<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 Berylliosis and explain in detail? [/INST] Berylliosis, or chronic beryllium disease (CBD), is a chronic allergic-type lung response and chronic lung disease caused by exposure to beryllium and its compounds, a form of beryllium poisoning. It is distinct from acute beryllium poisoning, which became rare following occupational exposure limits established around 1950. Berylliosis is an occupational lung disease.
While there is no cure, symptoms can be treated.

Signs and symptoms
With single or prolonged exposure by inhalation the lungs may become sensitized to beryllium. Berylliosis has a slow onset and progression. Some people who are sensitized to beryllium may not have symptoms. Continued exposure causes the development of small inflammatory nodules, called granulomas. Of note, the authors of a 2006 study suggested that beryllium inhalation was not the only form of exposure and perhaps skin exposure was also a cause, as they found that a reduction in beryllium inhalation did not result in a reduction in CBD or beryllium sensitization.Granulomas are seen in other chronic diseases, such as tuberculosis and sarcoidosis, and it can occasionally be hard to distinguish berylliosis from these disorders. However, granulomas of CBD will typically be non-caseating, i.e. not characterized by necrosis and therefore not exhibiting a cheese-like appearance grossly.Ultimately, this process leads to restrictive lung disease (a decrease in diffusion capacity).
The earliest symptoms are typically cough and shortness of breath. Other symptoms include chest pain, joint aches, weight loss, and fever.
Rarely, one can get granulomas in other organs including the liver.
The onset of symptoms can range from weeks up to tens of years from the initial exposure. In some individuals, a single exposure to beryllium can cause berylliosis.

Pathogenesis
In susceptible persons, beryllium exposure can lead to a cell-mediated immune response. The T-cells become sensitized to beryllium. Each subsequent exposure leads to an immune response involving CD4+ helper T-lymphocytes and macrophages accumulating in the lungs. As this response continues macrophages, CD+4 T-lymphocytes and plasma cells aggregate together to form the noncaseating granulomas. When beryllium is phagocytized by macrophages, the beryllium triggers macrophage apoptosis, thereby reducing beryllium clearance from the lungs and eventually resulting in secondary necrosis and lysis. Eventually, the outcome is fibrosis of the lung.Several studies have shown that there is a genetic component to beryllium sensitivity. Specifically, those beryllium exposed workers with a mutation at the HLA-DPB1 Glu69 position have increased prevalence of beryllium sensitization and CBD.  The HLA-DPB1 gene is important for MHC class II molecule function on antigen presenting cells.According to the International Agency for Research on Cancer (IARC), beryllium and beryllium compounds are Category 1 carcinogens; they are carcinogenic to both animals and humans.

Diagnosis
The differential diagnosis for berylliosis includes:
Sarcoidosis
Granulomatous lung diseases
Tuberculosis
Fungal infections (e.g., histoplasmosis)
Granulomatosis with polyangiitis
Idiopathic pulmonary fibrosis
Hypersensitivity pneumonitis
AsthmaOf these possibilities, berylliosis presents most similarly to sarcoidosis. Some studies suggest that up to 6% of all cases of sarcoidosis are actually berylliosis.Definitive diagnosis of berylliosis is based on history of beryllium exposures, documented beryllium sensitivity and granulomatous inflammation on lung biopsy. Given the invasive nature of a lung biopsy, diagnosis can also be based on clinical history consistent with berylliosis, abnormal chest x-ray or CT scan findings, and abnormalities in pulmonary function tests.Establishing beryllium sensitivity is the first step in diagnosis. The beryllium lymphocyte proliferation test (BeLPT) is the standard way of determining sensitivity to beryllium. The test is performed by acquiring either peripheral blood or fluid from a bronchial alveolar lavage, and lymphocytes are cultured with beryllium sulfate. Cells are then counted and those with elevated number of cells are considered abnormal. Those exposed persons with two abnormal BeLPT tested with peripheral blood, or one abnormal and one borderline result, are considered beryllium sensitized. Also, those with one abnormal BeLPT tested with fluid from a bronchial alveolar lavage are considered sensitized.Chest radiography findings of berylliosis are non-specific. Early in the disease radiography findings are usually normal. In later stages interstitial fibrosis,  pleural irregularities, hilar lymphadenopathy and ground-glass opacities have been reported. Findings on CT are also not specific to berylliosis. Findings that are common in CT scans of people with berylliosis include parenchymal nodules in early stages. One study found that ground-glass opacities were more commonly seen on CT scan in berylliosis than in sarcoidosis. In later stages hilar lymphadenopathy, interstitial pulmonary fibrosis and pleural thickening.

Classification
Berylliosis is an occupational disease. Relevant occupations are those where beryllium is mined, processed or converted into metal alloys, or where machining of metals containing beryllium and recycling of scrap alloys occurs. It is associated with aerospace manufacturing, microwave semiconductor electronics, beryllium mining or manufacturing of fluorescent light bulbs (which once contained beryllium compounds in their internal phosphor coating). Beryllia was used in lamp manufacture because of ceramics obvious virtues for insulation and heat resistance, and also because beryllia could be made transparent. Certain welding anodes along with other electrical contacts and even non-sparking tools are made of beryllium copper alloy and the subsequent machining of such materials would cause the disease as well.

Prevention
Typical levels of beryllium that industries may release into the air are of the order of 0.01 µg/m3, averaged over a 30-day period, or 2 µg/m3 of workroom air for an 8-hour work shift. Compliance with the current U.S. Occupational Safety and Health Administration (OSHA) permissible exposure limit for beryllium of 2 µg/m3 has been determined to be inadequate to protect workers from developing beryllium sensitization and CBD. The American Conference of Governmental Industrial Hygienists (ACGIH), which is an independent organization of experts in the field of occupational health, has proposed a threshold limit value (TLV) of 0.05 µg/m3 in a 2006 Notice of Intended Change (NIC). This TLV is 40 times lower than the current OSHA permissible exposure limit, reflecting the ACGIH analysis of best available peer-reviewed research data concerning how little airborne beryllium is required to cause sensitization and CBD.Because it can be difficult to control industrial exposures to beryllium, it is advisable to use any methods possible to reduce airborne and surface contamination by beryllium, to minimize the use of beryllium and beryllium-containing alloys whenever possible, and to educate people about the potential hazards if they are likely to encounter beryllium dust or fumes. It is important to damp wipe metallographic preparation equipment to prevent accumulation of dry particles. Sectioning, grinding, and polishing must be performed under sufficiently vented hoods equipped with special filters.On 29 January 2009, the Los Alamos National Laboratory announced it was notifying nearly 2,000 current and former employees and visitors that they may have been exposed to beryllium in the lab and may be at risk of disease. Concern over possible exposure to the material was first raised in November 2008, when a box containing beryllium was received at the laboratorys short-term storage facility.

Treatment
There is no cure for berylliosis; the goals of treatment are to reduce symptoms and slow the progression of disease.Although the evidence that stopping exposure to beryllium decreases progression of the disease is limited, it is still considered to be an accepted approach to treatment in any stage of disease.People with early stages of disease, without lung function abnormalities or clinical symptoms, are periodically monitored with physical exams, pulmonary function testing and radiography.Once clinical symptoms or significant abnormalities in pulmonary function testing appear, treatments include oxygen and oral corticosteroids and whatever supportive therapy is required.

Outcomes
Overall mortality rates are 5–38%.

Epidemiology
The number of workers in the United States exposed to beryllium vary but has been estimated to be as high as 800,000 during the 1960s and 1970s. A more recent study from 2004 estimated the number of exposed workers in the United States to be around 134,000.The rate of workers becoming sensitized to beryllium varies based on genetics and exposure levels. In one study researchers found the prevalence of beryllium sensitization to range from 9 - 19% depending on the industry. Many workers who are found to be sensitive to beryllium also meet the diagnostic criteria for CBD. In one study of nuclear workers, among those who were sensitized to beryllium, 66% were found to have CBD as well. The rate of progression from beryllium sensitization to CBD has been estimated to be approximately 6-8% per year. Stopping exposure to beryllium in those sensitized has not been definitively shown to stop the progression to CBD.The overall prevalence of CBD among workers exposed to beryllium has ranged from 1 – 5% depending on industry and time period of study.The general population is unlikely to develop acute or chronic beryllium disease because ambient air levels of beryllium are normally very low (<0.03 ng/m3).  However, a study found 1% of people living within 3/4 of a mile of a beryllium plant in Lorain, Ohio, had berylliosis after exposure to concentrations estimated to be less than 1 milligram per cubic metre of air. In the United States the Beryllium Case Registry contained 900 records, early cases relating to extraction and fluorescent lamp manufacture, later ones coming from the aerospace, ceramics and metallurgical industries.

History
Since the 1920s, beryllium has been used in electronics, ceramics, research and development labs, aircraft, and the atomic energy and defense industry. Cases of bronchitis and pneumonia-like symptoms were reported in Germany and Russia in the 1930s among workers mining and refining beryllium. By 1946, a cluster of cases associated with fluorescent lamp manufacturers were apparent in the United States, and the lamp industry stopped using beryllium in 1949. At that time, most construction trades and industries were unaware of the potential risks associated with beryllium exposure.It occasionally killed early workers in nuclear weapons design, such as Herbert L </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 Pre-eclampsia and explain in detail? [/INST] Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease there may be red blood cell breakdown, a low blood platelet count, impaired liver function, kidney dysfunction, swelling, shortness of breath due to fluid in the lungs, or visual disturbances. Pre-eclampsia increases the risk of undesirable outcomes for both the mother and the fetus. If left untreated, it may result in seizures at which point it is known as eclampsia.Risk factors for pre-eclampsia include obesity, prior hypertension, older age, and diabetes mellitus. It is also more frequent in a womans first pregnancy and if she is carrying twins. The underlying mechanism involves abnormal formation of blood vessels in the placenta amongst other factors. Most cases are diagnosed before delivery. Commonly, pre-eclampsia continues into the period after delivery, then known as postpartum pre-eclampsia. Rarely, pre-eclampsia may begin in the period after delivery. While historically both high blood pressure and protein in the urine were required to make the diagnosis, some definitions also include those with hypertension and any associated organ dysfunction. Blood pressure is defined as high when it is greater than 140 mmHg systolic or 90 mmHg diastolic at two separate times, more than four hours apart in a woman after twenty weeks of pregnancy. Pre-eclampsia is routinely screened during prenatal care.Recommendations for prevention include: aspirin in those at high risk, calcium supplementation in areas with low intake, and treatment of prior hypertension with medications. In those with pre-eclampsia, delivery of the baby and placenta is an effective treatment but full recovery can take days or weeks. When delivery becomes recommended depends on how severe the pre-eclampsia and how far along in pregnancy a woman is. Blood pressure medication, such as labetalol and methyldopa, may be used to improve the mothers condition before delivery. Magnesium sulfate may be used to prevent eclampsia in those with severe disease. Bed rest and salt intake have not been found to be useful for either treatment or prevention.Pre-eclampsia affects 2–8% of pregnancies worldwide. Hypertensive disorders of pregnancy (which include pre-eclampsia) are one of the most common causes of death due to pregnancy. They resulted in 46,900 deaths in 2015. Pre-eclampsia usually occurs after 32 weeks; however, if it occurs earlier it is associated with worse outcomes. Women who have had pre-eclampsia are at increased risk of heart disease and stroke later in life.The word "eclampsia" is from the Greek term for lightning. The first known description of the condition was by Hippocrates in the 5th century BC.

Signs and symptoms
Oedema (especially in the hands and face) was originally considered an important sign for a diagnosis of pre-eclampsia. However, because oedema is a common occurrence in pregnancy, its utility as a distinguishing factor in pre-eclampsia is not high. Pitting edema (unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant, and should be reported to a health care provider.
In general, none of the signs of pre-eclampsia are specific, and even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Further, a symptom such as epigastric pain may be misinterpreted as heartburn. Common features of pre-eclampsia which are screened for during pre-natal visits include elevated blood pressure and excess protein in the urine. Diagnosis depends on finding a coincidence of several pre-eclamptic features, the final proof being their regression within the days and weeks after delivery.

Causes
There is no definitive known cause of pre-eclampsia, though it is likely related to a number of factors. Some of these factors include:
Abnormal placentation (formation and development of the placenta)
Immunologic factors
Prior or existing maternal pathology—pre-eclampsia is seen more at a higher incidence in individuals with pre-existing hypertension, obesity, or antiphospholipid antibody syndrome or those with a history of pre-eclampsia
Dietary factors, e.g. calcium supplementation in areas where dietary calcium intake is low has been shown to reduce the risk of pre-eclampsia
Environmental factors, e.g. air pollutionThose with long term high blood pressure have a risk 7 to 8 times higher than those without.Physiologically, research has linked pre-eclampsia to the following physiologic changes: alterations in the interaction between the maternal immune response and the placenta, placental injury, endothelial cell injury, altered vascular reactivity, oxidative stress, imbalance among vasoactive substances, decreased intravascular volume, and disseminated intravascular coagulation.While the exact cause of pre-eclampsia remains unclear, there is strong evidence that a major cause predisposing a susceptible woman to pre-eclampsia is an abnormally implanted placenta. This abnormally implanted placenta may result in poor uterine and placental perfusion, yielding a state of hypoxia and increased oxidative stress and the release of anti-angiogenic proteins along with inflammatory mediators into the maternal plasma. A major consequence of this sequence of events is generalized endothelial dysfunction. The abnormal implantation may stem from the maternal immune systems response to the placenta, specifically a lack of established immunological tolerance in pregnancy. Endothelial dysfunction results in hypertension and many of the other symptoms and complications associated with pre-eclampsia. Those with pre-eclampsia may have a lower risk of breast cancer.Abnormal chromosome 19 microRNA cluster (C19MC) impairs extravillus trophoblast cell invasion to the spiral arteries, causing high resistance, low blood flow, and low nutrient supply to the fetus.

Genetic factors
Despite a lack of knowledge on specific causal mechanisms of pre-eclampsia, there is strong evidence to suggest it results from both environmental and heritable factors. A 2005 study showed that women with a first-degree relative who had a pre-eclamptic birth are twice as likely to develop it themselves. Furthermore, men related to someone with affected birth have an increased risk of fathering a pre-eclamptic pregnancy. Fetuses affected by pre-eclampsia have a higher chance of later pregnancy complications including growth restriction, prematurity, and stillbirth.The onset of pre-eclampsia is thought to be caused by several complex interactions between genetics and environmental factors. Our current understanding of the specifically heritable cause involves an imbalance of angiogenic factors in the placenta. Angiogenesis involves the growth of new blood vessels from existing vessels, and an imbalance during pregnancy can affect the vascularization, growth, and biological function of the fetus. The irregular expression of these factors is thought to be controlled by multiple loci on different chromosomes. Research on the topic has been limited because of the heterogeneous nature of the disease. Maternal, paternal, and fetal genotypes all play a role as well as complex epigenetic factors such as whether the parents smoke, maternal age, sexual cohabitation, and obesity. Currently, there is very little understanding behind the mechanisms of these interactions. Due to the polygenic nature of pre-eclampsia, a majority of the studies that have been conducted thus far on the topic have utilized genome-wide association studies.One known effector of pre-eclampsia is the fetal loci FLT1. Located on chromosome 13 in the q12 region, FLT1 codes for Fms-like tyrosine kinase 1, an angiogenic factor expressed in fetal trophoblasts. Angiogenic factors are crucial for vascular growth in the placenta. An FLT1 soluble isoform caused by a splice variant is sFLT1, which works as an antiangiogenic factor, reducing vascular growth in the placenta. A healthy, normotensive pregnancy is characterized by a balance between these factors. However, upregulation of this variant and overexpression of sFL1 can contribute to endothelial dysfunction. Reduced vascular growth and endothelial dysfunction manifest primarily in maternal symptoms such as renal failure, edema, and seizures. However, these factors can also lead to inadequate oxygen, nutrient, or blood supply to the fetus. Furthermore, in this loci region, several single-nucleotide polymorphisms (SNPs) have been observed to impact the overexpression of sFL1. Specifically, SNPs rs12050029 and rs4769613s risk alleles are linked with low red blood cell counts and carry an increased risk of late-onset pre-eclampsia.
Patau syndrome, or Trisomy 13, is also associated with the upregulation of sFLT1 due to the extra copy of the 13th chromosome. Because of this upregulation of an antiangiogenic factor, women with trisomy 13 pregnancies often experience reduced placental vascularization and are at higher risk for developing pre-eclampsia.Beyond fetal loci, there have been some maternal loci identified as effectors of pre-eclampsia. Alpha-ketoglutarate-dependent hydroxylase expression on chromosome 16 in the q12 region is also associated with pre-eclampsia. Specifically, allele rs1421085 heightens the risk of not just pre-eclampsia but also an increase in BMI and hypertension. This pleiotropy is one of the reasons why these traits are considered to be a risk factor. Furthermore, ZNF831 (zinc finger protein 831) and its loci on chromosome 20q13 were identified as another significant factor in pre-eclampsia. The risk allele rs259983 is also associated with both pre-eclampsia and hypertension, further evidence that the two traits are possibly linked.
While the current understanding suggests that maternal alleles are the main hereditary cause of pre-eclampsia, paternal loci have also been implicated. In one study, paternal DLX5 (Distal-Less Homeobox 5) was identified as an imprinted gene. Located on chromosome 7 in the q21 region, DLX5 serves as a transcription factor often linked with the developmental growth of organs. When paternally inherited, DLX5 and its SNP rs73708843 are shown to play a role in trophoblast proliferation, affecting vascular growth and nutrient delivery.Besides specific loci, several important genetic regulatory factors contribute to the development of pre-eclampsia. Micro RNAs, or miRNAs, are noncoding mRNAs that down-regulate posttranscriptional gene expression through RNA-induced silencing complexes. In the placenta, miRNAs are crucial for regulating cell growth, angiogenesis, cell proliferation, and metabolism. These placental-specific miRNAs are clustered in large groups, mainly on chromosomes 14 and 19, and irregular expression of either is associated with an increased risk of an affected pregnancy. For instance, miR-16 and miR-29 are vascular endothelial growth factors (VEGFs) and play a role in upregulating sFLT-1. In particular, the overexpression of miRNA miR-210 has been shown to induce hypoxia, which affects spiral artery remodeling, an important part of the pathogenesis of pre-eclampsia.

Risk factors
Known risk factors for pre-eclampsia include:
Having never previously given birth
Diabetes mellitus
Kidney disease
Chronic hypertension
Prior history of pre-eclampsia
Family history of pre-eclampsia
Advanced maternal age (>35 years)
Obesity
Antiphospholipid antibody syndrome
Multiple gestation
Having donated a kidney
Having sub-clinical hypothyroidism or thyroid antibodies
Placental abnormalities such as placental ischemia

Pathogenesis
Although much research into mechanism of pre-eclampsia has taken place, its exact pathogenesis remains uncertain. Pre-eclampsia is thought to result from an abnormal placenta, the removal of which ends the disease in most cases. During normal pregnancy, the placenta vascularizes to allow for the exchange of water, gases, and solutes, including nutrients and wastes, between maternal and fetal circulations. Abnormal development of the placenta leads to poor placental perfusion. The placenta of women with pre-eclampsia is abnormal and characterized by poor trophoblastic invasion. It is thought that this results in oxidative stress, hypoxia, and the release of factors that promote endothelial dysfunction, inflammation, and other possible reactions.The clinical manifestations of pre-eclampsia are associated with general endothelial dysfunction, including vasoconstriction and end-organ ischemia. Implicit in this generalized endothelial dysfunction may be an imbalance of angiogenic and anti-angiogenic factors. Both circulating and placental levels of soluble fms-like tyrosine kinase-1 (sFlt-1) are higher in women with pre-eclampsia than in women with normal pregnancy. sFlt-1 is an anti-angiogenic protein that antagonizes vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), both of which are proangiogenic factors. Soluble endoglin (sEng) has also been shown to be elevated in women with pre-eclampsia and has anti-angiogenic properties, much like sFlt-1 does.Both sFlt-1 and sEng are upregulated in all pregnant women to some extent, supporting the idea that hypertensive disease in pregnancy is a normal pregnancy adaptation gone awry. As natural killer cells are intimately involved in placentation and placentation involves a degree of maternal immune tolerance for a foreign placenta, it is not surprising that the maternal immune system might respond more negatively to the arrival of some placentae under certain circumstances, such as a placenta which is more invasive than normal. Initial maternal rejection of the placental cytotrophoblasts may be the cause of the inadequately remodeled spiral arteries in those cases of pre-eclampsia associated with shallow implantation, leading to downstream hypoxia and the appearance of maternal symptoms in response to upregulated sFlt-1 and sEng.
Oxidative stress may also play an important part in the pathogenesis of pre-eclampsia. The main source of reactive oxygen species (ROS) is the enzyme xanthine oxidase (XO) and this enzyme mainly occurs in the liver. One hypothesis is that the increased purine catabolism from placental hypoxia results in increased ROS production in the maternal liver and release into the maternal circulation that causes endothelial cell damage.Abnormalities in the maternal immune system and insufficiency of gestational immune tolerance seem to play major roles in pre-eclampsia. One of the main differences found in pre-eclampsia is a shift toward Th1 responses and the production of IFN-γ. The origin of IFN-γ is not clearly identified and could be the natural killer cells of the uterus, the placental dendritic cells modulating responses of T helper cells, alterations in synthesis of or response to regulatory molecules, or changes in the function of regulatory T cells in pregnancy. Aberrant immune responses promoting pre-eclampsia may also be due to an altered fetal allorecognition or to inflammatory triggers. It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop pre-eclampsia. These findings have given rise to the hypothesis that pre-eclampsia is a disease process by which a placental lesion such as hypoxia allows increased fetal material into the maternal circulation, that in turn leads to an immune response and endothelial damage, and that ultimately results in pre-eclampsia and eclampsia.
One hypothesis for vulnerability to pre-eclampsia is the maternal-fetal conflict between the maternal organism and fetus. After the first trimester trophoblasts enter the spiral arteries of the mother to alter the spiral arteries and thereby gain more access to maternal nutrients. Occasionally there is impaired trophoblast invasion that results in inadequate alterations to the uterine spiral arteries. It is hypothesized that the developing embryo releases biochemical signals that result in the woman developing hypertension and pre-eclampsia so that the fetus can benefit from a greater amount of maternal circulation of nutrients due to increased blood flow to the impaired placenta. This results in a conflict between maternal and fetal fitness and survival because the fetus is invested in only its survival and fitness while the mother is invested in this and subsequent pregnancies.Another evolutionary hypothesis for vulnerability to pre-eclampsia is the idea of ensuring pair-bonding between the mother and father and paternal investment in the fetus. Researchers posit that pre-eclampsia is an adaptation for the mother to terminate investment in a fetus that might have an unavailable father, as determined by repeated semen exposure of the father to the mother. Various studies have shown that women who frequently had exposure to partners semen before conception had a reduced risk of pre-eclampsia. Also, subsequent pregnancies by the same father had a reduced risk of pre-eclampsia while subsequent pregnancies by a different father had a higher risk of developing pre-eclampsia.In normal early embryonic development, the outer epithelial layer contains cytotrophoblast cells, a stem cell type found in the trophoblast that later differentiates into the fetal placenta. These cells differentiate into many placental cells types, including extravillous trophoblast cells. Extravillous trophoblast cells are an invasive cell type which remodel the maternal spiral arteries by replacing the maternal epithelium and smooth muscle lining the spiral arteries causing artery dilation. This prevents maternal vasoconstriction in the spiral arteries and allows for continued blood and nutrient supply to the growing fetus with low resistance and high blood flow.In pre-eclampsia, abnormal expression of chromosome 19 microRNA cluster (C19MC) in placental cell lines reduces extravillus trophoblast migration. Specific microRNAs in this cluster which might cause abnormal spiral artery invasion include miR-520h, miR-520b, and 520c-3p. This impairs extravillus trophoblast cells invasion to the maternal spiral arteries, causing high resistance and low blood flow and low nutrient supply to the fetus. There is tentative evidence that vitamin supplementation can decrease the risk.Immune factors may also play a role.

Diagnosis
Testing for pre-eclampsia is recommended throughout pregnancy via measuring a womans blood pressure.

Diagnostic criteria
Pre-eclampsia is diagnosed when a pregnant woman develops:
Blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic on two separate readings taken at least four to six hours apart after 20 weeks gestation in an individual with previously normal blood pressure.
In a woman with essential hypertension beginning before 20 weeks gestational age, the diagnostic criteria are an increase in systolic blood pressure (SBP) of ≥30 mmHg or an increase in diastolic blood pressure (DBP) of ≥15 mmHg.
Proteinuria ≥ 0.3 grams (300 mg) or more of protein in a 24-hour urine sample or a SPOT urinary protein to creatinine ratio ≥0.3 or a urine dipstick reading of 1+ or greater (dipstick reading should only be used if other quantitative methods are not available).Suspicion for pre-eclampsia should be maintained in any pregnancy complicated by elevated blood pressure, even in the absence of proteinuria. Ten percent of individuals with other signs and symptoms of pre-eclampsia and 20% of individuals diagnosed with eclampsia show no evidence of proteinuria. In the absence of proteinuria, the presence of new-onset hypertension (elevated blood pressure) and the new onset of one or more of the following is suggestive of the diagnosis of pre-eclampsia:
Evidence of kidney dysfunction (oliguria, elevated creatinine levels)
Impaired liver function (noted by liver function tests)
Thrombocytopenia (platelet count <100,000/microliter)
Pulmonary edema
Ankle edema (pitting type)
Cerebral or visual disturbancesPre-eclampsia is a progressive disorder and these signs of organ dysfunction are indicative of severe pre-eclampsia. A systolic blood pressure ≥160 or diastolic blood pressure ≥110 and/or proteinuria >5g in a 24-hour period is also indicative of severe pre-eclampsia. Clinically, individuals with severe pre-eclampsia may also present epigastric/right upper quadrant abdominal pain, headaches, and vomiting. Severe pre-eclampsia is a significant risk factor for intrauterine fetal death.
A rise in baseline blood pressure (BP) of 30 mmHg systolic or 15 mmHg diastolic, while not meeting the absolute criteria of 140/90, is important to note but is not considered diagnostic.

Predictive tests
There have been many assessments of tests aimed at predicting pre-eclampsia, though no single biomarker is likely to be sufficiently predictive of the disorder. Predictive tests that have been assessed include those related to placental perfusion, vascular resistance, kidney dysfunction, endothelial dysfunction, and oxidative stress. Examples of notable tests include:

Doppler ultrasonography of the uterine arteries to investigate for signs of inadequate placental perfusion. This test has a high negative predictive value among those individuals with a history of prior pre-eclampsia.
Elevations in serum uric acid (hyperuricemia) is used by some to "define" pre-eclampsia, though it has been found to be a poor predictor of the disorder. Elevated levels in the blood (hyperuricemia) are likely due to reduced uric acid clearance secondary to impaired kidney function.
Angiogenic proteins such as vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) and anti-angiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt-1) have shown promise for potential clinical use in diagnosing pre-eclampsia, though evidence is insufficient to recommend a clinical use for these markers.A recent study, ASPRE, known to be the largest multi-country prospective trial, has reported a significant performance in identifying pregnant women at high risk of pre-eclampsia yet during the first trimester of pregnancy. Utilizing a combination of maternal history, mean arterial blood pressure, intrauterine Doppler and PlGF measurement, the study has shown a capacity to identify more than 75% of the women that will develop pre-eclampsia, allowing early intervention to prevent development of later symptoms. This approach is now officially recommended by the International Federation of Gynecologists & Obstetricians (FIGO)
Recent studies have shown that looking for podocytes (specialized cells of the kidney) in the urine has the potential to aid in the prediction of pre-eclampsia. Studies have demonstrated that finding podocytes in the urine may serve as an early marker of and diagnostic test for pre-eclampsia.

Differential diagnosis
Pre-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic renal disease, primary seizure disorders, gallbladder and pancreatic disease, immune or thrombotic thrombocytopenic purpura, antiphospholipid syndrome and hemolytic-uremic syndrome. It must be considered a possibility in any pregnant woman beyond 20 weeks of gestation. It is particularly difficult to diagnose when pre-existing conditions such as hypertension are present. Women with acute fatty liver of pregnancy may also present with elevated blood pressure and protein in the urine, but differ by the extent of liver damage. Other disorders that can cause high blood pressure include thyrotoxicosis, pheochromocytoma, and drug misuse.

Prevention
Preventive measures against pre-eclampsia have been heavily studied. Because the pathogenesis of pre-eclampsia is not completely understood, prevention remains a complex issue. Some currently accepted recommendations are:

Diet
Supplementation with a balanced protein and energy diet does not appear to reduce the risk of pre-eclampsia. Further, there is no evidence that changing salt intake has an effect.Supplementation with antioxidants such as vitamin C, D and E has no effect on pre-eclampsia incidence; therefore, supplementation with vitamins C, E, and D is not recommended for reducing the risk of pre-eclampsia.Calcium supplementation of at least 1 gram per day is recommended during pregnancy as it prevents pre-eclampsia where dietary calcium intake is low, especially for those at high risk. Higher selenium level is associated with lower incidence of pre-eclampsia. Higher cadmium level is associated with higher incidence of pre-eclampsia.

Aspirin
Taking aspirin is associated with a 1 to 5% reduction in pre-eclampsia and a 1 to 5% reduction in premature births in women at high risk. The World Health Organization recommends low-dose aspirin for the prevention of pre-eclampsia in women at high risk and recommends it be started before 20 weeks of pregnancy. The United States Preventive Services Task Force recommends a low-dose regimen for women at high risk beginning in the 12th week. Benefits are less if started after 16 weeks.The more recent study ASPRE, besides its efficacy in identifying women suspected to develop pre-eclampsia, has also been able to demonstrate a strong drop in the rate of early pre-eclampsia (-82%) and preterm pre-eclampsia (-62%). The efficacy of aspirin is due to screening to identify high risk women, adjusted prophylaxis dosage (150 mg/day), timing of the intake (bedtime) and must start before week 16 of pregnancy.

Physical activity
There is insufficient evidence to recommend either exercise or strict bedrest as preventive measures of pre-eclampsia.

Smoking cessation
In low-risk pregnancies, the association between cigarette smoking and a reduced risk of pre-eclampsia has been consistent and reproducible across epidemiologic studies. High-risk pregnancies (those with pregestational diabetes, chronic hypertension, history of pre-eclampsia in a previous pregnancy, or multifetal gestation) showed no significant protective effect. The reason for this discrepancy is not definitively known; research supports speculation that the underlying pathology increases the risk of pre-eclampsia to such a degree that any measurable reduction of risk due to smoking is masked. However, the damaging effects of smoking on overall health and pregnancy outcomes outweighs the benefits in decreasing the incidence of pre-eclampsia. It is recommended that smoking be stopped prior to, during and after pregnancy.

Immune modulation
Some studies have suggested the importance of a womans gestational immunological tolerance to her babys father, as the baby and father share genetics. There is tentative evidence that ongoing exposure either by vaginal or oral sex to the same semen that resulted in the pregnancy decreases the risk of pre-eclampsia. As one early study described, "although pre-eclampsia is a disease of first pregnancies, the protective effect of multiparity is lost with change of partner". The study also concluded that although women with changing partners are strongly advised to use condoms to prevent sexually transmitted diseases, "a certain period of sperm exposure within a stable relation, when pregnancy is aimed for, is associated with protection against pre-eclampsia".Several other studies have since investigated the decreased incidence of pre-eclampsia in women who had received blood transfusions from their partner, those with long preceding histories of sex without barrier contraceptives, and in women who had been regularly performing oral sex.Having already noted the importance of a womans immunological tolerance to her babys paternal genes, several Dutch reproductive biologists decided to take their research a step further. Consistent with the fact that human immune systems tolerate things better when they enter the body via the mouth, the Dutch researchers conducted a series of studies that confirmed a surprisingly strong correlation between a diminished incidence of pre-eclampsia and a womans practice of oral sex, and noted that the protective effects were strongest if she swallowed her partners semen. A team from the University of Adelaide has also investigated to see if men who have fathered pregnancies which have ended in miscarriage or pre-eclampsia had low seminal levels of critical immune modulating factors such as TGF-beta. The team has found that certain men, dubbed "dangerous males", are several times more likely to father pregnancies that would end in either pre-eclampsia or miscarriage. Among other things, most of the "dangerous males" seemed to lack sufficient levels of the seminal immune factors necessary to induce immunological tolerance in their partners.As the theory of immune intolerance as a cause of pre-eclampsia has become accepted, women who with repeated pre-eclampsia, miscarriages, or in vitro fertilization failures could potentially be administered key immune factors such as TGF-beta along with the fathers foreign proteins, possibly either orally, as a sublingual spray, or as a vaginal gel to be applied onto the vaginal wall before intercourse.

Treatment
The definitive treatment for pre-eclampsia is the delivery of the baby and placenta, but danger to the mother persists after delivery, and full recovery can take days or weeks. The timing of delivery should balance the desire for optimal outcomes for the baby while reducing risks for the mother. The severity of disease and the maturity of the baby are primary considerations. These considerations are situation-specific and management will vary with situation, location, and institution. Treatment can range from expectant management to expedited delivery by induction of labor or Caesarean section, in addition to medications. Important in management is the assessment of the mothers organ systems, management of severe hypertension, and prevention and treatment of eclamptic seizures. Separate interventions directed at the baby may also be necessary. Bed rest has not been found to be useful and is thus not routinely recommended.

Blood pressure
The World Health Organization recommends that women with severe hypertension during pregnancy should receive treatment with anti-hypertensive agents. Severe hypertension is generally considered systolic BP of at least 160 or diastolic BP of at least 110. Evidence does not support the use of one anti-hypertensive over another. The choice of which agent to use should be based on the prescribing clinicians experience with a particular agent, its cost, and its availability. Diuretics are not recommended for prevention of pre-eclampsia and its complications. Labetalol, hydralazine and nifedipine are commonly used antihypertensive agents for hypertension in pregnancy. ACE inhibitors and angiotensin receptor blockers are contraindicated as they affect fetal development.The goal of treatment of severe hypertension in pregnancy is to prevent cardiovascular, kidney, and cerebrovascular complications. The target blood pressure has been proposed to be 140–160 mmHg systolic and 90–105 mmHg diastolic, although values are variable.

Prevention of eclampsia
The intrapartum and postpartum administration of magnesium sulfate is recommended in severe pre-eclampsia for the prevention of eclampsia. Further, magnesium sulfate is recommended for the treatment of eclampsia over other anticonvulsants. Magnesium sulfate acts by interacting with NMDA receptors.

Epidemiology
Pre-eclampsia affects approximately 2–8% of all pregnancies worldwide. The incidence of pre-eclampsia has risen in the U.S. since the 1990s, possibly as a result of increased prevalence of predisposing disorders, such as chronic hypertension, diabetes, and obesity.Pre-eclampsia is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. Nearly one-tenth of all maternal deaths in Africa and Asia and one-quarter in Latin America are associated with hypertensive diseases in pregnancy, a category that encompasses pre-eclampsia.Pre-eclampsia is much more common in women who are pregnant for the first time. Women who have previously been diagnosed with pre-eclampsia are also more likely to experience pre-eclampsia in subsequent pregnancies. Pre-eclampsia is also more common in women who have pre-existing hypertension, obesity, diabetes, autoimmune diseases such as lupus, various inherited thrombophilias such as Factor V Leiden, renal disease, multiple gestation (twins or multiple birth), and advanced maternal age. Women who live at high altitude are also more likely to experience pre-eclampsia. Pre-eclampsia is also more common in some ethnic groups (e.g. African-Americans, Sub-Saharan Africans, Latin Americans, African Caribbeans, and Filipinos). Change of paternity in a subsequent pregnancy has been implicated as affecting risk, except in those with a family history of hypertensive pregnancy.Eclampsia is a major complication of pre-eclampsia. Eclampsia affects 0.56 per 1,000 pregnant women in developed countries and almost 10 to 30 times as many women in low-income countries as in developed countries.

Complications
Complications of pre-eclampsia can affect both the mother and the fetus. Acutely, pre-eclampsia can be complicated by eclampsia, the development of HELLP syndrome, hemorrhagic or ischemic stroke, liver damage and dysfunction, acute kidney injury, and acute respiratory distress syndrome (ARDS).Pre-eclampsia is also associated with increased frequency of Caesarean section, preterm delivery, and placental abruption. Furthermore, an elevation in blood pressure can occur in some individuals in the first week postpartum attributable to volume expansion and fluid mobilization. Fetal complications include fetal growth restriction and potential fetal or perinatal death.Long-term, an individual with pre-eclampsia is at increased risk for recurrence of pre-eclampsia in subsequent pregnancies.

Eclampsia
Eclampsia is the development of new convulsions in a pre-eclamptic patient that may not be attributed to other causes. It is a sign that the underlying pre-eclamptic condition is severe and is associated with high rates of perinatal and maternal morbidity and mortality. Warning symptoms for eclampsia in an individual with current pre-eclampsia may include headaches, visual disturbances, and right upper quadrant or epigastric abdominal pain, with a headache being the most consistent symptom </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 Genital leiomyoma and explain in detail? [/INST] Genital leiomyomas (also known as "Dartoic leiomyomas") are leiomyomas that originate in the dartos muscles, or smooth muscles, of the genitalia, areola, and nipple. They are a subtype of cutaneous leiomyomas that affect smooth muscle found in the scrotum, labia, or nipple. They are benign tumors, but may cause pain and discomfort to patients. Signs and symptoms of Genital leiomyoma can be symptomatic or asymptomatic and is dependent on the type of leiomyoma. In most cases, pain in the affected area or region is most common. For vaginal leiomyoma, vaginal bleeding and pain may occur. Uterine leiomyoma may exhibit pain in the area as well as painful bowel movement and/or sexual intercourse. Nipple pain, enlargement, and tenderness can be a symptom of nipple-areolar leiomyomas. Genital leiomyomas can be caused by multiple factors, one can be genetic mutations that affect hormones such as estrogen and progesterone. Moreover, risk factors to the development of genital leiomyomas include age, race, and gender. Ultrasound and imaging procedures are used to diagnose genital leiomyomas, while surgically removing the tumor is the most common treatment of these diseases. Case studies for nipple areolar, scrotal, and uterine leiomyoma were used, since there were not enough secondary resources to provide more evidence.

Types of genital leiomyomas
Uterine
Uterine Leiomyomas are benign tumors that affect 70% of European people with uteri and more than 80% African descent people with uteri by the time they turn 50 years of age. Although, only 30% of people with uteri experience symptoms. Of those with uterine leiomyomas, 29% result in hospitalizations. One-third of patients with these fibroids experience life-threatening anemia, a condition where the body does not have enough oxygen due to lack of red blood cells to carry oxygen throughout the body. These tumors are mainly treated by performing hysterectomies, a procedure in which the uterus is removed, and account for approximately 40-60% of all performed hysterectomies. Symptoms are dependent on the location of the tumor, which may occur in the submucosal (under the mucous membranes and lines the inner part of some organs), intramural (within the walls of the organs), or subserosal areas (under the serosa and lines the outer part of some organs).

Nipple-areolar
Nipple-Areolar leiomyoma is a rare type of genital leiomyoma. It presents as either unilateral or bilateral growth of benign tumor of the smooth muscle that can be painful, tender, and inflamed. They are typically less than 2 cm in length. Since this is an extremely rare tumor, with only 50 cases reported in literature, it often only reported to physicians due to chronic nipple pain.

Vaginal
Vaginal paraurethral leiomyoma is another type of genital leiomyoma that is also less common compared to other types of leiomyoma. It presents as a benign tumor of the smooth muscle in the genitourinary tract, which includes urinary and genital organs, that can grow rapidly during pregnancy. On the other hand, the tumor tend to decrease in size upon menopause. This may be due to the growth of tumor that is dependent on hormones. There is not a definite cause for the development of the disease, but one that was hypothesized is that it originates from a blood vessel tissue and smooth muscle fiber residue in an embryo. Imaging and histopathological examination is used for diagnosis of the disease. Furthermore, treatment of the disease is to surgically remove the tumor.Vulvar Leiomyomas are one the most prominent types of genital leiomyomas. Lesions to the vulva may be up to 15 cm in length and they are reported to be acutely painful. Enlargement of these leiomyomas may occur during pregnancy.

Scrotal
Scrotal leiomyoma is considered to be an extremely rare type of genital leiomyoma. Because leiomyomas in the scrotum are usually painless and slowly grows over time, there is a delay in physician referral, with an average of 6–7 years. Physician referral usually occurs when people notice their testicles growing and getting heavier. A review of 11,000 cases of benign and malignant tumors of the scrotum found 11 cases of scrotal leiomyoma. Scrotal leiomyomas can affect males of any age and race, but are more common in Caucasians from the ages of 40-60. The tumor in the scrotum has an average diameter of 6.4 cm.

Signs and symptoms
People with leiomyoma can be presented as asymptomatic, or having no symptoms. However, some people may experience severe symptoms that can interfere with daily activities. Common symptoms are recurrent pain and pressure in the affected region. People with uterine leiomyoma can experience pain during urination, bowel movements, and sexual intercourse. Other symptoms are abnormal vaginal bleeding and severe menstrual cramps.Nipple-Areolar leiomyomas can affect one or both nipples, presenting with symptoms of nipple tenderness. People with leiomyomas in the scrotum generally notice a growing testicle over a span of multiple years, where it can grow and become heavy to the point of discomfort. Due to the painless and slow, progressive growth of the tumor, the time frame between recognizing the tumor and surgical removal can be anywhere from 2 to 20 years.

Causes
Uterine
Genetics
Development and progression of uterine leiomyomas may be contributed by changes in gene regulation or mutation of genes found to be associated with uterine fibroids. Abnormalities of these genes may initiate the formation or growth of these tumors. Modification of signaling pathways and genes (e.g. CYP1A1, CYP1b1, and MED12) exhibits a correlation with the development and growth of tumors in the uterus.

Hormones
The occurrence of uterine leiomyomas is mostly common during reproductive years. This suggests that the role of ovarian hormones, estrogen and progesterone, is important in the development of this disease. Studies have shown that the development of tumors rely on these hormones and that tumors have shown to affect estrogen metabolism as it can increase the amount both its estrogen and progesterone receptors.

Diet and nutrition
Long-term results suggests that diets that are mostly plant-based, composed of fruits and vegetables, and rich in Vitamin D have a positive effect on the development of diseases, including uterine leiomyomas. On the other hand, alcohol, coffee, and red meat may have an effect on the progression or growth of these diseases based on observational and epidemiological studies.

Risk Factors
Uterine
Race
At the age of 35, incidence is reported to be 60% in African-American with-uterus persons and 40% in Caucasian with-uterus persons. By the age of 50, the incidence of uterine fibroids was >80% in African-American with uterus persons and >70% of Caucasian with uterus persons.Recurrence of uterine leiomyomas 4–5 years after removal occurs up to 59% of the time for with-uterus persons of African origin.

Age
People with uteri who delay their first pregnancy past the age of 30 are at a higher risk for uterine fibroids.

Genetic factors
Specific genetic alterations may play a role in the development of uterine leiomyomas. A mutation of a single mesenchymal cell, a stem cell that plays an important role in making and repairing bone, and fat - found in the bone marrow and adipose tissues, with the involvement of progesterone and 17 b-estrodiol can lead to these fibroids.

Early menarche
Some early studies report early age onset of menstruation increases the risk of developing fibroids. However, the biological mechanism of how this occurs is not well understood and further investigation is needed.

Nipple-Areolar
Age
The occurrence of benign tumors of the nipple commonly starts at the age of 20 and peaks around the age of 40 to 50. Growth of nipple-areolar leiomyomas may increase even after menopause.

Diagnosis
There are many ways genital leiomyomas can be diagnosed. Those who have genital leiomyomas can be asymptomatic or symptomatic. Symptoms including but not limited to pelvic pain or abnormal menstrual bleeding are used to assess fibroids. Imaging are often used to detect the presence of fibroids, particularly uterine fibroids. This includes ultrasonography, a procedure that uses high-frequency sound waves to capture tissue and organ images; Sonohysterography, a painless procedure similar to ultrasonography to capture images inside the uterus; Hysteroscopy, which examines the inside of the uterus and cervix using a flexible tube called hysteroscope.

Treatment
Treatment for genital leiomyomas primarily consist of removal by surgeries. However, genital leiomyomas typically re-occur and may reappear from 6 weeks to over 15 years post-removal. When managing leiomyomas, radiation treatment should be avoided due to the inducing effect of malignant transformation in the smooth muscle of the tumor.For uterine leiomyomas, complete removal of the uterus is required. There is minimal evidence to support the use of myomectomy to preserve fertility. Evidence shows that preoperative use of gonadotropin-releasing hormone agonists, which prevents or lessen the production of hormones like progesterone, estrogen, and testosterone, can reduce surgical complications.Subareolar leiomyomas require surgical removals. Precise surgical margins are needed to prevent re-occurrences.Leiomyomas in the scrotum require an orchidectomy, or surgical removal of one or two testicles.
To manage pain that arises from the fibroids, drugs that affect smooth muscle contraction such as nitroglycerin, nifedipine, phenoxybenzamine and doxazosin can be employed to ease the pain. For nerve pain or tenderness, gabapentin and topical analgesics may be employed.

Clinical cases
Nipple-areolar leiomyomas
41-year-old-male
A 41-year-old-male presented with a yellow nodule in the upper left areola. He reported mild pain and itching, but denied other symptoms. Sebaceous glands, epidermal hyperplasia, and tumor nests were among the numerous findings that lead to preceded a diagnosis of diagnosis of areolar leiomyoma with sebaceous hyperplasia. Characteristics of the leiomyoma included positive for estrogen and progesterone receptors and high expression of epidermal growth factor, insulin-like growth factor 1, and fibroblast growth factor-2. It is suspected that these growth factors led to the growth of the leiomyoma through an autocrine process.. The patient declined resection and the region has remained stable since.

67-year-old-female
A 67-year-old-female presented with a growing mass on the left breast areolar region. The patient had been taking methotrexate to treat her rheumatoid arthritis. Magnetic resonance imaging revealed led to a conclusion that the tumor arose from the areola. A biopsy led to a diagnosis of diffuse large, non GC B-cell lymphoma that was suspected to be associated with methotrexate. The tumor reduced in size following the withdrawal of methotrexate. Three months later, another tumor developed in the areolar region of the opposite breast.

35-year-old-female
A 35-year-old-female presented with a painful lump in the right nipple. The patient reported the lump occurred after a breastfeeding injury 3 years prior to coming into the outpatient center. The tumor has been growing ever since. A biopsy was performed to confirm the leiomyoma in the nipple.

Uterine Leiomyomas
48-year-old-female
A 48-year-old-female presented with several uterine fibroids that were asymptomatic </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 Platelet storage pool deficiency and explain in detail? [/INST] Platelet storage pool deficiency is a type of coagulopathy characterized by defects in the granules in platelets, particularly a lack of granular non-metabolic adenosine diphosphate. Individuals with adenosine diphosphate deficient storage pool disease present a prolonged bleeding time due to impaired aggregation response to fibrillar collagen.

Symptoms and signs
The presentation (signs/symptoms) of an individual with  platelet storage pool deficiency is as follows:
Unusual bleeding(after surgical procedure)
Anemia
Decrease mean platelet volume
Myelodysplasia

Cause
The condition of platelet storage pool deficiency can be acquired  or inherited (genetically passed on from the individuals parents). Some of the causes of platelet storage pool deficiency when acquired are:
Hairy-cell leukemia
Cardiovascular bypass

Mechanism
In terms of the pathophysiology of platelet storage pool deficiency one must consider several factors including the human bodys normal function prior to such a deficiency, such as platelet alpha-granules one of three types of platelet secretory granulePlatelet α–granules are important in platelet activity, α–granules connect with plasma membrane. This in turn increases the size of the platelet. Platelet α–granules have an important role in hemostasis as well as thrombosis. SNARE accessory proteins control the secretion of α–granule.

Diagnosis
The diagnosis of this condition can be done via the following:
Flow cytometry
Bleeding time analysis
Platelet aggregation function study:

Types
This condition may involve the alpha granules or the dense granules.
Therefore, the following examples include:

Platelet alpha-granules
Gray platelet syndrome
Quebec platelet disorder
Dense granules
δ-Storage pool deficiency
Hermansky–Pudlak syndrome
Chédiak–Higashi syndrome

Treatment
Platelet storage pool deficiency has no treatment however management consists of antifibrinolytic medications if the individual has unusual bleeding event, additionally caution should be taken with usage of NSAIDS

See also
Hypocoagulability
Hypercoagulability

References
Further reading
Sandrock, Kirstin; Zieger, Barbara (2010). "Current Strategies in Diagnosis of Inherited Storage Pool Defects" </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 Hemoglobinopathy and explain in detail? [/INST] Hemoglobinopathy is the medical term for a group of inherited blood disorders and diseases that primarily affect red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits.There are two main groups: abnormal structural hemoglobin variants caused by mutations in the hemoglobin genes, and the thalassemias, which are caused by an underproduction of otherwise normal hemoglobin molecules. The main structural hemoglobin variants are HbS, HbE and HbC. The main types of thalassemia are alpha-thalassemia and beta thalassemia.The two conditions may overlap because some conditions which cause abnormalities in hemoglobin proteins  also affect their production.  Some hemoglobin variants do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies.

Hemoglobin structural biology
Normal human hemoglobins are tetrameric proteins composed of two pairs of globin chains, each of which contains one alpha-like (α-like) chain and one beta-like (β-like) chain. Each globin chain is associated with an iron-containing heme moiety. Throughout life, the synthesis of the alpha-like and the beta-like (also called non-alpha-like) chains is balanced so that their ratio is relatively constant and there is no excess of either type.The specific alpha and beta-like chains that are incorporated into Hb are highly regulated during development:
Embryonic Hbs are expressed as early as four to six weeks of embryogenesis and disappear around the eighth week of gestation as they are replaced by fetal Hb. Embryonic Hbs include:
Hb Gower-1, composed of two ζ globins (zeta globins) and two ε globins (epsilon globins) (ζ2ε2)
Hb Gower-2, composed of two alpha globins and two epsilon globins (α2ε2)
Hb Portland, composed of two zeta globins and two gamma globins (ζ2γ2)
Fetal Hb (Hb F) is produced from approximately eight weeks of gestation through birth and constitutes approximately 80 percent of Hb in the full-term neonate. It declines during the first few months of life and, in the normal state, constitutes <1 percent of total Hb by early childhood. Hb F is composed of two alpha globins and two gamma globins (α2γ2).
Adult Hb (Hb A) is the predominant Hb in children by six months of age and onward; it constitutes 96-97% of total Hb in individuals without a hemoglobinopathy. It is composed of two alpha globins and two beta globins (α2β2).
Hb A2 is a minor adult Hb that normally accounts for approximately 2.5-3.5% of total Hb from six months of age onward. It is composed of two alpha globins and two delta globins (α2δ2).

Classification of hemoglobinopathies
A)  Qualitative
Structural abnormalities
Hb variants: Hb structural variants are qualitative defects that cause a change in the structure (primary, secondary, tertiary, and/or quaternary) of the Hb molecule. The majority of Hb variants do not cause disease and are most commonly discovered either incidentally or through newborn screening. A subset of Hb variants can cause severe disease when inherited in the homozygous or compound heterozygous state in combination with another structural variant or a thalassemia mutation. When clinical consequences occur, they may include anemia due to hemolysis or polycythemia due to alterations in the oxygen affinity of the abnormal Hb. Common examples of hemoglobin variants associated with hemolysis include sickle Hb (Hb S) and Hb C. Hb variants can usually be detected by protein-based assay methods; however, DNA-based methods may be required for variants with ambiguous or unusual results from protein analysis.The major functional consequences of Hb structural variants can be classified as follows:
Change in physical properties (solubility): Common beta globin mutations can alter the solubility of the Hb molecule: Hb S polymerizes when deoxygenated and Hb C crystallizes.
Reduced protein stability (instability): Unstable Hb variants are mutations that cause the Hb molecule to precipitate, spontaneously or upon oxidative stress, resulting in hemolytic anemia. Precipitated, denatured Hb can attach to the inner layer of the plasma membrane of the red blood cell (RBC) and form Heinz bodies.
Change in oxygen affinity: High or low oxygen affinity Hb molecules are more likely than normal to adopt the relaxed (R, oxy) state or the tense (T, deoxy) state, respectively. High oxygen affinity variants (R state) cause polycythemia (e.g., Hb Chesapeake, Hb Montefiore). Low oxygen affinity variants can cause cyanosis (e.g., Hb Kansas, Hb Beth Israel).
Oxidation of heme iron: Mutations of the heme binding site, particularly those affecting the conserved proximal or distal histidine residues, can produce M-hemoglobin, in which the iron atom in heme is oxidized from the ferrous (Fe2+) state to the ferric (Fe3+) state, with resultant methemoglobinemia.

Chemical abnormalities
Methemoglobinemia:
a condition caused by elevated levels of methemoglobin in the blood. Methaemoglobin is a form of Hb that contains the ferric [Fe3+] form of iron. The affinity for oxygen of ferric iron is impaired. The binding of oxygen to methaemoglobin results in an increased affinity for oxygen in the remaining heme sites that are in ferrous state within the same tetrameric haemoglobin unit.

B)  Quantitative
Production abnormalities
Copy number variation (e.g., deletion, duplication, insertion) is also a common genetic cause of Hb disorders, and complex rearrangements and globin gene fusions can also occur.
Thalassemias: Thalassemias are quantitative defects that lead to reduced levels of one type of globin chain, creating an imbalance in the ratio of alpha-like chains to beta-like chains. As noted above, this ratio is normally tightly regulated to prevent excess globin chains of one type from accumulating. The excess chains that fail to incorporate into Hb form non-functional aggregates that precipitate within the RBC. This can lead to premature RBC destruction in the bone marrow (beta thalassemia) and/or in the peripheral blood (alpha thalassemia). Types:
Alpha
Beta (Major)
Beta (Minor)

Hemoglobin variants
Haemoglobin variant are not necessarily pathological. For example, haemoglobin Valletta and haemoglobin Marseille are two haemoglobin variants which are non-pathological

HbS
HbC
HbE
Hb Barts
Hb D-Punjab
HbO (Hb O-Arab)
Hb G-Philadelphia
Hb H
Hb Constant Spring
Hb Hasharon
Hemoglobin Kenya
Hb Korle-Bu
Hb Lepore
Hb M
Hb Kansas
Hb J
Hb N-Baltimore
Hb Hope
Hb Pisa

Electrophoretic migration patterns
Hemoglobin variants can be detected by gel electrophoresis.

Alkaline electrophoresis
In general on alkaline electrophoresis in order of increasing mobility are hemoglobins A2, E=O=C, G=D=S=Lepore, F, A, K, J, Barts, N, I, and H.In general a sickling test is performed on abnormal hemoglobins migrating in the S location to see if the hemoglobin precipitates in solution of sodium bisulfite.

Acid electrophoresis
In general on acid electrophoresis in order of increasing mobility are hemoglobins F, A=D=G=E=O=Lepore, S, and C.This is how abnormal hemoglobin variants are isolated and identified using these two methods </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 Progressive pseudorheumatoid dysplasia 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 Duodenal lymphocytosis and explain in detail? [/INST] Duodenal lymphocytosis, sometimes called lymphocytic duodenitis, lymphocytic duodenosis, or duodenal intraepithelial lymphocytosis, is a condition where an increased number of intra-epithelial lymphocytes is seen in biopsies of the duodenal mucosa when these are examined microscopically. This form of lymphocytosis is often a feature of coeliac disease but may be found in other disorders.

Presentation
The condition is characterised by an increased proportion of lymphocytes in the epithelium of the duodenum, usually when this is greater than 20-25 per 100 enterocytes.   Intra-epithelial lymphocyte (IEL) are normally present in intestine and numbers are normally greater in the crypts and in the jejunum; these are distinct from those found in the lamina propria of the intestinal mucosa.  IELs are mostly T cells.  Increased numbers of IELs are reported in around 3% of in duodenal biopsies, depending on case mix, but may be increasingly being found, in up to 7%.

Causes
The list of possible causes is wide, including coeliac disease, environmental enteropathy (tropical sprue), autoimmune enteropathy, small intestinal bacterial overgrowth, NSAID damage, Helicobacter pylori, other infections and Crohns disease.

Diagnosis
Diagnosis is made by accurate counting of intraepithelial lymphocytes during histological examination of the duodenum </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 Dents disease and explain in detail? [/INST] Dents disease (or Dent disease) is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, excess calcium in the urine, formation of calcium kidney stones, nephrocalcinosis, and chronic kidney failure.
"Dents disease" is often used to describe an entire group of familial disorders, including X-linked recessive nephrolithiasis with kidney failure, X-linked recessive hypophosphatemic rickets, and both Japanese and idiopathic low-molecular-weight proteinuria.  About 60% of patients have mutations in the CLCN5 gene (Dent 1), which encodes a kidney-specific chloride/proton antiporter, and 15% of patients have mutations in the OCRL1 gene (Dent 2).

Signs and symptoms
Dents disease often produces the following signs and symptoms:
Extreme thirst combined with dehydration, which leads to frequent urination
Nephrolithiasis (kidney stones)
Hypercalciuria (high urine calcium - >300 mg/d or >4 mg/kg per d with normal levels blood/serum calcium)
Aminoaciduria (amino acids in urine)
Phosphaturia (phosphate in urine)
Glycosuria (glucose in urine)
Kaliuresis (potassium in urine)
Hyperuricosuria (excessive amounts of uric acid in the urine)
Impaired urinary acidification
RicketsIn a study of 25 patients with Dents disease, 9 of 15 men, and one of 10 women had end-stage kidney disease by the age of 47.

Genetics
Dent disease 1
Dents disease is a X-linked recessive disorder. The males are prone to manifesting symptoms in early adulthood with symptoms of calculi, rickets or even with kidney failure in more severe cases.In humans, gene CLCN5 is located on chromosome Xp11.22, and has a 2238-bp coding sequence that consists of 11 exons that span 25 to 30 kb of genomic DNA and encode a 746-amino-acid protein.  CLCN5 belongs to the family of voltage-gated chloride channel genes (CLCN1-CLCN7, CLCKa and CLCKb) that have about 12 transmembrane domains. These chloride channels have an important role in the control of membrane excitability, transepithelial transport, and possibly cell volume.The mechanisms by which CLC-5 dysfunction results in hypercalciuria and the other features of Dents disease remain to be elucidated </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 Clear cell acanthoma 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 Neurapraxia and explain in detail? [/INST] Neurapraxia is a disorder of the peripheral nervous system in which there is a temporary loss of motor and sensory function due to blockage of nerve conduction, usually lasting an average of six to eight weeks before full recovery. Neurapraxia is derived from the word apraxia, meaning “loss or impairment of the ability to execute complex coordinated movements without muscular or sensory impairment”.
This condition is typically caused by a blunt neural injury due to external blows or shock-like injuries to muscle fibers and skeletal nerve fibers, which leads to repeated or prolonged pressure buildup on the nerve. As a result of this pressure, ischemia occurs, a neural lesion results, and the human body naturally responds with edema extending in all directions from the source of the pressure. This lesion causes a complete or partial action potential conduction block over a segment of a nerve fiber and thus a reduction or loss of function in parts of the neural connection downstream from the lesion, leading to muscle weakness.
Neurapraxia results in temporary damage to the myelin sheath but leaves the nerve intact and is an impermanent condition; thus, Wallerian degeneration does not occur in neurapraxia. In order for the condition to be considered neurapraxia, according to the Seddon classification system of peripheral nerve injury,  there must be a complete and relatively rapid recovery of motor and sensory function once nerve conduction has been restored; otherwise, the injury would be classified as axonotmesis or neurotmesis. Thus, neurapraxia is the mildest classification of peripheral nerve injury.
Neurapraxia is very common in professional athletes, especially American football players, and is a condition that can and should be treated by a physician.

Signs and symptoms
A variety of nerve types can be subjected to neurapraxia and therefore symptoms of the injury range in degree and intensity. Common symptoms of neurapraxia are disturbances in sensation, weakness of muscle, vasomotor and sudomotor paralysis in the region of the affected nerve or nerves, and abnormal sensitivity of the nerve at the point of injury. It has been observed that subjective sensory symptoms include numbness, tingling, and burning sensations at the site of the injury. Objective sensory symptoms are generally minimal in regards to touch, pain, heat, and cold. In cases of motor neuron neurapraxia, symptoms consist of flaccid paralysis of the muscles innervated by the injured nerve or nerves.
Symptoms are often transient and only last for a short period of time immediately following the injury. However, in severe cases of neurapraxia, symptoms can persist for weeks or months at a time.

Causes
The cause of neurapraxia is a neural lesion which causes a temporary block of nerve conduction without transection of the axon. A conduction block is classified as a 40% reduction in action potential amplitude over a short distance on the nerve, or a 50% reduction for a longer distance on the nerve. In neurapraxia, stimulation to the injured nerve results in a greater reduction in the action potential amplitude on the proximal site of the injury as opposed to the distal site.

Anatomy
Neurapraxia occurs in the peripheral nervous system typically in the ulnar, median, and radial nerves of the upper body and in the sciatic and peroneal nerves of the lower body. Peripheral nerves are myelinated, relatively large, spatially complex cells whose size and connectivity typically make them more susceptible to damage and compromise their capacity to self-repair, although this is not the case in neurapraxia. Microscopic evidence has shown that there is damage to the myelin sheath, but not to the axon. Therefore, distal nerve fibers do not degenerate and the myelin damage can be repaired.

Order of pathology
The order of pathology within the first 24 hours after injury follows a general pattern of nerve injury. The first physical manifestation of the injury is focal swelling adjacent to the site of the injury. In the cellular dimension, a fragmentation of neurotubules and neurofilaments occurs as a result of pressure exerted on the nerve. Axons swell at some sites and are compressed at others, leading to a beaded appearance.

Mechanisms of injury
There are several mechanisms of nerve injury including mechanical lesions, ischemia, immunologic attack, metabolic disorder, toxic agents, and exposure to radiation. The most common mechanism of injury is nerve compression in which external pressure causes decreased blood flow to the nerve and deformation of the nerve fibers. Repeated or prolonged compression of the nerve results in ischemia and ultimately edema above and below the source of the pressure (I). The thinning of myelin sheaths or focal demyelination are the main consequences of the injury that lead to conduction blockage.

Diagnosis
Seddon classification
There are three distinct classifications and degrees of nerve injury:

Neurotmesis is the most serious degree of nerve injury.  It involves the disruption of the nerve and the nerve sheath.
Axonotmesis occurs when the majority of the supporting structures of the nerve are preserved, but disruption of the nerve fibers is still observed.  Wallerian degeneration often occurs in the near the proximity of the injury site.
Neurapraxia is least serious form of nerve injury.There are two different forms of mechanical nerve injury involving neurapraxia.  The underlying causes of transient nerve injury typically include a brief ischemic episode or any form of compression. More persistent forms of nerve injury involve demyelination and axonal constriction. In certain circumstances, diagnosing neurapraxia can be uncomfortable because of the presence of severe neuropathic pain.  Neuropathic pain is an indication that the lesion of the nerve is still in progress. Diagnosis of neurapraxia is almost always followed by a quick and complete recovery period.

Treatment and recovery
The entire nerve is involved in the response to traumatic injuries. The outcome of nerve repair is dependent on the degree of the nerve injury and the circumstances at the site of injury. Since neurapraxia is the least serious form of peripheral nerve injury, recovery and treatment are not extensive.  Once the cause of neurapraxia is eliminated, recovery of the lesions in the nerve occurs within a short time span.

Non-operative treatment
Neurapraxia is often treated and cured by non-operative means.  The primary goals of treatment are to maintain the proper nutrition of the paralyzed muscles, prevent contraction by the antagonists of the paralyzed muscles, and to consistently keep the joints mobile. A splint is often used in cases of neurapraxia because it is able to maintain a relaxed position of the paralyzed muscle.  The splint prevents the paralyzed muscle from being overstretched either by the force of gravity or by other non-paralyzed antagonists.  During the recovery period of neurapraxia, it is essential that the joints constantly undergo passive movement in order to preserve proper mobility.  If joints are kept mobile, the limb has the best possible chance of benefit from the return of nervous function. Non-steroidal anti-inflammatory medications can also help to reduce swelling at the injury site. In addition to these non-operative remedies, it is suggested that muscles affected by neurapraxia be kept warm at all times.  Circulation in the limb is stimulated with the use of heat.
Once voluntary movement has returned to the muscle, recovery and treatment continues by the participation in active exercises.   Physical Therapy and Occupational Therapy are common sources of treatment during these early stages of restoration of active movement. Almost all cases of neurapraxia can be completely treated by non-operative means.

Treating cervical cord neurapraxia on the field
According to medical professionals with the Cleveland Clinic, once an athlete suffers from an episode of cervical spinal cord neurapraxia, team physician or athletic trainer first stabilize the head and neck followed by a thorough neurologic inspection. If the injury is deemed severe, injured parties should be taken to a hospital for evaluation. Athletes that suffer from severe episodes of neurapraxia are urged to consult orthopaedic or spinal medical specialists. In mild cases of neurapraxia, the athlete is able to remove themselves from the field of play. However, the athlete is still advised to seek medical consultation.

Prognosis
In cases of neurapraxia, the function of the nerves are temporarily impaired.  However, the prognosis for recovery from neurapraxia is efficient and quick.  Recovery begins within two to three weeks after the injury occurs, and it is complete within six to eight weeks.  There are instances when function is not completely restored until four months after the instance of injury. The recovery period of neurapraxia is not an entirely ordered process, but the recovery is always complete and fast.

Epidemiology
Neurapraxia is most commonly observed in athletes involved in collision sports, such as American football. Athletes participating in collision sports most often suffer from cervical cord neurapraxia, also known as transient neurapraxia. Cervical cord neurapraxia is the result of a severe collision in which a blow to the crown of the athletes head forcefully extends or compresses the neck. Numbness, stinging, and/or weakness in the arms, legs or both, distinguish cervical cord neurapraxia. Typical episodes of transient neurapraxia only last a few seconds and symptoms dissipate entirely. Though the severity of the injury can range, transient neurapraxia does not lead to permanent paralysis of the affected muscles </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 Volvulus and explain in detail? [/INST] A volvulus is when a loop of intestine twists around itself and the mesentery that supports it, resulting in a bowel obstruction. Symptoms include abdominal pain, abdominal bloating, vomiting, constipation, and bloody stool. Onset of symptoms may be rapid or more gradual. The mesentery may become so tightly twisted that blood flow to part of the intestine is cut off, resulting in ischemic bowel. In this situation there may be fever or significant pain when the abdomen is touched.Risk factors include a birth defect known as intestinal malrotation, an enlarged colon, Hirschsprung disease, pregnancy, and abdominal adhesions. Long term constipation and a high fiber diet may also increase the risk. The most commonly affected part of the intestines in adults is the sigmoid colon with the cecum being second most affected. In children the small intestine is more often involved. The stomach can also be affected. Diagnosis is typically with medical imaging such as plain X-rays, a GI series, or CT scan.Initial treatment for sigmoid volvulus may occasionally occur via sigmoidoscopy or with a barium enema. Due to the high risk of recurrence, a bowel resection within the next two days is generally recommended. If the bowel is severely twisted or the blood supply is cut off, immediate surgery is required. In a cecal volvulus, often part of the bowel needs to be surgically removed. If the cecum is still healthy, it may occasionally be returned to a normal position and sutured in place.Cases of volvulus were described in ancient Egypt as early as 1550 BC. It occurs most frequently in Africa, the Middle East, and India. Rates of volvulus in the United States are about 2–3 per 100,000 people per year. Sigmoid and cecal volvulus typically occurs between the ages of 30 and 70. Outcomes are related to whether or not the bowel tissue has died. The term volvulus is from the Latin "volvere"; which means "to roll".

Signs and symptoms
Regardless of cause, volvulus causes symptoms by two mechanisms:
Bowel obstruction manifested as abdominal distension and bilious vomiting.
Ischemia (loss of blood flow) to the affected portion of intestine.Depending on the location of the volvulus, symptoms may vary.  For example, in patients with cecal volvulus, the predominant symptoms may be those of small bowel obstruction (nausea, vomiting and lack of stool or flatus), because the obstructing point is close to the ileocecal valve and small intestine.  In patients with sigmoid volvulus, although abdominal pain may be present, symptoms of constipation may be more prominent.
Volvulus causes severe pain and progressive injury to the intestinal wall, with accumulation of gas and fluid in the portion of the bowel obstructed. Ultimately, this can result in necrosis of the affected intestinal wall, acidosis, and death.  This is known as a closed-loop obstruction because there exists an isolated ("closed") loop of bowel.  Acute volvulus often requires immediate surgical intervention to untwist the affected segment of bowel and possibly resect any unsalvageable portion.Volvulus occurs most frequently in middle-aged and elderly men.  Volvulus can also arise as a rare complication in persons with redundant colon, a normal anatomic variation resulting in extra colonic loops.Sigmoid volvulus is the most-common form of volvulus of the gastrointestinal tract. and is responsible for 8% of all intestinal obstructions. Sigmoid volvulus is particularly common in elderly persons and constipated patients. Patients experience abdominal pain, distension, and absolute constipation.
Cecal volvulus is slightly less common than sigmoid volvulus and is associated with symptoms of abdominal pain and small bowel obstruction.
Volvulus can also occur in patients with Duchenne muscular dystrophy due to smooth muscle dysfunction.Gastric volvulus causes nausea, vomiting, and pain in the upper abdomen. The Borchardt triad is a group of symptoms that help doctors to identify gastric volvulus. The symptoms are intractable retching, pain in the upper abdomen and inability to pass nasogastric tube into the stomach.

Complications
Strangulation
Gangrene
Perforation
Faecal peritonitis
Recurrent volvulus

Causes
Midgut volvulus occurs in people (usually babies) that are predisposed because of congenital intestinal malrotation. Segmental volvulus occurs in people of any age, usually with a predisposition because of abnormal intestinal contents (e.g. meconium ileus) or adhesions.  Volvulus of the cecum, transverse colon, or sigmoid colon occurs, usually in adults, with only minor predisposing factors such as redundant (excess, inadequately supported) intestinal tissue and constipation.

Types
volvulus neonatorum
volvulus of the small intestine
midgut volvulus (due to intestinal malrotation)
volvulus of the caecum (cecum), also cecal volvulus
sigmoid colon volvulus (sigmoid volvulus)
volvulus of the transverse colon
volvulus of the splenic flexure, the rarest
gastric volvulus
ileosigmoid knot

Diagnosis
After taking a thorough history, the diagnosis of colonic volvulus is usually easily included in the differential diagnosis.  Abdominal plain x-rays are commonly confirmatory for a volvulus, especially if a "bent inner tube" sign or a "coffee bean" sign are seen.  These refer to the shape of the air-filled closed loop of colon which forms the volvulus.  Should the diagnosis be in doubt, a barium enema may be used to demonstrate a "birds beak" at the point where the segment of proximal bowel and distal bowel rotate to form the volvulus.This area shows an acute and sharp tapering and looks like a birds beak.  If a perforation is suspected, barium should not be used due to its potentially lethal effects when distributed throughout the free intraperitoneal cavity. Gastrografin, which is safer, can be substituted for barium.The differential diagnosis includes the much more common constricting or obstructing carcinoma.  In approximately 80 percent of colonic obstructions, invasive carcinoma is found to be the cause of the obstruction.  This is usually easily diagnosed with endoscopic biopsies.
Diverticulitis is a common condition with different presentations.  Although diverticulitis may be the source of a colonic obstruction, it more commonly causes an ileus, which appears to be a colonic obstruction.
Endoscopic means can be used to secure a diagnosis although this may cause a perforation of the inflamed diverticular area </s>


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<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 Pathologic fracture 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 Brainstem stroke 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 Relative afferent pupillary defect and explain in detail? [/INST]  </s>