<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 Hydrolethalus syndrome and explain in detail? [/INST] Hydrolethalus syndrome (HLS) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and, most commonly, stillbirth.HLS is associated with HYLS1 mutations. The gene encoding HYLS1 is responsible for proper cilial development within the human body. Cilia are microscopic projections that allow sensory input and signalling output within cells, as well as cell motility. Dysfunction results in a range of abnormalities that are often the result of improper cell signalling. A variant form, HLS2, with additional mutations to the KIF7 gene, is less common. KIF7 also ensures correct cilia formation and function, specifically cilia stability and length.Hydrolethalus syndrome (HLS) was first mistakenly identified in Finland, during a study on Meckel syndrome. Like HLS, Meckel syndrome presents with severe physiological abnormalities, namely disruptions to the central nervous system and the presence of extra fingers or toes (polydactyly). HLS can be distinguished from Meckel syndrome by analysing kidney function, which is dysfunctional in Meckel syndrome as a result of cyst formation.

Signs and symptoms
HLS presents itself as various, lethal developmental abnormalities, which often result in either premature stillbirth or death shortly after birth. Rare cases of children born with HLS surviving for several months have been noted. A characteristic abnormality of HLS is an absence of brain tissue and midline structures, with the presence of excess brain fluid (hydrocephalus) as a result of abnormal development of the central nervous system. Other common defects include incomplete lung development, heart defects, a cleft lip or palate, polydactyly, and an abnormally small jaw. Stillbirth and an excess of amniotic fluid (polyhydramnios) are common during pregnancy with a HLS-affected foetus, with cases of up to 8 litres cited compared to the normal 1 litre. Less common symptoms such as abnormally small eyes and a broad nose are also possible.

Cause
Genetic
HLS is caused by a genetic missense mutation of the HYLS1 gene, encoding for Hydrolethalus syndrome protein 1, on chromosome 11; a single base change to the amino acid sequence for HYLS1 in exon 6 involves the replacement of aspartic acid 211 with glycine (D211G) in the polypeptide chain. Exon 6 is the only protein coding exon in HYLS1; proper functioning of exons 1-5 ensures regulation and expression of the entire protein.
HLS is an autosomal recessive syndrome; development is only possible if both parents carry the defective gene, and in that instance, the risk of the foetus developing the syndrome is 25%. HLS is a member of the Finnish disease heritage, with incidences more common in Finland than the rest of the world; roughly 1 in 20,000 developing foetuses are affected in Finland. Rare cases in other regions have also been documented, often with less severe phenotypes as a result of allele variability across countries, allowing survival of affected offspring for up to several months. Individuals of Finnish descent are advised to undergo genetic testing before attempting to conceive.Prior to the discovery of HLS, the HYLS1 gene was unknown, and similar genes within humans have not been identified. Orthologs, genes in other species with common ancestral heritage, have been examined to explain the pathophysiology of HLS; a similar gene within the roundworm, Caenorhabditis elegans, is responsible for the formation of cilia. Current hypotheses place a dysfunction of cilia as the main cause of HLS defects arising from the HYLS1 mutation in humans.
Differences between wild type and mutant HYLS1 have been clearly observed; the wild type form is localised to the cytoplasm, while the mutant form is localised to the nucleus and forms small clusters, suggesting that the mutant gene disrupts cellular localisation. The protein encoded by the HYLS1 mutant form is unable to carry out essential targeting of centrioles to the plasma membrane, disrupting ciliary function, which results in ciliopathy </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 Urethral caruncle 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 Respiratory failure and explain in detail? [/INST] Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type 1 or Type 2, based on whether there is a high carbon dioxide level, and can be acute or chronic. In clinical trials, the definition of respiratory failure usually includes increased respiratory rate, abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing. Respiratory failure causes an altered mental status due to ischemia in the brain.
The typical partial pressure reference values are oxygen Pa O2 more than 80 mmHg (11 kPa) and carbon dioxide Pa CO2 less than 45 mmHg (6.0 kPa).

Cause
Several types of conditions can potentially result in respiratory failure:

Conditions that reduce the flow of air into and out of the lungs, including physical obstruction by foreign bodies or masses and reduced breathing due to drugs or changes to the chest.
Conditions that impair the lungs blood supply. These include thromboembolic conditions and conditions that reduce the output of the right heart, such as right heart failure and some myocardial infarctions.
Conditions that limit the ability of the lung tissue to exchange oxygen and carbon dioxide between the blood and the air within the lungs. Any disease which can damage the lung tissue can fit into this category. The most common causes are (in no particular order) infections, interstitial lung disease, and pulmonary oedema.

Diagnosis
Type 1
Type 1 respiratory failure is defined as a low level of oxygen in the blood (hypoxemia) with either a standard (normocapnia) or low (hypocapnia) level of carbon dioxide (PaCO2) but not an increased level (hypercapnia). It is typically caused by a ventilation/perfusion (V/Q) mismatch; the volume of air flowing in and out of the lungs is not matched with the flow of blood to the lungs. The fundamental defect in type 1 respiratory failure is a failure of oxygenation characterized by:

This type of respiratory failure is caused by conditions that affect oxygenation, such as:

Low ambient oxygen (e.g. at high altitude)
Ventilation-perfusion mismatch (parts of the lung receive oxygen but not enough blood to absorb it, e.g. pulmonary embolism)
Alveolar hypoventilation (decreased minute volume due to reduced respiratory muscle activity, e.g. in acute neuromuscular disease); this form can also cause type 2 respiratory failure if severe.
Diffusion problem (oxygen cannot enter the capillaries due to parenchymal disease, e.g. in pneumonia or ARDS)
Shunt (oxygenated blood mixes with non-oxygenated blood from the venous system, e.g. right to left shunt)

Type 2
Hypoxemia (PaO2 <8kPa or normal) with hypercapnia (PaCO2 >6.0kPa).
The basic defect in type 2 respiratory failure is characterized by:

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected.  Defined as the buildup of carbon dioxide levels (PaCO2) that has been generated by the body but cannot be eliminated. The underlying causes include:

Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)
Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)
A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)
Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)
Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

Type 3
Type 3 respiratory failure results from lung atelectasis. Because atelectasis occurs so commonly in the perioperative period, this form is also called  perioperative respiratory failure.  After general anesthesia, decreases in functional residual capacity  leads to  collapse  of  dependent lung units.

Type 4
Type 4 respiratory failure results from hypoperfusion of respiratory muscles as in patients in shock. Patients in shock often experience respiratory distress due to pulmonary edema (e.g., in cardiogenic shock) </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 Subepithelial mucinous corneal dystrophy 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 Crome 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 Cerebral hypoxia and explain in detail? [/INST] Cerebral hypoxia is a form of hypoxia (reduced supply of oxygen), specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of increasing severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.Cases of total oxygen deprivation are termed "anoxia", which can be hypoxic in origin (reduced oxygen availability) or ischemic in origin (oxygen deprivation due to a disruption in blood flow). Brain injury as a result of oxygen deprivation either due to hypoxic or anoxic mechanisms are generally termed hypoxic/anoxic injuries (HAI). Hypoxic ischemic encephalopathy (HIE) is a condition that occurs when the entire brain is deprived of an adequate oxygen supply, but the deprivation is not total. While HIE is associated in most cases with oxygen deprivation in the neonate due to birth asphyxia, it can occur in all age groups, and is often a complication of cardiac arrest.

Signs and symptoms
The brain requires approximately 3.3 ml of oxygen per 100 g of brain tissue per minute. Initially the body responds to lowered blood oxygen by redirecting blood to the brain and increasing cerebral blood flow. Blood flow may increase up to twice the normal flow but no more.  If the increased blood flow is sufficient to supply the brains oxygen needs then no symptoms will result.However, if blood flow cannot be increased or if doubled blood flow does not correct the problem, symptoms of cerebral hypoxia will begin to appear. Mild symptoms include difficulties with complex learning tasks and reductions in short-term memory. If oxygen deprivation continues, cognitive disturbances, and decreased motor control will result. The skin may also appear bluish (cyanosis) and heart rate increases. Continued oxygen deprivation results in fainting, long-term loss of consciousness, coma, seizures, cessation of brain stem reflexes, and brain death.Objective measurements of the severity of cerebral hypoxia depend on the cause. Blood oxygen saturation may be used for hypoxic hypoxia, but is generally meaningless in other forms of hypoxia.  In hypoxic hypoxia 95–100% saturation is considered normal; 91–94% is considered mild and 86–90% moderate. Anything below 86% is considered severe.Cerebral hypoxia refers to oxygen levels in brain tissue, not blood.  Blood oxygenation will usually appear normal in cases of hypemic, ischemic, and hystoxic cerebral hypoxia. Even in hypoxic hypoxia blood measures are only an approximate guide; the oxygen level in the brain tissue will depend on how the body deals with the reduced oxygen content of the blood.

Causes
Cerebral hypoxia can be caused by any event that severely interferes with the brains ability to receive or process oxygen. This event may be internal or external to the body. Mild and moderate forms of cerebral hypoxia may be caused by various diseases that interfere with breathing and blood oxygenation. Severe asthma and various sorts of anemia can cause some degree of diffuse cerebral hypoxia. Other causes include status epilepticus, work in nitrogen-rich environments, ascent from a  deep-water dive, flying at high altitudes in an unpressurized cabin without supplemental oxygen, and intense exercise at high altitudes prior to acclimatization.
Severe cerebral hypoxia and anoxia is usually caused by traumatic events such as choking, drowning, strangulation, smoke inhalation, drug overdoses, crushing of the trachea, status asthmaticus, and shock. It is also recreationally self-induced in the fainting game and in erotic asphyxiation.

Transient ischemic attack (TIA), is often referred to as a "mini-stroke". The American Heart Association and American Stroke Association (AHA/ASA) refined the definition of transient ischemic attack. TIA is now defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. The symptoms of a TIA can resolve within a few minutes, unlike a stroke. TIAs share the same underlying  etiology as strokes; a disruption of cerebral blood flow. TIAs and strokes present with the same symptoms such as contralateral paralysis (opposite side of body from affected brain hemisphere), or sudden weakness or numbness. A TIA may cause sudden dimming or loss of vision, aphasia, slurred speech, and mental confusion. The symptoms of a TIA typically resolve within 24 hours, unlike a stroke. Brain injury may still occur in a TIA lasting only a few minutes. Having a TIA is a risk factor for eventually having a stroke.
Silent stroke is a stroke which does not have any outward symptoms, and the patient is typically unaware they have had a stroke. Despite its lack of identifiable symptoms, a silent stroke still causes brain damage and places the patient at increased risk for a major stroke in the future. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as fMRI. The risk of silent stroke increases with age but may also affect younger adults. Women appear to be at increased risk for silent stroke, with hypertension and current cigarette smoking being predisposing factors.

Pre- and postnatal
Hypoxic-anoxic events may affect the fetus at various stages of fetal development, during labor and delivery and in the postnatal period. Sometimes, even an infant that is still in the womb may exhibit signs of HIE or other hypoxic ischemic injury. Fetal distress being one of the most common signs of HIE or other oxygen-depriving event. Other problems during pregnancy may include preeclampsia, maternal diabetes with vascular disease, congenital fetal infections, substance/alcohol use, severe fetal anemia, cardiac disease, lung malformations, or problems with blood flow to the placenta.
Problems during labor and delivery can include umbilical cord occlusion, torsion or prolapse, rupture of the placenta or uterus, excessive bleeding from the placenta, abnormal fetal position such as the breech position, prolonged late stages of labor, or very low blood pressure in the mother. Problems after delivery can include severe prematurity, severe lung or heart disease, serious infections, trauma to the brain or skull, congenital malformations of the brain or very low blood pressure in the baby and due to suffocation in cases of Münchausen syndrome by proxy.The severity of a neonatal hypoxic-ischaemic brain injury may be assessed using Sarnat staging, which is based on clinical presentation and EEG findings, and also using MRI. Signs and symptoms of HIE may include:

Low Apgar scores, <5 at 5 minutes and 10 minutes.
Floppiness, or unreactive to sights or sounds, or more tense and agitated.
Low heart rate.
Low blood pressure.
Poor muscle tone and absent reflexes.
Weak breathing, no breathing at all, or rapid breathing.
Need for resuscitation after delivery.
Weak cry.
Bluish or pale skin color.
Excessive acid in the blood.
Seizures or abnormal movements.
Problems feeding

Mechanism
Details of the mechanism of damage from cerebral hypoxia, along with anoxic depolarization, can be found here: Mechanism of anoxic depolarization in the brain

Diagnosis
Classification
Cerebral hypoxia is typically grouped into four categories depending on the severity and location of the brains oxygen deprivation:

Diffuse cerebral hypoxia – A mild to moderate impairment of brain function due to low oxygen levels in the blood.
Focal cerebral ischemia – A stroke occurring in a localized area that can either be acute or transient. This may be due to a variety of medical conditions such as an aneurysm that causes a hemorrhagic stroke, or an occlusion occurring in the affected blood vessels due to a thrombus (thrombotic stroke) or embolus (embolic stroke). Focal cerebral ischemia constitutes a large majority of the clinical cases in stroke pathology with the infarct usually occurring in the middle cerebral artery (MCA).
Global cerebral ischemia – A complete stoppage of blood flow to the brain.
Cerebral infarction – A "stroke",  caused by complete oxygen deprivation due to an interference in cerebral blood flow which affects multiple areas of the brain.Cerebral hypoxia can also be classified by the cause of the reduced brain oxygen:
Hypoxic hypoxia – Limited oxygen in the environment causes reduced brain function. Divers, aviators, mountain climbers, and fire fighters are all at risk for this kind of cerebral hypoxia. The term also includes oxygen deprivation due to obstructions in the lungs. Choking, strangulation, the crushing of the windpipe all cause this sort of hypoxia. Severe asthmatics may also experience symptoms of hypoxic hypoxia.
Hypemic hypoxia – Reduced brain function is caused by inadequate oxygen in the blood despite adequate environmental oxygen.  Anemia and carbon monoxide poisoning are common causes of hypemic hypoxia.
Ischemic hypoxia ( or "stagnant hypoxia") – Reduced brain oxygen is caused by inadequate blood flow to the brain.  Stroke, shock, cardiac arrest and heart attack may cause stagnant hypoxia. Ischemic hypoxia can also be created by pressure on the brain.  Cerebral edema, brain hemorrhages and hydrocephalus exert pressure on brain tissue and impede their absorption of oxygen.
Histotoxic hypoxia – Oxygen is present in brain tissue but cannot be metabolized by the brain tissue.  Cyanide poisoning is a well-known example.

Treatment
For newborn infants starved of oxygen during birth there is now evidence that hypothermia therapy for neonatal encephalopathy applied within 6 hours of cerebral hypoxia effectively improves survival and neurological outcome. In adults, however, the evidence is less convincing and the first goal of treatment is to restore oxygen to the brain. The method of restoration depends on the cause of the hypoxia. For mild-to-moderate cases of hypoxia, removal of the cause of hypoxia may be sufficient. Inhaled oxygen may also be provided.  In severe cases treatment may also involve life support and damage control measures.
A deep coma will interfere with the bodys breathing reflexes even after the initial cause of hypoxia has been dealt with; mechanical ventilation may be required. Additionally, severe cerebral hypoxia causes an elevated heart rate, and in extreme cases the heart may tire and stop pumping. CPR, defibrilation, epinephrine, and atropine may all be tried in an effort to get the heart to resume pumping. Severe cerebral hypoxia can also cause seizures, which put the patient at risk of self-injury, and various anti-convulsant drugs may need to be administered before treatment.
There has long been a debate over whether newborn infants with cerebral hypoxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen.Brain damage can occur both during and after oxygen deprivation. During oxygen deprivation, cells die due to an increasing acidity in the brain tissue (acidosis). Additionally, during the period of oxygen deprivation, materials that can easily create free radicals build up. When oxygen enters the tissue these materials interact with oxygen to create high levels of oxidants. Oxidants interfere with the normal brain chemistry and cause further damage (this is known as "reperfusion injury").
Techniques for preventing damage to brain cells are an area of ongoing research. Hypothermia therapy for neonatal encephalopathy is the only evidence-supported therapy, but antioxidant drugs, control of blood glucose levels, and hemodilution (thinning of the blood) coupled with drug-induced hypertension are some treatment techniques currently under investigation. Hyperbaric oxygen therapy is being evaluated with the reduction in total and myocardial creatine phosphokinase levels showing a possible reduction in the overall systemic inflammatory process.In severe cases it is extremely important to act quickly.  Brain cells are very sensitive to reduced oxygen levels. Once deprived of oxygen they will begin to die off within five minutes.

Prognosis
Mild and moderate cerebral hypoxia generally has no impact beyond the episode of hypoxia; on the other hand, the outcome of severe cerebral hypoxia will depend on the success of damage control, amount of brain tissue deprived of oxygen, and the speed with which oxygen was restored.
If cerebral hypoxia was localized to a specific part of the brain, brain damage will be localized to that region. A general consequence may be epilepsy. The long-term effects will depend on the purpose of that portion of the brain </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 Pseudomelanoma and explain in detail? [/INST] Pseudomelanoma (also known as a "recurrent melanocytic nevus", and "recurrent nevus") is a cutaneous condition in which melanotic skin lesions clinically resemble a superficial spreading melanoma at the site of a recent shave removal of a melanocytic nevus.: 689

Problem with the recurrent nevus
The melanocytes left behind in the wound regrow in an abnormal pattern. Rather than the even and regular lace like network, the pigments tends to grow in streaks of varying width within the scar. This is often accompanied by scarring, inflammation, and blood vessel changes – giving both the clinical and histologic impression of a melanoma or a severe dysplastic nevus. When the patient is reexamined years later without the assistance of the original biopsy report, the physician will often require the removal of the scar with the recurrent nevus to assure that a melanoma is not missed.

Saucerization biopsy
Also known as "scoop", "scallop", or "shave" excisional biopsy, or "shave excision". A trend has occurred in dermatology over the last 10 years with the advocacy of a deep shave excision of a pigmented lesion An author published the result of this method and advocated it as better than standard excision and less time-consuming. The added economic benefit is that many surgeons bill the procedure as an excision, rather than a shave biopsy. This save the added time for hemostasis, instruments, and suture cost </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 Radiation proctitis and explain in detail? [/INST] Radiation proctitis or radiation proctopathy is condition characterized by damage to the rectum after exposure to x-rays or other ionizing radiation as a part of radiation therapy. Radiation proctopathy may occur as acute inflammation called "acute radiation proctitis" (and the related radiation colitis) or with chronic changes characterized by radiation associated vascular ectasiae (RAVE) and chronic radiation proctopathy.  Radiation proctitis most commonly occurs after pelvic radiation treatment for cancers such as cervical cancer, prostate cancer, bladder cancer, and rectal cancer. RAVE and chronic radiation proctopathy involves the lower intestine, primarily the sigmoid colon and the rectum, and was previously called chronic radiation proctitis, pelvic radiation disease and radiation enteropathy.

Signs and symptoms
Acute radiation proctopathy often causes pelvic pain, diarrhea, urgency, and the urge to defecate despite having an empty colon (tenesmus). Hematochezia and fecal incontinence may occur, but are less common. Chronic radiation damage to the rectum (>3 months) may cause rectal bleeding, incontinence, or a change in bowel habits secondary. Severe cases may lead to with strictures or fistulae formation. Chronic radiation proctopathy can present at a median time of 8-12 months following radiation therapy.

Histopathology
Acute radiation proctopathy occurs due to direct damage of the lining (epithelium) of the colon. Rectal biopsies of acute radiation proctopathy show superficial depletion of epithelial cells and acute inflammatory cells located in the lamina propria. By contrast, rectal biopsies of RAVE and chronic radiation proctopathy demonstrates ischemic endarteritis of the submucosal arterioles, submucosal fibrosis, and neovascularization.

Diagnosis
Where chronic radiation proctopathy or RAVE is suspected, a thorough evaluation of symptoms is essential. Evaluation should include an assessment of risk factors for alternate causes of proctitis, such as C. difficile colitis, NSAID use, and travel history. Symptoms such as diarrhea and painful defecation need to be systematically investigated and the underlying causes each carefully treated. Testing for parasitic infections (amebiasis, giardiasis) and sexually transmitted infections (Neisseria gonorrhoeae and herpes simplex virus) should be considered. The location of radiation treatment is important, as radiation directed at regions of the body other than the pelvis (eg brain, chest, etc) should not prompt consideration of radiation proctopathy.Endoscopy is the mainstay of diagnosis for radiation damage to the rectum, with either colonoscopy or flexible sigmoidoscopy. RAVE is usually recognized by the macroscopic appearances on endoscopy characterized by vascular ectasias. Mucosal biopsy may aid in ruling out alternate causes of proctitis, but is not routinely necessary and may increase the risk of fistulae development. Telangiectasias are characteristic and prone to bleeding. Additional endoscopic findings may include pallor (pale appearance), edema, and friability of the mucosa.

Classification
Radiation proctitis can occur a few weeks after treatment, or after several months or years:

Acute radiation proctitis — symptoms occur in the first 3 months after therapy. These symptoms include diarrhea and the urgent need to defecate.
Radiation associated vascular ectasias (RAVE) and Chronic radiation proctopathy — previously known as "chronic radiation proctitis" occur 3-6 months after the initial exposure </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 Myelopathy and explain in detail? [/INST] Myelopathy describes any neurologic deficit related to the spinal cord. When due to trauma, it is known as (acute) spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular myelopathy. The most common form of myelopathy in humans, cervical spondylotic myelopathy (CSM), also called degenerative cervical myelopathy is caused by arthritic changes (spondylosis) of the cervical spine, which result in narrowing of the spinal canal (spinal stenosis) ultimately causing compression of the spinal cord.  In Asian populations, spinal cord compression often occurs due to a different, inflammatory process affecting the posterior longitudinal ligament.

Presentation
Clinical signs and symptoms depend on which spinal cord level (cervical, thoracic, or lumbar) is affected and the extent (anterior, posterior, or lateral) of the pathology, and may include:
Upper motor neuron signs—weakness, spasticity, clumsiness, altered tonus, hyperreflexia and pathological reflexes, including Hoffmanns sign and inverted plantar reflex (positive Babinski sign)
Lower motor neuron signs—weakness, clumsiness in the muscle group innervated at the level of spinal cord compromise, muscle atrophy, hyporeflexia, muscle hypotonicity or flaccidity, fasciculations
Sensory deficits
Bowel/bladder symptoms and sexual dysfunction

Diagnosis
Diagnosis of myelopathy
Myelopathy is primarily diagnosed by clinical exam findings. Because the term myelopathy describes a clinical syndrome that can be caused by many pathologies the differential diagnosis of myelopathy is extensive. In some cases the onset of myelopathy is rapid, in others, such as CSM, the course may be insidious with symptoms developing slowly over a period of months. As a consequence, the diagnosis of CSM is often delayed. As the disease is thought to be progressive, this may impact negatively on outcome.

Diagnosis of etiology
Once the clinical diagnosis myelopathy is established, the underlying cause must be investigated. Most commonly this involves medical imaging </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 Cystathioninuria and explain in detail? [/INST] Cystathioninuria, also called cystathionase deficiency, is an autosomal recessive metabolic disorder. It is characterized by an abnormal accumulation of plasma cystathionine leading to excess cystathionine in the urine. Hereditary cystathioninuria is associated with the reduced activity of the enzyme cystathionine gamma-lyase. It is considered a biochemical anomaly. This is because it associated with a wide range of diseases and its inconsistency.
Cystathionase catalyzes cystathionine to cysteine and α-ketobutyrate. Cysteine is an essential amino acid and its conversion from cystathionine occurs in the trans-sulfuration pathway. The availability of cysteine is necessary for the synthesis of an important anti-oxidant, glutathione. Cystathionase has a co-enzyme, pyridoxal phosphate, which is the active form the vitamin B6.  This means that vitamin B6 is essential for the function of cystathionase.
Cystathioninuria can be broken down into two main categories. Primary cystathioninuria is caused by the recessive inherited deficiency of cystathionase enzyme. Secondary cystathioninuria is described by non-genetic conditions of excess cystathionine. Secondary cystathioninuria includes temporary excess cystathionine of premature infants, severe generalized liver damage, thyrotoxicosis, hepatoblastoma, or neuroblastoma. Cases of secondary cystathioninuria are not responsive to vitamin B6 administration.

Types
Under primary cystathioninuria, the inherited mutation of CTH gene, there are two forms. There is vitamin B6 – unresponsive and vitamin B6 – responsive cystathioninuria. The vitamin B6 – unresponsive form is thought to be from a lack of the synthesis of cystathionase. This means that the mutation in CTH from this form of cystathioninuria, results in the absence of cystathionase. It could also result from the synthesis of a cystathionase that is so greatly mutated it cannot function at all. On the other hand, vitamin B6 – responsive form still has synthesis of cystathionase. However, the cystathionase has an altered ability to bind to vitamin B6, its coenzyme. This changed interaction lowers the efficiency of cystathionase, so it cannot convert cystathionine as well.

Genetics
Cystathioninuria is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.Interestingly, homozygotes and heterozygotes were able to be distinguished in one study through both plasma and urinary levels of cystathionine. The homozygote individuals had cystathionine levels greater than 0.5 moles per milligram of creatinine </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 Relapsing fever and explain in detail? [/INST] Relapsing fever is a vector-borne disease caused by infection with certain bacteria in the genus Borrelia, which is transmitted through the bites of lice or soft-bodied ticks (genus Ornithodoros).

Signs and symptoms
Most people who are infected develop sickness between 5 and 15 days after they are bitten. The symptoms may include a sudden fever, chills, headaches, muscle or joint aches, and nausea. A rash may also occur. These symptoms usually continue for 2 to 9 days, then disappear. This cycle may continue for several weeks if the person is not treated.

Causes
Louse-borne relapsing fever
Along with Rickettsia prowazekii and Bartonella quintana, Borrelia recurrentis is one of three pathogens of which the body louse (Pediculus humanus humanus) is a vector. Louse-borne relapsing fever is more severe than the tick-borne variety.Louse-borne relapsing fever occurs in epidemics amid poor living conditions, famine and war in the developing world. It is currently prevalent in Ethiopia and Sudan.Mortality rate is 1% with treatment and 30–70% without treatment. Poor prognostic signs include severe jaundice, severe change in mental status, severe bleeding and a prolonged QT interval on ECG.Lice that feed on infected humans acquire the Borrelia organisms that then multiply in the gut of the louse. When an infected louse feeds on an uninfected human, the organism gains access when the victim crushes the louse or scratches the area where the louse is feeding. B. recurrentis infects the person via mucous membranes and then invades the bloodstream. No non-human, animal reservoir exists.

Tick-borne relapsing fever
Tick-borne relapsing fever is found primarily in Africa, Spain, Saudi Arabia, Asia, and certain areas of Canada and the western United States. Other relapsing infections are acquired from other Borrelia species, which can be spread from rodents, and serve as a reservoir for the infection, by a tick vector.
Borrelia crocidurae – occurs in Egypt, Mali, Senegal, Tunisia; vectors – Carios erraticus, Ornithodoros sonrai; animal host – shrew (Crocidura stampflii)
Borrelia duttoni, transmitted by the soft-bodied African tick Ornithodoros moubata, is responsible for the relapsing fever found in central, eastern, and southern Africa.
Borrelia hermsii
Borrelia hispanica
Borrelia miyamotoi
Borrelia parkeri
Borrelia turicatae
Borrelia persicaB. hermsii and B. recurrentis cause very similar diseases. However, one or two relapses are common with the disease associated with B. hermsii, which is also the most common cause of relapsing disease in the United States. (Three or four relapses are common with the disease caused by B. recurrentis, which has longer febrile and afebrile intervals and a longer incubation period than B. hermsii.)

Diagnosis
The diagnosis of relapsing fever can be made on blood smear as evidenced by the presence of spirochetes.  Other spirochete illnesses (Lyme disease, syphilis, leptospirosis) do not show spirochetes on blood smear. Although considered the gold standard,  this method lacks sensitivity and has been replaced by PCR in many settings.

Treatment
Relapsing fever is easily treated with a one- to two-week-course of antibiotics, and most people improve within 24 hours. Complications and death due to relapsing fever are rare.Tetracycline-class antibiotics are most effective. These can, however, induce a Jarisch–Herxheimer reaction in over half those treated, producing anxiety, diaphoresis, fever, tachycardia and tachypnea with an initial pressor response followed rapidly by hypotension. Recent studies have shown tumor necrosis factor-alpha  may be partly responsible for this reaction.

Research
Currently, no vaccine against relapsing fever is available, but research continues. Developing a vaccine is very difficult because the spirochetes avoid the immune response of the infected person (or animal) through antigenic variation. Essentially, the pathogen stays one step ahead of antibodies by changing its surface proteins. These surface proteins, lipoproteins called variable major proteins, have only 30–70% of their amino acid sequences in common, which is sufficient to create a new antigenic "identity" for the organism. Antibodies in the blood that are binding to and clearing spirochetes expressing the old proteins do not recognize spirochetes expressing the new ones.  Antigenic variation is common among pathogenic organisms. These include the agents of malaria, gonorrhea, and sleeping sickness. Important questions about antigenic variation are also relevant for such research areas as developing a vaccine against HIV and predicting the next influenza pandemic.

History
Relapsing fever has been described since the days of the ancient Greeks </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 Thrombophilia and explain in detail? [/INST] Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who have an episode of thrombosis (such as deep vein thrombosis in the leg) that was not provoked by other causes. A significant proportion of the population has a detectable thrombophilic abnormality, but most of these develop thrombosis only in the presence of an additional risk factor.There is no specific treatment for most thrombophilias, but recurrent episodes of thrombosis may be an indication for long-term preventive anticoagulation. The first major form of thrombophilia to be identified by medical science, antithrombin deficiency, was identified in 1965, while the most common abnormalities (including factor V Leiden) were described in the 1990s.

Signs and symptoms
The most common conditions associated with thrombophilia are deep vein thrombosis (DVT) and pulmonary embolism (PE), which are referred to collectively as venous thromboembolism (VTE). DVT usually occurs in the legs, and is characterized by pain, swelling and redness of the limb. It may lead to long-term swelling and heaviness due to damage to valves in the veins. The clot may also break off and migrate (embolize) to arteries in the lungs. Depending on the size and the location of the clot, this may lead to sudden-onset shortness of breath, chest pain, palpitations and may be complicated by collapse, shock and cardiac arrest.Venous thrombosis may also occur in more unusual places: in the veins of the brain, liver (portal vein thrombosis and hepatic vein thrombosis), mesenteric vein, kidney (renal vein thrombosis) and the veins of the arms. Whether thrombophilia also increases the risk of arterial thrombosis (which is the underlying cause of heart attacks and strokes) is less well established.Thrombophilia has been linked to recurrent miscarriage, and possibly various complications of pregnancy such as intrauterine growth restriction, stillbirth, severe pre-eclampsia and abruptio placentae.Protein C deficiency may cause purpura fulminans, a severe clotting disorder in the newborn that leads to both tissue death and bleeding into the skin and other organs. The condition has also been described in adults. Protein C and protein S deficiency have also been associated with an increased risk of skin necrosis on commencing anticoagulant treatment with warfarin or related drugs.

Causes
Thrombophilia can be congenital or acquired. Congenital thrombophilia refers to inborn conditions (and usually hereditary, in which case "hereditary thrombophilia" may be used) that increase the tendency to develop thrombosis, while, on the other hand, acquired thrombophilia refers to conditions that arise later in life.

Congenital
The most common types of congenital thrombophilia are those that arise as a result of overactivity of coagulation factors. They are relatively mild, and are therefore classified as "type II" defects. The most common ones are factor V Leiden (a mutation in the F5 gene at position 1691) and prothrombin G20210A, a mutation in prothrombin (at position 20210 in the 3 untranslated region of the gene).The rare forms of congenital thrombophilia are typically caused by a deficiency of natural anticoagulants. They are classified as "type I" and are more severe in their propensity to cause thrombosis. The main ones are antithrombin III deficiency, protein C deficiency and protein S deficiency. Milder rare congenital thrombophilias are factor XIII mutation and familial dysfibrinogenemia (an abnormal fibrinogen). It is unclear whether congenital disorders of fibrinolysis (the system that destroys clots) are major contributors to thrombosis risk. Congenital deficiency of plasminogen, for instance, mainly causes eye symptoms and sometimes problems in other organs, but the link with thrombosis has been more uncertain.Blood group determines thrombosis risk to a significant extent. Those with blood groups other than type O are at a 2- to 4-fold relative risk. O blood group is associated with reduced levels of von Willebrand factor – because of increased clearance – and factor VIII, which is related to thrombotic risk .

Acquired
A number of acquired conditions augment the risk of thrombosis. A prominent example is antiphospholipid syndrome, which is caused by antibodies against constituents of the cell membrane, particularly lupus anticoagulant (first found in people with the disease systemic lupus erythematosus but often detected in people without the disease), anti-cardiolipin antibodies, and anti-β2-glycoprotein 1 antibodies; it is therefore regarded as an autoimmune disease. In some cases, antiphospholipid syndrome can cause arterial as well as venous thrombosis. It is also more strongly associated with miscarriage, and can cause a number of other symptoms (such as livedo reticularis of the skin and migraine).Heparin-induced thrombocytopenia (HIT) is due to an immune system reaction against the anticoagulant drug heparin (or its derivatives).  Though it is named for associated low platelet counts, HIT is strongly associated with risk of venous and arterial thrombosis.  Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition resulting from acquired alterations in the PIGA gene, which plays a role in the protection of blood cells from the complement system. PNH increases the risk of venous thrombosis but is also associated with hemolytic anemia (anemia resulting from destruction of red blood cells). Both HIT and PNH require particular treatment.Hematologic conditions associated with sluggish blood flow can increase risk for thrombosis. For example, sickle-cell disease (caused by mutations of hemoglobin) is regarded as a mild prothrombotic state induced by impaired flow.  Similarly, myeloproliferative disorders, in which the bone marrow produces too many blood cells, predispose to thrombosis, particularly in polycythemia vera (excess red blood cells) and essential thrombocytosis (excess platelets). Again, these conditions usually warrant specific treatment when identified.Cancer, particularly when metastatic (spread to other places in the body), is a recognised risk factor for thrombosis. A number of mechanisms have been proposed, such as activation of the coagulation system by cancer cells or secretion of procoagulant substances. Furthermore, particular cancer treatments (such as the use of central venous catheters for chemotherapy) may increase the risk of thrombosis further.Nephrotic syndrome, in which protein from the bloodstream is released into the urine due to kidney diseases, can predispose to thrombosis; this is particularly the case in more severe cases (as indicated by blood levels of albumin below 25 g/L) and if the syndrome is caused by the condition membranous nephropathy. Inflammatory bowel disease (ulcerative colitis and Crohns disease) predispose to thrombosis, particularly when the disease is active. Various mechanisms have been proposed.Pregnancy is associated with an increased risk of thrombosis of 2- to 7-fold. This probably results from a physiological hypercoagulability in pregnancy that protects against postpartum hemorrhage. This hypercoagulability in turn is likely related to the high levels of estradiol and progesterone that occur during pregnancy.Estrogens, when used in combined hormonal birth control and in menopausal hormone therapy (in combination with progestogens), have been associated with a 2- to 6-fold increased risk of venous thrombosis. The risk depends on the types of hormones used, the dose of estrogen, and the presence of other thrombophilic risk factors. Various mechanisms, such as deficiency of protein S and tissue factor pathway inhibitor, are said to be responsible.Obesity has long been regarded as a risk factor for venous thrombosis. It more than doubles the risk in numerous studies, particularly in combination with the use of oral contraceptives or in the period after surgery. Various coagulation abnormalities have been described in the obese. Plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, is present in higher levels in people with obesity. Obese people also have larger numbers of circulating microvesicles (fragments of damaged cells) that bear tissue factor. Platelet aggregation may be increased, and there are higher levels of coagulation proteins such as von Willebrand factor, fibrinogen, factor VII and factor VIII. Obesity also increases the risk of recurrence after an initial episode of thrombosis.

Unclear
A number of conditions that have been linked with venous thrombosis are possibly genetic and possibly acquired. These include: elevated levels of factor VIII, factor IX, factor XI, fibrinogen and
thrombin-activatable fibrinolysis inhibitor, and decreased levels of tissue factor pathway inhibitor. Activated protein C resistance that is not attributable to factor V mutations is probably caused by other factors and remains a risk factor for thrombosis.There is an association between the blood levels of homocysteine and thrombosis, although this has not been reported consistently in all studies. Homocysteine levels are determined by mutations in the MTHFR and CBS genes, but also by levels of folic acid, vitamin B6 and vitamin B12, which depend on diet.

Mechanism
Thrombosis is a multifactorial problem because there are often multiple reasons why a person might develop thrombosis. These risk factors may include any combination of abnormalities in the blood vessel wall, abnormalities in the blood flow (as in immobilization), and abnormalities in the consistency of the blood. Thrombophilia is caused by abnormalities in blood consistency, which is determined by the levels of coagulation factors and other circulating blood proteins that participate in the "coagulation cascade".Normal coagulation is initiated by the release of tissue factor from damaged tissue. Tissue factor binds to circulating factor VIIa. The combination activates factor X to factor Xa and factor IX to factor IXa. Factor Xa (in the presence of factor V) activates prothrombin into thrombin. Thrombin is a central enzyme in the coagulation process: it generates fibrin from fibrinogen, and activates a number of other enzymes and cofactors (factor XIII, factor XI, factor V and factor VIII, TAFI) that enhance the fibrin clot. The process is inhibited by TFPI (which inactivates the first step catalyzed by factor VIIa/tissue factor), antithrombin (which inactivates thrombin, factor IXa, Xa and XIa), protein C (which inhibits factors Va and VIIIa in the presence of protein S), and protein Z (which inhibits factor Xa).In thrombophilia, the balance between "procoagulant" and "anticoagulant" activity is disturbed. The severity of the imbalance determines the likelihood that someone develops thrombosis. Even small perturbances of proteins, such as the reduction of antithrombin  to only 70–80% of the normal level, can increase the thrombosis risk; this is in contrast with hemophilia, which only arises if levels of coagulation factors are markedly decreased.In addition to its effects on thrombosis, hypercoagulable states may accelerate the development of atherosclerosis, the arterial disease that underlies myocardial infarction and other forms of cardiovascular disease.

Diagnosis
Tests for thrombophilia include complete blood count (with examination of the blood film), prothrombin time, partial thromboplastin time, thrombodynamics test, thrombin time and reptilase time, lupus anticoagulant, anti-cardiolipin antibody, anti-β2 glycoprotein 1 antibody, activated protein C resistance, fibrinogen tests, factor V Leiden and prothrombin mutation, and basal homocysteine levels. Testing may be more or less extensive depending on clinical judgement and abnormalities detected on initial evaluation.For hereditary cases, the patient must have at least two abnormal tests plus family history.

Screening
There are divergent views as to whether everyone with an unprovoked episode of thrombosis should be investigated for thrombophilia. Even those with a form of thrombophilia may not necessarily be at risk of further thrombosis, while recurrent thrombosis is more likely in those who have had previous thrombosis even in those who have no detectable thrombophilic abnormalities. Recurrent thromboembolism, or thrombosis in unusual sites (e.g. the hepatic vein in Budd-Chiari syndrome), is a generally accepted indication for screening. It is more likely to be cost-effective in people with a strong personal or family history of thrombosis.  In contrast, the combination of thrombophilia with other risk factors may provide an indication for preventive treatment, which is why thrombophilia testing may be performed even in those who would not meet the strict criteria for these tests. Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious trigger. For example, if the thrombosis is due to immobilization after recent orthopedic surgery, it is regarded as "provoked" by the immobilization and the surgery and it is less likely that investigations will yield clinically important results.When venous thromboembolism occurs when a patient is experiencing transient major risk factors such as prolonged immobility, surgery, or trauma, testing for thrombophilia is not appropriate because the outcome of the test would not change a patients indicated treatment. In 2013, the American Society of Hematology, as part of recommendations in the Choosing Wisely campaign, cautioned against overuse of thrombophilia screening; false positive results of testing would lead to people inappropriately being labeled as having thrombophilia, and being treated with anticoagulants without clinical needIn the United Kingdom, professional guidelines give specific indications for thrombophilia testing.  It is recommended that testing be done only after appropriate counseling, and hence the investigations are usually not performed at the time when thrombosis is diagnosed but at a later time. In particular situations, such as retinal vein thrombosis, testing is discouraged altogether because thrombophilia is not regarded as a major risk factor. In other rare conditions generally linked with hypercoagulability, such as cerebral venous thrombosis and portal vein thrombosis, there is insufficient data to state for certain whether thrombophilia screening is helpful, and decisions on thrombophilia screening in these conditions are therefore not regarded as evidence-based. If cost-effectiveness (quality-adjusted life years in return for expenditure) is taken as a guide, it is generally unclear whether thrombophilia investigations justify the often high cost, unless the testing is restricted to selected situations.Recurrent miscarriage is an indication for thrombophilia screening, particularly antiphospholipid antibodies (anti-cardiolipin IgG and IgM, as well as lupus anticoagulant), factor V Leiden and prothrombin mutation, activated protein C resistance and a general assessment of coagulation through an investigation known as thromboelastography.Women who are planning to use oral contraceptives do not benefit from routine screening for thrombophilias, as the absolute risk of thrombotic events is low. If either the woman or a first-degree relative has had thrombosis, the risk of developing thrombosis is increased. Screening this selected group may be beneficial, but even when negative may still indicate residual risk. Professional guidelines therefore suggest that alternative forms of contraception be used rather than relying on screening.Thrombophilia screening in people with arterial thrombosis is generally regarded as unrewarding and is generally discouraged, except possibly for unusually young patients (especially when precipitated by smoking or use of estrogen-containing hormonal contraceptives) and those in whom revascularization, such as coronary arterial bypass, fails because of rapid occlusion of the graft.

Treatment
There is no specific treatment for thrombophilia, unless it is caused by an underlying medical illness (such as nephrotic syndrome), where the treatment of the underlying disease is needed. In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most important decision is whether to use anticoagulation medications, such as warfarin, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result.Apart from the abovementioned forms of thrombophilia, the risk of recurrence after an episode of thrombosis is determined by factors such as the extent and severity of the original thrombosis, whether it was provoked (such as by immobilization or pregnancy), the number of previous thrombotic events, male sex, the presence of an inferior vena cava filter, the presence of cancer, symptoms of post-thrombotic syndrome, and obesity. These factors tend to be more important in the decision than the presence or absence of a detectable thrombophilia.Those with antiphospholipid syndrome may be offered long-term anticoagulation after a first unprovoked episode of thrombosis. The risk is determined by the subtype of antibody detected, by the antibody titer (amount of antibodies), whether multiple antibodies are detected, and whether it is detected repeatedly or only on a single occasion.Women with a thrombophilia who are contemplating pregnancy or are pregnant usually require alternatives to warfarin during pregnancy, especially in the first 13 weeks, when it may produce abnormalities in the unborn child. Low molecular weight heparin (LMWH, such as enoxaparin) is generally used as an alternative. Warfarin and LMWH may safely be used in breastfeeding.When women experience recurrent pregnancy loss secondary to thrombophilia, some studies have suggested that low molecular weight heparin reduces the risk of miscarriage. When the results of all studies are analysed together, no statistically significant benefit could be demonstrated.

Prognosis
In people without a detectable thrombophilia, the cumulative risk of developing thrombosis by the age of 60 is about 12%. About 60% of people who are deficient in antithrombin will have experienced thrombosis at least once by age 60, as will about 50% of people with protein C deficiency and about a third of those with protein S deficiency. People with activated protein C resistance (usually resulting from factor V Leiden), in contrast, have a slightly raised absolute risk of thrombosis, with 15% having had at least one thrombotic event by the age of sixty. In general, men are more likely than women to experience repeated episodes of venous thrombosis.People with factor V Leiden are at a relatively low risk of thrombosis, but may develop thrombosis in the presence of an additional risk factor, such as immobilization. Most people with the prothrombin mutation (G20210A) never develop thrombosis.

Epidemiology
The major ("type 1") thrombophilias are rare. Antithrombin deficiency is present in 0.2% of the general population and 0.5–7.5% of people with venous thrombosis. Protein C deficiency, too, is present in 0.2% of the population, and can be found in 2.5–6% of people with thrombosis. The exact prevalence of protein S deficiency in the population is unknown; it is found 1.3–5% of people with thrombosis.The minor ("type 2") thrombophilias are much more common. Factor V Leiden is present in 5% of the population of Northern European descent, but much rarer in those of Asian or African extraction. In people with thrombosis, 10% have factor V Leiden. In those who are referred for thrombophilia testing, 30–50% have the defect. The prothrombin mutation occurs at rates of 1–4% in the general population, 5–10% of people with thrombosis, and 15% of people referred for thrombophilia testing. Like factor V Leiden, this abnormality is uncommon in Africans and Asians.The exact prevalence of antiphospholipid syndrome is not well known, as different studies employ different definitions of the condition. Antiphospholipid antibodies are detected in 24% of those referred to thrombophilia testing.

History
German physician Rudolf Virchow categorized abnormalities in the consistency of the blood as a factor in the development of thrombosis in 1856. The exact nature of these abnormalities remained elusive until the first form of thrombophilia, antithrombin deficiency, was recognized in 1965 by the Norwegian hematologist Olav Egeberg </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 Monorchism 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 Tophus 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 Juvenile nephronophthisis 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 Antiphospholipid syndrome and explain in detail? [/INST] Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease. The diagnostic criteria require one clinical event (i.e. thrombosis or pregnancy complication) and two positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, or anti-cardiolipin antibodies.Antiphospholipid syndrome can be primary or secondary. Primary antiphospholipid syndrome occurs in the absence of any other related disease. Secondary antiphospholipid syndrome occurs with other autoimmune diseases, such as systemic lupus erythematosus. In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "catastrophic antiphospholipid syndrome" (CAPS or Asherson syndrome) and is associated with a high risk of death.
Antiphospholipid syndrome often requires treatment with anticoagulant medication such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin (brand name Coumadin) is not used during pregnancy because it can cross the placenta, unlike heparin, and is teratogenic.

Signs and symptoms
The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS).
Antiphospholipid syndrome can cause arterial or venous blood clots, in any organ system, or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke. In pregnant person affected by APS, there is an increased risk of recurrent miscarriage, intrauterine growth restriction, and preterm birth. A frequent cause of such complications is placental infarctions.
In some cases, APS seems to be the leading cause of intellectual and/or developmental disabilities in the newborn, due to an aPL-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome is responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.Other common findings, although not part of the APS classification criteria, are low platelet count, heart valve disease, and livedo reticularis. There are also associations between antiphospholipid antibodies and different neurologic manifestations including headache, migraine, epilepsy, and dementia. Some studies have shown the presence of antiphospholipid antibodies in the blood and spinal fluid of patients with psychological symptoms. Cancer is also observed to comorbid in patients with APS.

Risk factors
Risk factors for developing antiphospholipid syndrome include:

Genetic Markers: HLA-DR4, HLA-DR7, and HLA-DRw53
Race: Blacks, Hispanics, Asians, and Native Americans

Pathogenesis
Antiphospholipid syndrome is an autoimmune disease, in which "antiphospholipid antibodies" (anticardiolipin antibodies and lupus anticoagulant) react against proteins that bind to anionic phospholipids on plasma membranes. Like many autoimmune diseases, it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid antibodies (those that arise as a result of the autoimmune process) are associated with thrombosis and vascular disease.  The syndrome can be divided into primary (no underlying disease state) and secondary (in association with an underlying disease state) forms.Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH. ApoH inhibits protein C, a glycoprotein with important regulatory function of coagulation (inactivates Factor Va and Factor VIIIa). Lupus anticoagulant antibodies bind to prothrombin, thus increasing its cleavage to thrombin, its active form.In APS there are also antibodies binding to protein S, which is a co-factor of protein C. Thus, anti-protein S antibodies decrease protein C efficiency.Annexin A5 forms a shield around negatively charged phospholipid molecules, thus reducing their availability for coagulation. Thus, anti-annexin A5 antibodies increase phospholipid-dependent coagulation steps.The lupus anticoagulant antibodies are those that show the closest association with thrombosis; those that target β2glycoprotein 1 have a greater association with thrombosis than those that target prothrombin.
Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (over 40 GPLU or MPLU).
Patients with both lupus anticoagulant antibodies and moderate or high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone.The increased risks of recurrent miscarriage, intrauterine growth restriction and preterm birth by antiphospholipid antibodies, as supported by in vitro studies, include decreased trophoblast viability, syncytialization and invasion, deranged production of hormones and signalling molecules by trophoblasts, as well as activation of coagulation and complement pathways.

Diagnosis
Antiphospholipid syndrome is diagnosed using either liquid-phase coagulation assays to detect lupus anticoagulant or solid phase ELISA (enzyme-linked immunosorbent assay) to detect anti-cardiolipin antibodies or anti-apolipoprotein antibodies.Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some patients with APS. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus, genetic thrombophilia screening can consist of:
Screening for factor V Leiden variant and the prothrombin G20210A and MTHFR mutations.
Measuring serum levels of protein C, free and total protein S, factor VIII, antithrombin, plasminogen, tissue plasminogen activator and plasminogen activator inhibitor-1.Antiphospholipid antibodies do not recognize isolated cardiolipin, but bind to a cardiolipin-β2GPI (apolipoprotein H) complex.  The use of testing for antibodies specific for individual targets of aPL such as β2 glycoprotein 1 and phosphatidylserine is currently under debate.

Lupus anticoagulant
This is tested for by using a minimum of two coagulation tests that are phospholipid-sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged partial thromboplastin time (PTT) that does not correct in an 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The PTT (plus 80:20 mix), dilute Russells viper venom time, kaolin clotting time, dilute thromboplastin time, silica clotting time and prothrombin time (using a lupus-sensitive thromboplastin) are the principal tests used for the detection of lupus anticoagulant. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion, demonstrating persistent positivity, to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc.) being diagnosed as positive.Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: factor VIII) is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody.
The lupus anticoagulant will inhibit all the contact activation pathway factors (factor VIII, factor IX, factor XI and factor XII). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) whereas a specific factor antibody will rarely give a result higher than 10 iu/dl (10%).
Monitoring IV anticoagulant therapy by the PTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of factor Xa by antithrombin in the presence of heparin.

Anticardiolipin antibodies
Anti-cardiolipin antibodies can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which screens for the presence of β2glycoprotein 1 dependent anticardiolipin antibodies. A low platelet count and positivity for antibodies against β2-glycoprotein 1 or phosphatidylserine may also be observed in a positive diagnosis.

Criteria
Classification with APS requires evidence of both one or more specific, documented clinical events (either a vascular thrombosis and/or adverse obstetric event) and the confirmed presence of a repeated aPL. The Sapporo APS classification criteria (1998, published in 1999) were replaced by the Sydney criteria in 2006. Based on the most recent criteria, classification with APS requires one clinical and one laboratory manifestation:
Clinical:A documented episode of arterial, venous, or small vessel thrombosis — other than superficial venous thrombosis — in any tissue or organ by objective validated criteria with no significant evidence of inflammation in the vessel wall
1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or direct examination of the fetus) at or beyond the 10th week of gestation and/or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded or at least 1 premature birth of a morphologically normal neonate before the 34th week of gestation due to eclampsia or severe pre-eclampsia according to standard definitions, or recognized features of placental insufficiency
Laboratory:Anti-cardiolipin IgG and/or IgM measured by standardized, non-cofactor dependent ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (i.e., > 40 GPL or MPL, or > the 99th percentile)
Anti-β2 glycoprotein I IgG and/or IgM measured by standardized ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (> the 99th percentile)
Lupus anticoagulant detected on 2 occasions not less than 12 weeks apart according to the guidelines of the International Society of Thrombosis and Hemostasis.There are 3 distinct APS disease entities: primary (the absence of any comorbidity), secondary (when there is a pre-existing autoimmune condition, most frequently systemic lupus erythematosus, SLE), and catastrophic (when there is simultaneous multi-organ failure with small vessel occlusion).According to a 2006 consensus statement, it is advisable to classify APS into one of the following categories for research purposes:

I: more than one laboratory criterion present in any combination;
IIa: lupus anticoagulant present alone
IIb: anti-cardiolipin IgG and/or IgM present alone in medium or high titers
IIc: anti-β2 glycoprotein I IgG and/or IgM present alone in a titer greater than 99th percentileThe International Consensus Statement is commonly used for Catastrophic APS diagnosis. Based on this statement, Definite CAPS diagnosis requires:

a) Vascular thrombosis in three or more organs or tissues and
b) Development of manifestations simultaneously or in less than a week and
c) Evidence of small vessel thrombosis in at least one organ or tissue and
d) Laboratory confirmation of the presence of aPL.VDRL, which detects antibodies against syphilis, may have a false positive result in aPL-positive patients (aPL bind to the lipids in the test and make it come out positive), although the more specific test for syphilis, FTA-Abs, that use recombinant antigens will not have a false-positive result.

Treatment
In people without symptoms, no treatment is required. In people with antiphospholipid antibody-associated thrombosis, anticoagulants such as warfarin are used to prevent further thrombosis. If warfarin is used, the INR is kept between 2.0 and 3.0. Direct-acting oral anticoagulants may be used as an alternative to warfarin, but not in people who are "triple positive" with all types of antiphospholipid antibody (lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein I antibody).Anticoagulation appears to prevent miscarriage in pregnant people. In pregnancy, low molecular weight heparin and low-dose aspirin are used instead of warfarin because of warfarins teratogenicity. People with recurrent miscarriages are often advised to take aspirin and to start low molecular weight heparin treatment after missing a menstrual cycle. In refractory cases plasmapheresis may be used.

Prognosis
The long-term prognosis for APS is determined mainly by recurrent thrombosis, which may occur in up to 29% of patients, sometimes despite antithrombotic therapy.

History
Antiphospholipid syndrome was described in full in the 1980s, by E. Nigel Harris and Aziz Gharavi. They published the first papers in 1983. The syndrome was referred to as "Hughes syndrome" among colleagues after the rheumatologist Graham R.V. Hughes (St. Thomas Hospital, London, UK), who brought together the team.

Research
APS ACTION (the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking), is the first-ever international research network that has been created to design and conduct large-scale, multicenter clinical trials in persistently antiphospholipid antibody (aPL) positive patients. The network consists of a multidisciplinary group of physicians and investigators from around the world who are interested in antiphospholipid syndrome (APS) research. The primary mission of APS ACTION is to prevent, treat, and cure antiphospholipid antibody (aPL) associated clinical manifestations through high quality, multicenter, and multidisciplinary clinical research.

References
Bibliography
Triona Holden (2003). Positive Options for Antiphospholipid Syndrome (APS): Self-Help and Treatment </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 Pyometra and explain in detail? [/INST] Pyometra or pyometritis is a uterine infection. Though it is most commonly known as a disease of the unaltered female dog, it is also a notable human disease. It is also seen in female cattle, horses, goats, sheep, swine, cats, rabbits, hamsters, ferrets, rats and guinea pigs. Pyometra is an important disease to be aware of for any dog or cat owner because of the sudden nature of the disease and the deadly consequences if left untreated.  It has been compared to acute appendicitis in humans, because both are essentially empyemas within an abdominal organ.

Signs and symptoms
The most obvious symptom of open pyometra is a discharge of pus from the vulva in a female that has recently been in heat.  However, symptoms of closed pyometra are less obvious.  Symptoms of both types include vomiting, loss of appetite, depression, and increased drinking and urinating.  Fever is seen in less than a third of female dogs with pyometra.  Closed pyometra is a more serious condition than open pyometra not only because there is no outlet for the infection, but also because a diagnosis of closed pyometra can easily be missed due to its insidious nature.  Bloodwork may show dehydration and/or increased white blood cell count. X-rays will show an enlarged uterus, and ultrasound will confirm the presence of a fluid filled uterus.

Cause
The risk of developing pyometra differs between dog breeds. Pyometra is a result of hormonal and structural changes in the uterus lining.  This can happen at any age, whether she has bred or not, and whether it is her 1st or 10th heat, although it becomes more common as the dog gets older.  The main risk period for a female is for eight weeks after her peak standing heat has ended. Normally during this period, the cervix, which was open during her heat, begins to close, and the inner lining begins to adapt back to normal.  However, cystic hyperplasia of the endometrium (inner lining of the uterus) –  known as cystic endometrial hyperplasia (CEH) – may occur at this time for some animals, as an inappropriate response to progesterone.
Under these circumstances, bacteria (especially E. coli) that have migrated from the vagina into the uterus find the environment favorable to growth, especially since progesterone also causes mucus secretion, closes the cervix (preventing uterine drainage), and decreases uterine contractility.  The condition of the cervix is a major factor in the severity of the condition.

If the cervix is open, the infected material can leave the body, and this is far easier and safer to treat.  This is known as open pyometra.
If the cervix is fully closed, there is no discharge from the vulva, and like in appendicitis, the uterus may rupture and pus escapes into the abdomen, causing peritonitis and possible rapid death </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 Distichia and explain in detail? [/INST] A distichia is an eyelash that arises from an abnormal part of the eyelid </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 Smith–Magenis syndrome and explain in detail? [/INST] Smith–Magenis Syndrome (SMS), also known as 17p- syndrome, is a microdeletion syndrome characterized by an abnormality in the short (p) arm of chromosome 17. It has features including intellectual disability, facial abnormalities, difficulty sleeping, and numerous behavioral problems such as self-harm. Smith–Magenis syndrome affects an estimated between 1 in 15,000 to 1 in 25,000 individuals.

Signs and symptoms
Facial features of children with Smith–Magenis syndrome include a broad and square face, deep-set eyes, large cheeks, and a prominent jaw, as well as a flat nose bridge (in the young child; as the child ages it becomes more ski-jump shaped). Eyes tend to be deep-set, close together and upwards-slanted.  Eyebrows are heavy with lateral extension. The mouth is the most noticeable feature; both upper and lower lips are full, and the mouth is wide.  The mouth curves downwards and the upper lip curves outwards, due to a fleshy philtrum. These facial features become more noticeable as the individual ages, as Mandible growth outstrips that of the maxilla leading to a clear midface hypoplasia. There is also a mild brachycephaly.Disrupted sleep patterns are characteristic of Smith–Magenis syndrome, typically beginning early in life. Affected individuals may be very sleepy during the day, but have trouble falling asleep and awaken several times each night, due to an inverted circadian rhythm of melatonin.People with Smith–Magenis syndrome have engaging personalities, but all also have a lot of behavioral problems. These behavioral problems include frequent temper tantrums, meltdowns and outbursts, aggression, anger, fidgeting, compulsive behavior, anxiety, impulsiveness, and difficulty paying attention. Self-harm, including biting, hitting, head banging, and skin picking, is very common. Behavioral complications in Smith-Magenis syndrome are thought to be worsened by issues with sleeping.  Repetitive self-hugging is a behavioral trait that may be unique to Smith–Magenis syndrome. People with this condition may also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"), as well as possessing an impressive ability to recall a wide range of small details about people or subject-specific trivia.Other symptoms can include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia), strabismus, and other problems with vision. Heart and kidney defects also have been reported in people with Smith–Magenis syndrome, though they are less common.

Genetics
Smith–Magenis syndrome is a chromosomal condition related to low copy repeats of specific segments of chromosome 17. Most people with SMS have a deletion of genetic material from a specific region of chromosome 17 (17p11.2). Although this region contains multiple genes, recently researchers discovered that the loss of one particular gene the retinoic acid induced 1 or RAI1 is responsible for most of the characteristic features of this condition. Also, other genes within the chromosome 17 contribute to the variability and severity of the clinical features.  The loss of other genes in the deleted region may help explain why the features of Smith–Magenis syndrome vary among affected individuals. A small percentage of people with Smith–Magenis syndrome have a mutation in the RAI1 gene instead of a chromosomal deletion.
These deletions and mutations lead to the production of an abnormal or nonfunctional version of the RAI1 protein. RAI1 is a transcription factor that regulates the expression of multiple genes, including several that are involved in controlling circadian rhythm, such as CLOCK.   The groups led by James Lupski (Baylor College of Medicine) and Sarah Elsea (Virginia Commonwealth University) are in the process of studying the exact function of this gene in relation to Smith Magenis Syndrome.SMS is typically not inherited. This condition usually results from a genetic change that occurs during the formation of reproductive cells (eggs or sperm) or in early fetal development. People with Smith–Magenis syndrome most often have no history of the condition in their family.

Diagnosis
SMS is usually confirmed by blood tests called chromosome (cytogenetic) analysis and utilize a technique called FISH (fluorescent in situ hybridization). The characteristic  micro-deletion was sometimes overlooked in a standard FISH test, leading to a number of people with the symptoms of SMS with negative results.
The recent development of the FISH for 17p11.2 deletion test has allowed more accurate detection of this deletion </s>