<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 Hyperproinsulinemia 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 Chronic paroxysmal hemicrania and can you explain it in depth? [/INST] Chronic paroxysmal hemicrania (CPH) is a severe debilitating unilateral headache usually affecting the area around the eye.  It normally consists of multiple severe, yet short, headache attacks affecting only one side of the cranium. It is more commonly diagnosed in women than in men, but, unlike a migraine, has no neurological symptoms associated with it. CPH headaches are treated through the use of non-steroidal anti-inflammatory drugs, with indomethacin found to be usually effective in eliminating symptoms.
Paroxysmal hemicrania is classified by the frequency and duration of attacks experienced by patients.  Episodic paroxysmal hemicrania attacks occur at least twice a year and last anywhere from seven days to a year with pain free periods of a month or longer separating them. Chronic paroxysmal hemicrania attacks occur over the course of more than a year without remission or with remissions lasting less than a month.

Signs and symptoms
Individuals with CPH suffer multiple short, severe headaches a day, often more than five, with most lasting between 5 and 30 minutes each. When compared to cluster headaches, CPH attacks are typically shorter. Each headache is centered around the eye, temple and forehead and is localized to one side of the head. While redness and watering of the eye are associated with CPH, patients typically do not experience nausea or vomiting. Although less common, CPH may also present as severe unilateral ear pain accompanied by autonomic symptoms. Autonomic symptoms may include the presence of Red Ear Syndrome.Attacks hit the patient many times a day, from 5 times a day up to 40 times a day with an average of 11 a day. Mild background pain can persist between attacks. They come in bouts that last from 7 days to 1 year separated by remission periods that can last more than 3 months in episodic patients, or less than 3 months in chronic patients. Onset is in adulthood and the disorder may last indefinitely or spontaneously go into remission. Circadian mechanisms are likely involved in paroxysmal hemicrania due to its highly cyclic nature. No particular circannual recurrence characterizes symptomatic periods, although some patients can experience a seasonal preponderance.

Causes
The causes of paroxysmal hemicrania are ultimately still unknown. Sympathetic symptoms such as miosis and ptosis might be linked with a generalized sympathetic dysfunction. Neuropathic mechanisms may be involved, since attacks can be triggered by mechanical stimulation. Perivascular neurogenic inflammatory processes can worsen symptoms or increase pain. Dilated blood vessels may contribute in stimulating trigeminal nociceptors directly, although they cannot be the origin of pain, since even suppression of vasodilation does not stop it once it’s started.Many secondary conditions have been reported to be possible causes of CPH, according to Mehta et al., most of which are arterial abrasions or tumors. These include aneurysms in the circle of Willis, middle cerebral artery infarction, parietal arteriovenous malformation, cavernous sinus and petrous ridge meningiomas, pituitary adenoma, Pancoast tumor, gangliocytoma of the sella turcica, and malignant frontal tumors. This accentuates the urgency for those diagnosed with CPH to receive an MRI head scan.

Diagnosis
CPH is a long-term disease with symptoms lasting for longer than a year, either without remission or with remissions that last less than a month. In order to be diagnosed with CPH, a patient needs to have had at least 20 attacks filling the following criteria:
Attacks of severe unilateral orbital, supraorbital, or temporal pain lasting between 2 and 30 minutes.
The headache needs to take place with one of the following:
Ipsilateral conjunctival injection and/or lacrimation
Ipsilateral nasal congestion and/or rhinorrhoea
Ipsilateral eyelid oedema
Ipsilateral forehead and facial sweating
Ipsilateral miosis and/or ptosis
Attacks need to occur more than five times a day for more than half of the time, although periods of lower frequency can occur.
The symptoms cannot be attributed to another disorder.
Attacks can be prevented completely by therapeutic doses of indomethacin.In addition, diagnosis of CPH requires that neuropathy of the supraorbital area in the temporal branch of the facial nerve be ruled out.

Comparison to cluster headaches
Though outwardly similar to cluster headaches, chronic paroxysmal hemicrania is rather different, and the two headaches are not a subset of one or the other </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 Hypertryptophanemia and can you explain it in depth? [/INST] Hypertryptophanemia is a rare autosomal recessive metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria (-uria denotes "in the urine").Elevated levels of tryptophan are also seen in Hartnup disease, a disorder of amino acid transport </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 Linear and whorled nevoid hypermelanosis 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 Cold autoimmune hemolytic anemia and can you explain it in depth? [/INST] Cold autoimmune hemolytic anemia caused by cold-reacting antibodies. Autoantibodies that bind to the erythrocyte membrane leading to premature erythrocyte destruction (hemolysis) characterize autoimmune hemolytic anemia.

Presentation
A common complaint among patients with cold agglutinin disease is painful fingers and toes with purplish discoloration associated with cold exposure. In chronic cold agglutinin disease, the patient is more symptomatic during the colder months.
Cold agglutinin mediated acrocyanosis differs from Raynaud phenomenon. In Raynaud phenomena, caused by vasospasm, a triphasic color change occurs, from white to blue to red, based on vasculature response. No evidence of such a response exists in cold agglutinin disease.
Other symptoms

Respiratory symptoms: May be present in patients with M pneumoniae infection.
Hemoglobinuria (the passage of dark urine that contains hemoglobin), A rare symptom that results from hemolysis, this may be reported following prolonged exposure to cold, hemoglobinuria is more commonly seen in paroxysmal cold hemoglobinuria.
Chronic fatigue, Due to anemia.

Causes
Cold agglutinins develop in more than 60% of patients with infectious mononucleosis, but hemolytic anemia is rare.
Classic chronic cold agglutinin disease is idiopathic, associated with symptoms and signs in relation to cold exposure.
Causes of the monoclonal secondary disease include the following:

B-cell neoplasms - Waldenström macroglobulinemia, lymphoma, chronic lymphoid leukemia, myeloma
Non hematologic neoplasmsCauses of polyclonal secondary cold agglutinin disease include the following:

Mycoplasma infections.
Viral infections: Infectious mononucleosis due to Epstein-Barr virus (EBV) or CMV, Mumps, varicella, rubella, adenovirus, HIV, influenza, hepatitis C.
Bacterial infections: Legionnaire disease, syphilis, listeriosis and Escherichia coli.
Parasitic infections: Malaria and trypanosomiasis.
Trisomy and translocation: Cytogenetic studies in patients with cold agglutinin disease have revealed the presence of trisomy 3 and trisomy 12. Translocation (8;22) has also been reported in association with cold agglutinin disease.
Transplantation: Cold agglutinin–mediated hemolytic anemia has been described in patients after living-donor liver transplantation treated with tacrolimus and after bone marrow transplantation with cyclosporine treatments. It is postulated that such calcineurin inhibitors, which selectively affect T-cell function and spare B-lymphocytes, may interfere with the deletion of autoreactive T-cell clones, resulting in autoimmune disease.
Systemic sclerosis: Cold agglutinin disease has been described in patients with sclerodermic features, with the degree of anemia being associated with increasing disease activity of the patients systemic sclerosis. This may suggest a close association between systemic rheumatic disease and autoimmune hematologic abnormalities.
Hyperreactive malarial splenomegaly: Hyperreactive malarial splenomegaly (HMS) is an immunopathologic complication of recurrent malarial infection. Patients with HMS develop splenomegaly, acquired clinical immunity to malaria, high serum concentrations of anti-Plasmodium antibodies, and high titers of IgM, with a complement-fixing IgM that acts as a cold agglutinin.
DPT vaccination: Diphtheria-pertussis-tetanus (DPT) vaccination has been implicated in the development of autoimmune hemolytic anemia caused by IgM autoantibody with a high thermal range. A total of 6 cases have been reported; 2 followed the initial vaccination and 4 followed the second or third vaccinations.
Other: Equestrian perniosis is a rare cause of persistent elevated titers of cold agglutinins. Also rarely, the first manifestations of cold agglutinin disease can develop when a patient is subjected to hypothermia for cardiopulmonary bypass surgery.

Pathophysiology
Cold agglutinins, or cold autoantibodies, occur naturally in nearly all individuals. These natural cold autoantibodies occur at low titers, less than 1:64 measured at 4 °C, and have no activity at higher temperatures. Pathologic cold agglutinins occur at titers over 1:1000 and react at 28-31 °C and sometimes at 37 °C.
Cold agglutinin disease usually results from the production of a specific IgM antibody directed against the I/i antigens (precursors of the ABH and Lewis blood group substances) on red blood cells (RBCs). Cold agglutinins commonly have variable heavy-chain regions encoded by VH, with a distinct idiotype identified by the 9G4 rat murine monoclonal antibody.

Diagnosis
Classification
AIHA can be classified as warm autoimmune hemolytic anemia  or cold autoimmune hemolytic anemia, which includes cold agglutinin disease and paroxysmal cold hemoglobinuria. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA.
Autoimmune hemolytic anemiaWarm-antibody typePrimary
Secondary  (lymphoproliferative disorders, autoimmune disorders) : 259 Cold-antibody type (anemia)Primary cold agglutinin disease
Secondary cold agglutinin syndromeAssociated with malignant disease
Acute, transient, infection-associated  (acute cold antibody mediated AIHA complicating Mycoplasma pneumoniae or viral infections )
Chronic (lymphoproliferative disorders) : 259 Paroxysmal cold hemoglobinuria: 259 Idiopathic
SecondaryAcute, transient (Infections other than syphilis): 259
Chronic (syphilis): 259 Mixed cold- and warm-antibody typeIdiopathic
Secondary (lymphoproliferative disorders, autoimmune disorders) Drug-induced immune hemolytic anemia : 259 Autoimmune type
Drug absorption type
Neoantigen type

Treatment
Cold agglutinin disease may be managed successfully using protective measures (clothing) alone in most cases </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 Limbic encephalitis and can you explain it in depth? [/INST] Limbic encephalitis is a form of encephalitis, a disease characterized by inflammation of the brain. Limbic encephalitis is caused by autoimmunity: an abnormal state where the body produces antibodies against itself. Some cases are associated with cancer and some are not. Although the disease is known as "limbic" encephalitis, it is seldom limited to the limbic system and post-mortem studies usually show involvement of other parts of the brain. The disease was first described by Brierley and others in 1960 as a series of three cases. The link to cancer was first noted in 1968 and confirmed by later investigators.The majority of cases of limbic encephalitis are associated with a tumor (diagnosed or undiagnosed). In cases caused by tumor, recovery can only occur following complete removal of the tumor, which is not always possible. Limbic encephalitis is classified according to the auto-antibody that causes the disease. The most common types are:

Anti-Hu, which is associated with small-cell carcinoma of the lungs.
Anti-Ma2, associated with germ-cell tumours of the testis.
Anti-NMDAR, associated with tumors of the ovaries, commonly teratomata.Since 1999, following the publication of a case report of a 15-year-old teenager of Indian descent from South Africa who developed subacute memory loss subsequent to herpes simplex type 1 encephalitis, similar cases of non-paraneoplastic LE have been described, as has its association with auto-antibodies and response to steroid. Limbic encephalitis associated with voltage-gated potassium channel antibodies (VGKC-Abs) may frequently be non-paraneoplastic. A recent study of 15 cases of limbic encephalitis found raised VGKC-Abs associated with non-paraneoplastic disorders and remission following immunosuppressive treatment.

Classification
Limbic encephalitis is broadly grouped into two types: paraneoplastic limbic encephalitis and non-paraneoplastic limbic encephalitis.
Paraneoplastic limbic encephalitis (PNLE) is caused by cancer or tumor, and may be treated by removal of the tumor.
Non-paraneoplastic limbic encephalitis (NPLE) is not associated with cancer. More common than PNLE, it is caused by an infection, auto-immune disorder, or other condition that may never be identified.

Symptoms and signs
Symptoms develop over days or weeks. The subacute development of short-term memory deficits is considered the hallmark of this disease, but this symptom is often overlooked, because it is overshadowed by other more obvious symptoms such as headache, irritability, sleep disturbance, delusions, hallucinations, agitation, seizures and psychosis, or because the other symptoms mean the patient has to be sedated, and it is not possible to test memory in a sedated patient.

Cause
Limbic encephalitis is associated with an autoimmune reaction. In non-paraneoplastic limbic encephalitis, this is typically due to infection (commonly herpes simplex virus) or as a systemic autoimmune disorder. Limbic encephalitis associated with cancer or tumors is called paraneoplastic limbic encephalitis.

Diagnosis
The diagnosis of limbic encephalitis is extremely difficult and it is usual for the diagnosis to be delayed for weeks. The key diagnostic test (detection of specific auto-antibodies in cerebrospinal fluid) is not routinely offered by most immunology laboratories. Some of the rarer auto-antibodies (e.g., NMDAR) have no commercially available assay and can only be measured by a very small number of research laboratories worldwide, further delaying diagnosis by weeks or months. Most patients with limbic encephalitis are initially diagnosed with herpes simplex encephalitis, because the two syndromes cannot be distinguished clinically. HHV-6 (human herpes virus 6) encephalitis is also clinically indistinguishable from limbic encephalitis.There are two sets of diagnostic criteria used. The oldest are those proposed by Gultekin et al. in 2000.
A revised set of criteria were proposed by Graus and Saiz in 2005.
The main distinction between the two sets of criteria is whether or not the detection of a paraneoplastic antibody is needed for diagnosis.

Antibodies against intracellular neuronal antigens
The main antibodies within this group are those against Hu, Ma2, CV2, amphiphysin and Ri. The syndrome of anti-Ma2 encephalitis may be clinically mistaken for Whipples disease.

Antibodies against cell membrane antigens
The main antibodies within this group are those against N-methyl-D-aspartate receptors (NMDAR) and the voltage-gated potassium channel-complex (VGKC-complex) </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 Botryomycosis 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 Stannosis and can you explain it in depth? [/INST] Stannosis is an occupational, non-fibrotic pneumoconiosis caused by chronic exposure and inhalation of tin. Pneumoconiosis is essentially when inorganic dust is found on the lung tissue; in this case, caused by tin oxide minerals. Dust particles and fumes from tin industries, stannous oxide (SnO) and stannic oxide (SnO2), are specific to stannosis diagnoses. Hazardous occupations such as, tinning, tin-working, and smelting are where most cases of stannosis are documented. When melted tin ions are inhaled as a fume, the tin oxides deposit onto the lung nodules and immune response cells. If a worker is exposed to tin oxides over multiple events for an extended time, they are at risk of developing stannosis.

Toxicology and Physiology
Workers with acute exposures, short duration with varying dose concentrations, to tin oxides develop a mild irritation on the eyes, skin, and mucous membranes. When the inorganic metal materials are inhaled, the body activates the immune system and sends macrophages to the lungs. The macrophages try removing xenobiotic particles; however, stannous and stannic oxide interfere with the cells function. Tin deposition on lung nodules becomes apparent after X-ray imaging, although the stannosis does not appear to damage the lung tissues. Since the macrophages are laden with tin oxides but little to no fibrosis, stannosis is classified as a non-fibrotic pneumoniosis. Stannosis is an rare disease with only case-by-case appearances throughout history. Therefore, a diagnostic treatment plan has not yet been created by health officials.

Control and Prevention
Characteristics of Tin for Industrial Uses
Tin oxide metals are used for their variable valence state and positive charge deficit from their oxygen vacancy. When heated to temperatures above 2602 °C or 2875 K, tin oxides start to boil and produce fumes. For example, tin forms Sn2when heated in oxygenated environments; also called feebly acid. Tin oxide is known for being a good catalyst in solid photochemical reactions (photocatalysis) and electric production from light (photoelectrocatalysis). The energy produced form splitting water in photoelectrocatalysis is used for the creation of dehydrated dyes.Tin is found in nature as an off-white or gray crystal mineral called cassiterite. The corrosion resistant metal is harvested primarily in Malaya, Bolivia, Indonesia, Zaire, thailand, and Nigeria. Traditionally, tin was used to create containers; however, since the increase use of plastics and aluminum its no longer common. There are two allotropic forms of tin, depending on the temperature. A variety of tin alloys morphologies exist including the following metals: soft solder, fusible, pewter, bronze, Babbit, White, and phosphor bronze metal. Tin oxide metals are corrosive resistant which is important in industrial uses.

Industrial Applications of Tin oxides
Stannous oxide (SnO)
Stannous oxide (SnO) is used for manufacturing glass materials, like ceramics. The compound is insoluble in water and takes the form of a brow-black powder or blue-black crystalline solid. It is labeled as both an irritant and health hazard in the chemical safety sections of safety data sheets.

Stannic oxide (SnO2)
The primary uses for stannic oxide (SnO2) include polishing glass, marble, silver, and jewelry in addition to creating dyes for fabrics, paper, ceramic glazes, printing inks, coatings, and pigments in food polymers </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 Palatal myoclonus 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 Discitis and can you explain it in depth? [/INST] Discitis, or diskitis, is an infection in the intervertebral disc space that affects different age groups. In adults, it can lead to severe consequences, such as sepsis or epidural abscess, but it can also spontaneously resolve, especially in children under 8 years of age. Discitis occurs post-surgically in approximately 1–2 percent of patients after spinal surgery.

Signs and symptoms
Symptoms include severe back pain, leading to lack of mobility. Some very young children may refuse to walk and arching of the back is possible. In post-operative situations, the symptoms occur within a week and result in severe low back pain or neck pain (depending on the surgical location). If untreated, the discitis may resolve on its own, causing spontaneous fusion of the intervertebral disc space,  cause a chronic low grade infection, or progress to osteomyelitis and possibly even an epidural abscess. In case of concomitant inflammation of one or more vertebrae (in such cases usually involving the areas adjacent to the intervertebral disc spaces) the condition is called spondylodiscitis.

Causes
There is debate as to the cause, although hematogenous seeding of the offending organism is favored as well as direct spread. It is important to differentiate between spontaneous discitis which is usually from hematologic spread from a urinary or respiratory infection versus that from a post-operative complication which usually involves skin flora such as staph aureus.
It can be caused due to spinal tuberculosis and spread along spinal ligament to involve  the adjacent anterior vertebral bodies, causing angulation of the vertebrae with subsequent kyphosis. The cause may be aseptic.

Diagnosis
Diagnosis is usually apparent on MRI although plain X-rays and CT examinations can be suggestive </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 Unequal leg length and can you explain it in depth? [/INST] Unequal leg length (also termed leg length inequality, LLI or leg length discrepancy, LLD) is where the legs are either different lengths or appear to be different lengths because of misalignment. The condition has been estimated to affect between 40% and 70% of the population, with at least 0.1% having a difference greater than 20 mm (0.79 in).

Classification
There are two main types of leg length inequalities:

Structural differences are caused by the legs themselves being measurably different in length, usually due to differences in the length of the femur in the thigh or the tibia and fibula bones in the lower leg.  This may be a birth defect or it may occur after a broken leg, serious infection, or local damage to one of the growth plates in a leg.
The other, more common, type is seen when the legs themselves are the same length, but due to neuromuscular injuries in the pelvis or upper leg, one leg or hip is held higher and tighter than the other (hypertonicity in the musculature of the pelvis or leg).  These unequally tightened muscles cause the legs to seem to be different lengths, even though careful measurement would show equal lengths of the actual leg.  This is called leg length alignment asymmetry (LLAA) and can be seen while lying down.

Diagnosis and workup
Unequal leg length in children is frequently first suspected by parents noticing a limp that appears to be getting worse. The standard workup in children is a thorough physical examination, including observing the child while walking and running. Also, at least in United States, standard workup in children also includes X-rays to quantify actual length of the bones of the legs.On X-rays, there is generally measurement of both the femur and the tibia, as well as both combined. Various measuring points for these have been suggested, but a functional method is to measure the distances between joint surfaces:
Femur length: The superior aspect of the femoral head and the distal portion of the medial femoral condyle.
Tibial length: The medial tibial plateau and the tibial plafondA leg length difference can result from a pelvic torsion.
Abnormal (gravity drive) pronation will drive the innominate bones forward (anteriorly).  The forward rotation of the innominate will shorten the leg (See Rothbart 2006).  The more pronated foot will have the more forwardly rotated innominate bone </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 Burning feet syndrome and can you explain it in depth? [/INST] Burning feet syndrome, also known as Grierson-Gopalan syndrome, is a medical condition that causes severe burning and aching of the feet, hyperesthesia, and vasomotor changes of the feet that lead to excessive sweating. It can even affect the eyes, causing scotoma and amblyopia. The condition occurs more frequently in women, and usually manifests itself when a person is between twenty and forty years old.

Presentation
The burning heat is usually limited to the soles of the feet, but may extend up to the ankles or lower legs of some patients. The burning can sometimes be accompanied by feelings of pins and needles or tingling in these regions </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 inclusion body myopathy and can you explain it in depth? [/INST] Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.
HIBMs are a group of muscle wasting disorders that are uncommon in the general world population. One autosomal recessive form of HIBM is known as IBM2 or GNE myopathy, which is a common genetic disorder amongst people of Iranian Jewish descent. IBM2 has also been identified in other minorities throughout the world, including those of Asian, European, and South American, and Middle Eastern descent. In Japan and other East Asian countries, this disorder is known as Distal Myopathy with Rimmed Vacuoles (DMRV).
IBM2 causes progressive muscle weakness and wasting. Muscle wasting usually starts around the age of 20 – 30 years, although young onset at 17 and old onset at 52 has been recorded. It can progress to marked disability within 10 to 15 years, confining many people with IBM2 to a wheelchair. The weakness and severity can vary from person to person. In some, weakness in the legs is noticed first. In some others, the hands are weakened more rapidly than the legs. IBM2 does not seem to affect the brain, internal organs or sensation. The quadriceps are relatively spared, and remain strong until the late stages of disease, which is the reason IBM2 is often referred to as Quadriceps Sparing Myopathy (QSM).

Signs and symptoms
Some early signs of HIBMs includes:

Difficulty walking on heels, and difficulty running;
Weak index finger;
Frequent loss of balance.
On muscle biopsy, the typical finding includes inclusion bodies, rimmed vacuoles and accumulation of aberrant proteins similar to those found in senile plaques of Alzheimers disease (amyloid beta, hyperphosphorylated tau, amongst others)

Genetics
The different forms have different mutations and inheritance patterns. See the detailed descriptions for details

Mechanisms
The exact mechanisms of these diseases are not well understood.   GNE/MNK a key enzyme in the sialic acid biosynthetic pathway, and loss-of-function mutations in GNE/MNK may lead to a lack of sialic acid, which in turn could affect sialoglycoproteins.  GNE knockout mice show problems similar to people with IBM and in people with IBM dystroglycan has been found to lack sialic acid.  However, the part of the dystroglycan that is important in muscle function does not seem to be affected.  Another protein, neural cell adhesion molecule is under-sialyated in people with IBM, but as of 2016 it had no known role in muscle function.

Diagnosis
The most useful information for accurate diagnosis is the symptoms and weakness pattern. If the quadriceps are spared but the hamstrings and iliopsoas are severely affected in a person between ages of 20 - 40, it is very likely HIBM will be at the top of the differential diagnosis. The doctor may order any or all of the following tests to ascertain if a person has IBM2:

Blood test for serum Creatine Kinase (CK or CPK);
Nerve Conduction Study (NCS) / Electomyography (EMG);
Muscle Biopsy;
Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) Scan to determine true sparing of quadriceps;
Blood Test or Buccal swab for genetic testing;

Classification
Types of hereditary inclusion body myopathy:

IBM2 is the most common form, and is an autosomal recessive form, caused by mutations in the GNE gene; this form mainly affects leg muscles, but with an unusual distribution that spares the quadriceps. The incidence of this form is about 10 per million per year. There are two forms: a quadriceps sparing myopathy (autosomal recessive form of inclusion body myopathy) and Nonaka type distal myopathy (distal myopathy with rimmed vacuoles). While occurring worldside it is most common in Jews of Persian origin. The GNE gene ecodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, uridine diphosphate-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Disease occurs when both copies in the genome are non functional </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 Constipation and can you explain it in depth? [/INST] Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement. Complications from constipation may include hemorrhoids, anal fissure or fecal impaction. The normal frequency of bowel movements in adults is between three per day and three per week. Babies often have three to four bowel movements per day while young children typically have two to three per day.Constipation has many causes. Common causes include slow movement of stool within the colon, irritable bowel syndrome, and pelvic floor disorders. Underlying associated diseases include hypothyroidism, diabetes, Parkinsons disease, celiac disease, non-celiac gluten sensitivity, colon cancer, diverticulitis, and inflammatory bowel disease. Medications associated with constipation include opioids, certain antacids, calcium channel blockers, and anticholinergics. Of those taking opioids about 90% develop constipation. Constipation is more concerning when there is weight loss or anemia, blood is present in the stool, there is a history of inflammatory bowel disease or colon cancer in a persons family, or it is of new onset in someone who is older.Treatment of constipation depends on the underlying cause and the duration that it has been present. Measures that may help include drinking enough fluids, eating more fiber, consumption of honey and exercise. If this is not effective, laxatives of the bulk forming agent, osmotic agent, stool softener, or lubricant type may be recommended. Stimulant laxatives are generally reserved for when other types are not effective. Other treatments may include biofeedback or in rare cases surgery.In the general population rates of constipation are 2–30 percent. Among elderly people living in a care home the rate of constipation is 50–75 percent. People spend, in the United States, more than US$250 million on medications for constipation a year.

Definition
Constipation is a symptom, not a disease. Most commonly, constipation is thought of as infrequent bowel movements, usually fewer than 3 stools per week. However, people may have other complaints as well including:
Straining with bowel movements
Excessive time needed to pass a bowel movement
Hard stools
Pain with bowel movements secondary to straining
Abdominal pain
Abdominal bloating.
the sensation of incomplete bowel evacuation.The Rome III Criteria are a set of symptoms that help standardize the diagnosis of constipation in various age groups. These criteria help physicians to better define constipation in a standardized manner.

Causes
The causes of constipation can be divided into congenital, primary, and secondary. The most common kind is primary and not life-threatening. It can also be divided by the age group affected such as children and adults.
Primary or functional constipation is defined by ongoing symptoms for greater than six months not due to an underlying cause such as medication side effects or an underlying medical condition. It is not associated with abdominal pain, thus distinguishing it from irritable bowel syndrome. It is the most common kind of constipation, and is often multifactorial. In adults, such primary causes include: dietary choices such as insufficient dietary fiber or fluid intake, or behavioral causes such as decreased physical activity. In the elderly, common causes have been attributed to insufficient dietary fiber intake, inadequate fluid intake, decreased physical activity, side effects of medications, hypothyroidism, and obstruction by colorectal cancer. Evidence to support these factors however is poor.Secondary causes include side effects of medications such as opiates, endocrine and metabolic disorders such as hypothyroidism, and obstruction such as from colorectal cancer or ovarian cancer. Celiac disease and non-celiac gluten sensitivity may also present with constipation. Cystocele can develop as a result of chronic constipation.

Diet
Constipation can be caused or exacerbated by a low-fiber diet, low liquid intake, or dieting. Dietary fiber helps to decrease colonic transport time, increases stool bulk but simultaneously softens stool. Therefore, diets low in fiber can lead to primary constipation.

Medications
Many medications have constipation as a side effect. Some include (but are not limited to) opioids, diuretics, antidepressants, antihistamines, antispasmodics, anticonvulsants, tricyclic antidepressants, antiarrythmics, beta-adrenoceptor antagonists, anti-diarrheals, 5-HT3 receptor antagonists such as ondansetron, and aluminum antacids. Certain calcium channel blockers such as nifedipine and verapamil can cause severe constipation due to dysfunction of motility in the rectosigmoid colon. Supplements such as calcium and iron supplements can also have constipation as a notable side effect.

Medical conditions
Metabolic and endocrine problems which may lead to constipation include: pheochromocytoma, hypercalcemia, hypothyroidism, hyperparathyroidism, porphyria, chronic kidney disease, pan-hypopituitarism, diabetes mellitus, and cystic fibrosis. Constipation is also common in individuals with muscular and myotonic dystrophy.Systemic diseases that may present with constipation include celiac disease and systemic sclerosis.Constipation has a number of structural (mechanical, morphological, anatomical) causes, namely through creating space-occupying lesions within the colon that stop the passage of stool, such as colorectal cancer, strictures, rectocoles, anal sphincter damage or malformation and post-surgical changes. Extra-intestinal masses such as other malignancies can also lead to constipation from external compression.Constipation also has neurological causes, including anismus, descending perineum syndrome, and Hirschsprungs disease. In infants, Hirschsprungs disease is the most common medical disorder associated with constipation. Anismus occurs in a small minority of persons with chronic constipation or obstructed defecation.Spinal cord lesions and neurological disorders such as Parkinsons disease and pelvic floor dysfunction can also lead to constipation.
Chagas disease may cause constipation through the destruction of the myenteric plexus.

Psychological
Voluntary withholding of the stool is a common cause of constipation. The choice to withhold can be due to factors such as fear of pain, fear of public restrooms, or laziness. When a child holds in the stool a combination of encouragement, fluids, fiber, and laxatives may be useful to overcome the problem. Early intervention with withholding is important as this can lead to anal fissures.

Congenital
A number of diseases present at birth can result in constipation in children. They are as a group uncommon with Hirschsprungs disease (HD) being the most common. There are also congenital structural anomalies that can lead to constipation, including anterior displacement of the anus, imperforate anus, strictures, and small left colon syndrome.

Pathophysiology
Diagnostic approach
The diagnosis is typically made based on a persons description of the symptoms. Bowel movements that are difficult to pass, very firm, or made up of small hard pellets (like those excreted by rabbits) qualify as constipation, even if they occur every day. Constipation is traditionally defined as three or fewer bowel movements per week. Other symptoms related to constipation can include bloating, distension, abdominal pain, headaches, a feeling of fatigue and nervous exhaustion, or a sense of incomplete emptying. Although constipation may be a diagnosis, it is typically viewed as a symptom that requires evaluation to discern a cause.

Description
Distinguish between acute (days to weeks) or chronic (months to years) onset of constipation because this information changes the differential diagnosis. This in the context of accompanied symptoms helps physicians discover the cause of constipation. People often describe their constipation as bowel movements that are difficult to pass, firm stool with lumpy or hard consistency, and excessive straining during bowel movements. Bloating, abdominal distension, and abdominal pain often accompany constipation. Chronic constipation (symptoms present at least three days per month for more than three months) associated with abdominal discomfort is often diagnosed as irritable bowel syndrome (IBS) when no obvious cause is found.Poor dietary habits, previous abdominal surgeries, and certain medical conditions can contribute to constipation. Diseases associated with constipation include hypothyroidism, certain types of cancer, and irritable bowel syndrome. Low fiber intake, inadequate amounts of fluids, poor ambulation or immobility, or medications can contribute to constipation. Once the presence of constipation is identified based on a culmination of the symptoms described above, then the cause of constipation should be figured out.
Separating non-life-threatening from serious causes may be partly based on symptoms. For example, colon cancer may be suspected if a person has a family history of colon cancer, fever, weight loss, and rectal bleeding. Other alarming signs and symptoms include family or personal history of inflammatory bowel disease, age of onset over 50, change in stool caliber, nausea, vomiting, and neurological symptoms like weakness, numbness and difficulty urinating.

Examination
A physical examination should involve at least an abdominal exam and rectal exam. Abdominal exam may reveal an abdominal mass if there is significant stool burden and may reveal abdominal discomfort. Rectal examination gives an impression of the anal sphincter tone and whether the lower rectum contains any feces or not. Rectal examination also gives information on the consistency of the stool, the presence of hemorrhoids, blood and whether any perineal irregularities are present including skin tags, fissures, anal warts. Physical examination is done manually by a physician and is used to guide which diagnostic tests to order.

Diagnostic tests
Functional constipation is common and does not warrant diagnostic testing. Imaging and laboratory tests are typically recommended for those with alarm signs or symptoms.The laboratory tests performed depends on the suspected underlying cause of the constipation. Tests may include CBC (complete blood count), thyroid function tests, serum calcium, serum potassium, etc.Abdominal X-rays are generally only performed if bowel obstruction is suspected, may reveal extensive impacted fecal matter in the colon, and may confirm or rule out other causes of similar symptoms.Colonoscopy may be performed if an abnormality in the colon like a tumor is suspected. Other tests rarely ordered include anorectal manometry, anal sphincter electromyography, and defecography.Colonic propagating pressure wave sequences (PSs) are responsible for discrete movements of the bowel contents and are vital for normal defecation. Deficiencies in PS frequency, amplitude, and extent of propagation are all implicated in severe defecatory dysfunction (SDD). Mechanisms that can normalize these aberrant motor patterns may help rectify the problem. Recently the novel therapy of sacral nerve stimulation (SNS) has been utilized for the treatment of severe constipation.

Criteria
The Rome III Criteria for functional constipation must include two or more of the following and present for the past three months, with symptoms starting for at least 6 months prior to diagnosis.
Straining during defecation for at least 25% of bowel movements
Lumpy or hard stools in at least 25% of defecations
Sensation of incomplete evacuation for at least 25% of defecations
Sensation of anorectal obstruction/blockage for at least 25% of defecations
Manual maneuvers to facilitate at least 25% of defecations
Fewer than 3 defecations per week
Loose stools are rarely present without the use of laxatives
There are insufficient criteria for irritable bowel syndrome

Prevention
Constipation is usually easier to prevent than to treat. Following the relief of constipation, maintenance with adequate exercise, fluid intake, and high-fiber diet is recommended.

Treatment
A limited number of cases require urgent medical intervention or will result in severe consequences.The treatment of constipation should focus on the underlying cause if known. The National Institute of Health and Care Excellence (NICE) break constipation in adults into two categories - chronic constipation of unknown cause and constipation due to opiates.In chronic constipation of unknown cause, the main treatment involves the increased intake of water and fiber (either dietary or as supplements). The routine use of laxatives or enemas is discouraged, as having bowel movements may come to be dependent upon their use.

Fiber supplements
Soluble fiber supplements such as psyllium are generally considered first-line treatment for chronic constipation, compared to insoluble fibers such as wheat bran. Side effects of fiber supplements include bloating, flatulence, diarrhea, and possible malabsorption of iron, calcium, and some medications. However, patients with opiate-induced constipation will likely not benefit from fiber supplements.

Laxatives
If laxatives are used, milk of magnesia or polyethylene glycol are recommended as first-line agents due to their low cost and safety. Stimulants should only be used if this is not effective. In cases of chronic constipation, polyethylene glycol appears superior to lactulose. Prokinetics may be used to improve gastrointestinal motility. A number of new agents have shown positive outcomes in chronic constipation; these include prucalopride and lubiprostone. Cisapride is widely available in third world countries, but has been withdrawn in most of the west. It has not been shown to have a benefit on constipation, while potentially causing cardiac arrhythmias and deaths.

Enemas
Enemas can be used to provide a form of mechanical stimulation. A large volume or high enema can be given to cleanse as much of the colon as possible of feces, and the solution administered commonly contains castile soap which irritates the colons lining resulting in increased urgency to defecate. However, a low enema is generally useful only for stool in the rectum, not in the intestinal tract.

Physical intervention
Constipation that resists the above measures may require physical intervention such as manual disimpaction (the physical removal of impacted stool using the hands; see fecal impaction).

Regular exercise
Regular exercise can help improve chronic constipation.

Surgical intervention
In refractory cases, procedures can be performed to help relieve constipation. Sacral nerve stimulation has been demonstrated to be effective in a minority of cases. Colectomy with ileorectal anastomosis is another intervention performed only in patients known to have a slow colonic transit time and in whom a defecation disorder has either been treated or is not present. Because this is a major operation, side effects can include considerable abdominal pain, small bowel obstruction, and post-surgical infections. Furthermore, it has a very variable rate of success and is very case dependent.

Prognosis
Complications that can arise from constipation include hemorrhoids, anal fissures, rectal prolapse, and fecal impaction. Straining to pass stool may lead to hemorrhoids. In later stages of constipation, the abdomen may become distended, hard and diffusely tender. Severe cases ("fecal impaction" or malignant constipation) may exhibit symptoms of bowel obstruction (nausea, vomiting, tender abdomen) and encopresis, where soft stool from the small intestine bypasses the mass of impacted fecal matter in the colon.

Epidemiology
Constipation is the most common chronic gastrointestinal disorder in adults. Depending on the definition employed, it occurs in 2% to 20% of the population. It is more common in women, the elderly and children. Specifically constipation with no known cause affects females more often affected than males. The reasons it occurs more frequently in the elderly is felt to be due to an increasing number of health problems as humans age and decreased physical activity.
12% of the population worldwide reports having constipation.
Chronic constipation accounts for 3% of all visits annually to pediatric outpatient clinics.
Constipation-related health care costs total $6.9 billion in the US annually.
More than four million Americans have frequent constipation, accounting for 2.5 million physician visits a year.
Around $725 million is spent on laxative products each year in America.

History
Since ancient times different societies have published medical opinions about how health care providers should respond to constipation in patients. In various times and places, doctors have made claims that constipation has all sorts of medical or social causes. Doctors in history have treated constipation in reasonable and unreasonable ways, including use of a spatula mundani.After the advent of the germ theory of disease then the idea of "auto-intoxication" entered popular Western thought in a fresh way. Enema as a scientific medical treatment and colon cleansing as alternative medical treatment became more common in medical practice.Since the 1700s in the West there has been some popular thought that people with constipation have some moral failing with gluttony or laziness.

Special populations
Children
Approximately 3% of children have constipation, with girls and boys being equally affected. With constipation accounting for approximately 5% of general pediatrician visits and 25% of pediatric gastroenterologist visits, the symptom carries a significant financial impact upon the healthcare system. While it is difficult to assess an exact age at which constipation most commonly arises, children frequently experience constipation in conjunction with life-changes. Examples include: toilet training, starting or transferring to a new school, and changes in diet. Especially in infants, changes in formula or transitioning from breast milk to formula can cause constipation </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 Syringoma and can you explain it in depth? [/INST] Syringomas are benign eccrine sweat duct tumors, typically found clustered on eyelids, although they may also be found in the armpits, abdomen, chest, neck, scalp, or groin area, including genitals, in a symmetric pattern.: 663   They are skin-colored or yellowish firm, rounded bumps, 1–3 mm in diameter, and may be confused with xanthoma, milia, hidrocystoma, trichoepithelioma, and xanthelasma.  They are more common in women and are most commonly found in middle-aged Asian women.  While they can present at any time in life, they typically present during adolescence.  They are usually not associated with any other symptoms, although can sometimes cause itchiness or irritation.

Types
The eruptive form typically presents on the anterior chest, abdomen, neck, and arms.  It presents in successive crops with periods of relief in between times of active rash.
The milia-like  type of syringoma is typically smaller lesions that have a milky white center that can look like milia.
The plaque type is more commonly associated with itchiness and chronic scratching that leads to epidermal thickening similar to lichen planus.
The familial form, in some cases of syringoma, exhibits a familial pattern in an autosomal-dominant pattern of inheritance.  Chromosome 16q22 has been shown to be involved in the genetic links of syringoma.

Presentation
Associated syndromes
Syringomas can be found in association with other symptoms as part of a syndrome.  Hailey–Hailey disease (also known as familial benign chronic pemphigus) is a blistering disease that can also include syringomas.Several systemic syndromes have also been associated with syringoma including diabetes mellitus, Down syndrome, Brooke–Spiegler syndrome, and Nicolau–Balus syndrome.  Specifically, diabetes mellitus is strongly associated with clear cell syringoma consisting of nests of clear cells containing glycogen.  A phosphorylase deficiency, resulting from elevated glucose levels seen in diabetes, is thought to lead to an accumulation of glycogen in the skin and within the clear cells.  The incidence of syringomas has been reported in up to 40% of people with Down syndrome, and can be associated with a condition calcinosis cutis, which requires prompt medical attention.  Brooke–Spiegler syndrome is a rare autosomal-dominant syndrome with cutaneous manifestations including syringomas and trichoepitheliomas.  Nicolau–Balus syndrome is a rare autosomal-dominant disorder consisting of atrophoderma vermiculata and syringomas.

Pathophysiology
The pathophysiology of syringomas remains largely unknown.  Familial patterns presenting in an autosomal-dominant pattern suggest a genetic link that can result in varying genetic aberrations in lesions, specifically chromosome 16q22.  The most commonly accepted theory is that syringomas are benign growths that arise from the intraepidermal portion of eccrine ducts.  Another theory suggests that syringomas are a reactive hyperplasia rather than a true neoplasm resulting after inflammatory processes such as eczema.  A hamartomatous process possibly could explain eruptive syringomas.  A hamartoma of pluripotent stem cells could precede the pathological process.  Syringomas may also be under hormonal influence, explaining the female predominance.

Diagnosis
Syringomas can often be diagnosed clinically based on presentation, distribution patterns over the body, lack of associated symptoms, and family history </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 Multiple epiphyseal dysplasia and can you explain it in depth? [/INST] Fairbanks disease or multiple epiphyseal dysplasia (MED) is a rare genetic disorder (dominant form: 1 in 10,000 births) that affects the growing ends of bones. Long bones normally elongate by expansion of cartilage in the growth plate (epiphyseal plate) near their ends. As it expands outward from the growth plate, the cartilage mineralizes and hardens to become bone (ossification). In MED, this process is defective.

Signs and symptoms
Children with autosomal dominant MED experience joint pain and fatigue after exercising. Their x-rays show small and irregular ossifications centers, most apparent in the hips and knees. There are very small capital femoral epiphyses and hypoplastic, poorly formed acetabular roofs. A waddling gait may develop. Knees have metaphyseal widening and irregularity while hands have brachydactyly (short fingers) and proximal metacarpal rounding. Flat feet are very common. The spine is normal but may have a few irregularities, such as scoliosis.By adulthood, people with MED are of short stature or in the low range of normal and have short limbs relative to their trunks. Frequently, movement becomes limited at the major joints, especially at the elbows and hips. However, loose knee and finger joints can occur. Signs of osteoarthritis usually begin in early adulthood.Children with recessive MED experience joint pain, particularly of the hips and knees, and commonly have deformities of the hands, feet, knees, or vertebral column (like scoliosis). Approximately 50% of affected children have abnormal findings at birth (such as club foot or twisted metatarsals, cleft palate, inward curving fingers due to underdeveloped bones and brachydactyly, or ear swelling caused by injury during birth). Height is in the normal range before puberty. As adults, people with recessive MED are only slightly more diminished in stature, but within the normal range. Lateral knee radiography can show multi-layered patellae.

Genetics
Multiple epiphyseal dysplasia (MED) encompasses a spectrum of skeletal disorders, most of which are inherited in an autosomal dominant form. However, there is an autosomal recessive form.Associated genes include COL9A1, COL9A2, COL9A3, COMP, and MATN3.Types include:

In the dominant form, mutations in five genes are causative: COMP (chromosome 19), COL9A1 (chromosome 6), COL9A2 (chromosome 1), COL9A3 (chromosome 20), and MATN3 (chromosome 2). However, in approximately 10%–20% of samples analyzed, a mutation cannot be identified in any of the five genes above, suggesting that mutations in other as-yet unidentified genes are involved in the pathogenesis of dominant MED.The COMP gene is mutated in 70% of the molecularly confirmed MED patients. Mutations are in the exons encoding the type III repeats (exons 8–14) and C-terminal domain (exons 15–19). The most common mutations in COL9A1 are in exons 8-10, in COL9A2 in exons 2-4, and in COL9A3 in exons 2-4. Altogether, those mutations cover 10% of the patients. The other 20% of affected people have mutations in MATN3 gene, all found within exon 2. The following testing regime has been recommended by the European Skeletal Dysplasia Network:
Level 1: COMP (exons 10–15) and MATN3 (exon 2)
Level 2: COMP (exons 8 & 9 and 16–19)
Level 3: COL9A1 (exon 8), COL9A2 and COL9A3 (exon 3)All those genes are involved in the production of the extracellular matrix (ECM). The role of COMP gene remains unclear. It is a noncollagenous protein of the ECM. Mutations in this gene can cause the pseudoachondroplasia (PSACH). It should play a role in the structural integrity of cartilage by its interaction with other extracellular matrix proteins and can be part of the interaction of the chondrocytes with the matrix and it is also a potent suppressor of apoptosis in chondrocytes. Another role is maintaining a vascular smooth muscle cells contractile under physiological or pathological stimuli.Since 2003, the European Skeletal Dysplasia Network has used an online system to diagnose cases referred to the network before mutation analysis to study the mutations causing PSACH or MED.COL9A1, COL9A2, COL9A3 are genes coding for collagen type IX, that is a component of hyaline cartilage. MATN3 protein may play a role in the formation of the extracellular filamentous networks and in the development and homeostasis of cartilage and bone.In the recessive form, the DTDST gene, also known as SLC26A2, is mutated in almost 90% of the patients, causing diastrophic dysplasia. It is a sulfate transporter, transmembrane glycoprotein implicated in several chondrodysplasias. It is important for sulfation of proteoglycans and matrix organization.

Diagnosis
Diagnosis should be based on the clinical and radiographic findings and a genetic analysis can be assessed.

Treatment
Symptomatic individuals should be seen by an orthopedist to assess the possibility of treatment (physiotherapy for muscular strengthening, cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs). Although there is no cure, surgery is sometimes used to relieve symptoms. Surgery may be necessary to treat misalignment of the hip (osteotomy of the pelvis or the collum femoris) and, in some cases, malformation (e.g., genu varum or genu valgum). In some cases, total hip replacement may be necessary. However, surgery is not always necessary or appropriate.Sports involving joint overload are to be avoided, while swimming or cycling are strongly suggested. Cycling has to be avoided in people having ligamentous laxity.
Weight control is suggested.The use of crutches, other deambulatory aids or wheelchair is useful to prevent hip pain. Pain in the hand while writing can be avoided using a pen with wide grip.

History
Multiple epiphyseal dysplasia was described separately by Seved Ribbing and Harold Arthur Thomas Fairbank in the 1930s.In 1994, Ralph Oehlmanns group mapped MED to the peri-centromeric region of chromosome 19, using genetic linkage analysis. Michael Briggs group mapped PSACH to the same area. COMP gene was firstly linked to MED and PSACH in 1995. In 1995, the group led by Knowlton did a "high-resolution genetic and physical mapping of multiple epiphyseal dysplasia and pseudoachondroplasia mutations at chromosome 19p13.1-p12."Research on COMP led to mouse models of the pathology of MED. In 2002, Svenssons group generated a COMP-null mouse to study the COMP protein in vivo. These mice showed no anatomical, histological, or even ultrastructural abnormalities and none of the clinical signs of PSACH or MED </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 angiopathy with nephropathy, aneurysms, and muscle cramps syndrome 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 Orbital emphysema and can you explain it in depth? [/INST] Orbital emphysema (/ˈɔː(r)bɪt(ə)l ˌemfɪˈsiːmə/, also known as pneumo-orbit) is a medical condition that refers to the trapping of air within the loose subcutaneous around the orbit that is generally characterized by sudden onset swelling and bruising at the impacted eye, with or without deterioration of vision, which the severity depends on the density of air trapped under the orbital soft tissue spaces.It is most commonly result from forceful sneezing, nose blowing, or coughing among patients with a history of periorbital trauma or orbital fractures that happened several hours-days in advance. Rare occasions have also been reported in relation to individuals with no traumatic past events that include: infection, esophageal rupture, postoperative complications, pulmonary barotrauma, with the same predisposing factors (sneezing, nose blowing, or coughing). A four-stage system of orbital emphysema was developed for severity classification. Clinical diagnosis can be made based on a combination of medical history, physical examination, and computed tomography. There are three kinds of orbital emphysema including palpebral emphysema, true orbital emphysema, and orbitopalpebral emphysema.Orbital emphysema on its own is a mild and self-limiting disease, and usually requires no treatment. If related visual symptoms or other acute orbital compression symptoms are present, lateral canthotomy or cantholysis, orbital decompression by needle aspiration, and bone decompression may be required to relieve orbital pressure and preserve vision.

Cause
Trauma
Blunt trauma caused by a direct blow at the orbital is the major leading cause of orbital emphysema. Any object with force and/or speed, typically a ball, fist or vehicle accidents, can result in orbital floor and/or medial wall fractures. These disruptions permit air entry into the orbital subcutaneous from the sinus, with a one-way check valve mechanism that forbids the air from exiting. Victims are often found in sport-related concussion, automobile vehicle accidents, or snowboarding accidents.
Traumatic injuries do not cause onset swelling unless there is a forceful injection of air from vigorous sneezing, nose-blowing, or coughing. These generate an acute increase in intraorbital pressure, compromising the intraorbital neurovascular structures, which subsequently trigger the development of orbital emphysema.

Postoperative complications
Orbital emphysema is a common result of certain types of surgery, in particular the ones that involve orbital medial wall. It may also occur in other oral, nasal, and maxillofacial surgical interventions, in which the occurrence is unexpected. They can weaken sinuses, bony structure, induce deep orbital tissue damages, or globe perforation that cause air leakage into the periorbital soft tissues and superiorly into the supraorbital fat. These surgical procedures may possibly introduce staphylococci, streptococci, and anaerobic bacteria via a compromised bony wall that can cause periorbital infection. The corresponding weakened or degenerated tissues cannot withstand the sudden increase in intraocular pressure and impaired ocular perfusion, driven by severe coughing or sneezing. It subsequently results in air trapped in the periorbital subcutaneous tissue and the development of orbital emphysema, which is often mistaken as allergic reactions. Without proper management can lead to cardiac life-threatening conditions such as cardiopulmonary embolism, cardiac tamponade, and respiratory distress, depending on the volume of air trapped under the facial soft tissues.

Infection
Infections can spread beyond their initial location, including lamina papyracea.

Signs and Symptoms
The signs and symptoms of orbital emphysema vary depending on the original cause, but it is preliminary associated with swelling, bruising, and tenderness around the impacted eye. It may also involve proptosis or the deterioration of vision, typically diplopia. The entrapped air may cause an acute increase in the intraocular pressure or vascular compromise that restrict ocular motility, prohibit the closure of eyelids, and the loss of sensation over the upper cheek areas.Server entrapment in the soft tissues tends to stimulate oculocardiac reflex, which is likely to generate significant vagal responses including nausea, dizziness, vomiting, bradycardia, syncope and heart block. Without treating it promptly may subsequently result in compromisation of ocular function and visual impairment.

Pathophysiology
Orbital emphysema occurs following forceful injection of air into the soft tissues of the orbit through a breach in one of the orbital walls which is typically associated with orbital fracture after blunt trauma, or less frequently with compressed air injuries, tumours and infections of the sinonasal region or complications after surgery.Orbital emphysema develops after an orbital fracture in a three-step process. After the fracture has occurred on one of the orbital walls, a sino-orbital communication is established. The communication will allow air to be forced from the sinuses into the orbit in the presence of a pressure gradient from forceful expiratory efforts, nose-blowing or even a sneeze. Orbital emphysema is typically a harmless disorder because air escapes as quickly as it enters the fracture site, and the increase in intraorbital pressure is usually transient, lasting for as long as the sneeze or nose blowing. However, when orbital soft tissues, such as fat, falls back on the sino-orbital communication, a one-way ball valve will be created, leading to the entrapment of air. When sufficient air accumulates, it will result in acute compartment syndrome and vascular compromise, causing complications including proptosis, visual impairment, central retinal artery occlusion, compressive optic neuropathy, and other severe complications caused by orbital compartment syndrome.There are three variations of orbital emphysema, namely palpebral emphysema, true orbital emphysema, and orbitopalpebral emphysema.

Palpebral emphysema
Palpebral emphysema refers to emphysema of the eyelids alone. It is a rare kind of orbital emphysema which is usually caused by fractures of the lacrimal bone. The lacrimal sac ruptures as a result of the fracture, allowing air from the nasal cavity to enter the tissues of the eyelid. Alternatively, facial subcutaneous air may simply pass into the eyelids along fascial plane to produce palpebral emphysema. As long as the orbital septum is intact, air is confined in the eyelids.

True orbital emphysema
True orbital emphysema occurs when there is air behind an intact orbital septum. This condition arises due to a fracture of more than one bony orbital walls of paranasal sinuses and tearing of adjacent sinus mucosa, and communication of a sinus with the orbit is established. This fracture usually involves the ethmoid, and sometimes involves frontal, sphenoid, and maxillary sinuses. The air usually enters the orbit when the pressure within the upper respiratory tract is increased due to expiratory efforts, nose blowing or sneezing.

Orbitopalperbal emphysema
Orbitopalpebral emphysema refers to the trapping of air inside both the soft tissues of the orbit and the eyelid. It is usually a sequelae of a true orbital emphysema. When too much air accumulates inside the orbit, the orbital septum ruptures due to high intraorbital pressure. Air may then pass freely from the orbit into the eyelids through the break in the orbital septum.

Stages
There are four stages of orbital emphysema.

Stage I
Stage I orbital emphysema can only be diagnosed with radiological films. There is only a small amount of intraorbital air, and the patient does not show any clinical signs or symptoms.

Stage II
Stage II orbital emphysema develops as the intraorbital air volume increases, causing the eyeball to displace horizontally or vertically (globe dystopia) or to protrude anteriorly (proptosis). The patient may experience diplopia as a result of the globe displacement.

Stage III
Stage III orbital emphysema develops when the limits of spontaneous decompression are exceeded. The pressure will be transmitted to orbital tissues and then to the globe, resulting in an increase in intraocular pressure which may cause visual loss when the nutrient vessels supplying the optic nerve are compressed.

Stage IV
Stage IV orbital emphysema develops when the intraorbital air mass  results in an intraocular pressure of more than 60 to 70 mmHg. The significantly elevated intraocular pressure will lead to central retinal artery occlusion, which may result in permanent and irreversible damage to the retina.

Clinical Diagnosis
The diagnosis of orbital emphysema is usually made by physical examination of the eyelids, and, or by computer tomography (CT).

Physical examination
Physical examination of the eyelid can be done by the palpation for the pathognomonic cracking, crepitation, and tense tissue on the upper and lower eyelids. The findings of the examination are supported with the medical history of the patient and confirmed with orbital CT.

Computed tomography (CT)
Computed tomography is effective and sensitive in the diagnosis of orbital emphysema, as it can confirm the anatomical location and size of air, bony defects, indentation of the eyeball, and the condition of the optic nerve, as well as the presence of any extraocular muscle entrapment and herniation of preorbital fat into the sinus cavities. The location of the orbital emphysema is present near the site of the fracture. The scans are usually taken along the transverse plane. Transverse images allow the evaluation of fractures in medial and lateral orbital walls. By reformatting these transverse images or taking coronal images, the examination of orbital floor and roof is permitted. Helical scanning is preferred as it has a lower imaging time and radiation dose comparing to conventional scanning, especially when reforming transverse helical scans into coronal images. The staging of orbital emphysema can then be determined with visual acuity examination and ophthalmoscopy. A disadvantage of using a CT scan is that when detecting air after orbital trauma, the presence of a wooden foreign object can give a false positive result of orbital emphysema </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 Microcystic adnexal carcinoma and can you explain it in depth? [/INST] Microcystic adnexal carcinoma (MAC) is a rare sweat gland cancer, which often appears as a yellow spot or bump in the skin. It usually occurs in the neck or head, although cases have been documented in other areas of the body. Most diagnosis occur past the age of 50. Although considered an invasive cancer, metastasis rarely occurs. If the tumor spreads, it can grow and invade fat, muscles, and other types of tissue. Main treatments are wide local excision or Mohs micrographic surgery, which ensures that most, if not all, cancer cells are removed surgically.

Presentation
MACs usually present as a smooth, flesh or yellow colored, slow-growing nodule or bump somewhere on the face or neck with typical development being 3–5 years. The most common location is the mouth (occurring in 74% of cases), however cases have been documented on the scalp, tongue, trunk, upper extremities, and genitals. Patients are more likely to be white, female, and middle aged or elderly, although cases have been documented in children.
Although usually presenting with no visual or physical symptoms, some patients do experience numbness, paresthesia, burning, or tingling. This may be due to the invasive nature of MACs, which can burrow deep into underlying tissues and nerves in the face. MAC is very difficult to recognize and differentiate from other conditions. Specialists may suggest a series of tests including a biopsy, an MRI, or a CT scan. The average tumor size is less than 2 cm, however cases have been documented where tumor size exceeds 7.9 cm </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 Endometrial intraepithelial neoplasia and can you explain it in depth? [/INST] Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion of the uterine lining that predisposes to endometrioid endometrial adenocarcinoma.  It is composed of a collection of abnormal endometrial cells, arising from the glands that line the uterus, which have a tendency over time to progress to the most common form of uterine cancer—endometrial adenocarcinoma, endometrioid type.

History
EIN lesions have been discovered by a combination of molecular, histologic, and clinical outcome studies beginning in the 1990s which provide a multifaceted characterization of this disease.  They are a subset of a larger mixed group of lesions previously called "endometrial hyperplasia". The EIN diagnostic schema is intended to replace the previous "endometrial hyperplasia" classification as defined by the World Health Organization in 1994, which have been separated into benign (benign endometrial hyperplasia) and premalignant (EIN) classes in accordance with their behavior and clinical management.
EIN should not be confused with an unrelated entity, serous intraepithelial carcinoma ("serous EIC"), which is an early stage of a different tumor type known as papillary serous adenocarcinoma that also occurs in the same location within the uterus.

Clinical aspects
The average age at time of EIN diagnosis is approximately 52 years, compared to approximately 61 years for carcinoma.  The timeframe and likelihood of EIN progression to cancer, however, is not constant amongst all women.  Some cases of EIN are first detected as residual premalignant disease in women who already have carcinoma, whereas other EIN lesions disappear entirely and never lead to cancer.  For this reason, treatment benefits and risks must be individualized for each patient under the guidance of an experienced physician.
Risk factors for development of EIN and the endometrioid type of endometrial carcinoma include exposure to estrogens without opposing progestins, obesity, diabetes, and rare hereditary conditions such as hereditary nonpolyposis colorectal cancer.  Protective factors include use of combined oral contraceptive pills (low dose estrogen and progestin), and prior use of a contraceptive intrauterine device.

Biology
EIN lesions demonstrate all of the behaviors and characteristics of a premalignant, or precancerous, lesion.
Precancer Features of EIN (Table I). The cells of an EIN lesion are genetically different than normal and malignant tissues, and have a distinctive appearance under the light microscope </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 Nasal septal hematoma and can you explain it in depth? [/INST] Nasal septal hematoma is a condition affecting the nasal septum. It can be associated with trauma.A septal hematoma is blood that collects in the space between the septal cartilage and the overlying perichondrium (a cross section of the cartilaginous portion of the nasal septum). A hematoma may deprive the septal cartilage of its blood supply from the overlying mucosa and can lead to permanent sequelae.The septal cartilage has no blood supply of its own and will receives all of its nutrients and oxygen from the perichondrium. An untreated septal hematoma may lead to the destruction of the septum and immediate drainage is necessary. Timely diagnosis and/or treatment of septal hematomas can cause what is called a saddle nose deformity.This condition is more common in children because the septum is thicker and the lining more flexible.

Signs and symptoms
A normal nasal septum is rigid and thin. If you have a septal hematoma, your doctor will be able to press it down with a swab as the area will be soft. A quick check in the nose will show any swelling between the nostrils.Symptoms can include:

blockage in breathing
change in nose shape
painful swelling of nasal septum
nasal congestion.On occasion, it is possible for people with a septal hematoma to experience headache, nausea, vomiting, and fainting.

Causes
The most common causes of nasal septal hematomas include:

broken nose (nasal fracture)
medication
surgery or injury to the soft tissue area.In adults, nasal septal hematoma typically occur with significant facial trauma and/or nasal fracture. However, in children, due to their thicker septum and more flexible lining, nasal septal hematoma can be caused from minor nasal trauma such as simple falls, collisions with stationary objects, or minor altercations with siblings.

Mechanism and pathophysiology
The exact mechanism for the formation of hematoma from nasal trauma is controversial, but thought to occur in nasal septal hematomas when there is force to the nasal cartilage. The force causes the perichondrial blood vessels to leak and rupture in the nasal septum. The cartilage in the septum is avascular and can be 2–4 mm thick. The septum gets its blood supply from the ethmoid and sphenopalatine arteries.The nasal septum is composed of cartilaginous, membranous, and bony components overlaid by mucoperichondrium and mucoperiosteum. Bleeding within the confines of the mucoperichnondrium leads to a septal hematoma, where as external bleeding from Kiesselbachs plexus results in epistaxis. The Kiesselbach plexus is located anterior inferior of the nasal septum, where the anastomosis of blood vessels is located.Normal nasal mucosa is pink and healthy appearing, without ulcerations, crusting, or bleeding. Some common, abnormal variations include septal deviations, spurs, and an enlarged, aerated middle turbinate. Pale or inflamed mucosa, purulence, nasal polyps, or a septal perforation are all common pathologic features that may or may not be combined with the abnormal variations listed above.

Diagnosis
The doctor will use a nasal speculum for visualization of the nasal septum, the inferior turbinate, and a portion of the middle turbinate. The view of the nasal passage may be partially obstructed by the tools used. When there is minimal obstruction, it is often possible to visualize the nasopharynx.Identifying the Nasal Septal Hematoma
If lateral bulging of the septum and fluctuance persist after the nasal administration of a vasoconstrictive agent, such as oxymetazoline, it is a strong indicator of a nasal septal hematoma.  A septal hematoma is highly likely in patients who have had trauma or a sudden onset of nasal blockage that does not resolve with the removal of blood clots and the administration of a vasoconstrictive agent.Diagnosis can be made by a medical professional after performing an anterior rhinoscopy examination, by using an otoscope or a nasal speculum and overhead light source.Sometimes palpitation is used to diagnose the hematoma.

Treatment
A septal hematoma requires urgent treatment from a doctor in order to stop any further complications arising.Prompt treatment of septal hematomas can prevent complications such as ischemia of the septal cartilage, which can lead to permanent necrosis and a saddle-nose deformity. Such complication can occur rapidly, within as few as 3 days.There are two different procedures used to achieve this and will be selected upon the size of the swelling or clot. If the condition is being treated promptly and is still relatively small, then a small incision can be made to allow the blood to flow out. If the septal hematoma has been left untreated, then a doctor may need to insert a mechanism in order to fully remove the blood from the area.If left untreated, the hematoma can cause bacterial colonization that leads to infection. Within 72 hours, the infection can form a septal abscess.Treating a septal hematoma requires it to be incised and drained to prevent avascular necrosis of the septal hyaline cartilage. This will depend on diffusion of nutrients from its attached nasal mucosa.The septum can generally heal within 1 week, without any evidence of the incision. The mucosa will appear healthy and smooth.Secondary infections can be prevented by starting the patient on an antibiotic regimen immediately after the procedure and continuing the treatment while the nasal packs are in place. If an abscess is present, a specimen of the abscess can be sent for culture to ensure that the antibiotics prescribed have provided adequate coverage. Culture-directed therapy can help avert dangerous late sequalae, including the intracranial extension of a septal abscess. If the hematoma is not promptly drained, the septal cartilage may be destroyed. In such cases, a saddle-nose deformity may develop.

Prognosis
As long as the septal hematoma is treated promptly, a full recovery is common.  If the condition is left untreated and develops complications such as fever, infection, or an abscess, then the nasal septal hematoma is still very treatable if seen by a doctor. If saddle nose is developed, surgery could be required.

Epidemiology
Septal hematomas are rare but can effect everyone in every age group. There is no exact number  of the incidence that occur because a lot of the cases will remain undiagnosed </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 Enterolith and can you explain it in depth? [/INST] An enterolith is a mineral concretion or calculus formed anywhere in the gastrointestinal system.  Enteroliths are uncommon and usually incidental findings but, once found, they require at a minimum watchful waiting.  If there is evidence of complications, they must be removed. An enterolith may form around a nidus, a small foreign object such as a seed, pebble, or piece of twine that serves as an irritant. In this respect, an enterolith forms by a process similar to the creation of a pearl. An enterolith is not to be confused with a gastrolith, which helps digestion.

In equines
Equine enteroliths are found by walking pastures or turning over manure compost piles to find small enteroliths, during necroscopy, and increasingly, during surgery for colic.  Therefore, the incidence of asymptomatic enteroliths is unknown.
Equine enteroliths are typically smoothly spherical or tetrahedral, consist mostly of the mineral struvite (ammonium magnesium phosphate), and have concentric rings of mineral precipitated around a nidus.Enteroliths in horses were reported widely in the 19th century, infrequently in the early 20th century, and now increasingly.  They have also been reported in zebras: five in a zoo in California and one in a zoo in Wisconsin.  Struvite enteroliths are associated with elevated pH and mineral concentrations in the lumen.  In California, struvite enteroliths are associated also with a high proportion of alfalfa in the feed and less access to grass pasture.  This association has been attributed to the cultivation of alfalfa on serpentine soils, resulting in high concentrations of magnesium in the alfalfa.

In humans
In humans, enteroliths are rare and may be difficult to distinguish from gall stones. Their chemical composition is diverse, and rarely can a nidus be found.  A differential diagnosis of an enterolith requires the enterolith, a normal gallbladder, and a diverticulum.An enterolith typically forms within a diverticulum.  An enterolith formed in a Meckels diverticulum sometimes is known as a Meckels enterolith.  Improper use of magnesium oxide as a long-term laxative has been reported to cause enteroliths and/or medication bezoars.Most enteroliths are not apparent and cause no complications </s>