<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Uremia and can you explain it in depth? [/INST] Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess of amino acid and protein metabolism end products, such as urea and creatinine, in the blood that would be normally excreted in the urine. Uremic syndrome can be defined as the terminal clinical manifestation of kidney failure (also called renal failure). It is the signs, symptoms and results from laboratory tests which result from inadequate excretory, regulatory, and endocrine function of the kidneys. Both uremia and uremic syndrome have been used interchangeably to denote a very high plasma urea concentration that is the result of renal failure. The former denotation will be used for the rest of the article.
Azotemia is a similar, less severe condition with high levels of urea, where the abnormality can be measured chemically but is not yet so severe as to produce symptoms. Uremia describes the pathological and symptomatic manifestations of severe azotemia.There is no specific time for the onset of uremia for people with progressive loss of kidney function. People with kidney function below 50% (i.e. a glomerular filtration rate [GFR] between 50 and 60 mL/min) and over 30 years of age may have uremia to a degree. This means an estimated 8 million people in the United States with a GFR of less than 60 mL/min have uremic symptoms.  The symptoms, such as fatigue, can be very vague, making the diagnosis of impaired kidney function difficult. Treatment can be by dialysis or a kidney transplant, though some patients choose to pursue symptom control and conservative care instead.

Signs and symptoms
Classical signs of uremia are: progressive weakness and easy fatigue, loss of appetite due to nausea and vomiting, muscle atrophy, tremors, abnormal mental function, frequent shallow respiration, and metabolic acidosis. Without intervention via dialysis or kidney transplant, uremia due to renal failure will progress and cause stupor, coma, and death. Because uremia is mostly a consequence of kidney failure, its signs and symptoms often occur concomitantly with other signs and symptoms of kidney failure.
Glomerular filtration rate (GFR) measures the amount of plasma in millilitres being filtered through the kidneys each minute. As the GFR decreases, the prognosis worsens. Some of the effects can be reversed, albeit temporarily, with dialysis.

Residual syndrome
People on dialysis acquire what is known as "residual syndrome".  Residual syndrome is a non-life-threatening disease which is displayed as toxic effects causing many of the same signs and symptoms that uremia displays. There are several hypotheses why residual syndrome is present. They are:  the accumulation of large molecular weight solutes that are poorly dialyzed (e.g. β2-microglobulin); the accumulation of protein-bound small molecular weight solutes that are poorly dialyzed (e.g. p-cresyl sulfate and indoxyl sulfate); the accumulation of dialyzable solutes that are incompletely removed (e.g. sequestered solutes like phosphate in cells or insufficient elimination of other more toxic solutes); indirect phenomena such as carbamylation of proteins, tissue calcification, or a toxic effect of hormone imbalance (e.g. parathyroid hormone) and; the toxic effects of dialysis itself (e.g. removal of unknown important vitamins or minerals). Dialysis increases life span but patients may have more limited function. They have physical limitations which include impairment of balance, walking speed, and sensory functions. They also have cognitive impairments such as impairment in attention, memory, and performance of higher-order tasks. Patients have been maintained longer than three decades on dialysis, but average mortality rates and hospitalizations are high. Also, patient rehabilitation and quality of life is poor.

Causes
Conditions causing increased blood urea fall into three different categories: prerenal, renal, and postrenal.Prerenal azotemia can be caused by decreased blood flow through the kidneys (e.g. low blood pressure, congestive heart failure, shock, bleeding, dehydration) or by increased production of urea in the liver via a high protein diet or increased protein catabolism (e.g. stress, fever, major illness, corticosteroid therapy, or gastrointestinal bleeding).Renal causes can be attributed to decreased kidney function. These include acute and chronic kidney failure, acute and chronic glomerulonephritis, tubular necrosis, and other kidney diseases.Postrenal causes can be due to decreased elimination of urea. These could be due to urinary outflow obstruction such as by calculi, tumours of the bladder or prostate, or a severe infection.

Diagnosis
A detailed and accurate history and physical examination will help determine if uremia is acute or chronic.  In the cases of acute uremia, causes may be identified and eliminated, leading to a higher chance for recovery of normal kidney function, if treated correctly.

Blood tests
Primary tests performed for the diagnosis of uremia are basic metabolic panel with serum calcium and phosphorus to evaluate the GFR, blood urea nitrogen and creatinine as well as serum potassium, phosphate, calcium and sodium levels. Principal abnormality is very low GFR (<30 mL/min).  Uremia will demonstrate elevation of both urea and creatinine, likely elevated potassium, high phosphate and normal or slightly high sodium, as well as likely depressed calcium levels.  As a basic work up a physician will also evaluate for anemia, and thyroid and parathyroid functions.  Chronic anemia may be an ominous sign of established renal failure.  The thyroid and parathyroid panels will help work up any symptoms of fatigue, as well as determine calcium abnormalities as they relate to uremia versus longstanding or unrelated illness of calcium metabolism.

Urine tests
A 24-hour urine collection for determination of creatinine clearance may be an alternative, although not a very accurate test due to the collection procedure. Another laboratory test that should be considered is urinalysis with microscopic examination for the presence of protein, casts, blood and pH.

Radioisotope tests
The most trusted test for determining GFR is iothalamate clearance. However, it may be cost-prohibitive and time-consuming.  Clinical laboratories generally calculate the GFR with the modification of diet in renal disease (MDRD) formula or the  Cockcroft-Gault formula.

Other
In addition, coagulation studies may indicate prolonged bleeding time with otherwise normal values.

Mechanism
Uremia results in many different compounds being retained by the body. With the failure of the kidneys, these compounds can build up to dangerous levels. There are more than 90 different compounds that have been identified. Some of these compounds can be toxic to the body.

Uremic toxins
Uremic toxins are any biologically active compounds that are retained due to kidney impairment. Many uremic salts can also be uremic toxins.Urea was one of the first metabolites identified. Its removal is directly related to patient survival but its effect on the body is not yet clear. Still, it is not certain that the symptoms currently associated with uremia are actually caused by excess urea, as one study showed that uremic symptoms were relieved by initiation of dialysis, even when urea was added to the dialysate to maintain the blood urea nitrogen level at approximately 90 mg per deciliter (that is, approximately 32 mmol per liter). Urea could be the precursor of more toxic molecules but it is more likely that damage done to the body is from a combination of different compounds which may act as enzyme inhibitors or derange membrane transport. Indoxyl sulfate is one of the better characterized uremic toxins. Indoxyl sulfate has been shown to aggravate vascular inflammation in atherosclerosis by modulating macrophage behavior.

Biochemical characteristics
Many regulatory functions of the body are affected. Regulation of body fluids, salt retention, acid and nitrogenous metabolite excretion are all impaired and can fluctuate widely. Body fluid regulation is impaired due to a failure to excrete fluids, or due to fluid loss from vomiting or diarrhea. Regulation of salt is impaired when salt intake is low or the vascular volume is inadequate. Acid excretion and nitrogenous metabolite excretion are impaired with the loss of kidney function.

History
Urea was crystallized and identified between 1797 and 1808. Urea was hypothesized to be the source of urinary ammonia during this time and was confirmed in 1817. It was hypothesized that excess urea may lead to specific disorders. Later in 1821, it was confirmed that the body did produce urea and that it was excreted by the kidneys. In 1827, urea was first synthesized in the lab, confirming the composition of urea and making it the first biological substance synthesized. In 1856, urea was produced in vitro via oxidation of proteins. It was in 1827 that Henri Dutrochet seeded the idea of dialysis with the discovery of separating smaller molecules from larger molecules through a semipermeable membrane. It was in 1829 and 1831 when convincing proof was obtained that in certain patients, blood urea was elevated. They also suggested that harm may be caused by this. Later research suggested that major neurological disorders like coma and convulsions did not correlate with physical findings which included generalized edema of the brain. This suggested that uremia was a form of blood poisoning. In 1851, E.T. Frerich described clinical uremic syndrome and suggested that a toxicity was the mechanism of its cause. It was in 1856 that J. Picard developed a sensitive method to reproducibly measure blood urea. He was able to detect a 40% decrease of urea concentration between the renal artery and the renal vein. This work solidified the fact that renal failure coincided with an increase in blood urea. It was J. Picard with E.T. Frerichs work that made the term uremia popular.

Oral manifestations
Oral symptoms of uremia can be found in up to 90% of renal patients. The patients may present with ammonia-like taste and smell in mouth, stomatitis, gingivitis, decreased salivary flow, xerostomia and parotitis.One of the early symptoms of renal failure is uremic fetor. It is an ammonia odour in the mouth caused by the high concentration of urea in the saliva which subsequently breaks down to ammonia. As the blood urea nitrogen (BUN) level increases, patient might develop uremic stomatitis. Uremic stomatitis appears as a pseudo membrane or the frank ulcerations with redness and a pultaceous coat in the mouth. These lesions could be related to high BUN level >150 mg/dl and disappear spontaneously when the BUN level is reduced with medical treatment. It is believed to be caused by loss of tissue resistance and failure to withstand traumatic influences. Besides that, the patient may develop a rare manifestation which is uremic frost. It is a white plaque found on the skin or in the mouth, it is caused by residual urea crystals left on the epithelial surface after perspiration and saliva evaporation or as a result of reduced salivary flow. Xerostomia is a common oral finding, it results from a combination of direct involvement of salivary glands, chemical inflammation, dehydration and mouth breathing. It may be due to restricted fluid intake, adverse effect of drug therapy or low salivary rate. Salivary swelling can be seen sometimes.In patients with renal disease, pallor of the oral mucosa can sometimes be noticed due to anaemia caused by reduction of erythropoietin. Uraemia can lead to alteration of platelet aggregation. This situation, combined with the use of heparin and other anticoagulants in haemodialysis, causes the patients to become predisposed to ecchymosis, petechiae, and haemorrhages in the oral cavity. It can also lead to mucositis and glossitis which can bring about pain and inflammation of the tongue and oral mucosa. In addition, patients might also experience altered taste sensations, dysgeusia, and be predisposed to bacterial and candidiasis infections. Candidiasis is more frequent in renal transplant patients because of generalized immunosuppression.In children with renal disease, enamel hypoplasia of the primary and permanent dentition has been observed. The abnormalities of dental development correlate with the age at which metabolic disturbances occur. For example, enamel hypoplasia in the form of white or brown discoloration of primary teeth is commonly seen in young children with early-onset renal disease. Poor oral hygiene, a carbohydrate-rich diet, disease-related debilitation, hypoplastic enamel, low salivary flow rate and long-term medication contribute to increased risk of caries formation. However, the patients usually have low caries activity, particularly in children. This is due to the presence of highly buffered and alkaline saliva caused by the high concentration of urea nitrogen and phosphate in saliva. The salivary pH will usually be above the critical pH level for demineralization of the enamel to occur and this helps to prevent the formation of caries. Besides that, pulpal narrowing and calcifications is a frequent finding in patients with renal disease. For patients who are on dialysis, the nausea and vomiting resulting from dialysis treatment may lead to severe tooth erosion.

Dental considerations
When treating patients with renal insufficiency, a dentist should collect a complete medical history, with particular attention to ESRD-related illnesses, drugs with prescribed dosages, blood parameters, timing, and type of dialysis performed. These aspects can be directly discussed with the nephrologist when necessary. Any alterations in drugs or other aspects of treatment must be previously agreed upon by the nephrologist.Dental examination for such patients consists of a non-invasive complete assessment of dental, periodontal, and mucosal tissues, with radiographs to aid with the diagnostic process. All potential foci of infection should be intercepted; these include periodontal and endodontic lesions, residual roots, partially erupted and malpositioned third molars, peri-implantitis, and mucosal lesions. When periodontitis is suspected, a periodontal chart should be recorded. Orthodontic appliances can be maintained if they do not interfere with oral hygiene.Uremia is commonly seen in patients who undergo dialysis due to renal insufficiency. For hemodialysis patients, it is important to determine the treatment schedule. Dental treatment should be started on the day after hemodialysis due to several reasons: there is no accumulation of uremic toxins in the blood, and circulating heparin is absent. Treatment should not commence on the same day as hemodialysis as patients usually feel unwell and their blood is heparinized, which might cause excessive bleeding. For patients undergoing peritoneal dialysis, there are no contraindications to dental treatment except in cases of acute peritoneal infections, where elective procedure should be deferred.Special care should be taken when positioning the patient, avoiding compression of the arm with the vascular access for hemodialysis. Any injections or blood pressure measurement should not be performed on an arm with an arteriovenous (AV) fistula. If the AV site is located on a leg, the patient should avoid sitting for lengthy periods, as venous drainage may be obstructed. During long dental procedures, the dentist should allow patients with AV sites on their legs to take a brief walk or stand for a while every hour.Hemostatic aids should be instituted in cases of excessive bleeding, which is commonly seen in uremia and renal failure. To manage postoperative bleeding, primary closure techniques and local hemostatic agents should be used routinely. To reduce bleeding during and after a procedure, tranexamic acid, both as a rinse or administered orally, can be used.Patients undergoing dialysis are exposed to numerous transfusions and renal failure-related immunosuppression; thus, they are at greater risks of infection by human immunodeficiency virus (HIV) and hepatitis types B and C </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hereditary motor and sensory neuropathy and can you explain it in depth? [/INST] Hereditary motor and sensory neuropathies (HMSN) is a name sometimes given to a group of different neuropathies which are all characterized by their impact upon both afferent and efferent neural communication. HMSN are characterised by atypical neural development and degradation of neural tissue. The two common forms of HMSN are either hypertrophic demyelinated nerves or complete atrophy of neural tissue. Hypertrophic condition causes neural stiffness and a demyelination of nerves in the peripheral nervous system, and atrophy causes the breakdown of axons and neural cell bodies. In these disorders, a patient experiences progressive muscle atrophy and sensory neuropathy of the extremities.The term "hereditary motor and sensory neuropathy" was used mostly historically to denote the more common forms Charcot–Marie–Tooth disease (CMT). With the identification of a wide number of genetically and phenotypically distinct forms of CMT, the term HMSN is now used less frequently.

Symptoms and signs
Neuropathy disorders usually have onset in childhood or young adulthood. Motor symptoms seem to be more predominant than sensory symptoms. Symptoms of these disorders include: fatigue, pain, lack of balance, lack of feeling, lack of reflexes, and lack of sight and hearing, which result from muscle atrophy. Patients can also have high arched feet, hammer toes, foot drop, foot deformities, and scoliosis. These symptoms are a result of severe muscular weakness and atrophy. In patients with demyelinating neuropathy, symptoms are due to slow nerve conduction velocities; however people with axonal degradation have average-to-normal nerve conduction velocities.

Causes
All hereditary motor and sensory neuropathies are inherited. Chromosomes 17 and 1 seem to be the most common chromosomes with mutations. The disease can be inherited in an autosomal dominant, autosomal recessive or X-linked manner.

Diagnosis
Patients with hereditary motor and sensory neuropathies are diagnosed through a physical evaluation that looks for muscle atrophy, weakness, and sensory responses. In addition to this, electromyography and motor nerve conduction tests can help clinicians decide what type of motor and sensory neuropathy it is and how severe the disease is. Final confirmation can come through genetic testing.

Classification
Charcot–Marie–Tooth disease was first described in 1886 by Jean-Martin Charcot, Pierre Marie, and independently Howard Henry Tooth. In the 1950s, further classification occurred and separated patients into two distinct groups. Group one was characterized by slow nerve conduction velocities and demyelinating neuropathy. Group two was characterized by mostly normal nerve conduction velocities and degeneration of axons. In 1968, HMSN were classified again into seven groups:

Treatment
There is currently no known pharmacological treatment to hereditary motor and sensory neuropathy. However, the majority of people with these diseases are able to walk and be self-sufficient. Some methods of relief for the disease include physical therapy, stretching, braces, and sometimes orthopedic surgery. Since foot disorders are common with neuropathy, precautions must be taken to strengthen these muscles and use preventative care and physical therapy to prevent injury and deformities.

Prognosis
Hereditary motor and sensory neuropathy are relatively common and are often inherited with other neuromuscular conditions, and these comorbidities cause an accelerated progression of the disease.Most forms of HMSN affect males earlier and more severely than females, but others show no predilection to either sex. HMSN affects all ethnic groups, with the most common forms having no racial predilection, but other recessively inherited forms tending to impact specific ethnic groups </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Osteoma cutis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Otospondylomegaepiphyseal dysplasia and can you explain it in depth? [/INST] Otospondylomegaepiphyseal dysplasia (OSMED) is an autosomal recessive disorder of bone growth that results in skeletal abnormalities, severe hearing loss, and distinctive facial features. The name of the condition indicates that it affects hearing (oto-) and the bones of the spine (spondylo-), and enlarges the ends of bones (megaepiphyses).
The features of OSMED are similar to those of another skeletal disorder, Weissenbacher-Zweymüller syndrome. Otospondylomegaepiphyseal dysplasia is a subtype of collagenopathy, types II and XI.

Pathophysiology
Mutations in the COL11A2 gene cause otospondylomegaepiphyseal dysplasia. The protein made by the COL11A2 gene is involved in the production of type XI collagen. This type of collagen is important for the normal development of bone and other connective tissues. Mutations in the COL11A2 gene lead to a loss of function of this type of collagen, resulting in the signs and symptoms of OSMED.
OSMED is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - must be inherited for a person to be affected by the disorder. The parents of a child with an autosomal recessive disorder are usually not affected but are carriers of one copy of the altered gene. A recessive pattern of inheritance makes OSMED unique among the type II and type XI collagenopathies.

Diagnosis
The distinctive characteristics of OSMED include severe bone and joint problems and very severe hearing loss. This disorder affects the epiphyses, the parts of the bone where growth occurs. People with the condition are often shorter than average because the bones in their arms and legs are unusually short. Other skeletal signs include enlarged joints, short hands and fingers, and flat bones of the spine (vertebrae). People with the disorder often experience back and joint pain, limited joint movement, and arthritis that begins early in life. Severe high-tone hearing loss is common. Typical facial features include protruding eyes; a sunken nasal bridge; an upturned nose with a large, rounded tip; and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth, which is called a cleft palate.

Treatment
Treatment is symptomatic only, involving closure of the cleft palate, audiometry and adapted management of the hearing loss, and treatment of the joint pain.

Epidemiology
The frequency of this disorder is unknown, but it is very rare. Only a few families with the condition have been reported.

References
Melkoniemi M, Brunner HG, Manouvrier S, Hennekam R, Superti-Furga A, Kaariainen H, Pauli RM, van Essen T, Warman ML, Bonaventure J, Miny P, Ala-Kokko L (2000). "Autosomal recessive disorder otospondylomegaepiphyseal dysplasia is associated with loss-of-function mutations in the COL11A2 gene". Am J Hum Genet. 66 (2): 368–77 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Brainstem death and can you explain it in depth? [/INST] Brainstem death is a clinical syndrome defined by the absence of reflexes with pathways through the brainstem – the "stalk" of the brain, which connects the spinal cord to the mid-brain, cerebellum and cerebral hemispheres – in a deeply comatose, ventilator-dependent patient.
Identification of this state carries a very grave prognosis for survival; cessation of heartbeat often occurs within a few days, although it may continue for weeks if intensive support is maintained.In the United Kingdom, death can be certified on the basis of a formal diagnosis of brainstem death, so long as this is done in accordance with a procedure established in "A Code of Practice for the Diagnosis and Confirmation of Death", published in 2008 by the Academy of Medical Royal Colleges. The premise of this is that a person is dead when consciousness and the ability to breathe are permanently lost, regardless of continuing life in the body and parts of the brain, and that death of the brainstem alone is sufficient to produce this state.This concept of brainstem death is also accepted as grounds for pronouncing death for legal purposes in India and Trinidad & Tobago. Elsewhere in the world, the concept upon which the certification of death on neurological grounds is based is that of permanent cessation of all function in all parts of the brain – whole brain death – with which the British concept should not be confused. The United States Presidents Council on Bioethics made it clear, for example, in its White Paper of December 2008, that the British concept and clinical criteria are not considered sufficient for the diagnosis of death in the United States.

Evolution of diagnostic criteria
The United Kingdom (UK) criteria were first published by the Conference of Medical Royal Colleges (with advice from the Transplant Advisory Panel) in 1976, as prognostic guidelines. They were drafted in response to a perceived need for guidance in the management of deeply comatose patients with severe brain damage who were being kept alive by mechanical ventilators but showing no signs of recovery. The Conference sought "to establish diagnostic criteria of such rigour that on their fulfilment the mechanical ventilator can be switched off, in the secure knowledge that there is no possible chance of recovery". The published criteria – negative responses to bedside tests of some reflexes with pathways through the brainstem and a specified challenge to the brainstem respiratory centre, with caveats about exclusion of endocrine influences, metabolic factors and drug effects – were held to be "sufficient to distinguish between those patients who retain the functional capacity to have a chance of even partial recovery and those where no such possibility exists". Recognition of that state required the withdrawal of further artificial support so that death is allowed to occur, thus "sparing relatives from the further emotional trauma of sterile hope".In 1979, the Conference of Medical Royal Colleges promulgated its conclusion that identification of the state defined by those same criteria – then thought sufficient for a diagnosis of brain death – "means that the patient is dead". Death certification on those criteria has continued in the United Kingdom (where there is no statutory legal definition of death) since that time, particularly for organ transplantation purposes, although the conceptual basis for that use has changed.
In 1995, after a review by a Working Group of the Royal College of Physicians of London, the Conference of Medical Royal Colleges formally adopted the "more correct" term for the syndrome, "brainstem death" – championed by Pallis in a set of 1982 articles in the British Medical Journal – and advanced a new definition of human death as the basis for equating this syndrome with the death of the person. The suggested new definition of death was the "irreversible loss of the capacity for consciousness, combined with irreversible loss of the capacity to breathe". It was stated that the irreversible cessation of brainstem function will produce this state and "therefore brainstem death is equivalent to the death of the individual".

Diagnosis
In the UK, the formal rules for the diagnosis of brainstem death have undergone only minor modifications since they were first published in 1976. The most recent revision of the UKs Department of Health Code of Practice governing use of that procedure for the diagnosis of death reaffirms the preconditions for its consideration. These are:

There should be no doubt that the patients condition – deeply comatose, unresponsive and requiring artificial ventilation – is due to irreversible brain damage of known cause.
There should be no evidence that this state is due to depressant drugs.
Primary hypothermia as the cause of unconsciousness must have been excluded, and
Potentially reversible circulatory, metabolic and endocrine disturbances likewise.
Potentially reversible causes of apnoea (dependence on the ventilator), such as muscle relaxants and cervical cord injury, must be excluded.With these pre-conditions satisfied, the definitive criteria are:

Fixed pupils which do not respond to sharp changes in the intensity of incident light.
No corneal reflex.
Absent oculovestibular reflexes – no eye movements following the slow injection of at least 50ml of ice-cold water into each ear in turn (the caloric reflex test).
No response to supraorbital pressure.
No cough reflex to bronchial stimulation or gagging response to pharyngeal stimulation.
No observed respiratory effort in response to disconnection of the ventilator for long enough (typically 5 minutes) to ensure elevation of the arterial partial pressure of carbon dioxide to at least 6.0 kPa (6.5 kPa in patients with chronic carbon dioxide retention). Adequate oxygenation is ensured by pre-oxygenation and diffusion oxygenation during the disconnection (so the brainstem respiratory centre is not challenged by the ultimate, anoxic, drive stimulus). This test – the apnoea test – is dangerous, and may prove lethal.Two doctors, of specified status and experience, are required to act together to diagnose death on these criteria and the tests must be repeated after "a short period of time ... to allow return of the patients arterial blood gases and baseline parameters to the pre-test state". These criteria for the diagnosis of death are not applicable to infants below the age of two months.

Prognosis and management
With due regard for the cause of the coma, and the rapidity of its onset, testing for the purpose of diagnosing death on brainstem death grounds may be delayed beyond the stage where brainstem reflexes may be absent only temporarily – because the cerebral blood flow is inadequate to support synaptic function, although there is still sufficient blood flow to keep brain cells alive and capable of recovery. There has recently been renewed interest in the possibility of neuronal protection during this phase by use of moderate hypothermia and by correction of the neuroendocrine abnormalities commonly seen in this early stage.Published studies of patients meeting the criteria for brainstem death or whole brain death – the American standard which includes brainstem death diagnosed by similar means – record that even if ventilation is continued after diagnosis, the heart stops beating within only a few hours or days. However, there have been some very long-term survivals and it is noteworthy that expert management can maintain the bodily functions of pregnant brain dead women for long enough to bring them to term.

Criticism
The diagnostic criteria were originally published for the purpose of identifying a clinical state associated with a fatal prognosis (see above). The change of use, in the UK, to criteria for the diagnosis of death itself was protested immediately. The initial basis for the change of use was the claim that satisfaction of the criteria sufficed for the diagnosis of the death of the brain as a whole, despite the persistence of demonstrable activity in parts of the brain. In 1995, that claim was abandoned and the diagnosis of death (acceptable for legal purposes in the UK in the context of organ procurement for transplantation) by the specified testing of brainstem functions was based on a new definition of death – the permanent loss of the capacity for consciousness and spontaneous breathing. There are doubts that this concept is generally understood and accepted and that the specified testing is stringent enough to determine that state. It is, however, associated with substantial risk of exacerbating the brain damage and even causing the death of the apparently dying patient so tested (see "the apnoea test" above). This raises ethical problems which seem not to have been addressed.
It has been argued that sound scientific support is lacking for the claim that the specified purely bedside tests have the power to diagnose true and total death of the brainstem, the necessary condition for the assumption of permanent loss of the intrinsically untestable consciousness-arousal function of those elements of the reticular formation which lie within the brainstem (there are elements also within the higher brain). Knowledge of this arousal system is based upon the findings from animal experiments as illuminated by pathological studies in humans. The current neurological consensus is that the arousal of consciousness depends upon reticular components which reside in the midbrain, diencephalon and pons </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hermaphrodite and can you explain it in depth? [/INST] In reproductive biology, a hermaphrodite () is an organism that has both kinds of reproductive organs and can produce both gametes associated with male and female sexes.Many taxonomic groups of animals (mostly invertebrates) do not have separate sexes. In these groups, hermaphroditism is a normal condition, enabling a form of sexual reproduction in which either partner can act as the female or male. For example, the great majority of tunicates, pulmonate molluscs, opisthobranch, earthworms, and slugs are hermaphrodites. Hermaphroditism is also found in some fish species and to a lesser degree in other vertebrates. Most plants are also hermaphrodites. Animal species having different sexes, male and female, are called gonochoric, which is the opposite of hermaphrodite.There are also species where hermaphrodites exist alongside males (called androdioecy) or alongside females (called gynodioecy), or all three exist in the same  species (called trioecy); these three systems are sometimes called mixed breeding systems. In plants there are cases where male flowers and hermaphrodite flowers occur on the same plant (andromonoecy) or female flowers and hermaphrodite flowers on the same plant (gynomonoecy).The term hermaphrodite is commonly used for abnormal cases of dioecious animal species but according to geneticist Michael Majerus this definition should be distinguished from the scientific definition.In recent years the term hermaphrodite applied to humans has fallen out of favor since there have been no identified cases of a human reproducing as both male and female, with some biologists saying hermaphroditism does not occur in humans. Intersex activists have preferred the word intersex, since the word hermaphrodite is considered to be stigmatizing, as well as "scientifically specious and clinically problematic."There are no hermaphroditic species among mammals or birds. According to David B. Rivers there is controversy around hermaphroditism in insects with some experts believing it does not occur. Hermaphroditism is said to occur in one or two insect species.A rough estimate of the number of hermaphroditic animal species is 65,000. The percentage of animal species that are hermaphroditic is about 5% in all animal species, or 33% excluding insects. (Although the current estimated total number of animal species is about 7.7 million, the study, which estimated the number, 65,000, used an estimated total number of animal species, 1,211,577 from "Classification phylogénétique du vivant (Vol. 2)" - Lecointre and Le Guyader (2001)). Most hermaphroditic species exhibit some degree of self-fertilization. The distribution of self-fertilization rates among animals is similar to that of plants, suggesting that similar pressures are operating to direct the evolution of selfing in animals and plants.

Etymology
The term derives from the Latin: hermaphroditus, from Ancient Greek: ἑρμαφρόδιτος, romanized: hermaphroditos, which derives from Hermaphroditus (Ἑρμαφρόδιτος), the son of Hermes and Aphrodite in Greek mythology. According to Ovid, he fused with the nymph Salmacis resulting in one individual possessing physical traits of male and female sexes; according to the earlier Diodorus Siculus, he was born with a physical body combining male and female sexes. The word hermaphrodite entered the English lexicon as early as the late fourteenth century. Alexander ab Alexandro stated, using the term hermaphrodite, that the people who bore the sexes of both man and woman were regarded by the Athenians and the Romans as monsters, and thrown into the sea at Athens and into the Tiber at Rome.

Animals
Sequential hermaphrodites
Sequential hermaphrodites (dichogamy) occur in species in which the individual is born as one sex, but can later change into the opposite sex. This contrasts simultaneous hermaphrodites, in which an individual may possess fully functional male and female genitalia. Sequential hermaphroditism is common in fish (particularly teleost fish) and many gastropods (such as the common slipper shell), and some flowering plants. Sequential hermaphrodites can only change sex once. Sequential hermaphroditism can best be understood in terms of behavioral ecology and evolutionary life history theory, as described in the size-advantage mode first proposed by Michael T. Ghiselin which states that if an individual of a certain sex could significantly increase its reproductive success after reaching a certain size, it would be to their advantage to switch to that sex.
Sequential hermaphrodites can be divided into three broad categories:

Protandry: Where an organism is born as a male, and then changes sex to a female.Example: The clownfish (genus Amphiprion) are colorful reef fish found living in symbiosis with sea anemones. Generally one anemone contains a harem, consisting of a large female, a smaller reproductive male, and even smaller non-reproductive males. If the female is removed, the reproductive male will change sex and the largest of the non-reproductive males will mature and become reproductive. It has been shown that fishing pressure can change when the switch from male to female occurs, since fishermen usually prefer to catch the larger fish. The populations are generally changing sex at a smaller size, due to natural selection.
Protogyny: Where the organism is born as a female, and then changes sex to a male.Example: Wrasses (Family Labridae) are a group of reef fish in which protogyny is common. Wrasses also have an uncommon life history strategy, which is termed diandry (literally, two males). In these species, two male morphs exists: an initial phase male and a terminal phase male. Initial phase males do not look like males and spawn in groups with females. They are not territorial. They are, perhaps, female mimics (which is why they are found swimming in group with females). Terminal phase males are territorial and have a distinctively bright coloration. Individuals are born as males or females, but if they are born males, they are not born as terminal phase males. Females and initial phase males can become terminal phase males. Usually, the most dominant female or initial phase male replaces any terminal phase male when those males die or abandon the group.
Bidirectional sex changers: Where an organism has female and male reproductive organs, but act as either female or male during different stages in life.Example: Lythrypnus dalli (Family Lythrypnus) are a group of coral reef fish in which bidirectional sex change occurs. Once a social hierarchy is established a fish changes sex according to its social status, regardless of the initial sex, based on a simple principle: if the fish expresses subordinate behavior then it changes its sex to female, and if the fish expresses dominant or not subordinate behavior then the fish changes its sex to male.Dichogamy can have both conservation-related implications for humans, as mentioned above, as well as economic implications. For instance, groupers are favoured fish for eating in many Asian countries and are often aquacultured. Since the adults take several years to change from female to male, the broodstock are extremely valuable individuals.

Simultaneous hermaphrodites
A simultaneous (or synchronous) hermaphrodite (or homogamous) is an adult organism that has both male and female sexual organs at the same time. Simultaneous hermaphrodites can be regarded as both sexes present in the same individual. Self-fertilization often occurs.

Reproductive system of gastropods: Pulmonate land snails and land slugs are perhaps the best-known kind of simultaneous hermaphrodite, and are the most widespread of terrestrial animals possessing this sexual polymorphism. Sexual material is exchanged between both animals via spermatophore, which can then be stored in the spermatheca. After exchange of spermatozoa, both animals will lay fertilized eggs after a period of gestation; then the eggs will proceed to hatch after a development period. Snails typically reproduce from early spring through late autumn.
Banana slugs are another example of a hermaphroditic gastropod. Mating with a partner is more desirable biologically, as the genetic material of the resultant offspring is varied, but if mating with a partner is not possible, self-fertilization is practiced. The male sexual organ of an adult banana slug is quite large in proportion to its size, as well as compared to the female organ. It is possible for banana slugs, while mating, to become stuck together. If a substantial amount of wiggling fails to separate them, the male organ will be bitten off (using the slugs radula), see apophallation. If a banana slug has lost its male sexual organ, it can still mate as a female, making its hermaphroditic quality a valuable adaptation.
The species of colourful sea slugs Goniobranchus reticulatus is hermaphroditic, with both male and female organs active at the same time during copulation.  After mating, the external portion of the penis detaches, but is able to regrow within 24 hours.
Hamlets, unlike other fish, seem quite at ease mating in front of divers, allowing observations in the wild to occur readily. They do not practice self-fertilization, but when they find a mate, the pair takes turns between which one acts as the male and which acts as the female through multiple matings, usually over the course of several nights.
Earthworms are another example of a simultaneous hermaphrodite. Although they possess ovaries and testes, they have a protective mechanism against self-fertilization. Sexual reproduction occurs when two worms meet and exchange gametes, copulating on damp nights during warm seasons. Fertilized eggs are protected by a cocoon, which is buried on or near the surface of the ground.
The free-living hermaphroditic nematode Caenorhabditis elegans reproduces primarily by self-fertilization, but infrequent out-crossing events occur at a rate of approximately 1%.
The mangrove killifish (Kryptolebias marmoratus) is a species of fish that lives along the east coast of North, Central and South America. These fish are simultaneous hermaphrodites. K. marmoratus produces eggs and sperm by meiosis and routinely reproduces by self-fertilization. Each individual hermaphrodite normally fertilizes itself when an egg and sperm produced by an internal organ unite inside the fishs body. This species is also regarded as the only known vertebrate species that can reproduce by self fertilization.

Pseudohermaphroditism
When spotted hyenas were first scientifically observed by explorers, they were thought to be hermaphrodites. Early observations of spotted hyenas in the wild led researchers to believe that all spotted hyenas, male and female, were born with what appeared to be a penis. The apparent penis in female spotted hyenas is in fact an enlarged clitoris, which contains an external birth canal. It can be difficult to determine the sex of wild spotted hyenas until sexual maturity, when they may become pregnant. When a female spotted hyena gives birth, they pass the cub through the cervix internally, but then pass it out through the elongated clitoris.

Plants
Hermaphrodite is used in botany to describe, for example, a flower that has both staminate (male, pollen-producing) and carpellate (female, ovule-producing) parts.

Monoecy
Flowering plant species with separate male and female flowers on the same individual are called monoecious. Monoecious plants are often referred to as hermaphroditic because they produce both male and female gametes. However, the individual flowers are not hermaphroditic because they are only one sex. Monoecy only occurs in about 7% of angiosperm species. Conifers are almost all monoecious, but 65% of gymnosperm species are dioecious. Some plants can change their sex throughout their lifetime. This process is called Sequential hermaphroditism.

Andromonecy
In andromonecious species, the plants produce perfect (hermaphrodite) flowers and separate staminate flowers that function as male but are sterile as female. Andromonecy occurs in about 4000 species of flowering plants (2% of flowering plants).

Use regarding humans
Historically, the term hermaphrodite was used in law to refer to people whose sex was in doubt. The 12th-century Decretum Gratiani states that "Whether an hermaphrodite may witness a testament, depends on which sex prevails" ("Hermafroditus an ad testamentum adhiberi possit, qualitas sexus incalescentis ostendit."). Similarly, the 17th-century English jurist and judge Edward Coke (Lord Coke), wrote in his Institutes of the Lawes of England on laws of succession stating, "Every heire is either a male, a female, or an hermaphrodite, that is both male and female. And an hermaphrodite (which is also called Androgynus) shall be heire, either as male or female, according to that kind of sexe which doth prevaile."During the Victorian era, medical authors attempted to ascertain whether or not humans could be hermaphrodites, adopting a precise biological definition to the term. From that period until the early 21st century, intersex individuals were termed true hermaphrodites if their gonadal tissue contained both testicular and ovarian tissue, or pseudohermaphrodites if their external appearance (phenotype) differed from sex expected from internal gonads. This language has fallen out of favor due to misconceptions and pejorative connotations associated with the terms, and also a shift to nomenclature based on genetics.
The term intersex describes a wide variety of combinations of what are considered male and female biological characteristics. Intersex biology may include, for example, ambiguous-looking external genitalia, karyotypes that include mixed XX and XY chromosome pairs (46XX/46XY, 46XX/47XXY or 45X/XY mosaic). Clinically, medicine currently describes intersex people as having disorders of sex development, a term vigorously contested. This is particularly because of a relationship between medical terminology and medical intervention.Intersex civil society organizations, and many human rights institutions, have criticized medical interventions designed to make intersex bodies more typically male or female.
In some cases, intersex traits are caused by unusual levels of sex hormones, which may be the result of an atypical set of sex chromosomes. One possible pathophysiological explanation of intersex in humans is a parthenogenetic division of a haploid ovum into two haploid ova. Upon fertilization of the two ova by two sperm cells (one carrying an X chromosome and the other carrying a Y chromosome), the two fertilized ova are then fused together resulting in a person having dual genitalial, gonadal (ovotestes) and genetic sex. Another common cause of being intersex is the crossing over of the testis-determining factor (SRY) from the Y chromosome to the X chromosome during meiosis </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Oslers node and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Mitral stenosis and can you explain it in depth? [/INST] Mitral stenosis is a valvular heart disease characterized by the narrowing of the opening of the mitral valve of the heart. It is almost always caused by rheumatic valvular heart disease. Normally, the mitral valve is about 5 cm2 during diastole. Any decrease in area below 2 cm2 causes mitral stenosis. Early diagnosis of mitral stenosis in pregnancy is very important as the heart cannot tolerate increased cardiac output demand as in the case of exercise and pregnancy. Atrial fibrillation is a common complication of resulting left atrial enlargement, which can lead to systemic thromboembolic complications like stroke.

Signs and symptoms
Signs and symptoms of mitral stenosis include the following:

Heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea (PND)
Palpitations
Chest pain
Hemoptysis
Thromboembolism in later stages when the left atrial volume is increased (i.e., dilation). The latter leads to increase risk of atrial fibrillation, which increases the risk of blood stasis (motionless). This increases the risk of coagulation.
Ascites and edema and hepatomegaly (if right-side heart failure develops)Fatigue and weakness increase with exercise and pregnancy.

Natural history
The natural history of mitral stenosis secondary to rheumatic fever (the most common cause) is an asymptomatic latent phase following the initial episode of rheumatic fever.  This latent period lasts an average of 16.3 ± 5.2 years.  Once symptoms of mitral stenosis begin to develop, progression to severe disability takes 9.2 ± 4.3 years.In individuals having been offered mitral valve surgery but refused, survival with medical therapy alone was 44 ± 6% at 5 years, and 32 ± 8% at 10 years after they were offered correction.

Cause
Almost all cases of mitral stenosis are due to disease in the heart secondary to rheumatic fever and the consequent rheumatic heart disease. Uncommon causes of mitral stenosis are calcification of the mitral valve leaflets, and as a form of congenital heart disease. However, there are primary causes of mitral stenosis that emanate from a cleft mitral valve.  It is the most common valvular heart disease in pregnancy.Other causes include infective endocarditis where the vegetations may favor increase risk of stenosis. Other rare causes include mitral annular calcification, endomyocardial fibroelastosis, malignant carcinoid syndrome, systemic lupus erythematosus, whipple disease, fabry disease, and rheumatoid arthritis. hurler disease, hunters disease, amyloidosis.

Pathophysiology
The normal area of the mitral valve orifice is about 4 to 6 cm2. In normal cardiac physiology, the mitral valve opens during left ventricular diastole, to allow blood to flow from the left atrium to the left ventricle. A normal mitral valve will not impede the flow of blood from the left atrium to the left ventricle during (ventricular) diastole, and the pressures in the left atrium and the left ventricle during ventricular diastole will be equal.  The result is that the left ventricle gets filled with blood during early ventricular diastole, with only a small portion of extra blood contributed by contraction of the left atrium (the "atrial kick") during late ventricular diastole.When the mitral valve area goes below 2 cm2, the valve causes an impediment to the flow of blood into the left ventricle, creating a pressure gradient across the mitral valve.  This gradient may be increased by increases in the heart rate or cardiac output.  As the gradient across the mitral valve increases, the amount of time necessary to fill the left ventricle with blood increases.  Eventually, the left ventricle requires the atrial kick to fill with blood.  As the heart rate increases, the amount of time that the ventricle is in diastole and can fill up with blood (called the diastolic filling period) decreases.  When the heart rate goes above a certain point, the diastolic filling period is insufficient to fill the ventricle with blood and pressure builds up in the left atrium, leading to pulmonary congestion.When the mitral valve area goes less than 1 cm2, there will be an increase in the left atrial pressures (required to push blood through the stenotic valve). Since the normal left ventricular diastolic pressures is about 5 mmHg, a pressure gradient across the mitral valve of 20 mmHg due to severe mitral stenosis will cause a left atrial pressure of about 25 mmHg. This left atrial pressure is transmitted to the pulmonary vasculature and causes pulmonary hypertension.  Pulmonary capillary pressures in this level cause an imbalance between the hydrostatic pressure and the oncotic pressure, leading to extravasation of fluid from the vascular tree and pooling of fluid in the lungs (congestive heart failure causing pulmonary edema).The constant pressure overload of the left atrium will cause the left atrium to increase in size.  As the left atrium increases in size, it becomes more prone to develop atrial fibrillation (AF).  When atrial fibrillation develops, the atrial kick is lost (since it is due to the normal atrial contraction).In individuals with severe mitral stenosis, the left ventricular filling is dependent on the atrial kick.  The loss of the atrial kick due to atrial fibrillation ( i.e. blood cannot flow into the left ventricle thus accumulating in the left atrium )  can cause a precipitous decrease in cardiac output and sudden congestive heart failure.Patients with mitral stenosis prompts a series of hemodynamic changes that frequently cause deterioration of the patients clinical status. A reduction in cardiac output, associated with acceleration of heart rate and shortening of the diastolic time, frequently leads to congestive heart failure. In addition, when AF sets in, systemic embolization becomes a real danger.Mitral stenosis typically progresses slowly (over decades) from the initial signs of mitral stenosis to NYHA functional class II symptoms to the development of atrial fibrillation to the development of NYHA functional class III or IV symptoms.  Once an individual develops NYHA class III or IV symptoms, the progression of the disease accelerates and the patients condition deteriorates.

Diagnosis
Physical examination
Upon auscultation of an individual with mitral stenosis, the first heart sound is usually loud and may be palpable (tapping apex beat) because of increased force in closing the mitral valve. The first heart sound is made by the mitral and tricuspid heart valves closing. These are normally synchronous, and the sounds are termed M1 and T1, respectively. M1 becomes louder in mitral stenosis. It may be the most prominent sign.If pulmonary hypertension secondary to mitral stenosis is severe, the P2 (pulmonic) component of the second heart sound (S2) will become loud.An opening snap that is a high-pitch additional sound may be heard after the A2 (aortic) component of the second heart sound (S2), which correlates to the forceful opening of the mitral valve.  The mitral valve opens when the pressure in the left atrium is greater than the pressure in the left ventricle.  This happens in ventricular diastole (after closure of the aortic valve), when the pressure in the ventricle precipitously drops.  In individuals with mitral stenosis, the pressure in the left atrium correlates with the severity of the mitral stenosis.  As the severity of the mitral stenosis increases, the pressure in the left atrium increases, and the mitral valve opens earlier in ventricular diastole.A mid-diastolic rumbling murmur with presystolic accentuation will be heard after the opening snap. The murmur is best heard at the apical region and is not radiated. Since it is a low-pitch sound, it is heard best with the bell of the stethoscope. Its duration increases with worsening disease. Rolling the patient toward left as well as isometric exercise will accentuate the murmur. A thrill might be present when palpating at the apical region of the precordium.Advanced disease may present with signs of right-sided heart failure such as parasternal heave, jugular venous distension, hepatomegaly, ascites and/or pulmonary hypertension, the latter often presenting with a loud P2.Almost all signs increase with exercise and pregnancy.Other peripheral signs include:

Malar flush - due to back pressure and buildup of carbon dioxide (CO2). CO2 is a natural vasodilator.
Atrial fibrillation - irregular pulse and loss of a wave in jugular venous pressure
Left parasternal heave - presence of right ventricular hypertrophy due to pulmonary hypertension
Tapping apex beat that is not displacedMedical signs of atrial fibrillation include:Heart rate is about 100-150/min.
Irregularly irregular pulse with a pulse deficit>10.
Varying first heart sound intensity.
Opening snap is not heard sometimes.
Absent a waves in the neck veins.
Presystolic accentuation of diastolic murmur disappears.
Embolic manifestations may appear.

Associated lesions
With severe pulmonary hypertension, a pansystolic murmur produced by functional tricuspid regurgitation may be audible along the left sternal border. This murmur is usually louder during inspiration and diminishes during forced expiration (Carvallos sign). When the cardiac output is markedly reduced in MS, the typical auscultatory findings, including the diastolic rumbling murmur, may not be detectable (silent
MS), but they may reappear as compensation is restored. The Graham Steell murmur of pulmonary regurgitation, a high-pitched, diastolic, decrescendo blowing murmur along the left sternal border, results from dilation of the pulmonary valve ring and occurs in patients with mitral valve disease and severe pulmonary hypertension. This murmur may be indistinguishable from the more common murmur produced by aortic regurgitation (AR), although it may increase in intensity with inspiration and is accompanied by a loud and often palpable P2.

Echocardiography
In most cases, the diagnosis of mitral stenosis is most easily made by echocardiography, which shows left atrial enlargement, thick and calcified mitral valve with narrow and "fish-mouth"-shaped orifice and signs of right ventricular failure in advanced disease. It can also show decreased opening of the mitral valve leaflets, and increased blood flow velocity during diastole. The trans-mitral gradient as measured by Doppler echocardiography is the gold standard in the evaluation of the severity of mitral stenosis.

Cardiac chamber catheterization
Another method of measuring the severity of mitral stenosis is the simultaneous left and right heart chamber catheterization. The right heart catheterization (commonly known as Swan-Ganz catheterization) gives the physician the mean pulmonary capillary wedge pressure, which is a reflection of the left atrial pressure.  The left heart catheterization, on the other hand, gives the pressure in the left ventricle.  By simultaneously taking these pressures, it is possible to determine the gradient between the left atrium and left ventricle during ventricular diastole, which is a marker for the severity of mitral stenosis.  This method of evaluating mitral stenosis tends to overestimate the degree of mitral stenosis, however, because of the time lag in the pressure tracings seen on the right-heart catheterization and the slow Y descent seen on the wedge tracings.  If a trans-septal puncture is made during right heart catheterization, however, the pressure gradient can accurately quantify the severity of mitral stenosis.

Other techniques
Chest X-ray may also assist in diagnosis, showing left atrial enlargement.Electrocardiography may show P mitrale, that is, broad, notched P waves in several or many leads with a prominent late negative component to the P wave in lead V1, and may also be seen in mitral regurgitation, and, potentially, any cause of overload of the left atrium. Thus, P-sinistrocardiale may be a more appropriate term.

Treatment
Treatment is not necessary in asymptomatic patients.The treatment options for mitral stenosis include mitral valve replacement by surgery, and percutaneous mitral valvuloplasty by balloon catheter.The indication for invasive treatment with either a mitral valve replacement or valvuloplasty is NYHA functional class III or IV symptoms.Another option is balloon dilatation. To determine which patients would benefit from percutaneous balloon mitral valvuloplasty, a scoring system has been developed. Scoring is based on 4 echocardiographic criteria: leaflet mobility, leaflet thickening, subvalvular thickening, and calcification.  Individuals with a score of ≥ 8 tended to have suboptimal results.  Superb results with valvotomy are seen in individuals with a crisp opening snap, score < 8, and no calcium in the commissures.Treatment also focuses on concomitant conditions often seen in mitral stenosis:

Any angina is treated with short-acting nitrovasodilators, beta-blockers and/or calcium blockers
Any hypertension is treated aggressively, but caution must be taken in administering beta-blockers
Any heart failure is treated with digoxin, diuretics, nitrovasodilators and, if not contraindicated, cautious inpatient administration of ACE inhibitors

Mitral valvuloplasty
Mitral valvuloplasty is a minimally invasive therapeutic procedure to correct an uncomplicated mitral stenosis by dilating the valve using a balloon.
Under local anaesthetic, a catheter with a special balloon is passed from the right femoral vein, up the inferior vena cava and into the right atrium. The interatrial septum is punctured and the catheter passed into the left atrium using a "trans-septal technique." The balloon is sub-divided into 3 segments and is dilated in 3 stages. First, the distal portion (lying in the left ventricle) is inflated and pulled against the valve cusps </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Achlorhydria and can you explain it in depth? [/INST] Achlorhydria and hypochlorhydria refer to states where the production of hydrochloric acid in gastric secretions of the stomach and other digestive organs is absent or low, respectively. It is associated with various other medical problems.

Signs and symptoms
Irrespective of the cause, achlorhydria can result as known complications of bacterial overgrowth and intestinal metaplasia and symptoms are often consistent with those diseases:

gastroesophageal reflux disease
abdominal discomfort
early satiety
weight loss
diarrhea
constipation
abdominal bloating
anemia
stomach infection
malabsorption of food
carcinoma of stomachSince acidic pH facilitates the absorption of iron, achlorhydric patients often develop iron deficiency anemia.
Acidic environment of stomach helps conversion of pepsinogen into pepsin, which is highly important in digesting the protein into smaller components, such as a complex protein into simple peptides and amino acids inside the stomach, which are later absorbed by the gastrointestinal tract.
Bacterial overgrowth and B12 deficiency (pernicious anemia) can cause micronutrient deficiencies that result in various clinical neurological manifestations, including visual changes, paresthesias, ataxia, limb weakness, gait disturbance, memory defects, hallucinations and personality and mood changes.
Risk of particular infections, such as Vibrio vulnificus (commonly from seafood) is increased. Even without bacterial overgrowth, low stomach acid (high pH) can lead to nutritional deficiencies through decreased absorption of basic electrolytes (magnesium, zinc, etc.) and vitamins (including vitamin C, vitamin K, and the B complex of vitamins). Such deficiencies may be involved in the development of a wide range of pathologies, from fairly benign neuromuscular issues to life-threatening diseases.

Causes
The slowing of the bodys basal metabolic rate associated with hypothyroidism
Pernicious anemia where there is antibody production against parietal cells which normally produce gastric acid.
The use of antacids or drugs that decrease gastric acid production (such as H2-receptor antagonists) or transport (such as proton pump inhibitors).
A symptom of rare diseases such as mucolipidosis (type IV).
A symptom of Helicobacter pylori infection which neutralizes and decreases secretion of gastric acid to aid its survival in the stomach.
A symptom of atrophic gastritis or of stomach cancer.
Radiation therapy involving the stomach.
Gastric bypass procedures such as a duodenal switch and RNY, where the largest acid producing parts of the stomach are either removed, or blinded.
VIPomas (vasoactive intestinal peptides) and somatostatinomas are both islet cell tumors of the pancreas.
Pellagra, caused by niacin deficiency.
Chloride, sodium, potassium, zinc and/or iodine deficiency, as these elements are needed to produce adequate levels of stomach acid (HCl).
Sjögrens syndrome, an autoimmune disorder that destroys many of the bodys moisture-producing enzymes
Ménétriers disease, characterized by hyperplasia of mucous cells in the stomach also causing excess protein loss, leading to hypoalbuminemia. Presents with abdominal pain and edema

Risk Factors
Age
It was found that the incidence of achlorhydria in patients under the age of 60 was around 2.3%, whereas it was 5% in patients over the age of 60. In a persons 30s, the prevalence is about 2.5%, and increases to 12% in a persons 80s.
An absence of hydrochloric acid increases with advancing age. A lack of hydrochloric acid produced by the stomach is one of the most common age-related causes of a harmed digestive system.Among men and women, 27% experience a varying degree of achlorhydria. US researchers found that over 30% of women and men over the age of 60 have little to no acid secretion in the stomach. Additionally, 40% of postmenopausal women have shown to have no basal gastric acid secretion in the stomach, with 39.8% occurring in females 80 to 89 years old Autoimmune Disorders
Autoimmune disorders are also linked to advancing age, specifically autoimmune gastritis, which is when the body produces unwelcomed antibodies and causes inflammation of the stomach. Autoimmune disorders are also a cause for small bacterial growth in the bowel and a deficiency of Vitamin B-12. These have also proved to be factors of acid secretion in the stomach.Hypothyroidism: Thyroid hormones are a factor in the decreasing of hydrochloric acid in the stomach, thus hypothyroidism is associated with a greater risk of developing achlorhydria.Autoimmune conditions are often managed using various treatments; however, these treatments have no known effect on achlorhydria.

Other
Other risk factors include, over the counter acid-blocking medications and antibiotics that may be used to block stomach acid. These medications are often taken by individuals for a longer than recommended period, even for years, despite causing adverse effects on stomach acid secretion.Stress has also been proven to be linked to symptoms associated with achlorhydria including constant belching, constipation, and abdominal pain.

Diagnosis
For practical purposes, gastric pH and endoscopy should be done in someone with suspected achlorhydria. Older testing methods using fluid aspiration through a nasogastric tube can be done, but these procedures can cause significant discomfort and are less efficient ways to obtain a diagnosis.
A complete 24-hour profile of gastric acid secretion is best obtained during an esophageal pH monitoring study.
Achlorhydria may also be documented by measurements of extremely low levels of pepsinogen A (PgA) (< 17 µg/L) in blood serum. The diagnosis may be supported by high serum gastrin levels (> 500–1000 pg/mL).The "Heidelberg test" is an alternative way to measure stomach acid and diagnose hypochlorhydria/achlorhydria.
A check can exclude deficiencies in iron, calcium, prothrombin time, vitamin B-12, vitamin D, and thiamine </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cavernous sinus and can you explain it in depth? [/INST] The cavernous sinus within the human head is one of the dural venous sinuses creating a cavity called the lateral sellar compartment bordered by the temporal bone of the skull and the sphenoid bone, lateral to the sella turcica.

Structure
The cavernous sinus is one of the dural venous sinuses of the head. It is a network of veins that sit in a cavity. It sits on both sides of the sphenoidal bone and pituitary gland, approximately 1 × 2 cm in size in an adult. The carotid siphon of the internal carotid artery, and cranial nerves III, IV, V (branches V1 and V2) and VI all pass through this blood filled space. Both sides of cavernous sinus is connected to each other via intercavernous sinuses. The cavernous sinus lies in between the inner and outer layers of dura mater.

Nearby structures
Above: optic tract, optic chiasma, internal carotid artery.
Inferiorly: foramen lacerum, and the junction of the body and greater wing of sphenoid bone.
Medially: pituitary gland (hypophysis cerebri), and sphenoidal air sinus.
Laterally: temporal lobe with uncus.
Anteriorly: superior orbital fissure, and the apex of the orbit.
Posteriorly: apex of petrous temporal bone.

Venous connections
The cavernous sinus receives blood from:
Superior and inferior ophthalmic veins
Sphenoparietal sinus
Superficial middle cerebral veins
Inferior cerebral veinsBlood leaves the sinus via superior and inferior petrosal sinuses as well as via the emissary veins through the foramina of the skull (mostly through foramen ovale). There are also connections with the pterygoid plexus of veins via inferior ophthalmic vein, deep facial vein and emissary veins.

Contents
Apart from the blood which passes through a venous sinus, several anatomical structures, including some cranial nerves and their branches, also pass through the sinus.Structures within the outer (lateral) wall of the compartment from superior to inferior:
Oculomotor nerve
Trochlear nerve
Ophthalmic and maxillary branches of the trigeminal nerveStructures passing through the midline (medial) wall:
Abducens nerve
Internal carotid artery accompanied by the internal carotid plexusThese nerves, with the exception of CN V2, pass through the cavernous sinus to enter the orbital apex through the superior orbital fissure. The maxillary nerve, division V2 of the trigeminal nerve travels through the lower portion of the sinus and exits via the foramen rotundum. The maxillary branch passes external to, but immediately adjacent to, the lateral wall of the sinus.The optic nerve lies just above and outside the cavernous sinus, superior and lateral to the pituitary gland on each side, and enters the orbital apex via the optic canal.

Function
Venous drainage
As a venous sinus, the cavernous sinus receives blood from the superior and inferior ophthalmic veins and from superficial cortical veins, and is connected to the basilar plexus of veins posteriorly. The cavernous sinus drains by two larger channels, the superior and inferior petrosal sinuses, ultimately into the internal jugular vein via the sigmoid sinus, also draining with emissary vein to pterygoid plexus.

Clinical significance
It is the only anatomic location in the body in which an artery travels completely through a venous structure. If the internal carotid artery ruptures within the cavernous sinus, an arteriovenous fistula is created (more specifically, a carotid-cavernous fistula) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Male accessory gland infection and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Anejaculation and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Rhinophyma and can you explain it in depth? [/INST] Rhinophyma is a condition causing development of a large, bulbous nose associated with granulomatous infiltration, commonly due to untreated rosacea. The condition is most common in older white males.Colloquial terms for the rhinophyma include "whiskey nose", "gin blossom", "toros nose", and "potato nose".

Signs and symptoms
Rhinophyma is characterised by prominent pores and a fibrous thickening of the nose, sometimes with papules. It is associated with the common skin condition rosacea and it can be classified clinically into 5 grades of increasing severity.

Complications
Tissue thickening may come to cause airway obstruction and impede breathing.Rhynophyma cause psychological distress due to its effect on ones personal appearance and social perceptions of a link with alcoholism.

Causes
Rhinophyma develops in certain individuals with an unknown predisposition from long-standing rosacea which has progressed to a severe form.Although rhinophyma has been commonly presumed to be linked to alcoholism, a direct causal relationship between the condition and excessive alcohol consumption has not been substantiated. Alcohol may cause increased flushing in those affected.

Pathophysiology
Rhinophyma develops in some individuals after long-standing rosacea that has progressed to acne rosacea.Rosacea usually commences in people between the age of 20-30 years. Rosacea begins with facial flushing (pre-rosacea). The nasal skin then thickens and hypervascularises, leading to persistent erythema (vascular rosacea). Papules and pustules then develop, marking the beginning of acne (inflammatory) rosacea. A subset of those affected by acne rosacea go on to develop rhinophyma. Chronic infection is common as the thickened sebaceous fluid traps bacteria.Rhinophyma is characterised by hypertrophy of nasal skin, with hyperplasia and fibrosis of the sebaceous glands and connective tissue. The nasal tip and alae are preferentially affected by the hypertrophy, and the lower portion of the nose is predominantly affected. The underlying bony structure is not affected.The exact pathophysiological mechanism underlying the development of rosacea and rhinophyma is unknown, but a combination of neurovascular and immune disturbance is thought to be involved, causing inflammation, fibrosis, and vascularisation.

Male predisposition
Even though females are more often affected by acne rosacea, they seldom go on to develop rhinophyma </s>


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Monosomy 9p and can you explain it in depth? [/INST] Monosomy 9p (also known as Alfis Syndrome or simply 9P-) is a rare chromosomal disorder in which some DNA is missing or has been deleted on the short arm region, “p”, of one of the 9th Chromosomes (9p22.2-p23). This deletion either happens de novo or a result of a parent having the chromosome abnormality. This rare chromosome abnormality is often diagnosed after birth when development delay, irregular facial features, and structural irregularities within the heart, and genital defects are noticed. Treatments for this syndrome usually focus on fixing the common malformations associated with this syndrome. Chromosome 9p deletion syndrome was first discovered in 1973 when 3 infants with similar clinical features were observed to have a partial deletion of the short arm of Chromosome 9. Symptoms include microgenitalia, intellectual disability with microcephaly and dysmorphic features.

Signs and Symptoms
Psychomotor Development Delays
Psychomotor development refers to the changes experienced directly after birth through adolescence. Development occurs in cognitive, emotional, motor, and social skills over the childs growth and a delay can result in lagging development of language, motor skills, cognition, or social skills, however these delays can vary in severity.

Facial Dysmorphism
Facial Dysmorphisms broadly describe any abnormalities in facial structure. Facial Dysmorphisms include slopping forehead, frontal bossing (prominent protruding forehead), hemifacial microsomia (one side of the face underdeveloped), and otocephaly (absence of mandible and fusion of ears under chin).

Malformation of Limbs
Congenital limb defects occur when a fetus limbs, either upper or lower, experience altered development. These developmental abnormalities include absence of the limb, failure of portions of the limb to separate (commonly fingers and toes), duplication of digits, or overgrowth or undergrowth of limbs.

Genetics
Inheritance Pattern
The inheritance pattern for the Chromosome 9p deletion syndrome is inherited in an autosomal dominant inheritance pattern. This means that a single copy of the deletion is sufficient to cause the disease.

Mutation
The mutation, which occurs in the form of a deletion of the short arm of chromosome 9, causes the cell to not express the gene products normally controlled by the genes within the chromosome 9 deletion.

Genes Involved
The 9p deletion causes a loss of genes that would normally be there. Which genes are lost on the short arm of chromosome 9 dictates the symptoms that are present within the individual and the spectrum of disease severity. Most of the genes involved are associated with the development of tissues.There are many possible genes that can be deleted, but two particular genes that are proven to be involved in the emergence of the symptoms associated with Chromosome 9p deletion syndrome are DMRT1 and DMRT2. When DMRT1 and DMRT2 are deleted, genital malformations and mental retardation are evident although, the direct mechanisms as to how this occurs remains undefined.

Location
Geneticists originally had the syndrome narrowed down to the short arm region of Chromosome 9. Now, the location of the deletion has recently been narrowed to 9p22.2-p23.

Diagnosis
Diagnoses can occur at any age. Most of time chromosome 9p deletion syndrome is diagnosed after birth by the detection of symptoms via clinical evaluation </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Steroid diabetes and can you explain it in depth? [/INST] Steroid diabetes is a medical term referring to prolonged hyperglycemia due to glucocorticoid therapy for another medical condition.  It is usually, but not always, a transient condition.

Cause
The most common glucocorticoids which cause steroid diabetes are prednisolone and dexamethasone given systemically in "pharmacologic doses" for days or weeks.  Typical medical conditions in which steroid diabetes arises during high-dose glucocorticoid treatment include severe asthma, organ transplantation, cystic fibrosis, inflammatory bowel disease, and induction chemotherapy for leukemia or other cancers.

Mechanism
Glucocorticoids oppose insulin action and stimulate gluconeogenesis, especially in the liver, resulting in a net increase in hepatic glucose output </s>


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