<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 Ocular ischemic syndrome and explain in detail? [/INST] Ocular ischemic syndrome is the constellation of ocular signs and symptoms secondary to severe, chronic arterial hypoperfusion to the eye. Amaurosis fugax is a form of acute vision loss caused by reduced blood flow to the eye; it may be a warning sign of an impending stroke, as both stroke and retinal artery occlusion can be caused by thromboembolism due to atherosclerosis elsewhere in the body (such as coronary artery disease and especially carotid atherosclerosis). Consequently, those with transient blurring of vision are advised to urgently seek medical attention for a thorough evaluation of the carotid artery. Anterior segment ischemic syndrome is a similar ischemic condition of anterior segment usually seen in post-surgical cases. Retinal artery occlusion (such as central retinal artery occlusion or branch retinal artery occlusion) leads to rapid death of retinal cells, thereby resulting in severe loss of vision.

Symptoms and signs
Those with ocular ischemic syndrome are typically between the ages of 50 and 80 (patients over 65); twice as many men as women are affected.  More than 90% of those presenting with the condition have vision loss. Patients may report a dull, radiating ache over the eye and eyebrow. Those with ocular ischemic syndrome may also present with a history of other systemic diseases including arterial hypertension, diabetes mellitus, coronary artery disease, previous stroke, and hemodialysis.The condition presents with visual loss secondary to hypoperfusion of the eye structures. The patient presents with intractable pain or ocular angina. On dilated examination, there may be blot retinal hemorrhages along with dilated and beaded retinal veins. The ocular perfusion pressure is decreased.
The corneal layers show edema and striae. There is mild anterior uveitis. A cherry-red spot may be seen in the macula, along with cotton-wool spots elsewhere, due to retinal nerve fiber layer hemorrhages.  The retinal arteries may show spontaneous pulsations.

Complications
If carotid occlusive disease results in ophthalmic artery occlusion, general ocular ischemia may result in retinal neovascularization, rubeosis iridis, cells and flare, iris necrosis, and cataract. The condition leads to neovascularization in various eye tissues due to the ischemia. The eye pressure may become high due to associated neovascular glaucoma. An ischemic optic neuropathy may eventually occur.

Causes
Severe ipsilateral or bilateral carotid artery stenosis or occlusion is the most common cause of ocular ischemic syndrome. The syndrome has been associated with occlusion of the common carotid artery, internal carotid artery, and less frequently the external carotid artery. Other causes include:

Takayasus arteritis
Giant cell arteritis
Severe ophthalmic artery occlusion, due to thromboembolism.
Surgical interruption of anterior ciliary blood vessels supplying the eye, particularly during extensive strabismus surgery on 3 or more rectus muscles, leading to an anterior segment ischemic syndrome.

Diagnosis
Differential diagnoses
Central retinal vein occlusion
Diabetic retinopathy: The presence of retinal hemorrhages, particularly in those who have diabetes, may also be caused by diabetic retinopathy. Given the bilateral nature of diabetic retinopathy, however, one should suspect ocular ischemic syndrome when retinal ischemia is unilateral.

Treatment
Quick determination of the cause may lead to urgent measures to save the eye and life of the patient. High clinical suspicion should be kept for painless vision loss in patients with atherosclerosis, deep venous thrombosis, atrial fibrillation, pulmonary thromboembolism or other previous embolic episodes </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 Dyskinesia and explain in detail? [/INST] Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the upper body or lower extremities. Discoordination can also occur internally especially with the respiratory muscles and it often goes unrecognized. Dyskinesia is a symptom of several medical disorders that are distinguished by their underlying cause.

Types
Medication-induced dyskinesias
Acute dystonia is a sustained muscle contraction that sometimes appears soon after administration of antipsychotic medications. Any muscle in the body may be affected, including the jaw, tongue, throat, arms, or legs. When the throat muscles are involved, this type of dystonia is called an acute laryngospasm and is a medical emergency because it can impair breathing. Older antipsychotics such as Haloperidol or Fluphenazine are more likely to cause acute dystonia than newer agents. Giving high doses of antipsychotics by injection also increases the risk of developing acute dystonia.Methamphetamine, other amphetamines and dopaminergic stimulants including cocaine and pemoline can produce choreoathetoid dyskinesias; the prevalence, time-frame and prognosis are not well established.  Amphetamines also cause a dramatic increase in choreoathetoid symptoms in patients with underlying chorea such as Sydenhams, Huntingtons, and Lupus. Long-term use of amphetamines may increase the risk of Parkinsons disease (PD):  in one retrospective study with over 40,000 participants it was concluded that amphetamine abusers generally had a 200% higher chance of developing PD versus those with no history of abuse; the risk was much higher in women, almost 400%. There remains some controversy as of 2017.Levodopa-induced dyskinesia (LID) is evident in patients with Parkinsons disease who have been on levodopa (L‑DOPA) for prolonged periods of time. LID commonly first appears in the foot, on the most affected side of the body. There are three main types that can be classified on the basis of their course and clinical presentation following an oral dose of L‑DOPA:
Off-period dystonia – correlated to the akinesia that occurs before the full effect of L‑DOPA sets in, when the plasma levels of L‑DOPA are low </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 Hypervitaminosis A and explain in detail? [/INST] Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A (retinyl esters, retinol, and retinal). Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hypervitaminosis A is believed to have occurred in early humans, and the problem has persisted throughout human history. Toxicity results from ingesting too much preformed vitamin A from foods (such as fish liver or animal liver), supplements, or prescription medications and can be prevented by ingesting no more than the recommended daily amount.
Diagnosis can be difficult, as serum retinol is not sensitive to toxic levels of vitamin A, but there are effective tests available. Hypervitaminosis A is usually treated by stopping intake of the offending food(s), supplement(s), or medication. Most people make a full recovery. High intake of provitamin carotenoids (such as beta-carotene) from vegetables and fruits does not cause hypervitaminosis A.

Signs and symptoms
Symptoms may include:

Causes
Hypervitaminosis A results from excessive intake of preformed vitamin A. Genetic variations in tolerance to vitamin A intake may occur, so the toxic dose will not be the same for everyone. Children are particularly sensitive to vitamin A, with daily intakes of 1500 IU/kg body weight reportedly leading to toxicity.

Types of vitamin A
It is "largely impossible" for provitamin carotenoids, such as beta-carotene, to cause toxicity, as their conversion to retinol is highly regulated. No vitamin A toxicity has ever been reported from ingestion of excessive amounts. Overconsumption of beta-carotene can only cause carotenosis, a harmless and reversible cosmetic condition in which the skin turns orange.
Preformed vitamin A absorption and storage in the liver occur very efficiently until a pathologic condition develops. When ingested, 70–90% of preformed vitamin A is absorbed and used.

Sources of toxicity
Diet – Liver is high in vitamin A. The liver of certain animals, including the polar bear, bearded seal, fish, walrus, and moose, are particularly toxic (see Liver (food) § Poisoning). It has been estimated that consumption of 500 grams of polar bear liver would result in a toxic dose for a human.
Supplements – Dietary supplements can be toxic when taken above recommended dosages.

Types of toxicity
Acute toxicity occurs over a period of hours or a few days, and is less of a problem than chronic toxicity.
Chronic toxicity results from daily intakes greater than 25,000 IU for 6 years or longer and more than 100,000 IU for 6 months or longer.

Mechanism
Absorption and storage in the liver of retinol occur very efficiently until a pathologic condition develops.

Delivery to tissues
Absorption
When ingested, 70–90% of preformed vitamin A is absorbed and used.According to a 2003 review, water-miscible, emulsified, and solid forms of vitamin A supplements are more toxic than oil-based supplement and liver sources.

Storage
80–90% of the total body reserves of preformed vitamin A are in the liver (with 80–90% of this amount being stored in hepatic stellate cells and the remaining 10–20% being stored in hepatocytes). Fat is another significant storage site, while the lungs and kidneys may also be capable of storage.

Transport
Until recently, it was thought that the sole important retinoid delivery pathway to tissues involved retinol bound to retinol-binding protein (RBP4). More recent findings, however, indicate that retinoids can be delivered to tissues through multiple overlapping delivery pathways, involving chylomicrons, very low density lipoprotein (VLDL) and low density lipoprotein (LDL), retinoic acid bound to albumin, water-soluble β-glucuronides of retinol and retinoic acid, and provitamin A carotenoids.The range of serum retinol concentrations under normal conditions is 1–3 μmol/L. Elevated amounts of retinyl ester (i.e., >10% of total circulating vitamin A) in the fasting state have been used as markers for chronic hypervitaminosis A in humans. Candidate mechanisms for this increase include decreased hepatic uptake of vitamin A and the leaking of esters into the bloodstream from saturated hepatic stellate cells.

Effects
Effects include increased bone turnover and altered metabolism of fat-soluble vitamins. More research is needed to fully elucidate the effects.

Increased bone turnover
Retinoic acid suppresses osteoblast activity and stimulates osteoclast formation in vitro, resulting in increased bone resorption and decreased bone formation. It is likely to exert this effect by binding to specific nuclear receptors (members of the retinoic acid receptor or retinoid X receptor nuclear transcription family) which are found in every cell (including osteoblasts and osteoclasts).This change in bone turnover is likely to be the reason for numerous effects seen in hypervitaminosis A, such as hypercalcemia and numerous bone changes such as bone loss that potentially leads to osteoporosis, spontaneous bone fractures, altered skeletal development in children, skeletal pain, radiographic changes, and bone lesions.

Altered fat-soluble vitamin metabolism
Preformed vitamin A is fat-soluble and high levels have been reported to affect metabolism of the other fat-soluble vitamins D, E, and K.
The toxic effects of preformed vitamin A might be related to altered vitamin D metabolism, concurrent ingestion of substantial amounts of vitamin D, or binding of vitamin A to receptor heterodimers. Antagonistic and synergistic interactions between these two vitamins have been reported, as they relate to skeletal health.
Stimulation of bone resorption by vitamin A has been reported to be independent of its effects on vitamin D.

Mitochondrial toxicity
Preformed vitamin A and retinoids exerts several toxic effects regarding redox environment and mitochondrial function.

Diagnosis
Retinol concentrations are nonsensitive indicators
Assessing vitamin A status in persons with subtoxicity or toxicity is complicated because serum retinol concentrations are not sensitive indicators in this range of liver vitamin A reserves. The range of serum retinol concentrations under normal conditions is 1–3 μmol/L and, because of homeostatic regulation, that range varies little with widely disparate vitamin A intakes.

Retinol esters have been used as markers
Retinyl esters can be distinguished from retinol in serum and other tissues and quantified with the use of methods such as high-performance liquid chromatography.Elevated amounts of retinyl ester (i.e., >10% of total circulating vitamin A) in the fasting state have been used as markers for chronic hypervitaminosis A in humans and monkeys. This increased retinyl ester may be due to decreased hepatic uptake of vitamin A and the leaking of esters into the bloodstream from saturated hepatic stellate cells.

Prevention
Hypervitaminosis A can be prevented by not ingesting more than the US Institute of Medicine Daily Tolerable Upper Level of intake for Vitamin A. This level is for synthetic and natural retinol ester forms of vitamin A. Carotene forms from dietary sources are not toxic. Possible pregnancy, liver disease, high alcohol consumption, and smoking are indications for close monitoring and limitation of vitamin A administration.

Daily tolerable upper level
Treatment
Stopping high vitamin A intake is the standard treatment. Most people fully recover.
Phosphatidylcholine (in the form of PPC or DLPC), the substrate for Lecithin retinol acyltransferase, which converts retinol into Retinyl esters (the storage forms of vitamin A).
Vitamin E may alleviate hypervitaminosis A.
Liver transplantation may be a valid option if no improvement occurs.If liver damage has progressed into fibrosis, synthesizing capacity is compromised and supplementation can replenish PC </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 Boil and explain in detail? [/INST] A boil, also called a furuncle, is a deep folliculitis, which is an infection of the hair follicle. It is most commonly caused by infection by the bacterium Staphylococcus aureus, resulting in a painful swollen area on the skin caused by an accumulation of pus and dead tissue. Boils which are expanded are basically pus-filled nodules. Individual boils clustered together are called carbuncles.
Most human infections are caused by coagulase-positive S. aureus strains, notable for the bacterias ability to produce coagulase, an enzyme that can clot blood. Almost any organ system can be infected by S. aureus.

Signs and symptoms
Boils are bumpy, red, pus-filled lumps around a hair follicle that are tender, warm, and painful.  They range from pea-sized to golf ball-sized. A yellow or white point at the center of the lump can be seen when the boil is ready to drain or discharge pus. In a severe infection, an individual may experience fever, swollen lymph nodes, and fatigue. A recurring boil is called chronic furunculosis. Skin infections tend to be recurrent in many patients and often spread to other family members. Systemic factors that lower resistance commonly are detectable, including: diabetes, obesity, and hematologic disorders. Boils can be caused by other skin conditions that cause the person to scratch and damage the skin.Boils may appear on the buttocks or near the anus, the back, the neck, the stomach, the chest, the arms or legs, or even in the ear canal. Boils may also appear around the eye, where they are called styes. A boil on the gum is called intraoral dental sinus, or more commonly, a gumboil.

Complications
The most common complications of boils are scarring and infection or abscess of the skin, spinal cord, brain, kidneys, or other organs. Infections may also spread to the bloodstream (bacteremia) and become life-threatening.  S. aureus strains first infect the skin and its structures (for example, sebaceous glands, hair follicles) or invade damaged skin (cuts, abrasions). Sometimes the infections are relatively limited (such as a stye, boil, furuncle, or carbuncle), but other times they may spread to other skin areas (causing cellulitis, folliculitis, or impetigo). Unfortunately, these bacteria can reach the bloodstream (bacteremia) and end up in many different body sites, causing infections (wound infections, abscesses, osteomyelitis, endocarditis, pneumonia) that may severely harm or kill the infected person. S. aureus strains also produce enzymes and exotoxins that likely cause or increase the severity of certain diseases. Such diseases include food poisoning, septic shock, toxic shock syndrome, and scalded skin syndrome. Almost any organ system can be infected by S. aureus. Squeezing or cutting boils in the danger triangle of the face can be particularly dangerous if done outside a medical setting, as blood vessels in this area drain into the brain and can carry serious infections there.When a boil bursts, a seemingly solid, whitish colored pus initially appears then the pus and some blood follows.

Causes
Bacteria
Naturally the cause is bacteria such as staphylococci that are present on the skin. Bacterial colonisation begins in the hair follicles and can cause local cellulitis and inflammation. Myiasis caused by the tumbu fly in Africa usually presents with cutaneous furuncles. Risk factors for furunculosis include bacterial carriage in the nostrils, diabetes mellitus, obesity, lymphoproliferative neoplasms, malnutrition, and use of immunosuppressive drugs.

Family history
People with recurrent boils are as well more likely to have a positive family history, take antibiotics, and to have been hospitalised, anemic, or diabetic; they are also more likely to have associated skin diseases and multiple lesions.

Other
Other causes include poor immune system function such as from HIV/AIDS, diabetes, malnutrition, or alcoholism. Poor hygiene and obesity have also been linked. It may occur following antibiotic use due to the development of resistance to the antibiotics used. An associated skin disease favors recurrence. This may be attributed to the persistent colonization of abnormal skin with S. aureus strains, such as is the case in persons with atopic dermatitis.
Boils which recur under the arm, breast or in the groin area may be associated with hidradenitis suppurativa (HS).

Diagnosis
Diagnosis is made through clinical evaluation by a physician, which may include culturing of the lesion.

Treatment
A boil may clear up on its own without bursting, but more often it will need to be opened and drained. This will usually happen spontaneously within two weeks </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 Neonatal sepsis and explain in detail? [/INST] Neonatal sepsis is a type of neonatal infection and specifically refers to the presence in a newborn baby of a bacterial blood stream infection (BSI) (such as meningitis, pneumonia, pyelonephritis, or gastroenteritis) in the setting of fever. Older textbooks may refer to neonatal sepsis as "sepsis neonatorum". Criteria with regards to hemodynamic compromise or respiratory failure are not useful clinically because these symptoms often do not arise in neonates until death is imminent and unpreventable. Neonatal sepsis is divided into two categories: early-onset sepsis (EOS) and late-onset sepsis (LOS). EOS refers to sepsis presenting in the first 7 days of life (although some refer to EOS as within the first 72 hours of life), with LOS referring to presentation of sepsis after 7 days (or 72 hours, depending on the system used). Neonatal sepsis is the single most common cause of neonatal death in hospital as well as community in developing country.
It is difficult to clinically exclude sepsis in newborns less than 90 days old that have fever (defined as a temperature > 38 °C (100.4 °F). Except in the case of obvious acute viral bronchiolitis, the current practice in newborns less than 30 days old is to perform a complete workup including complete blood count with differential, blood culture, urinalysis, urine culture, and cerebrospinal fluid (CSF) studies and CSF culture, admit the newborn to the hospital, and treat empirically for serious bacterial infection for at least 48 hours until cultures are demonstrated to show no growth. Attempts have been made to see whether it is possible to risk stratify newborns in order to decide if a newborn can be safely monitored at home without treatment despite having a fever. One such attempt is the Rochester criteria.

Signs and symptoms
The signs of sepsis are non-specific and include:
Body temperature changes
Breathing problems
Diarrhea
Low blood sugar (hypoglycemia)
Reduced movements
Reduced sucking
Seizures
Bradycardia
Swollen belly area
Vomiting
Yellow skin and whites of the eyes (jaundice).
hemorrhagic rashA heart rate above 160 can also be an indicator of sepsis, this tachycardia can present up to 24 hours before the onset of other signs.

Risk factors
A study performed at Strong Memorial Hospital in Rochester, New York, showed that infants ≤ 60 days old meeting the following criteria were at low-risk for having a serious bacterial illness:
generally well-appearing
previously healthy
full term (at ≥37 weeks gestation)
no antibiotics perinatally
no unexplained hyperbilirubinemia that required treatment
no antibiotics since discharge
no hospitalizations
no chronic illness
discharged at the same time or before the mother
no evidence of skin, soft tissue, bone, joint, or ear infection
White blood cells (WBCs) count 5,000-15,000/mm3
absolute band count ≤ 1,500/mm3
urine WBC count ≤ 10 per high power field (hpf)
stool WBC count ≤ 5 per high power field (hpf) only in infants with diarrheaThose meeting these criteria likely do not require a lumbar puncture, and are felt to be safe for discharge home without antibiotic treatment, or with a single dose of intramuscular antibiotics, but will still require close outpatient follow-up.
One risk for Group B streptococcal infection (GBS) is preterm rupture of membranes. Screening women for GBS (via vaginal and rectal swabbing) and treating culture positive women with intrapartum chemoprophylaxis is reducing the number of neonatal sepsis caused by GBS.
Abnormal heart rate characteristics (HRC) of transient decelerations and reduced baseline variability in heart rate are a risk factor for impending neonatal sepsis.

Diagnosis
Neonatal sepsis screening:
DLC (differential leukocyte count) showing increased numbers of polymorphs.
DLC: band cells > 20%.
increased haptoglobins.
micro ESR (erythrocyte sedimentation rate) titer > 15mm.
gastric aspirate showing > 5 polymorphs per high power field.
newborn CSF (cerebrospinal fluid) screen: showing increased cells and proteins.
suggestive history of chorioamnionitis, PROM (premature rupture of membranes), etc...Culturing for microorganisms from a sample of CSF, blood or urine, is the gold standard test for definitive diagnosis of neonatal sepsis. This can give false negatives due to the low sensitivity of culture methods and because of concomitant antibiotic therapy. Lumbar punctures should be done when possible as 10-15% presenting with sepsis also have meningitis, which warrants an antibiotic with a high CSF penetration.CRP is not very accurate in picking up cases.

Treatment
Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is  a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, Escherichia coli, and Listeria monocytogenes (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as Streptococcus pneumoniae and Neisseria meningitidis. Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving surviva.

Antibiotic Overtreatment
In cases of suspected Early Onset Sepsis (EOS) one of the treatments is empirical antibiotics. The strategy of clinicians utilizing antibiotics as a course of treatment for EOS has resulted in the overtreatment of antibiotics to infants suspected of having signs of EOS. There are several consequences to the overtreatment of antibiotics in newborns including "microbiome alterations, which are linked to the development of asthma, food allergies, and childhood obesity". Another risk in the early introduction of antibiotics in infants is the increase in the development of antibiotic-resistant strains of infectious disease. Current methods of treatment for EOS are often implemented before a positive sepsis blood culture is found. In the last two decades (2000-2020), the use of intrapartum antibiotics has reduced the incidence of EOS. The current challenge faced by clinicians is mainly weighing the risk and benefits of the possibility of antibiotic overtreatment vs. the effects of sepsis.

Epidemiology
Since the 1990s early-onset sepsis has declined because of screening of group B streptococcus. The cause of early-onset neonatal sepsis are pathogens that contaminate the placenta, vaginal canal, cervix, or amniotic fluid, and these pathogens can affect the baby either in the womb or during labor. Early-onset neonatal sepsis is found to be 0.77 to 1 per 100,000 live births in the U.S. In premature babies, the incidence and mortality rates are higher due to the weakness of their immune system. For infants with low birth weight, cases of early-onset sepsis is found to be about 26 per 1,000 and 8 per 1,000 live births. Certain populations of babies are at more risk as well. Mothers who have poor healthcare, low socioeconomic status, substance abuse, or are African American have higher rates of neonatal sepsis. In fact, African American preterm babies have the highest rate of infection and mortality. 5.14 of every 1,000 live births and 24.4% case fatality ratio, respectively. The mother is not the only one who can contract the bacteria that contributes to sepsis. The child can contribute to the onset of sepsis through multiple factors. Mothers contribute to the risk through a variety of ways like diets during pregnancy and potential intake of foods that are contaminated, through invasive procedures like amniocentesis and cervical cerclage, or contamination of bacteria in the vaginal canal. Infants can contribute to early-onset sepsis through prematurity, congenital anomalies, complicated birth or instrument assisted birth, and low APGAR scores. Testing for neonatal sepsis is done because of how little it physically presents itself in babies. Infants showing no signs of neonatal sepsis will have a sepsis workup done only if concerning factors are shown. Only a small percentage of infants will have a sepsis workup done. Of this small population only 3% to 8% will show positive cultures.

Research
Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was Lactobacillus plantarum.
A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it </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 Cardiomyopathy and explain in detail? [/INST] Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and  swelling of the legs may occur, due to the onset of heart failure. An irregular heart beat and fainting may occur. Those affected are at an increased risk of sudden cardiac death.Types of cardiomyopathy include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular dysplasia, and Takotsubo cardiomyopathy (broken heart syndrome). In hypertrophic cardiomyopathy the heart muscle enlarges and thickens. In dilated cardiomyopathy the ventricles enlarge and weaken. In restrictive cardiomyopathy the ventricle stiffens.In many cases, the cause cannot be determined. Hypertrophic cardiomyopathy is usually inherited, whereas dilated cardiomyopathy is inherited in about one third of cases. Dilated cardiomyopathy may also result from alcohol, heavy metals, coronary artery disease, cocaine use, and viral infections. Restrictive cardiomyopathy may be caused by amyloidosis, hemochromatosis, and some cancer treatments. Broken heart syndrome is caused by extreme emotional or physical stress.Treatment depends on the type of cardiomyopathy and the severity of symptoms. Treatments may include lifestyle changes, medications, or surgery. Surgery may include a ventricular assist device or heart transplant. In 2015 cardiomyopathy and myocarditis affected 2.5 million people. Hypertrophic cardiomyopathy affects about 1 in 500 people while dilated cardiomyopathy affects 1 in 2,500. They resulted in 354,000 deaths up from 294,000 in 1990. Arrhythmogenic right ventricular dysplasia is more common in young people.

Signs and symptoms
Symptoms of cardiomyopathies may include fatigue, swelling of the lower extremities and shortness of breath after exertion. Additional symptoms of the condition may include arrhythmia, fainting, and dizziness.

Causes
Cardiomyopathies can be of genetic (familial) or non-genetic (acquired) origin. Genetic cardiomyopathies usually are caused by sarcomere or cytoskeletal diseases, neuromuscular disorders, inborn errors of metabolism, malformation syndromes and sometimes are unidentified. Non-genetic cardiomyopathies can have a definitive causes such as viral infections, myocarditis and others.Cardiomyopathies are either confined to the heart or are part of a generalized systemic disorder, both often leading to cardiovascular death or progressive heart failure-related disability. Other diseases that cause heart muscle dysfunction are excluded, such as coronary artery disease, hypertension, or abnormalities of the heart valves. Often, the underlying cause remains unknown, but in many cases the cause may be identifiable. Alcoholism, for example, has been identified as a cause of dilated cardiomyopathy, as has drug toxicity, and certain infections (including Hepatitis C). Untreated celiac disease can cause cardiomyopathies, which can completely reverse with a timely diagnosis. In addition to acquired causes, molecular biology and genetics have given rise to the recognition of various genetic causes.A more clinical categorization of cardiomyopathy as hypertrophied, dilated, or restrictive, has become difficult to maintain because some of the conditions could fulfill more than one of those three categories at any particular stage of their development.
The current American Heart Association (AHA) definition divides cardiomyopathies into primary, which affect the heart alone, and secondary, which are the result of illness affecting other parts of the body. These categories are further broken down into subgroups which incorporate new genetic and molecular biology knowledge.

Mechanism
The pathophysiology of cardiomyopathies is better understood at the cellular level with advances in molecular techniques. Mutant proteins can disturb cardiac function in the contractile apparatus (or mechanosensitive complexes). Cardiomyocyte alterations and their persistent responses at the cellular level cause changes that are correlated with sudden cardiac death and other cardiac problems.Cardiomyopathies are generally varied individually. Different factors can cause Cardiomyopathies in adults as well as children. To exemplify, Dilated Cardiomyopathy in adults is associated with Ischemic Cardiomyopathy, Hypertension, Valvular diseases, and Genetics. While in Children, Neuromuscular diseases such as Becker muscular dystrophy, including X-linked genetic disorder, are directly linked with their Cardiomyopathies.

Diagnosis
Among the diagnostic procedures done to determine a cardiomyopathy are:
Physical exam
Family history
Blood test
ECG
Echocardiogram
Stress test
Genetic testing

Classification
Cardiomyopathies can be classified using different criteria:
Primary/intrinsic cardiomyopathiesCongenital
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Left ventricular noncompaction
Ion Channelopathies like the Long QT syndrome and the very rare Short QT syndrome
Catecholaminergic polymorphic ventricular tachycardia
Mixed
Dilated cardiomyopathy (DCM)
Restrictive cardiomyopathy (RCM)
Brugada syndrome
Acquired
Stress cardiomyopathy
Myocarditis, inflammation of and injury to heart tissue due in part to its infiltration by lymphocytes and monocytes
Eosinophilic myocarditis, inflammation of and injury to heart tissue due in part to its infiltration by eosinophils
Ischemic cardiomyopathy (not formally included in the classification, due to ischemic cardiomyopathy being a direct result of another cardiac problem)
Secondary/extrinsic cardiomyopathiesMetabolic/storage
Fabrys disease
Hemochromatosis
Endomyocardial
Endomyocardial fibrosis
Hypereosinophilic syndrome
Endocrine
Diabetes mellitus
Hyperthyroidism
Acromegaly
Cardiofacial
Noonan syndrome
Neuromuscular
Muscular dystrophy
Friedreichs ataxia
Other
Obesity-associated cardiomyopathy

Treatment
Treatment may include suggestion of lifestyle changes to better manage the condition. Treatment depends on the type of cardiomyopathy and condition of disease, but may include medication (conservative treatment) or iatrogenic/implanted pacemakers for slow heart rates, defibrillators for those prone to fatal heart rhythms, ventricular assist devices (VADs) for severe heart failure, or catheter ablation for recurring dysrhythmias that cannot be eliminated by medication or mechanical cardioversion. The goal of treatment is often symptom relief, and some patients may eventually require a heart transplant.

See also
Myopathy, a condition affecting skeletal muscles
Fibrosing cardiomyopathy, a disease in great apes
Basic Research in Cardiology

References
Further reading
Boudina, Sihem; Abel, Evan Dale (1 March 2010). "Diabetic cardiomyopathy, causes and effects". Reviews in Endocrine & Metabolic Disorders. 11 (1): 31–39. doi:10.1007/s11154-010-9131-7. ISSN 1389-9155. PMC 2914514. PMID 20180026.
Marian, A. J.; Roberts, Robert (1 April 2001). "The Molecular Genetic Basis for Hypertrophic Cardiomyopathy". Journal of Molecular and Cellular Cardiology. 33 (4): 655–670. doi:10.1006/jmcc.2001.1340. ISSN 0022-2828. PMC 2901497. PMID 11273720.
Acton, Q. Ashton (2013). Advances in Heart Research and Application: 2013 Edition. Scholarly Editions. ISBN 978-1-481-68280-0.
Towbin, JA (2014). "Inherited cardiomyopathies". Circulation Journal. 78 (10): 2347–56. doi:10.1253/circj.cj-14-0893. ISSN 1347-4820. PMC 4467885. PMID 25186923.
Maron, Barry J.; Udelson, James E.; Bonow, Robert O.; Nishimura, Rick A.; Ackerman, Michael J.; Estes, N </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 Mietens 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 Fumarase deficiency and explain in detail? [/INST] Fumarase deficiency (or fumaric aciduria) is an exceedingly rare autosomal recessive metabolic disorder in the Krebs cycle, characterized by a deficiency of the enzyme fumarate hydratase, which causes a buildup of fumaric acid in the urine and a deficiency of malate.  Only 13 cases were known worldwide in 1990, after which a cluster of 20 cases was documented in a community in Arizona that has practiced successive endogamy.

Presentation
Fumarase deficiency causes encephalopathy, severe intellectual disabilities, unusual facial features, brain malformation, and epileptic seizures due to an abnormally low amount of fumarase in cells. It can initially present with polyhydramnios on prenatal ultrasound. Affected neonates may demonstrate nonspecific signs of poor feeding and hypotonia. Laboratory findings in neonates may indicate polycythemia, leukopenia, or neutropenia. As they age, neurological deficits begin to manifest with seizures, dystonias, and severe developmental delay.

Pathophysiology
Fumarase deficiency is caused by a mutation in the fumarate hydratase (FH) gene in humans, which encodes the enzyme that converts fumarate to malate in the mitochondria.  Other mutant alleles of the FH gene, located on human Chromosome 1 at position 1q42.1, cause multiple cutaneous and uterine leiomyomata, hereditary leiomyomatosis and renal cell cancer. Fumarase deficiency is one of the few known deficiencies of the Krebs cycle or tricarboxylic acid cycle, the main enzymatic pathway of cellular aerobic respiration.

The condition is an autosomal recessive disorder, and it is therefore usually necessary for an affected individual to receive the mutant allele from both parents </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 Kyphosis and explain in detail? [/INST] Kyphosis is an abnormally excessive convex curvature of the spine as it occurs in the thoracic and sacral regions. Abnormal inward concave lordotic curving of the cervical and lumbar regions of the spine is called lordosis. It can result from degenerative disc disease; developmental abnormalities, most commonly Scheuermanns disease; Copenhagen disease, osteoporosis with compression fractures of the vertebra; multiple myeloma; or trauma. A normal thoracic spine extends from the 1st thoracic to the 12th thoracic vertebra and should have a slight kyphotic angle, ranging from 20° to 45°. When the "roundness" of the upper spine increases past 45° it is called kyphosis or "hyperkyphosis". Scheuermanns kyphosis is the most classic form of hyperkyphosis and is the result of wedged vertebrae that develop during adolescence. The cause is not currently known and the condition appears to be multifactorial and is seen more frequently in males than females.In the sense of a deformity, it is the pathological curving of the spine, where parts of the spinal column lose some or all of their lordotic profile. This causes a bowing of the back, seen as a slouching posture. Kyphosis is distinguished from scoliosis, a condition in which the spine has a sideways curve.
While most cases of kyphosis are mild and only require routine monitoring, serious cases can be debilitating. High degrees of kyphosis can cause severe pain and discomfort, breathing and digestion difficulties, cardiovascular irregularities, neurological compromise and, in the more severe cases, significantly shortened life spans. These types of high-end curves typically do not respond well to conservative treatment and almost always warrant spinal fusion surgery, which can restore the bodys natural degree of curvature. The term is from Greek κυφός kyphos, a hump.

Signs and symptoms
Complications
The risk of serious complications from spinal fusion surgery for kyphosis is estimated to be 5%, similar to the risks of surgery for scoliosis. Possible complications include inflammation of the soft tissue or deep inflammatory processes, breathing impairments, bleeding, and nerve injuries. According to the latest evidence, the actual rate of complications may be substantially higher. Even among those who do not develop serious complications, 5% of patients require reoperation within five years of the procedure, and in general it is not yet clear what one would expect from spine surgery during the long-term. Given that the signs and symptoms of spinal deformity cannot be changed by surgical intervention, surgery remains essentially a cosmetic choice. However, the cosmetic effects of surgery are not necessarily stable.

Diagnosis
Classification
There are several kinds of kyphosis (ICD-10 codes are provided):

Postural kyphosis (M40.0), the most common type, normally attributed to slouching, can occur in both the old and the young. In the young, it can be called "slouching" and is reversible by correcting muscular imbalances. In the old, it may be a case of hyperkyphosis and called "dowagers hump". About one third of the most severe hyperkyphosis cases in older people have vertebral fractures. Otherwise, the aging body does tend towards a loss of musculoskeletal integrity, and hyperkyphosis can develop due to aging alone.
Scheuermanns kyphosis (M42.0) is significantly worse cosmetically and can cause varying degrees of pain, and can also affect different areas of the spine (the most common being the midthoracic area). Scheuermanns kyphosis is considered a form of juvenile osteochondrosis of the spine and is more commonly called Scheuermanns disease. It is found mostly in teenagers and presents a significantly worse deformity than postural kyphosis. A patient with Scheuermanns kyphosis cannot consciously correct posture. The apex of the curve, located in the thoracic vertebrae, is quite rigid. The patient may feel pain at this apex, which can be aggravated by physical activity and by long periods of standing or sitting. This can have a significantly detrimental effect on their lives, as their level of activity is curbed by their condition; they may feel isolated or uneasy amongst peers if they are children, depending on the level of deformity. Whereas in postural kyphosis, the vertebrae and discs appear normal, in Scheuermanns kyphosis, they are irregular, often herniated, and wedge-shaped over at least three adjacent levels. Fatigue is a very common symptom, most likely because of the intense muscle work that has to be put into standing or sitting properly. The condition appears to run in families. Most patients who undergo surgery to correct their kyphosis have Scheuermanns disease.
Congenital kyphosis (Q76.4) can result in infants whose spinal column has not developed correctly in the womb. Vertebrae may be malformed or fused together and can cause further progressive kyphosis as the child develops. Surgical treatment may be necessary at a very early stage and can help maintain a normal curve in coordination with consistent follow-ups to monitor changes. However, the decision to carry out the procedure can be very difficult due to the potential risks to the child. A congenital kyphosis can also suddenly appear in the teenage years, more commonly in children with cerebral palsy and other neurological disorders.
Nutritional kyphosis can result from nutritional deficiencies, especially during childhood, such as vitamin D deficiency (producing rickets), which softens bones and results in the curving of the spine and limbs under the childs body weight.
Gibbus deformity is a form of structural kyphosis, often a sequela to tuberculosis.
Post-traumatic kyphosis (M84.0) can arise from untreated or ineffectively treated vertebral fractures.

Grading
Kyphosis can be graded in severity by the Cobb angle. Also, sagittal balance can be measured. The sagittal balance is the horizontal distance between the center of C7 and the superior-posterior border of the endplate of S1 on a lateral radiograph.

Treatments
A diagnosis of kyphosis is generally made through observation and measurement. Idiopathic causes, such as vertebral wedging or other abnormalities, can be confirmed through X-ray. Osteoporosis, a potential cause of kyphosis, can be confirmed with a bone density scan. Postural thoracic kyphosis can often be treated with posture reeducation and focused strengthening exercises. Idiopathic thoracic kyphosis due to vertebral wedging, fractures, or vertebral abnormalities is more difficult to manage, since assuming a correct posture may not be possible with structural changes in the vertebrae. Children who have not completed their growth may show long-lasting improvements with bracing. Exercises may be prescribed to alleviate discomfort associated with overstretched back 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 Superior mesenteric artery syndrome and explain in detail? [/INST] Superior mesenteric artery (SMA) syndrome is a gastro-vascular disorder in which the third and final portion of the duodenum is compressed between the abdominal aorta (AA) and the overlying superior mesenteric artery.  This rare, potentially life-threatening syndrome is typically caused by an angle of 6°–25° between the AA and the SMA, in comparison to the normal range of 38°–56°, due to a lack of retroperitoneal and visceral fat (mesenteric fat). In addition, the aortomesenteric distance is  2–8 millimeters, as opposed to the typical 10–20. However, a narrow SMA angle alone is not enough to make a diagnosis, because patients with a low BMI, most notably children, have been known to have a narrow SMA angle with no symptoms of SMA syndrome.SMA syndrome is also known as Wilkies syndrome, cast syndrome, mesenteric root syndrome, chronic duodenal ileus and intermittent arterio-mesenteric occlusion.
It is distinct from nutcracker syndrome, which is the entrapment of the left renal vein between the AA and the SMA, although it is possible to be diagnosed with both conditions.

Signs and symptoms
Signs and symptoms include early satiety, nausea, vomiting, extreme "stabbing" postprandial abdominal pain (due to both the duodenal compression and the compensatory reversed peristalsis), abdominal distention/distortion, burping, external hypersensitivity or tenderness of the abdominal area, reflux, and heartburn. In infants, feeding difficulties and poor weight gain are also frequent symptoms.In some cases of SMA syndrome, severe malnutrition accompanying spontaneous wasting may occur. This, in turn, increases the duodenal compression, which worsens the underlying cause, creating a cycle of worsening symptoms.Fear of eating is commonly seen among those with the chronic form of SMA syndrome. For many, symptoms are partially relieved when in the left lateral decubitus or knee-to-chest position, or in the prone (face down) position. A Hayes maneuver, which corresponds to applying pressure below the umbilicus in cephalad and dorsal direction, elevates the root of the SMA, also slightly easing the constriction. Symptoms can be aggravated when leaning to the right or taking a face up position.

Causes
Retroperitoneal fat and lymphatic tissue normally serve as a cushion for the duodenum, protecting it from compression by the SMA. SMA syndrome is thus triggered by any condition involving an insubstantial cushion and narrow mesenteric angle. SMA syndrome can present in two forms: chronic/congenital or acute/induced.Patients with the chronic, congenital form of SMA syndrome predominantly have a lengthy or even lifelong history of abdominal complaints with intermittent exacerbations depending on the degree of duodenal compression. Risk factors include anatomic characteristics such as: asthenic (very thin or "lanky") body build, an unusually high insertion of the duodenum at the ligament of Treitz, a particularly low origin of the SMA, or intestinal malrotation around an axis formed by the SMA.  Predisposition is easily aggravated by any of the following: poor motility of the digestive tract, retroperitional tumors, loss of appetite, malabsorption, cachexia, exaggerated lumbar lordosis, visceroptosis, abdominal wall laxity, peritoneal adhesions, abdominal trauma, rapid linear adolescent growth spurt, weight loss, starvation, catabolic states (as with cancer and burns), and history of neurological injury.The acute form of SMA syndrome develops rapidly after traumatic incidents that forcibly hyper-extend the SMA across the duodenum, inducing the obstruction, or sudden weight loss for any reason. Causes include prolonged supine bed rest, scoliosis surgery, left nephrectomy, ileo-anal pouch surgery.SMA syndrome is usually difficult to differentiate with anorexia nervosa. Patients with SMA syndrome can be hindered restoring weight in those with anorexia nervosa.

Diagnosis
Diagnosis is very difficult, and usually one of exclusion. SMA syndrome is thus considered only after patients have undergone an extensive evaluation of their gastrointestinal tract including upper endoscopy, and evaluation for various malabsorptive, ulcerative and inflammatory intestinal conditions with a higher diagnostic frequency. Diagnosis may follow X-ray examination revealing duodenal dilation followed by abrupt constriction proximal to the overlying SMA, as well as a delay in transit of four to six hours through the gastroduodenal region.  Standard diagnostic exams include abdominal and pelvic computed tomography (CT) scan with oral and IV contrast, upper gastrointestinal series (UGI), and, for equivocal cases, hypotonic duodenography.  In addition, vascular imaging studies such as ultrasound and contrast angiography may be used to indicate increased bloodflow velocity through the SMA or a narrowed SMA angle.Despite multiple case reports, there has been controversy surrounding the diagnosis and even the existence of SMA syndrome since symptoms do not always correlate well with radiologic findings, and may not always improve following surgical correction. However, the reason for the persistence of gastrointestinal symptoms even after surgical correction in some cases has been traced to the remaining prominence of reversed peristalsis in contrast to direct peristalsis.Since females between the ages of 10 and 30 are most frequently affected, it is not uncommon for physicians to initially and incorrectly assume that emaciation is a choice of the patient instead of a consequence of SMA syndrome.  Patients in the earlier stages of SMA syndrome often remain unaware that they are ill until substantial damage to their health is done, since they may attempt to adapt to the condition by gradually decreasing their food intake or naturally gravitating toward a lighter and more digestible diet.

Treatment
SMA syndrome can present in acute, acquired form (e.g. abruptly emerging within an inpatient stay following scoliosis surgery) as well as chronic form (i.e. developing throughout the course of a lifetime and advancing due to environmental triggers, life changes, or other illnesses). According to a number of recent sources, at least 70% of cases can typically be treated with medical treatment, while the rest require surgical treatment.Medical treatment is attempted first in many cases. In some cases, emergency surgery is necessary upon presentation. A six-week trial of medical treatment is recommended in pediatric cases. The goal of medical treatment for SMA syndrome is resolution of underlying conditions and weight gain. Medical treatment may involve nasogastric tube placement for duodenal and gastric decompression, mobilization into the prone or left lateral decubitus position, the reversal or removal of the precipitating factor with proper nutrition and replacement of fluid and electrolytes, either by surgically inserted jejunal feeding tube, nasogastric intubation, or peripherally inserted central catheter (PICC line) administering total parenteral nutrition (TPN). Pro-motility agents such as metoclopramide may also be beneficial.  Symptoms may improve after restoration of weight, except when reversed peristalsis persists, or if regained fat refuses to accumulate within the mesenteric angle. Most patients seem to benefit from nutritional support with hyperalimentation irrespective of disease history.If medical treatment fails, or is not feasible due to severe illness, surgical intervention is required. The most common operation for SMA syndrome, duodenojejunostomy, was first proposed in 1907 by Bloodgood. Performed as either an  open surgery or laparoscopically, duodenojejunostomy involves the creation of an anastomosis between the duodenum and the jejunum, bypassing the compression caused by the AA and the SMA.  Less common surgical treatments for SMA syndrome include Roux-en-Y duodenojejunostomy, gastrojejunostomy, anterior transposition of the third portion of the duodenum, intestinal derotation, division of the ligament of Treitz (Strongs operation), and transposition of the SMA. Both transposition of the SMA and lysis of the duodenal suspensory muscle have the advantage that they do not involve the creation of an intestinal anastomosis.The possible persistence of symptoms after surgical bypass can be traced to the remaining prominence of reversed peristalsis in contrast to direct peristalsis, although the precipitating factor (the duodenal compression) has been bypassed or relieved </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 Carotid sinus and explain in detail? [/INST] In human anatomy, the carotid sinus is a dilated area at the base of the internal carotid artery just superior to the bifurcation of the internal carotid and external carotid at the level of the superior border of thyroid cartilage. The carotid sinus extends from the bifurcation to the "true" internal carotid artery. The carotid sinus is sensitive to pressure changes in the arterial blood at this level. It is the major baroreception site in humans and most mammals.

Structure
The carotid sinus is the reflex area of the carotid artery, consisting of baroreceptors which monitor blood pressure.

Function
The carotid sinus contains numerous baroreceptors which function as a "sampling area" for many homeostatic mechanisms for maintaining blood pressure.  The carotid sinus baroreceptors are innervated by the carotid sinus nerve, which is a branch of the glossopharyngeal nerve (CN IX). The neurons which innervate the carotid sinus centrally project to the solitary nucleus in the medulla of the brainstem. The solitary nucleus indirectly modulates the activity of sympathetic and parasympathetic neurons in the medulla and pons through the hypothalamus. These neurons then regulate the autonomic control of the heart and blood vessels. The aortic arch baroreceptors are innervated by the aortic nerve (nerve of Cyon, Ludwig nerve), which combines with CN X (vagus nerve) and travels to the NTS.

Clinical significance
It is a sensitive site of the body because stimulation can drive large-scale reflex effects throughout the body. This can be used therapeutically in treatment of resistant hypertension by baroreflex activation </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 Bartter syndrome and explain in detail? [/INST] Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome.

Signs and symptoms
In 90% of cases, neonatal Bartter syndrome is seen between 24 and 30 weeks of gestation with excess amniotic fluid (polyhydramnios). After birth, the infant is seen to urinate and drink excessively (polyuria, and polydipsia, respectively). Life-threatening dehydration may result if the infant does not receive adequate fluids. About 85% of infants dispose of excess amounts of calcium in the urine (hypercalciuria) and kidneys (nephrocalcinosis), which may lead to kidney stones. In rare occasions, the infant may progress to kidney failure.Patients with classic Bartter syndrome may have symptoms in the first two years of life, but they are usually diagnosed at school age or later. Like infants with the neonatal subtype, patients with classic Bartter syndrome also have polyuria, polydipsia, and a tendency to dehydration, but normal or just slightly increased urinary calcium excretion without the tendency to develop kidney stones. These patients also have vomiting and growth retardation. Kidney function is also normal if the disease is treated, but occasionally patients proceed to end-stage kidney failure.
Bartter syndrome consists of low levels of potassium in the blood, alkalosis, normal to low blood pressures, and elevated plasma renin and aldosterone. Numerous causes of this syndrome probably exist. Diagnostic pointers include high urinary potassium and chloride despite low serum values, increased plasma renin, hyperplasia of the juxtaglomerular apparatus on kidney biopsy, and careful exclusion of diuretic abuse. Excess production of prostaglandins by the kidneys is often found. Magnesium wasting may also occur. Homozygous patients experience severe hypercalciuria and nephrocalcinosis.

Pathophysiology
Bartter syndrome is caused by mutations of genes encoding proteins that transport ions across renal cells in the thick ascending limb of the nephron also called as the ascending loop of Henle. Specifically, mutations directly or indirectly involving the Na-K-2Cl cotransporter are key. The Na-K-2Cl cotransporter is involved in electroneutral transport of one sodium, one potassium, and two chloride ions across the apical membrane of the tubule. The basolateral calcium-sensing receptor has the ability to downregulate the activity of this transporter upon activation. Once transported into the tubule cells, sodium ions are actively transported across the basolateral membrane by Na+/K+-ATPases, and chloride ions pass by facilitated diffusion through basolateral chloride channels. Potassium, however, is able to diffuse back into the tubule lumen through apical potassium channels, returning a net positive charge to the lumen and establishing a positive voltage between the lumen and interstitial space. This charge gradient is obligatory for the paracellular reabsorption of both calcium and magnesium ions.Proper function of all of these transporters is necessary for normal ion reabsorption along the thick ascending limb, and loss of any component can result in functional inactivation of the system as a whole and lead to the presentation of Bartter syndrome. Loss of function of this reabsorption system results in decreased sodium, potassium, and chloride reabsorption in the thick ascending limb, as well as abolishment of the lumen-positive voltage, resulting in decreased calcium and magnesium reabsorption. Loss of reabsorption of sodium here also has the undesired effect of abolishing the hypertonicity of the renal medulla, severely impairing the ability to reabsorb water later in the distal nephron and collecting duct system, leading to significant diuresis and the potential for volume depletion. Finally, increased sodium load to the distal nephron elicits compensatory reabsorption mechanisms, albeit at the expense of potassium by excretion by principal cells and resulting hypokalemia. This increased potassium excretion is partially compensated by α-intercalated cells at the expense of hydrogen ions, leading to metabolic alkalosis.Bartter and Gitelman syndromes can be divided into different subtypes based on the genes involved:

Diagnosis
People with Bartter syndrome present symptoms that are identical to those of patients who are on loop diuretics like furosemide, given that the loop diuretics target the exact transport protein that is defective in the syndrome (at least for type 1 Bartter syndrome). The other subtypes of the syndrome involve mutations in other transporters that result in functional loss of the target transporter. Patients often admit to a personal preference for salty foods.The clinical findings characteristic of Bartter syndrome is hypokalemia, metabolic alkalosis, and normal to low blood pressure. These findings may also be caused by other conditions, which may cause confusion </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 Acanthamoeba keratitis and explain in detail? [/INST] Acanthamoeba keratitis (AK) is a rare disease in which amoebae of the genus Acanthamoeba invade the clear portion of the front (cornea) of the eye. It affects roughly 100 people in the United States each year. Acanthamoeba are protozoa found nearly ubiquitously in soil and water and can cause infections of the skin, eyes, and central nervous system.Infection of the cornea by Acanthamoeba is difficult to treat with conventional medications, and AK may cause permanent visual impairment or blindness, due to damage to the cornea or through damage to other structures important to vision. Recently, AK has been recognized as an orphan disease and a funded project, orphan diseases Acanthamoeba keratitis (ODAK), has tested the effects of a diverse range drugs and biocides on AK.

Pathogenesis
In the United States, Acanthamoeba keratitis is nearly always associated with soft contact lens use. Acanthamoeba spp. is most commonly introduced to the eye by contact lenses that have been exposed to the organism through the use of contaminated lens solution, using homemade saline-based solution or tap water, or from wearing contact lenses while bathing or swimming. However, it may also be introduced to the eye by exposure to soil or vegetation, or by trauma. In fact, the first case of Acanthamoeba keratitis described was due to ocular trauma. Once on the contact lens, Acanthamoeba is able to survive in the space between the contact lens and the surface of the eye. Soft contact lenses are more adherent to the corneal surface than hard lenses, which allows the Acanthamoeba organism to bind to mannosylated glycoproteins on the corneal surface. Expression of these proteins on the corneal surface is increased by contact lens use. This increase in glycoprotein content, along with microtrauma to the corneal epithelial surface due to contact lens use increases the risk for infection. Once the organism has gained access to the surface of the eye, it is able to invade through the epithelium and Bowmans layer. In some cases, the infection can then group around corneal nerves, producing radial deposits (radial keratoneuritis), and causing extreme pain. These are features also seen in viral and bacterial keratitis, and may be misleading. The organism is also capable of invading deeper into the cornea; using metalloproteases it is able to penetrate deep into the stroma of the cornea. As the disease progresses, it may penetrate through the cornea but very rarely causes infection inside the eye (endophthalmitis) due to a robust neutrophil response in the anterior chamber.While the vast majority of cases of Acanthamoeba keratitis occur in contact lens wearers, there have been many cases of Acanthamoeba described in those who do not wear contact lenses, especially outside the United States. In non-contact lens users, the greatest risks for developing Acanthamoeba infection are trauma and exposure to contaminated water. Further predisposing factors include contaminated home water supply, and low socioeconomic status. Infection is also more commonly seen in tropical or sub-tropical climates.Beyond the route of inoculation into the eye and external risk factors, host factors are also likely to play a significant role in the development of Acanthamoeba keratitis. In fact, studies of contact lens users in the United Kingdom, Japan, and New Zealand found that 400 to 800 per 10,000 asymptomatic contact lens users had lens storage cases contaminated with Acanthamoeba spp. However, the rate of Acanthamoeba keratitis among these patients was only 0.01 to 1.49 per 10,000 contact lens users. Although the exact host factors have not been fully described, it is likely that corneal epithelial defects, tear film composition, eye surface pH, and the level of anti-Acanthamoeba IgA antibodies in the tear film play a role in the development of Acanthamoeba keratitis.

Life cycle
Species within the genus, Acanthamoeba, are generally free-living trophozoites. These trophozoites are relatively ubiquitous and can live in, but are not restricted to, tap water, freshwater lakes, rivers and soil. In addition to the trophozoite stage, the organism can also form a double-walled cyst which may also be present in the environment, and can be very difficult to eradicate through medical treatment. Both of these stages are usually non-nucleated and reproduce by the means of binary fission.

Diagnosis
Due to the relative rarity of Acanthamoeba keratitis (AK) compared to other causes of keratitis (bacterial, viral, etc.), it is often misdiagnosed, especially in the early stages of the disease. AK should be considered in all patients who use contact lenses, and following corneal abrasions or trauma. A thorough history should be obtained, especially relating to contact lens use and any recent changes contact in lens solution, exposure of the eyes to water or foreign objects, and symptoms that the patient is experiencing. The symptoms classically attributed to AK include decreased or blurred vision, sensitivity to light (photophobia), redness of the eye (conjunctival hyperemia), and pain out of proportion to physical exam findings. Another clinical feature that can distinguish Acanthamoeba from bacterial causes of keratitis is a lack of discharge from the eye.On physical exam, findings will depend on the stage of the disease. Early manifestations in the cornea can be seen as punctate keratopathy, pseudodendrites, and epithelial or subepithelial corneal deposits. These features can lead an examiner to confuse AK with a viral keratitis, such as that caused by varicella zoster virus or herpes simplex virus. As the disease progresses and infiltrates the corneal stroma, a classic "ring infiltrate" may be present on examination (although this is only seen in about 50% of cases). Corneal ulceration, or in severe cases, perforation, can also occur and may be accompanied by hypopyon.In cases of keratitis, diagnosis is typically achieved through evaluation of corneal scrapings. Scrapings are taking from the cornea, and plated on agar for culture, and also can be stained using Gram stain and Giemsa stain to differentiate between bacterial keratitis and AK. To culture Acanthamoeba, scrapings are placed on a non-nutrient agar saline plate seeded with a gram-negative bacteria such as E. coli. If Acanthamoeba are present, they will reproduce readily and become visible on the plate under 10–20 times objective on an inverted microscope. Polymerase chain reaction (PCR) can be used to confirm a diagnosis of Acanthamoeba keratitis, especially when contact lenses are not involved. Confocal microscopy is a non-invasive technique that allows visualization of Acanthamoeba in vivo in cases in which corneal scraping, culture, and cytology do not yield a diagnosis.

Treatment
Once Acanthamoeba keratitis is diagnosed, initiation of timely and appropriate treatment will have a significant impact on visual outcomes. Medical therapy aims to eradicate both trophozoite and cystic forms of Acanthamoeba and also control the inflammatory response.

Medical therapy
Multiple classes of drugs have been found to be effective in killing the trophozoite form of Acanthamoeba, including anti-bacterial, anti-fungal, anti-protozoal, and anti-neoplastic agents. However, no single therapy has been found to eliminate both trophozoite and cystic forms, and to eradicate corneal infection.One class of medications used in treatment is the biguanides, which include polyhexamethylene biguanide (PHMB) 0.02% to 0.06% drops, and chlorhexidine 0.02 to 0.2% drops. These medications disrupt the cell wall of the trophozoite organism, leading to its death. However, these agents have shown limited efficacy against the cystic forms. Due to the efficacy of these drugs against the Acanthamoeba, as well as their low toxicity to the cornea, they are commonly used as the first line medications in the treatment of AK. Biguanides have also been found to act synergistically when used in combination with diamidines, with propamidine isethionate and hexamidine being the most commonly used. A limitation of diamidine use is relative corneal toxicity with long term use. A combined regimen of propamidine, miconazole nitrate, and neomycin has also been suggested. Due to the potential for negative longterm visual outcomes with AK, therapy is usually started with a combination of a biguanide and a diamidine. Early use of high dose dual therapy helps to eliminate both trophozoite and cyst forms of the organism, while also preventing deep penetration of cysts into the corneal stroma. Cysts that are not eradicated from the cornea will cause recurrence. The treatment is often initiated by instilling drops onto the surface of the eye every hour, 24 hours a day, for at least the first 48–72 hours. If an appropriate response to therapy, this may be reduced to hourly administrations during the day only, which is continued for several weeks to months.Beyond anti-amoebic therapies, there is also a role for topical steroids of anti-inflammatory medications in the treatment of Acanthamoeba keratitis. During infection, severe inflammation in the cornea and anterior chamber can cause more severe symptoms including pain and visual disturbance. Topical steroids may be used to reduce this inflammation and thereby alleviate symptoms. However, the role of steroids is typically very limited, because their dampening of the immune response may lead to worsening of the infection. Additionally, steroids can increase the number of trophozoites in the cornea by inducing excystation. Therefore it is typically recommended that steroids be used briefly to aid in symptom resolution, and that anti-amoebic agents be used both during, and for several weeks after topical steroid use.

Surgical treatment
Surgical debridement of an infected cornea can also be used to reduce organism load and excise devitalized tissue from the cornea. It may also improve the efficacy of medical therapy by promoting penetration of medication into deeper layers of the cornea. In cases of corneal ulceration or perforation, or if corneal scarring is severe, corneal transplant may be required. This typically involves full thickness transplantation of the cornea from a healthy donor eye </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 Viral hepatitis and explain in detail? [/INST] Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form.The most common causes of viral hepatitis are the five unrelated hepatotropic viruses hepatitis A, B, C, D, and E. Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein–Barr virus, and yellow fever. There also have been scores of recorded cases of viral hepatitis caused by herpes simplex virus.

Mode Of Transmission
Viral hepatitis is either transmitted through contaminated food or water (A, E) or via blood and body fluids (B, C). The viruses transmitted through water and food are mostly self-limited, resulting in acute illness with full resolution. The blood borne viruses (B, C) can cause both acute and chronic liver disease and can be transmitted from mother to child during birth, through contact with body fluids during sex, unsafe injections and through unscreened blood transfusions.The most common types of hepatitis can be prevented or treated. Hepatitis A and hepatitis B can be prevented by vaccination. Effective treatments for hepatitis C are available but costly.In 2013, about 1.5 million people died from viral hepatitis, most commonly due to hepatitis B and C. East Asia, in particular Mongolia, is the region most affected.

Hepatitis viruses
The most common cause of hepatitis is viral. Although the effects of various viruses are all classified under the disease hepatitis, these viruses are not all related.

Viral hepatitis types
Hepatitis A
Hepatitis A or infectious jaundice is caused by hepatitis A virus (HAV), a picornavirus transmitted by the fecal-oral route often associated with ingestion of contaminated food. It causes an acute form of hepatitis and does not have a chronic stage. A patients immune system makes antibodies against HAV that confer immunity against future infection. People with hepatitis A are advised to rest, stay hydrated and avoid alcohol. A vaccine is available that will prevent HAV infection for up to 10 years. Hepatitis A can be spread through personal contact, consumption of raw sea food, or drinking contaminated water. This occurs primarily in third world countries. Strict personal hygiene and the avoidance of raw and unpeeled foods can help prevent an infection. Infected people excrete HAV with their feces two weeks before and one week after the appearance of jaundice. The time between the infection and the start of the illness averages 28 days. (ranging from 15 to 50 days), Most patients recover fully within 2 months, although approximately 15% of affected people may experience continuous or relapsing symptoms from six months to a year following initial diagnosis.

Hepatitis B
Hepatitis B is caused by the hepatitis B virus, a hepadnavirus that can cause both acute and chronic hepatitis. Chronic hepatitis develops in the 15% of adults who are unable to eliminate the virus after an initial infection. Identified methods of transmission include contact with blood, blood transfusion (now rare), unsanitary tattoos, sex (through sexual intercourse or contact with bodily fluids), or mother-to-child by breast feeding; there is minimal evidence of transplacental crossing. However, in about half of cases the source of infection cannot be determined. Blood contact can occur by sharing syringes in intravenous drug use, shaving accessories such as razor blades, or touching wounds on infected persons. Needle-exchange programmes have been created in many countries as a form of prevention.Patients with chronic hepatitis B have antibodies against the virus, but not enough to clear the infected liver cells. The continued production of virus and countervailing antibodies is a likely cause of the immune complex disease seen in these patients. A vaccine is available to prevent infection for life. Hepatitis B infections result in 500,000 to 1,200,000 deaths per year worldwide due to the complications of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Hepatitis B is endemic in a number of (mainly South-East Asian) countries, making cirrhosis and hepatocellular carcinoma big killers. There are eight treatment options approved by the U.S. Food and Drug Administration (FDA) available for persons with a chronic hepatitis B infection: alpha-interferon, pegylated interferon, adefovir, entecavir, telbivudine, lamivudine, tenofovir disoproxil and tenofovir alafenamide with a 65% rate of sustained response.

Hepatitis C
Hepatitis C (originally "non-A non-B hepatitis") is caused by hepatitis C virus (HCV), an RNA virus of the family Flaviviridae. HCV can be transmitted through contact with blood (including through sexual contact if the two parties blood is mixed) and can also cross the placenta. Hepatitis C usually leads to chronic hepatitis, culminating in cirrhosis in some people. It usually remains asymptomatic for decades. Patients with hepatitis C are susceptible to severe hepatitis if they contract either hepatitis A or B, so all persons with hepatitis C should be immunized against hepatitis A and hepatitis B if they are not already immune, and avoid alcohol. HCV can lead to the development of hepatocellular carcinoma, however, only a minority of HCV-infected individuals develop cancer (1–4% annually), suggesting a complex interplay between viral gene expression and host and environmental factors to promote carcinogenesis. The risk is increased two-fold with active HBV coinfection and a 21% increase in mortality compared to those with latent HBV and HCV. HCV viral levels can be reduced to undetectable levels by a combination of interferon and the antiviral drug ribavirin. The genotype of the virus is the primary determinant of the rate of response to this treatment regimen, with genotype 1 being the most resistant.Hepatitis C is the most common chronic blood-borne infection in the United States.

Hepatitis D
Hepatitis D is caused by the hepatitis D virus (HDV), or hepatitis delta virus; it belongs to the genus Deltavirus. HDV is similar to a satellite virus as it can only propagate in the presence of the hepatitis B virus, depending on the helper function of HBV for its replication and expression. It has no independent life cycle, but can survive and replicate as long as HBV infection persists in the host body. It can only cause infection when encapsulated by hepatitis B virus surface antigens. The vaccine for hepatitis B protects against hepatitis D virus because of the latters dependence on the presence of hepatitis B virus for it to replicate.

Hepatitis E
Hepatitis E is caused by the Hepatitis E virus (HEV), from the family Hepeviridae. It produces symptoms similar to hepatitis A, although it can take a fulminant course in some patients, particularly pregnant women (mortality rate about 20%); chronic infections may occur in immune-compromised patients </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 Infantilism 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 White piedra 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 Gorhams disease and explain in detail? [/INST] Gorhams disease (pronounced GOR-amz), also known as Gorham vanishing bone disease and phantom bone disease, is a very rare skeletal condition of unknown cause, characterized by the uncontrolled proliferation of distended, thin-walled vascular or lymphatic channels within bone, which leads to resorption and replacement of bone with angiomas and/or fibrosis.

Signs and symptoms
The symptoms of Gorhams disease vary depending on the bones involved. It may affect any part of the skeleton, but the most common sites of disease are the shoulder, skull, pelvic girdle, jaw, ribs, and spine.In some cases, no symptoms are seen until a fracture occurs either spontaneously or following minor trauma, such as a fall. An acute onset of localized pain and swelling may occur. More commonly, pain of no apparent cause increases in frequency and intensity over time and may eventually be accompanied by weakness and noticeable deformity of the area. The rate of progression is unpredictable, and the prognosis can be difficult. The disease may stabilize after a number of years, go into spontaneous remission, or in cases involving the chest and upper spine, prove fatal. Recurrence of the disease following remission can also occur. Involvement of the spine and skull base may cause a poor outcome from neurological complications. In many cases, the result of Gorhams disease is severe deformity and functional disability.Symptoms such as difficulty breathing and chest pain may be present if the disease is present in the ribs, scapula, or thoracic vertebrae. These may indicate that the disease has spread from the bone into the chest cavity. The breathing problems may be misdiagnosed as asthma, because the damage done to the lungs can cause the same types of changes to lung function testing as seen in asthma. Extension of the lesions into the chest may lead to the development of chylous pleural and pericardial effusions. Chyle is rich in protein and white blood cells that are important in fighting infection. The loss of chyle into the chest can have serious consequences, including infection, malnutrition, and respiratory distress and failure. These complications or their symptoms, such as difficulty breathing, chest pain, poor growth or weight loss, and infection have sometimes been the first indications of the condition.

Causes
The specific cause of Gorhams disease remains unknown. Bone mass and strength are obtained and maintained through a process of bone destruction and replacement that occurs at the cellular level throughout a persons life. Cells called osteoclasts secrete enzymes that dissolve old bone, allowing another type of cells called osteoblasts to form new bone. Except in growing bone, the rate of breakdown equals the rate of building, thereby maintaining bone mass. In Gorhams disease, that process is disrupted.Gorham and Stout found that vascular anomalies always occupied space that normally would be filled with new bone and speculated that the presence of angiomatosis may lead to chemical changes in the bone. Gorham and others speculated that such a change in the bone chemistry might cause an imbalance in the rate of osteoclast to osteoblast activity such that more bone is dissolved than is replaced. Beginning in the 1990s, elevated levels of a protein called interleukin-6 (IL-6) being detected in people with the disease were reported, leading some to suggest that increased levels of IL-6 and vascular endothelial growth factor (VEGF) may contribute to the chemical changes Gorham and others believed were the cause of this type of osteolysis.In 1999, Möller and colleagues concluded, "The Gorham-Stout syndrome may be, essentially, a monocentric bone disease with a focally increased bone resorption due to an increased number of paracrine – or autocrine – stimulated hyperactive osteoclasts. The resorbed bone is replaced by a markedly vascularized  fibrous tissue. The apparent contradiction concerning the presence or absence or the number of osteoclasts, may be explained by the different phases of the syndrome." They further stated that their histopathological study provided good evidence that osteolytic changes seen in Gorhams disease are the result of hyperactive osteoclastic bone. However, others have concluded that lymphangiomatosis and Gorhams disease should be considered as a spectrum of disease rather than separate diseases.While a consensus exists that Gorhams is caused by deranged osteoclastic activity, no conclusive evidence has been found as to what causes this behavior to begin.

Diagnosis
In 1983, Heffez and colleagues published a case report in which they suggested eight criteria for a definitive diagnosis of Gorhams disease:
Positive biopsy with the presence of angiomatous tissue
Absence of cellular atypia
Minimal or no osteoblastic response or dystrophic calcifications
Evidence of local bone progressive osseous resorption
Nonexpansile, nonulcerative lesions
No involvement of viscera
Osteolytic radiographic pattern
Negative hereditary, metabolic, neoplastic, immunologic, or infectious etiologyIn the early stages of the disease, X-rays reveal changes resembling patchy osteoporosis. As the disease progresses, bone deformity occurs with further loss of bone mass, and in the tubular bones (the long bones of the arms and legs), a concentric shrinkage is often seen which has been described as having a "sucked candy" appearance. Once the cortex (the outer shell) of the bone has been disrupted, and vascular channels may invade adjacent soft tissues and joints. Eventually, complete or near-complete resorption of the bone occurs and may extend to adjacent bones, though spontaneous arrest of bone loss has been reported on occasion. Throughout this process, as the bone is destroyed, it is replaced by angiomatous and/or fibrous tissue.Often, Gorhams disease is not recognized until a fracture occurs, with subsequent improper bone healing. The diagnosis essentially is one of exclusion and must be based on combined clinical, radiological, and histopathological findings. X-rays, CT scans, MRIs, ultrasounds, and nuclear medicine (bone scans) are all important tools in the diagnostic workup and surgical planning, but none has the ability alone to produce a definitive diagnosis. Surgical biopsy with histological identification of the vascular or lymphatic proliferation within a generous section of the affected bone is an essential component in the diagnostic process.Recognition of the disease requires a high index of suspicion and an extensive workup. Because of its serious morbidity, Gorhams must always be considered in the differential diagnosis of osteolytic lesions.

Management
Treatment of Gorhams disease is for the most part palliative and limited to symptom management.Sometimes, the bone destruction spontaneously ceases and no treatment is required, but when the disease is progressive, aggressive intervention may be necessary. Duffy and colleagues reported that around 17% of people with Gorhams disease in the ribs, shoulder, or upper spine experience extension of the disease into the chest, leading to chylothorax with its serious consequences, and that the mortality rate in this group can reach as high as 64% without surgical intervention.
A search of the medical literature reveals multiple case reports of interventions with varying rates of success as follows:Cardiothoracic (heart and lung):

Skeletal:

To date, no known interventions are consistently effective for Gorhams, and all reported interventions are considered experimental treatments, though many are routine for other conditions. Some people may require a combination of these approaches. Unfortunately, some people will not respond to any intervention.

Epidemiology
Gorhams disease is extremely rare and may occur at any age, though it is most often recognized in children and young adults. It strikes males and females of all races and exhibits no inheritance pattern. The medical literature contains case reports from every continent. Because it is so rare, and commonly misdiagnosed,  exactly how many people are affected by this disease is not known. The literature frequently cites that fewer than 200 cases have been reported, though a consensus is building that many more cases occur around the world than have been reported.

History
The first known report of the condition came in 1838 in an article titled "A Boneless Arm" in what was then The Boston Medical and Surgical Journal (now The New England Journal of Medicine). It is a brief report chronicling the case of Mr. Brown who had, in 1819 at age 18 years, broken his right upper arm in an accident. The person had two subsequent accidents, which fractured the arm twice more "before the curative process had been completed." At the time of the report in 1838, the person was reported as having remarkable use of the arm, in spite of the humerus bone having apparently disappeared – X-rays did not yet exist. Thirty-four years later,  a follow-up report was published in the same journal, following Mr. Browns death from pneumonia at the age of 70 years. The person had requested the arm "be dissected and preserved for the benefit of medical science" and this report contains a detailed pathological description of the arm and shoulder. Abnormalities of the remaining bones of the arm and shoulder are noted and the authors report that the arteries, veins, and nerves appeared normal. No mention was made of lymphatic vessels. Though several reports of similar cases were published in the interim, more than 80 years passed before another significant report of the condition appeared in the medical literature.Both born in 1885, Lemuel Whittington Gorham, MD, and Arthur Purdy Stout, MD, had long, distinguished careers in medicine and shared a lifelong interest in pathology. Dr. Gorham practiced and taught medicine and oncology and from the mid-1950s through the early 1960s conducted and reported the classical clinicopathological investigations of pulmonary embolism. During this time, he also authored several case series on osteolysis of bone. Dr. Stout began his career as a surgeon and became a pioneer in tumor pathology, publishing Human Cancer in 1932. This work became the model for the Atlas of Tumor Pathology project, which Stout oversaw as chairman of the National Research Council in the 1950s. In his later years, Dr. Stout embarked on a systematic study of soft tissue tumors in children and was among the first to link cigarette smoking to lung cancer.In 1954, Gorham and three others published a two case series, with a brief review of 16 similar cases from the medical literature, that advanced the hypothesis that angiomatosis was responsible for this unusual form of massive osteolysis. That same year, Gorham and Stout presented to the American Association of Physicians their paper (in abstract form), "Massive Osteolysis (Acute Spontaneous Absorption of Bone, Phantom Bone, Disappearing Bone): Its Relation to Hemangiomatosis". The paper was published in its entirety in October 1955 in The Journal of Bone and Joint Surgery, concluding that:

There now exists the basis for a new syndrome which is supported by a remarkable similarity of clinical and [x-ray] findings in twenty-four cases, and by an equally convincing similarity of the histological picture in eight of these, which we have personally studied.
However it is accomplished, the progressive osteolysis is always associated with an angiomatosis of blood and sometimes of lymphatic vessels, which seemingly are responsible for it.The most typical presentation is that of osteolysis of a single bone or the bones connected by a shared joint, such as the shoulder. Although the disease can attack any bone, the shoulder is one of the most commonly involved areas, along with the skull and pelvic girdle. Spontaneous fractures are common and may be the first sign of the disease. A hallmark of the disease is the lack of bone healing following fracture.

References
Further reading
Dellinger, M. T., Garg, N, Olsen, B.R., 2014. Viewpoints on vessels and vanishing bones in Gorham-Stout disease. Bone </s>