<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 Myasthenia gravis and can you explain it in depth? [/INST] Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, trouble talking, and trouble walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma.Myasthenia gravis is an autoimmune disease of the neuro-muscular junction which results from antibodies that block or destroy nicotinic acetylcholine receptors (AChR) at the junction between the nerve and muscle. This prevents nerve impulses from triggering muscle contractions. Most cases are due to immunoglobulin G1 (IgG1) and IgG3 antibodies that attack AChR in the postsynaptic membrane, causing complement-mediated damage and muscle weakness. Rarely, an inherited genetic defect in the neuromuscular junction results in a similar condition known as congenital myasthenia. Babies of mothers with myasthenia may have symptoms during their first few months of life, known as neonatal myasthenia. Diagnosis can be supported by blood tests for specific antibodies, the edrophonium test, or a nerve conduction study.MG is generally treated with medications known as acetylcholinesterase inhibitors, such as neostigmine and pyridostigmine. Immunosuppressants, such as prednisone or azathioprine, may also be used. The surgical removal of the thymus may improve symptoms in certain cases. Plasmapheresis and high-dose intravenous immunoglobulin may be used during sudden flares of the condition. If the breathing muscles become significantly weak, mechanical ventilation may be required. Once intubated acetylcholinesterase inhibitors may be temporarily held to reduce airway secretions.MG affects 50 to 200 per million people. It is newly diagnosed in three to 30 per million people each year. Diagnosis has become more common due to increased awareness. MG most commonly occurs in women under the age of 40 and in men over the age of 60. It is uncommon in children. With treatment, most of those affected lead relatively normal lives and have a normal life expectancy. The word is from the Greek mys, "muscle" and astheneia "weakness", and the Latin gravis, "serious".

Signs and symptoms
The initial, main symptom in MG is painless weakness of specific muscles, not fatigue. The muscle weakness becomes progressively worse during periods of physical activity and improves after periods of rest. Typically, the weakness and fatigue are worse toward the end of the day. MG generally starts with ocular (eye) weakness; it might then progress to a more severe generalized form, characterized by weakness in the extremities or in muscles that govern basic life functions.

Eyes
In about two-thirds of individuals, the initial symptom of MG is related to the muscles around the eye. Eyelid drooping (ptosis may occur due to weakness of m. levator palpebrae superioris) and double vision (diplopia, due to weakness of the extraocular muscles). Eye symptoms tend to get worse when watching television, reading, or driving, particularly in bright conditions. Consequently, some affected individuals choose to wear sunglasses. The term "ocular myasthenia gravis" describes a subtype of MG where muscle weakness is confined to the eyes, i.e. extraocular muscles, m. levator palpebrae superioris, and m. orbicularis oculi. Typically, this subtype evolves into generalized MG, usually after a few years.

Eating
The weakness of the muscles involved in swallowing may lead to swallowing difficulty (dysphagia). Typically, this means that some food may be left in the mouth after an attempt to swallow, or food and liquids may regurgitate into the nose rather than go down the throat (velopharyngeal insufficiency). Weakness of the muscles that move the jaw (muscles of mastication) may cause difficulty chewing. In individuals with MG, chewing tends to become more tiring when chewing tough, fibrous foods. Difficulty in swallowing, chewing, and speaking is the first symptom in about one-sixth of individuals.

Speaking
Weakness of the muscles involved in speaking may lead to dysarthria and hypophonia. Speech may be slow and slurred, or have a nasal quality. In some cases, a singing hobby or profession must be abandoned.

Head and neck
Due to weakness of the muscles of facial expression and muscles of mastication, facial weakness may manifest as the inability to hold the mouth closed (the "hanging jaw sign") and as a snarling expression when attempting to smile. With drooping eyelids, facial weakness may make the individual appear sleepy or sad. Difficulty in holding the head upright may occur.

Other
The muscles that control breathing and limb movements can also be affected; rarely do these present as the first symptoms of MG, but develop over months to years. In a myasthenic crisis, a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life. Crises may be triggered by various biological stressors such as infection, fever, an adverse reaction to medication, or emotional stress.

Pathophysiology
MG is an autoimmune synaptopathy. The disorder occurs when the immune system malfunctions and generates antibodies that attack the bodys tissues. The antibodies in MG attack a normal human protein, the nicotinic acetylcholine receptor, or a related protein called MuSK, a muscle-specific kinase. Other, less frequent antibodies are found against LRP4, agrin, and titin proteins.Human leukocyte antigen haplotypes are associated with increased susceptibility to myasthenia gravis and other autoimmune disorders. Relatives of people with myasthenia gravis have a higher percentage of other immune disorders.The thymus gland cells form part of the bodys immune system. In those with myasthenia gravis, the thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells.

In pregnancy
For women who are pregnant and already have MG, in a third of cases, they have been known to experience an exacerbation of their symptoms, and in those cases, it usually occurs in the first trimester of pregnancy. Signs and symptoms in pregnant mothers tend to improve during the second and third trimesters. Complete remission can occur in some mothers. Immunosuppressive therapy should be maintained throughout pregnancy, as this reduces the chance of neonatal muscle weakness, and controls the mothers myasthenia.About 10–20% of infants with mothers affected by the condition are born with transient neonatal myasthenia (TNM), which generally produces feeding and respiratory difficulties that develop about 12 hours to several days after birth. A child with TNM typically responds very well to acetylcholinesterase inhibitors, and the condition generally resolves over a period of three weeks, as the antibodies diminish, and generally does not result in any complications. Very rarely, an infant can be born with arthrogryposis multiplex congenita, secondary to profound intrauterine weakness. This is due to maternal antibodies that target an infants acetylcholine receptors. In some cases, the mother remains asymptomatic.

Diagnosis
MG can be difficult to diagnose, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders.Three types of myasthenic symptoms in children can be distinguished:
Transient neonatal myasthenia occurs in 10 to 15% of babies born to mothers afflicted with the disorder, and disappears after a few weeks.
Congenital myasthenia, the rarest form, occurs when genes are present from both parents.
Juvenile myasthenia gravis is most common in females.Congenital myasthenias cause muscle weakness and fatigability similar to those of MG.
The signs of congenital myasthenia usually are present in the first years of childhood, although they may not be recognized until adulthood.

Classification
When diagnosed with MG, a person is assessed for his or her neurological status and the level of illness is established. This is usually done using the accepted Myasthenia Gravis Foundation of America Clinical Classification scale.

Physical examination
During a physical examination to check for MG, a doctor might ask the person to perform repetitive movements. For instance, the doctor may ask one to look at a fixed point for 30 seconds and to relax the muscles of the forehead, because a person with MG and ptosis of the eyes might be involuntarily using the forehead muscles to compensate for the weakness in the eyelids. The clinical examiner might also try to elicit the "curtain sign" in a person by holding one of the persons eyes open, which in the case of MG will lead the other eye to close.

Blood tests
If the diagnosis is suspected, serology can be performed:

One test is for antibodies against the acetylcholine receptor; the test has a reasonable sensitivity of 80–96%, but in ocular myasthenia, the sensitivity falls to 50%.
A proportion of the people without antibodies against the acetylcholine receptor have antibodies against the MuSK protein.
In specific situations, testing is performed for Lambert-Eaton syndrome.

Electrodiagnostics
Muscle fibers of people with MG are easily fatigued, which the repetitive nerve stimulation test can help diagnose. In single-fiber electromyography, which is considered to be the most sensitive (although not the most specific) test for MG, a thin needle electrode is inserted into different areas of a particular muscle to record the action potentials from several samplings of different individual muscle fibers. Two muscle fibers belonging to the same motor unit are identified, and the temporal variability in their firing patterns is measured. Frequency and proportion of particular abnormal action potential patterns, called "jitter" and "blocking", are diagnostic. Jitter refers to the abnormal variation in the time interval between action potentials of adjacent muscle fibers in the same motor unit. Blocking refers to the failure of nerve impulses to elicit action potentials in adjacent muscle fibers of the same motor unit.

Ice test
Applying ice for 2–5 minutes to the muscles reportedly has a sensitivity and specificity of 76.9% and 98.3%, respectively, for the identification of MG. Acetylcholinesterase is thought to be inhibited at the lower temperature, which is the basis for this diagnostic test. This generally is performed on the eyelids when ptosis is present and is deemed positive if a ≥2-mm rise in the eyelid occurs after the ice is removed.

Edrophonium test
This test requires the intravenous administration of edrophonium chloride or neostigmine, drugs that block the breakdown of acetylcholine by cholinesterase (acetylcholinesterase inhibitors). This test is no longer typically performed, as its use can lead to life-threatening bradycardia (slow heart rate) which requires immediate emergency attention. Production of edrophonium was discontinued in 2008.

Imaging
A chest X-ray may identify widening of the mediastinum suggestive of thymoma, but computed tomography or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas and are generally done for this reason. MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles.

Pulmonary function test
The forced vital capacity may be monitored at intervals to detect increasing muscular weakness. Acutely, negative inspiratory force may be used to determine adequacy of ventilation; it is performed on those individuals with MG.

Management
Treatment is by medication and/or surgery. Medication consists mainly of acetylcholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process. Thymectomy is a surgical method to treat MG.

Medication
Worsening may occur with medication such as fluoroquinolones, aminoglycosides, and magnesium. About 10% of people with generalized MG are considered treatment-refractory. Autologous hematopoietic stem cell transplantation (HSCT) is sometimes used in severe, treatment-refractory MG. Available data provide preliminary evidence that HSCT can be an effective therapeutic option in carefully selected cases.Efgartigimod alfa was approved for medical use in the United States in December 2021.

Acetylcholinesterase inhibitors
Acetylcholinesterase inhibitors can provide symptomatic benefit and may not fully remove a persons weakness from MG. While they might not fully remove all symptoms of MG, they still may allow a person the ability to perform normal daily activities. Usually, acetylcholinesterase inhibitors are started at a low dose and increased until the desired result is achieved. If taken 30 minutes before a meal, symptoms will be mild during eating, which is helpful for those who have difficulty swallowing due to their illness. Another medication used for MG, atropine, can reduce the muscarinic side effects of acetylcholinesterase inhibitors. Pyridostigmine is a relatively long-acting drug (when compared to other cholinergic agonists), with a half-life around four hours with relatively few side effects. Generally, it is discontinued in those who are being mechanically ventilated, as it is known to increase the amount of salivary secretions. A few high-quality studies have directly compared cholinesterase inhibitors with other treatments (or placebo); their practical benefit may be such that conducting studies in which they would be withheld from some people would be difficult.

Immune suppressants
The steroid prednisone might also be used to achieve a better result, but it can lead to the worsening of symptoms for 14 days and takes 6–8 weeks to achieve its maximal effectiveness. Due to the myriad symptoms that steroid treatments can cause, it is not the preferred method of treatment. Other immune suppressing medications may also be used including rituximab.

Plasmapheresis and IVIG
If the myasthenia is serious (myasthenic crisis), plasmapheresis can be used to remove the putative antibodies from the circulation. Also, intravenous immunoglobulins (IVIGs) can be used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks, and often are associated with high costs, which make them prohibitive; they are generally reserved for when MG requires hospitalization.

Surgery
As thymomas are seen in 10% of all people with the MG, they are often given a chest X-ray and CT scan to evaluate their need for surgical removal of their thymus glands and any cancerous tissue that may be present. Even if surgery is performed to remove a thymoma, it generally does not lead to the remission of MG. Surgery in the case of MG involves the removal of the thymus, although in 2013, no clear benefit was indicated except in the presence of a thymoma. A 2016 randomized, controlled trial, however, found some benefits.

Physical measures
People with MG should be educated regarding the fluctuating nature of their symptoms, including weakness and exercise-induced fatigue. Exercise participation should be encouraged with frequent rest. In people with generalized MG, some evidence indicates a partial home program including training in diaphragmatic breathing, pursed-lip breathing, and interval-based muscle therapy may improve respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance.

Medical imaging
In people with myasthenia gravis, older forms of iodinated contrast used for medical imaging have caused an increased risk of exacerbation of the disease, but modern forms have no immediate increased risk.

Prognosis
The prognosis of people with MG is generally good, as is quality of life, given very good treatment. Monitoring of a person with MG is very important, as at least 20% of people diagnosed with it will experience a myasthenic crisis within two years of their diagnosis, requiring rapid medical intervention. Generally, the most disabling period of MG might be years after the initial diagnosis. In the early 1900s, 70% of detected cases died from lung problems; now, that number is estimated to be around 3–5%, which is attributed to increased awareness and medications to manage symptoms.

Epidemiology
MG occurs in all ethnic groups and both sexes. It most commonly affects women under 40 and people from 50 to 70 years old of either sex, but it has been known to occur at any age. Younger people rarely have thymoma. Prevalence in the United States is estimated at between 0.5 and 20.4 cases per 100,000, with an estimated 60,000 Americans affected. Within the United Kingdom, an estimated 15 cases of MG occur per 100,000 people.

History
The first to write about MG were Thomas Willis, Samuel Wilks, Erb, and Goldflam. The term "myasthenia gravis pseudo-paralytica" was proposed in 1895 by Jolly, a German physician. Mary Walker treated a person with MG with physostigmine in 1934. Simpson and Nastuck detailed the autoimmune nature of the condition. In 1973, Patrick and Lindstrom used rabbits to show that immunization with purified muscle-like acetylcholine receptors caused the development of MG-like symptoms.

Research
Immunomodulating substances, such as drugs that prevent acetylcholine receptor modulation by the immune system, are currently being researched. Some research recently has been on anti-c5 inhibitors for treatment research as they are safe and used in the treatment of other diseases. Ephedrine seems to benefit some people more than other medications, but it has not been properly studied as of 2014.
In the laboratory, MG is mostly studied in model organisms, such as rodents. In addition, in 2015, scientists developed an in vitro functional, all-human, neuromuscular junction assay from human embryonic stem cells and somatic-muscle stem cells </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 Arteriovenous malformation and can you explain it in depth? [/INST] Arteriovenous malformation is an abnormal connection between arteries and veins, bypassing the capillary system. This vascular anomaly is widely known because of its occurrence in the central nervous system (usually cerebral AVM), but can appear in any location. Although many AVMs are asymptomatic, they can cause intense pain or bleeding or lead to other serious medical problems.AVMs are usually congenital and belong to the RASopathies.
The genetic transmission patterns of AVMs are incomplete, but there are known genetic mutations (for instance in the epithelial line, tumor suppressor PTEN gene) which can lead to an increased occurrence throughout the body.

Signs and symptoms
Symptoms of AVM vary according to the location of the malformation. Roughly 88% of people with an AVM are asymptomatic; often the malformation is discovered as part of an autopsy or during treatment of an unrelated disorder (called in medicine an "incidental finding"); in rare cases, its expansion or a micro-bleed from an AVM in the brain can cause epilepsy, neurological deficit, or pain.The most general symptoms of a cerebral AVM include headaches and epileptic seizures, with more specific symptoms occurring that normally depend on the location of the malformation and the individual. Such possible symptoms include:
Difficulties with movement coordination, including muscle weakness and even paralysis;
Vertigo (dizziness);
Difficulties of speech (dysarthria) and communication, such as aphasia;
Difficulties with everyday activities, such as apraxia;
Abnormal sensations (numbness, tingling, or spontaneous pain);
Memory and thought-related problems, such as confusion, dementia or hallucinations.Cerebral AVMs may present themselves in a number of different ways:

Bleeding (45% of cases)
Acute onset of severe headache. May be described as the worst headache of the patients life. Depending on the location of bleeding, may be associated with new fixed neurologic deficit. In unruptured brain AVMs, the risk of spontaneous bleeding may be as low as 1% per year. After a first rupture, the annual bleeding risk may increase to more than 5%.
Seizure or brain seizure (46%) Depending on the place of the AVM, it can cause loss of vision in one place.
Headache (34%)
Progressive neurologic deficit (21%)
May be caused by mass effect or venous dilatations. Presence and nature of the deficit depend on location of lesion and the draining veins.
Pediatric patients
Heart failure
Macrocephaly
Prominent scalp veins

Pulmonary arteriovenous malformations
Pulmonary arteriovenous malformations are abnormal communications between the veins and arteries of the pulmonary circulation, leading to a right-to-left blood shunt.
They have no symptoms in up to 29% of all cases, however they can give rise to serious complications including hemorrhage, and infection. They are most commonly associated with hereditary hemorrhagic telangiectasia.

Genetics
Can occur due to autosomal dominant diseases, such as hereditary hemorrhagic telangiectasia.

Pathophysiology
Arteries and veins are part of the vascular system. Arteries carry blood away from the heart to the lungs or the rest of the body, where the blood passes through capillaries, and veins return the blood to the heart. An AVM interferes with this process by forming a direct connection of the arteries and veins. AVMs can cause intense pain and lead to serious medical problems. Although AVMs are often associated with the brain and spinal cord, they can develop in other parts of the body.Normally, the arteries in the vascular system carry oxygen-rich blood, except in the case of the pulmonary artery. Structurally, arteries divide and sub-divide repeatedly, eventually forming a sponge-like capillary bed. Blood moves through the capillaries, giving up oxygen and taking up waste products, including CO2, from the surrounding cells. Capillaries in turn successively join to form veins that carry blood away. The heart acts to pump blood through arteries and uptake the venous blood.As an AVM lacks the dampening effect of capillaries on the blood flow, the AVM can get progressively larger over time as the amount of blood flowing through it increases, forcing the heart to work harder to keep up with the extra blood flow. It also causes the surrounding area to be deprived of the functions of the capillaries—removal of CO2 and delivery of nutrients to the cells. The resulting tangle of blood vessels, often called a nidus (Latin for "nest"), has no capillaries. It can be extremely fragile and prone to bleeding because of the abnormally direct connections between high-pressure arteries and low-pressure veins. The resultant sign, audible via stethoscope, is a rhythmic, whooshing sound caused by excessively rapid blood flow through the arteries and veins. It has been given the term "bruit", French for noise. On some occasions, a patient with a brain AVM may become aware of the noise, which can compromise hearing and interfere with sleep in addition to causing psychological distress.

Diagnosis
AVMs are diagnosed primarily by the following imaging methods:
Computerized tomography (CT) scan is a noninvasive X-ray to view the anatomical structures within the brain to detect blood in or around the brain. A newer technology called CT angiography involves the injection of contrast into the blood stream to view the arteries of the brain. This type of test provides the best pictures of blood vessels through angiography and soft tissues through CT.
Magnetic resonance imaging (MRI) scan is a noninvasive test, which uses a magnetic field and radio-frequency waves to give a detailed view of the soft tissues of the brain.
Magnetic resonance angiography (MRA) – scans created using magnetic resonance imaging to specifically image the blood vessels and structures of the brain. A magnetic resonance angiogram can be an invasive procedure, involving the introduction of contrast dyes (e.g., gadolinium MR contrast agents) into the vasculature of a patient using a catheter inserted into an artery and passed through the blood vessels to the brain. Once the catheter is in place, the contrast dye is injected into the bloodstream and the MR images are taken.  Additionally or alternatively, flow-dependent or other contrast-free magnetic resonance imaging techniques can be used to determine the location and other properties of the vasculature.AVMs can occur in various parts of the body:

brain (cerebral AV malformation)
spleen
lung
kidney
spinal cord
liver
intercostal space
iris
spermatic cord
extremities – arm, shoulder, etc.AVMs may occur in isolation or as a part of another disease (for example, Von Hippel-Lindau disease or hereditary hemorrhagic telangiectasia).AVMs have been shown to be associated with aortic stenosis.Bleeding from an AVM can be relatively mild or devastating. It can cause severe and less often fatal strokes. If a cerebral AVM is detected before a stroke occurs, usually the arteries feeding blood into the nidus can be closed off to avert the danger. However, interventional therapy may also be relatively risky.

Treatment
Treatment for brain AVMs can be symptomatic, and patients should be followed by a neurologist for any seizures, headaches, or focal neurologic deficits. AVM-specific treatment may also involve endovascular embolization, neurosurgery or radiosurgery.
Embolization, that is, cutting off the blood supply to the AVM with coils, particles, acrylates, or polymers introduced by a radiographically guided catheter, may be used in addition to neurosurgery or radiosurgery, but is rarely successful in isolation except in smaller AVMs. Gamma knife may also be used.Treatment of lung AVMs is typically performed with endovascular embolization alone, which is considered the standard of care.

Epidemiology
The estimated detection rate of AVM in the US general population is 1.4/100,000 per year. This is approximately one fifth to one seventh the incidence of intracranial aneurysms. An estimated 300,000 Americans have AVMs, of whom 12% (approximately 36,000) will exhibit symptoms of greatly varying severity.

History
Luschka (1820–1875) and Virchow (1821–1902) first described arteriovenous malformations in the mid-1800s. Olivecrona (1891–1980) performed the first surgical excision of an intracranial AVM in 1932.

Society and culture
Notable cases
Indonesian actress Egidia Savitri died from complications of AVM on November 29, 2013.
Phoenix Suns point guard AJ Price nearly died from AVM in 2004 while a student at the University of Connecticut.
On December 13, 2006, Senator Tim Johnson of South Dakota was diagnosed with AVM and treated at George Washington University Hospital.
On August 3, 2011, Mike Patterson of the Philadelphia Eagles collapsed on the field and had a seizure during a practice, leading to him being diagnosed with AVM.
Actor Ricardo Montalbán was born with spinal AVM. During the filming of the 1951 film Across the Wide Missouri, Montalbán was thrown from his horse, knocked unconscious, and trampled by another horse which aggravated his AVM and resulted in a painful back injury that never healed. The pain increased as he aged, and in 1993, Montalbán underwent 9+1⁄2 hours of spinal surgery which left him paralyzed below the waist and using a wheelchair.
Actor/comedian T </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 Soft tissue injury and can you explain it in depth? [/INST] A soft tissue injury is the damage of muscles, ligaments and tendons throughout the body. Common soft tissue injuries usually occur from a sprain, strain, a one-off blow resulting in a contusion or overuse of a particular part of the body. Soft tissue injuries can result in pain, swelling, bruising and loss of function.

Signs and symptoms
Sprains
A sprain is a type of acute injury which results from the stretching or tearing of a ligament. Depending on the severity of the sprain, the movement on the joint can be compromised since ligaments aid in the stability and support of joints. Sprains are commonly seen in vulnerable areas such as the wrists, knees and ankles. They can occur from movements such as falling on an outstretched hand or a twisting of the ankle or foot.The severity of a sprain can be classified:

Grade 1: Only some of the fibers in the ligament are torn, and the injured site is moderately painful and swollen. Function in the joint will be unaffected for the most part.
Grade 2: Many of the ligament fibers are torn, and pain and swelling is moderate. The functionality of the joint is compromised.
Grade 3: The soft tissue is completely torn, and functionality and strength on the joint is completely compromised. In most cases, surgery is needed to repair the damage.

Strains
A strain is a type of acute injury that occurs to the muscle or tendon. Similar to sprains, it can vary in severity, from a stretching of the muscle or tendon to a complete tear of the tendon from the muscle. Some of the most common places that strains occur are in the foot, back of the leg (hamstring), or back.

Bruising (contusion)
A contusion is the discoloration of the skin, which results from underlying muscle fibers and connective tissue being crushed. This can happen in a variety of ways such as a direct blow to the skin, or a fall taken against a hard surface. The discoloration in the skin is present when blood begins to pool around the injury.

Tendinitis
Tendinitis is a type of overuse injury to the tendons, which demonstrates signs of inflammation of tendons around a joint. Tendinitis is the most common cause of shoulder pain and also leg pain . Tendinitis occurs when there is repetitive stress on the subacromial bursa, which causes the bones to make contact with the tendons and irritate them.

Diagnosis
Classifications
Acute injuries
Any type of injury that occurs to the body through sudden trauma, such as a fall, twist or blow to the body. A few examples of this type of injury would be sprains, strains and contusions.

Overuse injuries
An overuse injury occurs when a certain activity is repeated frequently and the body does not have enough time to recover between occurrences. Examples include bursitis and tendinitis.

Commonly injured tissues
With examples of each. Parentheses indicate location in body

LigamentsAnterior cruciate ligament (knee), medial collateral ligament (knee), ulnar collateral ligaments (wrist/hand), interspinous ligaments (vertebrae)MusclesBiceps brachii (upper arm), rectus femoris (thigh), transverse abdominis (abdominals)TendonsPatellar tendon (knee), calcaneal/Achilles tendon (foot/lower leg), biceps tendon (shoulder/elbow)NervesBrachial plexus (shoulder), ulnar nerve (elbow/hand), peroneal nerve (ankle/foot), cranial nerves I-XII(head)BonesFemur (leg), humerus (arm), ribs (torso), metatarsals I-VI (foot), metacarpals I-VI (hand)CartilageMenisci (knee), intervertebral discs (spine), acetabulum (hip)

Management
RICE method
The RICE method is an effective procedure used in the initial treatment of a soft tissue injury.

Rest
It is suggested that the patient take a break from the activity that caused the injury in order to give the injury time to heal.
Ice
The injury should be iced on and off in 20 minute intervals, avoiding direct contact of the ice with the skin.
Compression
Bandaging the injury will compress it, and prevent any further bleeding or swelling from occurring.
Elevation
Elevating the injury above the heart while resting will aid in the reduction of swelling.

No HARM protocol
This mnemonic indicates what  not  to do within the first 48–72 hours after the injury in order to speed up the recovery process.

Heat
Applying heat to the injured area can cause blood flow and swelling to increase.
Alcohol
Alcohol can inhibit the ability to feel if the injury is becoming more aggravated, as well as increasing blood flow and swelling.
Re-injury
Avoid any activities that could aggravate the injury and cause further damage.
Massage
Massaging an injured area can promote blood flow and swelling, and potentially cause more damage if done too early.

Treatment
If severe pain persists after the first 24hours it is recommended that an individual consult with a professional who can make a diagnosis and implement a treatment plan so the patient can return to everyday activities. To make a full diagnosis, a professional may use nerve conduction studies to localize nerve dysfunction (e.g. carpal tunnel syndrome), assess severity, and help with prognosis. Electrodiagnosis also helps differentiate between myopathy and neuropathy. Using the RICE method can somewhat be controversial as the science behind using ice is not necessarily very clear. On one hand, ice diminishes pain, metabolism, and muscle spasms.  It also minimizes the inflammatory process and edema, which helps one recover from a soft-tissue injury. However, creatine kinase-MB isoform and myoglobin levels circulating in the blood increased after exercising. Ice impedes the recovery process by keeping the Creatine kinase-MB isoform and myoglobin levels increased 2–3 days post exercise. It is therefore important to weigh the pros and cons before applying any treatment, including the use of ice.
Ultimately, the best method of imaging soft tissue is magnetic resonance imaging (MRI), though it is cost-prohibitive and carries a high false positive rate.

References
Sources
Flegel, Melinda J. (2004). Sport first aid: A coach’s guide to preventing and responding to injuries. Hong Kong, Japan: Human Kinetics.
Lindsay, R., Watson, G., Hickmont, D., Broadfoot, A., & Bruynel, L. (1994). Treat your own strains sprains and bruises. New Zealand: Spinal Publications.
Lovering, R.M. (2008). "Physical therapy and related interventions" </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 Venezuelan hemorrhagic fever and can you explain it in depth? [/INST] Venezuelan hemorrhagic fever (VHF) is a zoonotic human illness first identified in 1989. The disease is most prevalent in several rural areas of central Venezuela and is caused by Guanarito mammarenavirus (GTOV) which belongs to the Arenaviridae family. The short-tailed cane mouse (Zygodontomys brevicauda) is the main host for GTOV  which is spread mostly by inhalation of aerosolized droplets of saliva, respiratory secretions, urine, or blood from infected rodents. Person-to-person spread is possible, but uncommon.

Presentation
VHF has many similarities to Lassa fever and to the arenavirus hemorrhagic fevers that occur in Argentina and Bolivia. It causes fever and malaise followed by hemorrhagic manifestations and convulsions. Some presentations of the virus are also characterized by vascular damage, bleeding diathesis, fever, and multiple organ involvement.  Clinical diagnosis of VHF has proven to be difficult based on the nonspecific symptoms. The disease is fatal in 30% of cases and is endemic to Portuguesa state and Barinas state in Venezuela.
Treatment and prevention for the VHF virus are limited and there are currently no licensed vaccines available that can act to prevent the disease. However, once infected, ribavirin, an anti-viral drug given intravenously, is one way to treat VHF.

Virus
Arenaviruses are enveloped, single-stranded, bisegmented RNA viruses with antisense genomes </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 Retinoschisis and can you explain it in depth? [/INST] Retinoschisis is an eye disease characterized by the abnormal splitting of the retinas neurosensory layers, usually in the outer plexiform layer. Retinoschisis can be divided into degenerative forms which are very common and almost exclusively involve the peripheral retina and hereditary forms which are rare and involve the central retina and sometimes the peripheral retina. The degenerative forms are asymptomatic  and involve the peripheral retina only and do not affect the visual acuity. Some rarer forms result in a loss of vision in the corresponding visual field.Almost all cases are X-linked recessive and caused by a mutation in the retinoschisin gene (RS1).

Classification
Hereditary
X linked juvenile retinoschisis
Familial foveal retinoschisis
Tractional
Exudative
Secondary to Optic disc pit
Degenerative
Typical
Reticular

Degenerative retinoschisis
This type of retinoschisis is very common with a prevalence of up to 7 percent in normal persons.  Its cause is unknown.  It can easily be confused with retinal detachment by the non-expert observer and in difficult cases even the expert may have difficulty differentiating the two.  Such differentiation is important since retinal detachment almost always requires treatment while retinoschisis never itself requires treatment and leads to retinal detachment (and hence to visual loss) only occasionally.  Unfortunately one still sees cases of uncomplicated retinoschisis treated by laser retinopexy or cryopexy in an attempt to stop its progression towards the macula.  Such treatments are not only ineffective but unnecessarily risk complications.  There is no documented case in the literature of degenerative retinoschisis itself (as opposed to the occasional situation of retinal detachment complicating retinoschisis) in which the splitting of the retina has progressed through the fovea.  There is no clinical utility in differentiating between typical and reticular retinoschisis.  Degenerative retinoschisis is not known to be a genetically inherited condition.
There is always vision loss in the region of the schisis as the sensory retina is separated from the ganglion layer.  But as the loss is in the periphery, it goes unnoticed.  It is the very rare schisis that encroaches on the macula where retinopexy is then properly used.

Hereditary retinoschisis
Hereditary retinoschisis is derived from a defective retinoschisin protein, which is due to an X-linked genetic defect. The genetic form of this disease usually starts during childhood and is called  X-linked Juvenile Retinoschisis (XLRS) or Congenital Retinoschisis. Affected males are usually identified in grade school, but occasionally are identified as young infants.
It is estimated that this much less common form of retinoschisis affects one in 5,000 to 25,000 individuals, primarily young males. Schisis is derived from the Greek word meaning splitting, describing the splitting of the retinal layers from each other. However, schisis is a word fragment, and the term retinoschisis should be used, as should the term iridoschisis when describing splitting of the iris.  If the retinoschisis involves the macula, then the high-resolution central area of vision used to view detail is lost, and this is one form of macular disease.  Although it might be described by some as a "degeneration", the term macular degeneration should be reserved for the specific disease "age-related macular degeneration".
Very few affected individuals go completely blind from retinoschisis, but some sufferers have very limited reading vision and are "legally blind". Visual acuity can be reduced to less than 20/200 in both eyes.  Individuals affected by XLRS are at an increased risk for retinal detachment and eye hemorrhage, among other potential complications.
Retinoschisis causes acuity loss in the center of the visual field through the formation of tiny cysts in the retina, often forming a "spoke-wheel" pattern that can be very subtle. The cysts are usually only detectable by a trained clinician. In some cases vision cannot be improved by glasses, as the nerve tissue itself is damaged by these cysts.
The National Eye Institute (NEI) of the National Institutes of Health (NIH) is conducting clinical and genetic studies of X-Linked Juvenile Retinoschisis. This study began in 2003 and as of 2018 is continuing to recruit patients.   A better understanding of why and how XLRS develops might lead to improved treatments.  Males diagnosed with X-linked juvenile retinoschisis and females who are suspected carriers may be eligible to participate </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 Cervical pregnancy and can you explain it in depth? [/INST] A cervical pregnancy is an ectopic pregnancy that has implanted in the uterine endocervix. Such a pregnancy typically aborts within the first trimester, however, if it is implanted closer to the uterine cavity – a so-called cervico-isthmic pregnancy – it may continue longer </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 Vaginal atresia and can you explain it in depth? [/INST] Vaginal atresia is a condition in which the vagina is abnormally closed or absent. The main causes can either be complete vaginal hypoplasia, or a vaginal obstruction, often caused by an imperforate hymen or, less commonly, a transverse vaginal septum. It results in uterovaginal outflow tract obstruction. This condition does not usually occur by itself within an individual, but coupled with other developmental disorders within the female. The disorders that are usually coupled with a female who has vaginal atresia are Mayer-Rokitansky-Küster-Hauser syndrome, Bardet-Biedl syndrome, or Fraser syndrome. One out of every 5,000 women have this abnormality.

Symptoms and signs
Symptoms and signs in the newborn can be sepsis, abdominal mass, and respiratory distress. Other abdominopelvic or perineal congenital anomalies frequently prompt radiographic evaluation in the newborn, resulting in a diagnosis of coincident vaginal atresia. Symptoms for vaginal atresia include cyclical abdominal pain, the inability to start having menstrual cycles, a small pouch or dimple where a vaginal opening should be, and pelvic mass when the upper vagina becomes filled with menstrual blood. Signs and symptoms of vaginal atresia or vaginal agenesis can often go unnoticed in females until they reach the age of menstruation. Women may also experience some form of abdominal pain or cramping.

Causes
The cause for vaginal atresia is unknown. Typically, the creation of the vaginal canal is completed within the fetus by the 20th week of gestation. Researchers believe in patients with vaginal atresia, tubes known as the Müllerian ducts do not develop correctly within the first 20 weeks of gestation/pregnancy. Typically, one of these ducts develops in the fallopian tubes while the other ducts develop into the vagina and uterus. Vaginal atresia is found to occur when the urogenital sinus does not contribute to the formation of the lower portion of the vagina. As previously mentioned, there are other disorders or syndromes that are found in conjunction with individuals living with vaginal atresia. These disorders are:

Rokitansky-Mayer-Küster-Hauser syndrome
Rokitansky-Mayer-Küster-Hauser syndrome is a disorder in females that causes the uterus and vagina to be absent or underdeveloped. Those born with this disorder are considered to be genetic female and have a 46XX chromosomes. Kidney anomalies often accompany this disorder as well. Also referred to as Müllerian agenesis, vaginal agenesis, or Müllerian aplasia, this disorder affects 1 in every 4,000-5,000 females. A cloacal malformation often accompanies this disorder, which is the surgical treatment that incorporates several vaginal replacement techniques. This disorder is caused by an implication in the WNT4 protein coding gene, which is found on the short arm (p) of chromosome 1. A genetic mutation occurs causing a substitution of leucine to proline residue at position 12 on the amino acid in the WNT4 protein. Essentially, this will cause a reduction in the intranuclear levels of β catenin. Additionally, steroidogenic enzymes such as 17α-hydroxylase and 3β-hydroxysteriod dehydrogenase are inhibited because of this mutation, which leads to an excess amount to androgen in the system. As the WNT4 gene is essential for developing a protein that is essential for female sex development, the Müllerian duct is either absent or deformed when this gene is not present. The development of the female reproductive system may be disrupted in the absence of the WNT4 proteins regulation. Abnormal androgen production is also induced, eventually leading to hyperandrogenism and Müllerian aplasia.

Bardet-Biedl Syndrome
Bardet-Biedl syndrome (BBS) is a ciliopathic human genetic disorder that can affect various parts of the body. Parts of the urogenital system where the effects of BBS are seen include: ectopic urethra, kidney failure, uterus duplex, hypogonadism, septate vagina, and hypoplasia of the fallopian tubes, uterus, ovaries. Some of the common characteristics associated with this syndrome include intellectual disorders, loss of vision, kidney problems, and obesity.The mechanism that causes BBS is still remains unclear. Mutations in more than 20 genes can cause BBS and is an inherited recessive condition. Some of the gene mutations that occur in BBS are listed below:
BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), CEP290 (BBS14), WDPCP (BBS15), SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), IFT27 (BBS19), IFT72 (BBS20), and C8ORF37(BBS21) The majority of the genes that are related to BBS encode proteins which are called cilia and basal bodies, which are related structures.

Fraser Syndrome
Fraser syndrome is a disorder that affects the development of the child prior to birth. Infants born with Fraser syndrome often have eyes that are malformed and completely covered by skin. Also the child is born with fingers and toes that are fused together along with abnormalities within the urine tract. As this disorder relates to vaginal atresia, infants born with Fraser syndrome are also born with malformations in their genitals.

McKusick-Kaufman syndrome
A female with McKusick-Kaufman syndrome has vaginal atresia that is often present with imperforate anus, heart defects, hydrometrocolpos, and/or polydactyly,  The female will still develop secondary sexual characteristics.

Mechanism
The exact mechanism for vaginal atresia is not well known, as specific molecular mechanisms which lead to the closing or absence of the vagina are unclear. There are various pathways that may support or restrict regular vaginal development. Research has shown that changing factors may also include paracrine and autocrine signals and changes in the basis of developing organs. Specific patterns of genetic transmission have not been identified for this condition. Normal reproductive organ production requires timely coordination of the following systems: external genitalia, internal ductal system, and gonadal structure. The abnormal development of the vagina results in an incomplete unit (low, mid, high transverse septum), failure of epithelium degeneration (imperforate hymen), and vaginal atresia.According to a number of medical professionals, timely coordination of interdependent systems is required for normal reproductive organ development in both males and females. The description of vaginal atresia mechanism can be explained in several steps of development of the uterovaginal canal per the information provided by these medical professionals. These interdependent systems are external genitalia, gonadal structures, and internal ductal system. The absence of androgens, Müllerian-inhibiting substance (MIS), and testes causes the continuous differentiation of the Müllerian ducts with reversion of the wolffian ducts in the female embryo. The Müllerian duct will then elongate to reach the urogenital sinus within 9 weeks of gestation; this forms the uterovaginal canal. By 15–26 weeks of gestation, cephalic growth of the sinovaginal bulb is completed. The vaginal plate is also formed from the fusion of vaginal cord with the sinovaginal bulb.
The formation of the uterovaginal canal is thought to occur from the caudal to the cephalic portion, all while the urogenital sinus is used to create the epithelial lining. Development of the vagina is completed by the fifth month of gestation. While the mesenchyme that surrounds the structures transitions into musculature of the genital tract, the fallopian tubes are formed via the cephalic remnants of the Müllerian duct. This developmental process attributes to the process of how proper vaginal development takes place. Failure of the septum to regress between the fused Müllerian ducts results in a septate uterus. The incomplete fusion of the Müllerian ducts attributes to the formation of arcuate, bicornuate, or didelphid uteri.Females who have both Rokitansky-Mayer-Küster-Hauser syndrome and uterovaginal atresia are theorized to have a failing caudal development within the Müllerian ducts. Variations of transverse vaginal septum might be described by the malfunctions at the level of the vaginal plate. Though the Müllerian and urogenital sinuses play a huge role in the derivation of the vagina, it is unclear how much of a role each of these play normal vaginal development.

Diagnosis
Vaginal atresia can sometimes be diagnosed by physical examination soon after birth. A child with vaginal atresia often has other congenital abnormalities and other tests such as X-ray and tests to evaluate the kidneys are done. Findings in adolescents may include abdominal pain, difficulty voiding, and backache, but most present with amenorrhea. Difficulties with sexual intercourse can suggest atresia. In the event that the condition is not caught shortly after birth, vaginal atresia becomes more evident when no menstrual cycle is occurs. If vaginal atresia is suspected by the doctor, a blood test may also be request for any of the previously mentioned syndromes, a magnetic resonance imaging (MRI) test, or an ultrasound. A regular evaluation of children born with an imperforate anus or anorectal malformation should be paired with the assessment of the results from these tests.

Treatment
There are several methods of treatment for individuals with vaginal atresia. The first method of treatment that is recommended would be self-dilation of the vagina. A doctor may first recommend that the patient first attempts to create a vagina themselves through the process self-dilation. The self dilation technique consists of using vaginal dilators, which are small round tubes that vary in size and are similar in size and shape to tampons. Vaginal dilators may be pressed alongside the vaginal area on a regular basis in order to further open the vaginal canal. Franks procedure is a technique that used a progressive series of vaginal dilators that are inserted into the dimple of the vagina while using pressure. This will widen any space that exists between the bladder and the rectum. Franks procedure can be performed directly by the patient, therefore requiring no surgery or anesthesia. The procedure/technique can take months to complete, with regular compliance necessary. The overall success rate for females who use Franks procedure is 80%. If this procedure does not work, then surgery would be the next method of treatment. Another alternative form of treatment would be surgery, or the creation of a new vagina.

Prognosis
The prognosis for vaginal atresia is one that is complicated. There are variations in patients anatomic findings as well as an absence in consistent surgical techniques which makes it difficult to give a prognosis for this condition. Along with other conditions that give rise to an abnormal perineum (i.e. ambiguous genitalia and other various abnormalities that range from cloaca to urogenital sinus), individuals with vaginal atresia often report reconstruction as an outcome of treatment. Due to this, it is difficult to compare outcomes between individuals with vaginal atresia.

Rokitansky-Mayer-Küster-Hauser Syndrome
Fertility options for girls and women with Rokitansky-Mayer-Küster-Hauser syndrome has a bit more information. Girls and women who are born without a complete vagina, but still have a regular sized uterus more than likely will be able to become pregnant and have a baby </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 Congenital dermal sinus and can you explain it in depth? [/INST] Congenital dermal sinus is an uncommon form of cranial or spinal dysraphism. It occurs in 1 in 2500 live births. It occurs as a dermal indentation, found along the midline of the neuraxis and often presents alongside infection and neurological deficit. Congenital dermal sinus form due to a focal failure of dysjunction between the cutaneous ectoderm and neuroectoderm during the third to eight week of gestation. Typically observed in the lumbar and lumbosacral region, congenital dermal sinus can occur from the nasion and occiput region down.Early diagnosis and treatment is crucial for cases of congenital dermal sinus. It ensures that neurological condition does not degrade and prevents infection. Diagnosis can be confirmed through the use of advanced neuroimaging to observe the tract and associated lesions.

Embryogenesis
During normal development, cutaneous ectoderm separates from neuroectoderm to allow for the insertion of mesoderm. That is, the skin separates from the tissue of the spinal cord to allow proper formation of the vertebral column.
In cases of congenital dermal sinus there is a failure in this process, resulting in formation of a persistent connection between the skin and neural tissue. This manifests as a tract extending from the surface of the skin to the spinal cord lined with stratified squamous epithelium, surrounded by dermal and neurological tissue. The tract may terminate in the deep fascia, or even make contact with neural elements.
Congenital dermal sinus may form at any point along the midline of the neuraxis, however, the majority form in the lumbar and lumbosacral region (41% and 35% of cases respectively).

Diagnosis
Congenital dermal sinus is often diagnosed in infants and children. Early diagnosis is important in congenital dermal sinus, so that treatment can be provided early, to prevent progression of associated complications.

Clinical features
There three key hallmarks of congenital dermal sinus: cutaneous abnormalities, infection, and neurological deficits.

Cutaneous abnormalities
Congenital dermal sinus is a tract from the surface layer of the skin, through the deeper tissues into the cranial or spinal cavity.
The skin findings of this tract can include:

Pit along neuraxis
Flat capillary hemangioma
Hypertrichosis
Skin tag
Abnormal pigmentation
Subcutaneous lipoma
Signs of local infection

Infection
The stratified squamous epithelium of the congenital dermal sinus tract can extend to the spinal fascia of the dura mater or all the way to the spinal cord. Thus, the congenital dermal sinus forms a point of entry for infection, this can allow for the formation of an abscess, especially among children. Infection can then travel up the spinal cord to result in meningitis, which can be fatal if left untreated.

Neurological deficit
Congenital dermal sinus is often also associated with spinal fluid drainage, intradural cysts and spinal cord tethering; conveying neurological deficit. Neurological deficit can occur due to spinal cord compression from intradural dermoid cyst growth in the epidermis and dermis.
Tethered spinal cord can result in gait difficulties and sphincter dysfunction, as well as compressing the spine.
Neurological deficits are more likely to occur where diagnosis has not been timely, allowing cysts and or infection.

Imaging
Magnetic Resonance Imaging (MRI) is the preferred tool for diagnostic and preoperative imaging of congenital dermal sinus. MRI allows the neural structures to be observed, visualizing the tract and its anomalies and lesions </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 Limb–girdle muscular dystrophy and can you explain it in depth? [/INST] Limb–girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of rare muscular dystrophies that share a set of clinical characteristics. It is characterised by progressive muscle wasting which affects predominantly hip and shoulder muscles. LGMD usually has an autosomal pattern of inheritance. It currently has no known cure or treatment.

Signs and symptoms
By definition, all limb girdle muscular dystrophies (LGMD) cause progressive proximal weakness, meaning weakness of the muscles on or close to the torso that worsens over time. Explicitly, LGMD preferentially affects muscles of the hip girdle, thigh, shoulder girdle, and/or upper arm. The muscle weakness is generally symmetric. Usually, the hip girdle is the first area to exhibit weakness, manifesting as difficulty walking, going up and/or down stairs, rising from a chair, bending at the waist, or squatting. Because of these difficulties, falling can occur frequently. Weakness of the shoulder girdle can make lifting objects, or even elevating the arms, difficult or impossible. Rate of progression varies between patients. Eventually, the abilities to run and walk can deteriorate. The disease commonly leads to dependence on a wheelchair within years of symptom onset, although some patients maintain mobility. Eventually the disease can affect other muscles such as the ones located in the face.
By definition, LGMDs primarily affect skeletal muscles, although cardiac muscle can be affected to a lesser degree in select subtypes, which can cause palpitations
There can be significant variability in disease features and severity between LGMD subtypes, and even within any given LGMD subtype. Additional possible presentations include:

In most cases, pain is not present with LGMD, and mental function is not affected. LGMD can begin in childhood, adolescence, young adulthood or even later, the age of onset is usually between 10 and 30. Both genders are affected equally. When limb-girdle muscular dystrophy begins in childhood, the progression appears to be faster and the disease more disabling. When the disorder begins in adolescence or adulthood the disease is generally not as severe and progresses more slowly. There is no sensory neuropathy or autonomic or visceral dysfunction at presentation.

Genetics
LGMD is a genetic and heritable disorder, due to one of many genetic mutations of proteins involved in muscle function. All currently identified LGMDs have an inheritance pattern that is dominant or recessive, although the definition of LGMD allows for diseases with more complicated inheritance patterns to be classified as LGMD. Examples of proteins affected in LGMD are α, β, γ and δ sarcoglycans.

Diagnosis
The diagnosis of limb–girdle muscular dystrophy can be done via muscle biopsy, which will show the presence of muscular dystrophy, and genetic testing is used to determine which type of muscular dystrophy a patient has. Immunohistochemical dystrophin tests can indicate a decrease in dystrophin detected in sarcoglycanopathies. In terms of sarcoglycan deficiency there can be variance (if α-sarcoglycan and γ-sarcoglycan are not present then theres a mutation in LGMD2D).The 2014 Evidence-based guideline summary: Diagnosis and treatment of limb–girdle and distal dystrophies indicates that individuals suspected of having the inherited disorder should have genetic testing. Other tests/analysis are:
High CK levels(x10-150 times normal)
MRI can indicate different types of LGMD.
EMG can confirm the myopathic characteristic of the disease.
Electrocardiography (cardiac arrhythmias in LGMD1B can occur)

Types
The "LGMD D" family is autosomal dominant, and the "LGMD R" family is autosomal recessive. Limb–girdle muscular dystrophy is explained in terms of gene, locus, OMIM and type as follows:

LGMD criteria
For a disease entity to be classified as an LGMD, the following criteria must be met:
genetic, with an identifiable inheritance pattern such as autosomal dominant, autosomal recessive, digenic, or polygenic.
relatively selective to skeletal muscle
predominantly proximal muscle involvement
independent walking is achieved at one point in life
elevated serum creatine kinase
muscle fiber loss
dystrophic changes in muscle histology
degenerative changes on medical imaging
end-stage pathology seen in the most affected muscles
described in at least two unrelated families

Differential
Many diseases can manifest similarly to LGMD. Dystrophinopathies, including Duchenne muscular dystrophy, Becker muscular dystrophy, and manifesting dystrophinopathy in female carriers, can present similarly to LGMD. Facioscapulohumeral muscular dystrophy can appear similarly, especially when it spares the facial muscles. Also in the differential are Emery-Dreifuss muscular dystrophies, Pompe disease, later-onset congenital myasthenic syndromes, and proximal-predominant hereditary motor neuropathies.

Treatment
There are few studies corroborating the effectiveness of exercise for limb–girdle muscular dystrophy. However studies have shown that exercise can, in fact, damage muscles permanently due to intense muscle contraction. Physical therapy may be required to maintain as much muscle strength and joint flexibility as possible. Calipers may be used to maintain mobility and quality of life. Careful attention to lung and heart health is required, corticosteroids in LGMD 2C-F individuals, shows some improvement. Additionally individuals can follow management that follows:
Occupational therapy
Respiratory therapy
Speech therapy
Neutralizing antibody to myostatin should not be pursuedThe sarcoglycanopathies could be possibly amenable to gene therapy.

Prognosis
In terms of the prognosis of limb–girdle muscular dystrophy in its mildest form, affected individuals have near-normal muscle strength and function. LGMD isnt typically a fatal disease, though it may eventually weaken the heart and respiratory muscles, leading to illness or death due to secondary disorders.

Epidemiology
The minimum prevalence of limb–girdle muscular dystrophy, as a group, likely ranges from 2.27-10 per 100,000 (1:44,000 to 1:10,000). LGMD is the fourth most common muscular dystrophy, after the dystrophinopathies, myotonic dystrophies, and facioscapulohumeral muscular dystrophy. The prevalence of individual LGMDs, as studied in the United States, in descending order, are those due to mutation of 1) calpain, 2) dysferlin, 3) collagen VI, 4) sarcoglycans, 5) anoctamin 5, and 6) fukutin-related protein. It is difficult to calculate the worldwide prevalence of even the most common LGMD types, due to the founder effect causing varying prevalence by region. The less common types are very rare, often only described is limited regions of the world.

History
The term limb girdle muscular dystrophy was published in 1954, describing a group of heterogeneous conditions that clinicians noticed to be distinct from Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. The genetics of LGMDs began to be understood in the late 1900s, which led the European Neuromuscular Centre (ENMC) to establish a consensus on classification of LGMDs in 1995. The classification scheme at that time denoted autosomal dominant LGMDs as LGMD1 and autosomal recessive LGMDs as LGMD2. A letter was appended to the names of LGMDs according to the order of discovery of the causal genetic mutation. As LGMD2Z was established, the question arose of what letter to assign the next discovered LGMD2. With this issue, among other motives, the ENMC established a new consensus on the classification and definition of LGMD in 2017. With the new definition, several diseases were removed from the LGMD category:

Research
There is a variety of research under way targeted at various forms of limb–girdle muscular dystrophy. Among the treatments thought to hold promise is gene therapy, which is the delivery of genetic material, often a copy of a healthy gene, into cells.According to a review by Bengtsson et al. some success with AAV-mediated gene therapies (for different disorders) have increased interest in researchers, with CRISPR/Cas9 and exon-skipping helping these therapeutic goals along. Limb–girdle muscular dystrophies have many different types which are due to different gene mutations. LGMD2D is caused by a mutation in the α-sarcoglycan gene. Future treatment could be had by gene therapy through recombinant adeno-associated vectors.According to a review by Straub, et al., there are several research issues that need to be addressed: the rareness of the disease, poor understanding of the mechanism of LGMD R, and absence of patient cohorts, all contributing to lack of biomarkers for LGMD. The review goes on to state that animal models for LGMD R have been used to analyze therapeutic medications. Also, although prednisone has been used and has had positive effects on affected LGMD2 individuals, there is still no evidence of its effectiveness in trials that are placebo-controlled.

See also
Muscle atrophy

References
Further reading
Cotta, Ana; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Paim, Júlia Filardi; Navarro, Monica M.; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier Neto, Rafael (2014). "Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?". Arquivos de Neuro-Psiquiatria. 72 (9): 721–734. doi:10.1590/0004-282X20140110. ISSN 0004-282X. PMID 25252238.
Liu, Jian; Harper, Scott Q. (2012-08-01). "RNAi-based Gene Therapy for Dominant Limb Girdle Muscular Dystrophies". Current Gene Therapy. 12 (4): 307–314 </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 Erythrocyanosis crurum and can you explain it in depth? [/INST] Erythrocyanosis crurum is a skin condition, a variant  of acrocyanosis caused by chronic exposure to cold.

See also
Chilblains
List of cutaneous conditions

References
Otto Braun-Falco; G. Plewig; H. H. Wolff; Walter H. 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 Aortoiliac occlusive disease and can you explain it in depth? [/INST] In medicine, aortoiliac occlusive disease is a form of central artery disease involving the blockage of the abdominal aorta as it transitions into the common iliac arteries.

Signs and symptoms
Classically, it is described in male patients as a triad of the following signs and symptoms:
claudication of the buttocks and thighs
absent or decreased femoral pulses
erectile dysfunctionThis combination is known as Leriche syndrome.  However, any number of symptoms may present, depending on the distribution and severity of the disease, such as muscle atrophy, slow wound healing in the legs, and critical limb ischemia.

Diagnosis
The physical examination usually shows weakened femoral pulses and a reduced ankle-brachial index </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 Myopericarditis 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 Pearly penile papules and can you explain it in depth? [/INST] Pearly penile papules (PPP) are benign small bumps on the human penis. They vary in size from 1–4 mm, are pearly or flesh-colored, smooth and dome-topped or filiform, and appear in one or several rows around the corona, the ridge of the head of the penis and sometimes on the penile shaft. They are painless, non-cancerous and not harmful.

Symptoms and signs
PPPs are small bumps on the human penis. They vary in size from 1–4 mm, are pearly or flesh-colored, smooth and dome-topped or filiform, and appear in one or several rows around the corona, the ridge of the glans and sometimes on the penile shaft. They are painless, non-cancerous and not harmful.

Cause and mechanism
PPPs are a type of angiofibroma. Their function is not well-understood. They are sometimes described as vestigial remnants of penile spines, sensitive features found in the same location in other primates. PPPs secrete oil that moistens the glans of the penis. They do not spread and often spontaneously regress. Along with Fordyce glands PPPs secrete oils to keep the skin of the head of penis in good condition. Smegma can accumulate if these oils are produced in excess or there is inadequate washing under the foreskin.

Diagnosis
Diagnosis is by visualisation. On dermoscopy, the white-pink papules appear in a cobblestone-like pattern and contain a central dotted or comma-shaped blood vessels. There is no scale. PPPs are sometimes mistaken for genital warts due to a perceived similarity in appearance. They can also appear similar to molluscum contagiosum, sebaceous hyperplasia and lichen nitidus. Histopathology shows dense connective tissue, fibroblasts and many blood vessels.

Treatment
Generally, reassurance is given and no treatment is needed </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 Parapharyngeal abscess 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 Romano–Ward syndrome and can you explain it in depth? [/INST] Romano–Ward syndrome is the most common form of congenital Long QT syndrome (LQTS), a genetic heart condition that affects the electrical properties of heart muscle cells.  Those affected are at risk of abnormal heart rhythms which can lead to fainting, seizures, or sudden death. Romano–Ward syndrome can be distinguished clinically from other forms of inherited LQTS as it affects only the electrical properties of the heart, while other forms of LQTS can also affect other parts of the body.
Romano–Ward syndrome is caused by abnormal variants in the genes responsible for producing certain proteins used to transport charged particles (ion channels) within the heart.  These abnormalities interfere with the electrical signals that heart cells use to coordinate contractions, causing the heart to take longer to recharge in between beats. The condition is usually diagnosed using an electrocardiogram, but other tests sometimes used include Holter monitoring, exercise testing, and genetic testing.  It may be treated using medications such as beta-blockers, an implantable cardioverter-defibrillator, or surgery to disrupt the sympathetic nervous system. Romano–Ward syndrome is estimated to affect 1 in every 7,000 people.

Signs and symptoms
Romano–Ward syndrome increases the risk of abnormal heart rhythms or arrhythmias.  These are typically a form of ventricular tachycardia known as Torsades de pointes which can cause faints, seizures, or even sudden death. Less dangerous arrhythmias such as atrial fibrillation also occur, causing symptoms of heart racing or palpitations. However, many of those with Romano–Ward syndrome will remain free from arrhythmias and therefore free from symptoms. Certain situations are more likely to precipitate arrhythmias such as exercise or mental stress in the LQT1 subtype, sudden loud noise in the LQT2 subtype, and during sleep or immediately upon waking in the LQT3 subtype.Romano–Ward syndrome can be differentiated from other forms of long QT syndrome by Romano-Wards sole involvement of the heart.  While other forms of long QT syndrome are associated with deafness (Jervell and Lange-Nielsen syndrome), intermittent weakness and bone abormailities (LQT7, Andersen–Tawil syndrome), and autism spectrum disorder (LQT8, Timothy syndrome), these extra-cardiac manifestations are not seen in Romano-Ward.

Causes
Romano–Ward syndrome is a descriptive term for a group of subtypes of long QT syndrome, specifically subtypes LQT1-6 and LQT9-16. Several subtypes of Romano–Ward syndrome have been described based on the underlying genetic variant. These subtypes differ in clinical presentation and their response to treatment. There is robust evidence that the genetic variants associated with the three most common subtypes (LQT1, LQT2 and LQT3) are truly causative of the syndrome. However, there is uncertainty as to whether some of the other rarer subtypes are truly disease-causing by themselves or instead make individuals more susceptible to QT prolongation in response to other factors such as medication or low blood potassium levels (hypokalaemia).

LQT1
LQT1 is the most common subtype of Romano–Ward syndrome, responsible for 30 to 35% of all cases.  The gene responsible, KCNQ1, has been isolated to chromosome 11p15.5 and encodes the alpha subunit of the KvLQT1 potassium channel.  This subunit interacts with other proteins (in particular, the minK beta subunit) to create the channel, which carries the delayed potassium rectifier current IKs responsible for the repolarisation phase of the cardiac action potential.Variants in KCNQ1 cause the LQT1 subtype of Romano–Ward syndrome when a single copy of the variant is inherited (heterozygous, autosomal dominant inheritance). When two copies of the variant are inherited (homozygous, autosomal recessive inheritance) the more severe Jervell and Lange-Nielsen syndrome is found, associated with more marked QT prolongation, congenital sensorineural deafness, and a greater risk of arrhythmias.LQT1 is associated with a high risk of faints but lower risk of sudden death than LQT2.LQT1 may also affect glucose regulation. After ingesting glucose, those with LQT1 produce more insulin than would be expected, which is followed by a period of insulin resistance. When the resistance diminishes, abnormally low blood glucose levels (hypoglycaemia) are sometimes seen.

LQT2
The LQT2 subtype is the second-most common form of Romano–Ward syndrome, responsible for 25 to 30% of all cases.  This form of Romano–Ward syndrome is caused by variants in the KCNH2 gene on chromosome 7.  KCNH2 (also known as hERG) encodes the potassium channel which carries the rapid inward rectifier current IKr. This current contributes to the terminal repolarisation phase of the cardiac action potential, and therefore the length of the QT interval.

LQT3
The LQT3 subtype of Romano–Ward syndrome is caused by variants in the SCN5A gene located on chromosome 3p21-24.  SCN5A encodes the alpha subunit of the cardiac sodium channel, NaV1.5, responsible for the sodium current INa which depolarises cardiac cells at the start of the action potential.  Cardiac sodium channels normally inactivate rapidly, but the mutations involved in LQT3 slow their inactivation leading to a small sustained late sodium current.  This continued inward current prolongs the action potential and thereby the QT interval.A large number of mutations have been characterized as leading to or predisposing to LQT3.  Calcium has been suggested as a regulator of SCN5A protein, and the effects of calcium on SCN5A may begin to explain the mechanism by which some of these mutations cause LQT3. Furthermore, mutations in SCN5A can cause Brugada syndrome, cardiac conduction disease, and dilated cardiomyopathy. In rare situations, some individuals can have combinations of these diseases.

Other subtypes
LQT5 is caused by variants in the KCNE1 gene.  This gene is responsible for the potassium channel beta subunit MinK which, in conjunction with the alpha subunit encoded by KCNQ1, is responsible for the potassium current IKs, and variants associated with prolonged QT intervals decrease this current.  The same variants in KCNE1 can cause the more severe Jervell and Lange-Nielsen syndrome when two copies are inherited (homozygous inheritance) and the milder LQT5 subtype of Romano–Ward syndrome when a single copy of the variant is inherited (heterozygous inheritance).The LQT6 subtype is caused by variants in the KCNE2 gene.  This gene is responsible for the potassium channel beta subunit MiRP1 which generates the potassium current IKr, and variant that decrease this current have been associated with prolongation of the QT interval.  However, subsequent evidence such as the relatively common finding of variants in the gene in those without long QT syndrome, and the general need for a second stressor such as hypokalaemia to be present to reveal the QT prolongation, has suggested that this gene instead represents a modifier to susceptibility to QT prolongation. Some, therefore, dispute whether variants in the gene are sufficient to cause Romano–Ward syndrome by themselves.LQT9 is caused by variants in the membrane structural protein, caveolin-3. Caveolins form specific membrane domains called caveolae in which voltage-gated sodium channels sit. Similar to LQT3, these caveolin variants increase the late sustained sodium current, which impairs cellular repolarization.LQT10 is an extremely rare subtype, caused by variants in the SCN4B gene.  The product of this gene is an auxiliary beta-subunit (NaVβ4) forming cardiac sodium channels, variants in which increase the late sustained sodium current. LQT13 is caused by variants in GIRK4, a protein involved in the parasympathetic modulation of the heart. Clinically, the patients are characterized by only modest QT prolongation, but an increased propensity for atrial arrhythmias. LQT14, LQT15 and LQT16 are caused by variants in the genes responsible for calmodulin (CALM1, CALM2, and CALM3 respectively). Calmodulin interacts with several ion channels and its roles include modulation of the L-type calcium current in response to calcium concentrations, and trafficking the proteins produced by KCNQ1 and thereby influencing potassium currents.  The precise mechanisms by which means these genetic variants prolong the QT interval remain uncertain.Table of causative genes

Mechanism
In the Romano-Ward forms of Long QT syndrome, genetic mutations affect how positively-charged ions, such as potassium, sodium and calcium ions are transported in and out of heart cells.  Many of these genes encode proteins which form or interact with ion channels. In cardiac muscle, these ion channels play critical roles in maintaining the hearts normal rhythm. Mutations in any of these genes alter the structure or function of channels, which changes the flow of ions between cells, a disruption in ion transport alters the way the heart beats, leading to abnormal heart rhythm characteristic of the syndrome.The protein made by the ANK2 gene ensures that other proteins, particularly ion channels, are inserted into the cell membrane appropriately. A mutation in the ANK2 gene likely alters the flow of ions between cells in the heart, which disrupts the hearts normal rhythm and results in the features of Romano–Ward syndrome.

Diagnosis
Romano–Ward syndrome is principally diagnosed by measuring the QT interval corrected for heart rate (QTc) on a 12-lead electrocardiogram (ECG). Romano–Ward syndrome is associated with a prolonged QTc, although in some genetically proven cases of Romano–Ward syndrome this prolongation can be hidden, known as concealed Long QT syndrome. The QTc is less than 450 ms in 95% of normal males, and less than 460 ms in 95% of normal females. Romano–Ward syndrome is suggested if the QTc is longer than these cutoffs. However, as 5% of normal people also fall into this category, some suggest cutoffs of 470 and 480 ms for males and females respectively, corresponding with the 99th centiles of normal values.The major subtypes of Romano–Ward syndrome are associated with specific ECG features. LQT1 is typically associated with broad-based T-waves, whereas the T-waves in LQT2 are notched and of lower amplitude, whilst in LQT3 the T-waves are often late onset, being preceded by a long isoelectric segment.Other factors beyond the QT interval should be taken into account when making a diagnosis, some of which have been incorporated into scoring systems such as the Schwartz score.  These factors include a history of characteristic abnormal heart rhythms (Torsades de Pointes), unexplained blackouts (syncope), and a family history of confirmed LQT syndrome.  Other investigations that may suggest a diagnosis of the LQT1 form of Romano–Ward syndrome include paradoxical lengthening of the QT interval in response to exercise (QTc >470 ms at 2–4 minutes of recovery) or during an artificial infusion of adrenaline (lengthening of the absolute QT interval >30 ms during low dose adrenaline).

Treatment
The treatment for Romano–Ward syndrome aims to reduce the risk of arrhythmias.  Lifestyle measures include avoiding very strenuous or competitive exercise. Those with the LQT2 form of Romano–Ward syndrome should avoid sudden loud noises such as alarm clocks as these may trigger arrhythmias.  Fevers should be treated promptly with paracetamol.  Grapefruit juice should be avoided as it contains a chemical which decreases IKr and further prolongs the QT interval. Medications that further prolong the QT interval such as sotalol should be avoided, lists of which can be found in publicly accessible online databases.Beta blockers such as propranolol or nadolol blunt the effects of adrenaline on the heart and thereby reduce the risk of arrhythmias.  Mexiletine, flecainide and ranolazine decrease the  late sodium current and are of particular use in the LQT3 form of Romano–Ward syndrome, and mexiletine may also be of benefit in other subtypes. Potassium supplements may be used at times when potassium is being lost such as when experiencing diarrhoea or vomiting, but medications that encourage the retention of potassium such as spironolactone or amiloride may also be required.An implantable defibrillator, a small device that monitors the heart rhythm and can automatically deliver an electric shock to restart the heart, may be recommended. These devices are recommended for those with Romano–Ward syndrome who have experienced a cardiac arrest or a blackout whilst taking beta blockers. In those who experience recurrent arrhythmias despite medical therapy, a surgical procedure called sympathetic denervation can be used to interrupt the nerves that stimulate the heart.

Epidemiology
Romano–Ward syndrome is the most common form of inherited long QT syndrome, affecting an estimated 1 in 7,000 people worldwide.

See also
Long QT syndrome
Jervell and Lange-Nielsen syndrome
Andersen-Tawil syndrome
Timothy syndrome

References
Further reading
Kelly, Evelyn B. (2013-01-07). Encyclopedia of Human Genetics and Disease </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 Erythema nodosum and can you explain it in depth? [/INST] Erythema nodosum (EN) is an inflammatory condition characterized by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It can be caused by a variety of conditions, and typically resolves spontaneously within 30 days. It is common in young people aged 12–20 years.

Signs and symptoms
Pre-eruptive phase
The first signs of erythema nodosum are often flu-like symptoms such as a fever, cough, malaise, and aching joints. Some people also experience stiffness or swelling in the joints and weight loss.

Eruptive stage
Erythema nodosum is characterised by 1–2-inch (25–51 mm) nodules (rounded lumps) below the skin surface, usually on the shins. These subcutaneous nodules can appear anywhere on the body, but the most common sites are the shins, arms, thighs, and torso. Each nodule typically disappears after around two weeks, though new ones may continue to form for up to six or eight weeks. A new nodule usually appears red and is hot and firm to the touch. The redness starts to fade and it gradually becomes softer and smaller until it disappears. Each nodule usually heals completely without scarring over the course of about two weeks. Joint pain and inflammation sometimes continue for several weeks or months after the nodules appear.Less common variants of erythema nodosum include:

Ulcerating forms, seen in Crohns disease
Erythema contusiforme,  when a subcutaneous hemorrhage (bleeding under the skin) occurs with an erythema nodosum lesion, causing the lesion to look like a contusion (bruise)
Erythema nodosum migrans (also known as subacute nodular migratory panniculitis), a rare form of chronic erythema nodosum characterized by asymmetrical nodules that are mildly tender and migrate over time.

Causes
EN is associated with a wide variety of conditions.

Idiopathic
About 30–50% of EN cases are idiopathic (of an unknown cause).

Infection
Infections associated with EN include:
Streptococcal infection which, in children, is by far the most common precipitant
Primary infection of tuberculosis
Mycoplasma pneumoniae
Histoplasma capsulatum
Yersinia
Lymphogranuloma venereum (LGV), caused by the bacteria Chlamydia trachomatis
Epstein-Barr virus
Coccidioides immitis (Valley fever)
Cat scratch disease

Autoimmune disorders
Autoimmune disorders associated with EN include:
Inflammatory bowel disease (IBD): about 15% of patients develop erythema nodosum.
Behçets disease
Sarcoidosis

Pregnancy
Pregnancy may be associated with EN.

Medications
Medications associated with EN include:
Omeprazole
Sulfonamides
Penicillins
Bromides
Hepatitis B vaccination

Cancer
Cancers associated with EN include:
Non-Hodgkins lymphoma (NHL)
Carcinoid tumours
Pancreatic cancerEN may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes.There is an association with the HLA-B27 histocompatibility antigen, which is present in 65% of patients with erythema nodosum.A useful mnemonic for causes is SORE SHINS (Streptococci, OCP, Rickettsia, Eponymous (Behçet), Sulfonamides, Hansens Disease (Leprosy), IBD, NHL, Sarcoidosis.

Pathophysiology
Erythema nodosum is probably a delayed hypersensitivity reaction to a variety of antigens. Although circulating immune complexes have been demonstrated in patients with inflammatory bowel disease, they have not been found in idiopathic or uncomplicated cases.

Diagnosis
Erythema nodosum is diagnosed clinically. A biopsy can be taken and examined microscopically to confirm an uncertain diagnosis. Microscopic examination usually reveals a neutrophilic infiltrate surrounding capillaries that results in septal thickening, with fibrotic changes in the fat around blood vessels. A characteristic microscopic finding is radial granulomas, well-defined nodular aggregates of histiocytes surrounding a stellate cleft.Additional evaluation should be performed to determine the underlying cause of erythema nodosum. This may include a full blood count, erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer and throat culture, urinalysis, intradermal tuberculin test, and a chest x-ray. The ESR is typically high, the C-reactive protein elevated, and the blood showing an increase in white blood cells.The ESR is initially very high and falls as the nodules of erythema nodosum. The ASO titer is high in cases associated with a streptococcal throat infection </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 Ascites and can you explain it in depth? [/INST] Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, abdominal discomfort, and shortness of breath. Complications can include spontaneous bacterial peritonitis.In the developed world, the most common cause is liver cirrhosis. Other causes include cancer, heart failure, tuberculosis, pancreatitis, and blockage of the hepatic vein. In cirrhosis, the underlying mechanism involves high blood pressure in the portal system and dysfunction of blood vessels. Diagnosis is typically based on an examination together with ultrasound or a CT scan. Testing the fluid can help in determining the underlying cause.Treatment often involves a low-salt diet, medication such as diuretics, and draining the fluid. A transjugular intrahepatic portosystemic shunt (TIPS) may be placed but is associated with complications. Attempts to treat the underlying cause, such as by a liver transplant may be considered. Of those with cirrhosis, more than half develop ascites in the ten years following diagnosis. Of those in this group who develop ascites, half will die within three years. The term is from the Greek askítes meaning "baglike".

Signs and symptoms
Mild ascites is hard to notice, but severe ascites leads to abdominal distension. People with ascites generally will complain of progressive abdominal heaviness and pressure as well as shortness of breath due to mechanical impingement on the diaphragm.Ascites is detected with physical examination of the abdomen by visible bulging of the flanks in the reclining person ("flank bulging"), "shifting dullness" (difference in percussion note in the flanks that shifts when the person is turned on the side), or in massive ascites, with a "fluid thrill" or "fluid wave" (tapping or pushing on one side will generate a wave-like effect through the fluid that can be felt in the opposite side of the abdomen).
Other signs of ascites may be present due to its underlying cause. For instance, in portal hypertension (perhaps due to cirrhosis or fibrosis of the liver) people may also complain of leg swelling, bruising, gynecomastia, hematemesis, or mental changes due to encephalopathy. Those with ascites due to cancer (peritoneal carcinomatosis) may complain of chronic fatigue or weight loss. Those with ascites due to heart failure may also complain of shortness of breath as well as wheezing and exercise intolerance.

Complications
Complications may include spontaneous bacterial peritonitis, hepatorenal syndrome, and thrombosis. Portal vein thrombosis and splenic vein thrombosis involve clotting of blood affects the hepatic portal vein or varices associated with splenic vein. This can lead to portal hypertension and a reduction in blood flow. When a person with liver cirrhosis has thrombosis, it is not possible to perform a liver transplant, unless the thrombosis is very minor. In case of minor thrombosis, there are some chances of survival using cadaveric liver transplant.

Causes
Causes of high serum-ascites albumin gradient (SAAG or transudate) are
Cirrhosis – 81% (alcoholic in 65%, viral in 10%, cryptogenic in 6%)
Heart failure – 3%
Hepatic venous occlusion: Budd–Chiari syndrome or veno-occlusive disease
Constrictive pericarditis
Kwashiorkor (childhood protein-energy malnutrition)Causes of low SAAG ("exudate") areCancer (metastasis and primary peritoneal carcinomatosis) – 10%
Infection: Tuberculosis – 2% or spontaneous bacterial peritonitis
Pancreatitis – 1%
Serositis
Nephrotic syndrome
Hereditary angioedemaOther rare causesMeigs syndrome
Vasculitis
Hypothyroidism
Renal dialysis
Peritoneum mesothelioma
Abdominal tuberculosis
Mastocytosis

Diagnosis
Routine complete blood count (CBC), basic metabolic profile, liver enzymes, and coagulation should be performed. Most experts recommend a diagnostic paracentesis be performed if the ascites is new or if the person with ascites is being admitted to the hospital. The fluid is then reviewed for its gross appearance, protein level, albumin, and cell counts (red and white). Additional tests will be performed if indicated such as microbiological culture, Gram stain and cytopathology.The serum-ascites albumin gradient (SAAG) is probably a better discriminant than older measures (transudate versus exudate) for the causes of ascites. A high gradient (> 1.1 g/dL) indicates the ascites is due to portal hypertension. A low gradient (< 1.1 g/dL) indicates ascites of non-portal hypertensive as a cause.Ultrasound investigation is often performed prior to attempts to remove fluid from the abdomen. This may reveal the size and shape of the abdominal organs, and Doppler studies may show the direction of flow in the portal vein, as well as detecting Budd-Chiari syndrome (thrombosis of the hepatic vein) and portal vein thrombosis. Additionally, the sonographer can make an estimation of the amount of ascitic fluid, and difficult-to-drain ascites may be drained under ultrasound guidance. An abdominal CT scan is a more accurate alternate to reveal abdominal organ structure and morphology.

Classification
Ascites exists in three grades:
Grade 1: mild, only visible on ultrasound and CT
Grade 2: detectable with flank bulging and shifting dullness
Grade 3: directly visible, confirmed with the fluid wave/thrill test

Pathophysiology
Ascitic fluid can accumulate as a transudate or an exudate. Amounts of up to 35 liters are possible.
Roughly, transudates are a result of increased pressure in the hepatic portal vein (>8 mmHg, usually around 20 mmHg (e.g., due to cirrhosis), while exudates are actively secreted fluid due to inflammation or malignancy. As a result, exudates are high in protein and lactate dehydrogenase and have a low pH (<7.30), a low glucose level, and more white blood cells. Transudates have low protein (<30 g/L), low LDH, high pH, normal glucose, and fewer than 1 white cell per 1000 mm3. Clinically, the most useful measure is the difference between ascitic and serum albumin concentrations. A difference of less than 1 g/dl (10 g/L) implies an exudate.Portal hypertension plays an important role in the production of ascites by raising capillary hydrostatic pressure within the splanchnic bed.
Regardless of the cause, sequestration of fluid within the abdomen leads to additional fluid retention by the kidneys due to stimulatory effect on blood pressure hormones, notably aldosterone. The sympathetic nervous system is also activated, and renin production is increased due to decreased perfusion of the kidney. Extreme disruption of the renal blood flow can lead to hepatorenal syndrome. Other complications of ascites include spontaneous bacterial peritonitis (SBP), due to decreased antibacterial factors in the ascitic fluid such as complement.

Treatment
Ascites is generally treated while an underlying cause is sought, in order to prevent complications, relieve symptoms, and prevent further progression. In people with mild ascites, therapy is usually as an outpatient. The goal is weight loss of no more than 1.0 kg/day for people with both ascites and peripheral edema and no more than 0.5 kg/day for people with ascites alone. In those with severe ascites causing a tense abdomen, hospitalization is generally necessary for paracentesis.

High serum-ascites albumin gradient (transudative) ascites
Diet
Salt restriction is the initial treatment, which allows diuresis (production of urine) since the person now has more fluid than salt concentration. Salt restriction is effective in about 15% of these people. Water restriction is needed if serum sodium levels drop below 130 mmol L−1.

Diuretics
Since salt restriction is the basic concept in treatment, and aldosterone is one of the hormones that acts to increase salt retention, a medication that counteracts aldosterone should be sought. Spironolactone (or other distal-tubule diuretics such as triamterene or amiloride) is the drug of choice since they block the aldosterone receptor in the collecting tubule. This choice has been confirmed in a randomized controlled trial. Diuretics for ascites should be dosed once per day. Generally, the starting dose is oral spironolactone 100 mg/day (max 400 mg/day).
40% of people will respond to spironolactone. For nonresponders, a loop diuretic may also be added and generally, furosemide is added at a dose of 40 mg/day (max 160 mg/day), or alternatively (bumetanide or torasemide). The ratio of 100:40 reduces risks of potassium imbalance. Serum potassium level and renal function should be monitored closely while on these medications.Monitoring diuresis: Diuresis can be monitored by weighing the person daily. The goal is weight loss of no more than 1.0 kg/day for people with both ascites and peripheral edema and no more than 0.5 kg/day for people with ascites alone.
If daily weights cannot be obtained, diuretics can also be guided by the urinary sodium concentration. Dosage is increased until a negative sodium balance occurs </s>