<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Variant angina and explain in detail? [/INST] Variant angina, also known as Prinzmetal angina, vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina (cardiac chest pain). Variant angina differs from stable angina in that it commonly occurs in individuals who are at rest or even asleep, whereas stable angina is generally triggered by exertion or intense exercise. Variant angina is caused by vasospasm, a narrowing of the coronary arteries due to contraction of the hearts smooth muscle tissue in the vessel walls. In comparison, stable angina is caused by the permanent occlusion of these vessels by atherosclerosis, which is the buildup of fatty plaque and hardening of the arteries.

Signs and symptoms
In contrast to those with angina secondary to atherosclerosis, people with variant angina are generally younger and have fewer risk factors for coronary artery disease with the exception of smoking, which is a common and significant risk factor for both types of angina. Affected people usually have repeated episodes of unexplained (e.g., in the absence of exertion and occurring at sleep or in the early morning hours) chest pain, tightness in throat, chest pressure, light-headedness, excessive sweating, and/or reduced exercise tolerance that, unlike atherosclerosis-related angina, typically does not progress to myocardial infarction (heart attack). Unlike cases of atherosclerosis-related stable angina, these symptoms are often unrelated to exertion and occur in night or early morning hours. However, individuals with atherosclerosis-related unstable angina may similarly exhibit night to early morning hour symptoms that are unrelated to exertion.Cardiac examination of individuals with variant angina is usually normal in the absence of current symptoms. Two-thirds of these individuals do have concurrent atherosclerosis of a major coronary artery, but this is often mild or not in proportion to the degree of their symptoms. Persons who have atherosclerosis-based occlusion that is ≥70% in a single coronary artery or that involves multiple coronary arteries are predisposed to develop a variant angina form that has a poorer prognosis than most other forms of this disorder. In these individuals but also in a small percentage of individuals without appreciable atherosclerosis of their coronary arteries, attacks of coronary artery spasm can have far more serious presentations such as fainting, shock, and cardiac arrest. Typically, these presentations reflect the development of a heart attack and/or a potentially lethal heart arrhythmia; they require immediate medical intervention as well as consideration for the presence of, and specific treatment regimens for, their disorder.Variant angina should be suspected by a cardiologist when a) an individuals symptoms occur at rest or during sleep; b) an individuals symptoms occur in clusters; c) an individual with a history of angina does not develop angina during treadmill stress testing (variant angina is exercise tolerant); d) an individual with a history of angina shows no evidence of other forms of cardiac disease; and/or e) an individual without features of coronary artery atherosclerotic heart disease has a history of unexplained fainting.Complaints of chest pain should be immediately checked for an abnormal electrocardiogram (ECG). ECG changes compatible but not indicative of variant angina include elevations rather than depressions of the ST segment or an elevated ST segment plus a widening of the R wave to create a single, broad QRS complex peak termed the "monophasic curve". Associated with these ECG changes, there may be small elevations in the blood levels of cardiac damage marker enzymes, especially during long attacks. Some individuals with otherwise typical variant angina may show depressions, rather than elevations in the ST segments of their ECGs during angina pain; they may also show new U waves on ECGs during angina attacks.A significant percentage of those with variant angina have symptom-free episodes of coronary artery spasm. These episodes may be far more frequent than expected, cause myocardial ischemia (i.e. insufficient blood flow to portions of the heart), and be accompanied by potentially serious abnormalities in the rhythm of heart beats, i.e. arrythmias. The only evidence of the presence of totally asymptomatic variant angina would be detection of diagnostic changes on fortuitously conducted ECGs.

Risk factors
The intake of certain agents have been reported to trigger an attack of variant angina. These agents include:

recreational agents (e.g. nicotine in tobacco and other forms, alcoholic beverages, marijuana, cocaine);
catecholamine-like stimulants (e.g. epinephrine, dopamine, various amphetamines);
the uterus-contracting drug, ergonovine;
parasympathomimetic drugs (e.g. acetylcholine, methacholine);
anti-migraine drugs (e.g. various triptans);
chemotherapeutic drugs (e.g. 5-fluorouracil, capecitabine);
high consumption of energy drinks have been associated with variant angina.In addition, hyperventilation and virtually any stressful emotional or physical (e.g. cold exposure) event that is suspected of causing significant rises in the blood levels of catecholamines may trigger variant angina.

Mechanism
The mechanism that causes such intense vasospasm, as to cause a clinically significant narrowing of the coronary arteries is so far unknown, but there are three relevant hypotheses:

Enhanced contractility of coronary vascular smooth muscle due to reduced nitric oxide bioavailability caused by a defect in the endothelial nitric oxide synthetase enzyme which leads to endothelial function abnormalities.Acetylcholine is normally released by the parasympathetic nervous system (PSNS) at rest, and causes dilation of the coronary arteries. While acetylcholine induces vasoconstriction of vascular smooth muscle cells through a direct mechanism, acetylcholine also stimulates endothelial cells to produce nitric oxide (NO). NO then diffuses out of the endothelial cells, stimulating relaxation of the nearby smooth muscle cells. In healthy arterial walls, the overall indirect relaxation induced by acetylcholine (via nitric oxide) is of greater effect than any contraction that is induced.
When the endothelium is dysfunctional, stimulation with acetylcholine will fail to produce, or produce very little, nitric oxide. Thus, acetylcholine released by the PSNS at rest will simply cause contraction of the vascular smooth muscle.
Thromboxane A2, serotonin, histamine, and endothelin are vasoconstrictor which activated platelets release and/or cause to be released. Abnormal platelet activation (e.g. by lipoprotein(a) interference with fibrinolysis by competing with plasminogen to thereby impair fibrinolysis and promote platelet activation) results in the release of these mediators and coronary vasospasm.
Increased alpha-adrenergic receptor activity in epicardial coronary arteries or the excessive release of the "flight or fight" catecholamines (e.g. norepinephrine) that activate these receptors may lead to coronary vasospasm.Other factors thought to be associated with the development of variant angina include: intrinsic hypercontractility of coronary artery smooth muscle; existence of significant atherosclerotic coronary artery disease; and reduced activity of the parasympathetic nervous system (which normally functions to dilate blood vessels).

Diagnosis
Although variant angina has been documented in between 2% to 10% of angina patients, it can be overlooked by cardiologists who stop further evaluations after ruling out typical angina. Individuals who develop cardiac chest pain are generally treated empirically as an "acute coronary syndrome", and are immediately tested for elevations in their blood levels of enzymes such as creatine kinase isoenzymes or troponin that are markers for cardiac damage. They are also tested by ECG which may suggest variant angina if it shows elevations in the ST segment or an elevated ST segment plus a widening of the R wave during symptoms that are triggered by a provocative agent (e.g. ergonovine or acetylcholine). The electrocardiogram may show depressions rather than elevations in ST segments but in all diagnosable cases clinical symptoms should be promptly relieved and ECG changes should be promptly reversed by rapidly acting sublingual or intravenous nitroglycerin. However, the gold standard for diagnosing variant angina is to visualize coronary arteries by angiography before and after injection of a provocative agent such as ergonovine, methylergonovine or acetylcholine to precipitate an attack of vasospasm. A positive test to these inducing agents is defined as a ≥90% (some experts require lesser, e.g. ≥70%) constriction of involved arteries. Typically, these constrictions are fully reversed by rapidly acting nitroglycerin.Individuals with variant angina may have many undocumented episodes of symptom-free coronary artery spasm that are associated with poor blood flow to portions of the heart and subsequent irregular and potentially serious heart arrhythmias. Accordingly, individuals with variant angina should be intermittently evaluated for this using long-term ambulatory cardiac monitoring.

Prevention
Numerous methods are recommended to avoid attacks of variant angina. Affected individuals should not smoke tobacco products. Smoke cessation significantly reduces the incidence of patient-reported variant angina attacks. They should also avoid any trigger known to them to trigger these attacks such as emotional distress, hyperventilation, unnecessary exposure to cold, and early morning exertion. And, they should avoid any of the recreational and therapeutic drugs listed in the above signs and symptoms and risk factors sections as well as blockers of beta receptors such as propranolol which may theoretically worsen vasospasm by inhibiting beta-2 adrenergic receptors vasodilation effect mediated by these receptors naturally occurring stimulator i.e. epinephrine. In addition, aspirin should be used with caution and at low doses since at high doses it inhibits the production of the naturally occurring vasodilator, prostacyclin.

Treatment
Acute attacks
During acute attacks, individuals typically respond well to fast-acting sublingual, intravenous, or spray nitroglycerin formulations. The onset of symptom relief in response to intravenous administration, which is used in more severe attacks of angina, occurs almost immediately while sublingual formulations of it act within 1–5 minutes. Spray formulations also require ~1–5 minutes to act.

Maintenance
As maintenance therapy, sublingual nitroglycerin tablets can be taken 3-5 min before conducting activity that causes angina by the small percentage of patients who experience angina infrequently and only when doing such activity. For most affected individuals, antianginals are used as maintenance therapy to avoid attacks of variant angina. Calcium channel blockers of the dihydropyridine class (e.g. nifedipine, amlodipine) or non-dihydropyridine class (e.g. verapamil, diltiazem) are regarded as first-line drugs to avoid angina attacks. Long-acting nitroglycerins such as isosorbide dinitrate or intermittent use of short-acting nitroglycerin (to treat acute symptoms) may be added to the calcium channel blocker regimen in individuals responding sub-optimally to the channel blockers. However, individuals commonly develop tolerance, i.e. resistance, to the efficacy of continuously used long-acting nitroglycerin formulations. One strategy to avoid this development is to schedule nitroglycerin-free periods of between 12 and 14 hours between doses of long-acting nitroglycerin formulations. Individuals whose symptoms are poorly controlled by a calcium blocker may benefit from addition of a long-acting nitroglycerin and/or a second calcium channel blocker of a different class than the blocker already in use. Nevertheless, about 20% of individuals fail to respond adequately to the two-drug calcium blocker plus long-acting nitroglycerin regimen. If these individuals have significant permanent occlusion of their coronary arteries, they may benefit by stenting their occluded arteries. However, coronary stenting is contraindicated in drug- refractory individuals who do not have significant organic occlusion of their coronary arteries. For the latter individuals, other, less fully investigated drugs may provide symptom relief. Statins, e.g. fluvastatin, while not evaluated in large-scale double-blind studies, are reportedly helpful in reducing variant angina attacks and should be considered in patients when calcium channel blockers and nitroglycerin fail to achieve good results. There is also interest in using rho-kinase inhibitors, such as fasudil (available in Japan and China but not the USA), and blocker of alpha-1 adrenergic receptors such as prazosin (which when activated cause vasodilation) but studies are needed to support their clinical utility in variant angina.

Emergency
Individuals with certain severe complications of variant angina require immediate therapy. Individuals presenting with potentially lethal irregularities in the rhythm of their heart beating or a history of episodic fainting spells due to such arrhythmias require implantation of an internal defibrillator and/or cardiac pacemaker to stop such arrhythmias and restore normal heart beating. Other rare but severe complications of variant angina viz., myocardial infarction, severe congestive heart failure, and cardiogenic shock require the same immediate medical interventions that are used for other causes of these extremis conditions. In all of these emergency cases, percutaneous coronary intervention to stent areas where coronary arteries evidence spasm is only useful in individuals who have concomitant coronary atherosclerosis on coronary angiogram.

Prognosis
Most individuals with variant angina have a favorable prognosis provided they are maintained on calcium channel blockers and/or long-acting nitrates; five-year survival rates in this group are estimated as over 90%. The Japanese Coronary Spasm Association established a clinical risk scoring system to predict outcomes for variant angina. Seven major factors (i.e. history of out of hospital cardiac arrest [score = 4]; smoking, angina at rest, physically obstructive coronary artery disease, and spasm in multiple coronary arteries [score = 2]; and presence of ST segment elevations on ECG and history of using beta blockers [score = 1]) where assigned the indicated scores. Individuals with scores of 0 to 2, 3 to 5, and ≥6 experienced an incidence of a major cardiovascular event in 2.5, 7.0, and 13.0% of cases.

History
Dr. William Heberden is credited with being the first to describe in a 1768 publication the occurrence of chest pain attacks (i.e. angina pectoris) that appeared due to pathologically occluded coronary arteries. These attacks were triggered by exercise or other forms of exertion and relieved by rest and nitroglycerin. In 1959, Dr. Myron Prinzmetal described a type of angina that differed from the classic cases of Heberden angina in that it commonly occurred in the absence of exercise or exertion. Indeed, it often woke patients from their normal sleep. This variant angina differed from the classical angina described by Dr. Heberden in that it appeared due to episodic vasospasm of coronary arteries that were typically not occluded by pathological processes such as atherosclerosis, emboli, or spontaneous dissection (i.e. tears in the walls of coronary arteries). Variant angina had been described twice in the 1930s by other authors and was referred to as cardiac syndrome X (CSX) by Kemp in 1973, in reference to patients with exercise-induced angina who nonetheless had normal coronary angiograms. CSX is now termed microvascular angina, i.e. angina caused by disease of the hearts small arteries.Some key features of variant angina are chest pain that is concurrently associated with elevations in the ST segment on electrocardiography recordings, that often occurs during the late evening or early morning hours in individuals who are at rest, doing non-strenuous activities, or asleep, and that is not associated with permanent occlusions of their coronary vessels. The disorder seems to occur more often in women than men, has a particularly high incidence in Japanese males as well as females, and affects individuals who may smoke tobacco products but exhibit few other cardiovascular risk factors. However, individuals exhibiting angina symptoms that are associated with depressions in their electrocardiogram ST segments, that are triggered by exertion, and/or who have atherosclerotic coronary artery disease are still considered to have variant angina if their symptoms are caused by coronary artery spasms. Finally, rare cases may exhibit symptom-free coronary artery spasm that is nonetheless associated with cardiac muscle ischemia (i.e </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Antithrombin III deficiency and explain in detail? [/INST] Antithrombin III deficiency (abbreviated ATIII deficiency) is a deficiency of antithrombin III. This deficiency may be inherited or acquired. It is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism, and repetitive intrauterine fetal death (IUFD). Hereditary antithrombin deficiency results in a state of increased coagulation which may lead to venous thrombosis. Inheritance is usually autosomal dominant, though a few recessive cases have been noted. The disorder was first described by Egeberg in 1965. The causes of acquired antithrombin deficiency are easier to find than the hereditary deficiency.The prevalence of antithrombin deficiency is estimated at ~0.02 to 0.2% of the general population, and 1-5% of patients with venous thromboembolism.  There is an elevated risk of thrombosis, whereby 50% patients with AT deficiency were found to have venous thromboembolism by age 50.

Cause
Diagnosis
A clinical suspicion for antithrombin deficiency can be made in patients with: 1. recurrent venous thromboembolic disease, 2 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hemoglobinemia and explain in detail? [/INST] Hemoglobinemia (or haemoglobinaemia) is a medical condition in which there is an excess of hemoglobin in the blood plasma. This is an effect of intravascular hemolysis, in which hemoglobin separates from red blood cells, a form of anemia.
Hemoglobinemia can be caused by intrinsic or extrinsic factors. When hemoglobinemia is internally caused, it is a result of recessive genetic defects that cause the red blood cells to lyse, letting the hemoglobin spill out of the cell into the blood plasma.
In intravascular hemolysis, hemoglobin is released and binds with haptoglobin. This causes haptoglobin levels to decrease.
Once haptoglobin is saturated, free hemoglobin readily distributes to tissues where it might be exposed to oxidative conditions. In such conditions, heme can be released from ferric hemoglobin. The free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. Hemopexin (Hx) is another plasma glycoprotein able to bind heme with high affinity. Hx sequesters heme in an inert, non-toxic form and transports it to the liver for catabolism and excretion. As long as both haptoglobin and hemopexin are saturated, the remaining free hemoglobins are filtered in the kidney and some of them will be reabsorbed by way of proximal tubules.
In externally caused hemoglobinemia, an outside attacker acts as an antibody against the red blood cells. This can cause the cells to be destroyed and their hemoglobin released. In extravascular hemolysis, red blood cells are phagocytized by macrophages in the spleen and liver.Abnormal value of hemoglobin does not necessarily indicate a medical problem needing treatment. Diet, activity level, medications, a womens menstrual cycle, and other considerations can affect the results. Additionally to these, one may have higher than normal hemoglobin if he/she lives in a high altitude area.

Causes
There are other causes besides what happens within the body in the blood cells </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Vaginal adenosis and explain in detail? [/INST] Vaginal adenosis is a benign  abnormality in the vagina, commonly thought to be caused by intrauterine and neonatal exposure of diethylstilbestrol and other progestogens and nonsteroidal estrogens, however it has also been observed in otherwise healthy women and has been considered at times idiopathic or congenital. Postpubertal lesions have also been observed to grow de novo. It has a rather common incidence, of about 10% of adult women.

Causes
Vaginal adenosis is characterised by the presence of metaplastic cervical or endometrial epithelium within the vaginal wall, considered as derived from Müllerian epithelium islets in later life. In women who were exposed to certain chemicals, vaginal adenosis may arise in up to 90%. Since these contraceptives were discontinued, incidence has dropped dramatically. Risk is however still present in subsequent generations due to recent exposure.It is thought steroid hormones play a stimulatory growth in adenosis formation. Vaginal adenosis is also often observed in adenocarcinoma patients.

Diagnosis
Colposcopically, it presents itself similarly to columnar epithelium on the cervix, assisted with lugols solution application for diagnosis. It can be discovered as nodules or cysts on the vaginal tube, with biopsy needed for further diagnosis. As seen cytologically, epithelial and stromal cells in vaginal adenosis show characteristic fusion through the basal lamina or with stromal fibroblasts. Adenosal cells can be distinguished as mucinous, tuboendometrial, and embryonic. Its mucinous cells resemble the normal cervical lining, while its tuboendometrial cells resemble the lining of normal fallopian tubes or endometrium.It is sometimes considered a precancerous lesion, given clear-cell adenocarcinoma patients present these lesions in close proximity to atypical tuboendometrial glands, and microglandular hyperplasia has been seen to arise from these lesions.

References
Further reading
OBrien, P. C.; Noller, K. L.; Robboy, S. J.; Barnes, A. B.; Kaufman, R. H.; Tilley, B. C.; Townsend, D. E. (March 1979). "Vaginal epithelial changes in young women enrolled in the National Cooperative Diethylstilbestrol Adenosis (DESAD) project". Obstetrics & Gynecology. 53 (3): 300–308. PMID 424101.
Laronda, Monica M.; Unno, Kenji; Butler, Lindsey M.; Kurita, Takeshi (2012). "The development of cervical and vaginal adenosis as a result of diethylstilbestrol exposure in utero". Differentiation. 84 (3): 252–260. doi:10.1016/j.diff.2012.05.004. ISSN 0301-4681. PMC 3443265. PMID 22682699. PMID 22682699.
Ganesan, R.; Ferryman, S. R.; Waddell, C. A. (1999). "Vaginal adenosis in a patient on Tamoxifen therapy: a case report". Cytopathology. 10 (2): 127–130. doi:10.1046/j.1365-2303.1999.00162.x. ISSN 0956-5507. PMID 10211619. S2CID 33999959.
Laronda, M. M.; Unno, K.; Ishi, K.; Serna, V </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cerebral softening and explain in detail? [/INST] Cerebral softening, also known as encephalomalacia, is a localized softening of the substance of the brain, due to bleeding or inflammation. Three varieties, distinguished by their color and representing different stages of the disease progress, are known respectively as red, yellow, and white softening.

Causes
Stroke
Ischemia: A decreased or restriction of circulating blood flow to a region of the brain which deprives neurons of the necessary substrates (primarily glucose); represents 80% of all strokes. A thrombus or embolus plugs an artery so there is a reduction or cessation of blood flow. This hypoxia or anoxia leads to neuronal injury, which is known as a stroke. The death of neurons leads to a so-called softening of the cerebrum in the affected area.Hemorrhage: Intracerebral hemorrhage occurs in deep penetrating vessels and disrupts the connecting pathways, causing a localized pressure injury and in turn injury to brain tissue in the affected area. Hemorrhaging can occur in instances of embolic ischemia, in which the previously obstructed region spontaneously restores blood flow. This is known as a hemorrhagic infarction and a resulting red infarct occurs, which points to a type of cerebral softening known as red softening.

Circle of Willis
In a study on the circle of Willis and its relation to cerebral vascular disorders, a comparison on various anomalies between normal brains (those without the condition of cerebral softening) and brains with cerebral softening were looked at to observe trends in the differences of the anatomical structure of the circle of Willis. Statistically significant results were found in the percentage of normal brains that had a normal circle of Willis and those that had cerebral softening and had a normal circle of Willis. The results yielded 52% of normal brains having a normal circle of Willis, while only 33% of brains with cerebral softening had a normal circle of Willis. There were also a higher number of string-like vessels in brains with cerebral softening (42%), than there were in normal brains (27%). These results point to an assumption of a higher incidence rate of anomalies in brains with cerebral softening versus those that do not have cerebral softening.

Types of softening
Red softening
Red softening is one of the three types of cerebral softening. As its name suggests, certain regions of cerebral softening result in a red color. This is due to a hemorrhagic infarct, in which blood flow is restored to an area of the brain that was previously restricted by an embolism. This is termed a "red infarct" or also known as red softening.Upon autopsy of several subjects, Dr. Cornelio Fazio found that the most common areas of this type of softening occurred where there was a hemorrhage of the middle cerebral artery or the superior or deep branches to it. The subjects softened area was not always near the arteries but where the capillaries perfused the brain tissue. The symptoms were similar to that of a stroke.

White softening
White softening is another form of cerebral softening. This type of softening occurs in areas that continue to be poorly perfused, with little to no blood flow. These are known as "pale" or "anemic infarcts" and are areas that contain dead neuronal tissue, which result in a softening of the cerebrum.

Yellow softening
Yellow softening is the third type of cerebral softening. As its name implies, the affected softened areas of the brain have a yellow appearance. This yellow appearance is due to atherosclerotic plaque build-up in interior brain arteries coupled with yellow lymph around the choroid plexus, which occurs in specific instances of brain trauma.

Stages
Early life
Newborn cerebral softening has traditionally been attributed to trauma at birth and its effect on brain tissue into adulthood. However, more recent research shows that cerebral softening in newborns and the degeneration of white matter is caused by asphyxia and/or later infection.  There is no causal evidence to support the hypothesis that problems in labor contribute to the development of softening in infant white matter. Also, further evidence shows a possible connection between low sugar and high protein levels in cerebral spinal fluid that can contribute to disease or virus susceptibility leading to cerebral softening.

Later life
Cases of cerebral softening in infancy versus in adulthood are much more severe due to an infants inability to sufficiently recover brain tissue loss or compensate the loss with other parts of the brain.  Adults can more easily compensate and correct for the loss of tissue use and therefore the mortality likelihood in an adult with cerebral softening is less than in an infant.

Documented cases
In this late 19th-century case study, a 10-year-old boy was found to have cerebral softening in specific parts of the brain, limiting specific sensory function.  The identifiable softening enabled researchers to detect and partition cerebral areas related to different sensory perceptions.Another case in the late 19th century showed that cerebral softening, when caused by hemorrhaging, can affect various neural pathways leading to convulsions, spasms, coma and death.A third case in 1898 followed the ten-day decline of a 66-year-old woman with cerebral softening. She had yellow softening which led to symptoms that started slowly with transient facial paralysis on the right side of the face. The limbs later became cold and the right side of the body transiently progressed between semi-paralysis and tetanus. Her heart rate and respiration rate became slow by days three and four. Later she developed a yellow jaundiced appearance in the sclera and skin that the doctor proposed as paroxysmal hemoglobinuria upon autopsy. On the last days, the paralysis became more frequent, respiration rose and she developed tachycardia </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Nezelof syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Targetoid hemosiderotic hemangioma and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Exostosis and explain in detail? [/INST] An exostosis, also known as bone spur, is the formation of new bone on the surface of a bone. Exostoses can cause chronic pain ranging from mild to debilitatingly severe, depending on the shape, size, and location of the lesion. It is most commonly found in places like the ribs, where small bone growths form, but sometimes larger growths can grow on places like the ankles, knees, shoulders, elbows and hips. Very rarely are they on the skull.
Exostoses are sometimes shaped like spurs, such as calcaneal spurs.
Osteomyelitis, a bone infection, may leave the adjacent bone with exostosis formation. Charcot foot, the neuropathic breakdown of the feet seen primarily in diabetics, can also leave bone spurs that may then become symptomatic.
They normally form on the bones of joints, and can grow upwards. For example, if an extra bone formed on the ankle, it might grow up to the shin.
When used in the phrases "cartilaginous exostosis" or "osteocartilaginous exostosis", the term is considered synonymous with osteochondroma </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is MORM syndrome and explain in detail? [/INST] MORM syndrome is an autosomal recessive congenital disorder characterized by mental retardation, truncal obesity, retinal dystrophy, and micropenis". The disorder shares similar characteristics with Bardet–Biedl syndrome and Cohen syndrome, both of which are autosomal recessive genetic disorders. MORM syndrome can be distinguished from the above disorders because symptoms appear at a young age. The disorder is not dependent on sex of the offspring, both male and female offspring are equally likely to inherit the disorder.
The syndrome is caused by a mutation in the INPP5E gene which can be located on chromosome 9 in humans.  Further mapping resulted in the identification of a MORM syndrome locus on chromosome 9q34.3 between the genetic markers D9S158 and D9S905.

Presentation
For individuals with MORM syndrome, symptoms do not appear until about one year of age. From conception to birth, individuals with MORM syndrome appear asymptotic, with no abnormal characteristics. Vision is negatively affected within the first year of life, particularly night vision. Individuals with MORM syndrome experience decreased visual acuity, meaning their ability to see distinct sharp lines decreases. Vision quality continues to deteriorate until age three. Any further reduction in vision acuity is not observed until the individual is between the ages thirty to forty. Delayed sentence processing and intellectual disability is associated with individuals with MORM syndrome, primarily observed at age four. Individuals continue to develop and grow until they are five to twelve years old. During this age bracket, truncal obesity can develop, characterized by the buildup of fat around ones trunk or torso as opposed to the persons extremities. Males enter puberty at around age twelve and develop normally, except for their penis, which will remain at the prepubescent size, resulting in a micropenis. Both the life span and fertility of individuals with MORM syndrome is unclear .

Genetic
MORM syndrome is associated with the gene INPP5E. INPP5E is a gene whose function is not well understood. It is hypothesized to play a role in primary cilia stability. A homozygous mutation in the INPP5E gene, on chromosome 9q34, is the cause for MORM syndrome. The mutation causes a homozygous transition in the last exon of the INPP5E gene. This transition results in the DNA bases changing from a cytosine residue to a thymine residue.
The resulting protein will then have an altered amino acid sequence. In unaffected individuals this specific codon (region of DNA bases) is supposed to code for the amino acid glutamine. In cases of MORM syndrome this codon codes for a termination sequence, which prematurely stops the production of the protein </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Thyrotoxic myopathy and explain in detail? [/INST] Thyrotoxic myopathy (TM) is a neuromuscular disorder that develops due to the overproduction of the thyroid hormone thyroxine. Also known as hyperthyroid myopathy, TM is one of many myopathies that lead to muscle weakness and muscle tissue breakdown. Evidence indicates the onset may be caused by hyperthyroidism. There are two known causes of hyperthyroidism that lead to development thyrotoxic myopathy including a multinodular goiter and Graves disease. Physical symptoms of TM may include muscle weakness, the breakdown of muscle tissue, fatigue, and heat intolerance. Physical acts such as lifting objects and climbing stairs may become increasingly difficult. If untreated, TM can be an extremely debilitating disorder that can, in extreme rare cases, lead to death. If diagnosed and treated properly the effects can be controlled and in most cases reversed leaving no lasting effects.

Symptoms and signs
Physical symptoms may include:
Muscle weakness
Degeneration of muscle tissue
Fatigue
Heat intolerance

Chronic TM
Symptoms of chronic TM arise slowly. Patients usually cite decreased exercise tolerance, increased fatigue, and difficulty completing certain tasks after six months of onset. If chronic TM goes untreated worse symptoms may develop including difficulty swallowing and respiratory distress. These occurrences are rare since diagnosis of chronic TM usually occurs during the early stages of onset, before these symptoms develop.

Acute TM
Acute TM is rarer than chronic TM and symptoms appear within days of onset. Acute TM degrades muscle fibers rapidly. Due to the rapid degradation of muscle fibers patients usually cite severe muscle cramps and muscle pain. Some acute TM patients may present symptoms of blurred vision and bulging eyes due to eye muscle degradation and inflammation, but documented cases are rare. Acute TM patients usually have very weak respiratory muscles and often severe respiratory failure occurs.

Cause
TM is directly related to thyroxine toxicity. It is believed this disorder is a direct result of hyperthyroidism, specifically hyperthyroidism caused by Graves disease or a multinodular goiter. Both cause the thyroid gland to overproduce thyroxine.  A multinodular goiter is a condition where the thyroid develops nodules. Overproduction of thyroxine is due to the enlargement of the thyroid gland. Graves disease is an autoimmune condition where the immune system chronically stimulates the TSH receptor in the thyroid and induces overproduction of the thyroxine hormone.

Pathophysiology
Excess thyroxine is believed to bring about the onset of thyrotoxic myopathy and eventually cause the degradation of muscle tissue. Thyroxine is a hormone produced in the thyroid gland that regulates the growth metabolism of the nervous system and regulates basal metabolic rate of many cell types.  Scientists agree thyroxine brings about the degradation of muscle fibers specifically at the motor end plates of neuromuscular junctions. There is debate as to whether thyroxine degrades the motor end plates from the muscular side, from the nervous system side, or a combination.To understand how high levels of thyroxine can be toxic and lead to thyrotoxic myopathy physiologically, consider basic neuromuscular junction function. Under normal circumstances, muscle contraction occurs when electrical impulses travel down descending axons from the brain or spinal cord towards the neuromuscular junction. The axon terminal depolarizes and releases Acetylcholine (ACh), a neurotransmitter, which in turn stimulates the motor end plate (MEP) of the muscle fiber the nerve is innervating. When the MEP depolarizes the muscle fiber releases calcium initiating the process of muscle contraction.With the onset of TM due to thyroxine toxicity, there is evidence to suggest that structural changes in MEPs could lead to muscle fiber degradation, weakness, and fatigue. Research indicates that decreased levels of Acetylcholinesterase AChE, an enzyme that breaks down ACh, was observed within the neuromuscular junction. This decrease in AChE blocks degradation of ACh causing ACh to increasingly stimulate the MEP of the muscle fiber. Over stimulation of MEP could cause more muscle contractions which eventually evoke muscle fiber fatigue, weakness, and finally degradation, which are characteristic symptoms of TM. It is believed this decrease in AChE and MEP structural changes could be the result of over stimulation of thyroxin blocking the axoplasmic flow of trophic factors down the axon terminal especially considering thyroxines role in nervous system growth and metabolism regulation.
Other research indicates muscle fiber fatigue, weakness, and degradation associated with TM is the direct action thyroxine has on the muscle fibers themselves. Research suggests thyroxine directly causes a decrease in protein kinase affinity to cAMP within muscle fibers  This causes an increase in cAMP within the muscle fibers since protein kinases are not inactivating cAMP. Increased levels of cAMP within the muscle fibers cause increased release of Ca2+ from the muscle fibers sarcoplasmic reticulum which eventually leads to more muscle contractions. Like the nervous system proposal increased muscle contractions eventually evoke muscle fiber fatigue, weakness, and finally degradation, which are characteristic symptoms of TM. There is evidence to support both theories; it has been suggested that toxic levels of thyroxine may ultimately attack muscle fibers directly and indirectly by the motor neurons that innervate the affected muscle fibers.

Diagnosis
Thyrotoxic myopathy is usually diagnosed by a neurologist who has extensive experience diagnosing neuromuscular disorders. There are many types of neuromuscular disorders that present similar physical symptoms. Extensive clinical tests are performed first to determine if there is a neuromuscular disorder and then to determine which disorder it is. Electromyography is used to diagnose myopathies by comparing muscle contraction responses to electrical stimulus. For TM results may indicate normal responses or myopathic responses depending on how the disorder has progressed. Early detection may indicate normal contractual responses while highly progressed TM may show a significant decrease in contraction response.Blood tests are then conducted to determine the specific myopathy. For TM, blood tests reveal increased thyroxine levels.  Increased thyroxine levels accompanied with decreased neuromuscular responses together provide best evidence for TM diagnosis.  Creatine phosphokinase levels are also examined during the blood tests. Normal or increased levels may be observed with TM depending on the severity of TMs progression. Normal levels indicate possible early stages of progression while increased levels may indicate later stages of thyrotoxic myopathy. Muscle biopsies may also be taken and examined to determine TMs progression with respect to physical degradation. Like measured creatine phosphokinase levels results from the muscle biopsy characteristic of TM typically show normal to severe fiber degradation with respective indications to the severity of progression.

Treatment
Treatment for TM is typically done with the collaboration of many medical specialists. Usually a neuromuscular specialist, an endocrinologist, a surgeon, and an ophthalmologist will combine their efforts to successfully treat patients with TM. If a patient develops significant to severe muscle degradation as a result of TM, a physical therapist may be consulted for rehabilitation.  Since excess thyroxine leads to onset of TM, the overall goal of treatment is to reduce the overproduction of thyroxine from the thyroid gland and restore normal thyroid homeostasis. This can be accomplished three ways including using medication, radiation, and surgery.The first choice involves using medications to alleviate the symptoms and reverse the damage by blocking the production of thyroxine from the thyroid gland. Beta-blockers are used to alleviate the symptoms associated with TM. But beta-blockers do not reduce the damage done by excess thyroxine. Medications such as propylthiouracil and methimazole are administered to block the release of thyroxine from the thyroid and to block the damage thyroxine inflicts on muscle fiber tissue.One treatment option is the use of radioactive iodine which directly destroys the overactive thyroid gland. The thyroid gland naturally uses iodine to produce thyroxine and other hormones. It cannot distinguish between normal iodine and the radioactive version. Administering the radioactive isotope causes the thyroid to take in the lethal iodine and quickly radiation destroys it. Typically overproduction of thyroxine using radio-iodine is blocked with one dose. The drawback to this treatment is the thyroid gland is completely destroyed and patients often develop hypothyroidism. Some do so only a few months after treatment while others may not be affected for 20–30 years. Hypothyroidism patients must begin a lifelong regimen of thyroid replacement hormones. While the onset of hypothyroidism is most common with radio-iodine treatment, the condition has been observed in patients treated with medication series and surgery.The last option for TM treatment includes surgical removal of portions of the thyroid which can also be performed to restore thyroid homeostasis. This treatment option usually is done when overproduction of TM is caused by multinodular goiters </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is First arch syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Jamaican vomiting sickness and explain in detail? [/INST] Jamaican vomiting sickness, also known as toxic hypoglycemic syndrome (THS), acute ackee fruit intoxication, or ackee poisoning, is an acute illness caused by the toxins hypoglycin A and hypoglycin B, which are present in fruit of the ackee tree.  While in the fully ripened arils, hypoglycin A is at levels of less than 0.1 ppm, in unripe arils it can be over 1000 ppm and can cause vomiting and even death. Some countries in the Caribbean and Western Africa experience frequent cases.

Presentation
Abdominal discomfort begins two to six hours after eating unripe ackee fruit, followed by sudden onset vomiting. In severe cases, profound dehydration, seizures, coma, and death may ensue.  Children and those who are malnourished are more susceptible to the disease.

Pathophysiology
When ingested, hypoglycin A is metabolized to produce methylenecyclopropylacetic acid (MCPA) </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bertolottis syndrome and explain in detail? [/INST] Bertolottis syndrome is a commonly missed cause of back pain which occurs due to lumbosacral transitional vertebrae (LSTV). It is a congenital condition but is not usually symptomatic until ones later twenties or early thirties. However, there are a few cases of Bertolottis that become symptomatic at a much earlier age.
It is named for Mario Bertolotti, an Italian physician who first described it in 1917.

Presentation
A chronic, persistent low back pain along with buttock pain is the most important presentation. Radicular pain is observed.

Pathophysiology
Bertolottis syndrome is characterized by sacralization of the lowest lumbar vertebral body and lumbarization of the uppermost sacral segment. It involves a total or partial unilateral or bilateral fusion of the transverse process of the lowest lumbar vertebra to the sacrum, leading to the formation of a transitional 5th lumbar vertebra. Of importance is that this syndrome will result in a pain generating 4th lumbar disc resulting in a "sciatic" type of a pain correlating to the 5th lumbar nerve root. Usually the transitional vertebra will have a "spatulated" transverse process on one side resulting in articulation or partial articulation with the sacrum or at time the ilium and in some cases with both. This results in limited / altered motion at the lumbo-sacral articulation. This loss of motion will then be compensated for at segments superior to the transitional vertebra resulting in accelerated degeneration and strain through the L4 disc level which can become symptomatic and inflame the adjacent L5 nerve root resulting in "sciatic" or radicular pain patterns. Scoliosis is frequently found to be associated.

Diagnosis
The diagnosis depends on appropriate patient history backed by imaging studies like X ray and MRI. Lumbosacral spine radiographs help in the identification of the skeletal abnormality </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Abdominal pregnancy and explain in detail? [/INST] An abdominal pregnancy is a rare type of ectopic pregnancy where the embryo or fetus is growing and developing outside the womb in the abdomen, but not in the Fallopian tube (usual location), ovary or broad ligament.Because tubal, ovarian and broad ligament pregnancies are as difficult to diagnose and treat as abdominal pregnancies, their exclusion from the most common definition of abdominal pregnancy has been debated.Others—in the minority—are of the view that abdominal pregnancy should be defined by a placenta implanted into the peritoneum.

Signs and symptoms
Symptoms may include abdominal pain or vaginal bleeding during pregnancy. As this is nonspecific in areas where ultrasound is not available the diagnosis was often only discovered during surgery to investigate the abnormal symptoms. They are typically diagnosed later in the developing world than the developed. In about half of cases from a center in the developing world the diagnosis was initially missed.It is a dangerous condition as there can be bleeding into the abdomen that results in low blood pressure and can be fatal. Other causes of death in women with an abdominal pregnancy include anemia, pulmonary embolus, coagulopathy, and infection.

Risk factors
Risk factors are similar to tubal pregnancy with sexually transmitted disease playing a major role; however about half of those with ectopic pregnancy have no known risk factors (which include damage to the Fallopian tubes from previous surgery or from previous ectopic pregnancy, and tobacco smoking).

Mechanism
Implantation sites can be anywhere in the abdomen but can include the peritoneum outside of the uterus, the rectouterine pouch (culdesac of Douglas), omentum, bowel and its mesentery, mesosalpinx, and the peritoneum of the pelvic wall and the abdominal wall. The growing placenta may be attached to several organs including tube and ovary.  Rare other sites have been the liver and spleen, giving rise to a hepatic pregnancy or splenic pregnancy, respectively. Even an early diaphragmatic pregnancy has been described in a patient where an embryo began growing on the underside of the diaphragm.

Primary versus secondary implantation
A primary abdominal pregnancy refers to a pregnancy that first implanted directly in the peritoneum, save for the tubes and ovaries; such pregnancies are very rare, only 24 cases having been reported by 2007. Typically an abdominal pregnancy is a secondary implantation which means that it originated from a tubal (less common an ovarian) pregnancy and re-implanted. Other mechanisms for secondary abdominal pregnancy include uterine rupture, rupture of a uterine rudimentary horn and fimbrial abortion.

Diagnosis
Suspicion of an abdominal pregnancy is raised when the fetal anatomy can be easily felt, or the lie is abnormal, the cervix is displaced, or there is failed induction of labor. X-rays can be used to aid diagnosis. Sonography can demonstrate that the pregnancy is outside an empty uterus, there is reduced to no amniotic fluid between the placenta and the fetus,  no uterine wall surrounding the fetus, fetal parts are close to the abdominal wall, the fetus has an abnormal lie, the placenta looks abnormal and there is free fluid in the abdomen. MRI has also been used with success to diagnose abdominal pregnancy and plan for surgery. Elevated alpha-fetoprotein levels are another clue of the presence of an abdominal pregnancy.

Ultrasound
Most cases can be diagnosed by ultrasound. The diagnosis however may be missed with ultrasound depending on the operators skill.

Criteria
To diagnose the rare primary abdominal pregnancy, Studdifords criteria need to be fulfilled: tubes and ovaries should be normal, there is no abnormal connection (fistula) between the uterus and the abdominal cavity, and the pregnancy is related solely to the peritoneal surface without signs that there was a tubal pregnancy first. Studdifords criteria were refined in 1968 by Friedrich and Rankin to include microscopic findings.

Differential diagnosis
Depending on gestational age the differential diagnoses for abdominal pregnancy include miscarriage, intrauterine fetal death, placental abruption, an acute abdomen with an intrauterine pregnancy and a fibroid uterus with an intrauterine pregnancy .

Treatment
Ideally the management of abdominal pregnancy should be done by a team that has medical personnel from multiple specialties. Potential treatments consist of surgery with termination of the pregnancy (removal of the fetus) via laparoscopy or laparotomy, use of methotrexate, embolization, and combinations of these.  Sapuri and Klufio indicate that conservative treatment is also possible if the following criteria are met: 1. there are no major congenital malformations; 2. the fetus is alive; 3. there is continuous hospitalization in a well-equipped and well-staffed maternity unit which has immediate blood transfusion facilities; 4. there is careful monitoring of maternal and fetal well-being; and 5. placental implantation is in the lower abdomen away from the liver and spleen. The choice is largely dictated by the clinical situation.  Generally, treatment is indicated when the diagnosis is made; however, the situation of the advanced abdominal pregnancy is more complicated.

Advanced abdominal pregnancy
Advanced abdominal pregnancy refers to situations where the pregnancy continues past 20 weeks of gestation (versus early abdominal pregnancy < 20 weeks). In those situations, live births have been reported in the lay press where the babies are not uncommonly referred to as Miracle babies. A patient may carry a dead fetus but will not go into labor. Over time, the fetus calcifies and becomes a lithopedion.It is generally recommended to perform a laparotomy when the diagnosis of an abdominal pregnancy is made. However, if the baby is alive and medical support systems are in place, careful watching could be considered to bring the baby to viability. Women with an abdominal pregnancy will not go into labor. Delivery in a case of an advanced abdominal pregnancy will have to be via laparotomy. The survival of the baby is reduced and high perinatal mortality rates between 40% and 95% have been reported.Babies of abdominal pregnancies are prone to birth defects due to compression in the absence of the uterine wall and the often reduced amount of amniotic fluid surrounding the unborn baby. The rate of malformations and deformations is estimated to be about 21%; typical deformations are facial and cranial asymmetries and joint abnormalities and the most common malformations are limb defects and central nervous malformations.Once the baby has been delivered placental management becomes an issue </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Catastrophic antiphospholipid syndrome and explain in detail? [/INST] Catastrophic antiphospholipid syndrome (CAPS), also known as Ashersons syndrome, is a rare autoimmune disease in which widespread, intravascular clotting causes multi-organ failure. The syndrome is caused by antiphospholipid antibodies that target a group of proteins in the body that are associated with phospholipids. These antibodies activate endothelial cells, platelets, and immune cells, ultimately causing a large inflammatory immune response and widespread clotting. CAPS was first described by Ronald Asherson in 1992. The syndrome exhibits thrombotic microangiopathy, multiple organ thromboses, and in some cases  tissue necrosis and is considered an extreme or catastrophic variant of the antiphospholipid syndrome.
CAPS has a mortality rate of about 50%. With the establishment of a CAPS-Registry more has been learned about this syndrome, but its cause remains unknown. Infection, trauma, medication, and/or surgery can be identified in about half the cases as a "trigger". It is thought that cytokines are activated leading to a cytokine storm with the potentially fatal consequences of organ failure. A low platelet count is a common finding.

Presentation
Clinically, the syndrome affects at least three organs and may affect many organ systems. The syndrome usually occurs with small vessel thromboses affecting organ systems such as the gastrointestinal tract and manifestations of the acute respiratory distress syndrome (ARDS), a type of systemic inflammatory response syndrome (SIRS). Peripheral thrombosis may be encountered affecting veins and arteries. Intra-abdominal thrombosis may lead to pain. A thrombotic storm may also occur due to the following precipitating events: alterations in coagulation and fibrinolysis, which induce high mortality rates, and infections amongst pediatric patients where IgM and IgG anti-β2-GPI antibodies induce an endothelial signal, leading to a procoagulant state. It is also hypothesized that thrombotic storms occur due to prothrombotic genetic risk factors, which trigger a sped-up form of thrombosis after its first occurrence, rather than being caused solely by environmental factors. Cardiovascular, nervous, kidney, and lung system complications are common. More specifically with the heart, Ashersons syndrome can lead to complications such as mitral valve regurgitation (MVR) in which the mitral valve does not shut properly allowing backflow of blood into the heart as well as angina (chest pain) and myocardial infarction (heart attack). Furthermore, complications in the kidneys may occur, including low urine production and high blood pressure, while complications with the lungs can result in rapid breathing (hyperventilation) and low oxygen levels (hypoxemia). The affected individual may exhibit skin purpura and necrosis. Cerebral manifestations may lead to encephalopathy and seizures. Myocardial infarctions may occur. Strokes may occur due to the arterial clotting involvement. Death may result from multiple organ failure.
Furthermore, the syndrome has been shown to manifest multi-organ failures and miscarriages in the context of pregnancies. 54% of pregnant mothers with the disease experienced fetal loss, and around 50% of pregnant mothers died from complications associated with the syndrome.

Diagnosis
Two specific types of blood tests are used to aid in the diagnosis of Ashersons Syndrome </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Foreign body and explain in detail? [/INST] A foreign body (FB) is any object originating outside the body of an organism. In machinery, it can mean any unwanted intruding object.
Most references to foreign bodies involve propulsion through natural orifices into hollow organs.
Foreign bodies can be inert or irritating. If they irritate they will cause inflammation and scarring. They can bring infection into the body or acquire infectious agents and protect them from the bodys immune defenses. They can obstruct passageways either by their size or by the scarring they cause. Some can be toxic or generate toxic chemicals from reactions with chemicals produced by the body, as is the case with many examples of ingested metal objects.
With sufficient force (as in firing of bullets), a foreign body can become lodged into nearly any tissue.

Gastrointestinal tract
One of the most common locations for a foreign body is the alimentary tract.
It is possible for foreign bodies to enter the tract from the mouth or rectum.
Both children and adults experience problems caused by foreign objects becoming lodged within their bodies. Young children, in particular, are naturally curious and may intentionally put shiny objects, such as coins or button batteries, into their mouths. They also like to insert objects into their ear canals and nostrils. The severity of a foreign body can range from unconcerning to a life-threatening emergency. For example, a coin causes local pressure on the tissue but generally is not a medical emergency to remove. A button battery, which can be a very similar size to a coin, generates hydroxide ions at the anode and causes a chemical burn in two hours.  An ingested button battery that is stuck in the esophagus is a medical emergency. In 2009, Avolio Luigi and Martucciello Giuseppe showed that although ingested nonmagnetic foreign bodies are likely to be passed spontaneously without consequence, ingested magnets (magnetic toys) may attract each other through childrens intestinal walls and cause severe damage, such as pressure necrosis, perforation, intestinal fistulas, volvulus, and obstruction.

Pancreas
Sometimes foreign bodies can pass spontaneously through the gastrointestinal tract and perforate or penetrate the wall of stomach and duodenum and migrate into pancreas. The laparoscopic approach before open surgery could be performed safely for the removal of foreign bodies embedded in the pancreas.

Airways
It is possible for a foreign body to enter the airways and cause choking. A choking case can require the fast usage of basic anti-choking techniques to clear the airway.
In one study, peanuts were the most common obstruction. In addition to peanuts, hot dogs, grapes, and latex balloons are also serious choking hazards in children that can result in death. A latex balloon will conform to the shape of the trachea, blocking the airway and making it difficult to expel with basic anti-choking techniques.

Eyes
Airborne particles can lodge in the eyes of people at any age. These foreign bodies often result in allergies which are either temporary or even turn into a chronic allergy. This is especially evident in the case of dust particles.
It is also possible for larger objects to lodge in the eye. The most common cause of intraocular foreign bodies is hammering. Corneal foreign bodies are often encountered due to occupational exposure and can be prevented by instituting safety eye-wear at work place.Foreign bodies in the eye affect about 2 per 1,000 people per year.

Skin
Splinters are common foreign bodies in skin. Staphylococcus aureus infection often causes boils to form around them.Tetanus prophylaxis may be appropriate.

Peritoneum
Foreign bodies in the peritoneum can include retained surgical instruments after abdominal surgery. Rarely, an intrauterine device can perforate the uterine wall and enter the peritoneum.
Foreign bodies in the peritoneum eventually become contained in a foreign body granuloma. In the extremely rare case of retained ectopic pregnancy, this forms a lithopedion.

Other
Foreign bodies can also become lodged in other locations:

anus or rectum
blood vessels or thoracic system
ears
nose
teeth and periodontium
urethra
vagina

Other animals
Foreign bodies are common in animals, especially young dogs and cats. Dogs will readily eat toys, bones, and any object that either has food on it or retains the odor of food. Unlike humans, dogs are susceptible to gastrointestinal obstruction due to their ability to swallow relatively large objects and pass them through the esophagus. Foreign bodies most commonly become lodged in the stomach because of the inability to pass through the pyloric sphincter into the jejunum. Symptoms of gastrointestinal obstruction include vomiting, abdominal pain often characterized by aggression, acute infection, and depression due to dehydration. Treatment of a foreign body is determined by its severity. The amount of time a foreign body is present, location of the object, degree of obstruction, previous health status of the animal and the type of material from which the foreign body is made can all determine the severity of the condition. Peritonitis results if either the stomach or intestine has ruptured. Foreign bodies in the stomach can sometimes be removed by endoscopic retrieval or if necessary by gastrotomy. Very often, a simple instrument to remove foreign bodies without operation endoscopy is the Hartmann Alligator Forceps. The instrument is manufactured from 8 cm to 1 m length. Foreign bodies in the jejunum are removed by enterotomy.
Certain foreign bodies in animals are especially problematic. Bones or objects with sharp edges may cause tearing of the wall of the esophagus, stomach, or small intestine and lead to peritonitis </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Leukodystrophy and explain in detail? [/INST] Leukodystrophies are a group of usually inherited disorders characterized by degeneration of the white matter in the brain. The word leukodystrophy comes from the Greek roots leuko, "white", dys, "abnormal" and troph, "growth". The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty insulating covering around nerve fibers. Leukodystrophies may be classified as hypomyelinating or demyelinating diseases, depending on whether the damage is present before birth or occurs after. Other demyelinating diseases are usually not congenital and have a toxic or autoimmune cause.When damage occurs to white matter, immune responses can lead to inflammation in the central nervous system (CNS), along with loss of myelin. The degeneration of white matter can be seen in an MRI scan and used to diagnose leukodystrophy. Leukodystrophy is characterized by specific symptoms including decreased motor function, muscle rigidity, and eventual degeneration of sight and hearing. While the disease is fatal, the age of onset is a key factor, as infants have a typical life expectancy  of 2–8 years, while adults typically live more than a decade after onset. Treatment options are limited, although hematopoietic stem cell transplantations using bone marrow or cord blood seem to help in certain types while further research is being done.
The combined incidence of the leukodystrophies is estimated at 1 in 7,600. The majority of types involve the inheritance of an X-linked recessive, or X-linked dominant trait, while others, although involving a defective gene, are the result of spontaneous mutation rather than genetic inheritance.

Symptoms and signs
Some specific symptoms vary from one type of leukodystrophy to the next, but the vast majority of symptoms are shared as the causes for the disease generally have the same effects. Symptoms are dependent on the age of onset, which is predominantly in infancy and early childhood, although the exact time of onset may be difficult to determine. Hyperirritability and hypersensitivity to the environment are common, as well as some tell-tale physical signs including muscle rigidity and a backwards-bent head. Botox therapy is often used to treat patients with spasticity. Juvenile and adult onsets display similar symptoms including a decrease or loss in hearing and vision. While children do experience optic and auditory degeneration, the course of the disease is usually too rapid, causing death relatively quickly, whereas adults may live with these conditions for many years. In children, spastic activity often precedes progressive ataxia and rapid cognitive deterioration which has been described as mental retardation. Epilepsy is commonplace for patients of all ages. More progressed patients show weakness in deglutition, leading to spastic coughing fits due to inhaled saliva. Classic symptomatic progression of juvenile X-linked adrenoleukodystrophy is shown in the 1992 film, Lorenzos Oil.Course and timetable are dependent on the age of onset with infants showing a lifespan of 2–8 years, juveniles 2–10 years and adults typically 10+ years. Adults typically see an extended period of stability followed by a decline to a vegetative state and death. While treatments do exist, most are in the experimental phase and can only promise a halt in the progression of symptoms, although some gene therapies have shown some symptomatic improvement. The debilitating course of the disease has led to numerous philosophical and ethical arguments over experimental clinical trials, patients rights and physician-assisted suicide.

Causes
While the more specific underlying causes of leukodystrophy are dependent upon the type, there are, however, common pathophysiological patterns that can be seen amongst all types. First and foremost, leukodystrophy is a neurodegenerative disease that is always the result of both impairment and maintenance of myelin sheaths surrounding neuronal axons in the central nervous system as the result of a genetic mutation. Myelin is a fatty white substance that acts as an electrical insulator and coats axons in order to speed up impulses (i.e., action potentials) traveling down the axon. Thus, the natural result of a loss of this substance is decreased efficiency in impulse propagation. As myelin is produced by oligodendrocytes (a type of glial cell) in the central nervous system, an easy place to look for the cause is a mutation or malfunctioning of these cells and in other glial cells.

Genetic influence
Leukodystrophy is most often an inherited disease that is usually the result of an autosomal recessive inheritance pattern, although dominant inheritance patterns are not unheard of, as in the case of adult-onset leukodystrophy. This means that the affected allele is carried on an autosomal, or non-sex, chromosome and is masked by the dominant, unaffected phenotype. In other words, for an individual to inherit the leukodystrophy phenotype, he or she must carry two of the recessive, mutant alleles. Krabbe disease and metachromatic leukodystrophy (MLD) are two of such type. MLD is found on human chromosome 22 at position q13.31. Another type of inherited leukodystrophy is X-linked adrenoleukodystrophy (X-ALD). As its name implies, this type of leukodystrophy is the result of a mutation found on the X-chromosome. It is also carried in a recessive pattern. The X chromosome is a sex chromosome, and since women have two "chances" of acquiring a normal X chromosome (one maternal, one paternal), and males only one (one maternal), this disease is more likely to be seen in men than in women. The mutation resulting in adult-onset leukodystrophy is mapped at 5q23.

Pathophysiology
Although there are nearly forty different types of leukodystrophies, many are lacking in formal and comprehensive research. Most of the research so far has been done on five types: (1) metachromatic leukodystrophy (MLD), (2) Krabbe disease, (3) X-Linked adrenoleukodystrophy (ALD), (4) Canavan disease, and (5) Alexander disease. Each type of leukodystrophy has a unique pathophysiology, but all five of these in some way affect a subset of glial cells, therefore disrupting myelin production and maintenance, and usually involve a mutation involving genes that code for enzymes necessary for the catabolism of very long chain fatty acids (VLCFAs) that are toxic to the myelin-producing cells of the central nervous system.

Metachromatic leukodystrophy
Metachromatic leukodystrophy is the result of genetic defects in the enzymes associated with the cellular compartment the lysosome. MLD is one of two leukodystophies that are also a lysosomal storage disorder. MLD is inherited in an autosomal recessive way and is the result of mutations in three different ARSA alleles that encode the enzyme arylsulfatase A (ASA or sometimes ARSA), also called sulfatide sulfatase. ASA is responsible for the breakdown of sulfatides, sphingolipids present in neuronal membranes as well as in myelin. When there is a mutation in the gene that encodes ASA, the result is it decreases production, which subsequently leads to diminished degradation of sulfatides, thus causing them to accumulate. This accumulation of sulfatides is poisonous to oligodendrocytes, the myelin-producing cells of the CNS, effectively leading to a disturbance in myelin structure followed by demyelination. The pattern of inheritance of the three different alleles affects what type of MLD a person develops. Two null alleles are responsible for the infantile version, and do not allow for any production of ASA. A heterozygous individual (one null allele, one non-null allele) develops the juvenile form and sees some production of ASA, while an individual with two non-null alleles (but still mutated) develops the adult form.

Krabbe disease
Like MLD, Krabbe disease is another type of leukodystrophy with autosomal recessive inheritance that is the result of a lysosomal storage disorder. It is due to a deletion in exon 16 of the GALC gene that causes a frameshift mutation leading to a premature stop codon. The GALC gene, found on chromosome 14 at position 31 (14q31), codes for the enzyme beta-galactocerebrosidase (GALC). GALC is a lysosomal enzyme responsible for the catabolism of galactolipids, especially psychosine, that are heavily distributed throughout the brain. A deficiency in GALC thus causes a buildup of these fatty acids known as globoid macrophages that destroy oligodendrocytes, thereby inhibiting myelin formation.Because of the presence of globoid cells clustered near white matter, Krabbe disease often goes by the name globoid cell leukodystrophy. Furthermore, new research has shown that Krabbe disease and globoid cell leukodystrophy may be distinct disease entities due to the secretion of inflammatory mediators by natural killer cells in some cases. This research has shown that Natural Killer cells have receptors (TDAG8) for certain glycosphingolipids that build up in an individual with leukodystrophy, again due to insufficient GALC levels, and when bound, target the Natural Killer cells for destruction thereby preventing their cytotoxic effects. These sphingolipids have been identified as galactosyl sphingosine and glycosyl sphingosine and are not present in unaffected individuals.

Canavan disease
Canavan disease is a lesser-studied type of leukodystrophy that, like MLD and Krabbe disease, is also passed on in an autosomal recessive inheritance pattern. It is due to a mutation in the ASPA gene that encodes aspartoacylase, an enzyme needed to metabolize N-acetyl-L-aspartate (NAA). The mutation causes a deficiency of aspartoacyclase. NAA is involved in the formation of lipids, and if it is not broken down by aspartoacylase, excess levels of it build up causing demyelination.

X-linked adrenoleukodystrophy
In X-linked adrenoleukodystrophy (X-ALD), a mutation occurs in the peroxisomal ATP-binding cassette (ABC transporter). This leads to cerebral inflammatory demyelination caused by the myelin destabilization that occurs in these patients. The inflammatory demyelination begins in the corpus callosum and it slowly progresses outwards towards both hemispheres. In X-ALD patients, abnormally high levels of very long chain fatty acid (VLCFA) accumulate in various body tissues and fluids. This increased concentration then incorporates into various complex lipids where they are not normally found. This has been found to be directly involved in the cerebral inflammation. The accumulated and embedded VLCFA in the complex lipids could lead to the destabilization of myelin sheath and eventually to demyelination.

Alexander disease
Alexander disease is unique from the leukodystrophies mentioned above in that it is the result of spontaneous mutation, that is it is not inherited. This means that the mutation found in the affected individual is not found in either of his or her parents. It is due to the accumulation of Glial fibrillary acidic protein (GFAP) as the result of a mutation in the GFAP gene; which, rather than being found in association with lysosomes or peroxisomes, is an intermediate filament linked to the nuclear envelope. Intermediate filaments are proteins responsible for the makeup of the cellular cytoskeleton, and thus this type of mutation is involved in malfunctioning structural development of the cells. In fact, cytoskeletal and transporter molecule defects have been observed in the astrocytes (type of glial cell) of affected individuals. These astrocytes have an unhealthily large amount of GFAP that affects astrocyte formation and function.

Diagnosis
The degeneration of white matter, which shows the degeneration of myelin, can be seen in a basic MRI and used to diagnose leukodystrophies of all types. T-1 and T-2 weighted FLAIR images are the most useful. FLAIR stands for fluid-attenuated inversion recovery. Electrophysiological and other kinds of laboratory testing can also be done. In particular, nerve conduction velocity is looked at to distinguish between leukodystrophy and other demyelinating diseases, as well as to distinguish between individual leukodystrophies. For example, individuals with X-ALD have normal conduction velocities, while those with Krabbe disease or metachromatic leukodystrophy have abnormalities in their conduction velocities. Next generation multigene sequencing panels for undifferentiated leukodystrophy can now be offered for rapid molecular diagnosis after appropriate genetic counselling.

Types
Specific types of leukodystrophies include the following with their respective ICD-10 codes when available:
(E71.3) Adrenomyeloneuropathy
(E75.2) Alexander disease
(E75.5) Cerebrotendineous xanthomatosis
Hereditary CNS demyelinating disease
(E75.2) Krabbe disease
(E75.2) Metachromatic leukodystrophy
(E75.2) Pelizaeus–Merzbacher disease
(E75.2) Canavan disease
(E75.2) Hypomyelinating leukodystrophy type 7 (4H syndrome)
(G93.49) Leukoencephalopathy with vanishing white matter
(E71.3) Adrenoleukodystrophy
(G60.1) Refsum disease

Treatment
With many different types of leukodystrophies and causes, treatment therapies vary for each type. Many studies and clinical trials are in progress to find treatment and therapies for each of the different leukodystrophies. Stem cell transplants and gene therapy appear to be the most promising in treating all leukodystrophies providing it is done as early as possible.
For hypomyelinating leukodystrophies, therapeutic research into cell-based therapies appears promising. Oligodendrocyte precursor cells and neural stem cells have been transplanted successfully and have shown to be healthy a year later. Fractional anisotropy and radial diffusivity maps showed possible myelination in the region of the transplant. Induced pluripotent stem cells, oligodendrocyte precursor cells, gene correction, and transplantation to promote the maturation, survival, and myelination of oligodendrocytes seem to be the primary routes for possible treatments.For three types of leukodystrophies (X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD) and Krabbe Disease (globoid cell leukodystrophy - GLD), gene therapy using autologous hematopoietic stem cells to transfer the disease gene with lentiviral vectors have shown to be successful and are currently being used in clinical trials for X-ALD and MLD. The progression of X-ALD has shown to be disrupted with hematopoietic stem cell gene therapy but the exact reason why demyelination stops and the amount of stem cells needed is unclear. While there is an accumulation of very long chain fatty acids in the brain, it does not seem to be the reason behind the disease as gene therapy does not correct it.For those leukodystrophies that result from a deficiency of lysozyme enzymes, such as Krabbe disease, enzyme replacement therapy seems hopeful. However, enzyme delivery proves difficult, because the blood-brain barrier severely limits what can pass into the central nervous system. Current gene therapy research for metachromatic leukodystrophy has been reviewed with an emphasis on ex vivo transplantation of genetically modified hematopoietic stem cells.

Epidemiology
Currently, no research has shown a higher prevalence of most leukodystrophy types in any one place around the world. There is, however, a higher prevalence of the Canavan disease in the Jewish population. 1 in 40 individuals of Ashkenazi Jewish descent are carriers of Canavan disease. This estimates to roughly 2.5%. Additionally, due to an autosomal recessive inheritance patterns, there is no significant difference found between affected males and affected females for most types of leukodystrophy including, but not limited to, metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Rapidly progressive glomerulonephritis and explain in detail? [/INST] Rapidly progressive glomerulonephritis (RPGN) is a syndrome of the kidney that is characterized by a rapid loss of kidney function, (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months) with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies. If left untreated, it rapidly progresses into acute kidney failure and death within months. In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus or granulomatosis with polyangiitis; the remaining cases are idiopathic. Regardless of the underlying cause, RPGN involves severe injury to the kidneys glomeruli, with many of the glomeruli containing characteristic glomerular crescents (crescent-shaped scars).

Signs and symptoms
Most types of RPGN are characterized by severe and rapid loss of kidney function with marked hematuria; red blood cell casts in the urine; and proteinuria sometimes exceeding three grams in twenty-four hours, a range associated with nephrotic syndrome. Some patients also experience hypertension and edema. Severe disease is characterized by pronounced oliguria or anuria, which portends a poor prognosis.

Pathophysiology
It is thought that antineutrophil cytoplasmic antibodies (ANCA) interact with antigens in the cytoplasm of neutrophils to cause an early degranulation, triggering the release of lytic enzymes at the site of injury and leading to the formation of glomerular crescents that consist primarily of parietal epithelial cells from Bowmans capsule and in some cases podocytes.

Diagnosis
Serum analysis often aids in the diagnosis of a specific underlying disease. The presence of anti-glomerular basement membrane (GBM) antibodies suggests type I RPGN; antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus and type II RPGN; and type III and idiopathic RPGN are frequently associated with anti-neutrophil cytoplasmic antibodies (ANCA)-positive serum.Impaired kidney function in an individual who has had the condition for fewer than three months is characteristic of RPGN. An ultrasonographic examination of the abdomen should be obtained. Although the presence of sediment in the urine on examination can indicate proliferative glomerulonephritis, many cases of rapidly progressive glomerulonephritis need a renal biopsy to make a diagnosis.

Classification
RPGN can be classified into three types, based upon the immunofluorescence patterns:

Type I
Accounting for approximately 20% of RPGN, type I RPGN, also called anti-GBM glomerulonephritis, is characterized by the presence of autoantibodies directed against type IV collagen (specifically, the noncollagenous region of its α3 chain) in the glomerular basement membrane (GBM). Some cases are associated with antibodies directed against the basement membrane of lung alveoli, producing Goodpasture syndrome. The majority of type I disease, however, features anti-GBM antibodies alone; these cases are considered idiopathic.

Type II
Characterized by deposition of immune complexes in glomerular tissues, type II RPGN accounts for 25% of cases. Any immune complex disease—including systemic lupus erythematosus, acute proliferative glomerulonephritis, Henoch–Schönlein purpura, and IgA nephropathy—that involves the glomerulus may progress to RPGN if severe enough.

Type III
Also known as pauci-immune RPGN, type III RPGN accounts for 55% of RPGN and features neither immune complex deposition nor anti-GBM antibodies. Instead, the glomeruli are damaged in an undefined manner, perhaps through the activation of neutrophils in response to ANCA. Type III RPGN may be isolated to the glomerulus (primary, or idiopathic) or associated with a systemic disease (secondary). In most cases of the latter, the systemic disease is an ANCA-associated vasculitis such as granulomatosis with polyangiitis, microscopic polyangiitis or eosinophilic granulomatosis with polyangiitis.

Treatment
Therapy consists of a combination of rituximab, corticosteroids, and cyclophosphamide, with a substitution of azathioprine for cyclophosphamide after a ninety-day initial period being another option </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Acrania and explain in detail? [/INST] Acrania is a rare congenital disorder that occurs in the human fetus in which the flat bones in the cranial vault are either completely or partially absent. The cerebral hemispheres develop completely but abnormally. The condition is frequently, though not always, associated with anencephaly. The fetus is said to have acrania if it meets the following criteria: the fetus should have a perfectly normal facial bone, a normal cervical column but without the fetal skull and a volume of brain tissue equivalent to at least one-third of the normal brain size.

Causes
Genetics
There are no known family ties in acrania and recurrence rates are extremely low. Not much is known about the exact mechanism involved in acrania. It is hypothesized that, like other developmental malformations, there are multiple origins for acrania.Recent work has identified mutations in the hedgehog acyltransferase (HHAT) gene that have caused acrania along with holoprosencephaly and agnathia. The mutation in HHAT which causes this disease is a loss-of-function mutation. Before this discovery in 2010, HHAT was known to play a role in the sonic hedgehog pathway. When HHAT contains a loss-of-function mutation, less HHAT protein is produced. HHAT is necessary for the production of Hedgehog (Hh) proteins post-transcriptionally. As HHAT production decreases, production of long-range Hh proteins decreases proportionally. Decreases in Hh| production disturb the production of extracellular signal-regulated kinases, bone morphogenetic proteins, and fibroblast growth factors, all of which play important roles in craniofacial patterning. Disruption of these pathways leads to abnormal bone and cartilage formation causing acrania and multiple other craniofacial patterning problems.

Genetic counseling
Little genetic counseling can be offered for acrania because the genetic origins are not fully understood. In order to make genetic counseling for families easier this disease is often differentially diagnosed with other diseases that can occur at the same time such as anencephaly and acalvaria, though these diseases may not always occur simultaneously. Recurrence rates are extremely low, so genetic counseling is not always necessary.

Amniotic band syndrome
During amniotic band syndrome (ABS), fibrous bands may entrap various parts of the developing fetus causing malformations. When these fibrous bands form around the developing skull, the bones will not form properly. ABS occurring in the developing brain neural tissue is one cause of acrania. When ABS is the cause of acrania the fibrous bands cannot be detected through ultrasound.

Mechanism
During the fourth week of human development the neuropore in a normally developing fetus closes. When this process is either interrupted or never initiated, acrania occurs. The desmocranium becomes a membranous coverage instead of forming the epidermis of the scalp. Whether from being blocked by amniotic bands or by just not initiating, the migration of mesenchyme under the ectoderm does not occur. Because this migration does not occur, the skull, and all involved muscles, are never formed. Without the presence of the neurocranium, the brain fails to separate into two separate lobes. The hindbrain proceeds to develop normally, allowing for the child to be carried to term, but the diencephalon and ocular lobe remain small and underdeveloped.

Ectodermal mesenchyme
Mesenchyme is formed in the developing embryo and will eventually become cartilage and bone. When ectodermal mesenchyme fails to migrate into the head region of the embryo, the skull will not be able to form </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Disorganized schizophrenia and explain in detail? [/INST]  </s>