. An alternate class III agent, sotalol, was also effective for the prevention of VT. However, one month after switching over nifekalant to sotalol, a short duration of ST elevation was documented in ECG monitoring at almost the same time for three consecutive days. ST elevation with chest discomfort disappeared since he began taking long-acting diltiazem. Coronary vasospasm may be induced by the non-selective beta-blocking properties of sotalol.
15609701	0	7	Sotalol	Chemical	D013015
15609701	16	30	coronary spasm	Disease	D003329
15609701	49	71	dilated cardiomyopathy	Disease	D002311
15609701	98	121	ventricular tachycardia	Disease	D017180
15609701	158	181	ventricular dysfunction	Disease	D018754
15609701	189	211	dilated cardiomyopathy	Disease	D002311
15609701	277	300	ventricular tachycardia	Disease	D017180
15609701	302	304	VT	Disease	D017180
15609701	335	359	nifekalant hydrochloride	Chemical	C076259
15609701	371	373	VT	Disease	D017180
15609701	420	427	sotalol	Chemical	D013015
15609701	470	472	VT	Disease	D017180
15609701	514	524	nifekalant	Chemical	C076259
15609701	528	535	sotalol	Chemical	D013015
15609701	736	745	diltiazem	Chemical	D004110
15609701	747	765	Coronary vasospasm	Disease	D003329
15609701	830	837	sotalol	Chemical	D013015
15609701	CID	D013015	D003329

15614572|t|Effects of the antidepressant trazodone, a 5-HT 2A/2C receptor antagonist, on dopamine-dependent behaviors in rats.
15614572|a|RATIONALE: 5-Hydroxytryptamine, via stimulation of 5-HT 2C receptors, exerts a tonic inhibitory influence on dopaminergic neurotransmission, whereas activation of 5-HT 2A receptors enhances stimulated DAergic neurotransmission. The antidepressant trazodone is a 5-HT 2A/2C receptor antagonist. OBJECTIVES: To evaluate the effect of trazodone treatment on behaviors dependent on the functional status of the nigrostriatal DAergic system. METHODS: The effect of pretreatment with trazodone on dexamphetamine- and apomorphine-induced oral stereotypies, on catalepsy induced by haloperidol and apomorphine (0.05 mg/kg, i.p.), on ergometrine-induced wet dog shake (WDS) behavior and fluoxetine-induced penile erections was studied in rats. We also investigated whether trazodone induces catalepsy in rats. RESULTS: Trazodone at 2.5-20 mg/kg i.p. did not induce catalepsy, and did not antagonize apomorphine (1.5 and 3 mg/kg) stereotypy and apomorphine (0.05 mg/kg)-induced catalepsy. However, pretreatment with 5, 10 and 20 mg/kg i.p. trazodone enhanced dexamphetamine stereotypy, and antagonized haloperidol catalepsy, ergometrine-induced WDS behavior and fluoxetine-induced penile erections. Trazodone at 30, 40 and 50 mg/kg i.p. induced catalepsy and antagonized apomorphine and dexamphetamine stereotypies. CONCLUSIONS: Our results indicate that trazodone at 2.5-20 mg/kg does not block pre- and postsynaptic striatal D2 DA receptors, while at 30, 40 and 50 mg/kg it blocks postsynaptic striatal D2 DA receptors. Furthermore, at 5, 10 and 20 mg/kg, trazodone blocks 5-HT 2A and 5-HT 2C receptors. We suggest that trazodone (5, 10 and 20 mg/kg), by blocking the 5-HT 2C receptors, releases the nigrostriatal DAergic neurons from tonic inhibition caused by 5-HT, and thereby potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.
15614572	30	39	trazodone	Chemical	D014196
15614572	43	47	5-HT	Chemical	D012701
15614572	78	86	dopamine	Chemical	D004298
15614572	127	146	5-Hydroxytryptamine	Chemical	D012701
15614572	167	171	5-HT	Chemical	D012701
15614572	279	283	5-HT	Chemical	D012701
15614572	363	372	trazodone	Chemical	D014196
15614572	378	382	5-HT	Chemical	D012701
15614572	448	457	trazodone	Chemical	D014196
15614572	594	603	trazodone	Chemical	D014196
15614572	607	621	dexamphetamine	Chemical	D003913
15614572	627	638	apomorphine	Chemical	D001058
15614572	647	664	oral stereotypies	Disease	D009062
15614572	669	678	catalepsy	Disease	D002375
15614572	690	701	haloperidol	Chemical	D006220
15614572	706	717	apomorphine	Chemical	D001058
15614572	741	752	ergometrine	Chemical	D004874
15614572	794	804	fluoxetine	Chemical	D005473
15614572	880	889	trazodone	Chemical	D014196
15614572	898	907	catalepsy	Disease	D002375
15614572	926	935	Trazodone	Chemical	D014196
15614572	972	981	catalepsy	Disease	D002375
15614572	1006	1017	apomorphine	Chemical	D001058
15614572	1051	1062	apomorphine	Chemical	D001058
15614572	1084	1093	catalepsy	Disease	D002375
15614572	1146	1155	trazodone	Chemical	D014196
15614572	1165	1179	dexamphetamine	Chemical	D003913
15614572	1208	1219	haloperidol	Chemical	D006220
15614572	1220	1229	catalepsy	Disease	D002375
15614572	1231	1242	ergometrine	Chemical	D004874
15614572	1268	1278	fluoxetine	Chemical	D005473
15614572	1305	1314	Trazodone	Chemical	D014196
15614572	1351	1360	catalepsy	Disease	D002375
15614572	1377	1388	apomorphine	Chemical	D001058
15614572	1393	1407	dexamphetamine	Chemical	D003913
15614572	1461	1470	trazodone	Chemical	D014196
15614572	1664	1673	trazodone	Chemical	D014196
15614572	1681	1685	5-HT	Chemical	D012701
15614572	1693	1697	5-HT	Chemical	D012701
15614572	1728	1737	trazodone	Chemical	D014196
15614572	1776	1780	5-HT	Chemical	D012701
15614572	1870	1874	5-HT	Chemical	D012701
15614572	1900	1914	dexamphetamine	Chemical	D003913
15614572	1942	1953	haloperidol	Chemical	D006220
15614572	1954	1963	catalepsy	Disease	D002375
15614572	CID	D001058	D002375
15614572	CID	D006220	D002375

15625689|t|Swallowing abnormalities and dyskinesia in Parkinson's disease.
15625689|a|Gastrointestinal abnormalities in Parkinson's disease (PD) have been known for almost two centuries, but many aspects concerning their pathophysiology have not been completely clarified. The aim of this study was to characterize the oropharyngeal dynamics in PD patients with and without levodopa-induced dyskinesia. Fifteen dyskinetic, 12 nondyskinetic patients, and a control group were included. Patients were asked about dysphagia and evaluated with the Unified Parkinson's Disease Rating Scale Parts II and III and the Hoehn and Yahr scale. Deglutition was assessed using modified barium swallow with videofluoroscopy. Nondyskinetic patients, but not the dyskinetic ones, showed less oropharyngeal swallowing efficiency (OPSE) for liquid food than controls (Dunnett, P = 0.02). Dyskinetic patients tended to have a greater OPSE than nondyskinetic (Dunnett, P = 0.06). Patients who were using a higher dose of levodopa had a greater OPSE and a trend toward a smaller oral transit time (Pearson's correlation, P = 0.01 and 0.08, respectively). Neither the report of dysphagia nor any of the PD severity parameters correlated to the videofluoroscopic variables. In the current study, dyskinetic patients performed better in swallowing function, which could be explained on the basis of a greater levodopa dose. Our results suggest a role for levodopa in the oral phase of deglutition and confirm that dysphagia is not a good predictor of deglutition alterations in PD.
15625689	0	24	Swallowing abnormalities	Disease	D020447
15625689	29	39	dyskinesia	Disease	D004409
15625689	43	62	Parkinson's disease	Disease	D010300
15625689	64	94	Gastrointestinal abnormalities	Disease	D005767
15625689	98	117	Parkinson's disease	Disease	D010300
15625689	119	121	PD	Disease	D010300
15625689	323	325	PD	Disease	D010300
15625689	352	360	levodopa	Chemical	D007980
15625689	369	379	dyskinesia	Disease	D004409
15625689	389	399	dyskinetic	Disease	D004409
15625689	489	498	dysphagia	Disease	D003680
15625689	530	549	Parkinson's Disease	Disease	D010300
15625689	650	656	barium	Chemical	D001464
15625689	724	734	dyskinetic	Disease	D004409
15625689	847	857	Dyskinetic	Disease	D004409
15625689	978	986	levodopa	Chemical	D007980
15625689	1133	1142	dysphagia	Disease	D003680
15625689	1158	1160	PD	Disease	D010300
15625689	1250	1260	dyskinetic	Disease	D004409
15625689	1362	1370	levodopa	Chemical	D007980
15625689	1408	1416	levodopa	Chemical	D007980
15625689	1467	1476	dysphagia	Disease	D003680
15625689	1531	1533	PD	Disease	D010300
15625689	CID	D007980	D004409

15627798|t|Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.
15627798|a|BACKGROUND: Animals treated with gentamicin can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases and macrophages in the renal cortex and structural and functional renal changes of rats treated with gentamicin or gentamicin + pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. METHODS: 38 female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, 38 with gentamicin + PDTC, and 28 with 0.15 M NaCl solution. The animals were killed 5 and 30 days after these injections and the kidneys were removed for histological and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining. The fractional interstitial area was determined by morphometry. RESULTS: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. Increased ED-1, MAP kinases and NF-kappaB staining were also observed in the renal cortex from all gentamicin-treated rats compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis in the renal cortex despite the recovery of renal function. Treatment with PDTC reduced the functional and structural changes induced by gentamicin. CONCLUSIONS: These data show that inhibition of NF-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.
15627798	58	86	tubulointerstitial nephritis	Disease	D009395
15627798	98	108	gentamicin	Chemical	D005839
15627798	143	153	gentamicin	Chemical	D005839
15627798	194	202	fibrosis	Disease	D005355
15627798	442	452	gentamicin	Chemical	D005839
15627798	456	466	gentamicin	Chemical	D005839
15627798	469	496	pyrrolidine dithiocarbamate	Chemical	C020972
15627798	498	502	PDTC	Chemical	C020972
15627798	579	589	gentamicin	Chemical	D005839
15627798	633	643	gentamicin	Chemical	D005839
15627798	646	650	PDTC	Chemical	C020972
15627798	671	675	NaCl	Chemical	D012965
15627798	995	1005	Gentamicin	Chemical	D005839
15627798	1061	1071	creatinine	Chemical	D003404
15627798	1179	1189	gentamicin	Chemical	D005839
15627798	1279	1287	fibrosis	Disease	D005355
15627798	1363	1367	PDTC	Chemical	C020972
15627798	1425	1435	gentamicin	Chemical	D005839
15627798	1517	1545	tubulointerstitial nephritis	Disease	D009395
15627798	1557	1567	gentamicin	Chemical	D005839
15627798	CID	D005839	D009395

15630069|t|Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis.
15630069|a|BACKGROUND: While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes. OBJECTIVE: To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test. DESIGN: A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis. SETTING: Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis. MAIN OUTCOME MEASURES: Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness. RESULTS: The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapine<olanzapine<risperidone), with subjects who received clozapine and olanzapine exhibiting significant insulin resistance compared with subjects who were treated with risperidone (clozapine vs risperidone, t(33) = -4.29; P<.001; olanzapine vs risperidone, t(33) = -3.62; P = .001 [P<.001]). The homeostasis model assessment of insulin resistance also differed significantly among groups (F(33) = 4.92; P = .01) (clozapine>olanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine<olanzapine<risperidone) with significant differences between clozapine and risperidone (t(30) = -2.59; P = .02) and olanzapine and risperidone (t(30) = -2.34, P = .03). CONCLUSIONS: Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects. Patients taking clozapine and olanzapine must be examined for insulin resistance and its consequences.
15630069	0	7	Glucose	Chemical	D005947
15630069	36	49	schizophrenia	Disease	D012559
15630069	127	134	glucose	Chemical	D005947
15630069	223	240	diabetes mellitus	Disease	D003920
15630069	276	289	schizophrenia	Disease	D012559
15630069	408	415	glucose	Chemical	D005947
15630069	471	479	diabetes	Disease	D003920
15630069	538	547	clozapine	Chemical	D003024
15630069	552	562	olanzapine	Chemical	C076029
15630069	568	579	risperidone	Chemical	D018967
15630069	619	626	glucose	Chemical	D005947
15630069	709	722	schizophrenia	Disease	D012559
15630069	772	779	glucose	Chemical	D005947
15630069	1069	1076	glucose	Chemical	D005947
15630069	1127	1140	schizophrenia	Disease	D012559
15630069	1144	1168	schizoaffective disorder	Disease	D011618
15630069	1221	1230	clozapine	Chemical	D003024
15630069	1232	1242	olanzapine	Chemical	C076029
15630069	1247	1258	risperidone	Chemical	D018967
15630069	1329	1336	glucose	Chemical	D005947
15630069	1371	1390	insulin sensitivity	Disease	D007333
15630069	1430	1448	insulin resistance	Disease	D007333
15630069	1454	1461	glucose	Chemical	D005947
15630069	1599	1608	clozapine	Chemical	D003024
15630069	1633	1643	olanzapine	Chemical	C076029
15630069	1665	1676	risperidone	Chemical	D018967
15630069	1764	1773	clozapine	Chemical	D003024
15630069	1774	1784	olanzapine	Chemical	C076029
15630069	1785	1796	risperidone	Chemical	D018967
15630069	1835	1844	clozapine	Chemical	D003024
15630069	1849	1860	risperidone	Chemical	D018967
15630069	1889	1899	olanzapine	Chemical	C076029
15630069	1904	1915	risperidone	Chemical	D018967
15630069	1979	1998	insulin sensitivity	Disease	D007333
15630069	2043	2052	clozapine	Chemical	D003024
15630069	2053	2063	olanzapine	Chemical	C076029
15630069	2064	2075	risperidone	Chemical	D018967
15630069	2105	2114	clozapine	Chemical	D003024
15630069	2119	2129	olanzapine	Chemical	C076029
15630069	2153	2171	insulin resistance	Disease	D007333
15630069	2217	2228	risperidone	Chemical	D018967
15630069	2230	2239	clozapine	Chemical	D003024
15630069	2243	2254	risperidone	Chemical	D018967
15630069	2279	2289	olanzapine	Chemical	C076029
15630069	2293	2304	risperidone	Chemical	D018967
15630069	2377	2395	insulin resistance	Disease	D007333
15630069	2462	2471	clozapine	Chemical	D003024
15630069	2472	2482	olanzapine	Chemical	C076029
15630069	2483	2494	risperidone	Chemical	D018967
15630069	2497	2506	clozapine	Chemical	D003024
15630069	2510	2521	risperidone	Chemical	D018967
15630069	2547	2557	olanzapine	Chemical	C076029
15630069	2561	2572	risperidone	Chemical	D018967
15630069	2649	2656	glucose	Chemical	D005947
15630069	2696	2705	clozapine	Chemical	D003024
15630069	2706	2716	olanzapine	Chemical	C076029
15630069	2717	2728	risperidone	Chemical	D018967
15630069	2767	2776	clozapine	Chemical	D003024
15630069	2781	2792	risperidone	Chemical	D018967
15630069	2822	2832	olanzapine	Chemical	C076029
15630069	2837	2848	risperidone	Chemical	D018967
15630069	2902	2911	clozapine	Chemical	D003024
15630069	2917	2927	olanzapine	Chemical	C076029
15630069	2965	2983	insulin resistance	Disease	D007333
15630069	3002	3009	glucose	Chemical	D005947
15630069	3038	3049	risperidone	Chemical	D018967
15630069	3084	3093	clozapine	Chemical	D003024
15630069	3098	3108	olanzapine	Chemical	C076029
15630069	3130	3148	insulin resistance	Disease	D007333
15630069	CID	C076029	D007333
15630069	CID	D003024	D007333

15815446|t|Focal cerebral ischemia in rats: effect of phenylephrine-induced hypertension during reperfusion.
15815446|a|After 180 min of temporary middle cerebral artery occlusion in spontaneously hypertensive rats, the effect of phenylephrine-induced hypertension on ischemic brain injury and blood-brain barrier permeability was determined. Blood pressure was manipulated by one of the following schedules during 120 min of reperfusion: Control, normotensive reperfusion; 90/hypertension (90/HTN), blood pressure was increased by 35 mm Hg during the initial 90 min of reperfusion only; 15/hypertension (15/HTN), normotensive reperfusion for 30 min followed by 15 min of hypertension and 75 min of normotension. Part A, for eight rats in each group brain injury was evaluated by staining tissue using 2,3,5-triphenyltetrazolium chloride and edema was evaluated by microgravimetry. Part B, for eight different rats in each group blood-brain barrier permeability was evaluated by measuring the amount and extent of extravasation of Evans Blue dye. Brain injury (percentage of the ischemic hemisphere) was less in the 15/HTN group (16 +/- 6, mean +/- SD) versus the 90/HTN group (30 +/- 6), which was in turn less than the control group (42 +/- 5). Specific gravity was greater in the 15/HTN group (1.043 +/- 0.002) versus the 90/HTN (1.036 +/- 0.003) and control (1.037 +/- 0.003) groups. Evans Blue (mug g-1 of brain tissue) was greater in the 90/HTN group (24.4 +/- 6.0) versus the control group (12.3 +/- 4.1), which was in turn greater than the 15/HTN group (7.3 +/- 3.2). This study supports a hypothesis that during reperfusion, a short interval of hypertension decreases brain injury and edema; and that sustained hypertension increases the risk of vasogenic edema.
15815446	6	23	cerebral ischemia	Disease	D002545
15815446	43	56	phenylephrine	Chemical	D010656
15815446	65	77	hypertension	Disease	D006973
15815446	125	157	middle cerebral artery occlusion	Disease	D020244
15815446	175	187	hypertensive	Disease	D006973
15815446	208	221	phenylephrine	Chemical	D010656
15815446	230	242	hypertension	Disease	D006973
15815446	246	267	ischemic brain injury	Disease	D001930
15815446	455	467	hypertension	Disease	D006973
15815446	472	475	HTN	Disease	D006973
15815446	569	581	hypertension	Disease	D006973
15815446	586	589	HTN	Disease	D006973
15815446	650	662	hypertension	Disease	D006973
15815446	728	740	brain injury	Disease	D001930
15815446	780	815	2,3,5-triphenyltetrazolium chloride	Chemical	C009591
15815446	820	825	edema	Disease	D004487
15815446	1025	1037	Brain injury	Disease	D001930
15815446	1057	1076	ischemic hemisphere	Disease	D002545
15815446	1097	1100	HTN	Disease	D006973
15815446	1145	1148	HTN	Disease	D006973
15815446	1264	1267	HTN	Disease	D006973
15815446	1306	1309	HTN	Disease	D006973
15815446	1366	1376	Evans Blue	Chemical	D005070
15815446	1425	1428	HTN	Disease	D006973
15815446	1529	1532	HTN	Disease	D006973
15815446	1632	1644	hypertension	Disease	D006973
15815446	1655	1667	brain injury	Disease	D001930
15815446	1672	1677	edema	Disease	D004487
15815446	1698	1710	hypertension	Disease	D006973
15815446	1733	1748	vasogenic edema	Disease	D001929
15815446	CID	D010656	D006973

15817013|t|People aged over 75 in atrial fibrillation on warfarin: the rate of major hemorrhage and stroke in more than 500 patient-years of follow-up.
15817013|a|OBJECTIVES: To determine the incidence of major hemorrhage and stroke in people aged 76 and older with atrial fibrillation on adjusted-dose warfarin who had been recently been admitted to hospital. DESIGN: A retrospective observational cohort study. SETTING: A major healthcare network involving four tertiary hospitals. PARTICIPANTS: Two hundred thirty-five patients aged 76 and older admitted to a major healthcare network between July 1, 2001, and June 30, 2002, with atrial fibrillation on warfarin were enrolled. MEASUREMENTS: Information regarding major bleeding episodes, strokes, and warfarin use was obtained from patients, relatives, primary physicians, and medical records. RESULTS: Two hundred twenty-eight patients (42% men) with a mean age of 81.1 (range 76-94) were included in the analysis. Total follow-up on warfarin was 530 years (mean 28 months). There were 53 major hemorrhages, for an annual rate of 10.0%, including 24 (45.3%) life-threatening and five (9.4%) fatal bleeds. The annual stroke rate after initiation of warfarin was 2.6%. CONCLUSION: The rate of major hemorrhage was high in this old, frail group, but excluding fatalities, resulted in no long-term sequelae, and the stroke rate on warfarin was low, demonstrating how effective warfarin treatment is.
15817013	23	42	atrial fibrillation	Disease	D001281
15817013	46	54	warfarin	Chemical	D014859
15817013	74	84	hemorrhage	Disease	D006470
15817013	89	95	stroke	Disease	D020521
15817013	189	199	hemorrhage	Disease	D006470
15817013	204	210	stroke	Disease	D020521
15817013	244	263	atrial fibrillation	Disease	D001281
15817013	281	289	warfarin	Chemical	D014859
15817013	612	631	atrial fibrillation	Disease	D001281
15817013	635	643	warfarin	Chemical	D014859
15817013	701	709	bleeding	Disease	D006470
15817013	720	727	strokes	Disease	D020521
15817013	733	741	warfarin	Chemical	D014859
15817013	967	975	warfarin	Chemical	D014859
15817013	1028	1039	hemorrhages	Disease	D006470
15817013	1149	1155	stroke	Disease	D020521
15817013	1181	1189	warfarin	Chemical	D014859
15817013	1230	1240	hemorrhage	Disease	D006470
15817013	1345	1351	stroke	Disease	D020521
15817013	1360	1368	warfarin	Chemical	D014859
15817013	1406	1414	warfarin	Chemical	D014859
15817013	CID	D014859	D006470

15859361|t|Safety of celecoxib in patients with adverse skin reactions to acetaminophen (paracetamol) and nimesulide associated or not with common non-steroidal anti-inflammatory drugs.
15859361|a|BACKGROUND: Acetaminophen (paracetamol--P) and Nimesulide (N) are widely used analgesic-antipyretic/anti-inflammatory drugs. The rate of adverse hypersensitivity reactions to these agents is generally low. On the contrary non-steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in such reactions. Celecoxib (CE) is a novel drug, with high selectivity and affinity for COX-2 enzyme. OBJECTIVE: We evaluated the tolerability of CE in a group of patients with documented history of adverse cutaneous reactions to P and N associated or not to classic NSAIDs. METHODS: We studied 9 patients with hypersensitivity to P and N with or without associated reactions to classic NSAIDs. The diagnosis of P and N-induced skin reactions was based in vivo challenge. The placebo was blindly administered at the beginning of each challenge. After three days, a cumulative dosage of 200 mg of CE in refracted doses were given. After 2-3 days, a single dose of 200 mg was administered. All patients were observed for 6 hours after each challenge, and controlled again after 24 hours to exclude delayed reactions. The challenge was considered positive if one or more of the following appeared: erythema, rush or urticaria-angioedema. RESULTS: No reaction was observed with placebo and eight patients (88.8%) tolerated CE. Only one patient developed a moderate angioedema of the lips. CONCLUSION: Only one hypersensitivity reaction to CE was documented among 9 P and N-highly NSAIDs intolerant patients. Thus, we conclude that CE is a reasonably safe alternative to be used in subjects who do not tolerate P and N.
15859361	10	19	celecoxib	Chemical	C105934
15859361	45	59	skin reactions	Disease	D003875
15859361	63	76	acetaminophen	Chemical	D000082
15859361	78	89	paracetamol	Chemical	D000082
15859361	95	105	nimesulide	Chemical	C012655
15859361	187	200	Acetaminophen	Chemical	D000082
15859361	202	213	paracetamol	Chemical	D000082
15859361	215	216	P	Chemical	D000082
15859361	222	232	Nimesulide	Chemical	C012655
15859361	234	235	N	Chemical	C012655
15859361	320	336	hypersensitivity	Disease	D004342
15859361	485	494	Celecoxib	Chemical	C105934
15859361	496	498	CE	Chemical	C105934
15859361	614	616	CE	Chemical	C105934
15859361	675	694	cutaneous reactions	Disease	D003875
15859361	698	699	P	Chemical	D000082
15859361	704	705	N	Chemical	C012655
15859361	779	795	hypersensitivity	Disease	D004342
15859361	799	800	P	Chemical	D000082
15859361	805	806	N	Chemical	C012655
15859361	880	881	P	Chemical	D000082
15859361	886	887	N	Chemical	C012655
15859361	896	910	skin reactions	Disease	D003875
15859361	1064	1066	CE	Chemical	C105934
15859361	1363	1371	erythema	Disease	D004890
15859361	1381	1390	urticaria	Disease	D014581
15859361	1391	1401	angioedema	Disease	D000799
15859361	1487	1489	CE	Chemical	C105934
15859361	1529	1539	angioedema	Disease	D000799
15859361	1574	1590	hypersensitivity	Disease	D004342
15859361	1603	1605	CE	Chemical	C105934
15859361	1629	1630	P	Chemical	D000082
15859361	1635	1636	N	Chemical	C012655
15859361	1695	1697	CE	Chemical	C105934
15859361	1774	1775	P	Chemical	D000082
15859361	1780	1781	N	Chemical	C012655
15859361	CID	C105934	D000799
15859361	CID	D000082	D003875
15859361	CID	C012655	D003875

15882284|t|Case-control study of regular analgesic and nonsteroidal anti-inflammatory use and end-stage renal disease.
15882284|a|BACKGROUND: Studies on the association between the long-term use of aspirin and other analgesic and nonsteroidal anti-inflammatory drugs (NSAIDs) and end-stage renal disease (ESRD) have given conflicting results. In order to examine this association, a case-control study with incident cases of ESRD was carried out. METHODS: The cases were all patients entering the local dialysis program because of ESRD in the study area between June 1, 1995 and November 30, 1997. They were classified according to the underlying disease, which had presumably led them to ESRD. Controls were patients admitted to the same hospitals from where the cases arose, also matched by age and sex. Odds ratios were calculated using a conditional logistic model, including potential confounding factors, both for the whole study population and for the various underlying diseases. RESULTS: Five hundred and eighty-three cases and 1190 controls were included in the analysis. Long-term use of any analgesic was associated with an overall odds ratio of 1.22 (95% CI, 0.89-1.66). For specific groups of drugs, the risks were 1.56 (1.05-2.30) for aspirin, 1.03 (0.60-1.76) for pyrazolones, 0.80 (0.39-1.63) for paracetamol, and 0.94 (0.57-1.56) for nonaspirin NSAIDs. The risk of ESRD associated with aspirin was related to the cumulated dose and duration of use, and it was particularly high among the subset of patients with vascular nephropathy as underlying disease [2.35 (1.17-4.72)]. CONCLUSION: Our data indicate that long-term use of nonaspirin analgesic drugs and NSAIDs is not associated with an increased risk of ESRD. However, the chronic use of aspirin may increase the risk of ESRD.
15882284	83	106	end-stage renal disease	Disease	D007676
15882284	176	183	aspirin	Chemical	D001241
15882284	258	281	end-stage renal disease	Disease	D007676
15882284	283	287	ESRD	Disease	D007676
15882284	403	407	ESRD	Disease	D007676
15882284	509	513	ESRD	Disease	D007676
15882284	667	671	ESRD	Disease	D007676
15882284	1228	1235	aspirin	Chemical	D001241
15882284	1258	1269	pyrazolones	Chemical	D047069
15882284	1292	1303	paracetamol	Chemical	D000082
15882284	1361	1365	ESRD	Disease	D007676
15882284	1382	1389	aspirin	Chemical	D001241
15882284	1517	1528	nephropathy	Disease	D007674
15882284	1705	1709	ESRD	Disease	D007676
15882284	1739	1746	aspirin	Chemical	D001241
15882284	1772	1776	ESRD	Disease	D007676
15882284	CID	D001241	D007676

15953230|t|Two cases of amisulpride overdose: a cause for prolonged QT syndrome.
15953230|a|Two cases of deliberate self-poisoning with 5 g and 3.6 g of amisulpride, respectively, are reported. In both cases, QT prolongation and hypocalcaemia were noted. The QT prolongation appeared to respond to administration of i.v. calcium gluconate.
15953230	13	24	amisulpride	Chemical	C012052
15953230	25	33	overdose	Disease	D062787
15953230	47	68	prolonged QT syndrome	Disease	D008133
15953230	99	108	poisoning	Disease	D011041
15953230	131	142	amisulpride	Chemical	C012052
15953230	187	202	QT prolongation	Disease	D008133
15953230	207	220	hypocalcaemia	Disease	D006996
15953230	237	252	QT prolongation	Disease	D008133
15953230	299	316	calcium gluconate	Chemical	D002125
15953230	CID	C012052	D008133
15953230	CID	C012052	D006996

15987266|t|Growth-associated protein 43 expression in hippocampal molecular layer of chronic epileptic rats treated with cycloheximide.
15987266|a|PURPOSE: GAP43 has been thought to be linked with mossy fiber sprouting (MFS) in various experimental models of epilepsy. To investigate how GAP43 expression (GAP43-ir) correlates with MFS, we assessed the intensity (densitometry) and extension (width) of GAP43-ir in the inner molecular layer of the dentate gyrus (IML) of rats subject to status epilepticus induced by pilocarpine (Pilo), previously injected or not with cycloheximide (CHX), which has been shown to inhibit MFS. METHODS: CHX was injected before the Pilo injection in adult Wistar rats. The Pilo group was injected with the same drugs, except for CHX. Animals were killed between 30 and 60 days later, and brain sections were processed for GAP43 immunohistochemistry. RESULTS: Densitometry showed no significant difference regarding GAP43-ir in the IML between Pilo, CHX+Pilo, and control groups. However, the results of the width of the GAP43-ir band in the IML showed that CHX+Pilo and control animals had a significantly larger band (p = 0.03) as compared with that in the Pilo group. CONCLUSIONS: Our current finding that animals in the CHX+Pilo group have a GAP43-ir band in the IML, similar to that of controls, reinforces prior data on the blockade of MFS in these animals. The change in GAP43-ir present in Pilo-treated animals was a thinning of the band to a very narrow layer just above the granule cell layer that is likely to be associated with the loss of hilar cell projections that express GAP-43.
15987266	82	91	epileptic	Disease	D004827
15987266	110	123	cycloheximide	Chemical	D003513
15987266	237	245	epilepsy	Disease	D004827
15987266	465	483	status epilepticus	Disease	D013226
15987266	495	506	pilocarpine	Chemical	D010862
15987266	508	512	Pilo	Chemical	D010862
15987266	547	560	cycloheximide	Chemical	D003513
15987266	562	565	CHX	Chemical	D003513
15987266	614	617	CHX	Chemical	D003513
15987266	642	646	Pilo	Chemical	D010862
15987266	683	687	Pilo	Chemical	D010862
15987266	739	742	CHX	Chemical	D003513
15987266	953	957	Pilo	Chemical	D010862
15987266	959	962	CHX	Chemical	D003513
15987266	963	967	Pilo	Chemical	D010862
15987266	1067	1070	CHX	Chemical	D003513
15987266	1071	1075	Pilo	Chemical	D010862
15987266	1168	1172	Pilo	Chemical	D010862
15987266	1233	1236	CHX	Chemical	D003513
15987266	1237	1241	Pilo	Chemical	D010862
15987266	1407	1411	Pilo	Chemical	D010862
15987266	CID	D010862	D013226

15991002|t|Nicotine antagonizes caffeine- but not pentylenetetrazole-induced anxiogenic effect in mice.
15991002|a|RATIONALE: Nicotine and caffeine are widely consumed licit psychoactive drugs worldwide. Epidemiological studies showed that they were generally used concurrently. Although some studies in experimental animals indicate clear pharmacological interactions between them, no studies have shown a specific interaction on anxiety responses. OBJECTIVES: The present study investigates the effects of nicotine on anxiety induced by caffeine and another anxiogenic drug, pentylenetetrazole, in mice. The elevated plus-maze (EPM) test was used to evaluate the effects of drugs on anxiety. METHODS: Adult male Swiss Webster mice (25-32 g) were given nicotine (0.05-0.25 mg/kg s.c.) or saline 10 min before caffeine (70 mg/kg i.p.) or pentylenetetrazole (15 and 30 mg/kg i.p.) injections. After 15 min, mice were evaluated for their open- and closed-arm time and entries on the EPM for a 10-min session. Locomotor activity was recorded for individual groups by using the same treatment protocol with the EPM test. RESULTS: Nicotine (0.05-0.25 mg/kg) itself did not produce any significant effect in the EPM test, whereas caffeine (70 mg/kg) and pentylenetetrazole (30 mg/kg) produced an anxiogenic effect, apparent with decreases in open-arm time and entry. Nicotine (0.25 mg/kg) pretreatment blocked the caffeine- but not pentylenetetrazole-induced anxiety. Administration of each drug and their combinations did not produce any effect on locomotor activity. CONCLUSIONS: Our results suggest that the antagonistic effect of nicotine on caffeine-induced anxiety is specific to caffeine, instead of a non-specific anxiolytic effect. Thus, it may extend the current findings on the interaction between nicotine and caffeine.
15991002	0	8	Nicotine	Chemical	D009538
15991002	21	29	caffeine	Chemical	D002110
15991002	39	57	pentylenetetrazole	Chemical	D010433
15991002	104	112	Nicotine	Chemical	D009538
15991002	117	125	caffeine	Chemical	D002110
15991002	409	416	anxiety	Disease	D001008
15991002	486	494	nicotine	Chemical	D009538
15991002	498	505	anxiety	Disease	D001008
15991002	517	525	caffeine	Chemical	D002110
15991002	555	573	pentylenetetrazole	Chemical	D010433
15991002	663	670	anxiety	Disease	D001008
15991002	732	740	nicotine	Chemical	D009538
15991002	788	796	caffeine	Chemical	D002110
15991002	816	834	pentylenetetrazole	Chemical	D010433
15991002	1104	1112	Nicotine	Chemical	D009538
15991002	1202	1210	caffeine	Chemical	D002110
15991002	1226	1244	pentylenetetrazole	Chemical	D010433
15991002	1339	1347	Nicotine	Chemical	D009538
15991002	1386	1394	caffeine	Chemical	D002110
15991002	1404	1422	pentylenetetrazole	Chemical	D010433
15991002	1431	1438	anxiety	Disease	D001008
15991002	1606	1614	nicotine	Chemical	D009538
15991002	1618	1626	caffeine	Chemical	D002110
15991002	1635	1642	anxiety	Disease	D001008
15991002	1658	1666	caffeine	Chemical	D002110
15991002	1781	1789	nicotine	Chemical	D009538
15991002	1794	1802	caffeine	Chemical	D002110
15991002	CID	D010433	D001008
15991002	CID	D002110	D001008

16034922|t|Long term hormone therapy for perimenopausal and postmenopausal women.
16034922|a|BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women but the evidence supporting its use for these indications is largely observational. OBJECTIVES: To assess the effect of long-term HT on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, gallbladder disease, cognitive function, dementia, fractures and quality of life. SEARCH STRATEGY: We searched the following databases up to November 2004: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biological Abstracts. Relevant non-indexed journals and conference abstracts were also searched. SELECTION CRITERIA: Randomised double-blind trials of HT (oestrogens with or without progestogens) versus placebo, taken for at least one year by perimenopausal or postmenopausal women. DATA COLLECTION AND ANALYSIS: Fifteen RCTs were included. Trials were assessed for quality and two review authors extracted data independently. They calculated risk ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Clinical heterogeneity precluded meta-analysis for most outcomes. MAIN RESULTS: All the statistically significant results were derived from the two biggest trials. In relatively healthy women, combined continuous HT significantly increased the risk of venous thromboembolism or coronary event (after one year's use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long-term oestrogen-only HT also significantly increased the risk of stroke and gallbladder disease. Overall, the only statistically significant benefits of HT were a decreased incidence of fractures and colon cancer with long-term use. Among relatively healthy women over 65 years taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thromboembolism. No trials focussed specifically on younger women. However, one trial analysed subgroups of 2839 relatively healthy 50 to 59 year-old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT; their absolute risk remained very low. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.
16034922	135	154	menopausal symptoms	Disease	D008594
16034922	215	237	cardiovascular disease	Disease	D002318
16034922	239	251	osteoporosis	Disease	D010024
16034922	256	264	dementia	Disease	D003704
16034922	427	440	heart disease	Disease	D006331
16034922	442	464	venous thromboembolism	Disease	D054556
16034922	466	472	stroke	Disease	D020521
16034922	474	501	transient ischaemic attacks	Disease	D002546
16034922	503	516	breast cancer	Disease	D001943
16034922	518	535	colorectal cancer	Disease	D015179
16034922	537	551	ovarian cancer	Disease	D010051
16034922	553	571	endometrial cancer	Disease	D016889
16034922	573	592	gallbladder disease	Disease	D005705
16034922	614	622	dementia	Disease	D003704
16034922	624	633	fractures	Disease	D050723
16034922	1032	1042	oestrogens	Chemical	D004967
16034922	1059	1071	progestogens	Chemical	D011374
16034922	1664	1686	venous thromboembolism	Disease	D054556
16034922	1729	1735	stroke	Disease	D020521
16034922	1753	1766	breast cancer	Disease	D001943
16034922	1787	1806	gallbladder disease	Disease	D005705
16034922	1818	1827	oestrogen	Chemical	D004967
16034922	1877	1883	stroke	Disease	D020521
16034922	1888	1907	gallbladder disease	Disease	D005705
16034922	1998	2007	fractures	Disease	D050723
16034922	2012	2024	colon cancer	Disease	D003110
16034922	2188	2196	dementia	Disease	D003704
16034922	2215	2237	cardiovascular disease	Disease	D002318
16034922	2315	2337	venous thromboembolism	Disease	D054556
16034922	2524	2533	oestrogen	Chemical	D004967
16034922	2635	2657	venous thromboembolism	Disease	D054556
16034922	2809	2824	chronic disease	Disease	D002908
16034922	CID	D011374	D005705
16034922	CID	D004967	D003704
16034922	CID	D004967	D054556
16034922	CID	D004967	D002318
16034922	CID	D004967	D005705
16034922	CID	D011374	D054556
16034922	CID	D004967	D020521
16034922	CID	D011374	D002318
16034922	CID	D011374	D001943
16034922	CID	D011374	D020521
16034922	CID	D011374	D003704
16034922	CID	D004967	D001943

16083708|t|Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period.
16083708|a|BACKGROUND & AIMS: Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. METHODS: A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. RESULTS: Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001). CONCLUSIONS: Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.
16083708	0	25	Drug-induced liver injury	Disease	D056486
16083708	192	217	drug-induced liver injury	Disease	D056486
16083708	219	223	DILI	Disease	D056486
16083708	417	421	DILI	Disease	D056486
16083708	474	486	liver damage	Disease	D056486
16083708	534	545	cholestatic	Disease	D002779
16083708	812	816	DILI	Disease	D056486
16083708	889	912	amoxicillin-clavulanate	Chemical	D019980
16083708	1221	1229	jaundice	Disease	D007565
16083708	1368	1393	fulminant hepatic failure	Disease	D017114
16083708	1536	1545	bilirubin	Chemical	D001663
16083708	1650	1658	jaundice	Disease	D007565
16083708	1721	1744	Amoxicillin-clavulanate	Chemical	D019980
16083708	1791	1795	DILI	Disease	D056486
16083708	CID	D019980	D056486
16083708	CID	D019980	D007565

16092435|t|Morphological evaluation of the effect of d-ribose on adriamycin-evoked cardiotoxicity in rats.
16092435|a|The influence of d-ribose on adriamycin-induced myocardiopathy in rats was studied. Adriamycin in the cumulative dose of 25 mg/kg evoked fully developed cardiac toxicity. D-ribose in the multiple doses of 200 mg/kg did not influence ADR cardiotoxicity.
16092435	42	50	d-ribose	Chemical	D012266
16092435	54	64	adriamycin	Chemical	D004317
16092435	72	86	cardiotoxicity	Disease	D066126
16092435	113	121	d-ribose	Chemical	D012266
16092435	125	135	adriamycin	Chemical	D004317
16092435	144	158	myocardiopathy	Disease	D009202
16092435	180	190	Adriamycin	Chemical	D004317
16092435	249	265	cardiac toxicity	Disease	D066126
16092435	267	275	D-ribose	Chemical	D012266
16092435	329	332	ADR	Chemical	D004317
16092435	333	347	cardiotoxicity	Disease	D066126
16092435	CID	D004317	D009202

16112787|t|In vivo evidences suggesting the role of oxidative stress in pathogenesis of vancomycin-induced nephrotoxicity: protection by erdosteine.
16112787|a|The aims of this study were to examine vancomycin (VCM)-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of erdosteine, an expectorant agent, which has also antioxidant properties, on kidney tissue against the possible VCM-induced renal impairment in rats. Rats were divided into three groups: sham, VCM and VCM plus erdosteine. VCM was administrated intraperitoneally (i.p.) with 200mgkg(-1) twice daily for 7 days. Erdosteine was administered orally. VCM administration to control rats significantly increased renal malondialdehyde (MDA) and urinary N-acetyl-beta-d-glucosaminidase (NAG, a marker of renal tubular injury) excretion but decreased superoxide dismutase (SOD) and catalase (CAT) activities. Erdosteine administration with VCM injections caused significantly decreased renal MDA and urinary NAG excretion, and increased SOD activity, but not CAT activity in renal tissue when compared with VCM alone. Erdosteine showed histopathological protection against VCM-induced nephrotoxicity. There were a significant dilatation of tubular lumens, extensive epithelial cell vacuolization, atrophy, desquamation, and necrosis in VCM-treated rats more than those of the control and the erdosteine groups. Erdosteine caused a marked reduction in the extent of tubular damage. It is concluded that oxidative tubular damage plays an important role in the VCM-induced nephrotoxicity and the modulation of oxidative stress with erdosteine reduces the VCM-induced kidney damage both at the biochemical and histological levels.
16112787	77	87	vancomycin	Chemical	D014640
16112787	96	110	nephrotoxicity	Disease	D007674
16112787	126	136	erdosteine	Chemical	C048498
16112787	177	187	vancomycin	Chemical	D014640
16112787	189	192	VCM	Chemical	D014640
16112787	256	262	oxygen	Chemical	D010100
16112787	308	318	erdosteine	Chemical	C048498
16112787	419	422	VCM	Chemical	D014640
16112787	431	447	renal impairment	Disease	D007674
16112787	500	503	VCM	Chemical	D014640
16112787	508	511	VCM	Chemical	D014640
16112787	517	527	erdosteine	Chemical	C048498
16112787	529	532	VCM	Chemical	D014640
16112787	617	627	Erdosteine	Chemical	C048498
16112787	653	656	VCM	Chemical	D014640
16112787	718	733	malondialdehyde	Chemical	D008315
16112787	735	738	MDA	Chemical	D008315
16112787	802	822	renal tubular injury	Disease	D007674
16112787	848	858	superoxide	Chemical	D013481
16112787	906	916	Erdosteine	Chemical	C048498
16112787	937	940	VCM	Chemical	D014640
16112787	989	992	MDA	Chemical	D008315
16112787	1104	1107	VCM	Chemical	D014640
16112787	1115	1125	Erdosteine	Chemical	C048498
16112787	1170	1173	VCM	Chemical	D014640
16112787	1182	1196	nephrotoxicity	Disease	D007674
16112787	1294	1301	atrophy	Disease	D001284
16112787	1303	1315	desquamation	Disease	-1
16112787	1321	1329	necrosis	Disease	D009336
16112787	1333	1336	VCM	Chemical	D014640
16112787	1389	1399	erdosteine	Chemical	C048498
16112787	1408	1418	Erdosteine	Chemical	C048498
16112787	1555	1558	VCM	Chemical	D014640
16112787	1567	1581	nephrotoxicity	Disease	D007674
16112787	1626	1636	erdosteine	Chemical	C048498
16112787	1649	1652	VCM	Chemical	D014640
16112787	1661	1674	kidney damage	Disease	D007674
16112787	CID	D014640	D007674

16309808|t|Does domperidone potentiate mirtazapine-associated restless legs syndrome?
16309808|a|There is now evidence to suggest a central role for the dopaminergic system in restless legs syndrome (RLS). For example, the symptoms of RLS can be dramatically improved by levodopa and dopamine agonists, whereas central dopamine D2 receptor antagonists can induce or aggravate RLS symptoms. To our knowledge, there is no previous report regarding whether domperidone, a peripheral dopamine D2 receptor antagonist, can also induce or aggravate symptoms of RLS. Mirtazapine, the first noradrenergic and specific serotonergic antidepressant (NaSSA), has been associated with RLS in several recent publications. The authors report here a depressed patient comorbid with postprandial dyspepsia who developed RLS after mirtazapine had been added to his domperidone therapy. Our patient started to have symptoms of RLS only after he had been treated with mirtazapine, and his RLS symptoms resolved completely upon discontinuation of his mirtazapine. Such a temporal relationship between the use of mirtazapine and the symptoms of RLS in our patient did not support a potentiating effect of domperione on mirtazapine-associated RLS. However, physicians should be aware of the possibility that mirtazapine can be associated with RLS in some individuals, especially those receiving concomitant dopamine D2 receptor antagonists.
16309808	5	16	domperidone	Chemical	D004294
16309808	28	39	mirtazapine	Chemical	C035133
16309808	51	73	restless legs syndrome	Disease	D012148
16309808	154	176	restless legs syndrome	Disease	D012148
16309808	178	181	RLS	Disease	D012148
16309808	213	216	RLS	Disease	D012148
16309808	249	257	levodopa	Chemical	D007980
16309808	262	270	dopamine	Chemical	D004298
16309808	297	305	dopamine	Chemical	D004298
16309808	354	357	RLS	Disease	D012148
16309808	432	443	domperidone	Chemical	D004294
16309808	458	466	dopamine	Chemical	D004298
16309808	532	535	RLS	Disease	D012148
16309808	537	548	Mirtazapine	Chemical	C035133
16309808	649	652	RLS	Disease	D012148
16309808	743	765	postprandial dyspepsia	Disease	D004415
16309808	780	783	RLS	Disease	D012148
16309808	790	801	mirtazapine	Chemical	C035133
16309808	824	835	domperidone	Chemical	D004294
16309808	885	888	RLS	Disease	D012148
16309808	925	936	mirtazapine	Chemical	C035133
16309808	946	949	RLS	Disease	D012148
16309808	1007	1018	mirtazapine	Chemical	C035133
16309808	1068	1079	mirtazapine	Chemical	C035133
16309808	1100	1103	RLS	Disease	D012148
16309808	1160	1170	domperione	Chemical	D004294
16309808	1174	1185	mirtazapine	Chemical	C035133
16309808	1197	1200	RLS	Disease	D012148
16309808	1262	1273	mirtazapine	Chemical	C035133
16309808	1297	1300	RLS	Disease	D012148
16309808	1361	1369	dopamine	Chemical	D004298
16309808	CID	C035133	D012148

16323982|t|Antiandrogenic therapy can cause coronary arterial disease.
16323982|a|AIM: To study the change of lipid metabolism by antiandrogen therapy in patients with prostate cancer. MATERIALS AND METHODS: We studied with a 2.5 years follow-up the changes in plasma cholesterols (C), triglycerides (TG), lipoproteins (LP), and apolipoproteins (Apo) B-100, A-I, and A-II pro fi les in 24 patients of mean age 60 years with low risk prostate cancer (stage: T1cN0M0, Gleason score: 2-5) during treatment with cyproterone acetate (CPA) without surgical management or radiation therapy. RESULTS: Significant decreases of HDL-C, Apo A-I and Apo A-II and an increase of triglyceride levels in VLDL were induced by CPA. After a period of 2.5 years on CPA treatment, four patients out of twenty-four were found to be affected by coronary heart disease. CONCLUSIONS: Ischaemic coronary arteriosclerosis with an incidence rate of 16.6% as caused by prolonged CPA therapy is mediated through changes in HDL cholesterol, Apo A-I and Apo A-II pro fi les, other than the well-known hyperglyceridemic effect caused by estrogen.
16323982	33	58	coronary arterial disease	Disease	D003324
16323982	146	161	prostate cancer	Disease	D011471
16323982	246	258	cholesterols	Chemical	D002784
16323982	260	261	C	Chemical	D002784
16323982	264	277	triglycerides	Chemical	D014280
16323982	279	281	TG	Chemical	D014280
16323982	411	426	prostate cancer	Disease	D011471
16323982	486	505	cyproterone acetate	Chemical	D017373
16323982	507	510	CPA	Chemical	D017373
16323982	643	655	triglyceride	Chemical	D014280
16323982	687	690	CPA	Chemical	D017373
16323982	723	726	CPA	Chemical	D017373
16323982	800	822	coronary heart disease	Disease	D003327
16323982	847	872	coronary arteriosclerosis	Disease	D003324
16323982	928	931	CPA	Chemical	D017373
16323982	975	986	cholesterol	Chemical	D002784
16323982	1047	1071	hyperglyceridemic effect	Disease	D050171
16323982	1082	1090	estrogen	Chemical	D004967
16323982	CID	D017373	D050171
16323982	CID	D017373	D003324

16369751|t|5-Fluorouracil cardiotoxicity induced by alpha-fluoro-beta-alanine.
16369751|a|Cardiotoxicity is a rare complication occurring during 5-fluorouracil (5-FU) treatment for malignancies. We herein report the case of a 70-year-old man with 5-FU-induced cardiotoxicity, in whom a high serum level of alpha-fluoro-beta-alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5-FU (1000 mg/day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng/ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5-FU. As the precordial pain in this patient was considered to have been due to 5-FU-induced cardiotoxicity, the administration of 5-FU was abandoned. Instead, oral administration of S-1 (a derivative of 5-FU), at 200 mg/day twice a week, was instituted, because S-1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5-FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng/ml, the same as the value measured on the first day of S-1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S-1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5-FU-induced cardiotoxicity. S-1 may be administered safely to patients with 5-FU-induced cardiotoxicity.
16369751	0	14	5-Fluorouracil	Chemical	D005472
16369751	15	29	cardiotoxicity	Disease	D066126
16369751	41	66	alpha-fluoro-beta-alanine	Chemical	C032348
16369751	68	82	Cardiotoxicity	Disease	D066126
16369751	123	137	5-fluorouracil	Chemical	D005472
16369751	139	143	5-FU	Chemical	D005472
16369751	159	171	malignancies	Disease	D009369
16369751	225	229	5-FU	Chemical	D005472
16369751	238	252	cardiotoxicity	Disease	D066126
16369751	284	309	alpha-fluoro-beta-alanine	Chemical	C032348
16369751	311	315	FBAL	Chemical	C032348
16369751	365	377	colon cancer	Disease	D003110
16369751	579	583	5-FU	Chemical	D005472
16369751	612	627	precordial pain	Disease	D002637
16369751	633	658	right bundle branch block	Disease	D002037
16369751	700	704	FBAL	Chemical	C032348
16369751	743	758	precordial pain	Disease	D002637
16369751	851	855	5-FU	Chemical	D005472
16369751	864	879	precordial pain	Disease	D002637
16369751	931	935	5-FU	Chemical	D005472
16369751	944	958	cardiotoxicity	Disease	D066126
16369751	982	986	5-FU	Chemical	D005472
16369751	1055	1059	5-FU	Chemical	D005472
16369751	1152	1169	dihydropyrimidine	Chemical	C020047
16369751	1220	1224	5-FU	Chemical	D005472
16369751	1230	1234	FBAL	Chemical	C032348
16369751	1246	1250	FBAL	Chemical	C032348
16369751	1388	1404	cardiac symptoms	Disease	D009461
16369751	1597	1601	FBAL	Chemical	C032348
16369751	1616	1620	5-FU	Chemical	D005472
16369751	1629	1643	cardiotoxicity	Disease	D066126
16369751	1693	1697	5-FU	Chemical	D005472
16369751	1706	1720	cardiotoxicity	Disease	D066126
16369751	CID	D005472	D002637
16369751	CID	D005472	D002037

16565833|t|The influence of the time interval between monoHER and doxorubicin administration on the protection against doxorubicin-induced cardiotoxicity in mice.
16565833|a|PURPOSE: Despite its well-known cardiotoxicity, the anthracyclin doxorubicin (DOX) continues to be an effective and widely used chemotherapeutic agent. DOX-induced cardiac damage presumably results from the formation of free radicals by DOX. Reactive oxygen species particularly affect the cardiac myocytes because these cells seem to have a relatively poor antioxidant defense system. The semisynthetic flavonoid monohydroxyethylrutoside (monoHER) showed cardioprotection against DOX-induced cardiotoxicity through its radical scavenging and iron chelating properties. Because of the relatively short final half-life of monoHER (about 30 min), it is expected that the time interval between monoHER and DOX might be of influence on the cardioprotective effect of monoHER. Therefore, the aim of the present study was to investigate this possible effect. METHODS: Six groups of 6 BALB/c mice were treated with saline, DOX alone or DOX (4 mg/kg i.v.) preceded by monoHER (500 mg/kg i.p.) with an interval of 10, 30, 60 or 120 min. After a 6-week treatment period and additional observation for 2 weeks, the mice were sacrificed. Their cardiac tissues were processed for light microscopy, after which cardiomyocyte damage was evaluated according to Billingham (in Cancer Treat Rep 62(6):865-872, 1978). Microscopic evaluation revealed that treatment with DOX alone induced significant cardiac damage in comparison to the saline control group (P<0.001). RESULTS: The number of damaged cardiomyocytes was 9.6-fold (95% CI 4.4-21.0) higher in mice treated with DOX alone than that in animals of the control group. The ratio of aberrant cardiomyocytes in mice treated with DOX preceded by monoHER and those in mice treated with saline ranged from 1.6 to 2.8 (mean 2.2, 95% CI 1.2-4.1, P=0.019). The mean protective effect by adding monoHER before DOX led to a significant 4.4-fold reduction (P<0.001, 95% CI 2.3-8.2) of abnormal cardiomyocytes. This protective effect did not depend on the time interval between monoHER and DOX administration (P=0.345). CONCLUSION: The results indicate that in an outpatient clinical setting monoHER may be administered shortly before DOX.
16565833	43	50	monoHER	Chemical	C522803
16565833	55	66	doxorubicin	Chemical	D004317
16565833	108	119	doxorubicin	Chemical	D004317
16565833	128	142	cardiotoxicity	Disease	D066126
16565833	184	198	cardiotoxicity	Disease	D066126
16565833	217	228	doxorubicin	Chemical	D004317
16565833	230	233	DOX	Chemical	D004317
16565833	304	307	DOX	Chemical	D004317
16565833	316	330	cardiac damage	Disease	D006331
16565833	389	392	DOX	Chemical	D004317
16565833	403	409	oxygen	Chemical	D010100
16565833	556	565	flavonoid	Chemical	D005419
16565833	566	590	monohydroxyethylrutoside	Chemical	C522803
16565833	592	599	monoHER	Chemical	C522803
16565833	633	636	DOX	Chemical	D004317
16565833	645	659	cardiotoxicity	Disease	D066126
16565833	695	699	iron	Chemical	D007501
16565833	773	780	monoHER	Chemical	C522803
16565833	843	850	monoHER	Chemical	C522803
16565833	855	858	DOX	Chemical	D004317
16565833	915	922	monoHER	Chemical	C522803
16565833	1068	1071	DOX	Chemical	D004317
16565833	1081	1084	DOX	Chemical	D004317
16565833	1112	1119	monoHER	Chemical	C522803
16565833	1349	1369	cardiomyocyte damage	Disease	D009202
16565833	1412	1418	Cancer	Disease	D009369
16565833	1503	1506	DOX	Chemical	D004317
16565833	1533	1547	cardiac damage	Disease	D006331
16565833	1706	1709	DOX	Chemical	D004317
16565833	1817	1820	DOX	Chemical	D004317
16565833	1833	1840	monoHER	Chemical	C522803
16565833	1976	1983	monoHER	Chemical	C522803
16565833	1991	1994	DOX	Chemical	D004317
16565833	2156	2163	monoHER	Chemical	C522803
16565833	2168	2171	DOX	Chemical	D004317
16565833	2270	2277	monoHER	Chemical	C522803
16565833	2313	2316	DOX	Chemical	D004317
16565833	CID	D004317	D009202

16723784|t|Clinical evaluation of adverse effects during bepridil administration for atrial fibrillation and flutter.
16723784|a|BACKGROUND: Bepridil hydrochloride (Bpd) has attracted attention as an effective drug for atrial fibrillation (AF) and atrial flutter (AFL). However, serious adverse effects, including torsade de pointes (Tdp), have been reported. METHODS AND RESULTS: Adverse effects of Bpd requiring discontinuation of treatment were evaluated. Bpd was administered to 459 patients (361 males, 63+/-12 years old) comprising 378 AF and 81 AFL cases. Mean left ventricular ejection fraction and atrial dimension (LAD) were 66+/-11% and 40+/-6 mm, respectively. Adverse effects were observed in 19 patients (4%) during an average follow-up of 20 months. There was marked QT prolongation greater than 0.55 s in 13 patients, bradycardia less than 40 beats/min in 6 patients, dizziness and general fatigue in 1 patient each. In 4 of 13 patients with QT prolongation, Tdp occurred. The major triggering factors of Tdp were hypokalemia and sudden decrease in heart rate. There were no differences in the clinical backgrounds of the patients with and without Tdp other than LAD and age, which were larger and older in the patients with Tdp. CONCLUSION: Careful observation of serum potassium concentration and the ECG should always be done during Bpd administration, particularly in elderly patients.
16723784	46	54	bepridil	Chemical	D015764
16723784	74	105	atrial fibrillation and flutter	Disease	D001281|D001282	atrial fibrillation|atrial flutter
16723784	119	141	Bepridil hydrochloride	Chemical	D015764
16723784	143	146	Bpd	Chemical	D015764
16723784	197	216	atrial fibrillation	Disease	D001281
16723784	218	220	AF	Disease	D001281
16723784	226	240	atrial flutter	Disease	D001282
16723784	242	245	AFL	Disease	D001282
16723784	292	310	torsade de pointes	Disease	D016171
16723784	312	315	Tdp	Disease	D016171
16723784	378	381	Bpd	Chemical	D015764
16723784	437	440	Bpd	Chemical	D015764
16723784	520	522	AF	Disease	D001281
16723784	530	533	AFL	Disease	D001282
16723784	760	775	QT prolongation	Disease	D008133
16723784	812	823	bradycardia	Disease	D001919
16723784	862	871	dizziness	Disease	D004244
16723784	884	891	fatigue	Disease	D005221
16723784	936	951	QT prolongation	Disease	D008133
16723784	953	956	Tdp	Disease	D016171
16723784	999	1002	Tdp	Disease	D016171
16723784	1008	1019	hypokalemia	Disease	D007008
16723784	1142	1145	Tdp	Disease	D016171
16723784	1219	1222	Tdp	Disease	D016171
16723784	1265	1274	potassium	Chemical	D011188
16723784	1330	1333	Bpd	Chemical	D015764
16723784	CID	D015764	D008133
16723784	CID	D015764	D016171
16723784	CID	D015764	D001919
16723784	CID	D015764	D004244
16723784	CID	D015764	D005221
16723784	CID	D011188	D016171

16731636|t|Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen.
16731636|a|We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the beta-adrenoceptor (beta-AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+dP/dt(max)) in the TGR than in the Sprague-Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt/100 g body wt, 0.28 +/- 0.004 vs. 0.24 +/- 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of beta-AR and upregulation of LV beta-AR kinase-1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the beta-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (-9.9 +/- 1.7% vs. -18.1 +/- 1.5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to beta-AR agonist-induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart.
16731636	9	22	isoproterenol	Chemical	D007545
16731636	31	50	cardiac hypertrophy	Disease	D006332
16731636	174	185	angiotensin	Chemical	D000804
16731636	406	419	isoproterenol	Chemical	D007545
16731636	421	424	Iso	Chemical	D007545
16731636	511	514	Iso	Chemical	D007545
16731636	677	691	LV hypertrophy	Disease	D006332
16731636	703	706	Iso	Chemical	D007545
16731636	854	868	LV hypertrophy	Disease	D006332
16731636	1097	1107	metoprolol	Chemical	D008790
16731636	1270	1278	atropine	Chemical	D001285
16731636	1392	1409	cardiac inotropic	Disease	D006331
16731636	1423	1434	hypertrophy	Disease	D006984
16731636	CID	D007545	D006332

16801510|t|Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors.
16801510|a|BACKGROUND: Drug-induced long QT syndrome is a serious adverse drug reaction. Methadone prolongs the QT interval in vitro in a dose-dependent manner. In the inpatient setting, the frequency of QT interval prolongation with methadone treatment, its dose dependence, and the importance of cofactors such as drug-drug interactions remain unknown. METHODS: We performed a systematic, retrospective study comparing active or former intravenous drug users receiving methadone and those not receiving methadone among all patients hospitalized over a 5-year period in a tertiary care hospital. A total of 167 patients receiving methadone fulfilled the inclusion criteria and were compared with a control group of 80 injection drug users not receiving methadone. In addition to methadone dose, 15 demographic, biological, and pharmacological variables were considered as potential risk factors for QT prolongation. RESULTS: Among 167 methadone maintenance patients, the prevalence of QTc prolongation to 0.50 second((1/2)) or longer was 16.2% compared with 0% in 80 control subjects. Six patients (3.6%) in the methadone group presented torsades de pointes. QTc length was weakly but significantly associated with methadone daily dose (Spearman rank correlation coefficient, 0.20; P<.01). Multivariate regression analysis allowed attribution of 31.8% of QTc variability to methadone dose, cytochrome P-450 3A4 drug-drug interactions, hypokalemia, and altered liver function. CONCLUSIONS: QT interval prolongation in methadone maintenance patients hospitalized in a tertiary care center is a frequent finding. Methadone dose, presence of cytochrome P-450 3A4 inhibitors, potassium level, and liver function contribute to QT prolongation. Long QT syndrome can occur with low doses of methadone.
16801510	13	29	long QT syndrome	Disease	D008133
16801510	64	73	methadone	Chemical	D008691
16801510	158	174	long QT syndrome	Disease	D008133
16801510	211	220	Methadone	Chemical	D008691
16801510	326	350	QT interval prolongation	Disease	D008133
16801510	356	365	methadone	Chemical	D008691
16801510	593	602	methadone	Chemical	D008691
16801510	627	636	methadone	Chemical	D008691
16801510	753	762	methadone	Chemical	D008691
16801510	876	885	methadone	Chemical	D008691
16801510	902	911	methadone	Chemical	D008691
16801510	1022	1037	QT prolongation	Disease	D008133
16801510	1058	1067	methadone	Chemical	D008691
16801510	1235	1244	methadone	Chemical	D008691
16801510	1261	1280	torsades de pointes	Disease	D016171
16801510	1338	1347	methadone	Chemical	D008691
16801510	1497	1506	methadone	Chemical	D008691
16801510	1558	1569	hypokalemia	Disease	D007008
16801510	1612	1636	QT interval prolongation	Disease	D008133
16801510	1640	1649	methadone	Chemical	D008691
16801510	1733	1742	Methadone	Chemical	D008691
16801510	1794	1803	potassium	Chemical	D011188
16801510	1844	1859	QT prolongation	Disease	D008133
16801510	1861	1877	Long QT syndrome	Disease	D008133
16801510	1906	1915	methadone	Chemical	D008691
16801510	CID	D008691	D008133

16810074|t|Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on venous function.
16810074|a|Loss of endothelial cell-derived nitric oxide (NO) in hypertension is a hallmark of arterial dysfunction. Experimental hypertension created by the removal of NO, however, involves mechanisms in addition to decreased arterial vasodilator activity. These include augmented endothelin-1 (ET-1) release, increased sympathetic nervous system activity, and elevated tissue oxidative stress. We hypothesized that increased venous smooth muscle (venomotor) tone plays a role in Nomega-nitro-L-arginine (LNNA) hypertension through these mechanisms. Rats were treated with the NO synthase inhibitor LNNA (0.5 g/L in drinking water) for 2 weeks. Mean arterial pressure of conscious rats was 119 +/- 2 mm Hg in control and 194 +/- 5 mm Hg in LNNA rats (P<0.05). Carotid arteries and vena cava were removed for measurement of isometric contraction. Maximal contraction to norepinephrine was modestly reduced in arteries from LNNA compared with control rats whereas the maximum contraction to ET-1 was significantly reduced (54% control). Maximum contraction of vena cava to norepinephrine (37% control) also was reduced but no change in response to ET-1 was observed. Mean circulatory filling pressure, an in vivo measure of venomotor tone, was not elevated in LNNA hypertension at 1 or 2 weeks after LNNA. The superoxide scavenger tempol (30, 100, and 300 micromol kg(-1), IV) did not change arterial pressure in control rats but caused a dose-dependent decrease in LNNA rats (-18 +/- 8, -26 +/- 15, and -54 +/- 11 mm Hg). Similarly, ganglionic blockade with hexamethonium caused a significantly greater fall in LNNA hypertensive rats (76 +/- 9 mm Hg) compared with control rats (35 +/- 10 mm Hg). Carotid arteries, vena cava, and sympathetic ganglia from LNNA rats had higher basal levels of superoxide compared with those from control rats. These data suggest that while NO deficiency increases oxidative stress and sympathetic activity in both arterial and venous vessels, the impact on veins does not make a major contribution to this form of hypertension.
16810074	14	26	hypertension	Disease	D006973
16810074	38	50	nitric oxide	Chemical	D009569
16810074	52	54	NO	Chemical	D009569
16810074	127	139	nitric oxide	Chemical	D009569
16810074	141	143	NO	Chemical	D009569
16810074	148	160	hypertension	Disease	D006973
16810074	178	198	arterial dysfunction	Disease	D018754
16810074	213	225	hypertension	Disease	D006973
16810074	252	254	NO	Chemical	D009569
16810074	564	587	Nomega-nitro-L-arginine	Chemical	D019335
16810074	589	593	LNNA	Chemical	D019335
16810074	595	607	hypertension	Disease	D006973
16810074	661	663	NO	Chemical	D009569
16810074	683	687	LNNA	Chemical	D019335
16810074	824	828	LNNA	Chemical	D019335
16810074	953	967	norepinephrine	Chemical	D009638
16810074	1006	1010	LNNA	Chemical	D019335
16810074	1155	1169	norepinephrine	Chemical	D009638
16810074	1342	1346	LNNA	Chemical	D019335
16810074	1347	1359	hypertension	Disease	D006973
16810074	1382	1386	LNNA	Chemical	D019335
16810074	1392	1402	superoxide	Chemical	D013481
16810074	1413	1419	tempol	Chemical	C001803
16810074	1548	1552	LNNA	Chemical	D019335
16810074	1641	1654	hexamethonium	Chemical	D018738
16810074	1694	1698	LNNA	Chemical	D019335
16810074	1699	1711	hypertensive	Disease	D006973
16810074	1838	1842	LNNA	Chemical	D019335
16810074	1875	1885	superoxide	Chemical	D013481
16810074	1955	1957	NO	Chemical	D009569
16810074	2129	2141	hypertension	Disease	D006973
16810074	CID	D009569	D006973

16867246|t|Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients.
16867246|a|AIM: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients. METHODS: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). RESULTS: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. CONCLUSION: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.
16867246	38	52	chlorpromazine	Chemical	D002746
16867246	61	84	extrapyramidal syndrome	Disease	D001480
16867246	96	109	schizophrenic	Disease	D012559
16867246	125	148	Extrapyramidal syndrome	Disease	D001480
16867246	150	153	EPS	Disease	D001480
16867246	414	427	schizophrenia	Disease	D012559
16867246	576	590	chlorpromazine	Chemical	D002746
16867246	599	602	EPS	Disease	D001480
16867246	606	619	schizophrenic	Disease	D012559
16867246	785	798	schizophrenic	Disease	D012559
16867246	819	822	EPS	Disease	D001480
16867246	838	841	EPS	Disease	D001480
16867246	893	907	chlorpromazine	Chemical	D002746
16867246	1531	1545	chlorpromazine	Chemical	D002746
16867246	1581	1594	schizophrenia	Disease	D012559
16867246	1672	1675	EPS	Disease	D001480
16867246	CID	D002746	D001480

16876986|t|Physical training decreases susceptibility to subsequent pilocarpine-induced seizures in the rat.
16876986|a|Regular motor activity has many benefits for mental and physical condition but its implications for epilepsy are still controversial. In order to elucidate this problem, we have studied the effect of long-term physical activity on susceptibility to subsequent seizures. Male Wistar rats were subjected to repeated training sessions in a treadmill and swimming pool. Thereafter, seizures were induced by pilocarpine injections in trained and non-trained control groups. During the acute period of status epilepticus, we measured: (1) the latency of the first motor sign, (2) the intensity of seizures, (3) the time when it occurred within the 6-h observation period, and (4) the time when the acute period ended. All these behavioral parameters showed statistically significant changes suggesting that regular physical exercises decrease susceptibility to subsequently induced seizures and ameliorate the course of experimentally induced status epilepticus.
16876986	57	68	pilocarpine	Chemical	D010862
16876986	77	85	seizures	Disease	D012640
16876986	198	206	epilepsy	Disease	D004827
16876986	358	366	seizures	Disease	D012640
16876986	476	484	seizures	Disease	D012640
16876986	501	512	pilocarpine	Chemical	D010862
16876986	594	612	status epilepticus	Disease	D013226
16876986	689	697	seizures	Disease	D012640
16876986	974	982	seizures	Disease	D012640
16876986	1035	1053	status epilepticus	Disease	D013226
16876986	CID	D010862	D012640
16876986	CID	D010862	D013226

16880771|t|Tonic dopaminergic stimulation impairs associative learning in healthy subjects.
16880771|a|Endogenous dopamine plays a central role in salience coding during associative learning. Administration of the dopamine precursor levodopa enhances learning in healthy subjects and stroke patients. Because levodopa increases both phasic and tonic dopaminergic neurotransmission, the critical mechanism mediating the enhancement of learning is unresolved. We here probed how selective tonic dopaminergic stimulation affects associative learning. Forty healthy subjects were trained in a novel vocabulary of 45 concrete nouns over the course of 5 consecutive training days in a prospective, randomized, double-blind, placebo-controlled design. Subjects received the tonically stimulating dopamine-receptor agonist pergolide (0.1 mg) vs placebo 120 min before training on each training day. The dopamine agonist significantly impaired novel word learning compared to placebo. This learning decrement persisted up to the last follow-up 4 weeks post-training. Subjects treated with pergolide also showed restricted emotional responses compared to the PLACEBO group. The extent of 'flattened' affect with pergolide was related to the degree of learning inhibition. These findings suggest that tonic occupation of dopamine receptors impairs learning by competition with phasic dopamine signals. Thus, phasic signaling seems to be the critical mechanism by which dopamine enhances associative learning in healthy subjects and stroke patients.
16880771	31	59	impairs associative learning	Disease	D007859
16880771	92	100	dopamine	Chemical	D004298
16880771	192	200	dopamine	Chemical	D004298
16880771	211	219	levodopa	Chemical	D007980
16880771	262	268	stroke	Disease	D020521
16880771	287	295	levodopa	Chemical	D007980
16880771	767	775	dopamine	Chemical	D004298
16880771	793	802	pergolide	Chemical	D010479
16880771	873	881	dopamine	Chemical	D004298
16880771	904	932	impaired novel word learning	Disease	D007859
16880771	1058	1067	pergolide	Chemical	D010479
16880771	1180	1189	pergolide	Chemical	D010479
16880771	1288	1296	dopamine	Chemical	D004298
16880771	1351	1359	dopamine	Chemical	D004298
16880771	1436	1444	dopamine	Chemical	D004298
16880771	1499	1505	stroke	Disease	D020521
16880771	CID	D010479	D007859

16906379|t|Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa.
16906379|a|A 47-year-old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C-reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline-induced vasculitis satisfying the criteria. Differential diagnosis for drug-induced disease is invaluable even for patients with classical polyarteritis nodosa.
16906379	0	11	Minocycline	Chemical	D008911
16906379	20	30	vasculitis	Disease	D014657
16906379	58	78	polyarteritis nodosa	Disease	D010488
16906379	118	129	minocycline	Chemical	D008911
16906379	134	157	palmoplantar pustulosis	Disease	D011565
16906379	168	173	fever	Disease	D005334
16906379	175	183	myalgias	Disease	D063806
16906379	185	199	polyneuropathy	Disease	D011115
16906379	205	220	testicular pain	Disease	D013733
16906379	456	476	polyarteritis nodosa	Disease	D010488
16906379	487	498	minocycline	Chemical	D008911
16906379	608	619	minocycline	Chemical	D008911
16906379	628	638	vasculitis	Disease	D014657
16906379	759	779	polyarteritis nodosa	Disease	D010488
16906379	CID	D008911	D010488

16911931|t|Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation.
16911931|a|BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in prophylaxis of the recurrence of hepatitis B after liver transplantation has significantly improved the survival of HBsAg positive patients. This study was undertaken to evaluate the outcomes of liver transplantation for patients with hepatitis B virus (HBV). METHODS: A retrospective chart analysis and a review of the organ transplant database identified 51 patients (43 men and 8 women) transplanted for benign HBV-related cirrhotic diseases between June 2002 and December 2004 who had survived more than 3 months. HBIg was administered intravenously during the first week and intramuscularly thereafter. RESULTS: At a median follow-up of 14.1 months, the overall recurrence rate in the 51 patients was 3.9% (2/51). The overall patient survival was 88.3%, and 82.4% after 1 and 2 years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before transplantation for 10 patients enabled 57.1% (4/7) and 62.5% (5/8) of HBV-DNA and HBeAg positive patients respectively to convert to be negative. Intramuscular HBIg was well tolerated in all patients. CONCLUSION: Lamivudine combined with intramuscular HBIg can effectively prevent allograft from the recurrence of HBV after liver transplantation.
16911931	14	25	hepatitis B	Disease	D006509
16911931	56	66	lamivudine	Chemical	D019259
16911931	84	95	hepatitis B	Disease	D006509
16911931	157	168	hepatitis B	Disease	D006509
16911931	196	206	lamivudine	Chemical	D019259
16911931	243	254	hepatitis B	Disease	D006509
16911931	326	331	HBsAg	Chemical	D006514
16911931	445	456	hepatitis B	Disease	D006509
16911931	636	654	cirrhotic diseases	Disease	D008103
16911931	1042	1052	lamivudine	Chemical	D019259
16911931	1155	1160	HBeAg	Chemical	D006513
16911931	1286	1296	Lamivudine	Chemical	D019259
16911931	CID	D006513	D006509

16920333|t|Anticonvulsant effect of eslicarbazepine acetate (BIA 2-093) on seizures induced by microperfusion of picrotoxin in the hippocampus of freely moving rats.
16920333|a|Eslicarbazepine acetate (BIA 2-093, S-(-)-10-acetoxy-10,11-dihydro-5H-dibenzo/b,f/azepine-5-carboxamide) is a novel antiepileptic drug, now in Phase III clinical trials, designed with the aim of improving efficacy and safety in comparison with the structurally related drugs carbamazepine (CBZ) and oxcarbazepine (OXC). We have studied the effects of oral treatment with eslicarbazepine acetate on a whole-animal model in which partial seizures can be elicited repeatedly on different days without changes in threshold or seizure patterns. In the animals treated with threshold doses of picrotoxin, the average number of seizures was 2.3+/-1.2, and average seizure duration was 39.5+/-8.4s. Pre-treatment with a dose of 30 mg/kg 2h before picrotoxin microperfusion prevented seizures in the 75% of the rats. Lower doses (3 and 10mg/kg) did not suppress seizures, however, after administration of 10mg/kg, significant reductions in seizures duration (24.3+/-6.8s) and seizure number (1.6+/-0.34) were found. No adverse effects of eslicarbazepine acetate were observed in the behavioral/EEG patterns studied, including sleep/wakefulness cycle, at the doses studied.
16920333	25	48	eslicarbazepine acetate	Chemical	C416835
16920333	50	59	BIA 2-093	Chemical	C416835
16920333	64	72	seizures	Disease	D012640
16920333	102	112	picrotoxin	Chemical	D010852
16920333	155	178	Eslicarbazepine acetate	Chemical	C416835
16920333	180	189	BIA 2-093	Chemical	C416835
16920333	191	258	S-(-)-10-acetoxy-10,11-dihydro-5H-dibenzo/b,f/azepine-5-carboxamide	Chemical	C416835
16920333	430	443	carbamazepine	Chemical	D002220
16920333	445	448	CBZ	Chemical	D002220
16920333	454	467	oxcarbazepine	Chemical	C036006
16920333	469	472	OXC	Chemical	C036006
16920333	526	549	eslicarbazepine acetate	Chemical	C416835
16920333	591	599	seizures	Disease	D012640
16920333	677	684	seizure	Disease	D012640
16920333	742	752	picrotoxin	Chemical	D010852
16920333	776	784	seizures	Disease	D012640
16920333	812	819	seizure	Disease	D012640
16920333	894	904	picrotoxin	Chemical	D010852
16920333	930	938	seizures	Disease	D012640
16920333	1008	1016	seizures	Disease	D012640
16920333	1086	1094	seizures	Disease	D012640
16920333	1122	1129	seizure	Disease	D012640
16920333	1184	1207	eslicarbazepine acetate	Chemical	C416835
16920333	CID	D010852	D012640

17028363|t|Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones.
17028363|a|Chinese herbal medicine preparations are widely available and often regarded by the public as natural and safe remedies for a variety of medical conditions. Nephropathy caused by Chinese herbs has previously been reported, usually involving the use of aristolochic acids. We report a 23-year-old woman who developed acute renal failure following prolonged use of a proprietary Chinese herbal slimming pill that contained anthraquinone derivatives, extracted from Rhizoma Rhei (rhubarb). The renal injury was probably aggravated by the concomitant intake of a non-steroidal anti-inflammatory drug, diclofenac. Renal pathology was that of hypocellular interstitial fibrosis. Spontaneous renal recovery occurred upon cessation of the slimming pills, but mild interstitial fibrosis and tubular atrophy was still evident histologically 4 months later. Although a causal relationship between the use of an anthraquinone-containing herbal agent and renal injury remains to be proven, phytotherapy-associated interstitial nephropathy should be considered in patients who present with unexplained renal failure.
17028363	0	19	Acute renal failure	Disease	D058186
17028363	82	96	anthraquinones	Chemical	D000880
17028363	98	112	Chinese herbal	Chemical	D004365
17028363	255	266	Nephropathy	Disease	D007674
17028363	277	290	Chinese herbs	Chemical	D004365
17028363	350	368	aristolochic acids	Chemical	D034341
17028363	414	433	acute renal failure	Disease	D058186
17028363	475	489	Chinese herbal	Chemical	D004365
17028363	519	532	anthraquinone	Chemical	D000880
17028363	589	601	renal injury	Disease	D058186
17028363	695	705	diclofenac	Chemical	D004008
17028363	761	769	fibrosis	Disease	D005355
17028363	867	875	fibrosis	Disease	D005355
17028363	888	895	atrophy	Disease	D001284
17028363	998	1011	anthraquinone	Chemical	D000880
17028363	1040	1052	renal injury	Disease	D058186
17028363	1112	1123	nephropathy	Disease	D007674
17028363	1186	1199	renal failure	Disease	D051437
17028363	CID	D004008	D058186
17028363	CID	D004365	D058186

17035713|t|Chloroacetaldehyde as a sulfhydryl reagent: the role of critical thiol groups in ifosfamide nephropathy.
17035713|a|Chloroacetaldehyde (CAA) is a metabolite of the alkylating agent ifosfamide (IFO) and putatively responsible for renal damage following anti-tumor therapy with IFO. Depletion of sulfhydryl (SH) groups has been reported from cell culture, animal and clinical studies. In this work the effect of CAA on human proximal tubule cells in primary culture (hRPTEC) was investigated. Toxicity of CAA was determined by protein content, cell number, LDH release, trypan blue exclusion assay and caspase-3 activity. Free thiols were measured by the method of Ellman. CAA reduced hRPTEC cell number and protein, induced a loss in free intracellular thiols and an increase in necrosis markers. CAA but not acrolein inhibited the cysteine proteases caspase-3, caspase-8 and cathepsin B. Caspase activation by cisplatin was inhibited by CAA. In cells stained with fluorescent dyes targeting lysosomes, CAA induced an increase in lysosomal size and lysosomal leakage. The effects of CAA on cysteine protease activities and thiols could be reproduced in cell lysate. Acidification, which slowed the reaction of CAA with thiol donors, could also attenuate effects of CAA on necrosis markers, thiol depletion and cysteine protease inhibition in living cells. Thus, CAA directly reacts with cellular protein and non-protein thiols, mediating its toxicity on hRPTEC. This effect can be reduced by acidification. Therefore, urinary acidification could be an option to prevent IFO nephropathy in patients.
17035713	0	18	Chloroacetaldehyde	Chemical	C004656
17035713	24	34	sulfhydryl	Chemical	-1
17035713	65	70	thiol	Chemical	D013438
17035713	81	91	ifosfamide	Chemical	D007069
17035713	92	103	nephropathy	Disease	D007674
17035713	105	123	Chloroacetaldehyde	Chemical	C004656
17035713	125	128	CAA	Chemical	C004656
17035713	170	180	ifosfamide	Chemical	D007069
17035713	182	185	IFO	Chemical	D007069
17035713	218	230	renal damage	Disease	D007674
17035713	246	251	tumor	Disease	D009369
17035713	265	268	IFO	Chemical	D007069
17035713	283	293	sulfhydryl	Chemical	-1
17035713	295	297	SH	Chemical	-1
17035713	399	402	CAA	Chemical	C004656
17035713	480	488	Toxicity	Disease	D064420
17035713	492	495	CAA	Chemical	C004656
17035713	557	568	trypan blue	Chemical	D014343
17035713	614	620	thiols	Chemical	D013438
17035713	660	663	CAA	Chemical	C004656
17035713	741	747	thiols	Chemical	D013438
17035713	767	775	necrosis	Disease	D009336
17035713	785	788	CAA	Chemical	C004656
17035713	797	805	acrolein	Chemical	D000171
17035713	820	828	cysteine	Chemical	D003545
17035713	899	908	cisplatin	Chemical	D002945
17035713	926	929	CAA	Chemical	C004656
17035713	991	994	CAA	Chemical	C004656
17035713	1071	1074	CAA	Chemical	C004656
17035713	1078	1086	cysteine	Chemical	D003545
17035713	1111	1117	thiols	Chemical	D013438
17035713	1198	1201	CAA	Chemical	C004656
17035713	1207	1212	thiol	Chemical	D013438
17035713	1253	1256	CAA	Chemical	C004656
17035713	1260	1268	necrosis	Disease	D009336
17035713	1278	1283	thiol	Chemical	D013438
17035713	1298	1306	cysteine	Chemical	D003545
17035713	1350	1353	CAA	Chemical	C004656
17035713	1408	1414	thiols	Chemical	D013438
17035713	1430	1438	toxicity	Disease	D064420
17035713	1558	1561	IFO	Chemical	D007069
17035713	1562	1573	nephropathy	Disease	D007674
17035713	CID	D007069	D007674

17042797|t|Stereological methods reveal the robust size and stability of ectopic hilar granule cells after pilocarpine-induced status epilepticus in the adult rat.
17042797|a|Following status epilepticus in the rat, dentate granule cell neurogenesis increases greatly, and many of the new neurons appear to develop ectopically, in the hilar region of the hippocampal formation. It has been suggested that the ectopic hilar granule cells could contribute to the spontaneous seizures that ultimately develop after status epilepticus. However, the population has never been quantified, so it is unclear whether it is substantial enough to have a strong influence on epileptogenesis. To quantify this population, the total number of ectopic hilar granule cells was estimated using unbiased stereology at different times after pilocarpine-induced status epilepticus. The number of hilar neurons immunoreactive for Prox-1, a granule-cell-specific marker, was estimated using the optical fractionator method. The results indicate that the size of the hilar ectopic granule cell population after status epilepticus is substantial, and stable over time. Interestingly, the size of the population appears to be correlated with the frequency of behavioral seizures, because animals with more ectopic granule cells in the hilus have more frequent behavioral seizures. The hilar ectopic granule cell population does not appear to vary systematically across the septotemporal axis, although it is associated with an increase in volume of the hilus. The results provide new insight into the potential role of ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy.
17042797	96	107	pilocarpine	Chemical	D010862
17042797	116	134	status epilepticus	Disease	D013226
17042797	163	181	status epilepticus	Disease	D013226
17042797	451	459	seizures	Disease	D012640
17042797	490	508	status epilepticus	Disease	D013226
17042797	800	811	pilocarpine	Chemical	D010862
17042797	820	838	status epilepticus	Disease	D013226
17042797	1066	1084	status epilepticus	Disease	D013226
17042797	1223	1231	seizures	Disease	D012640
17042797	1324	1332	seizures	Disease	D012640
17042797	1607	1618	pilocarpine	Chemical	D010862
17042797	1628	1650	temporal lobe epilepsy	Disease	D004833
17042797	CID	D010862	D004833
17042797	CID	D010862	D013226

17069550|t|A prospective, open-label trial of galantamine in autistic disorder.
17069550|a|OBJECTIVE: Post-mortem studies have reported abnormalities of the cholinergic system in autism. The purpose of this study was to assess the use of galantamine, an acetylcholinesterase inhibitor and nicotinic receptor modulator, in the treatment of interfering behaviors in children with autism. METHODS: Thirteen medication-free children with autism (mean age, 8.8 +/- 3.5 years) participated in a 12-week, open-label trial of galantamine. Patients were rated monthly by parents on the Aberrant Behavior Checklist (ABC) and the Conners' Parent Rating Scale-Revised, and by a physician using the Children's Psychiatric Rating Scale and the Clinical Global Impressions scale. RESULTS: Patients showed a significant reduction in parent-rated irritability and social withdrawal on the ABC as well as significant improvements in emotional lability and inattention on the Conners' Parent Rating Scale--Revised. Similarly, clinician ratings showed reductions in the anger subscale of the Children's Psychiatric Rating Scale. Eight of 13 participants were rated as responders on the basis of their improvement scores on the Clinical Global Impressions scale. Overall, galantamine was well-tolerated, with no significant adverse effects apart from headaches in one patient. CONCLUSION: In this open trial, galantamine was well-tolerated and appeared to be beneficial for the treatment of interfering behaviors in children with autism, particularly aggression, behavioral dyscontrol, and inattention. Further controlled trials are warranted.
17069550	35	46	galantamine	Chemical	D005702
17069550	50	67	autistic disorder	Disease	D001321
17069550	157	163	autism	Disease	D001321
17069550	216	227	galantamine	Chemical	D005702
17069550	356	362	autism	Disease	D001321
17069550	412	418	autism	Disease	D001321
17069550	496	507	galantamine	Chemical	D005702
17069550	808	820	irritability	Disease	D001523
17069550	1229	1240	galantamine	Chemical	D005702
17069550	1308	1317	headaches	Disease	D006261
17069550	1366	1377	galantamine	Chemical	D005702
17069550	1487	1493	autism	Disease	D001321
17069550	1508	1518	aggression	Disease	D001523
17069550	1520	1541	behavioral dyscontrol	Disease	D002653
17069550	1547	1558	inattention	Disease	D019958
17069550	CID	D005702	D006261

17151160|t|Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes.
17151160|a|OBJECTIVE: The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day). RESULTS: Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.
17151160	25	35	olanzapine	Chemical	C076029
17151160	43	54	risperidone	Chemical	D018967
17151160	90	103	schizophrenia	Disease	D012559
17151160	186	196	olanzapine	Chemical	C076029
17151160	204	215	risperidone	Chemical	D018967
17151160	247	260	schizophrenia	Disease	D012559
17151160	379	392	schizophrenia	Disease	D012559
17151160	400	425	schizophreniform disorder	Disease	D011618
17151160	436	460	schizoaffective disorder	Disease	D011618
17151160	507	517	olanzapine	Chemical	C076029
17151160	537	548	risperidone	Chemical	D018967
17151160	624	634	olanzapine	Chemical	C076029
17151160	667	678	risperidone	Chemical	D018967
17151160	766	776	olanzapine	Chemical	C076029
17151160	823	834	risperidone	Chemical	D018967
17151160	962	974	parkinsonism	Disease	D010302
17151160	979	988	akathisia	Disease	D017109
17151160	1025	1047	Extrapyramidal symptom	Disease	D001480
17151160	1095	1106	risperidone	Chemical	D018967
17151160	1137	1147	olanzapine	Chemical	C076029
17151160	1168	1179	weight gain	Disease	D015430
17151160	1194	1204	olanzapine	Chemical	C076029
17151160	1215	1226	risperidone	Chemical	D018967
17151160	1327	1337	olanzapine	Chemical	C076029
17151160	1373	1384	risperidone	Chemical	D018967
17151160	1494	1504	olanzapine	Chemical	C076029
17151160	1569	1580	risperidone	Chemical	D018967
17151160	1618	1629	risperidone	Chemical	D018967
17151160	1655	1665	olanzapine	Chemical	C076029
17151160	1700	1710	Olanzapine	Chemical	C076029
17151160	1799	1810	weight gain	Disease	D015430
17151160	1816	1827	weight gain	Disease	D015430
17151160	1845	1855	olanzapine	Chemical	C076029
17151160	CID	D018967	D001480
17151160	CID	C076029	D015430
17151160	CID	C076029	D001480
17151160	CID	D018967	D015430

17159032|t|Early paracentral visual field loss in patients taking hydroxychloroquine.
17159032|a|OBJECTIVE: To review the natural history and ocular and systemic adverse effects of patients taking hydroxychloroquine sulfate who attended an ophthalmic screening program. DESIGN: Retrospective study. RESULTS: Records of 262 patients who were taking hydroxychloroquine and screened in the Department of Ophthalmology were reviewed. Of the 262 patients, 14 (18%) of 76 who had stopped treatment at the time of the study experienced documented adverse effects. Systemic adverse effects occurred in 8 patients (10.5%) and ocular adverse effects, in 5 (6.5%). Thirty-five patients (13.4%) had visual field abnormalities, which were attributed to hydroxychloroquine treatment in 4 patients (1.5%). Three of the 4 patients were taking less than 6.5 mg/kg per day and all patients had normal renal and liver function test results. CONCLUSIONS: The current study used a protocol of visual acuity and color vision assessment, funduscopy, and Humphrey 10-2 visual field testing and shows that visual field defects appeared before any corresponding changes in any other tested clinical parameters; the defects were reproducible and the test parameters were reliable. Patients taking hydroxychloroquine can demonstrate a toxic reaction in the retina despite the absence of known risk factors. Screening, including Humphrey 10-2 visual field assessment, is recommended 2 years after the initial baseline and yearly thereafter.
17159032	18	35	visual field loss	Disease	D014786
17159032	55	73	hydroxychloroquine	Chemical	D006886
17159032	175	201	hydroxychloroquine sulfate	Chemical	D006886
17159032	326	344	hydroxychloroquine	Chemical	D006886
17159032	665	691	visual field abnormalities	Disease	D014786
17159032	718	736	hydroxychloroquine	Chemical	D006886
17159032	1059	1079	visual field defects	Disease	D014786
17159032	1248	1266	hydroxychloroquine	Chemical	D006886
17159032	CID	D006886	D014786

17223814|t|Peri-operative atrioventricular block as a result of chemotherapy with epirubicin and paclitaxel.
17223814|a|A 47-year-old woman presented for mastectomy and immediate latissimus dorsi flap reconstruction having been diagnosed with carcinoma of the breast 6 months previously. In the preceding months she had received neo-adjuvant chemotherapy with epirubicin, paclitaxel (Taxol) and cyclophosphamide. This had been apparently uncomplicated and she had maintained a remarkably high level of physical activity. She was found to be bradycardic at pre-operative assessment but had no cardiac symptoms. Second degree Mobitz type II atrioventricular block was diagnosed on electrocardiogram, and temporary transvenous ventricular pacing instituted in the peri-operative period. We discuss how evidence-based guidelines would not have been helpful in this case, and how chemotherapy can exhibit substantial cardiotoxicity that may develop over many years. We suggest that patients who have received chemotherapy at any time should have a pre-operative electrocardiogram even if they are asymptomatic.
17223814	15	37	atrioventricular block	Disease	D054537
17223814	71	81	epirubicin	Chemical	D015251
17223814	86	96	paclitaxel	Chemical	D017239
17223814	221	244	carcinoma of the breast	Disease	D001943
17223814	338	348	epirubicin	Chemical	D015251
17223814	350	360	paclitaxel	Chemical	D017239
17223814	362	367	Taxol	Chemical	D017239
17223814	373	389	cyclophosphamide	Chemical	D003520
17223814	519	530	bradycardic	Disease	D001919
17223814	617	639	atrioventricular block	Disease	D054537
17223814	890	904	cardiotoxicity	Disease	D066126
17223814	CID	D003520	D054537
17223814	CID	D017239	D054537
17223814	CID	D015251	D054537

17255138|t|Risks and benefits of COX-2 inhibitors vs non-selective NSAIDs: does their cardiovascular risk exceed their gastrointestinal benefit? A retrospective cohort study.
17255138|a|OBJECTIVES: The risk of acute myocardial infarction (AMI) with COX-2 inhibitors may offset their gastrointestinal (GI) benefit compared with non-selective (NS) non-steroidal anti-inflammatory drugs (NSAIDs). We aimed to compare the risks of hospitalization for AMI and GI bleeding among elderly patients using COX-2 inhibitors, NS-NSAIDs and acetaminophen. METHODS: We conducted a retrospective cohort study using administrative data of patients > or =65 years of age who filled a prescription for NSAID or acetaminophen during 1999-2002. Outcomes were compared using Cox regression models with time-dependent exposures. RESULTS: Person-years of exposure among non-users of aspirin were: 75,761 to acetaminophen, 42,671 to rofecoxib 65,860 to celecoxib, and 37,495 to NS-NSAIDs. Among users of aspirin, they were: 14,671 to rofecoxib, 22,875 to celecoxib, 9,832 to NS-NSAIDs and 38,048 to acetaminophen. Among non-users of aspirin, the adjusted hazard ratios (95% confidence interval) of hospitalization for AMI/GI vs the acetaminophen (with no aspirin) group were: rofecoxib 1.27 (1.13, 1.42), celecoxib 0.93 (0.83, 1.03), naproxen 1.59 (1.31, 1.93), diclofenac 1.17 (0.99, 1.38) and ibuprofen 1.05 (0.74, 1.51). Among users of aspirin, they were: rofecoxib 1.73 (1.52, 1.98), celecoxib 1.34 (1.19, 1.52), ibuprofen 1.51 (0.95, 2.41), diclofenac 1.69 (1.35, 2.10), naproxen 1.35 (0.97, 1.88) and acetaminophen 1.29 (1.17, 1.42). CONCLUSION: Among non-users of aspirin, naproxen seemed to carry the highest risk for AMI/GI bleeding. The AMI/GI toxicity of celecoxib was similar to that of acetaminophen and seemed to be better than those of rofecoxib and NS-NSAIDs. Among users of aspirin, both celecoxib and naproxen seemed to be the least toxic.
17255138	22	38	COX-2 inhibitors	Chemical	D052246
17255138	188	215	acute myocardial infarction	Disease	D009203
17255138	217	220	AMI	Disease	D009203
17255138	227	243	COX-2 inhibitors	Chemical	D052246
17255138	324	361	non-steroidal anti-inflammatory drugs	Chemical	D000894
17255138	425	428	AMI	Disease	D009203
17255138	433	444	GI bleeding	Disease	D006471
17255138	474	490	COX-2 inhibitors	Chemical	D052246
17255138	506	519	acetaminophen	Chemical	D000082
17255138	671	684	acetaminophen	Chemical	D000082
17255138	838	845	aspirin	Chemical	D001241
17255138	862	875	acetaminophen	Chemical	D000082
17255138	887	896	rofecoxib	Chemical	C116926
17255138	907	916	celecoxib	Chemical	C105934
17255138	958	965	aspirin	Chemical	D001241
17255138	988	997	rofecoxib	Chemical	C116926
17255138	1009	1018	celecoxib	Chemical	C105934
17255138	1053	1066	acetaminophen	Chemical	D000082
17255138	1087	1094	aspirin	Chemical	D001241
17255138	1172	1175	AMI	Disease	D009203
17255138	1186	1199	acetaminophen	Chemical	D000082
17255138	1209	1216	aspirin	Chemical	D001241
17255138	1230	1239	rofecoxib	Chemical	C116926
17255138	1259	1268	celecoxib	Chemical	C105934
17255138	1288	1296	naproxen	Chemical	D009288
17255138	1316	1326	diclofenac	Chemical	D004008
17255138	1349	1358	ibuprofen	Chemical	D007052
17255138	1393	1400	aspirin	Chemical	D001241
17255138	1413	1422	rofecoxib	Chemical	C116926
17255138	1442	1451	celecoxib	Chemical	C105934
17255138	1471	1480	ibuprofen	Chemical	D007052
17255138	1500	1510	diclofenac	Chemical	D004008
17255138	1530	1538	naproxen	Chemical	D009288
17255138	1561	1574	acetaminophen	Chemical	D000082
17255138	1625	1632	aspirin	Chemical	D001241
17255138	1634	1642	naproxen	Chemical	D009288
17255138	1680	1683	AMI	Disease	D009203
17255138	1684	1695	GI bleeding	Disease	D006471
17255138	1701	1704	AMI	Disease	D009203
17255138	1708	1716	toxicity	Disease	D064420
17255138	1720	1729	celecoxib	Chemical	C105934
17255138	1753	1766	acetaminophen	Chemical	D000082
17255138	1805	1814	rofecoxib	Chemical	C116926
17255138	1845	1852	aspirin	Chemical	D001241
17255138	1859	1868	celecoxib	Chemical	C105934
17255138	1873	1881	naproxen	Chemical	D009288
17255138	CID	D009288	D009203
17255138	CID	D000894	D006471
17255138	CID	C116926	D006471
17255138	CID	D009288	D006471
17255138	CID	D052246	D009203
17255138	CID	C116926	D009203
17255138	CID	D000894	D009203

17297207|t|Quinine-induced arrhythmia in a patient with severe malaria.
17297207|a|It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia (premature ventricular contraction) while getting quinine infusion was reported. A man, 25 years old, was admitted to hospital with high fever, chill, vomiting, jaundice. The patient was fully conscious, blood pressure 120/80 mmHg, pulse rate 100 x/minute, regular. On admission, laboratory examination showed Plasmodium falciparum (++++), total bilirubin 8.25 mg/dL, conjugated bilirubin 4.36 mg/dL, unconjugated bilirubin 3.89 mg/dL, potassium 3.52 meq/L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5% 500 mg/8 hour. On the second day the patient had vomitus, diarrhea, tinnitus, loss of hearing. After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x/minute, trigemini, constant type--sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5%/24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x/minute and on the third day ECG was normal, potassium level was 3.34 meq/L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti-arrhythmic property, although it also pro-arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro-arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases.
17297207	0	7	Quinine	Chemical	D011803
17297207	16	26	arrhythmia	Disease	D001145
17297207	45	59	severe malaria	Disease	D016778
17297207	102	116	severe malaria	Disease	D016778
17297207	130	138	jaundice	Disease	D007565
17297207	158	168	arrhythmia	Disease	D001145
17297207	170	203	premature ventricular contraction	Disease	D018879
17297207	219	226	quinine	Chemical	D011803
17297207	306	311	fever	Disease	D005334
17297207	313	318	chill	Disease	D023341
17297207	320	328	vomiting	Disease	D014839
17297207	330	338	jaundice	Disease	D007565
17297207	515	524	bilirubin	Chemical	D001663
17297207	548	557	bilirubin	Chemical	D001663
17297207	583	592	bilirubin	Chemical	D001663
17297207	605	614	potassium	Chemical	D011188
17297207	651	665	severe malaria	Disease	D016778
17297207	671	679	jaundice	Disease	D007565
17297207	688	695	quinine	Chemical	D011803
17297207	708	716	dextrose	Chemical	D005947
17297207	769	776	vomitus	Disease	D014839
17297207	778	786	diarrhea	Disease	D003967
17297207	788	796	tinnitus	Disease	D014012
17297207	798	813	loss of hearing	Disease	D034381
17297207	833	840	quinine	Chemical	D011803
17297207	867	878	palpitation	Disease	-1
17297207	926	959	premature ventricular contraction	Disease	D018879
17297207	961	964	PVC	Disease	D018879
17297207	1006	1022	sinoatrial block	Disease	D012848
17297207	1061	1070	lidocaine	Chemical	D008012
17297207	1123	1131	dextrose	Chemical	D005947
17297207	1147	1166	potassium aspartate	Chemical	D001224
17297207	1175	1182	Quinine	Chemical	D011803
17297207	1234	1241	quinine	Chemical	D011803
17297207	1311	1314	PVC	Disease	D018879
17297207	1378	1387	potassium	Chemical	D011188
17297207	1458	1465	Quinine	Chemical	D011803
17297207	1472	1481	quinidine	Chemical	D011802
17297207	1520	1530	arrhythmic	Disease	D001145
17297207	1562	1572	arrhythmic	Disease	D001145
17297207	1596	1607	arrhythmias	Disease	D001145
17297207	1626	1636	arrhythmia	Disease	D001145
17297207	1654	1657	PVC	Disease	D018879
17297207	1688	1695	quinine	Chemical	D011803
17297207	1764	1774	arrhythmic	Disease	D001145
17297207	1821	1835	heart diseases	Disease	D006331
17297207	1853	1873	electrolyte disorder	Disease	D014883
17297207	1875	1886	hypokalemia	Disease	D007008
17297207	1919	1927	vomiting	Disease	D014839
17297207	1935	1943	diarrhea	Disease	D003967
17297207	1947	1954	malaria	Disease	D008288
17297207	CID	D011803	D018879

17346443|t|Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a Wilson disease patient with hepatic presentation, anxiety and SPECT abnormalities.
17346443|a|Wilson's disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson's disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD-SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson's disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson's disease. Since most of Wilson's disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson's disease therapy, and in particular to differentiate specific therapies for different Wilson's disease phenotypes.
17346443	0	13	Penicillamine	Chemical	D010396
17346443	22	42	lichenoid dermatitis	Disease	D017512
17346443	58	70	zinc acetate	Chemical	D019345
17346443	76	90	Wilson disease	Disease	D006527
17346443	126	133	anxiety	Disease	D001008
17346443	159	175	Wilson's disease	Disease	D006527
17346443	222	228	copper	Chemical	D003300
17346443	256	262	copper	Chemical	D003300
17346443	280	288	toxicity	Disease	D064420
17346443	320	365	hepatic, neurologic and psychiatric disorders	Disease	D056486|D009422|D001523	hepatic disorders|neurologic disorders|psychiatric disorders
17346443	387	403	Wilson's disease	Disease	D006527
17346443	409	430	chronic liver disease	Disease	D008107
17346443	500	507	anxiety	Disease	D001008
17346443	516	526	depression	Disease	D003866
17346443	667	680	penicillamine	Chemical	D010396
17346443	723	743	lichenoid dermatitis	Disease	D017512
17346443	749	761	zinc acetate	Chemical	D019345
17346443	875	887	zinc acetate	Chemical	D019345
17346443	929	945	Wilson's disease	Disease	D006527
17346443	963	976	penicillamine	Chemical	D010396
17346443	1026	1038	zinc acetate	Chemical	D019345
17346443	1202	1218	Wilson's disease	Disease	D006527
17346443	1234	1250	Wilson's disease	Disease	D006527
17346443	1251	1264	penicillamine	Chemical	D010396
17346443	1310	1321	skin lesion	Disease	D012871
17346443	1465	1481	Wilson's disease	Disease	D006527
17346443	1559	1575	Wilson's disease	Disease	D006527
17346443	CID	D010396	D017512

17351238|t|A dramatic drop in blood pressure following prehospital GTN administration.
17351238|a|A male in his sixties with no history of cardiac chest pain awoke with chest pain following an afternoon sleep. The patient did not self medicate. The patient's observations were within normal limits, he was administered oxygen via a face mask and glyceryl trinitrate (GTN). Several minutes after the GTN the patient experienced a sudden drop in blood pressure and heart rate, this was rectified by atropine sulphate and a fluid challenge. There was no further deterioration in the patient's condition during transport to hospital. There are very few documented case like this in the prehospital scientific literature. The cause appears to be the Bezold-Jarish reflex, stimulation of the ventricular walls which in turn decreases sympathetic outflow from the vasomotor centre. Prehospital care providers who are managing any patient with a syncopal episode that fails to recover within a reasonable time frame should consider the Bezold-Jarisch reflex as the cause and manage the patient accordingly.
17351238	11	33	drop in blood pressure	Disease	D007022
17351238	56	59	GTN	Chemical	D005996
17351238	125	135	chest pain	Disease	D002637
17351238	147	157	chest pain	Disease	D002637
17351238	297	303	oxygen	Chemical	D010100
17351238	324	343	glyceryl trinitrate	Chemical	D005996
17351238	345	348	GTN	Chemical	D005996
17351238	377	380	GTN	Chemical	D005996
17351238	414	436	drop in blood pressure	Disease	D007022
17351238	475	492	atropine sulphate	Chemical	D001285
17351238	916	932	syncopal episode	Disease	D013575
17351238	CID	D010100	D007022
17351238	CID	D005996	D007022

17356399|t|Acute encephalopathy and cerebral vasospasm after multiagent chemotherapy including PEG-asparaginase and intrathecal cytarabine for the treatment of acute lymphoblastic leukemia.
17356399|a|A 7-year-old girl with an unusual reaction to induction chemotherapy for precursor B-cell acute lymphoblastic leukemia (ALL) is described. The patient developed acute encephalopathy evidenced by behavioral changes, aphasia, incontinence, visual hallucinations, and right-sided weakness with diffuse cerebral vasospasm on magnetic resonance angiography after the administration of intrathecal cytarabine. Vincristine, dexamethasone, and polyethylene glycol-asparaginase were also administered before the episode as part of induction therapy. Neurologic status returned to baseline within 10 days of the acute event, and magnetic resonance angiography findings returned to normal 4 months later.
17356399	0	20	Acute encephalopathy	Disease	D020803
17356399	25	43	cerebral vasospasm	Disease	D020301
17356399	84	100	PEG-asparaginase	Chemical	C042705
17356399	117	127	cytarabine	Chemical	D003561
17356399	149	177	acute lymphoblastic leukemia	Disease	D054198
17356399	269	297	acute lymphoblastic leukemia	Disease	D054198
17356399	299	302	ALL	Disease	D054198
17356399	340	360	acute encephalopathy	Disease	D020803
17356399	394	401	aphasia	Disease	D001037
17356399	403	415	incontinence	Disease	D014549
17356399	417	438	visual hallucinations	Disease	D006212
17356399	456	464	weakness	Disease	D018908
17356399	478	496	cerebral vasospasm	Disease	D020301
17356399	571	581	cytarabine	Chemical	D003561
17356399	583	594	Vincristine	Chemical	D014750
17356399	596	609	dexamethasone	Chemical	D003907
17356399	615	647	polyethylene glycol-asparaginase	Chemical	C042705
17356399	CID	D003561	D020301
17356399	CID	D014750	D020301
17356399	CID	D014750	D018908
17356399	CID	D003907	D018908
17356399	CID	D003561	D001037
17356399	CID	C042705	D006212
17356399	CID	D003561	D006212
17356399	CID	D003907	D001037
17356399	CID	D003561	D014549
17356399	CID	C042705	D018908
17356399	CID	C042705	D014549
17356399	CID	D003907	D014549
17356399	CID	D014750	D001037
17356399	CID	D014750	D006212
17356399	CID	D003907	D006212
17356399	CID	D014750	D014549
17356399	CID	D003561	D018908
17356399	CID	C042705	D001037
17356399	CID	C042705	D020301
17356399	CID	D003907	D020301

17379047|t|Comparison of valsartan/hydrochlorothiazide combination therapy at doses up to 320/25 mg versus monotherapy: a double-blind, placebo-controlled study followed by long-term combination therapy in hypertensive adults.
17379047|a|BACKGROUND: One third of patients treated for hypertension attain adequate blood pressure (BP) control, and multidrug regimens are often required. Given the lifelong nature of hypertension, there is a need to evaluate the long-term efficacy and tolerability of higher doses of combination anti-hypertensive therapies. OBJECTIVE: This study investigated the efficacy and tolerability of valsartan (VAL) or hydrochlorothiazide (HCTZ)-monotherapy and higher-dose combinations in patients with essential hypertension. METHODS: The first part of this study was an 8-week, multicenter, randomized, double-blind, placebo controlled, parallel-group trial. Patients with essential hypertension (mean sitting diastolic BP [MSDBP], > or =95 mm Hg and <110 mm Hg) were randomized to 1 of 8 treatment groups: VAL 160 or 320 mg; HCTZ 12.5 or 25 mg; VAL/HCTZ 160/12.5, 320/12.5, or 320/25 mg; or placebo. Mean changes in MSDBP and mean sitting systolic BP (MSSBP) were analyzed at the 8-week core study end point. VAL/HCTZ 320/12.5 and 320/25 mg were further investigated in a 54-week, open-label extension. Response was defined as MSDBP <90 mm Hg or a > or =10 mm Hg decrease compared to baseline. Control was defined as MSDBP <90 mm Hg compared with baseline. Tolerability was assessed by monitoring adverse events at randomization and all subsequent study visits and regular evaluation of hematology and blood chemistry. RESULTS: A total of 1346 patients were randomized into the 8-week core study (734 men, 612 women; 924 white, 291 black, 23 Asian, 108 other; mean age, 52.7 years; mean weight, 92.6 kg). All active treatments were associated with significantly reduced MSSBP and MSDBP during the core 8-week study, with each monotherapy significantly contributing to the overall effect of combination therapy (VAL and HCTZ, P < 0.001). Each combination was associated with significantly greater reductions in MSSBP and MSDBP compared with the monotherapies and placebo (all, P < 0.001). The mean reduction in MSSBP/MSDBP with VAL/HCTZ 320/25 mg was 24.7/16.6 mm Hg, compared with 5.9/7.0 mm Hg with placebo. The reduction in MSSBP was significantly greater with VAL/HCTZ 320/25 mg compared with VAL/HCTZ 160/12.5 mg (P < 0.002). Rates of response and BP control were significantly higher in the groups that received combination treatment compared with those that received monotherapy. The incidence of hypokalemia was lower with VAL/HCTZ combinations (1.8%-6.1%) than with HCTZ monotherapies (7.1%-13.3%). The majority of adverse events in the core study were of mild to moderate severity. The efficacy and tolerability of VAL/HCTZ combinations were maintained during the extension (797 patients). CONCLUSIONS: In this study population, combination therapies with VAL/HCTZ were associated with significantly greater BP reductions compared with either monotherapy, were well tolerated, and were associated with less hypokalemia than HCTZ alone.
17379047	14	23	valsartan	Chemical	C081489
17379047	24	43	hydrochlorothiazide	Chemical	D006852
17379047	195	207	hypertensive	Disease	D006973
17379047	262	274	hypertension	Disease	D006973
17379047	392	404	hypertension	Disease	D006973
17379047	510	522	hypertensive	Disease	D006973
17379047	602	611	valsartan	Chemical	C081489
17379047	613	616	VAL	Chemical	C081489
17379047	621	640	hydrochlorothiazide	Chemical	D006852
17379047	642	646	HCTZ	Chemical	D006852
17379047	706	728	essential hypertension	Disease	C562386
17379047	878	900	essential hypertension	Disease	C562386
17379047	1012	1015	VAL	Chemical	C081489
17379047	1031	1035	HCTZ	Chemical	D006852
17379047	1051	1054	VAL	Chemical	C081489
17379047	1055	1059	HCTZ	Chemical	D006852
17379047	1215	1218	VAL	Chemical	C081489
17379047	1219	1223	HCTZ	Chemical	D006852
17379047	2017	2020	VAL	Chemical	C081489
17379047	2025	2029	HCTZ	Chemical	D006852
17379047	2233	2236	VAL	Chemical	C081489
17379047	2237	2241	HCTZ	Chemical	D006852
17379047	2369	2372	VAL	Chemical	C081489
17379047	2373	2377	HCTZ	Chemical	D006852
17379047	2402	2405	VAL	Chemical	C081489
17379047	2406	2410	HCTZ	Chemical	D006852
17379047	2609	2620	hypokalemia	Disease	D007008
17379047	2636	2639	VAL	Chemical	C081489
17379047	2640	2644	HCTZ	Chemical	D006852
17379047	2680	2684	HCTZ	Chemical	D006852
17379047	2830	2833	VAL	Chemical	C081489
17379047	2834	2838	HCTZ	Chemical	D006852
17379047	2971	2974	VAL	Chemical	C081489
17379047	2975	2979	HCTZ	Chemical	D006852
17379047	3122	3133	hypokalemia	Disease	D007008
17379047	3139	3143	HCTZ	Chemical	D006852
17379047	CID	D006852	D007008

17384765|t|Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure.
17384765|a|BACKGROUND: There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb-exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure. OBJECTIVES: The present study was designed to answer these questions, using a rodent model of early childhood Pb exposure and treatment with succimer, a widely used chelating agent for the treatment of Pb poisoning. RESULTS: Pb exposure produced lasting impairments in learning, attention, inhibitory control, and arousal regulation, paralleling the areas of dysfunction seen in Pb-exposed children. Succimer treatment of the Pb-exposed rats significantly improved learning, attention, and arousal regulation, although the efficacy of the treatment varied as a function of the Pb exposure level and the specific functional deficit. In contrast, succimer treatment of rats not previously exposed to Pb produced lasting and pervasive cognitive and affective dysfunction comparable in magnitude to that produced by the higher Pb exposure regimen. CONCLUSIONS: These are the first data, to our knowledge, to show that treatment with any chelating agent can alleviate cognitive deficits due to Pb exposure. These findings suggest that it may be possible to identify a succimer treatment protocol that improves cognitive outcomes in Pb-exposed children. However, they also suggest that succimer treatment should be strongly discouraged for children who do not have elevated tissue levels of Pb or other heavy metals.
17384765	0	8	Succimer	Chemical	D004113
17384765	75	79	lead	Chemical	D007854
17384765	114	134	cognitive impairment	Disease	D003072
17384765	153	157	lead	Chemical	D007854
17384765	284	288	lead	Chemical	D007854
17384765	387	389	Pb	Chemical	D007854
17384765	505	507	Pb	Chemical	D007854
17384765	628	630	Pb	Chemical	D007854
17384765	659	667	succimer	Chemical	D004113
17384765	720	732	Pb poisoning	Disease	D007855
17384765	743	745	Pb	Chemical	D007854
17384765	772	850	impairments in learning, attention, inhibitory control, and arousal regulation	Disease	D007859|D019958	impairments in learning|impairments in attention, inhibitory control, and arousal regulation
17384765	897	899	Pb	Chemical	D007854
17384765	918	926	Succimer	Chemical	D004113
17384765	944	946	Pb	Chemical	D007854
17384765	1095	1097	Pb	Chemical	D007854
17384765	1163	1171	succimer	Chemical	D004113
17384765	1216	1218	Pb	Chemical	D007854
17384765	1250	1285	cognitive and affective dysfunction	Disease	D003072|D019964	cognitive dysfunction|affective dysfunction
17384765	1341	1343	Pb	Chemical	D007854
17384765	1481	1499	cognitive deficits	Disease	D003072
17384765	1507	1509	Pb	Chemical	D007854
17384765	1581	1589	succimer	Chemical	D004113
17384765	1645	1647	Pb	Chemical	D007854
17384765	1698	1706	succimer	Chemical	D004113
17384765	1803	1805	Pb	Chemical	D007854
17384765	CID	D004113	D003072
17384765	CID	D007854	D007859
17384765	CID	D007854	D019958

17445520|t|Caffeine challenge test in panic disorder and depression with panic attacks.
17445520|a|Our aim was to observe if patients with panic disorder (PD) and patients with major depression with panic attacks (MDP) (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) respond in a similar way to the induction of panic attacks by an oral caffeine challenge test. We randomly selected 29 patients with PD, 27 with MDP, 25 with major depression without panic attacks (MD), and 28 healthy volunteers. The patients had no psychotropic drug for at least a 4-week period. In a randomized double-blind experiment performed in 2 occasions 7 days apart, 480 mg caffeine and a caffeine-free (placebo) solution were administered in a coffee form and anxiety scales were applied before and after each test. A total of 58.6% (n = 17) of patients with PD, 44.4% (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n= 2) of control subjects had a panic attack after the 480-mg caffeine challenge test (chi(2)(3) = 16.22, P = .001). The patients with PD and MDP were more sensitive to caffeine than were patients with MD and healthy volunteers. No panic attack was observed after the caffeine-free solution intake. The patients with MD had a lower heart rate response to the test than all the other groups (2-way analysis of variance, group by time interaction with Greenhouse-Geisser correction: F(3,762) = 2.85, P = .026). Our data suggest that there is an association between panic attacks, no matter if associated with PD or MDP, and hyperreactivity to an oral caffeine challenge test.
17445520	0	8	Caffeine	Chemical	D002110
17445520	27	41	panic disorder	Disease	D016584
17445520	46	56	depression	Disease	D003866
17445520	62	75	panic attacks	Disease	D016584
17445520	117	131	panic disorder	Disease	D016584
17445520	133	135	PD	Disease	D016584
17445520	155	171	major depression	Disease	D003865
17445520	177	190	panic attacks	Disease	D016584
17445520	192	195	MDP	Disease	D003865|D016584
17445520	235	251	Mental Disorders	Disease	D001523
17445520	323	336	panic attacks	Disease	D016584
17445520	348	356	caffeine	Chemical	D002110
17445520	411	413	PD	Disease	D016584
17445520	423	426	MDP	Disease	D003865|D016584
17445520	436	452	major depression	Disease	D003865
17445520	461	474	panic attacks	Disease	D016584
17445520	476	478	MD	Disease	D003865
17445520	662	670	caffeine	Chemical	D002110
17445520	677	685	caffeine	Chemical	D002110
17445520	749	756	anxiety	Disease	D001008
17445520	848	850	PD	Disease	D016584
17445520	884	887	MDP	Disease	D003865|D016584
17445520	920	922	MD	Disease	D003865
17445520	966	978	panic attack	Disease	D016584
17445520	996	1004	caffeine	Chemical	D002110
17445520	1069	1071	PD	Disease	D016584
17445520	1076	1079	MDP	Disease	D003865|D016584
17445520	1103	1111	caffeine	Chemical	D002110
17445520	1136	1138	MD	Disease	D003865
17445520	1166	1178	panic attack	Disease	D016584
17445520	1202	1210	caffeine	Chemical	D002110
17445520	1251	1253	MD	Disease	D003865
17445520	1497	1510	panic attacks	Disease	D016584
17445520	1541	1543	PD	Disease	D016584
17445520	1547	1550	MDP	Disease	D003865|D016584
17445520	1583	1591	caffeine	Chemical	D002110
17445520	CID	D002110	D016584

17484470|t|Mitral annuloplasty as a ventricular restoration method for the failing left ventricle: a pilot study.
17484470|a|BACKGROUND AND AIM OF THE STUDY: Undersized mitral annuloplasty (MAP) is effective in patients with dilated cardiomyopathy and functional mitral regurgitation (MR) since, as well as addressing the MR, the MAP may also reshape the dilated left ventricular (LV) base. However, the direct benefits of this possible reshaping on LV function in the absence of underlying MR remain incompletely understood. The study aim was to identify these benefits in a canine model of acute heart failure. METHODS: Six dogs underwent MAP with a prosthetic band on the posterior mitral annulus, using four mattress sutures. The sutures were passed individually through four tourniquets and exteriorized untied via the left atriotomy. Sonomicrometry crystals were implanted around the mitral annulus and left ventricle to measure geometry and regional function. Acute heart failure was induced by propranolol and volume loading after weaning from cardiopulmonary bypass; an absence of MR was confirmed by echocardiography. MAP was accomplished by cinching the tourniquets. Data were acquired at baseline, after induction of acute heart failure, and after MAP. RESULTS: MAP decreased mitral annular dimensions in both commissure-commissure and septal-lateral directions. Concomitantly, the diastolic diameter of the LV base and LV sphericity decreased (i.e., improved) from 37.4 +/- 9.3 to 35.9 +/- 10 mm (p = 0.063), and from 67.9 +/- 18.6% to 65.3 +/- 18.9% (p = 0.016), respectively. Decreases were evident in both LV end-diastolic pressure (from 17 +/- 7 to 15 +/- 6 mmHg, p = 0.0480 and Tau (from 48 +/- 8 to 45 +/- 8 ms, p <0.01), while fractional shortening at the LV base increased from 7.7 +/- 4.5% to 9.4 +/- 4.5% (p = 0.045). After MAP, increases were identified in both cardiac output (from 1.54 +/- 0.57 to 1.65 +/- 0.57 1/min) and Emax (from 1.86 +/- 0.9 to 2.41 +/- 1.31 mmHg/ml). CONCLUSION: The data acquired suggest that isolated MAP may have certain benefits on LV dimension/function in acute heart failure, even in the absence of MR. However, further investigations are warranted in a model of chronic heart failure.
17484470	64	86	failing left ventricle	Disease	D006333
17484470	203	225	dilated cardiomyopathy	Disease	D002311
17484470	241	261	mitral regurgitation	Disease	D008944
17484470	263	265	MR	Disease	D008944
17484470	300	302	MR	Disease	D008944
17484470	469	471	MR	Disease	D008944
17484470	576	589	heart failure	Disease	D006333
17484470	951	964	heart failure	Disease	D006333
17484470	980	991	propranolol	Chemical	D011433
17484470	1068	1070	MR	Disease	D008944
17484470	1213	1226	heart failure	Disease	D006333
17484470	2094	2107	heart failure	Disease	D006333
17484470	2132	2134	MR	Disease	D008944
17484470	2204	2217	heart failure	Disease	D006333
17484470	CID	D011433	D006333

17496739|t|Piperacillin/tazobactam-induced seizure rapidly reversed by high flux hemodialysis in a patient on peritoneal dialysis.
17496739|a|Despite popular use of piperacillin, the dire neurotoxicity associated with piperacillin still goes unrecognized, leading to a delay in appropriate management. We report a 57-year-old woman with end-stage renal disease receiving continuous ambulatory peritoneal dialysis (CAPD), who developed slurred speech, tremor, bizarre behavior, progressive mental confusion, and 2 episodes of generalized tonic-clonic seizure (GTCS) after 5 doses of piperacillin/tazobactam (2 g/250 mg) were given for bronchiectasis with secondary infection. The laboratory data revealed normal plasma electrolyte and ammonia levels but leukocytosis. Neurologic examinations showed dysarthria and bilateral Babinski sign. Computed tomography of brain and electroencephalogram were unremarkable. Despite the use of antiepileptic agents, another GTCS episode recurred after the sixth dose of piperacillin/tazobactam. Brain magnetic resonance imaging did not demonstrate acute infarction and organic brain lesions. Initiation of high-flux hemodialysis rapidly reversed the neurologic symptoms within 4 hours. Piperacillin-induced encephalopathy should be considered in any uremic patients with unexplained neurological manifestations. CAPD is inefficient in removing piperacillin, whereas hemodialysis can rapidly terminate the piperacillin-induced encephalopathy.
17496739	0	23	Piperacillin/tazobactam	Chemical	C085143
17496739	32	39	seizure	Disease	D012640
17496739	143	155	piperacillin	Chemical	D010878
17496739	166	179	neurotoxicity	Disease	D020258
17496739	196	208	piperacillin	Chemical	D010878
17496739	315	338	end-stage renal disease	Disease	D007676
17496739	429	435	tremor	Disease	D014202
17496739	474	483	confusion	Disease	D003221
17496739	515	535	tonic-clonic seizure	Disease	D004830
17496739	537	541	GTCS	Disease	D004830
17496739	560	583	piperacillin/tazobactam	Chemical	C085143
17496739	612	626	bronchiectasis	Disease	D001987
17496739	632	651	secondary infection	Disease	D060085
17496739	712	719	ammonia	Chemical	D000641
17496739	731	743	leukocytosis	Disease	D007964
17496739	776	786	dysarthria	Disease	D004401
17496739	938	942	GTCS	Disease	D004830
17496739	984	1007	piperacillin/tazobactam	Chemical	C085143
17496739	1068	1078	infarction	Disease	D007238
17496739	1083	1104	organic brain lesions	Disease	-1
17496739	1200	1212	Piperacillin	Chemical	D010878
17496739	1221	1235	encephalopathy	Disease	D001927
17496739	1264	1270	uremic	Disease	D006463
17496739	1358	1370	piperacillin	Chemical	D010878
17496739	1419	1431	piperacillin	Chemical	D010878
17496739	1440	1454	encephalopathy	Disease	D001927
17496739	CID	C085143	D003221
17496739	CID	C085143	D004830
17496739	CID	C085143	D014202

17543491|t|Frequency of transient ipsilateral vocal cord paralysis in patients undergoing carotid endarterectomy under local anesthesia.
17543491|a|BACKGROUND: Especially because of improvements in clinical neurologic monitoring, carotid endarterectomy done under local anesthesia has become the technique of choice in several centers. Temporary ipsilateral vocal nerve palsies due to local anesthetics have been described, however. Such complications are most important in situations where there is a pre-existing contralateral paralysis. We therefore examined the effect of local anesthesia on vocal cord function to better understand its possible consequences. METHODS: This prospective study included 28 patients undergoing carotid endarterectomy under local anesthesia. Vocal cord function was evaluated before, during, and after surgery (postoperative day 1) using flexible laryngoscopy. Anesthesia was performed by injecting 20 to 40 mL of a mixture of long-acting (ropivacaine) and short-acting (prilocaine) anesthetic. RESULTS: All patients had normal vocal cord function preoperatively. Twelve patients (43%) were found to have intraoperative ipsilateral vocal cord paralysis. It resolved in all cases < or =24 hours. There were no significant differences in operating time or volume or frequency of anesthetic administration in patients with temporary vocal cord paralysis compared with those without. CONCLUSION: Local anesthesia led to temporary ipsilateral vocal cord paralysis in almost half of these patients. Because pre-existing paralysis is of a relevant frequency (up to 3%), a preoperative evaluation of vocal cord function before carotid endarterectomy under local anesthesia is recommended to avoid intraoperative bilateral paralysis. In patients with preoperative contralateral vocal cord paralysis, surgery under general anesthesia should be considered.
17543491	35	55	vocal cord paralysis	Disease	D014826
17543491	336	355	vocal nerve palsies	Disease	D014826
17543491	507	516	paralysis	Disease	D010243
17543491	951	962	ropivacaine	Chemical	C037663
17543491	982	992	prilocaine	Chemical	D011318
17543491	1143	1163	vocal cord paralysis	Disease	D014826
17543491	1341	1361	vocal cord paralysis	Disease	D014826
17543491	1449	1469	vocal cord paralysis	Disease	D014826
17543491	1525	1534	paralysis	Disease	D010243
17543491	1725	1734	paralysis	Disease	D010243
17543491	1780	1800	vocal cord paralysis	Disease	D014826
17543491	CID	D011318	D014826

17572393|t|Neuroprotective effects of melatonin upon the offspring cerebellar cortex in the rat model of BCNU-induced cortical dysplasia.
17572393|a|Cortical dysplasia is a malformation characterized by defects in proliferation, migration and maturation. This study was designed to evaluate the alterations in offspring rat cerebellum induced by maternal exposure to carmustine-[1,3-bis (2-chloroethyl)-1-nitrosoure] (BCNU) and to investigate the effects of exogenous melatonin upon cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses. Pregnant Wistar rats were assigned to five groups: intact-control, saline-control, melatonin-treated, BCNU-exposed and BCNU-exposed plus melatonin. Rats were exposed to BCNU on embryonic day 15 and melatonin was given until delivery. Immuno/histochemistry and electron microscopy were carried out on the offspring cerebellum, and levels of malondialdehyde and superoxide dismutase were determined. Histopathologically, typical findings were observed in the cerebella from the control groups, but the findings consistent with early embryonic development were noted in BCNU-exposed cortical dysplasia group. There was a marked increase in the number of TUNEL positive cells and nestin positive cells in BCNU-exposed group, but a decreased immunoreactivity to glial fibrillary acidic protein, synaptophysin and transforming growth factor beta1 was observed, indicating a delayed maturation, and melatonin significantly reversed these changes. Malondialdehyde level in BCNU-exposed group was higher than those in control groups and melatonin decreased malondialdehyde levels in BCNU group (P<0.01), while there were no significant differences in the superoxide dismutase levels between these groups. These data suggest that exposure of animals to BCNU during pregnancy leads to delayed maturation of offspring cerebellum and melatonin protects the cerebellum against the effects of BCNU.
17572393	27	36	melatonin	Chemical	D008550
17572393	94	98	BCNU	Chemical	D002330
17572393	107	125	cortical dysplasia	Disease	D054220
17572393	127	145	Cortical dysplasia	Disease	D054220
17572393	345	355	carmustine	Chemical	D002330
17572393	357	393	1,3-bis (2-chloroethyl)-1-nitrosoure	Chemical	D002330
17572393	396	400	BCNU	Chemical	D002330
17572393	446	455	melatonin	Chemical	D008550
17572393	472	476	BCNU	Chemical	D002330
17572393	485	503	cortical dysplasia	Disease	D054220
17572393	633	642	melatonin	Chemical	D008550
17572393	652	656	BCNU	Chemical	D002330
17572393	669	673	BCNU	Chemical	D002330
17572393	687	696	melatonin	Chemical	D008550
17572393	719	723	BCNU	Chemical	D002330
17572393	748	757	melatonin	Chemical	D008550
17572393	890	905	malondialdehyde	Chemical	D008315
17572393	910	920	superoxide	Chemical	D013481
17572393	1117	1121	BCNU	Chemical	D002330
17572393	1130	1148	cortical dysplasia	Disease	D054220
17572393	1251	1255	BCNU	Chemical	D002330
17572393	1442	1451	melatonin	Chemical	D008550
17572393	1490	1505	Malondialdehyde	Chemical	D008315
17572393	1515	1519	BCNU	Chemical	D002330
17572393	1578	1587	melatonin	Chemical	D008550
17572393	1598	1613	malondialdehyde	Chemical	D008315
17572393	1624	1628	BCNU	Chemical	D002330
17572393	1696	1706	superoxide	Chemical	D013481
17572393	1793	1797	BCNU	Chemical	D002330
17572393	1871	1880	melatonin	Chemical	D008550
17572393	1928	1932	BCNU	Chemical	D002330
17572393	CID	D002330	D054220

17828434|t|Myo-inositol-1-phosphate (MIP) synthase inhibition: in-vivo study in rats.
17828434|a|Lithium and valproate are the prototypic mood stabilizers and have diverse structures and targets. Both drugs influence inositol metabolism. Lithium inhibits IMPase and valproate inhibits MIP synthase. This study shows that MIP synthase inhibition does not replicate or augment the effects of lithium in the inositol sensitive pilocarpine-induced seizures model. This lack of effects may stem from the low contribution of de-novo synthesis to cellular inositol supply or to the inhibition of the de-novo synthesis by lithium itself.
17828434	0	24	Myo-inositol-1-phosphate	Chemical	C002647
17828434	26	29	MIP	Chemical	C002647
17828434	75	82	Lithium	Chemical	D008094
17828434	87	96	valproate	Chemical	D014635
17828434	195	203	inositol	Chemical	D007294
17828434	216	223	Lithium	Chemical	D008094
17828434	244	253	valproate	Chemical	D014635
17828434	263	266	MIP	Chemical	C002647
17828434	299	302	MIP	Chemical	C002647
17828434	368	375	lithium	Chemical	D008094
17828434	383	391	inositol	Chemical	D007294
17828434	402	413	pilocarpine	Chemical	D010862
17828434	422	430	seizures	Disease	D012640
17828434	527	535	inositol	Chemical	D007294
17828434	592	599	lithium	Chemical	D008094
17828434	CID	D010862	D012640

17879100|t|Non-steroidal anti-inflammatory drugs-associated acute interstitial nephritis with granular tubular basement membrane deposits.
17879100|a|Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure resulting from a variety of insults, including immune complex-mediated tubulo-interstitial injury, but drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) are a far more frequent cause. Overall, as an entity, ATIN remains under-diagnosed, as symptoms resolve spontaneously if the medication is stopped. We report on a 14-year-old boy who developed acute renal failure 2 weeks after aortic valve surgery. He was put on aspirin following surgery and took ibuprofen for fever for nearly a week prior to presentation. He then presented to the emergency department feeling quite ill and was found to have a blood urea nitrogen (BUN) concentration of of 147 mg/dl, creatinine of 15.3 mg/dl and serum potassium of 8.7 mEq/l. Dialysis was immediately initiated. A kidney biopsy showed inflammatory infiltrate consistent with ATIN. However, in the tubular basement membrane (TBM), very intense granular deposits of polyclonal IgG and C3 were noted. He needed dialysis for 2 weeks and was treated successfully with steroids for 6 months. His renal recovery and disappearance of proteinuria took a year. In conclusion, this is a first report of NSAIDs-associated ATIN, showing deposits of granular immune complex present only in the TBM and not in the glomeruli.
17879100	55	77	interstitial nephritis	Disease	D009395
17879100	128	163	Acute tubulo-interstitial nephritis	Disease	C564356
17879100	165	169	ATIN	Disease	C564356
17879100	196	215	acute renal failure	Disease	D058186
17879100	287	313	tubulo-interstitial injury	Disease	D009395
17879100	434	438	ATIN	Disease	C564356
17879100	573	592	acute renal failure	Disease	D058186
17879100	643	650	aspirin	Chemical	D001241
17879100	678	687	ibuprofen	Chemical	D007052
17879100	692	697	fever	Disease	D005334
17879100	827	846	blood urea nitrogen	Chemical	D001806
17879100	848	851	BUN	Chemical	D001806
17879100	884	894	creatinine	Chemical	D003404
17879100	919	928	potassium	Chemical	D011188
17879100	1042	1046	ATIN	Disease	C564356
17879100	1230	1238	steroids	Chemical	D013256
17879100	1293	1304	proteinuria	Disease	D011507
17879100	1377	1381	ATIN	Disease	C564356
17879100	CID	D007052	D058186
17879100	CID	D007052	D009395

17879217|t|Rifampicin-associated segmental necrotizing glomerulonephritis in staphylococcal endocarditis.
17879217|a|Segmental necrotising glomerulonephritis has been reported as complication of rifampicin therapy in patients receiving treatment for tuberculosis. Changing epidemiology of infections such as infective endocarditis (IE) has led to an increase in the use of rifampicin for Staphylococcal infections. We describe a case of a patient with Staphylococcal IE who developed acute renal failure secondary to a segmental necrotising glomerulonephritis while being treated with rifampicin, and review the literature regarding this complication of rifampicin therapy.
17879217	0	10	Rifampicin	Chemical	D012293
17879217	44	62	glomerulonephritis	Disease	D005921
17879217	66	93	staphylococcal endocarditis	Disease	D013203|D004696	staphylococcal|endocarditis
17879217	117	135	glomerulonephritis	Disease	D005921
17879217	173	183	rifampicin	Chemical	D012293
17879217	228	240	tuberculosis	Disease	D014376
17879217	267	277	infections	Disease	D007239
17879217	286	308	infective endocarditis	Disease	D004696
17879217	310	312	IE	Disease	D004696
17879217	351	361	rifampicin	Chemical	D012293
17879217	366	391	Staphylococcal infections	Disease	D013203
17879217	430	447	Staphylococcal IE	Disease	D013203|D004696	Staphylococcal|IE
17879217	462	481	acute renal failure	Disease	D058186
17879217	519	537	glomerulonephritis	Disease	D005921
17879217	563	573	rifampicin	Chemical	D012293
17879217	632	642	rifampicin	Chemical	D012293
17879217	CID	D012293	D058186
17879217	CID	D012293	D005921

17954033|t|Rate of YMDD motif mutants in lamivudine-untreated Iranian patients with chronic hepatitis B virus infection.
17954033|a|BACKGROUND: Lamivudine is used for the treatment of chronic hepatitis B patients. Recent studies show that the YMDD motif mutants (resistant hepatitis B virus) occur as natural genome variability in lamivudine-untreated chronic hepatitis B patients. In this study we aimed to determine the rate of YMDD motif mutants in lamivudine-untreated chronic hepatitis B patients in Iran. PATIENTS AND METHODS: A total of 77 chronic hepatitis B patients who had not been treated with lamivudine were included in the study. Serum samples from patients were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for detection of YMDD motif mutants. All patients were also tested for liver enzymes, anti-HCV, HBeAg, and anti-HBe. RESULTS: Of the 77 patients enrolled in the study, 73% were male and 27% were female. Mean ALT and AST levels were 124.4+/-73.4 and 103.1+/-81 IU/l, respectively. HBeAg was positive in 40% and anti-HBe in 60% of the patients. Anti-HCV was negative in all of them. YMDD motif mutants were not detected in any of the patients despite the liver enzyme levels and the presence of HBeAg or anti-HBe. CONCLUSION: Although the natural occurrence of YMDD motif mutants in lamivudine-untreated patients with chronic hepatitis B has been reported, these mutants were not detected in Iranian lamivudine-untreated chronic hepatitis B patients.
17954033	30	40	lamivudine	Chemical	D019259
17954033	73	108	chronic hepatitis B virus infection	Disease	D019694
17954033	122	132	Lamivudine	Chemical	D019259
17954033	162	181	chronic hepatitis B	Disease	D019694
17954033	251	262	hepatitis B	Disease	D006509
17954033	309	319	lamivudine	Chemical	D019259
17954033	330	349	chronic hepatitis B	Disease	D019694
17954033	430	440	lamivudine	Chemical	D019259
17954033	451	470	chronic hepatitis B	Disease	D019694
17954033	525	544	chronic hepatitis B	Disease	D019694
17954033	584	594	lamivudine	Chemical	D019259
17954033	840	845	HBeAg	Chemical	D006513
17954033	1024	1029	HBeAg	Chemical	D006513
17954033	1237	1242	HBeAg	Chemical	D006513
17954033	1325	1335	lamivudine	Chemical	D019259
17954033	1360	1379	chronic hepatitis B	Disease	D019694
17954033	1442	1452	lamivudine	Chemical	D019259
17954033	1463	1482	chronic hepatitis B	Disease	D019694
17954033	CID	D006513	D019694

18025637|t|Branch retinal vein occlusion and fluoxetine.
18025637|a|A case of branch retinal vein occlusion associated with fluoxetine-induced secondary hypertension is described. Although an infrequent complication of selective serotonin reuptake inhibitor therapy, it is important that ophthalmologists are aware that these agents can cause hypertension because this class of drugs is widely prescribed.
18025637	7	29	retinal vein occlusion	Disease	D012170
18025637	34	44	fluoxetine	Chemical	D005473
18025637	63	85	retinal vein occlusion	Disease	D012170
18025637	102	112	fluoxetine	Chemical	D005473
18025637	131	143	hypertension	Disease	D006973
18025637	207	216	serotonin	Chemical	D012701
18025637	321	333	hypertension	Disease	D006973
18025637	CID	D005473	D012170
18025637	CID	D005473	D006973

18165598|t|The differential effects of bupivacaine and lidocaine on prostaglandin E2 release, cyclooxygenase gene expression and pain in a clinical pain model.
18165598|a|BACKGROUND: In addition to blocking nociceptive input from surgical sites, long-acting local anesthetics might directly modulate inflammation. In the present study, we describe the proinflammatory effects of bupivacaine on local prostaglandin E2 (PGE2) production and cyclooxygenase (COX) gene expression that increases postoperative pain in human subjects. METHODS: Subjects (n = 114) undergoing extraction of impacted third molars received either 2% lidocaine or 0.5% bupivacaine before surgery and either rofecoxib 50 mg or placebo orally 90 min before surgery and for the following 48 h. Oral mucosal biopsies were taken before surgery and 48 h after surgery. After extraction, a microdialysis probe was placed at the surgical site for PGE2 and thromboxane B2 (TXB2) measurements. RESULTS: The bupivacaine/rofecoxib group reported significantly less pain, as assessed by a visual analog scale, compared with the other three treatment groups over the first 4 h. However, the bupivacaine/placebo group reported significantly more pain at 24 h and PGE2 levels during the first 4 h were significantly higher than the other three treatment groups. Moreover, bupivacaine significantly increased COX-2 gene expression at 48 h as compared with the lidocaine/placebo group. Thromboxane levels were not significantly affected by any of the treatments, indicating that the effects seen were attributable to inhibition of COX-2, but not COX-1. CONCLUSIONS: These results suggest that bupivacaine stimulates COX-2 gene expression after tissue injury, which is associated with higher PGE2 production and pain after the local anesthetic effect dissipates.
18165598	28	39	bupivacaine	Chemical	D002045
18165598	44	53	lidocaine	Chemical	D008012
18165598	57	73	prostaglandin E2	Chemical	D015232
18165598	118	122	pain	Disease	D010146
18165598	137	141	pain	Disease	D010146
18165598	278	290	inflammation	Disease	D007249
18165598	357	368	bupivacaine	Chemical	D002045
18165598	378	394	prostaglandin E2	Chemical	D015232
18165598	396	400	PGE2	Chemical	D015232
18165598	469	487	postoperative pain	Disease	D010149
18165598	601	610	lidocaine	Chemical	D008012
18165598	619	630	bupivacaine	Chemical	D002045
18165598	657	666	rofecoxib	Chemical	C116926
18165598	889	893	PGE2	Chemical	D015232
18165598	898	912	thromboxane B2	Chemical	D013929
18165598	914	918	TXB2	Chemical	D013929
18165598	947	958	bupivacaine	Chemical	D002045
18165598	959	968	rofecoxib	Chemical	C116926
18165598	1003	1007	pain	Disease	D010146
18165598	1127	1138	bupivacaine	Chemical	D002045
18165598	1181	1185	pain	Disease	D010146
18165598	1198	1202	PGE2	Chemical	D015232
18165598	1306	1317	bupivacaine	Chemical	D002045
18165598	1393	1402	lidocaine	Chemical	D008012
18165598	1418	1429	Thromboxane	Chemical	D013931
18165598	1625	1636	bupivacaine	Chemical	D002045
18165598	1676	1689	tissue injury	Disease	D017695
18165598	1723	1727	PGE2	Chemical	D015232
18165598	1743	1747	pain	Disease	D010146
18165598	CID	D002045	D007249
18165598	CID	D002045	D010149

18189308|t|p75NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide-induced cystitis.
18189308|a|A role for nerve growth factor (NGF) in contributing to increased voiding frequency and altered sensation from the urinary bladder has been suggested. Previous studies have examined the expression and regulation of tyrosine kinase receptors (Trks) in micturition reflexes with urinary bladder inflammation. The present studies examine the expression and regulation of another receptor known to bind NGF, p75(NTR), after various durations of bladder inflammation induced by cyclophosphamide (CYP). CYP-induced cystitis increased (P < or = 0.001) p75(NTR) expression in the superficial lateral and medial dorsal horn in L1-L2 and L6-S1 spinal segments. The number of p75(NTR)-immunoreactive (-IR) cells in the lumbosacral dorsal root ganglia (DRG) also increased (P < or = 0.05) with CYP-induced cystitis (acute, intermediate, and chronic). Quantitative, real-time polymerase chain reaction also demonstrated significant increases (P < or = 0.01) in p75(NTR) mRNA in DRG with intermediate and chronic CYP-induced cystitis. Retrograde dye-tracing techniques with Fastblue were used to identify presumptive bladder afferent cells in the lumbosacral DRG. In bladder afferent cells in DRG, p75(NTR)-IR was also increased (P < or = 0.01) with cystitis. In addition to increases in p75(NTR)-IR in DRG cell bodies, increases (P < or = 0.001) in pericellular (encircling DRG cells) p75(NTR)-IR in DRG also increased. Confocal analyses demonstrated that pericellular p75(NTR)-IR was not colocalized with the glial marker, glial fibrillary acidic protein (GFAP). These studies demonstrate that p75(NTR) expression in micturition reflexes is present constitutively and modified by bladder inflammation. The functional significance of p75(NTR) expression in micturition reflexes remains to be determined.
18189308	78	94	cyclophosphamide	Chemical	D003520
18189308	103	111	cystitis	Disease	D003556
18189308	328	336	tyrosine	Chemical	D014443
18189308	390	418	urinary bladder inflammation	Disease	D003556
18189308	554	574	bladder inflammation	Disease	D003556
18189308	586	602	cyclophosphamide	Chemical	D003520
18189308	604	607	CYP	Chemical	D003520
18189308	610	613	CYP	Chemical	D003520
18189308	622	630	cystitis	Disease	D003556
18189308	895	898	CYP	Chemical	D003520
18189308	907	915	cystitis	Disease	D003556
18189308	1112	1115	CYP	Chemical	D003520
18189308	1124	1132	cystitis	Disease	D003556
18189308	1349	1357	cystitis	Disease	D003556
18189308	1781	1801	bladder inflammation	Disease	D003556
18189308	CID	D003520	D003556

18340638|t|Azathioprine-induced suicidal erythrocyte death.
18340638|a|BACKGROUND: Azathioprine is widely used as an immunosuppressive drug. The side effects of azathioprine include anemia, which has been attributed to bone marrow suppression. Alternatively, anemia could result from accelerated suicidal erythrocyte death or eryptosis, which is characterized by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. METHODS: The present experiments explored whether azathioprine influences eryptosis. According to annexin V binding, erythrocytes from patients indeed showed a significant increase of PS exposure within 1 week of treatment with azathioprine. In a second series, cytosolic Ca2+ activity (Fluo3 fluorescence), cell volume (forward scatter), and PS-exposure (annexin V binding) were determined by FACS analysis in erythrocytes from healthy volunteers. RESULTS: Exposure to azathioprine (> or =2 microg/mL) for 48 hours increased cytosolic Ca2+ activity and annexin V binding and decreased forward scatter. The effect of azathioprine on both annexin V binding and forward scatter was significantly blunted in the nominal absence of extracellular Ca2+. CONCLUSIONS: Azathioprine triggers suicidal erythrocyte death, an effect presumably contributing to azathioprine-induced anemia.
18340638	0	12	Azathioprine	Chemical	D001379
18340638	61	73	Azathioprine	Chemical	D001379
18340638	139	151	azathioprine	Chemical	D001379
18340638	160	166	anemia	Disease	D000740
18340638	237	243	anemia	Disease	D000740
18340638	353	371	phosphatidylserine	Chemical	D010718
18340638	373	375	PS	Chemical	D010718
18340638	477	489	azathioprine	Chemical	D001379
18340638	611	613	PS	Chemical	D010718
18340638	655	667	azathioprine	Chemical	D001379
18340638	699	701	Ca	Chemical	D002118
18340638	714	719	Fluo3	Chemical	C059715
18340638	770	772	PS	Chemical	D010718
18340638	897	909	azathioprine	Chemical	D001379
18340638	963	965	Ca	Chemical	D002118
18340638	1044	1056	azathioprine	Chemical	D001379
18340638	1169	1171	Ca	Chemical	D002118
18340638	1188	1200	Azathioprine	Chemical	D001379
18340638	1275	1287	azathioprine	Chemical	D001379
18340638	1296	1302	anemia	Disease	D000740
18340638	CID	D001379	D000740

18399341|t|Clinical comparison of cardiorespiratory effects during unilateral and conventional spinal anaesthesia.
18399341|a|BACKGROUND: Spinal anaesthesia is widely employed in clinical practice but has the main drawback of post-spinal block hypotension. Efforts must therefore continue to be made to obviate this setback OBJECTIVE: To evaluate the cardiovascular and respiratory changes during unilateral and conventional spinal anaesthesia. METHODS: With ethical approval, we studied 74 American Society of Anesthesiologists (ASA), physical status class 1 and 2 patients scheduled for elective unilateral lower limb surgery. Patients were randomly allocated into one of two groups: lateral and conventional spinal anaesthesia groups. In the lateral position with operative side down, patients recived 10 mg (2mls) of 0.5% hyperbaric bupivacaine through a 25-gauge spinal needle. Patients in the unilateral group were maintained in the lateral position for 15 minutes following spinal injection while those in the conventional group were turned supine immediately after injection. Blood pressure, heart rate, respiratory rate and oxygen saturation were monitored over 1 hour. RESULTS: Three patients (8.1%) in the unilateral group and 5 (13.5%) in the conventional group developed hypotension, P= 0.71. Four (10.8%) patients in the conventional group and 1 (2.7%) in the unilateral group, P= 0.17 required epinephrine infusion to treat hypotension. Patients in the conventional group had statistically significant greater fall in the systolic blood pressures at 15, 30 and 45 minutes when compared to the baseline (P= 0.003, 0.001 and 0.004). The mean respiratory rate and oxygen saturations in the two groups were similar. CONCLUSION: Compared to conventional spinal anaesthesia, unilateral spinal anaesthesia was associated with fewer cardiovascular perturbations. Also, the type of spinal block instituted affected neither the respiratory rate nor the arterial oxygen saturation.
18399341	222	233	hypotension	Disease	D007022
18399341	815	826	bupivacaine	Chemical	D002045
18399341	1111	1117	oxygen	Chemical	D010100
18399341	1262	1273	hypotension	Disease	D007022
18399341	1387	1398	epinephrine	Chemical	D004837
18399341	1417	1428	hypotension	Disease	D007022
18399341	1654	1660	oxygen	Chemical	D010100
18399341	1945	1951	oxygen	Chemical	D010100
18399341	CID	D002045	D007022

18422462|t|Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients.
18422462|a|To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/microL) and peripheral neuropathy (9.0% and 348 cells/microL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available.
18422462	66	78	HIV-infected	Disease	D015658
18422462	249	261	HIV-infected	Disease	D015658
18422462	326	338	HIV-infected	Disease	D015658
18422462	528	531	3TC	Chemical	D019259
18422462	534	537	d4T	Chemical	D018119
18422462	540	550	nevirapine	Chemical	D019829
18422462	552	555	NVP	Chemical	D019829
18422462	566	576	zidovudine	Chemical	D015215
18422462	578	581	AZT	Chemical	D015215
18422462	585	588	3TC	Chemical	D019259
18422462	591	594	NVP	Chemical	D019829
18422462	604	607	3TC	Chemical	D019259
18422462	610	613	d4T	Chemical	D018119
18422462	616	625	efavirenz	Chemical	C098320
18422462	627	630	EFV	Chemical	C098320
18422462	645	648	AZT	Chemical	D015215
18422462	651	654	3TC	Chemical	D019259
18422462	657	660	EFV	Chemical	C098320
18422462	737	741	rash	Disease	D005076
18422462	777	798	peripheral neuropathy	Disease	D010523
18422462	851	857	anemia	Disease	D000740
18422462	940	949	hepatitis	Disease	D056486
18422462	960	968	jaundice	Disease	D007565
18422462	974	981	alanine	Chemical	D000409
18422462	1129	1144	lactic acidosis	Disease	D000140
18422462	1201	1231	immune reconstitution syndrome	Disease	D054019
18422462	1289	1292	NVP	Chemical	D019829
18422462	1346	1350	rash	Disease	D005076
18422462	1355	1358	d4T	Chemical	D018119
18422462	1383	1404	peripheral neuropathy	Disease	D010523
18422462	1417	1423	Anemia	Disease	D000740
18422462	1428	1437	hepatitis	Disease	D056486
18422462	1535	1545	toxicities	Disease	D064420
18422462	CID	D018119	D010523
18422462	CID	D019829	D005076

18450790|t|Thalidomide and sensory neurotoxicity: a neurophysiological study.
18450790|a|BACKGROUND: Recent studies confirmed a high incidence of sensory axonal neuropathy in patients treated with different doses of thalidomide. The study's aims were to measure variations in sural nerve sensory action potential (SAP) amplitude in patients with refractory cutaneous lupus erythematosus (CLE) treated with thalidomide and use these findings to identify the neurotoxic potential of thalidomide and the recovery capacity of sensory fibres after discontinuation of treatment. PATIENTS AND METHODS: Clinical and electrophysiological data in 12 female patients with CLE during treatment with thalidomide and up to 47 months after discontinuation of treatment were analysed. Sural nerve SAP amplitude reduction > or =40% was the criteria for discontinuing therapy. RESULTS: During treatment, 11 patients showed a reduction in sural nerve SAP amplitude compared to baseline values (9 with a reduction > or =50% and 2 <50%). One patient showed no changes in SAP amplitude. Five patients complained of paresthesias and leg cramps. After thalidomide treatment, sural SAP amplitude recovered in 3 patients. At detection of reduction in sural nerve SAP amplitude, the median thalidomide cumulative dose was 21.4 g. The threshold neurotoxic dosage is lower than previously reported. CONCLUSIONS: Sural nerve SAP amplitude reduction is a reliable and sensitive marker of degeneration and recovery of sensory fibres. This electrophysiological parameter provides information about subclinical neurotoxic potential of thalidomide but is not helpful in predicting the appearance of sensory symptoms.
18450790	0	11	Thalidomide	Chemical	D013792
18450790	16	37	sensory neurotoxicity	Disease	D010523
18450790	124	149	sensory axonal neuropathy	Disease	D010523
18450790	194	205	thalidomide	Chemical	D013792
18450790	335	364	cutaneous lupus erythematosus	Disease	D008178
18450790	366	369	CLE	Disease	D008178
18450790	384	395	thalidomide	Chemical	D013792
18450790	435	445	neurotoxic	Disease	D020258
18450790	459	470	thalidomide	Chemical	D013792
18450790	639	642	CLE	Disease	D008178
18450790	665	676	thalidomide	Chemical	D013792
18450790	1071	1083	paresthesias	Disease	D010292
18450790	1092	1098	cramps	Disease	D009120
18450790	1106	1117	thalidomide	Chemical	D013792
18450790	1241	1252	thalidomide	Chemical	D013792
18450790	1295	1305	neurotoxic	Disease	D020258
18450790	1555	1565	neurotoxic	Disease	D020258
18450790	1579	1590	thalidomide	Chemical	D013792
18450790	CID	D013792	D009120
18450790	CID	D013792	D010523
18450790	CID	D013792	D010292

18801087|t|Amiodarone-related pulmonary mass and unique membranous glomerulonephritis in a patient with valvular heart disease: Diagnostic pitfall and new findings.
18801087|a|Amiodarone is an anti-arrhythmic drug for life-threatening tachycardia, but various adverse effects have been reported. Reported herein is an autopsy case of valvular heart disease, in a patient who developed a lung mass (1.5 cm in diameter) and proteinuria (2.76 g/day) after treatment with amiodarone for a long time. The lung mass was highly suspected to be lung cancer on CT and positron emission tomography, but histologically the lesion was composed of lymphoplasmacytic infiltrates in alveolar walls and intra-alveolar accumulation of foamy macrophages containing characteristic myelinoid bodies, indicating that it was an amiodarone-related lesion. In addition, the lung tissue had unevenly distributed hemosiderin deposition, and abnormally tortuous capillaries were seen in the mass and in heavily hemosiderotic lung portions outside the mass. In the kidneys, glomeruli had membrane spikes, prominent swelling of podocytes and subepithelial deposits, which were sometimes large and hump-like. Autoimmune diseases, viral hepatitis, malignant neoplasms or other diseases with a known relationship to membranous glomerulonephritis were not found. The present case highlights the possibility that differential diagnosis between an amiodarone-related pulmonary lesion and a neoplasm can be very difficult radiologically, and suggests that membranous glomerulonephritis might be another possible complication of amiodarone treatment.
18801087	0	10	Amiodarone	Chemical	D000638
18801087	19	33	pulmonary mass	Disease	D055370
18801087	45	74	membranous glomerulonephritis	Disease	D015433
18801087	93	115	valvular heart disease	Disease	D006349
18801087	154	164	Amiodarone	Chemical	D000638
18801087	176	186	arrhythmic	Disease	D001145
18801087	213	224	tachycardia	Disease	D013610
18801087	312	334	valvular heart disease	Disease	D006349
18801087	365	374	lung mass	Disease	D055370
18801087	400	411	proteinuria	Disease	D011507
18801087	446	456	amiodarone	Chemical	D000638
18801087	478	487	lung mass	Disease	D055370
18801087	515	526	lung cancer	Disease	D008175
18801087	784	794	amiodarone	Chemical	D000638
18801087	865	876	hemosiderin	Disease	D006486
18801087	962	975	hemosiderotic	Disease	D006486
18801087	1157	1176	Autoimmune diseases	Disease	D001327
18801087	1178	1193	viral hepatitis	Disease	D006525
18801087	1205	1214	neoplasms	Disease	D009369
18801087	1262	1291	membranous glomerulonephritis	Disease	D015433
18801087	1391	1401	amiodarone	Chemical	D000638
18801087	1410	1426	pulmonary lesion	Disease	D055370
18801087	1433	1441	neoplasm	Disease	D009369
18801087	1498	1527	membranous glomerulonephritis	Disease	D015433
18801087	1570	1580	amiodarone	Chemical	D000638
18801087	CID	D000638	D055370
18801087	CID	D000638	D015433
18801087	CID	D000638	D006486

18945509|t|Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: a matched case-control study.
18945509|a|AIMS: This study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas. METHODS: In type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls. RESULTS: The 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3-4.3, P=0.004) with glibenclamide; 2-fold (0.9-4.6, P=0.099) with glipizide; 2.9-fold (1.6-5.1, P=0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7-1.7, P=0.385) with glimepiride, 0.4-fold (0.7-1.3, P=0.192) with gliclazide, and 0.4-fold (0.7-1.1, P=0.09) with either. CONCLUSIONS: Initiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents.
18945509	8	31	coronary artery disease	Disease	D003324
18945509	56	69	sulphonylurea	Chemical	-1
18945509	97	112	type 2 diabetes	Disease	D003924
18945509	201	224	coronary artery disease	Disease	D003324
18945509	226	229	CAD	Disease	D003324
18945509	268	283	type 2 diabetes	Disease	D003924
18945509	299	313	sulphonylureas	Chemical	-1
18945509	327	342	type 2 diabetic	Disease	D003924
18945509	373	376	CAD	Disease	D003324
18945509	455	458	CAD	Disease	D003324
18945509	475	483	diabetes	Disease	D003920
18945509	578	581	CAD	Disease	D003324
18945509	640	643	CAD	Disease	D003324
18945509	733	746	glibenclamide	Chemical	D005905
18945509	779	788	glipizide	Chemical	D005913
18945509	854	863	metformin	Chemical	D008687
18945509	919	930	glimepiride	Chemical	C057619
18945509	965	975	gliclazide	Chemical	D005907
18945509	1058	1073	type 2 diabetes	Disease	D003924
18945509	1079	1092	glibenclamide	Chemical	D005905
18945509	1096	1105	glipizide	Chemical	D005913
18945509	1143	1146	CAD	Disease	D003324
18945509	1164	1174	gliclazide	Chemical	D005907
18945509	1178	1189	glimepiride	Chemical	C057619
18945509	1282	1296	sulphonylureas	Chemical	-1
18945509	CID	D005905	D003324

18987260|t|Reduced progression of adriamycin nephropathy in spontaneously hypertensive rats treated by losartan.
18987260|a|BACKGROUND: The aim of the study was to investigate the antihypertensive effects of angiotensin II type-1 receptor blocker, losartan, and its potential in slowing down renal disease progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. METHODS: Six-month-old female SHR were randomly selected in six groups. Two control groups (SH(6), SH(12)) received vehicle. Groups ADR(6), ADR+LOS(6) and ADR(12), and ADR+LOS(12) received ADR (2 mg/kg/b.w. i.v.) twice in a 3-week interval. Group ADR+LOS(6) received losartan (10 mg/kg/b.w./day by gavages) for 6 weeks and group ADR+LOS(12) for 12 weeks after second injection of ADR. Animals were killed after 6 or 12 weeks, respectively. Haemodynamic measurements were performed on anaesthetized animals, blood and urine samples were taken for biochemical analysis and the left kidney was processed for morphological studies. RESULTS: Short-term losartan treatment, besides antihypertensive effect, improved glomerular filtration rate and ameliorated glomerulosclerosis resulting in decreased proteinuria. Prolonged treatment with losartan showed further reduction of glomerulosclerosis associated with reduced progression of tubular atrophy and interstitial fibrosis, thus preventing heavy proteinuria and chronic renal failure. Losartan reduced uraemia and increased urea clearance in advanced ADR nephropathy in SHR. Histological examination showed that losartan could prevent tubular atrophy, interstitial infiltration and fibrosis in ADR nephropathy. CONCLUSION: Losartan reduces the rate of progression of ADR-induced focal segmental glomerulosclerosis to end-stage renal disease in SHR.
18987260	23	33	adriamycin	Chemical	D004317
18987260	34	45	nephropathy	Disease	D007674
18987260	63	75	hypertensive	Disease	D006973
18987260	92	100	losartan	Chemical	D019808
18987260	186	200	angiotensin II	Chemical	D000804
18987260	226	234	losartan	Chemical	D019808
18987260	270	283	renal disease	Disease	D007674
18987260	313	325	hypertensive	Disease	D006973
18987260	342	352	adriamycin	Chemical	D004317
18987260	354	357	ADR	Chemical	D004317
18987260	359	370	nephropathy	Disease	D007674
18987260	504	507	ADR	Chemical	D004317
18987260	512	515	ADR	Chemical	D004317
18987260	516	519	LOS	Chemical	D019808
18987260	527	530	ADR	Chemical	D004317
18987260	540	543	ADR	Chemical	D004317
18987260	544	547	LOS	Chemical	D019808
18987260	561	564	ADR	Chemical	D004317
18987260	619	622	ADR	Chemical	D004317
18987260	623	626	LOS	Chemical	D019808
18987260	639	647	losartan	Chemical	D019808
18987260	701	704	ADR	Chemical	D004317
18987260	705	708	LOS	Chemical	D019808
18987260	752	755	ADR	Chemical	D004317
18987260	1020	1028	losartan	Chemical	D019808
18987260	1125	1143	glomerulosclerosis	Disease	D005921
18987260	1167	1178	proteinuria	Disease	D011507
18987260	1205	1213	losartan	Chemical	D019808
18987260	1242	1260	glomerulosclerosis	Disease	D005921
18987260	1308	1315	atrophy	Disease	D001284
18987260	1320	1341	interstitial fibrosis	Disease	D005355
18987260	1365	1376	proteinuria	Disease	D011507
18987260	1381	1402	chronic renal failure	Disease	D007676
18987260	1404	1412	Losartan	Chemical	D019808
18987260	1421	1428	uraemia	Disease	D014511
18987260	1443	1447	urea	Chemical	D014508
18987260	1470	1473	ADR	Chemical	D004317
18987260	1474	1485	nephropathy	Disease	D007674
18987260	1531	1539	losartan	Chemical	D019808
18987260	1562	1569	atrophy	Disease	D001284
18987260	1601	1609	fibrosis	Disease	D005355
18987260	1613	1616	ADR	Chemical	D004317
18987260	1617	1628	nephropathy	Disease	D007674
18987260	1642	1650	Losartan	Chemical	D019808
18987260	1686	1689	ADR	Chemical	D004317
18987260	1698	1732	focal segmental glomerulosclerosis	Disease	D005923
18987260	1736	1759	end-stage renal disease	Disease	D007676
18987260	CID	D004317	D014511
18987260	CID	D004317	D005923
18987260	CID	D004317	D011507

19020118|t|The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients.
19020118|a|BACKGROUND: Our aim was to investigate postoperative complications and mortality after administration of aprotinin compared to tranexamic acid in an unselected, consecutive cohort. METHODS: Perioperative data from consecutive cardiac surgery patients were prospectively collected between September 2005 and June 2006 in a university-affiliated clinic (n = 1188). During the first 5 mo, 596 patients received aprotinin (Group A); in the next 5 mo, 592 patients were treated with tranexamic acid (Group T). Except for antifibrinolytic therapy, the anesthetic and surgical protocols remained unchanged. RESULTS: The pre- and intraoperative variables were comparable between the treatment groups. Postoperatively, a significantly higher incidence of seizures was found in Group T (4.6% vs 1.2%, P < 0.001). This difference was also significant in the primary valve surgery and the high risk surgery subgroups (7.9% vs 1.2%, P = 0.003; 7.3% vs 2.4%, P = 0.035, respectively). Persistent atrial fibrillation (7.9% vs 2.3%, P = 0.020) and renal failure (9.7% vs 1.7%, P = 0.002) were also more common in Group T, in the primary valve surgery subgroup. On the contrary, among primary coronary artery bypass surgery patients, there were more acute myocardial infarctions and renal dysfunction in Group A (5.8% vs 2.0%, P = 0.027; 22.5% vs 15.2%, P = 0.036, respectively). The 1-yr mortality was significantly higher after aprotinin treatment in the high risk surgery group (17.7% vs 9.8%, P = 0.034). CONCLUSION: Both antifibrinolytic drugs bear the risk of adverse outcome depending on the type of cardiac surgery. Administration of aprotinin should be avoided in coronary artery bypass graft and high risk patients, whereas administration of tranexamic acid is not recommended in valve surgery.
19020118	27	42	tranexamic acid	Chemical	D014148
19020118	241	256	tranexamic acid	Chemical	D014148
19020118	592	607	tranexamic acid	Chemical	D014148
19020118	860	868	seizures	Disease	D012640
19020118	1146	1159	renal failure	Disease	D051437
19020118	1353	1375	myocardial infarctions	Disease	D009203
19020118	1380	1397	renal dysfunction	Disease	D007674
19020118	1849	1864	tranexamic acid	Chemical	D014148
19020118	CID	D014148	D051437
19020118	CID	D014148	D012640

19108278|t|The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias.
19108278|a|1. The optical isomers of propranolol have been compared for their beta-blocking and antiarrhythmic activities.2. In blocking the positive inotropic and chronotropic responses to isoprenaline, (+)-propranolol had less than one hundredth the potency of (-)-propranolol. At dose levels of (+)-propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of the PR interval of the electrocardiogram.3. The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (-)-propranolol. (+)-Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose.4. Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea-pigs.5. The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer.6. Both isomers of propranolol were capable of preventing adrenaline-induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (-)-propranolol was 0.09+/-0.02 mg/kg whereas that of (+)-propranolol was 4.2+/-1.2 mg/kg. At the effective dose level of (+)-propranolol there was a significant prolongation of the PR interval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline.7. Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of (-)-propranolol was significantly smaller than that of (+)-propranolol in both species but much higher than that required to produce evidence of beta-blockade.8. The implications of these results are discussed.
19108278	52	63	propranolol	Chemical	D011433
19108278	85	104	cardiac arrhythmias	Disease	D001145
19108278	132	143	propranolol	Chemical	D011433
19108278	285	297	isoprenaline	Chemical	D007545
19108278	303	314	propranolol	Chemical	D011433
19108278	362	373	propranolol	Chemical	D011433
19108278	397	408	propranolol	Chemical	D011433
19108278	443	455	isoprenaline	Chemical	D007545
19108278	568	580	isoprenaline	Chemical	D007545
19108278	617	624	glucose	Chemical	D005947
19108278	626	633	lactate	Chemical	D019344
19108278	643	654	fatty acids	Chemical	D005227
19108278	680	691	propranolol	Chemical	D011433
19108278	697	708	Propranolol	Chemical	D011433
19108278	726	736	fatty acid	Chemical	D005227
19108278	799	806	lactate	Chemical	D019344
19108278	811	818	glucose	Chemical	D005947
19108278	838	849	propranolol	Chemical	D011433
19108278	954	965	propranolol	Chemical	D011433
19108278	1095	1103	procaine	Chemical	D011343
19108278	1194	1205	propranolol	Chemical	D011433
19108278	1233	1243	adrenaline	Chemical	D004837
19108278	1252	1271	cardiac arrhythmias	Disease	D001145
19108278	1299	1308	halothane	Chemical	D006221
19108278	1335	1346	propranolol	Chemical	D011433
19108278	1389	1400	propranolol	Chemical	D011433
19108278	1457	1468	propranolol	Chemical	D011433
19108278	1563	1574	arrhythmias	Disease	D001145
19108278	1636	1646	adrenaline	Chemical	D004837
19108278	1666	1677	propranolol	Chemical	D011433
19108278	1709	1732	ventricular tachycardia	Disease	D017180
19108278	1743	1750	ouabain	Chemical	D010042
19108278	1799	1810	propranolol	Chemical	D011433
19108278	1854	1865	propranolol	Chemical	D011433
19108278	CID	D006221	D001145
19108278	CID	D010042	D017180
19108278	CID	D004837	D001145

19139825|t|Topotecan in combination with radiotherapy in unresectable glioblastoma: a phase 2 study.
19139825|a|Improving glioblastoma multiforme (GBM) treatment with radio-chemotherapy remains a challenge. Topotecan is an attractive option as it exhibits growth inhibition of human glioma as well as brain penetration. The present study assessed the combination of radiotherapy (60 Gy/30 fractions/40 days) and topotecan (0.9 mg/m(2)/day on days 1-5 on weeks 1, 3 and 5) in 50 adults with histologically proven and untreated GBM. The incidence of non-hematological toxicities was low and grade 3-4 hematological toxicities were reported in 20 patients (mainly lymphopenia and neutropenia). Partial response and stabilization rates were 2% and 32%, respectively, with an overall time to progression of 12 weeks. One-year overall survival (OS) rate was 42%, with a median OS of 40 weeks. Topotecan in combination with radiotherapy was well tolerated. However, while response and stabilization concerned one-third of the patients, the study did not show increased benefits in terms of survival in patients with unresectable GBM.
19139825	0	9	Topotecan	Chemical	D019772
19139825	59	71	glioblastoma	Disease	D005909
19139825	100	123	glioblastoma multiforme	Disease	D005909
19139825	125	128	GBM	Disease	D005909
19139825	185	194	Topotecan	Chemical	D019772
19139825	261	267	glioma	Disease	D005910
19139825	390	399	topotecan	Chemical	D019772
19139825	504	507	GBM	Disease	D005909
19139825	544	554	toxicities	Disease	D064420
19139825	591	601	toxicities	Disease	D064420
19139825	639	650	lymphopenia	Disease	D008231
19139825	655	666	neutropenia	Disease	D009503
19139825	865	874	Topotecan	Chemical	D019772
19139825	1100	1103	GBM	Disease	D005909
19139825	CID	D019772	D009503
19139825	CID	D019772	D008231

19154241|t|Long-term lithium therapy leading to hyperparathyroidism: a case report.
19154241|a|PURPOSE: This paper reviews the effect of chronic lithium therapy on serum calcium level and parathyroid glands, its pathogenesis, and treatment options. We examined the case of a lithium-treated patient who had recurrent hypercalcemia to better understand the disease process. CONCLUSION: Primary hyperparathyroidism is a rare but potentially life-threatening side effect of long-term lithium therapy. Careful patient selection and long-term follow-up can reduce morbidity. PRACTICAL IMPLICATIONS: As much as 15% of lithium-treated patients become hypercalcemic. By routinely monitoring serum calcium levels, healthcare providers can improve the quality of life of this patient group.
19154241	10	17	lithium	Chemical	D008094
19154241	37	56	hyperparathyroidism	Disease	D006961
19154241	123	130	lithium	Chemical	D008094
19154241	148	155	calcium	Chemical	D002118
19154241	253	260	lithium	Chemical	D008094
19154241	295	308	hypercalcemia	Disease	D006934
19154241	363	390	Primary hyperparathyroidism	Disease	D049950
19154241	459	466	lithium	Chemical	D008094
19154241	590	597	lithium	Chemical	D008094
19154241	622	635	hypercalcemic	Disease	D006934
19154241	667	674	calcium	Chemical	D002118
19154241	CID	D008094	D006961
19154241	CID	D008094	D006934

19178808|t|Comparison of laryngeal mask with endotracheal tube for anesthesia in endoscopic sinus surgery.
19178808|a|BACKGROUND: The purpose of this study was to compare surgical conditions, including the amount of intraoperative bleeding as well as intraoperative blood pressure, during functional endoscopic sinus surgery (FESS) using flexible reinforced laryngeal mask airway (FRLMA) versus endotracheal tube (ETT) in maintaining controlled hypotension anesthesia induced by propofol-remifentanil total i.v. anesthesia (TIVA). METHODS: Sixty normotensive American Society of Anesthesiologists I-II adult patients undergoing FESS under controlled hypotension anesthesia caused by propofol-remifentanil-TIVA were randomly assigned into two groups: group I, FRLMA; group II, ETT. Hemorrhage was measured and the visibility of the operative field was evaluated according to a six-point scale. RESULTS: Controlled hypotension was achieved within a shorter period using laryngeal mask using lower rates of remifentanil infusion and lower total dose of remifentanil. CONCLUSION: In summary, our results indicate that airway management using FRLMA during controlled hypotension anesthesia provided better surgical conditions in terms of quality of operative field and blood loss and allowed for convenient induced hypotension with low doses of remifentanil during TIVA in patients undergoing FESS.
19178808	209	217	bleeding	Disease	D006470
19178808	423	434	hypotension	Disease	D007022
19178808	457	465	propofol	Chemical	D015742
19178808	466	478	remifentanil	Chemical	C071741
19178808	628	639	hypotension	Disease	D007022
19178808	661	669	propofol	Chemical	D015742
19178808	670	682	remifentanil	Chemical	C071741
19178808	759	769	Hemorrhage	Disease	D006470
19178808	891	902	hypotension	Disease	D007022
19178808	982	994	remifentanil	Chemical	C071741
19178808	1028	1040	remifentanil	Chemical	C071741
19178808	1140	1151	hypotension	Disease	D007022
19178808	1288	1299	hypotension	Disease	D007022
19178808	1318	1330	remifentanil	Chemical	C071741
19178808	CID	D015742	D007022
19178808	CID	C071741	D007022

19184102|t|Nonalcoholic fatty liver disease during valproate therapy.
19184102|a|Valproic acid (VPA) is effective for the treatment of many types of epilepsy, but its use can be associated with an increase in body weight. We report a case of nonalcoholic fatty liver disease (NAFLD) arising in a child who developed obesity during VPA treatment. Laboratory data revealed hyperinsulinemia with insulin resistance. After the withdrawal of VPA therapy, our patient showed a significant weight loss, a decrease of body mass index, and normalization of metabolic and endocrine parameters; moreover, ultrasound measurements showed a complete normalization. The present case suggests that obesity, hyperinsulinemia, insulin resistance, and long-term treatment with VPA may be all associated with the development of NAFLD; this side effect is reversible after VPA withdrawal.
19184102	0	32	Nonalcoholic fatty liver disease	Disease	D065626
19184102	40	49	valproate	Chemical	D014635
19184102	59	72	Valproic acid	Chemical	D014635
19184102	74	77	VPA	Chemical	D014635
19184102	127	135	epilepsy	Disease	D004827
19184102	220	252	nonalcoholic fatty liver disease	Disease	D065626
19184102	254	259	NAFLD	Disease	D065626
19184102	294	301	obesity	Disease	D009765
19184102	309	312	VPA	Chemical	D014635
19184102	349	365	hyperinsulinemia	Disease	D006946
19184102	371	389	insulin resistance	Disease	D007333
19184102	415	418	VPA	Chemical	D014635
19184102	461	472	weight loss	Disease	D015431
19184102	660	667	obesity	Disease	D009765
19184102	669	685	hyperinsulinemia	Disease	D006946
19184102	687	705	insulin resistance	Disease	D007333
19184102	736	739	VPA	Chemical	D014635
19184102	786	791	NAFLD	Disease	D065626
19184102	830	833	VPA	Chemical	D014635
19184102	CID	D014635	D009765
19184102	CID	D014635	D006946
19184102	CID	D014635	D065626
19184102	CID	D014635	D007333

19263707|t|Carbimazole induced ANCA positive vasculitis.
19263707|a|Anti-thyroid drugs, like carbimazole and propylthiouracil (PTU) are commonly prescribed for the treatment of hyperthyroidism. One should be aware of the side effects of antithyroid medications. Antineutrophil cytoplasmic antibody (ANCA)--associated vasculitis is a potentially life-threatening adverse effect of antithyroidmedications. We report a patient with Graves' disease who developed ANCA positive carbimazole induced vasculitis. The episode was characterized by a vasculitic skin rash associated with large joint arthritis, pyrexia and parotiditis but no renal or pulmonary involvement. He was referred to us for neurological evaluation because he had difficulty in getting up from squatting position and was suspected to have myositis. Carbimazole and methimazole have a lower incidence of reported ANCA positive side effects than PUT. To the best of our knowledge this is the first ANCA positive carbimazole induced vasculitis case reported from India.
19263707	0	11	Carbimazole	Chemical	D002231
19263707	20	44	ANCA positive vasculitis	Disease	D056648
19263707	46	64	Anti-thyroid drugs	Chemical	D013956
19263707	71	82	carbimazole	Chemical	D002231
19263707	87	103	propylthiouracil	Chemical	D011441
19263707	105	108	PTU	Chemical	D011441
19263707	155	170	hyperthyroidism	Disease	D006980
19263707	215	238	antithyroid medications	Chemical	D013956
19263707	240	305	Antineutrophil cytoplasmic antibody (ANCA)--associated vasculitis	Disease	D056648
19263707	358	380	antithyroidmedications	Chemical	D013956
19263707	407	422	Graves' disease	Disease	D006111
19263707	451	462	carbimazole	Chemical	D002231
19263707	471	481	vasculitis	Disease	D014657
19263707	518	528	vasculitic	Disease	D014657
19263707	529	538	skin rash	Disease	D005076
19263707	567	576	arthritis	Disease	D001168
19263707	578	585	pyrexia	Disease	D005334
19263707	590	601	parotiditis	Disease	D010309
19263707	781	789	myositis	Disease	D009220
19263707	791	802	Carbimazole	Chemical	D002231
19263707	807	818	methimazole	Chemical	D008713
19263707	952	963	carbimazole	Chemical	D002231
19263707	972	982	vasculitis	Disease	D014657
19263707	CID	D013956	D010309
19263707	CID	D013956	D056648
19263707	CID	D013956	D001168
19263707	CID	D002231	D010309
19263707	CID	D002231	D005334
19263707	CID	D013956	D005334
19263707	CID	D002231	D001168
19263707	CID	D002231	D056648

19293073|t|Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force.
19293073|a|BACKGROUND: Coronary heart disease and cerebrovascular disease are leading causes of death in the United States. In 2002, the U.S. Preventive Services Task Force (USPSTF) strongly recommended that clinicians discuss aspirin with adults who are at increased risk for coronary heart disease. PURPOSE: To determine the benefits and harms of taking aspirin for the primary prevention of myocardial infarctions, strokes, and death. DATA SOURCES: MEDLINE and Cochrane Library (search dates, 1 January 2001 to 28 August 2008), recent systematic reviews, reference lists of retrieved articles, and suggestions from experts. STUDY SELECTION: English-language randomized, controlled trials (RCTs); case-control studies; meta-analyses; and systematic reviews of aspirin versus control for the primary prevention of cardiovascular disease (CVD) were selected to answer the following questions: Does aspirin decrease coronary heart events, strokes, death from coronary heart events or stroke, or all-cause mortality in adults without known CVD? Does aspirin increase gastrointestinal bleeding or hemorrhagic strokes? DATA EXTRACTION: All studies were reviewed, abstracted, and rated for quality by using predefined USPSTF criteria. DATA SYNTHESIS: New evidence from 1 good-quality RCT, 1 good-quality meta-analysis, and 2 fair-quality subanalyses of RCTs demonstrates that aspirin use reduces the number of CVD events in patients without known CVD. Men in these studies experienced fewer myocardial infarctions and women experienced fewer ischemic strokes. Aspirin does not seem to affect CVD mortality or all-cause mortality in either men or women. The use of aspirin for primary prevention increases the risk for major bleeding events, primarily gastrointestinal bleeding events, in both men and women. Men have an increased risk for hemorrhagic strokes with aspirin use. A new RCT and meta-analysis suggest that the risk for hemorrhagic strokes in women is not statistically significantly increased. LIMITATIONS: New evidence on aspirin for the primary prevention of CVD is limited. The dose of aspirin used in the RCTs varied, which prevented the estimation of the most appropriate dose for primary prevention. Several of the RCTs were conducted within populations of health professionals, which potentially limits generalizability. CONCLUSION: Aspirin reduces the risk for myocardial infarction in men and strokes in women. Aspirin use increases the risk for serious bleeding events.
19293073	0	7	Aspirin	Chemical	D001241
19293073	144	166	Coronary heart disease	Disease	D003327
19293073	171	194	cerebrovascular disease	Disease	D002561
19293073	348	355	aspirin	Chemical	D001241
19293073	398	420	coronary heart disease	Disease	D003327
19293073	477	484	aspirin	Chemical	D001241
19293073	515	537	myocardial infarctions	Disease	D009203
19293073	539	546	strokes	Disease	D020521
19293073	883	890	aspirin	Chemical	D001241
19293073	936	958	cardiovascular disease	Disease	D002318
19293073	960	963	CVD	Disease	D002318
19293073	1019	1026	aspirin	Chemical	D001241
19293073	1059	1066	strokes	Disease	D020521
19293073	1104	1110	stroke	Disease	D020521
19293073	1159	1162	CVD	Disease	D002318
19293073	1169	1176	aspirin	Chemical	D001241
19293073	1186	1211	gastrointestinal bleeding	Disease	D006471
19293073	1215	1234	hemorrhagic strokes	Disease	D020300|D020521	hemorrhagic|strokes
19293073	1492	1499	aspirin	Chemical	D001241
19293073	1526	1529	CVD	Disease	D002318
19293073	1563	1566	CVD	Disease	D002318
19293073	1607	1629	myocardial infarctions	Disease	D009203
19293073	1667	1674	strokes	Disease	D020521
19293073	1676	1683	Aspirin	Chemical	D001241
19293073	1708	1711	CVD	Disease	D002318
19293073	1780	1787	aspirin	Chemical	D001241
19293073	1840	1848	bleeding	Disease	D006470
19293073	1867	1892	gastrointestinal bleeding	Disease	D006471
19293073	1955	1974	hemorrhagic strokes	Disease	D020300|D020521	hemorrhagic|strokes
19293073	1980	1987	aspirin	Chemical	D001241
19293073	2047	2066	hemorrhagic strokes	Disease	D020300|D020521	hemorrhagic|strokes
19293073	2151	2158	aspirin	Chemical	D001241
19293073	2189	2192	CVD	Disease	D002318
19293073	2217	2224	aspirin	Chemical	D001241
19293073	2468	2475	Aspirin	Chemical	D001241
19293073	2497	2518	myocardial infarction	Disease	D009203
19293073	2530	2537	strokes	Disease	D020521
19293073	2548	2555	Aspirin	Chemical	D001241
19293073	2591	2599	bleeding	Disease	D006470
19293073	CID	D001241	D020521
19293073	CID	D001241	D020300
19293073	CID	D001241	D006471

19338378|t|Reducing harm associated with anticoagulation: practical considerations of argatroban therapy in heparin-induced thrombocytopenia.
19338378|a|Argatroban is a hepatically metabolized, direct thrombin inhibitor used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT) and for patients with or at risk of HIT undergoing percutaneous coronary intervention (PCI). The objective of this review is to summarize practical considerations of argatroban therapy in HIT. The US FDA-recommended argatroban dose in HIT is 2 microg/kg/min (reduced in patients with hepatic impairment and in paediatric patients), adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline (not >100 seconds). Contemporary experiences indicate that reduced doses are also needed in patients with conditions associated with hepatic hypoperfusion, e.g. heart failure, yet are unnecessary for renal dysfunction, adult age, sex, race/ethnicity or obesity. Argatroban 0.5-1.2 microg/kg/min typically supports therapeutic aPTTs. The FDA-recommended dose during PCI is 25 microg/kg/min (350 microg/kg initial bolus), adjusted to achieve activated clotting times (ACTs) of 300-450 sec. For PCI, argatroban has not been investigated in hepatically impaired patients; dose adjustment is unnecessary for adult age, sex, race/ethnicity or obesity, and lesser doses may be adequate with concurrent glycoprotein IIb/IIIa inhibition. Argatroban prolongs the International Normalized Ratio, and published approaches for monitoring the argatroban-to-warfarin transition should be followed. Major bleeding with argatroban is 0-10% in the non-interventional setting and 0-5.8% periprocedurally. Argatroban has no specific antidote, and if excessive anticoagulation occurs, argatroban infusion should be stopped or reduced. Improved familiarity of healthcare professionals with argatroban therapy in HIT, including in special populations and during PCI, may facilitate reduction of harm associated with HIT (e.g. fewer thromboses) or its treatment (e.g. fewer argatroban medication errors).
19338378	75	85	argatroban	Chemical	C031942
19338378	97	104	heparin	Chemical	D006493
19338378	113	129	thrombocytopenia	Disease	D013921
19338378	131	141	Argatroban	Chemical	C031942
19338378	235	245	thrombosis	Disease	D013927
19338378	249	256	heparin	Chemical	D006493
19338378	265	281	thrombocytopenia	Disease	D013921
19338378	283	286	HIT	Disease	D013921
19338378	324	327	HIT	Disease	D013921
19338378	454	464	argatroban	Chemical	C031942
19338378	476	479	HIT	Disease	D013921
19338378	504	514	argatroban	Chemical	C031942
19338378	523	526	HIT	Disease	D013921
19338378	572	590	hepatic impairment	Disease	D008107
19338378	869	882	heart failure	Disease	D006333
19338378	908	925	renal dysfunction	Disease	D007674
19338378	961	968	obesity	Disease	D009765
19338378	970	980	Argatroban	Chemical	C031942
19338378	1205	1215	argatroban	Chemical	C031942
19338378	1345	1352	obesity	Disease	D009765
19338378	1437	1447	Argatroban	Chemical	C031942
19338378	1537	1547	argatroban	Chemical	C031942
19338378	1551	1559	warfarin	Chemical	D014859
19338378	1597	1605	bleeding	Disease	D006470
19338378	1611	1621	argatroban	Chemical	C031942
19338378	1694	1704	Argatroban	Chemical	C031942
19338378	1772	1782	argatroban	Chemical	C031942
19338378	1876	1886	argatroban	Chemical	C031942
19338378	1898	1901	HIT	Disease	D013921
19338378	2001	2004	HIT	Disease	D013921
19338378	2058	2068	argatroban	Chemical	C031942
19338378	CID	C031942	D006470

19392810|t|Rhabdomyolysis and brain ischemic stroke in a heroin-dependent male under methadone maintenance therapy.
19392810|a|OBJECTIVE: There are several complications associated with heroin abuse, some of which are life-threatening. Methadone may aggravate this problem. METHOD: A clinical case description. RESULTS: A 33-year-old man presented with rhabdomyolysis and cerebral ischemic stroke after intravenous heroin. He had used heroin since age 20, and had used 150 mg methadone daily for 6 months. He was found unconsciousness at home and was sent to our hospital. In the ER, his opiate level was 4497 ng/ml. In the ICU, we found rhabdomyolysis, acute renal failure and acute respiratory failure. After transfer to an internal ward, we noted aphasia and weakness of his left limbs. After MRI, we found cerebral ischemic infarction. CONCLUSION: Those using methadone and heroin simultaneously may increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone maintenance therapy should be warned regarding these serious adverse events. Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are discussed.
19392810	0	14	Rhabdomyolysis	Disease	D012206
19392810	25	40	ischemic stroke	Disease	D002544
19392810	46	52	heroin	Chemical	D003932
19392810	74	83	methadone	Chemical	D008691
19392810	164	176	heroin abuse	Disease	D006556
19392810	214	223	Methadone	Chemical	D008691
19392810	331	345	rhabdomyolysis	Disease	D012206
19392810	359	374	ischemic stroke	Disease	D002544
19392810	393	399	heroin	Chemical	D003932
19392810	413	419	heroin	Chemical	D003932
19392810	454	463	methadone	Chemical	D008691
19392810	497	512	unconsciousness	Disease	D014474
19392810	616	630	rhabdomyolysis	Disease	D012206
19392810	632	651	acute renal failure	Disease	D058186
19392810	662	681	respiratory failure	Disease	D012131
19392810	728	735	aphasia	Disease	D001037
19392810	740	748	weakness	Disease	D018908
19392810	788	816	cerebral ischemic infarction	Disease	D002544
19392810	842	851	methadone	Chemical	D008691
19392810	856	862	heroin	Chemical	D003932
19392810	899	913	rhabdomyolysis	Disease	D012206
19392810	918	933	ischemic stroke	Disease	D002544
19392810	950	959	methadone	Chemical	D008691
19392810	1051	1057	heroin	Chemical	D003932
19392810	1066	1080	rhabdomyolysis	Disease	D012206
19392810	1085	1091	stroke	Disease	D020521
19392810	1095	1101	heroin	Chemical	D003932
19392810	CID	D003932	D012206
19392810	CID	D008691	D012206
19392810	CID	D003932	D020521
19392810	CID	D008691	D020521

19419794|t|Increased vulnerability to 6-hydroxydopamine lesion and reduced development of dyskinesias in mice lacking CB1 cannabinoid receptors.
19419794|a|Motor impairment, dopamine (DA) neuronal activity and proenkephalin (PENK) gene expression in the caudate-putamen (CPu) were measured in 6-OHDA-lesioned and treated (L-DOPA+benserazide) CB1 KO and WT mice. A lesion induced by 6-OHDA produced more severe motor deterioration in CB1 KO mice accompanied by more loss of DA neurons and increased PENK gene expression in the CPu. Oxidative/nitrosative and neuroinflammatory parameters were estimated in the CPu and cingulate cortex (Cg). CB1 KO mice exhibited higher MDA levels and iNOS protein expression in the CPu and Cg compared to WT mice. Treatment with L-DOPA+benserazide (12 weeks) resulted in less severe dyskinesias in CB1 KO than in WT mice. The results revealed that the lack of cannabinoid CB1 receptors increased the severity of motor impairment and DA lesion, and reduced L-DOPA-induced dyskinesias. These results suggest that activation of CB1 receptors offers neuroprotection against dopaminergic lesion and the development of L-DOPA-induced dyskinesias.
19419794	27	44	6-hydroxydopamine	Chemical	D016627
19419794	79	90	dyskinesias	Disease	D004409
19419794	152	160	dopamine	Chemical	D004298
19419794	162	164	DA	Chemical	D004298
19419794	188	201	proenkephalin	Chemical	C029992
19419794	203	207	PENK	Chemical	C029992
19419794	271	277	6-OHDA	Chemical	D016627
19419794	300	318	L-DOPA+benserazide	Chemical	C005177
19419794	360	366	6-OHDA	Chemical	D016627
19419794	451	453	DA	Chemical	D004298
19419794	476	480	PENK	Chemical	C029992
19419794	646	649	MDA	Chemical	D008315
19419794	739	757	L-DOPA+benserazide	Chemical	C005177
19419794	793	804	dyskinesias	Disease	D004409
19419794	943	945	DA	Chemical	D004298
19419794	966	972	L-DOPA	Chemical	D007980
19419794	981	992	dyskinesias	Disease	D004409
19419794	1123	1129	L-DOPA	Chemical	D007980
19419794	1138	1149	dyskinesias	Disease	D004409
19419794	CID	D007980	D004409

19447152|t|Animal model of mania induced by ouabain: Evidence of oxidative stress in submitochondrial particles of the rat brain.
19447152|a|The intracerebroventricular (ICV) administration of ouabain (a Na(+)/K(+)-ATPase inhibitor) in rats has been suggested to mimic some symptoms of human bipolar mania. Clinical studies have shown that bipolar disorder may be related to mitochondrial dysfunction. Herein, we investigated the behavioral and biochemical effects induced by the ICV administration of ouabain in rats. To achieve this aim, the effects of ouabain injection immediately after and 7 days following a single ICV administration (at concentrations of 10(-2) and 10(-3)M) on locomotion was measured using the open-field test. Additionally, thiobarbituric acid reactive substances (TBARSs) and superoxide production were measured in submitochondrial particles of the prefrontal cortex, hippocampus, striatum and amygdala. Our findings demonstrated that ouabain at 10(-2) and 10(-3)M induced hyperlocomotion in rats, and this response remained up to 7 days following a single ICV injection. In addition, we observed that the persistent increase in the rat spontaneous locomotion is associated with increased TBARS levels and superoxide generation in submitochondrial particles in the prefrontal cortex, striatum and amygdala. In conclusion, ouabain-induced mania-like behavior may provide a useful animal model to test the hypothesis of the involvement of oxidative stress in bipolar disorder.
19447152	16	21	mania	Disease	D001714
19447152	33	40	ouabain	Chemical	D010042
19447152	171	178	ouabain	Chemical	D010042
19447152	182	184	Na	Chemical	D012964
19447152	188	189	K	Chemical	D011188
19447152	270	283	bipolar mania	Disease	D001714
19447152	318	334	bipolar disorder	Disease	D001714
19447152	353	378	mitochondrial dysfunction	Disease	D028361
19447152	480	487	ouabain	Chemical	D010042
19447152	533	540	ouabain	Chemical	D010042
19447152	728	747	thiobarbituric acid	Chemical	C029684
19447152	781	791	superoxide	Chemical	D013481
19447152	940	947	ouabain	Chemical	D010042
19447152	978	993	hyperlocomotion	Disease	D009069
19447152	1211	1221	superoxide	Chemical	D013481
19447152	1327	1334	ouabain	Chemical	D010042
19447152	1343	1348	mania	Disease	D001714
19447152	1462	1478	bipolar disorder	Disease	D001714
19447152	CID	D010042	D001714

19515070|t|Intraoperative dialysis during liver transplantation with citrate dialysate.
19515070|a|Liver transplantation for acutely ill patients with fulminant liver failure carries high intraoperative and immediate postoperative risks. These are increased with the presence of concomitant acute kidney injury (AKI) and intraoperative dialysis is sometimes required to allow the transplant to proceed. The derangements in the procoagulant and anticoagulant pathways during fulminant liver failure can lead to difficulties with anticoagulation during dialysis, especially when continued in the operating room. Systemic anticoagulation is unsafe and regional citrate anticoagulation in the absence of a functional liver carries the risk of citrate toxicity. Citrate dialysate, a new dialysate with citric acid can be used for anticoagulation in patients who cannot tolerate heparin or regional citrate. We report a case of a 40-year-old female with acetaminophen-induced fulminant liver failure with associated AKI who underwent intraoperative dialytic support during liver transplantation anticoagulated with citrate dialysate during the entire procedure. The patient tolerated the procedure well without any signs of citrate toxicity and maintained adequate anticoagulation for patency of the dialysis circuit. Citrate dialysate is a safe alternative for intradialytic support of liver transplantation in fulminant liver failure.
19515070	58	65	citrate	Chemical	D019343
19515070	129	152	fulminant liver failure	Disease	D017114
19515070	269	288	acute kidney injury	Disease	D058186
19515070	290	293	AKI	Disease	D058186
19515070	452	475	fulminant liver failure	Disease	D017114
19515070	636	643	citrate	Chemical	D019343
19515070	717	724	citrate	Chemical	D019343
19515070	725	733	toxicity	Disease	D064420
19515070	735	742	Citrate	Chemical	D019343
19515070	775	786	citric acid	Chemical	D019343
19515070	851	858	heparin	Chemical	D006493
19515070	871	878	citrate	Chemical	D019343
19515070	926	939	acetaminophen	Chemical	D000082
19515070	948	971	fulminant liver failure	Disease	D017114
19515070	988	991	AKI	Disease	D058186
19515070	1087	1094	citrate	Chemical	D019343
19515070	1196	1203	citrate	Chemical	D019343
19515070	1204	1212	toxicity	Disease	D064420
19515070	1290	1297	Citrate	Chemical	D019343
19515070	1384	1407	fulminant liver failure	Disease	D017114
19515070	CID	D000082	D017114
19515070	CID	D000082	D058186

19531695|t|Delirium in a patient with toxic flecainide plasma concentrations: the role of a pharmacokinetic drug interaction with paroxetine.
19531695|a|OBJECTIVE: To describe a case of flecainide-induced delirium associated with a pharmacokinetic drug interaction with paroxetine. CASE SUMMARY: A 69-year-old white female presented to the emergency department with a history of confusion and paranoia over the past several days. On admission the patient was taking carvedilol 12 mg twice daily, warfarin 2 mg/day, folic acid 1 mg/day, levothyroxine 100 microg/day, pantoprazole 40 mg/day, paroxetine 40 mg/day, and flecainide 100 mg twice daily. Flecainide had been started 2 weeks prior for atrial fibrillation. Laboratory test findings on admission were notable only for a flecainide plasma concentration of 1360 microg/L (reference range 200-1000). A metabolic drug interaction between flecainide and paroxetine, which the patient had been taking for more than 5 years, was considered. Paroxetine was discontinued and the dose of flecainide was reduced to 50 mg twice daily. Her delirium resolved 3 days later. DISCUSSION: Flecainide and pharmacologically similar agents that interact with sodium channels may cause delirium in susceptible patients. A MEDLINE search (1966-January 2009) revealed one in vivo pharmacokinetic study on the interaction between flecainide, a CYP2D6 substrate, and paroxetine, a CYP2D6 inhibitor, as well as 3 case reports of flecainide-induced delirium. According to the Naranjo probability scale, flecainide was the probable cause of the patient's delirium; the Horn Drug Interaction Probability Scale indicates a possible pharmacokinetic drug interaction between flecainide and paroxetine. CONCLUSIONS: Supratherapeutic flecainide plasma concentrations may cause delirium. Because toxicity may occur when flecainide is prescribed with paroxetine and other potent CYP2D6 inhibitors, flecainide plasma concentrations should be monitored closely with commencement of CYP2D6 inhibitors.
19531695	0	8	Delirium	Disease	D003693
19531695	33	43	flecainide	Chemical	D005424
19531695	119	129	paroxetine	Chemical	D017374
19531695	164	174	flecainide	Chemical	D005424
19531695	183	191	delirium	Disease	D003693
19531695	248	258	paroxetine	Chemical	D017374
19531695	357	366	confusion	Disease	D003221
19531695	371	379	paranoia	Disease	D010259
19531695	444	454	carvedilol	Chemical	C043211
19531695	474	482	warfarin	Chemical	D014859
19531695	493	503	folic acid	Chemical	D005492
19531695	514	527	levothyroxine	Chemical	D013974
19531695	544	556	pantoprazole	Chemical	C064276
19531695	568	578	paroxetine	Chemical	D017374
19531695	594	604	flecainide	Chemical	D005424
19531695	625	635	Flecainide	Chemical	D005424
19531695	671	690	atrial fibrillation	Disease	D001281
19531695	754	764	flecainide	Chemical	D005424
19531695	868	878	flecainide	Chemical	D005424
19531695	883	893	paroxetine	Chemical	D017374
19531695	968	978	Paroxetine	Chemical	D017374
19531695	1012	1022	flecainide	Chemical	D005424
19531695	1061	1069	delirium	Disease	D003693
19531695	1105	1115	Flecainide	Chemical	D005424
19531695	1172	1178	sodium	Chemical	D012964
19531695	1198	1206	delirium	Disease	D003693
19531695	1339	1349	flecainide	Chemical	D005424
19531695	1375	1385	paroxetine	Chemical	D017374
19531695	1436	1446	flecainide	Chemical	D005424
19531695	1455	1463	delirium	Disease	D003693
19531695	1509	1519	flecainide	Chemical	D005424
19531695	1560	1568	delirium	Disease	D003693
19531695	1676	1686	flecainide	Chemical	D005424
19531695	1691	1701	paroxetine	Chemical	D017374
19531695	1733	1743	flecainide	Chemical	D005424
19531695	1776	1784	delirium	Disease	D003693
19531695	1794	1802	toxicity	Disease	D064420
19531695	1818	1828	flecainide	Chemical	D005424
19531695	1848	1858	paroxetine	Chemical	D017374
19531695	1895	1905	flecainide	Chemical	D005424
19531695	CID	D005424	D003693
19531695	CID	D017374	D003693

19549709|t|Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors.
19549709|a|BACKGROUND: Treatment options are scarce in pretreated advanced non-small-cell lung cancer (NSCLC) patients. RAD001, an oral inhibitor of the mammalian target of rapamycin (mTOR), has shown phase I efficacy in NSCLC. METHODS: Stage IIIb or IV NSCLC patients, with two or fewer prior chemotherapy regimens, one platinum based (stratum 1) or both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (stratum 2), received RAD001 10 mg/day until progression or unacceptable toxicity. Primary objective was overall response rate (ORR). Analyses of markers associated with the mTOR pathway were carried out on archival tumor from a subgroup using immunohistochemistry (IHC) and direct mutation sequencing. RESULTS: Eighty-five patients were enrolled, 42 in stratum 1 and 43 in stratum. ORR was 4.7% (7.1% stratum 1; 2.3% stratum 2). Overall disease control rate was 47.1%. Median progression-free survivals (PFSs) were 2.6 (stratum 1) and 2.7 months (stratum 2). Common > or =grade 3 events were fatigue, dyspnea, stomatitis, anemia, and thrombocytopenia. Pneumonitis, probably or possibly related, mainly grade 1/2, occurred in 25%. Cox regression analysis of IHC scores found that only phospho AKT (pAKT) was a significant independent predictor of worse PFS. CONCLUSIONS: RAD001 10 mg/day was well tolerated, showing modest clinical activity in pretreated NSCLC. Evaluation of RAD001 plus standard therapy for metastatic NSCLC continues.
19549709	12	22	everolimus	Chemical	C107135
19549709	24	30	RAD001	Chemical	C107135
19549709	58	63	NSCLC	Disease	D002289
19549709	213	239	non-small-cell lung cancer	Disease	D002289
19549709	241	246	NSCLC	Disease	D002289
19549709	258	264	RAD001	Chemical	C107135
19549709	311	320	rapamycin	Chemical	D020123
19549709	359	364	NSCLC	Disease	D002289
19549709	392	397	NSCLC	Disease	D002289
19549709	459	467	platinum	Chemical	D010984
19549709	544	552	tyrosine	Chemical	D014443
19549709	593	599	RAD001	Chemical	C107135
19549709	644	652	toxicity	Disease	D064420
19549709	787	792	tumor	Disease	D009369
19549709	1164	1171	fatigue	Disease	D005221
19549709	1173	1180	dyspnea	Disease	D004417
19549709	1182	1192	stomatitis	Disease	D013280
19549709	1194	1200	anemia	Disease	D000740
19549709	1206	1222	thrombocytopenia	Disease	D013921
19549709	1224	1235	Pneumonitis	Disease	D011014
19549709	1442	1448	RAD001	Chemical	C107135
19549709	1526	1531	NSCLC	Disease	D002289
19549709	1547	1553	RAD001	Chemical	C107135
19549709	1591	1596	NSCLC	Disease	D002289
19549709	CID	C107135	D013921
19549709	CID	C107135	D013280
19549709	CID	C107135	D000740
19549709	CID	C107135	D005221
19549709	CID	C107135	D004417

19553912|t|Posttransplant anemia: the role of sirolimus.
19553912|a|Posttransplant anemia is a common problem that may hinder patients' quality of life. It occurs in 12 to 76% of patients, and is most common in the immediate posttransplant period. A variety of factors have been identified that increase the risk of posttransplant anemia, of which the level of renal function is most important. Sirolimus, a mammalian target of rapamycin inhibitor, has been implicated as playing a special role in posttransplant anemia. This review considers anemia associated with sirolimus, including its presentation, mechanisms, and management.
19553912	15	21	anemia	Disease	D000740
19553912	35	44	sirolimus	Chemical	D020123
19553912	61	67	anemia	Disease	D000740
19553912	309	315	anemia	Disease	D000740
19553912	373	382	Sirolimus	Chemical	D020123
19553912	406	415	rapamycin	Chemical	D020123
19553912	491	497	anemia	Disease	D000740
19553912	521	527	anemia	Disease	D000740
19553912	544	553	sirolimus	Chemical	D020123
19553912	CID	D020123	D000740

19655282|t|Coronary computerized tomography angiography for rapid discharge of low-risk patients with cocaine-associated chest pain.
19655282|a|BACKGROUND: Most patients presenting to emergency departments (EDs) with cocaine-associated chest pain are admitted for at least 12 hours and receive a "rule out acute coronary syndrome" protocol, often with noninvasive testing prior to discharge. In patients without cocaine use, coronary computerized tomography angiography (CTA) has been shown to be useful for identifying a group of patients at low risk for cardiac events who can be safely discharged. It is unclear whether a coronary CTA strategy would be efficacious in cocaine-associated chest pain, as coronary vasospasm may account for some of the ischemia. We studied whether a negative coronary CTA in patients with cocaine-associated chest pain could identify a subset safe for discharge. METHODS: We prospectively evaluated the safety of coronary CTA for low-risk patients who presented to the ED with cocaineassociated chest pain (self-reported or positive urine test). Consecutive patients received either immediate coronary CTA in the ED (without serial markers) or underwent coronary CTA after a brief observation period with serial cardiac marker measurements. Patients with negative coronary CTA (maximal stenosis less than 50%) were discharged. The main outcome was 30-day cardiovascular death or myocardial infarction. RESULTS: A total of 59 patients with cocaine-associated chest pain were evaluated. Patients had a mean age of 45.6 +/- 6.6 yrs and were 86% black, 66% male. Seventy-nine percent had a normal or nonspecific ECG and 85% had a TIMI score <2. Twenty patients received coronary CTA immediately in the ED, 18 of whom were discharged following CTA (90%). Thirty-nine received coronary CTA after a brief observation period, with 37 discharged home following CTA (95%). Six patients had coronary stenosis >or=50%. During the 30-day follow-up period, no patients died of a cardiovascular event (0%; 95% CI, 0-6.1%) and no patient sustained a nonfatal myocardial infarction (0%; 95% CI, 0-6.1%). CONCLUSIONS: Although cocaine-associated myocardial ischemia can result from coronary vasoconstriction, patients with cocaine associated chest pain, a non-ischemic ECG, and a TIMI risk score <2 may be safely discharged from the ED after a negative coronary CTA with a low risk of 30-day adverse events.
19655282	91	98	cocaine	Chemical	D003042
19655282	110	120	chest pain	Disease	D002637
19655282	195	202	cocaine	Chemical	D003042
19655282	214	224	chest pain	Disease	D002637
19655282	284	307	acute coronary syndrome	Disease	D054058
19655282	390	397	cocaine	Chemical	D003042
19655282	649	656	cocaine	Chemical	D003042
19655282	668	678	chest pain	Disease	D002637
19655282	683	701	coronary vasospasm	Disease	D003329
19655282	730	738	ischemia	Disease	D007511
19655282	800	807	cocaine	Chemical	D003042
19655282	819	829	chest pain	Disease	D002637
19655282	1006	1016	chest pain	Disease	D002637
19655282	1297	1305	stenosis	Disease	D003251
19655282	1390	1411	myocardial infarction	Disease	D009203
19655282	1450	1457	cocaine	Chemical	D003042
19655282	1469	1479	chest pain	Disease	D002637
19655282	1891	1908	coronary stenosis	Disease	D023921
19655282	2054	2075	myocardial infarction	Disease	D009203
19655282	2120	2127	cocaine	Chemical	D003042
19655282	2139	2158	myocardial ischemia	Disease	D017202
19655282	2216	2223	cocaine	Chemical	D003042
19655282	2235	2245	chest pain	Disease	D002637
19655282	2253	2261	ischemic	Disease	D007511
19655282	CID	D003042	D002637
19655282	CID	D003042	D017202

19715529|t|Late fulminant posterior reversible encephalopathy syndrome after liver transplant.
19715529|a|OBJECTIVES: Posterior leukoencephalopathy due to calcineurin-inhibitor-related neurotoxicity is a rare but severe complication that results from treatment with immunosuppressive agents (primarily those administered after a liver or kidney transplant). The pathophysiologic mechanisms of that disorder remain unknown. CASE: We report the case of a 46-year-old woman who received a liver transplant in our center as treatment for alcoholic cirrhosis and in whom either a fulminant course of posterior leukoencephalopathy or posterior reversible encephalopathy syndrome developed 110 days after transplant. After an initially uneventful course after the transplant, the patient rapidly fell into deep coma. RESULTS: Cerebral MRI scan showed typical signs of enhancement in the pontine and posterior regions. Switching the immunosuppressive regimen from tacrolimus to cyclosporine did not improve the clinical situation. The termination of treatment with any calcineurin inhibitor resulted in a complete resolution of that complication. CONCLUSIONS: Posterior reversible encephalopathy syndrome after liver transplant is rare. We recommend a complete cessation of any calcineurin inhibitor rather than a dose reduction.
19715529	15	59	posterior reversible encephalopathy syndrome	Disease	D054038
19715529	96	125	Posterior leukoencephalopathy	Disease	D054038
19715529	163	176	neurotoxicity	Disease	D020258
19715529	512	531	alcoholic cirrhosis	Disease	D008104
19715529	573	602	posterior leukoencephalopathy	Disease	D054038
19715529	606	650	posterior reversible encephalopathy syndrome	Disease	D054038
19715529	934	944	tacrolimus	Chemical	D016559
19715529	948	960	cyclosporine	Chemical	D016572
19715529	1130	1174	Posterior reversible encephalopathy syndrome	Disease	D054038
19715529	CID	D016559	D054038

19728177|t|Prolonged hypothermia as a bridge to recovery for cerebral edema and intracranial hypertension associated with fulminant hepatic failure.
19728177|a|BACKGROUND: To review evidence-based treatment options in patients with cerebral edema complicating fulminant hepatic failure (FHF) and discuss the potential applications of hypothermia. METHOD: Case-based observations from a medical intensive care unit (MICU) in a tertiary care facility in a 27-year-old female with FHF from acetaminophen and resultant cerebral edema. RESULTS: Our patient was admitted to the MICU after being found unresponsive with presumed toxicity from acetaminophen which was ingested over a 2-day period. The patient had depressed of mental status lasting at least 24 h prior to admission. Initial evaluation confirmed FHF from acetaminophen and cerebral edema. The patient was treated with hyperosmolar therapy, hyperventilation, sedation, and chemical paralysis. Her intracranial pressure remained elevated despite maximal medical therapy. We then initiated therapeutic hypothermia which was continued for 5 days. At re-warming, patient had resolution of her cerebral edema and intracranial hypertension. At discharge, she had complete recovery of neurological and hepatic functions. CONCLUSION: In patients with FHF and cerebral edema from acetaminophen overdose, prolonged therapeutic hypothermia could potentially be used as a life saving therapy and a bridge to hepatic and neurological recovery. A clinical trial of hypothermia in patients with this condition is warranted.
19728177	10	21	hypothermia	Disease	D007035
19728177	50	64	cerebral edema	Disease	D001929
19728177	69	94	intracranial hypertension	Disease	D019586
19728177	111	136	fulminant hepatic failure	Disease	D017114
19728177	210	224	cerebral edema	Disease	D001929
19728177	238	263	fulminant hepatic failure	Disease	D017114
19728177	265	268	FHF	Disease	D017114
19728177	312	323	hypothermia	Disease	D007035
19728177	456	459	FHF	Disease	D017114
19728177	465	478	acetaminophen	Chemical	D000082
19728177	493	507	cerebral edema	Disease	D001929
19728177	600	608	toxicity	Disease	D064420
19728177	614	627	acetaminophen	Chemical	D000082
19728177	782	785	FHF	Disease	D017114
19728177	791	804	acetaminophen	Chemical	D000082
19728177	809	823	cerebral edema	Disease	D001929
19728177	876	892	hyperventilation	Disease	D006985
19728177	917	926	paralysis	Disease	D010243
19728177	1035	1046	hypothermia	Disease	D007035
19728177	1124	1138	cerebral edema	Disease	D001929
19728177	1143	1168	intracranial hypertension	Disease	D019586
19728177	1278	1281	FHF	Disease	D017114
19728177	1286	1300	cerebral edema	Disease	D001929
19728177	1306	1319	acetaminophen	Chemical	D000082
19728177	1320	1328	overdose	Disease	D062787
19728177	1352	1363	hypothermia	Disease	D007035
19728177	1486	1497	hypothermia	Disease	D007035
19728177	CID	D000082	D017114
19728177	CID	D000082	D019586
19728177	CID	D000082	D001929

19815465|t|Binasal visual field defects are not specific to vigabatrin.
19815465|a|This study investigated the visual defects associated with the antiepileptic drug vigabatrin (VGB). Two hundred four people with epilepsy were grouped on the basis of antiepileptic drug therapy (current, previous, or no exposure to VGB). Groups were matched with respect to age, gender, and seizure frequency. All patients underwent objective assessment of electrophysiological function (wide-field multifocal electroretinography) and conventional visual field testing (static perimetry). Bilateral visual field constriction was observed in 59% of patients currently taking VGB, 43% of patients who previously took VGB, and 24% of patients with no exposure to VGB. Assessment of retinal function revealed abnormal responses in 48% of current VGB users and 22% of prior VGB users, but in none of the patients without previous exposure to VGB. Bilateral visual field abnormalities are common in the treated epilepsy population, irrespective of drug history. Assessment by conventional static perimetry may neither be sufficiently sensitive nor specific to reliably identify retinal toxicity associated with VGB.
19815465	0	28	Binasal visual field defects	Disease	D014786
19815465	49	59	vigabatrin	Chemical	D020888
19815465	89	103	visual defects	Disease	D014786
19815465	143	153	vigabatrin	Chemical	D020888
19815465	155	158	VGB	Chemical	D020888
19815465	190	198	epilepsy	Disease	D004827
19815465	293	296	VGB	Chemical	D020888
19815465	352	359	seizure	Disease	D012640
19815465	635	638	VGB	Chemical	D020888
19815465	676	679	VGB	Chemical	D020888
19815465	721	724	VGB	Chemical	D020888
19815465	803	806	VGB	Chemical	D020888
19815465	830	833	VGB	Chemical	D020888
19815465	898	901	VGB	Chemical	D020888
19815465	903	939	Bilateral visual field abnormalities	Disease	D014786
19815465	966	974	epilepsy	Disease	D004827
19815465	1133	1149	retinal toxicity	Disease	D012164
19815465	1166	1169	VGB	Chemical	D020888
19815465	CID	D020888	D014786
19815465	CID	D020888	D012164

19841052|t|Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs.
19841052|a|BACKGROUND: Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, we sought to examine whether use of this illicit drug has become a risk factor for HIV infection. METHODS: We included data from people participating in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrolment, lived in the greater Vancouver area, were HIV-negative at enrolment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, we used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996-Nov. 30, 1999 (period 1), Dec. 1, 1999-Nov. 30, 2002 (period 2), and Dec. 1, 2002-Dec. 30, 2005 (period 3). RESULTS: Overall, 1048 eligible injection drug users were included in our study. Of these, 137 acquired HIV infection during follow-up. The mean proportion of participants who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, we found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57-1.85; period 2: HR 1.68, 95% CI 1.01-2.80; and period 3: HR 2.74, 95% CI 1.06-7.11). INTERPRETATION: Smoking of crack cocaine was found to be an independent risk factor for HIV seroconversion among people who were injection drug users. This finding points to the urgent need for evidence-based public health initiatives targeted at people who smoke crack cocaine.
19841052	11	24	crack cocaine	Chemical	D016578
19841052	46	59	HIV infection	Disease	D015658
19841052	163	176	crack cocaine	Chemical	D016578
19841052	201	214	HIV infection	Disease	D015658
19841052	244	257	crack cocaine	Chemical	D016578
19841052	342	355	HIV infection	Disease	D015658
19841052	684	702	HIV seroconversion	Disease	D006679
19841052	726	739	crack cocaine	Chemical	D016578
19841052	1065	1078	HIV infection	Disease	D015658
19841052	1163	1176	crack cocaine	Chemical	D016578
19841052	1301	1319	HIV seroconversion	Disease	D006679
19841052	1365	1378	crack cocaine	Chemical	D016578
19841052	1580	1593	crack cocaine	Chemical	D016578
19841052	1641	1659	HIV seroconversion	Disease	D006679
19841052	1817	1830	crack cocaine	Chemical	D016578
19841052	CID	D016578	D006679

19914299|t|Fluoxetine improves the memory deficits caused by the chemotherapy agent 5-fluorouracil.
19914299|a|Cancer patients who have been treated with systemic adjuvant chemotherapy have described experiencing deteriorations in cognition. A widely used chemotherapeutic agent, 5-fluorouracil (5-FU), readily crosses the blood-brain barrier and so could have a direct effect on brain function. In particular this anti mitotic drug could reduce cell proliferation in the neurogenic regions of the adult brain. In contrast reports indicate that hippocampal dependent neurogenesis and cognition are enhanced by the SSRI antidepressant Fluoxetine. In this investigation the behavioural effects of chronic (two week) treatment with 5-FU and (three weeks) with Fluoxetine either separately or in combination with 5-FU were tested on adult Lister hooded rats. Behavioural effects were tested using a context dependent conditioned emotional response test (CER) which showed that animals treated with 5-FU had a significant reduction in freezing time compared to controls. A separate group of animals was tested using a hippocampal dependent spatial working memory test, the object location recognition test (OLR). Animals treated only with 5-FU showed significant deficits in their ability to carry out the OLR task but co administration of Fluoxetine improved their performance. 5-FU chemotherapy caused a significant reduction in the number of proliferating cells in the sub granular zone of the dentate gyrus compared to controls. This reduction was eliminated when Fluoxetine was co administered with 5-FU. Fluoxetine on its own had no effect on proliferating cell number or behaviour. These findings suggest that 5-FU can negatively affect both cell proliferation and hippocampal dependent working memory and that these deficits can be reversed by the simultaneous administration of the antidepressant Fluoxetine.
19914299	0	10	Fluoxetine	Chemical	D005473
19914299	24	39	memory deficits	Disease	D008569
19914299	73	87	5-fluorouracil	Chemical	D005472
19914299	89	95	Cancer	Disease	D009369
19914299	258	272	5-fluorouracil	Chemical	D005472
19914299	274	278	5-FU	Chemical	D005472
19914299	592	596	SSRI	Chemical	D017367
19914299	612	622	Fluoxetine	Chemical	D005473
19914299	707	711	5-FU	Chemical	D005472
19914299	735	745	Fluoxetine	Chemical	D005473
19914299	787	791	5-FU	Chemical	D005472
19914299	972	976	5-FU	Chemical	D005472
19914299	1212	1216	5-FU	Chemical	D005472
19914299	1313	1323	Fluoxetine	Chemical	D005473
19914299	1352	1356	5-FU	Chemical	D005472
19914299	1541	1551	Fluoxetine	Chemical	D005473
19914299	1577	1581	5-FU	Chemical	D005472
19914299	1583	1593	Fluoxetine	Chemical	D005473
19914299	1690	1694	5-FU	Chemical	D005472
19914299	1879	1889	Fluoxetine	Chemical	D005473
19914299	CID	D005472	D008569

19920070|t|Liver-specific ablation of integrin-linked kinase in mice results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration.
19920070|a|We have recently demonstrated that disruption of extracellular matrix (ECM)/integrin signaling via elimination of integrin-linked kinase (ILK) in hepatocytes interferes with signals leading to termination of liver regeneration. This study investigates the role of ILK in liver enlargement induced by phenobarbital (PB). Wild-type (WT) and ILK:liver-/- mice were given PB (0.1% in drinking water) for 10 days. Livers were harvested on 2, 5, and 10 days during PB administration. In the hepatocyte-specific ILK/liver-/- mice, the liver:body weight ratio was more than double as compared to 0 h at day 2 (2.5 times), while at days 5 and 10, it was enlarged three times. In the WT mice, the increase was as expected from previous literature (1.8 times) and seems to have leveled off after day 2. There were slightly increased proliferating cell nuclear antigen-positive cells in the ILK/liver-/- animals at day 2 as compared to WT after PB administration. In the WT animals, the proliferative response had come back to normal by days 5 and 10. Hepatocytes of the ILK/liver-/- mice continued to proliferate up until day 10. ILK/liver-/- mice also showed increased expression of key genes involved in hepatocyte proliferation at different time points during PB administration. In summary, ECM proteins communicate with the signaling machinery of dividing cells via ILK to regulate hepatocyte proliferation and termination of the proliferative response. Lack of ILK in the hepatocytes imparts prolonged proliferative response not only to stimuli related to liver regeneration but also to xenobiotic chemical mitogens, such as PB.
19920070	115	127	hepatomegaly	Disease	D006529
19920070	134	147	phenobarbital	Chemical	D010634
19920070	464	477	phenobarbital	Chemical	D010634
19920070	479	481	PB	Chemical	D010634
19920070	532	534	PB	Chemical	D010634
19920070	623	625	PB	Chemical	D010634
19920070	1097	1099	PB	Chemical	D010634
19920070	1416	1418	PB	Chemical	D010634
19920070	1783	1785	PB	Chemical	D010634
19920070	CID	D010634	D006529

19967075|t|Decreased Expression of Na/K-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy.
19967075|a|The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na(+)/K(+)-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na(+)/K(+)-ATPase, NHE3, NBC1, AQP1 and OAT.
19967075	24	26	Na	Chemical	D012964
19967075	27	28	K	Chemical	D011188
19967075	65	75	Gentamicin	Chemical	D005839
19967075	84	95	Nephropathy	Disease	D007674
19967075	204	214	gentamicin	Chemical	D005839
19967075	223	234	nephropathy	Disease	D007674
19967075	307	317	gentamicin	Chemical	D005839
19967075	512	522	Gentamicin	Chemical	D005839
19967075	570	580	creatinine	Chemical	D003404
19967075	619	629	creatinine	Chemical	D003404
19967075	679	685	sodium	Chemical	D012964
19967075	865	867	Na	Chemical	D012964
19967075	871	872	K	Chemical	D011188
19967075	922	932	gentamicin	Chemical	D005839
19967075	999	1009	Gentamicin	Chemical	D005839
19967075	1018	1029	nephropathy	Disease	D007674
19967075	1102	1104	Na	Chemical	D012964
19967075	1108	1109	K	Chemical	D011188
19967075	CID	D005839	D007674

20024739|t|Longitudinal association of alcohol use with HIV disease progression and psychological health of women with HIV.
20024739|a|We evaluated the association of alcohol consumption and depression, and their effects on HIV disease progression among women with HIV. The study included 871 women with HIV who were recruited from 1993-1995 in four US cities. The participants had physical examination, medical record extraction, and venipuncture, CD4+T-cell counts determination, measurement of depression symptoms (using the self-report Center for Epidemiological Studies-Depression Scale), and alcohol use assessment at enrollment, and semiannually until March 2000. Multilevel random coefficient ordinal models as well as multilevel models with joint responses were used in the analysis. There was no significant association between level of alcohol use and CD4+ T-cell counts. When participants were stratified by antiretroviral therapy (ART) use, the association between alcohol and CD4+ T-cell did not reach statistical significance. The association between alcohol consumption and depression was significant (p<0.001). Depression had a significant negative effect on CD4+ T-cell counts over time regardless of ART use. Our findings suggest that alcohol consumption has a direct association with depression. Moreover, depression is associated with HIV disease progression. Our findings have implications for the provision of alcohol use interventions and psychological resources to improve the health of women with HIV.
20024739	28	35	alcohol	Chemical	D000431
20024739	45	56	HIV disease	Disease	D015658
20024739	145	152	alcohol	Chemical	D000431
20024739	169	179	depression	Disease	D003866
20024739	202	213	HIV disease	Disease	D015658
20024739	475	485	depression	Disease	D003866
20024739	553	563	Depression	Disease	D003866
20024739	576	583	alcohol	Chemical	D000431
20024739	825	832	alcohol	Chemical	D000431
20024739	956	963	alcohol	Chemical	D000431
20024739	1044	1051	alcohol	Chemical	D000431
20024739	1068	1078	depression	Disease	D003866
20024739	1106	1116	Depression	Disease	D003866
20024739	1232	1239	alcohol	Chemical	D000431
20024739	1282	1292	depression	Disease	D003866
20024739	1304	1314	depression	Disease	D003866
20024739	1334	1345	HIV disease	Disease	D015658
20024739	1411	1418	alcohol	Chemical	D000431
20024739	CID	D000431	D003866

20034406|t|Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus.
20034406|a|BACKGROUND: Neuroinflammation occurs after seizures and is implicated in epileptogenesis. CCR2 is a chemokine receptor for CCL2 and their interaction mediates monocyte infiltration in the neuroinflammatory cascade triggered in different brain pathologies. In this work CCR2 and CCL2 expression were examined following status epilepticus (SE) induced by pilocarpine injection. METHODS: SE was induced by pilocarpine injection. Control rats were injected with saline instead of pilocarpine. Five days after SE, CCR2 staining in neurons and glial cells was examined using imunohistochemical analyses. The number of CCR2 positive cells was determined using stereology probes in the hippocampus. CCL2 expression in the hippocampus was examined by molecular assay. RESULTS: Increased CCR2 was observed in the hippocampus after SE. Seizures also resulted in alterations to the cell types expressing CCR2. Increased numbers of neurons that expressed CCR2 was observed following SE. Microglial cells were more closely apposed to the CCR2-labeled cells in SE rats. In addition, rats that experienced SE exhibited CCR2-labeling in populations of hypertrophied astrocytes, especially in CA1 and dentate gyrus. These CCR2+ astroctytes were not observed in control rats. Examination of CCL2 expression showed that it was elevated in the hippocampus following SE. CONCLUSION: The data show that CCR2 and CCL2 are up-regulated in the hippocampus after pilocarpine-induced SE. Seizures also result in changes to CCR2 receptor expression in neurons and astrocytes. These changes might be involved in detrimental neuroplasticity and neuroinflammatory changes that occur following seizures.
20034406	80	91	pilocarpine	Chemical	D010862
20034406	100	118	status epilepticus	Disease	D013226
20034406	132	149	Neuroinflammation	Disease	D007249
20034406	163	171	seizures	Disease	D012640
20034406	308	325	neuroinflammatory	Disease	D007249
20034406	438	456	status epilepticus	Disease	D013226
20034406	458	460	SE	Disease	D013226
20034406	473	484	pilocarpine	Chemical	D010862
20034406	505	507	SE	Disease	D013226
20034406	523	534	pilocarpine	Chemical	D010862
20034406	596	607	pilocarpine	Chemical	D010862
20034406	625	627	SE	Disease	D013226
20034406	941	943	SE	Disease	D013226
20034406	945	953	Seizures	Disease	D012640
20034406	1090	1092	SE	Disease	D013226
20034406	1166	1168	SE	Disease	D013226
20034406	1210	1212	SE	Disease	D013226
20034406	1255	1268	hypertrophied	Disease	D006984
20034406	1465	1467	SE	Disease	D013226
20034406	1556	1567	pilocarpine	Chemical	D010862
20034406	1576	1578	SE	Disease	D013226
20034406	1580	1588	Seizures	Disease	D012640
20034406	1734	1751	neuroinflammatory	Disease	D007249
20034406	1781	1789	seizures	Disease	D012640
20034406	CID	D010862	D013226

20046642|t|Metallothionein induction reduces caspase-3 activity and TNFalpha levels with preservation of cognitive function and intact hippocampal neurons in carmustine-treated rats.
20046642|a|Hippocampal integrity is essential for cognitive functions. On the other hand, induction of metallothionein (MT) by ZnSO(4) and its role in neuroprotection has been documented. The present study aimed to explore the effect of MT induction on carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats. A total of 60 male Wistar albino rats were randomly divided into four groups (15/group): The control group injected with single doses of normal saline (i.c.v) followed 24 h later by BCNU solvent (i.v). The second group administered ZnSO(4) (0.1 micromol/10 microl normal saline, i.c.v, once) then BCNU solvent (i.v) after 24 h. Third group received BCNU (20 mg/kg, i.v, once) 24 h after injection with normal saline (i.c.v). Fourth group received a single dose of ZnSO(4) (0.1 micromol/10 microl normal saline, i.c.v) then BCNU (20 mg/kg, i.v, once) after 24 h. The obtained data revealed that BCNU administration resulted in deterioration of learning and short-term memory (STM), as measured by using radial arm water maze, accompanied with decreased hippocampal glutathione reductase (GR) activity and reduced glutathione (GSH) content. Also, BCNU administration increased serum tumor necrosis factor-alpha (TNFalpha), hippocampal MT and malondialdehyde (MDA) contents as well as caspase-3 activity in addition to histological alterations. ZnSO(4) pretreatment counteracted BCNU-induced inhibition of GR and depletion of GSH and resulted in significant reduction in the levels of MDA and TNFalpha as well as the activity of caspase-3. The histological features were improved in hippocampus of rats treated with ZnSO(4) + BCNU compared to only BCNU-treated animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as it prevented GR inhibition and GSH depletion and counteracted the increased levels of TNFalpha, MDA and caspase-3 activity with subsequent preservation of cognition.
20046642	0	15	Metallothionein	Chemical	D008668
20046642	147	157	carmustine	Chemical	D002330
20046642	264	279	metallothionein	Chemical	D008668
20046642	281	283	MT	Chemical	D008668
20046642	288	295	ZnSO(4)	Chemical	D019287
20046642	398	400	MT	Chemical	D008668
20046642	414	424	carmustine	Chemical	D002330
20046642	426	430	BCNU	Chemical	D002330
20046642	452	473	cognitive dysfunction	Disease	D003072
20046642	665	669	BCNU	Chemical	D002330
20046642	715	722	ZnSO(4)	Chemical	D019287
20046642	780	784	BCNU	Chemical	D002330
20046642	832	836	BCNU	Chemical	D002330
20046642	947	954	ZnSO(4)	Chemical	D019287
20046642	1006	1010	BCNU	Chemical	D002330
20046642	1077	1081	BCNU	Chemical	D002330
20046642	1109	1156	deterioration of learning and short-term memory	Disease	D007859|D008569	deterioration of learning|deterioration of short-term memory
20046642	1247	1258	glutathione	Chemical	D005978
20046642	1295	1306	glutathione	Chemical	D005978
20046642	1308	1311	GSH	Chemical	D005978
20046642	1328	1332	BCNU	Chemical	D002330
20046642	1364	1369	tumor	Disease	D009369
20046642	1370	1378	necrosis	Disease	D009336
20046642	1416	1418	MT	Chemical	D008668
20046642	1423	1438	malondialdehyde	Chemical	D008315
20046642	1440	1443	MDA	Chemical	D008315
20046642	1525	1532	ZnSO(4)	Chemical	D019287
20046642	1559	1563	BCNU	Chemical	D002330
20046642	1606	1609	GSH	Chemical	D005978
20046642	1665	1668	MDA	Chemical	D008315
20046642	1796	1803	ZnSO(4)	Chemical	D019287
20046642	1806	1810	BCNU	Chemical	D002330
20046642	1828	1832	BCNU	Chemical	D002330
20046642	1865	1867	MT	Chemical	D008668
20046642	1884	1888	BCNU	Chemical	D002330
20046642	1909	1917	toxicity	Disease	D064420
20046642	1952	1955	GSH	Chemical	D005978
20046642	2017	2020	MDA	Chemical	D008315
20046642	CID	D002330	D008569
20046642	CID	D002330	D007859
20046642	CID	D002330	D003072

20129423|t|Fatal carbamazepine induced fulminant eosinophilic (hypersensitivity) myocarditis: emphasis on anatomical and histological characteristics, mechanisms and genetics of drug hypersensitivity and differential diagnosis.
20129423|a|The most severe adverse reactions to carbamazepine have been observed in the haemopoietic system, the liver and the cardiovascular system. A frequently fatal, although exceptionally rare side effect of carbamazepine is necrotizing eosinophilic (hypersensitivity) myocarditis. We report a case of hypersensitivity myocarditis secondary to administration of carbamazepine. Acute hypersensitivity myocarditis was not suspected clinically, and the diagnosis was made post-mortem. Histology revealed diffuse infiltration of the myocardium by eosinophils and lymphocytes with myocyte damage. Clinically, death was due to cardiogenic shock. To best of our knowledge this is the second case of fatal carbamazepine induced myocarditis reported in English literature.
20129423	6	19	carbamazepine	Chemical	D002220
20129423	28	50	fulminant eosinophilic	Disease	D004802
20129423	52	68	hypersensitivity	Disease	D004342
20129423	70	81	myocarditis	Disease	D009205
20129423	167	188	drug hypersensitivity	Disease	D004342
20129423	254	267	carbamazepine	Chemical	D002220
20129423	419	432	carbamazepine	Chemical	D002220
20129423	462	478	hypersensitivity	Disease	D004342
20129423	480	491	myocarditis	Disease	D009205
20129423	513	529	hypersensitivity	Disease	D004342
20129423	530	541	myocarditis	Disease	D009205
20129423	573	586	carbamazepine	Chemical	D002220
20129423	594	610	hypersensitivity	Disease	D004342
20129423	611	622	myocarditis	Disease	D009205
20129423	832	849	cardiogenic shock	Disease	D012770
20129423	909	922	carbamazepine	Chemical	D002220
20129423	931	942	myocarditis	Disease	D009205
20129423	CID	D002220	D012770
20129423	CID	D002220	D009205
20129423	CID	D002220	D004802
20129423	CID	D002220	D004342

20169779|t|Neuropsychiatric behaviors in the MPTP marmoset model of Parkinson's disease.
20169779|a|OBJECTIVES: Neuropsychiatric symptoms are increasingly recognised as a significant problem in patients with Parkinson's disease (PD). These symptoms may be due to 'sensitisation' following repeated levodopa treatment or a direct effect of dopamine on the disease state. The levodopa-treated MPTP-lesioned marmoset was used as a model of neuropsychiatric symptoms in PD patients. Here we compare the time course of levodopa-induced motor fluctuations and neuropsychiatric-like behaviors to determine the relationship between duration of treatment and onset of symptoms. METHODS: Marmosets were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2.0 mg/kg s.c.) for five days, resulting in stable parkinsonism. Levodopa (15 mg/kg and benserazide, 3.75 mg/kg) p.o. b.i.d, was administered for 30 days. Animals were evaluated for parkinsonian disability, dyskinesia and on-time (motor fluctuations) and neuropsychiatric-like behaviors on Day 0 (prior to levodopa) and on Days 1, 7, 13, 27 and 30 of treatment using post hoc DVD analysis by a trained rater, blind to the treatment day. RESULTS: The neuropsychiatric-like behavior rating scale demonstrated high interrater reliability between three trained raters of differing professional backgrounds. As anticipated, animals exhibited a progressive increase in levodopa-induced motor fluctuations, dyskinesia and wearing-off, that correlated with the duration of levodopa therapy. In contrast, levodopa-induced neuropsychiatric-like behaviors were present on Day 1 of levodopa treatment and their severity did not correlate with duration of treatment. CONCLUSIONS: The data suggest that neuropsychiatric disorders in PD are more likely an interaction between levodopa and the disease state than a consequence of sensitisation to repeated dopaminergic therapy.
20169779	34	38	MPTP	Chemical	D015632
20169779	57	76	Parkinson's disease	Disease	D010302
20169779	186	205	Parkinson's disease	Disease	D010302
20169779	207	209	PD	Disease	D010302
20169779	276	284	levodopa	Chemical	D007980
20169779	317	325	dopamine	Chemical	D004298
20169779	352	360	levodopa	Chemical	D007980
20169779	369	373	MPTP	Chemical	D015632
20169779	415	440	neuropsychiatric symptoms	Disease	D001523
20169779	444	446	PD	Disease	D010302
20169779	492	500	levodopa	Chemical	D007980
20169779	532	563	neuropsychiatric-like behaviors	Disease	D001523
20169779	684	728	1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine	Chemical	D015632
20169779	781	793	parkinsonism	Disease	D010302
20169779	795	803	Levodopa	Chemical	D007980
20169779	818	829	benserazide	Chemical	D001545
20169779	912	935	parkinsonian disability	Disease	D020734
20169779	937	947	dyskinesia	Disease	D004409
20169779	985	1016	neuropsychiatric-like behaviors	Disease	D001523
20169779	1036	1044	levodopa	Chemical	D007980
20169779	1180	1210	neuropsychiatric-like behavior	Disease	D001523
20169779	1393	1401	levodopa	Chemical	D007980
20169779	1430	1440	dyskinesia	Disease	D004409
20169779	1495	1503	levodopa	Chemical	D007980
20169779	1526	1534	levodopa	Chemical	D007980
20169779	1543	1574	neuropsychiatric-like behaviors	Disease	D001523
20169779	1600	1608	levodopa	Chemical	D007980
20169779	1719	1745	neuropsychiatric disorders	Disease	D001523
20169779	1749	1751	PD	Disease	D010302
20169779	1791	1799	levodopa	Chemical	D007980
20169779	CID	D007980	D004409
20169779	CID	D015632	D020734

20192893|t|Contrast medium nephrotoxicity after renal artery and coronary angioplasty.
20192893|a|BACKGROUND: Renal dysfunction induced by iodinated contrast medium (CM) administration can minimize the benefit of the interventional procedure in patients undergoing renal angioplasty (PTRA). PURPOSE: To compare the susceptibility to nephrotoxic effect of CM in patients undergoing PTRA with that of patients submitted to percutaneous coronary intervention (PCI). MATERIAL AND METHODS: A total of 33 patients successfully treated with PTRA (PTRA group, mean age 70+/-12 years, 23 female, basal creatinine 1.46+/-0.79, range 0.7-4.9 mg/dl) were compared with 33 patients undergoing successful PCI (PCI group), matched for basal creatinine (1.44+/-0.6, range 0.7-3.4 mg/dl), gender, and age. In both groups postprocedural (48 h) serum creatinine was measured. RESULTS: Postprocedural creatinine level decreased nonsignificantly in the PTRA group (1.46+/-0.8 vs. 1.34+/-0.5 mg/dl, P=NS) and increased significantly in the PCI group (1.44+/-0.6 vs. 1.57+/-0.7 mg/dl, P<0.02). Changes in serum creatinine after intervention (after-before) were significantly different between the PTRA and PCI groups (-0.12+/-0.5 vs. 0.13+/-0.3, P=0.014). This difference was not related to either a different clinical risk profile or to the volume of CM administered. CONCLUSION: In this preliminary study patients submitted to PTRA showed a lower susceptibility to renal damage induced by CM administration than PCI patients. The effectiveness of PTRA on renal function seems to be barely influenced by CM toxicity.
20192893	0	15	Contrast medium	Chemical	D003287
20192893	16	30	nephrotoxicity	Disease	D007674
20192893	88	105	Renal dysfunction	Disease	D007674
20192893	127	142	contrast medium	Chemical	D003287
20192893	144	146	CM	Chemical	D003287
20192893	311	322	nephrotoxic	Disease	D007674
20192893	333	335	CM	Chemical	D003287
20192893	571	581	creatinine	Chemical	D003404
20192893	704	714	creatinine	Chemical	D003404
20192893	810	820	creatinine	Chemical	D003404
20192893	859	869	creatinine	Chemical	D003404
20192893	1066	1076	creatinine	Chemical	D003404
20192893	1307	1309	CM	Chemical	D003287
20192893	1422	1434	renal damage	Disease	D007674
20192893	1446	1448	CM	Chemical	D003287
20192893	1560	1562	CM	Chemical	D003287
20192893	1563	1571	toxicity	Disease	D064420
20192893	CID	D003287	D007674

20408947|t|Medical and psychiatric outcomes for patients transplanted for acetaminophen-induced acute liver failure: a case-control study.
20408947|a|BACKGROUND: Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure (ALF) in the UK. Patients often consume the drug with suicidal intent or with a background of substance dependence. AIMS AND METHODS: We compared the severity of pretransplant illness, psychiatric co-morbidity, medical and psychosocial outcomes of all patients who had undergone liver transplantation (LT) emergently between 1999-2004 for acetaminophen-induced ALF (n=36) with age- and sex-matched patients undergoing emergent LT for non-acetaminophen-induced ALF (n=35) and elective LT for chronic liver disease (CLD, n=34). RESULTS: Acetaminophen-induced ALF patients undergoing LT had a greater severity of pre-LT illness reflected by higher Acute Physiology and Chronic Health Evaluation II scores and requirement for organ support compared with the other two groups. Twenty (56%) acetaminophen-induced ALF patients had a formal psychiatric diagnosis before LT (non-acetaminophen-induced ALF=0/35, CLD=2/34; P<0.01 for all) and nine (25%) had a previous suicide attempt. During follow-up (median 5 years), there were no significant differences in rejection (acute and chronic), graft failure or survival between the groups (acetaminophen-induced ALF 1 year 87%, 5 years 75%; non-acetaminophen-induced ALF 88%, 78%; CLD 93%, 82%: P>0.6 log rank). Two acetaminophen-induced ALF patients reattempted suicide post-LT (one died 8 years post-LT). CONCLUSIONS: Despite a high prevalence of psychiatric disturbance, outcomes for patients transplanted emergently for acetaminophen-induced ALF were comparable to those transplanted for non-acetaminophen-induced ALF and electively for CLD. Multidisciplinary approaches with long-term psychiatric follow-up may contribute to low post-transplant suicide rates seen and low rates of graft loss because of non-compliance.
20408947	63	76	acetaminophen	Chemical	D000082
20408947	85	104	acute liver failure	Disease	D017114
20408947	140	153	Acetaminophen	Chemical	D000082
20408947	162	176	hepatotoxicity	Disease	D056486
20408947	205	224	acute liver failure	Disease	D017114
20408947	226	229	ALF	Disease	D017114
20408947	564	577	acetaminophen	Chemical	D000082
20408947	586	589	ALF	Disease	D017114
20408947	663	676	acetaminophen	Chemical	D000082
20408947	685	688	ALF	Disease	D017114
20408947	716	737	chronic liver disease	Disease	D008107
20408947	739	742	CLD	Disease	D008107
20408947	760	773	Acetaminophen	Chemical	D000082
20408947	782	785	ALF	Disease	D017114
20408947	1010	1023	acetaminophen	Chemical	D000082
20408947	1032	1035	ALF	Disease	D017114
20408947	1095	1108	acetaminophen	Chemical	D000082
20408947	1117	1120	ALF	Disease	D017114
20408947	1127	1130	CLD	Disease	D008107
20408947	1353	1366	acetaminophen	Chemical	D000082
20408947	1375	1378	ALF	Disease	D017114
20408947	1408	1421	acetaminophen	Chemical	D000082
20408947	1430	1433	ALF	Disease	D017114
20408947	1444	1447	CLD	Disease	D008107
20408947	1479	1492	acetaminophen	Chemical	D000082
20408947	1501	1504	ALF	Disease	D017114
20408947	1687	1700	acetaminophen	Chemical	D000082
20408947	1709	1712	ALF	Disease	D017114
20408947	1759	1772	acetaminophen	Chemical	D000082
20408947	1781	1784	ALF	Disease	D017114
20408947	1804	1807	CLD	Disease	D008107
20408947	CID	D000082	D056486
20408947	CID	D000082	D017114

20447294|t|Studies of synergy between morphine and a novel sodium channel blocker, CNSB002, in rat models of inflammatory and neuropathic pain.
20447294|a|OBJECTIVE: This study determined the antihyperalgesic effect of CNSB002, a sodium channel blocker with antioxidant properties given alone and in combinations with morphine in rat models of inflammatory and neuropathic pain. DESIGN: Dose response curves for nonsedating doses of morphine and CNSB002 given intraperitoneally alone and together in combinations were constructed for antihyperalgesic effect using paw withdrawal from noxious heat in two rat pain models: carrageenan-induced paw inflammation and streptozotocin (STZ)-induced diabetic neuropathy. RESULTS: The maximum nonsedating doses were: morphine, 3.2 mg/kg; CNSB002 10.0 mg/kg; 5.0 mg/kg CNSB002 with morphine 3.2 mg/kg in combination. The doses calculated to cause 50% reversal of hyperalgesia (ED50) were 7.54 (1.81) and 4.83 (1.54) in the carrageenan model and 44.18 (1.37) and 9.14 (1.24) in the STZ-induced neuropathy model for CNSB002 and morphine, respectively (mg/kg; mean, SEM). These values were greater than the maximum nonsedating doses. The ED50 values for morphine when given in combination with CNSB002 (5 mg/kg) were less than the maximum nonsedating dose: 0.56 (1.55) in the carrageenan model and 1.37 (1.23) in the neuropathy model (mg/kg; mean, SEM). The antinociception after morphine (3.2 mg/kg) was increased by co-administration with CNSB002 from 28.0 and 31.7% to 114.6 and 56.9% reversal of hyperalgesia in the inflammatory and neuropathic models, respectively (P < 0.01; one-way analysis of variance-significantly greater than either drug given alone). CONCLUSIONS: The maximum antihyperalgesic effect achievable with nonsedating doses of morphine may be increased significantly when the drug is used in combination with CNSB002.
20447294	27	35	morphine	Chemical	D009020
20447294	48	54	sodium	Chemical	D012964
20447294	72	79	CNSB002	Chemical	C401121
20447294	115	131	neuropathic pain	Disease	D009437
20447294	197	204	CNSB002	Chemical	C401121
20447294	208	214	sodium	Chemical	D012964
20447294	296	304	morphine	Chemical	D009020
20447294	339	355	neuropathic pain	Disease	D009437
20447294	411	419	morphine	Chemical	D009020
20447294	424	431	CNSB002	Chemical	C401121
20447294	586	590	pain	Disease	D010146
20447294	599	610	carrageenan	Chemical	D002351
20447294	623	635	inflammation	Disease	D007249
20447294	640	654	streptozotocin	Chemical	D013311
20447294	656	659	STZ	Chemical	D013311
20447294	669	688	diabetic neuropathy	Disease	D003929
20447294	735	743	morphine	Chemical	D009020
20447294	756	763	CNSB002	Chemical	C401121
20447294	786	793	CNSB002	Chemical	C401121
20447294	799	807	morphine	Chemical	D009020
20447294	880	892	hyperalgesia	Disease	D006930
20447294	940	951	carrageenan	Chemical	D002351
20447294	998	1001	STZ	Chemical	D013311
20447294	1010	1020	neuropathy	Disease	D009422
20447294	1031	1038	CNSB002	Chemical	C401121
20447294	1043	1051	morphine	Chemical	D009020
20447294	1168	1176	morphine	Chemical	D009020
20447294	1208	1215	CNSB002	Chemical	C401121
20447294	1290	1301	carrageenan	Chemical	D002351
20447294	1331	1341	neuropathy	Disease	D009422
20447294	1394	1402	morphine	Chemical	D009020
20447294	1455	1462	CNSB002	Chemical	C401121
20447294	1514	1526	hyperalgesia	Disease	D006930
20447294	1551	1562	neuropathic	Disease	D009422
20447294	1763	1771	morphine	Chemical	D009020
20447294	1845	1852	CNSB002	Chemical	C401121
20447294	CID	D013311	D003929
20447294	CID	D013311	D006930
20447294	CID	D002351	D007249
20447294	CID	D002351	D006930

20495512|t|Heparin-induced thrombocytopenia: a practical review.
20495512|a|Heparin-induced thrombocytopenia (HIT) remains under-recognized despite its potentially devastating outcomes. It begins when heparin exposure stimulates the formation of heparin-platelet factor 4 antibodies, which in turn triggers the release of procoagulant platelet particles. Thrombosis and thrombocytopenia that follow comprise the 2 hallmark traits of HIT, with the former largely responsible for significant vascular complications. The prevalence of HIT varies among several subgroups, with greater incidence in surgical as compared with medical populations. HIT must be acknowledged for its intense predilection for thrombosis and suspected whenever thrombosis occurs after heparin exposure. Early recognition that incorporates the clinical and serologic clues is paramount to timely institution of treatment, as its delay may result in catastrophic outcomes. The treatment of HIT mandates an immediate cessation of all heparin exposure and the institution of an antithrombotic therapy, most commonly using a direct thrombin inhibitor. Current "diagnostic" tests, which primarily include functional and antigenic assays, have more of a confirmatory than diagnostic role in the management of HIT. Special attention must be paid to cardiac patients who are often exposed to heparin multiple times during their course of treatment. Direct thrombin inhibitors are appropriate, evidence-based alternatives to heparin in patients with a history of HIT, who need to undergo percutaneous coronary intervention. As heparin remains one of the most frequently used medications today with potential for HIT with every heparin exposure, a close vigilance of platelet counts must be practiced whenever heparin is initiated.
20495512	0	7	Heparin	Chemical	D006493
20495512	16	32	thrombocytopenia	Disease	D013921
20495512	54	61	Heparin	Chemical	D006493
20495512	70	86	thrombocytopenia	Disease	D013921
20495512	88	91	HIT	Disease	D013921
20495512	179	186	heparin	Chemical	D006493
20495512	224	231	heparin	Chemical	D006493
20495512	333	343	Thrombosis	Disease	D013927
20495512	348	364	thrombocytopenia	Disease	D013921
20495512	411	414	HIT	Disease	D013921
20495512	510	513	HIT	Disease	D013921
20495512	619	622	HIT	Disease	D013921
20495512	677	687	thrombosis	Disease	D013927
20495512	711	721	thrombosis	Disease	D013927
20495512	735	742	heparin	Chemical	D006493
20495512	938	941	HIT	Disease	D013921
20495512	981	988	heparin	Chemical	D006493
20495512	1070	1095	direct thrombin inhibitor	Chemical	D000991
20495512	1252	1255	HIT	Disease	D013921
20495512	1333	1340	heparin	Chemical	D006493
20495512	1390	1416	Direct thrombin inhibitors	Chemical	D000991
20495512	1465	1472	heparin	Chemical	D006493
20495512	1503	1506	HIT	Disease	D013921
20495512	1567	1574	heparin	Chemical	D006493
20495512	1652	1655	HIT	Disease	D013921
20495512	1667	1674	heparin	Chemical	D006493
20495512	1749	1756	heparin	Chemical	D006493
20495512	CID	D006493	D013921
20495512	CID	D006493	D013927

20513036|t|Abductor paralysis after botox injection for adductor spasmodic dysphonia.
20513036|a|OBJECTIVES/HYPOTHESIS: Botulinum toxin (Botox) injections into the thyroarytenoid muscles are the current standard of care for adductor spasmodic dysphonia (ADSD). Reported adverse effects include a period of breathiness, throat pain, and difficulty with swallowing liquids. Here we report multiple cases of bilateral abductor paralysis following Botox injections for ADSD, a complication previously unreported. STUDY DESIGN: Retrospective case series. METHODS: Patients that received Botox injections for spasmodic dysphonia between January 2000 and October 2009 were evaluated. Patients with ADSD were identified. The number of treatments received and adverse effects were noted. For patients with bilateral abductor paralysis, age, sex, paralytic Botox dose, prior Botox dose, and course following paralysis were noted. RESULTS: From a database of 452 patients receiving Botox, 352 patients had been diagnosed with ADSD. Of these 352 patients, eight patients suffered bilateral abductor paralysis, and two suffered this complication twice. All affected patients were females over the age of 50 years. Most patients had received treatments prior to abductor paralysis and continued receiving after paralysis. Seven patients recovered after a brief period of activity restrictions, and one underwent a tracheotomy. The incidence of abductor paralysis after Botox injection for ADSD was 0.34%. CONCLUSIONS: Bilateral abductor paralysis is a rare complication of Botox injections for ADSD, causing difficulty with breathing upon exertion. The likely mechanism of paralysis is diffusion of Botox around the muscular process of the arytenoid to the posterior cricoarytenoid muscles. The paralysis is temporary, and watchful waiting with restriction of activity is the recommended management.
20513036	9	18	paralysis	Disease	D010243
20513036	25	30	botox	Chemical	C542870
20513036	45	73	adductor spasmodic dysphonia	Disease	D014826
20513036	115	120	Botox	Chemical	C542870
20513036	202	230	adductor spasmodic dysphonia	Disease	D014826
20513036	232	236	ADSD	Disease	D014826
20513036	297	308	throat pain	Disease	D010612
20513036	402	411	paralysis	Disease	D010243
20513036	422	427	Botox	Chemical	C542870
20513036	443	447	ADSD	Disease	D014826
20513036	560	565	Botox	Chemical	C542870
20513036	581	600	spasmodic dysphonia	Disease	D055154
20513036	669	673	ADSD	Disease	D014826
20513036	794	803	paralysis	Disease	D010243
20513036	825	830	Botox	Chemical	C542870
20513036	843	848	Botox	Chemical	C542870
20513036	876	885	paralysis	Disease	D010243
20513036	949	954	Botox	Chemical	C542870
20513036	993	997	ADSD	Disease	D014826
20513036	1065	1074	paralysis	Disease	D010243
20513036	1235	1244	paralysis	Disease	D010243
20513036	1275	1284	paralysis	Disease	D010243
20513036	1417	1426	paralysis	Disease	D010243
20513036	1433	1438	Botox	Chemical	C542870
20513036	1453	1457	ADSD	Disease	D014826
20513036	1501	1510	paralysis	Disease	D010243
20513036	1537	1542	Botox	Chemical	C542870
20513036	1558	1562	ADSD	Disease	D014826
20513036	1637	1646	paralysis	Disease	D010243
20513036	1663	1668	Botox	Chemical	C542870
20513036	1759	1768	paralysis	Disease	D010243
20513036	CID	C542870	D014826

20566328|t|Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: Prevention by the targeted antioxidant MitoQ.
20566328|a|The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction. We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction. Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III. ROS levels were increased, specifically in interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria. This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect.
20566328	0	24	Mitochondrial impairment	Disease	D028361
20566328	40	47	cocaine	Chemical	D003042
20566328	56	75	cardiac dysfunction	Disease	D006331
20566328	116	121	MitoQ	Chemical	C476756
20566328	230	237	cocaine	Chemical	D003042
20566328	246	265	cardiac dysfunction	Disease	D006331
20566328	288	301	cocaine abuse	Disease	D019970
20566328	368	396	left ventricular dysfunction	Disease	D018487
20566328	412	419	cocaine	Chemical	D003042
20566328	463	469	oxygen	Chemical	D010100
20566328	666	669	ATP	Chemical	D000255
20566328	848	855	cocaine	Chemical	D003042
20566328	879	906	mitochondrial abnormalities	Disease	D028361
20566328	979	986	cocaine	Chemical	D003042
20566328	988	993	MitoQ	Chemical	C476756
20566328	1071	1098	mitochondrial abnormalities	Disease	D028361
20566328	1110	1129	cardiac dysfunction	Disease	D006331
20566328	1154	1175	diastolic dysfunction	Disease	-1
20566328	1319	1326	cocaine	Chemical	D003042
20566328	1335	1354	cardiac dysfunction	Disease	D006331
20566328	1371	1391	mitochondrial defect	Disease	D028361
20566328	CID	D003042	D006331

20589632|t|Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction.
20589632|a|A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction.
20589632	0	12	Trimethoprim	Chemical	D014295
20589632	28	44	hemolytic anemia	Disease	D000743
20589632	156	170	acute leukemia	Disease	D015470
20589632	204	210	anemia	Disease	D000740
20589632	254	268	hemoglobinuria	Disease	D006456
20589632	332	348	hemolytic anemia	Disease	D000743
20589632	561	573	trimethoprim	Chemical	D014295
20589632	578	607	trimethoprim-sulfamethoxazole	Chemical	D015662
20589632	626	642	sulfamethoxazole	Chemical	D013420
20589632	743	749	anemia	Disease	D000740
20589632	808	814	anemia	Disease	D000740
20589632	848	857	hemolysis	Disease	D006461
20589632	CID	D014295	D000743

20682692|t|Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy.
20682692|a|OBJECTIVE: A multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard the progression of nephropathy, suggesting that other mechanism(s) are involved in the pathogenesis of early diabetic nephropathy (diabetic nephropathy). We have previously demonstrated that endothelial-mesenchymal-transition (EndoMT) contributes to the early development of renal interstitial fibrosis independently of microalbuminuria in mice with streptozotocin (STZ)-induced diabetes. In the present study, we hypothesized that blocking EndoMT reduces the early development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: EndoMT was induced in a mouse pancreatic microvascular endothelial cell line (MMEC) in the presence of advanced glycation end products (AGEs) and in the endothelial lineage-traceble mouse line Tie2-Cre;Loxp-EGFP by administration of AGEs, with nonglycated mouse albumin serving as a control. Phosphorylated Smad3 was detected by immunoprecipitation/Western blotting and confocal microscopy. Blocking studies using receptor for AGE siRNA and a specific inhibitor of Smad3 (SIS3) were performed in MMECs and in STZ-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice. RESULTS: Confocal microscopy and real-time PCR demonstrated that AGEs induced EndoMT in MMECs and in Tie2-Cre;Loxp-EGFP mice. Immunoprecipitation/Western blotting showed that Smad3 was activated by AGEs but was inhibited by SIS3 in MMECs and in STZ-induced diabetic nephropathy. Confocal microscopy and real-time PCR further demonstrated that SIS3 abrogated EndoMT, reduced renal fibrosis, and retarded progression of nephropathy. CONCLUSIONS: EndoMT is a novel pathway leading to early development of diabetic nephropathy. Blockade of EndoMT by SIS3 may provide a new strategy to retard the progression of diabetic nephropathy and other diabetes complications.
20682692	100	114	streptozotocin	Chemical	D013311
20682692	123	143	diabetic nephropathy	Disease	D003928
20682692	228	239	angiotensin	Chemical	D000804
20682692	264	279	type 1 diabetes	Disease	D003922
20682692	335	346	nephropathy	Disease	D007674
20682692	425	445	diabetic nephropathy	Disease	D003928
20682692	447	467	diabetic nephropathy	Disease	D003928
20682692	610	618	fibrosis	Disease	D005355
20682692	666	680	streptozotocin	Chemical	D013311
20682692	682	685	STZ	Chemical	D013311
20682692	695	703	diabetes	Disease	D003920
20682692	797	817	diabetic nephropathy	Disease	D003928
20682692	1357	1360	STZ	Chemical	D013311
20682692	1369	1389	diabetic nephropathy	Disease	D003928
20682692	1663	1666	STZ	Chemical	D013311
20682692	1675	1695	diabetic nephropathy	Disease	D003928
20682692	1798	1806	fibrosis	Disease	D005355
20682692	1836	1847	nephropathy	Disease	D007674
20682692	1920	1940	diabetic nephropathy	Disease	D003928
20682692	2025	2045	diabetic nephropathy	Disease	D003928
20682692	2056	2078	diabetes complications	Disease	D048909
20682692	CID	D013311	D003928

20828385|t|Cytostatic and anti-angiogenic effects of temsirolimus in refractory mantle cell lymphoma.
20828385|a|Mantle cell lymphoma (MCL) is a rare and aggressive type of B-cell non-Hodgkin's lymphoma. Patients become progressively refractory to conventional chemotherapy, and their prognosis is poor. However, a 38% remission rate has been recently reported in refractory MCL treated with temsirolimus, a mTOR inhibitor.Here we had the opportunity to study a case of refractory MCL who had tumor regression two months after temsirolimus treatment, and a progression-free survival of 10 months. In this case, lymph node biopsies were performed before and six months after temsirolimus therapy. Comparison of the two biopsies showed that temsirolimus inhibited tumor cell proliferation through cell cycle arrest, but did not induce any change in the number of apoptotic tumor cells. Apart from this cytostatic effect, temsirolimus had an antiangiogenic effect with decrease of tumor microvessel density and of VEGF expression. Moreover, numerous patchy, well-limited fibrotic areas, compatible with post-necrotic tissue repair, were found after 6-month temsirolimus therapy. Thus, temsirolimus reduced tumor burden through associated cytostatic and anti-angiogenic effects.This dual effect of temsirolimus on tumor tissue could contribute to its recently reported efficiency in refractory MCL resistant to conventional chemotherapy.
20828385	42	54	temsirolimus	Chemical	C401859
20828385	69	89	mantle cell lymphoma	Disease	D020522
20828385	91	111	Mantle cell lymphoma	Disease	D020522
20828385	113	116	MCL	Disease	D020522
20828385	151	180	B-cell non-Hodgkin's lymphoma	Disease	D008228
20828385	353	356	MCL	Disease	D020522
20828385	370	382	temsirolimus	Chemical	C401859
20828385	459	462	MCL	Disease	D020522
20828385	471	476	tumor	Disease	D009369
20828385	505	517	temsirolimus	Chemical	C401859
20828385	652	664	temsirolimus	Chemical	C401859
20828385	717	729	temsirolimus	Chemical	C401859
20828385	740	745	tumor	Disease	D009369
20828385	849	854	tumor	Disease	D009369
20828385	897	909	temsirolimus	Chemical	C401859
20828385	956	961	tumor	Disease	D009369
20828385	1083	1091	necrotic	Disease	D009336
20828385	1132	1144	temsirolimus	Chemical	C401859
20828385	1160	1172	temsirolimus	Chemical	C401859
20828385	1181	1186	tumor	Disease	D009369
20828385	1272	1284	temsirolimus	Chemical	C401859
20828385	1288	1293	tumor	Disease	D009369
20828385	1368	1371	MCL	Disease	D020522
20828385	CID	C401859	D009336

20859899|t|Syncope caused by hyperkalemia during use of a combined therapy with the angiotensin-converting enzyme inhibitor and spironolactone.
20859899|a|A 76 year-old woman with a history of coronary artery bypass grafting and prior myocardial infarction was transferred to the emergency room with loss of consciousness due to marked bradycardia caused by hyperkalemia. The concentration of serum potassium was high, and normal sinus rhythm was restored after correction of the serum potassium level. The cause of hyperkalemia was considered to be several doses of spiranolactone, an aldosterone antagonist, in addition to the long-term intake of ramipril, an ACE inhibitor. This case is a good example of electrolyte imbalance causing acute life-threatening cardiac events. Clinicians should be alert to the possibility of hyperkalemia, especially in elderly patients using ACE/ARB in combination with potassium sparing agents and who have mild renal disturbance.
20859899	0	7	Syncope	Disease	D013575
20859899	18	30	hyperkalemia	Disease	D006947
20859899	73	84	angiotensin	Chemical	D000809
20859899	117	131	spironolactone	Chemical	D013148
20859899	213	234	myocardial infarction	Disease	D009203
20859899	278	299	loss of consciousness	Disease	D014474
20859899	314	325	bradycardia	Disease	D001919
20859899	336	348	hyperkalemia	Disease	D006947
20859899	377	386	potassium	Chemical	D011188
20859899	464	473	potassium	Chemical	D011188
20859899	494	506	hyperkalemia	Disease	D006947
20859899	545	559	spiranolactone	Chemical	D013148
20859899	564	575	aldosterone	Chemical	D000450
20859899	627	635	ramipril	Chemical	D017257
20859899	804	816	hyperkalemia	Disease	D006947
20859899	883	892	potassium	Chemical	D011188
20859899	926	943	renal disturbance	Disease	D007674
20859899	CID	D011188	D001919
20859899	CID	D013148	D006947
20859899	CID	D017257	D006947

20927253|t|Diffuse skeletal pain after administration of alendronate.
20927253|a|BACKGROUND: Osteoporosis is caused by bone resorption in excess of bone formation, and bisphosphonates, are used to inhibit bone resorption. Alendronate, a biphosphonate, is effective for both the treatment and prevention of osteoporosis in postmenopausal women. Side effects are relatively few and prominently gastrointestinal. Musculoskeletal pain may be an important side effect in these patients. We presented a patient admitted to our out-patient clinic with diffuse skeletal pain after three consecutive administration of alendronate. CONCLUSION: We conclude that patients with osteoporosis can report pain, and bisphosphonate-related pain should also be considered before ascribing this complaint to osteoporosis.
20927253	17	21	pain	Disease	D010146
20927253	46	57	alendronate	Chemical	D019386
20927253	71	83	Osteoporosis	Disease	D010024
20927253	146	161	bisphosphonates	Chemical	D004164
20927253	200	211	Alendronate	Chemical	D019386
20927253	215	228	biphosphonate	Chemical	-1
20927253	284	296	osteoporosis	Disease	D010024
20927253	388	408	Musculoskeletal pain	Disease	D059352
20927253	540	544	pain	Disease	D010146
20927253	587	598	alendronate	Chemical	D019386
20927253	643	655	osteoporosis	Disease	D010024
20927253	667	671	pain	Disease	D010146
20927253	677	691	bisphosphonate	Chemical	D004164
20927253	700	704	pain	Disease	D010146
20927253	766	778	osteoporosis	Disease	D010024
20927253	CID	D019386	D010146

20959502|t|Cerebrospinal fluid penetration of high-dose daptomycin in suspected Staphylococcus aureus meningitis.
20959502|a|OBJECTIVE: To report a case of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia with suspected MSSA meningitis treated with high-dose daptomycin assessed with concurrent serum and cerebrospinal fluid (CSF) concentrations. CASE SUMMARY: A 54-year-old male presented to the emergency department with generalized weakness and presumed health-care-associated pneumonia shown on chest radiograph. Treatment was empirically initiated with vancomycin, levofloxacin, and piperacillin/tazobactam. Blood cultures revealed S. aureus susceptible to oxacillin. Empiric antibiotic treatment was narrowed to nafcillin on day 4. On day 8, the patient developed acute renal failure (serum creatinine 1.9 mg/dL, increased from 1.2 mg/dL the previous day and 0.8 mg/dL on admission). The patient's Glasgow Coma Score was 3, with normal findings shown on computed tomography scan of the head 72 hours following an episode of cardiac arrest on day 10. The patient experienced relapsing MSSA bacteremia on day 9, increasing the suspicion for a central nervous system (CNS) infection. Nafcillin was discontinued and daptomycin 9 mg/kg daily was initiated for suspected meningitis and was continued until the patient's death on day 16. Daptomycin serum and CSF trough concentrations were 11.21 ug/mL and 0.52 ug/mL, respectively, prior to the third dose. Lumbar puncture results were inconclusive and no further blood cultures were positive for MSSA. Creatine kinase levels were normal prior to daptomycin therapy and were not reassessed. DISCUSSION: Daptomycin was initiated in our patient secondary to possible nafcillin-induced acute interstitial nephritis and relapsing bacteremia. At a dose of 9 mg/kg, resultant penetration of 5% was higher than in previous reports, more consistent with inflamed meninges. CONCLUSIONS: High-dose daptomycin may be an alternative option for MSSA bacteremia with or without a CNS source in patients who have failed or cannot tolerate standard therapy. Further clinical evaluation in patients with confirmed meningitis is warranted.
20959502	45	55	daptomycin	Chemical	D017576
20959502	91	101	meningitis	Disease	D008581
20959502	134	145	methicillin	Chemical	D008712
20959502	185	195	bacteremia	Disease	D016470
20959502	216	226	meningitis	Disease	D008581
20959502	250	260	daptomycin	Chemical	D017576
20959502	426	434	weakness	Disease	D018908
20959502	471	480	pneumonia	Disease	D011014
20959502	549	559	vancomycin	Chemical	D014640
20959502	561	573	levofloxacin	Chemical	D064704
20959502	579	591	piperacillin	Chemical	D010878
20959502	592	602	tazobactam	Chemical	C043265
20959502	653	662	oxacillin	Chemical	D010068
20959502	709	718	nafcillin	Chemical	D009254
20959502	761	780	acute renal failure	Disease	D058186
20959502	788	798	creatinine	Chemical	D003404
20959502	1021	1035	cardiac arrest	Disease	D006323
20959502	1086	1096	bacteremia	Disease	D016470
20959502	1167	1176	infection	Disease	D007239
20959502	1178	1187	Nafcillin	Chemical	D009254
20959502	1209	1219	daptomycin	Chemical	D017576
20959502	1262	1272	meningitis	Disease	D008581
20959502	1328	1338	Daptomycin	Chemical	D017576
20959502	1543	1551	Creatine	Chemical	D003401
20959502	1587	1597	daptomycin	Chemical	D017576
20959502	1643	1653	Daptomycin	Chemical	D017576
20959502	1705	1714	nafcillin	Chemical	D009254
20959502	1729	1751	interstitial nephritis	Disease	D009395
20959502	1766	1776	bacteremia	Disease	D016470
20959502	1928	1938	daptomycin	Chemical	D017576
20959502	1977	1987	bacteremia	Disease	D016470
20959502	2137	2147	meningitis	Disease	D008581
20959502	CID	D009254	D009395

21195121|t|The role of nitric oxide in convulsions induced by lindane in rats.
21195121|a|Lindane is an organochloride pesticide and scabicide. It evokes convulsions mainly trough the blockage of GABA(A) receptors. Nitric oxide (NO), gaseous neurotransmitter, has contradictor role in epileptogenesis due to opposite effects of L-arginine, precursor of NO syntheses (NOS), and L-NAME (NOS inhibitor) observed in different epilepsy models. The aim of the current study was to determine the effects of NO on the behavioral and EEG characteristics of lindane-induced epilepsy in male Wistar albino rats. The administration of L-arginine (600, 800 and 1000 mg/kg, i.p.) in dose-dependent manner significantly increased convulsion incidence and severity and shortened latency time to first convulsion elicited by lower lindane dose (4 mg/kg, i.p.). On the contrary, pretreatment with L-NAME (500, 700 and 900 mg/kg, i.p.) decreased convulsion incidence and severity and prolonged latency time to convulsion following injection with a convulsive dose of lindane (8 mg/kg, i.p.). EEG analyses showed increase of number and duration of ictal periods in EEG of rats receiving l-arginine prior to lindane and decrease of this number in rats pretreated with L-NAME. These results support the conclusion that NO plays a role of endogenous convulsant in rat model of lindane seizures.
21195121	12	24	nitric oxide	Chemical	D009569
21195121	28	39	convulsions	Disease	D012640
21195121	51	58	lindane	Chemical	D001556
21195121	68	75	Lindane	Chemical	D001556
21195121	132	143	convulsions	Disease	D012640
21195121	174	178	GABA	Chemical	D005680
21195121	193	205	Nitric oxide	Chemical	D009569
21195121	207	209	NO	Chemical	D009569
21195121	306	316	L-arginine	Chemical	D001120
21195121	331	333	NO	Chemical	D009569
21195121	355	361	L-NAME	Chemical	D019331
21195121	400	408	epilepsy	Disease	D004827
21195121	478	480	NO	Chemical	D009569
21195121	526	533	lindane	Chemical	D001556
21195121	542	550	epilepsy	Disease	D004827
21195121	601	611	L-arginine	Chemical	D001120
21195121	693	703	convulsion	Disease	D012640
21195121	763	773	convulsion	Disease	D012640
21195121	792	799	lindane	Chemical	D001556
21195121	857	863	L-NAME	Chemical	D019331
21195121	905	915	convulsion	Disease	D012640
21195121	969	979	convulsion	Disease	D012640
21195121	1007	1017	convulsive	Disease	D012640
21195121	1026	1033	lindane	Chemical	D001556
21195121	1145	1155	l-arginine	Chemical	D001120
21195121	1165	1172	lindane	Chemical	D001556
21195121	1225	1231	L-NAME	Chemical	D019331
21195121	1275	1277	NO	Chemical	D009569
21195121	1332	1339	lindane	Chemical	D001556
21195121	1340	1348	seizures	Disease	D012640
21195121	CID	D001556	D012640

24055495|t|Long-term oral galactose treatment prevents cognitive deficits in male Wistar rats treated intracerebroventricularly with streptozotocin.
24055495|a|Basic and clinical research has demonstrated that dementia of sporadic Alzheimer's disease (sAD) type is associated with dysfunction of the insulin-receptor (IR) system followed by decreased glucose transport via glucose transporter GLUT4 and decreased glucose metabolism in brain cells. An alternative source of energy is d-galactose (the C-4-epimer of d-glucose) which is transported into the brain by insulin-independent GLUT3 transporter where it might be metabolized to glucose via the Leloir pathway. Exclusively parenteral daily injections of galactose induce memory deterioration in rodents and are used to generate animal aging model, but the effects of oral galactose treatment on cognitive functions have never been tested. We have investigated the effects of continuous daily oral galactose (200 mg/kg/day) treatment on cognitive deficits in streptozotocin-induced (STZ-icv) rat model of sAD, tested by Morris Water Maze and Passive Avoidance test, respectively. One month of oral galactose treatment initiated immediately after the STZ-icv administration, successfully prevented development of the STZ-icv-induced cognitive deficits. Beneficial effect of oral galactose was independent of the rat age and of the galactose dose ranging from 100 to 300 mg/kg/day. Additionally, oral galactose administration led to the appearance of galactose in the blood. The increase of galactose concentration in the cerebrospinal fluid was several times lower after oral than after parenteral administration of the same galactose dose. Oral galactose exposure might have beneficial effects on learning and memory ability and could be worth investigating for improvement of cognitive deficits associated with glucose hypometabolism in AD.
24055495	15	24	galactose	Chemical	D005690
24055495	44	62	cognitive deficits	Disease	D003072
24055495	122	136	streptozotocin	Chemical	D013311
24055495	188	196	dementia	Disease	D003704
24055495	209	228	Alzheimer's disease	Disease	D000544
24055495	329	336	glucose	Chemical	D005947
24055495	351	358	glucose	Chemical	D005947
24055495	391	398	glucose	Chemical	D005947
24055495	461	472	d-galactose	Chemical	D005690
24055495	492	501	d-glucose	Chemical	D005947
24055495	613	620	glucose	Chemical	D005947
24055495	688	697	galactose	Chemical	D005690
24055495	705	725	memory deterioration	Disease	D008569
24055495	806	815	galactose	Chemical	D005690
24055495	931	940	galactose	Chemical	D005690
24055495	970	988	cognitive deficits	Disease	D003072
24055495	992	1006	streptozotocin	Chemical	D013311
24055495	1016	1019	STZ	Chemical	D013311
24055495	1131	1140	galactose	Chemical	D005690
24055495	1183	1186	STZ	Chemical	D013311
24055495	1249	1252	STZ	Chemical	D013311
24055495	1265	1283	cognitive deficits	Disease	D003072
24055495	1311	1320	galactose	Chemical	D005690
24055495	1363	1372	galactose	Chemical	D005690
24055495	1432	1441	galactose	Chemical	D005690
24055495	1482	1491	galactose	Chemical	D005690
24055495	1522	1531	galactose	Chemical	D005690
24055495	1657	1666	galactose	Chemical	D005690
24055495	1678	1687	galactose	Chemical	D005690
24055495	1810	1828	cognitive deficits	Disease	D003072
24055495	1845	1867	glucose hypometabolism	Disease	D018149
24055495	1871	1873	AD	Disease	D000544
24055495	CID	D005947	D000544
24055495	CID	D013311	D000544
24055495	CID	D013311	D003072
24055495	CID	D005690	D003072

