<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Central diabetes insipidus and explain in detail? [/INST] Central diabetes insipidus, also called neurogenic diabetes insipidus, is a type of diabetes insipidus due to a lack of vasopressin (ADH) production in the brain.  Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced. Therefore, a lack of it causes increased urine production and volume depletion.
It is also known as neurohypophyseal diabetes insipidus, referring to the posterior pituitary (neurohypophysis), which is supplied by the hypothalamus in the brain. This condition has only polyuria in common with diabetes. Although not mutually exclusive, with most typical cases, the name diabetes insipidus is a misleading misnomer </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Gastritis and explain in detail? [/INST] Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Other possible symptoms include nausea and vomiting, bloating, loss of appetite and heartburn. Complications may include stomach bleeding, stomach ulcers, and stomach tumors. When due to autoimmune problems, low red blood cells due to not enough vitamin B12 may occur, a condition known as pernicious anemia.Common causes include infection with Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Less common causes include alcohol, smoking, cocaine, severe illness, autoimmune problems, radiation therapy and Crohns disease. Endoscopy, a type of X-ray known as an upper gastrointestinal series, blood tests, and stool tests may help with diagnosis. The symptoms of gastritis may be a presentation of a myocardial infarction. Other conditions with similar symptoms include inflammation of the pancreas, gallbladder problems, and peptic ulcer disease.Prevention is by avoiding things that cause the disease. Treatment includes medications such as antacids, H2 blockers, or proton pump inhibitors. During an acute attack drinking viscous lidocaine may help. If gastritis is due to NSAIDs these may be stopped. If H. pylori is present it may be treated with a combination of antibiotics such as amoxicillin and clarithromycin. For those with pernicious anemia, vitamin B12 supplements are recommended either by mouth or by injection. People are usually advised to avoid foods that bother them.Gastritis is believed to affect about half of people worldwide. In 2013 there were approximately 90 million new cases of the condition. As people get older the disease becomes more common. It, along with a similar condition in the first part of the intestines known as duodenitis, resulted in 50,000 deaths in 2015. H. pylori was first discovered in 1981 by Barry Marshall and Robin Warren.

Signs and symptoms
Many people with gastritis experience no symptoms at all. However, upper central abdominal pain is the most common symptom; the pain may be dull, vague, burning, aching, gnawing, sore, or sharp. Pain is usually located in the upper central portion of the abdomen, but it may occur anywhere from the upper left portion of the abdomen around to the back.
Other signs and symptoms may include the following:

Nausea
Vomiting (may be clear, green or yellow, blood-streaked or completely bloody depending on the severity of the stomach inflammation)
Belching (does not usually relieve stomach pain if present)
Bloating
Early satiety
Loss of appetite
Unexplained weight loss

Causes
There are two categories of gastritis depending on the cause of the disease. There is erosive gastritis, for which the common causes are stress, alcohol, some drugs, such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), and Crohns disease.  And, there is non-erosive gastritis, for which the most common cause is a Helicobacter pylori infection.

Helicobacter pylori
Helicobacter pylori colonizes the stomachs of more than half of the worlds population, and the infection continues to play a key role in the pathogenesis of a number of gastroduodenal diseases. Colonization of the gastric mucosa with Helicobacter pylori results in the development of chronic gastritis in infected individuals and, in a subset of patients, chronic gastritis progresses to complications (e.g., ulcer disease, stomach cancers, and some distinct extragastric disorders). However, more than 80% of individuals infected with the bacterium are asymptomatic and it has been postulated that it may play an important role in the natural stomach ecology.

Critical illness
Gastritis may also develop after major surgery or traumatic injury ("Cushing ulcer"), burns ("Curling ulcer"), or severe infections. Gastritis may also occur in those who have had weight loss surgery resulting in the banding or reconstruction of the digestive tract.

Diet
Evidence does not support a role for specific foods, including spicy foods and coffee, in the development of peptic ulcers. People are usually advised to avoid foods that bother them. There is little specific advice on diet published by authoritative sources. The website of the National Health Service of the United Kingdom advises "avoiding foods that can irritate the stomach, such as spicy, acidic or fried foods", and suggests that "you may want to talk to a GP about this".

Pathophysiology
Acute
Acute erosive gastritis typically involves discrete foci of surface necrosis due to damage to mucosal defenses. NSAIDs inhibit cyclooxygenase-1, or COX-1, an enzyme responsible for the biosynthesis of eicosanoids in the stomach, which increases the possibility of peptic ulcers forming.  Also, NSAIDs, such as aspirin, reduce a substance that protects the stomach called prostaglandin. These drugs used in a short period are not typically dangerous. However, regular use can lead to gastritis. Additionally, severe physiologic stress ("stress ulcers") from sepsis, hypoxia, trauma, or surgery is also a common etiology for acute erosive gastritis. This form of gastritis can occur in more than 5% of hospitalized patients.Also, note that alcohol consumption does not cause chronic gastritis.  It does, however, erode the mucosal lining of the stomach; low doses of alcohol stimulate hydrochloric acid secretion. High doses of alcohol do not stimulate secretion of acid.

Chronic
Chronic gastritis refers to a wide range of problems of the gastric tissues.  The immune system makes proteins and antibodies that fight infections in the body to maintain a homeostatic condition.  In some disorders the body targets the stomach as if it were a foreign protein or pathogen; it makes antibodies against, severely damages, and may even destroy the stomach or its lining.  In some cases bile, normally used to aid digestion in the small intestine, will enter through the pyloric valve of the stomach if it has been removed during surgery or does not work properly, also leading to gastritis.  Gastritis may also be caused by other medical conditions, including HIV/AIDS, Crohns disease, certain connective tissue disorders, and liver or kidney failure. Since 1992, chronic gastritis lesions are classified according to the Sydney system.

Metaplasia
Mucous gland metaplasia, the reversible replacement of differentiated cells, occurs in the setting of severe damage of the gastric glands, which then waste away (atrophic gastritis) and are progressively replaced by mucous glands. Gastric ulcers may develop; it is unclear if they are the causes or the consequences.  Intestinal metaplasia typically begins in response to chronic mucosal injury in the antrum and may extend to the body. Gastric mucosa cells change to resemble intestinal mucosa and may even assume absorptive characteristics. Intestinal metaplasia is classified histologically as complete or incomplete. With complete metaplasia, gastric mucosa is completely transformed into small-bowel mucosa, both histologically and functionally, with the ability to absorb nutrients and secrete peptides. In incomplete metaplasia, the epithelium assumes a histologic appearance closer to that of the large intestine and frequently exhibits dysplasia.

Diagnosis
Often, a diagnosis can be made based on  patients description of their symptoms. Other methods which may be used to verify gastritis include:

Blood tests:
Blood cell count
Presence of H. pylori
Liver, kidney, gallbladder, or pancreas functions
Urinalysis
Stool sample, to look for blood in the stool
X-rays
Endoscopy, to check for stomach lining inflammation and mucous erosion
Stomach biopsy, to test for gastritis and other conditionsThe OLGA staging frame of chronic gastritis on histopathology. Atrophy is scored as the percentage of atrophic glands and scored on a four-tiered scale. No atrophy (0%) = score 0; mild atrophy (1–30%) = score 1; moderate atrophy (31–60%) = score 2; 9 severe atrophy (>60%) = score 3. These scores (0–3) are used in the OLGA staging assessment in each 10 compartment:

Treatment
Antacids are a common treatment for mild to medium gastritis. When antacids do not provide enough relief, medications such as H2 blockers and proton-pump inhibitors that help reduce the amount of acid are often prescribed.Cytoprotective agents are designed to help protect the tissues that line the stomach and small intestine. They include the medications sucralfate and misoprostol. If NSAIDs are being taken regularly, one of these medications to protect the stomach may also be taken. Another cytoprotective agent is bismuth subsalicylateSeveral regimens are used to treat H. pylori infection. Most use a combination of two antibiotics and a proton pump inhibitor. Sometimes bismuth is added to the regimen.

History
In 1,000 A.D, Avicenna first gave the description of stomach cancer. In 1728, German physician Georg Ernst Stahl first coined the term "gastritis". Italian anatomical pathologist Giovanni Battista Morgagni further described the characteristics of gastric inflammation </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Urticarial vasculitis and explain in detail? [/INST] Urticarial vasculitis (also known as "chronic urticaria as a manifestation of venulitis", "hypocomplementemic urticarial vasculitis syndrome", "hypocomplementemic vasculitis" and "unusual lupus-like syndrome") is a skin condition characterized by fixed urticarial lesions that appear histologically as a vasculitis.: 834

Mechanism
Antibodies are usually raised against foreign proteins, such as those made by a replicating virus or invading bacterium. Virus or bacteria with antibodies opsonized or "stuck" to them highlight them to other cells of the immune system for clearance.
Antibodies against self proteins are known as autoantibodies, and are not found in healthy individuals. These autoantibodies can be used to detect certain diseases.

C1q
C1q is an integral component within the complement pathway – a complicated cascade of protein interactions, culminating in an immune response against a broad variety of pathogens. The anti-C1q antibodies found in patients with hypocomplementemic urticarial vasculitis activate C1q, which instigates activation of the entire complement pathway. Consequently, levels of all complement proteins become low.

Impaired classical complement pathway
The complement pathway is composed of several subset pathways: the lectin/mannose pathway, alternative pathway and the classical pathway. All pathways culminate in the production of a C3 convertase, which catalyses C3 into its constitutive parts (better detailed here – classical complement pathway).In brief, the crucial role of C1q in the pathway is its importance as the first protein to start the complement cascade (which ends in the destruction of the invading bacteria or virus), and its ability to link the two important arms of the immune system – the innate immune system: a broad defence system; and the adaptive immune system: the strong immune response capable of remembering previous infections, allowing fast response against recurrent infections, meaning that people with a normal immune system dont continually catch the same cold or same strain of flu repeatedly.Case studies of individuals with HUV have also highlighted other potential complicating factors which it seems the anti-C1q antibodies play a role in. This can mean in some cases the deposition of large immune complexes in the kidney which cannot be cleared by the usual cells of the immune system (e.g. macrophages which are unable to bind the Fc portion of the C1q antibody), leading to further complications </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pancreatic fistula and explain in detail? [/INST] A pancreatic fistula is an abnormal communication between the pancreas and other organs due to leakage of pancreatic secretions from damaged pancreatic ducts. An external pancreatic fistula is one that communicates with the skin, and is also known as a pancreaticocutaneous fistula, whereas an internal pancreatic fistula communicates with other internal organs or spaces. Pancreatic fistulas can be caused by pancreatic disease, trauma, or surgery.

Signs and symptoms
Marked recent weight loss is a major clinical manifestation, and unresponsiveness of the ascites to diuretics is an additional diagnostic clue.

Pathogenesis
Internal pancreatic fistulas are most commonly caused by disruption of the pancreatic duct due to chronic pancreatitis. The chronic pancreatitis is usually alcoholic in origin in adults, and traumatic in origin in children.  They may also be caused by leakage from a pancreatic pseudocyst.
Anterior disruption of a pseudocyst or a pancreatic duct leads to leakage of pancreatic secretions into the free peritoneal cavity, leading to pancreatic ascites </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Histidinemia and explain in detail? [/INST] Histidinemia is a rare autosomal recessive metabolic disorder caused by a deficiency of the enzyme histidase. Histidase is needed for the metabolism of the amino acid histidine.  Although originally thought to be linked to multiple developmental disorders histidinemia is now accepted as a relatively benign disorder, leading to a reduction in the prevalence of neonatal screening procedures.

Presentation
Histidinemia is considered benign as most patients remain asymptomatic, early correlational evidence from the first decade of histidinemia research lead to the theory that histidinemia was associated with multiple developmental symptoms including hyperactivity, speech impediment, developmental delay, learning difficulties, and sometimes mental retardation </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hepatosplenomegaly and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Benzodiazepine dependence and explain in detail? [/INST] Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, however, the continued use seems to be associated with the avoidance of unpleasant withdrawal reaction rather than from the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, without the described dependence behavior.Addiction consists of people misusing or craving the drug not to relieve withdrawal symptoms, but to experience its euphoric or intoxicating effects. It is necessary to distinguish between addiction to and abuse of benzodiazepines and physical dependence on them. The increased GABA inhibition on the neural systems caused by benzodiazepines is counteracted by the bodys development of tolerance to the drugs effects; the development of tolerance occurs as a result of neuroadaptations, which result in decreased GABA activity and increased excitability of the glutamate system; these adaptations occur as a result of the body trying to overcome the central nervous system depressant effects of the drug to restore homeostasis. When benzodiazepines are stopped, these neuroadaptations are "unmasked" leading to hyper-excitability of the nervous system and the appearance of withdrawal symptoms.Therapeutic dose dependence is the largest category of people dependent on benzodiazepines. These individuals typically do not escalate their doses to high levels and generally use their medication as intended by their prescriber. Smaller groups include patients escalating their dosage to higher levels and drug misusers as well. Tolerance develops within days or weeks to the anticonvulsant, hypnotic, muscle relaxant and after 4 months there is little evidence that benzodiazepines retain their anxiolytic properties. Some authors, however, disagree and feel that benzodiazepines retain their anxiolytic properties. Long-term benzodiazepine treatment may remain necessary in certain clinical conditions.Numbers of benzodiazepine prescriptions have been declining, due primarily to concerns of dependence. In the short term, benzodiazepines can be effective drugs for acute anxiety or insomnia. With longer-term use, other therapies, both pharmacological and psychotherapeutic, become more effective. This is in part due to the greater effectiveness over time of other forms of therapy, and also due to the eventual development of pharmacological benzodiazepine tolerance.

Signs and symptoms
The signs and symptoms of benzodiazepine dependence include feeling unable to cope without the drug, unsuccessful
attempts to cut down or stop benzodiazepine use, tolerance to the effects of benzodiazepines, and withdrawal symptoms when not taking the drug. Some withdrawal symptoms that may appear include anxiety, depressed mood, depersonalisation, derealisation, sleep disturbance, hypersensitivity to touch and pain, tremor, shakiness, muscular aches, pains, twitches, and headache. Benzodiazepine dependence and withdrawal have been associated with suicide and self-harming behaviors, especially in young people. The Department of Health substance misuse guidelines recommend monitoring for mood disorder in those dependent on or withdrawing from benzodiazepines.Benzodiazepine dependence is a frequent complication for those prescribed for or using for longer than four weeks, with physical dependence and withdrawal symptoms being the most common problem, but also occasionally drug-seeking behavior. Withdrawal symptoms include anxiety, perceptual disturbances, distortion of all the senses, dysphoria, and, in rare cases, psychosis and epileptic seizures.

Elderly
Long-term use and benzodiazepine dependence is a serious problem in the elderly. Failure to treat benzodiazepine dependence in the elderly can cause serious medical complications. The elderly have less cognitive reserve and are more sensitive to the short (e.g., in between dose withdrawal) and protracted withdrawal effects of benzodiazepines, as well as the side-effects both from short-term and long-term use. This can lead to excessive contact with their doctor. Research has found that withdrawing elderly people from benzodiazepines leads to a significant reduction in doctor visits per year, it is presumed, due to an elimination of drug side-effects and withdrawal effects.Tobacco and alcohol are the most common substances that elderly individuals develop dependence on or misuse. The next-most-common substance that elderly people develop a drug dependence to or misuse is benzodiazepines. Drug-induced cognitive problems can have serious consequences for elderly people and can lead to confusional states and "pseudo-dementia". About 10% of elderly patients referred to memory clinics actually have a drug-induced cause that most often is benzodiazepines. Benzodiazepines have also been linked to an increased risk of road traffic accidents and falls in the elderly. The long-term effects of benzodiazepines are still not fully understood. Long-term benzodiazepine use is associated with attentional and visuospatial functional impairments. Withdrawal from benzodiazepines can lead to improved alertness and decreased forgetfulness in the elderly. Withdrawal led to statistically significant improvements in memory function and performance-related skills in those having withdrawn successfully from benzodiazepines, whereas those having remained on benzodiazepines experienced worsening symptoms. People having withdrawn from benzodiazepines also felt their sleep was more refreshing, making statements such as "I feel sharper when I wake up" or "I feel better, more awake", or "It used to take me an hour to fully wake up." This suggests that benzodiazepines may actually make insomnia worse in the elderly.

Cause
Tolerance occurs to the muscle-relaxant, anticonvulsant, and sleep-inducing effects of benzodiazepines, and upon cessation a benzodiazepine withdrawal syndrome occurs. This can lead to benzodiazepines being taken for longer than originally intended, as people continue to take the drugs over a long period of time to suppress withdrawal symptoms. Some people use benzodiazepines at very high doses and devote a lot of time to doing so, satisfying the diagnostic criteria in DSM V for substance use disorder. Another group of people include those on low to moderate therapeutic doses of benzodiazepines who do not use their benzodiazepines differently than recommended by their prescriber but develop a physical tolerance and benzodiazepine dependence. A considerable number of individuals using benzodiazepines for insomnia escalate their dosage, sometimes above therapeutically-prescribed dose levels. Tolerance to the anxiolytic effect of benzodiazepines has been clearly demonstrated in rats. In humans, there is little evidence that benzodiazepines retain their anti-anxiety effects beyond four months of continuous treatment; there is evidence that suggests that long-term use of benzodiazepines may actually worsen anxiety, which in turn may lead to dosage escalation, with one study finding 25% of patients escalated their dosage. Some authors, however, consider benzodiazepines to be effective long-term; however, it is more likely that the drugs are acting to prevent rebound anxiety withdrawal effects which can be mistaken as continued drug efficacy. Tolerance to the anticonvulsant and muscle-relaxing effects of benzodiazepines occurs within a few weeks in most patients.

Risk factors
The risk factors for benzodiazepine dependence are long-term use beyond four weeks, use of high doses, use of potent short-acting benzodiazepines, dependent personalities, and proclivity for substance use. Use of short-acting benzodiazepines leads to repeated withdrawal effects that are alleviated by the next dose, which reinforce in the individual the dependence. A physical dependence develops more quickly with higher potency benzodiazepines such as alprazolam (Xanax) than with lower potency benzodiazepines such as chlordiazepoxide (Librium).Symptom severity is worse with the use of high doses, or with benzodiazepines of high potency or short half-life. Other cross-tolerant sedative hypnotics, such as barbiturates or alcohol, increase the risk of benzodiazepine dependence. Similar to opioids use for pain, therapeutic use of benzodiazepines rarely leads to a substance use disorder.

Mechanism
Tolerance and physical dependence
Tolerance develops rapidly to the sleep-inducing effects of benzodiazepines. The anticonvulsant and muscle-relaxant effects last for a few weeks before tolerance develops in most individuals. Tolerance results in a desensitization of GABA receptors and an increased sensitization of the excitatory neurotransmitter system, such as NMDA glutamate receptors. These changes occur as a result of the body trying to overcome the drugs effects. Other changes that occur are the reduction of the number of GABA receptors (downregulation) as well as possibly long-term changes in gene transcription coding of brain cells. The differing speed at which tolerance occurs to the therapeutic effects of benzodiazepines can be explained by the speed of changes in the range of neurotransmitter systems and subsystems that are altered by chronic benzodiazepine use. The various neurotransmitter systems and subsystems may reverse tolerance at different speeds, thus explaining the prolonged nature of some withdrawal symptoms. As a result of a physical dependence that develops due to tolerance, a characteristic benzodiazepine withdrawal syndrome often occurs after removal of the drug or a reduction in dosage. Changes in the expression of neuropeptides such as corticotropin-releasing hormone and neuropeptide Y may play a role in benzodiazepine dependence. Individuals taking daily benzodiazepine drugs have a reduced sensitivity to further additional doses of benzodiazepines. Tolerance to benzodiazepines can be demonstrated by injecting diazepam into long-term users. In normal subjects, increases in growth hormone occurs, whereas, in benzodiazepine-tolerant individuals, this effect is blunted.Animal studies have shown that repeated withdrawal from benzodiazepines leads to increasingly severe withdrawal symptoms, including an increased risk of seizures; this phenomenon is known as kindling. Kindling phenomena are well established for repeated ethanol (alcohol) withdrawal; alcohol has a very similar mechanism of tolerance and withdrawal to benzodiazepines, involving the GABAA, NMDA, and AMPA receptors.The shift of benzodiazepine receptors to an inverse agonist state after chronic treatment leads the brain to be more sensitive to excitatory drugs or stimuli. Excessive glutamate activity can result in excitotoxicity, which may result in neurodegeneration. The glutamate receptor subtype NMDA is well known for its role in causing excito-neurotoxicity. The glutamate receptor subtype AMPA is believed to play an important role in neuronal kindling as well as excitotoxicity during withdrawal from alcohol as well as benzodiazepines. It is highly possible that NMDA receptors are involved in the tolerance to some effects of benzodiazepines.Animal studies have found that glutamergic changes as a result of benzodiazepine use are responsible for a delayed withdrawal syndrome, which in mice peaks 3 days after cessation of benzodiazepines. This was demonstrated by the ability to avoid the withdrawal syndrome by the administration of AMPA antagonists. It is believed that different glutamate subreceptors, e.g., NMDA and AMPA, are responsible for different stages/time points of the withdrawal syndrome. NMDA receptors are upregulated in the brain as a result of benzodiazepine tolerance. AMPA receptors are also involved in benzodiazepine tolerance and withdrawal. A decrease in benzodiazepine binding sites in the brain may also occur as part of benzodiazepine tolerance.

Cross tolerance
Benzodiazepines share a similar mechanism of action with various sedative compounds that act by enhancing the GABAA receptor. Cross tolerance means that one drug will alleviate the withdrawal effects of another. It also means that tolerance of one drug will result in tolerance of another similarly-acting drug. Benzodiazepines are often used for this reason to detoxify alcohol-dependent patients and can have life-saving properties in preventing or treating severe life-threatening withdrawal syndromes from alcohol, such as delirium tremens. However, although benzodiazepines can be very useful in the acute detoxification of alcoholics, benzodiazepines in themselves act as positive reinforcers in alcoholics, by increasing the desire for alcohol. Low doses of benzodiazepines were found to significantly increase the level of alcohol consumed in alcoholics. Alcoholics dependent on benzodiazepines should not be abruptly withdrawn but be very slowly withdrawn from benzodiazepines, as over-rapid withdrawal is likely to produce severe anxiety or panic, which is well known for being a relapse risk factor in recovering alcoholics.There is cross tolerance between alcohol, the benzodiazepines, the barbiturates, the nonbenzodiazepine drugs, and corticosteroids, which all act by enhancing the GABAA receptors function via modulating the chloride ion channel function of the GABAA receptor.Neuroactive steroids, e.g., progesterone and its active metabolite allopregnanolone, are positive modulators of the GABAA receptor and are cross tolerant with benzodiazepines. The active metabolite of progesterone has been found to enhance the binding of benzodiazepines to the benzodiazepine binding sites on the GABAA receptor. The cross-tolerance between GABAA receptor positive modulators, including benzodiazepines, occurs because of the similar mechanism of action and the subunit changes that occur from chronic use from one or more of these compounds in expressed receptor isoforms. Abrupt withdrawal from any of these compounds, e.g., barbiturates, benzodiazepines, alcohol, corticosteroids, neuroactive steroids, and nonbenzodiazepines, precipitate similar withdrawal effects characterized by central nervous system hyper-excitability, resulting in symptoms such as increased seizure susceptibility and anxiety. While many of the neuroactive steroids do not produce full tolerance to their therapeutic effects, cross-tolerance to benzodiazepines still occurs as had been demonstrated between the neuroactive steroid ganaxolone and diazepam. Alterations of levels of neuroactive steroids in the body during the menstrual cycle, menopause, pregnancy, and stressful circumstances can lead to a reduction in the effectiveness of benzodiazepines and a reduced therapeutic effect. During withdrawal of neuroactive steroids, benzodiazepines become less effective.

Physiology of withdrawal
Withdrawal symptoms are a normal response in individuals having chronically used benzodiazepines, and an adverse effect and result of drug tolerance. Symptoms typically emerge when dosage of the drug is reduced. GABA is the second-most-common neurotransmitter in the central nervous system (the most common being glutamate) and by far the most abundant inhibitory neurotransmitter; roughly one-quarter to one-third of synapses use GABA. The use of benzodiazepines has a profound effect on almost every aspect of brain and body function, either directly or indirectly.Benzodiazepines cause a decrease in norepinephrine (noradrenaline), serotonin, acetylcholine, and dopamine. These neurotransmitters are needed for normal memory, mood, muscle tone and coordination, emotional responses, endocrine gland secretions, heart rate, and blood pressure control. With chronic benzodiazepine use, tolerance develops rapidly to most of its effects, so that, when benzodiazepines are withdrawn, various neurotransmitter systems go into overdrive due to the lack of inhibitory GABA-ergic activity. Withdrawal symptoms then emerge as a result, and persist until the nervous system physically reverses the adaptions (physical dependence) that have occurred in the CNS.Withdrawal symptoms typically consist of a mirror image of the drugs effects: Sedative effects and suppression of REM and SWS stages of sleep can be replaced by insomnia, nightmares, and hypnogogic hallucinations; its antianxiety effects are replaced with anxiety and panic; muscle-relaxant effects are replaced with muscular spasms or cramps; and anticonvulsant effects are replaced with seizures, especially in cold turkey or overly-rapid withdrawal.Benzodiazepine withdrawal represents in part excitotoxicity to brain neurons. Rebound activity of the hypothalamic-pituitary-adrenocortical axis also plays an important role in the severity of benzodiazepine withdrawal. Tolerance and the resultant withdrawal syndrome may be due to alterations in gene expression, which results in long-term changes in the function of the GABAergic neuronal system.During withdrawal from full or partial agonists, changes occur in benzodiazepine receptor with upregulation of some receptor subtypes and downregulation of other receptor subtypes.

Withdrawal
Long-term use of benzodiazepines leads to increasing physical and mental health problems, and as a result, discontinuation is recommended for many long-term users. The withdrawal syndrome from benzodiazepines can range from a mild and short-lasting syndrome to a prolonged and severe syndrome. Withdrawal symptoms can lead to continued use of benzodiazepines for many years, long after the original reason for taking benzodiazepines has passed. Many patients know that the benzodiazepines no longer work for them but are unable to discontinue benzodiazepines because of withdrawal symptoms.Withdrawal symptoms can emerge despite slow reduction but can be reduced by a slower rate of withdrawal. As a result, withdrawal rates have been recommended to be customized to each individual patient. The time needed to withdrawal can vary from a couple of months to a year or more and often depends on length of use, dosage taken, lifestyle, health, and social and environmental stress factors.Diazepam is often recommended due to its long elimination half-life and also because of its availability in low potency doses. The non-benzodiazepine Z drugs such as zolpidem, zaleplon, and zopiclone should not be used as a replacement for benzodiazepines, as they have a similar mechanism of action and can induce a similar dependence. The pharmacological mechanism of benzodiazepine tolerance and dependence is the internalization (removal) of receptor site in the brain and changes in gene transcription codes in the brain.With long-term use and during withdrawal of benzodiazepines, treatment-emergent depression and emotional blunting may emerge and sometimes also suicidal ideation. There is evidence that the higher the dose used the more likely it is benzodiazepine use will induce these feelings. Reducing the dose or discontinuing benzodiazepines may be indicated in such cases. Withdrawal symptoms can persist for quite some time after discontinuing benzodiazepines. Some common protracted withdrawal symptoms include anxiety, depression, insomnia, and physical symptoms such as gastrointestinal, neurologic, and musculoskeletal effects. The protracted withdrawal state may still occur despite slow titration of dosage. It is believed that the protracted withdrawal effects are due to persisting neuroadaptations.

Diagnosis
For a diagnosis of benzodiazepine dependence to be made, the ICD-10 requires that at least 3 of the below criteria are met and that they have been present for at least a month, or, if less than a month, that they appeared repeatedly during a 12-month period.
Behavioral, cognitive, and physiological phenomena that are associated with the repeated use and that typically include a strong desire to take the drug.
Difficulty controlling use
Continued use despite harmful consequences
Preference given to drug use rather than to other activities and obligations
Increased tolerance to effects of the drug and sometimes a physical withdrawal state.These diagnostic criteria are good for research purposes, but, in everyday clinical practice, they should be interpreted according to clinical judgement. In clinical practice, benzodiazepine dependence should be suspected in those having used benzodiazepines for longer than a month, in particular, if they are from a high-risk group. The main factors associated with an increased incidence of benzodiazepine dependence include:
Dose
Duration
Concomitant use of antidepressantsBenzodiazepine dependence should be suspected also in individuals having substance use disorders including alcohol, and should be suspected in individuals obtaining their own supplies of benzodiazepines. Benzodiazepine dependence is almost certain in individuals who are members of a tranquilizer self-help group.Research has found that about 40 percent of people with a diagnosis of benzodiazepine dependence are not aware that they are dependent on benzodiazepines, whereas about 11 percent of people judged not to be dependent believe that they are.
When assessing a person for benzodiazepine dependence, asking specific questions rather than questions based on concepts is recommended by experts as the best approach of getting a more accurate diagnosis. For example, asking persons if they "think about the medication at times of the day other than when they take the drug" would provide a more meaningful answer than asking "do you think you are psychologically dependent?". The Benzodiazepine Dependence Self Report Questionnaire is one questionnaire used to assess and diagnose benzodiazepine dependence.

Definition
Benzodiazepine dependence is the condition resulting from repeated use of benzodiazepine drugs. It can include both a physical dependence as well as a psychological dependence and is typified by a withdrawal syndrome upon a fall in blood plasma levels of benzodiazepines, e.g., during dose reduction or abrupt withdrawal.

Prevention
Due to the risk of developing tolerance, dependence, and adverse health effects, such as cognitive impairment, benzodiazepines are indicated for short-term use only - a few weeks, followed by a gradual dose reduction.

The Committee on the Review of Medicines (UK)
The Committee on the Review of Medicines carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence, benzodiazepine withdrawal problems, and other adverse effects and published the results in the British Medical Journal in March 1980. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are, therefore, unsuitable treatments for conditions such as depression, tension headaches, and dysmenorrhea. Benzodiazepines are also not beneficial in the treatment of psychosis. The committee also recommended against benzodiazepines for use in the treatment of anxiety or insomnia in children.The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there is little evidence that long-term use of benzodiazepine hypnotics are beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tend to lose their sleep-promoting properties within 3–14 days of continuous use, and, in the treatment of anxiety, the committee found that there was little convincing evidence that benzodiazepines retains efficacy in the treatment of anxiety after 4 months of continuous use due to the development of tolerance.The committee found that the regular use of benzodiazepines causes the development of dependence characterized by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremors, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tend to develop within 24 hours upon cessation of short-acting benzodiazepines, and 3–10 days after cessation of longer-acting benzodiazepines. Withdrawal effects could even occur after treatment lasting only 2 weeks at therapeutic dose levels; however, withdrawal effects tend to occur with habitual use beyond 2 weeks and are more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition.The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short-term use only. It was noted in the review that alcohol can potentiate the central nervous system-depressant effects of benzodiazepines and should be avoided. The central nervous system-depressant effects of benzodiazepines may make driving or operating machinery dangerous, and the elderly are more prone to these adverse effects. High single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia in the neonate, and irregularities in the fetal heart. The committee recommended that benzodiazepines be avoided in lactation.The committee recommended that withdrawal from benzodiazepines be gradual, as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhea.

Treatment
Benzodiazepines are regarded as a highly addictive drug class. A psychological and physical dependence can develop in as short as a few weeks but may take years to develop in other individuals. Patients wanting to withdraw from benzodiazepines typically receive little advice or support, and such withdrawal should be by small increments over a period of months.Benzodiazepines are usually prescribed only short-term, as there is little justification for their prescribing long-term. Some doctors however, disagree and believe long-term use beyond 4 weeks is sometimes justified, although there is little data to support this viewpoint. Such viewpoints are a minority in the medical literature.There is no evidence that "drug holidays" or periods of abstinence reduced the risk of dependence; there is evidence from animal studies that such an approach does not prevent dependence from happening. Use of short-acting benzodiazepines is associated with interdose withdrawal symptoms. Kindling has clinical relevance with regard to benzodiazepines; for example, there is an increasing shift to use of benzodiazepines with a shorter half-life and intermittent use, which can result in interdose withdrawal and rebound effects.

Cognitive behavioral therapy
Cognitive behavioral therapy has been found to be more effective for the long-term management of insomnia than sedative hypnotic drugs. No formal withdrawal programs for benzodiazepines exists with local providers in the UK. Meta-analysis of published data on psychological treatments for insomnia show a success rate between 70 and 80%. A large-scale trial utilizing cognitive behavioral therapy in chronic users of sedative hypnotics including nitrazepam, temazepam, and zopiclone found CBT to be a significantly more effective long-term treatment for chronic insomnia than sedative hypnotic drugs. Persisting improvements in sleep quality, sleep onset latency, increased total sleep, improvements in sleep efficiency, significant improvements in vitality, physical and mental health at 3-, 6-, and 12-month follow-ups were found in those receiving CBT. A marked reduction in total sedative hypnotic drug use was found in those receiving CBT, with 33% reporting zero hypnotic drug use. Age has been found not to be a barrier to successful outcome of CBT. It was concluded that CBT for the management of chronic insomnia is a flexible, practical, and cost-effective treatment, and it was also concluded that CBT leads to a reduction of benzodiazepine drug intake in a significant number of patients.Chronic use of hypnotic medications is not recommended due to their adverse effects on health and the risk of dependence. A gradual taper is usual clinical course in getting people off of benzodiazepines, but, even with gradual reduction, a large proportion of people fail to stop taking benzodiazepines. The elderly are particularly sensitive to the adverse effects of hypnotic medications. A clinical trial in elderly people dependent on benzodiazepine hypnotics showed that the addition of CBT to a gradual benzodiazepine reduction program increased the success rate of discontinuing benzodiazepine hypnotic drugs from 38% to 77% and at the 12-month follow-up from 24% to 70%. The paper concluded that CBT is an effective tool for reducing hypnotic use in the elderly and reducing the adverse health effects that are associated with hypnotics such as drug dependence, cognitive impairments, and increased road traffic accidents.A study of patients undergoing benzodiazepine withdrawal who had a diagnosis of generalized anxiety disorder showed that those having received CBT had a very high success rate of discontinuing benzodiazepines compared to those not having receive CBT. This success rate was maintained at the 12-month follow-up. Furthermore, it was found that, in patients having discontinued benzodiazepines, they no longer met the diagnosis of general anxiety disorder, and that the number of patients no longer meeting the diagnosis of general anxiety disorder was higher in the group having received CBT. Thus, CBT can be an effective tool to add to a gradual benzodiazepine dosage reduction program leading to improved and sustained mental health benefits (Disputed).

Letter to patients
Sending a letter to patients warning of the adverse effects of long-term use of benzodiazepines and recommending dosage reduction has been found to be successful and a cost-effective strategy in reducing benzodiazepine consumption in general practice. Within a year of the letters going out, there was found to be a 17% fall in the number of benzodiazepines being prescribed, with 5% of patients having totally discontinued benzodiazepines. A study in the Netherlands reported a higher success rate by sending a letter to patients who are benzodiazepine-dependent. The results of the Dutch study reported 11.3% of patients discontinuing benzodiazepines completely within a year.

Flumazenil
Flumazenil delivered via slow subcutaneous infusion represents a safe procedure for those withdrawing from long-term, high dose benzodiazepine dependency. It has a low risk of seizures even amongst those who have experienced convulsions when previously attempting benzodiazepine withdrawal.

Epidemiology
Research studies have come to different conclusions on the number of therapeutic dose users who develop a physical dependence and withdrawal syndrome. Researches estimate 20-100% (thats a wide range) of patients, taking benzodiazepines at therapeutic dosages for the long term, are physically dependent and will experience withdrawal symptoms.Benzodiazepines can be addictive and induce dependence even at low doses, with 23% becoming addicted within 3 months of use. Benzodiazepine addiction is considered a public health problem. Approximately 68.5% of prescriptions of benzodiazepines originate from local health centers, with psychiatry and general hospitals accounting for 10% each. A survey of general practitioners reported that the reason for initiating benzodiazepines was due to an empathy for the patients suffering and a lack of other therapeutic options rather than patients demanding them. However, long-term use was more commonly at the insistence of the patient, it is presumed, because physical dependence or addiction had developed.Approximately twice as many women as men are prescribed benzodiazepines. It is believed that this is largely because men typically turned to alcohol to cope with stress and women to prescription drugs. Biased perception of women by male doctors may also play a role in increased prescribing rates to women; however, increased anxiety features in women does not account for the wide gap alone between men and women.Based on findings in the US from the Treatment Episode Data Set (TEDS), an annual compilation of patient characteristics in substance use disorder treatment facilities in the United States, admissions due to "primary tranquilizer" (including, but not limited to, benzodiazepine-type) drug use increased 79% from 1992 to 2002.A study published in the British Journal of General Practice in July 2017 found that in a sample taken from a survey conducted in 2014–2015 in Bradford a mean of 0.69% of registered patients had been prescribed benzodiazepines for more than a year. This would suggest that there were around 300,000 long-term users of diazepine in the UK.

History
Previously, physical dependence on benzodiazepines was largely thought to occur only in people on high-therapeutic-dose ranges. Low- or normal-dose dependence was not suspected until the 1970s, and it was not until the early 1980s that it was confirmed. Low-dose dependence has now been clearly demonstrated in both animal studies and human studies, and is a recognized clinical disadvantage of benzodiazepines </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Gamma globulin and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Carbamate poisoning and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bednars aphthae and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Upington disease and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Juvenile xanthogranuloma and explain in detail? [/INST] Juvenile xanthogranuloma  is a form of histiocytosis, classified as "non-Langerhans cell histiocytosis", or more specifically, "type 2".It is a rare skin disorder that primarily affects children under one year of age but can also be found in older children and adults. It was first described in 1905 by Adamson. In 5% to 17% of people, the disorder is present at birth, but the median age of onset is two years.  JXG is a benign idiopathic cutaneous granulomatous tumor and the most common form of non-Langerhans cell histiocytosis (non-LHC). The lesions appear as orange-red macules or papules and are usually located on the face, neck, and upper trunk. They may also appear at the groin, scrotum, penis, clitoris, toenail, palms, soles, lips, lungs, bone, heart, and gastrointestinal tract more rarely. JXG usually manifests with multiple lesions on the head and neck in cases with children under six months of age. The condition usually resolves spontaneously over one to five years. A biopsy of the lesion is critical to confirm the diagnosis.

Ocular JXG manifests in up to 10% of people with JXG and may affect their vision. The presence of JXG in the eye can cause spontaneous hyphema, secondary glaucoma or even blindness. It is most often seen in the iris but may be found on the eyelid, corneoscleral limbus, conjunctiva, orbit, retina, choroid, disc, or optic nerve. Of patients with ocular JXG, 92% are younger than the age of two. Although cutaneous JXG usually disappear spontaneously, ocular lesions rarely improve spontaneously and require treatment </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bat ear and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Syphilid and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Ethylmalonic encephalopathy and explain in detail? [/INST] Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism.  Patients affected with EE are typically identified shortly after birth, with symptoms including diarrhea, petechiae and seizures.  The genetic defect in EE is thought to involve an impairment in the degradation of sulfide intermediates in the body.  Hydrogen sulfide then builds up to toxic levels.  EE was initially described in 1994.  Most cases of EE have been described in individuals of Mediterranean or Arabic origin.

Signs and symptoms
Neurologic signs and symptoms include progressively delayed development, weak muscle tone (hypotonia), seizures, and abnormal movements. The bodys network of blood vessels is also affected. Children with this disorder may experience rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). Chronic diarrhea is another common feature of ethylmalonic encephalopathy.  EE is often identified by urine organic acid analysis, the excretion of ethylmalonic acid, methylsuccinic acid, isobutyrylglycine and isovalerylglucine.  Patients will also often have elevated thiosulphate concentration in their urine.The signs and symptoms of ethylmalonic encephalopathy are apparent at birth or begin in the first few months of life. Problems with the nervous system typically worsen over time, and most affected individuals survive only into early childhood </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Femoral hernia and explain in detail? [/INST] Femoral hernias occur just below the inguinal ligament, when abdominal contents pass through a naturally occurring weakness in the abdominal wall called the femoral canal. Femoral hernias are a relatively uncommon type, accounting for only 3% of all hernias. While femoral hernias can occur in both males and females, almost all develop in women due to the increased width of the female pelvis. Femoral hernias are more common in adults than in children. Those that do occur in children are more likely to be associated with a connective tissue disorder or with conditions that increase intra-abdominal pressure. Seventy percent of pediatric cases of femoral hernias occur in infants under the age of one.

Definitions
A hernia is caused by the protrusion of a viscus (in the case of groin hernias, an intra-abdominal organ) through a weakness in the abdominal wall. This weakness may be inherent, as in the case of inguinal, femoral and umbilical hernias. On the other hand, the weakness may be caused by previous surgical incision through the muscles and fascia in the area; this is termed an incisional hernia.
A femoral hernia may be either reducible or irreducible, and each type can also present as obstructed and/or strangulated.A reducible femoral hernia occurs when a femoral hernia can be pushed back into the abdominal cavity, either spontaneously or with manipulation. However, it is more likely to occur spontaneously. This is the most common type of femoral hernia and is usually painless.
An irreducible femoral hernia occurs when a femoral hernia cannot be completely reduced, typically due to adhesions between the hernia and the hernial sac. This can cause pain and a feeling of illness.
An obstructed femoral hernia occurs when a part of the intestine involved in the hernia becomes twisted, kinked, or constricted, causing an intestinal obstruction.
A strangulated femoral hernia occurs when a constriction of the hernia limits or completely obstructs blood supply to part of the bowel involved in the hernia. Strangulation can occur in all hernias, but is more common in femoral and inguinal hernias due to their narrow "weaknesses" in the abdominal wall. Nausea, vomiting, and severe abdominal pain are characteristics of a strangulated hernia. This is a medical emergency as the loss of blood supply to the bowel can result in necrosis (tissue death) followed by gangrene (tissue decay). This is a life-threatening condition requiring immediate surgery.The term incarcerated femoral hernia is sometimes used, but may have different meanings to different authors and physicians. For example: "Sometimes the hernia can get stuck in the canal and is called an irreducible or incarcerated femoral hernia." "The term incarcerated is sometimes used to describe an [obstructed] hernia that is irreducible but not strangulated. Thus, an irreducible, obstructed hernia can also be called an incarcerated one." "Incarcerated hernia is a hernia that cannot be reduced. These may lead to bowel obstruction but are not associated with vascular compromise."A hernia can be described as reducible if the contents within the sac can be pushed back through the defect into the peritoneal cavity, whereas with an incarcerated hernia, the contents are stuck in the hernia sac. However, the term incarcerated seems to always imply that the femoral hernia is at least irreducible.

Signs and symptoms
Femoral hernias typically present as a groin lump or bulge, which may differ in size during the day, based on internal pressure variations of the intestine. This lump is typically retort shaped. The bulge or lump is typically smaller or may disappear completely in the prone position.They may or may not be associated with pain. Often, they present with a varying degree of complication ranging from irreducibility through intestinal obstruction to frank gangrene of contained bowel. The incidence of strangulation in femoral hernias is high. A femoral hernia has often been found to be the cause of unexplained small bowel obstruction.
The cough impulse is often absent and is not relied on solely when making a diagnosis of femoral hernia. The lump is more globular than the pear-shaped lump of the inguinal hernia. The bulk of a femoral hernia lies below an imaginary line drawn between the anterior superior iliac spine and the pubic tubercle (which essentially represents the inguinal ligament) whereas an inguinal hernia starts above this line. Nonetheless, it is often impossible to distinguish the two preoperatively.

Anatomy
The femoral canal is located below the inguinal ligament on the lateral aspect of the pubic tubercle. It is bounded by the inguinal ligament anteriorly, pectineal ligament posteriorly, lacunar ligament medially, and the femoral vein laterally. It normally contains a few lymphatics, loose areolar tissue, and occasionally a lymph node called Cloquets node. The function of this canal appears to be to allow the femoral vein to expand when necessary to accommodate increased venous return from the leg during periods of activity.

Diagnosis
The diagnosis is largely a clinical one, generally done by physical examination of the groin. However, in obese patients, imaging in the form of ultrasound, CT, or MRI may aid in the diagnosis. For example, an abdominal X-ray showing small bowel obstruction in a female patient with a painful groin lump needs no further investigation.
Several other conditions have a similar presentation and must be considered when forming the diagnosis: inguinal hernia, an enlarged femoral lymph node, aneurysm of the femoral artery, dilation of the saphenous vein, athletic pubalgia, and an abscess of the psoas.

Classification
Several subtypes of femoral hernia have been described.

Management
Femoral hernias, like most other hernias, usually need operative intervention. This should ideally be done as an elective (non-emergency) procedure </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cluttons joints and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sialodochitis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hypopyon and explain in detail? [/INST] Hypopyon is a medical condition involving inflammatory cells in the anterior chamber of the eye.
It is an exudate rich in white blood cells, seen in the anterior chamber, usually accompanied by redness of the conjunctiva and the underlying episclera </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Kleine–Levin syndrome and explain in detail? [/INST] Kleine–Levin syndrome (KLS) is a rare disorder characterized by persistent episodic hypersomnia and cognitive or mood changes. Many patients also experience hyperphagia, hypersexuality and other symptoms. Patients generally experience recurrent episodes of the condition for more than a decade and may return at a later age. Individual episodes generally last more than a week, sometimes lasting for months. The condition greatly affects the personal, professional, and social lives of those with KLS. The severity of symptoms and the course of the syndrome vary between those with KLS. Patients commonly have about 20 episodes over about a decade. Several months generally elapse between episodes.
The onset of the condition usually follows a viral infection; several different viruses have been observed to trigger KLS. It is generally only diagnosed after similar conditions have been excluded; MRI, CT scans, lumbar puncture, and toxicology tests are used to rule out other possibilities. The syndromes mechanism is not known, but the thalamus is thought to possibly play a role. SPECT has shown thalamic hypoperfusion of patients during episodes.
KLS is very rare, occurring at a rate of 1 in 1 million, which limits research into genetic factors. The condition primarily affects adolescent males, though females can also be affected and the age of onset varies. There is no known cure, and there is little evidence supporting drug treatment. Lithium has been reported to have limited effects in case reports, decreasing the length of episodes and duration between them in some patients. Stimulants have been shown to promote wakefulness during episodes, but they do not counteract cognitive symptoms or decrease the duration of episodes. The condition is named after Willi Kleine and Max Levin, who described cases of the disease in the early 20th century. It was added to the International Classification of Sleep Disorders in 1990.

Symptoms
Patients with Kleine–Levin syndrome (KLS) experience recurring episodes of prolonged sleep (hypersomnia). In most cases, patients sleep 15 to 21 hours a day during episodes.
Excessive appetite (hyperphagia) and unusual cravings are present in half to two thirds of cases. About half of patients, mainly male patients, experience dramatically increased sexual urges (hypersexuality). Several other symptoms usually accompany the syndrome, including marked changes in mood and cognitive ability. Derealization and severe apathy are present in at least 80 percent of cases. About one third of patients experience hallucinations or delusions. Depression and anxiety occur less commonly; one study found them in about 25 percent of patients. Individuals usually cannot remember what happened during episodes. Repetitive behaviors and headaches are commonly reported. Some patients act very childlike during episodes, and communication skills and coordination sometimes worsen.Sleep studies of KLS show varying results based on the amount of time the patient is observed. Slow wave sleep is often reduced at the beginning of episodes, and REM sleep is reduced near the end. Conversely, REM sleep is often normal at the beginning, and slow wave sleep is often normal by the conclusion. Stage two non-rapid eye movement sleep is often interrupted during KLS. Studies also show that stage one and three non-rapid eye movement sleep become more efficient when the episodes end. The Multiple Sleep Latency Test has yielded inconsistent results when given to KLS patients. In many cases, hours are spent in a withdrawn sleep-like state while awake during episodes. Most sleep studies have been performed while subject is near the end of their episodes. Some patients experience brief insomnia and become very happy and talkative after the episode ends.The first time a patient experiences KLS, it usually occurs along with symptoms that are similar to those of the flu or encephalitis. In at least 75 percent of cases, symptoms occur after an airway infection or a fever. Viruses observed before the development of the condition include Epstein–Barr virus, varicella zoster virus, herpes zoster virus, influenza A virus subtypes, and adenovirus. Several days after symptoms first occur, patients become very tired. In cases that occur after an infection, KLS usually starts within three to five days for teenagers and fewer for children. In other cases, alcohol consumption, head injury, or international travel precede symptoms. Lifestyle habits, such as stress, alcohol abuse and lack of sleep and stress, have also been proposed as possible triggers. First episodes of KLS are preceded by a clear event in about 90 percent of cases. Recurrences generally do not have clear triggers; only about 15 percent have a precipitating event.The condition generally disrupts the social lives and academic or professional obligations of those with KLS. Some patients also gain weight during episodes. The most severe cases cause a long-term impact on mood and cognitive attention. In rare cases, patients experience long-term memory problems.In patients with KLS, MRI and CT scans show normal brain morphology. When SPECT is performed, hypoperfusion can often be observed in the brain, particularly in the thalamic and frontotemporal areas. The hypoperfusion is significantly diminished between episodes. Serum biology, c-reactive proteins and leptins, the hormonal pituitary axis, and protein in the cerebral spinal fluid (CSF) are normal in KLS patients.

Cause
It is not known what causes KLS, but several mechanisms have been proposed. One possible explanation is hypothalamic or circadian dysfunction. The thalamus probably plays a role in the out-of-control sleeping, and patients with diencephalic–hypothalamic dysfunction caused by tumors experience symptoms similar to those of KLS patients. Specifically, the medial temporal regions of the thalamus may be involved, although examinations of KLS patients have not consistently found abnormalities in this area. The temporal lobe also appears to play a role in the condition, possibly causing cognitive difficulties. The apathy and disinhibition found in some with KLS suggest that the condition may include frontal lobe dysfunction as well. The involvement of the thalamus, temporal lobe, and frontal lobe of the brain suggests that there is a multifocal, localized encephalopathy. There are also persistent subclinical abnormalities in some with KLS.Another possible explanation concerns the metabolism of serotonin and dopamine. An imbalance in the neurotransmitter pathways of these chemicals could play a role. Viral infections have also been suggested as a possible cause. Evidence for their role includes lesions found in autopsies. CSF samples from KLS patients indicate that the condition has a different cause than influenza-associated encephalopathy. Triggers of KLS may also affect the blood-brain barrier, which could play a role in the condition. There is limited evidence of what role hypocretin may play, although it often influences hypersomnia.Androgen might (indirectly) block melatonin receptors, possibly by means of vasodilation, and cause cholinergic abnormalities in some cases of Kleine–Levin syndrome.Because KLS occurs at a much higher rate in Jews and in some families, it is likely that there is some genetic component in addition to environmental factors. Genetic studies hold promise for understanding the disease, but they have yielded inconsistent results and few patients are available for testing.Epilepsy and depression do not appear to cause KLS. The conditions rapid onset after infections indicates that the immune system is not to blame.One study has suggested a link to the gene LMOD3 on chromosome 3.

Diagnosis
KLS can be diagnosed when there is confusion, apathy, or derealization in addition to frequent bouts of extreme tiredness and prolonged sleep. The earliest it can be diagnosed is the second episode, this is not common. The condition is generally treated as a diagnosis of exclusion. Because KLS is rare, other conditions with similar symptoms are usually considered first.MRIs can determine if the symptoms are caused by certain brain disorders, stroke, and multiple sclerosis. Lumbar puncture can determine if encephalitis is the cause. KLS must be differentiated from substance abuse by toxicology tests. The use of electroencephalography (EEG) can exclude temporal status epilepticus from consideration. EEGs are normal in about 70% of KLS patients, but background slowing may sometimes be detected. In addition, low-frequency high-amplitude waves can be observed during waking hours.Initially, KLS appears similar to bipolar depression. Patients with frontal-lobe syndromes and Klüver–Bucy syndrome also display similar symptoms, but these conditions can be differentiated by the presence of brain lesions. KLS should also be distinguished from very rare cases of menstruation-caused hypersomnia.

Prevention
Lithium is the only drug that appears to have a preventive effect. In two studies of more than 100 patients, lithium helped prevent recurrence of symptoms in 20% to 40% of cases. The recommended blood level of lithium for KLS patients is 0.8–1.2 mEq/ml. It is not known if other mood stabilizers have an effect on the condition. Anti-depressants do not prevent recurrence.

Treatment
Several drug therapies have been used on patients with KLS, but none of them have been subject to randomized controlled trials. A 2016 Cochrane Review concluded that "No evidence indicates that pharmacological treatment for Kleine–Levin syndrome is effective and safe".In several cases, stimulants, including modafinil, have been reported to have a limited effect on patients, often alleviating sleepiness. They can cause behavioral problems, but they may pose fewer issues if used in older patients with mild symptoms. In some case reports, lithium has been reported to decrease the length of episodes and the severity of their symptoms and to increase the time between episodes. It has been reported to be effective in about 25 to 60 percent of cases. Its use carries the risk of side effects in the thyroid or kidneys. Antipsychotics and benzodiazepines can help alleviate psychotic and anxiety related symptoms, respectively. Carbamazepine has been reported to be less effective than lithium but more effective than some drugs in its class. Electroconvulsive therapy is not effective and worsens symptoms.KLS patients generally do not need to be admitted to hospitals. It is recommended that caregivers reassure them and encourage them to maintain sleep hygiene. It may also be necessary for patients to be prevented from putting themselves in dangerous situations, such as driving.

Prognosis
The frequency of KLS episodes can vary from attacks one week in length occurring twice a year to dozens of episodes that follow each other in close succession. The median duration of KLS episodes is about ten days, but some last several weeks or months. A study of 108 patients found an average of 19 episodes over the duration of the disease. Another study found a median of 3.5 months between episodes. Outside of episodes, there is no disturbance in patients sleep patterns and they are generally asymptomatic. Patients do not experience the same symptoms in each episode.About 80 percent of patients are adolescents when they first experience KLS. On some occasions though, its first occurrence comes in childhood or adulthood. In most adolescent-onset patients, symptoms cease by the time they are 30 years old. A French study of 108 patients found a median duration of 13 years, but a review of 186 cases found a median duration of 8 years. Unusually young or old patients and those who experience hypersexuality tend to have a more severe course. Patients who initially have frequent attacks generally see the disease cease earlier than others. The condition spontaneously resolves, and the patient is considered to be cured if there have been no symptoms for six years.

Epidemiology
Population-based studies of KLS have not been performed. Its prevalence is about 1 case per million people. In France, KLS has a prevalence of 1.5 per million people. It occurs most frequently among Jews in the US and Israel. First-degree relatives of people who have the syndrome are much more likely than the general population to have it, although only in about one percent of cases do family members contract it. About 70 to 90 percent of patients are male. Patients with the syndrome are more likely than the general population to have genetic disorders, and about a third of people with the syndrome encountered some form of birth difficulty. In a study of 186 older patients, about ten percent had preexisting psychiatric issues. One study found that about ten percent of patients had a neurological condition before KLS developed. The condition does not appear to occur most frequently in one season.

History
In 1815, there was a report of a young man who showed excessive appetite and prolonged sleep after experiencing a fever; this may have been an early description of the condition. Another case with similar symptoms was described by Brierre de Boismont in 1862.Five patients with symptoms of persistent sleepiness were described in detail in 1925 by Willi Kleine, a neurologist from Frankfurt. This report was followed four years later by details of a similar case by New York-based psychiatrist Max Levin. In 1935, Levin published information about several more cases, including one described by Kleine. Levin noted that some patients displayed an intense appetite in addition to their persistent tiredness. MacDonald Critchley, who first wrote about the condition in 1942, described 11 cases he had examined and reviewed 15 other published cases in a 1962 publication. In the report, which included patients he had examined in the Royal Navy during World War II, he observed that irritability and depersonalization often occurred while patients were awake. He named the condition Kleine–Levin syndrome and noted four common traits: hypersexuality, adolescent onset, spontaneous resolution, and compulsive eating. He believed that the condition only affected males, but later studies showed some female patients. In the 1970s, several psychoanalytic and psychodynamic explanations for the condition were proposed. In 1980, a Hawaiian–Caucasian family was found in which nine family members had the condition.Diagnostic criteria for KLS was established by Schmidt in 1990, and the International Classification of Sleep Disorders further refined them. KLS is classified as a sleep disorder, specifically one of recurrent hypersomnia. Before 2005, hyperphagia and hypersexuality were thought to occur in all cases. That was changed with the guidelines published that year, which noted that they did not always occur.

References
Bibliography
Arnulf, Isabelle; Rico, Thomas; Mignot, Emmanuel (2012). "Diagnosis, Disease Course, and Management of Patients with Kleine-Levin Syndrome". The Lancet Neurology. 11 (10): 918–28. doi:10.1016/S1474-4422(12)70187-4. PMID 22995695. S2CID 7636103.
Arnulf, Isabelle; Zeitzer, J. M.; Farber, N.; Mignot, Emmanuel (2005). "Kleine–Levin Syndrome: a Systematic Review of 186 Cases in the Literature". Brain. 128 (12): 2763–76. doi:10.1093/brain/awh620. PMID 16230322.
Billiard, Michel; Jaussent, Isabelle; Dauvilliers, Yves; Besset, Alain (2011). "Recurrent Hypersomnia: a Review of 339 Cases". Sleep Medicine Reviews. 15 (4): 247–57. doi:10.1016/j.smrv.2010.08.001. PMID 20970360.
Frenette, Eric; Kushida, Clete (2009). "Primary Hypersomnias of Central Origin". Seminars in Neurology. 29 (4): 354–67. doi:10.1055/s-0029-1237114. PMID 19742411.
Gupta, Ravi; Lahan, Vivekananda; Srivastava, Malini (2011). "Kleine-Levin Syndrome and Idiopathic Hypersomnia: Spectrum Disorders". Indian Journal of Psychological Medicine. 33 (2): 194–98. doi:10.4103/0253-7176.92048. PMC 3271500. PMID 22345850.
Huang, Yu-Shu; Lakkis, Clair; Guilleminault, Christian (2010). "Kleine-Levin Syndrome: Current Status". Medical Clinics of North America. 94 (3): 557–62. doi:10.1016/j.mcna.2010.02.011. PMID 20451032.
Kodaira, Minori; Yamamoto, Kanji (2012). "First Attack of Kleine-Levin Syndrome Triggered by Influenza B Mimicking Influenza-associated Encephalopathy". Internal Medicine. 51 (12): 1605–8. doi:10.2169/internalmedicine.51.7051. PMID 22728499.
Mignot, Emmanuel (2012). "A Practical Guide to the Therapy of Narcolepsy and Hypersomnia Syndromes". Neurotherapeutics. 9 (4): 739–52. doi:10.1007/s13311-012-0150-9. PMC 3480574. PMID 23065655.
Oliveira, Marcio; Conti, Cristiane; Prado, Gilmar (2016) [2013]. "Pharmacological Treatment for Kleine-Levin Syndrome". Cochrane Database of Systematic Reviews. 5 (5): CD006685. doi:10.1002/14651858.CD006685.pub4. PMC 7386458. PMID 27153153.
Pearce, J. M. (2008). "Kleine–Levin Syndrome: History and Brief Review" </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Dysbaric osteonecrosis and explain in detail? [/INST] Dysbaric osteonecrosis or DON is a form of avascular necrosis where there is death of a portion of the bone that is thought to be caused by nitrogen embolism (blockage of the blood vessels by a bubble of nitrogen coming out of solution) in divers. Although the definitive pathologic process is poorly understood, there are several hypotheses:

Intra- or extravascular nitrogen in bones, "nitrogen embolism".
Osmotic gas effects due to intramedullary pressure effects.
fat embolism
hemoconcentration and increased coagulability.

Presentation
The lesion begins as a localised area of infarction, usually without symptoms. Early identification of lesions by radiography is not possible, but over time areas of radiographic opacity develop in association with the damaged bone. Symptomatic lesions usually involve joint surfaces, and fracture where attempted healing occurs. This process takes place over months to years and eventually causes disabling arthritis, particularly of the femoral head (hip).Dysbaric osteonecrosis lesions are typically bilateral and usually occur at both ends of the femur and at the proximal end of the humerus. Symptoms are usually only present when a joint surface is involved, which typically does not occur until a long time after the causative exposure to a hyperbaric environment. The initial damage is attributed to the formation of bubbles, and one episode can be sufficient, however incidence is sporadic and generally associated with relatively long periods of hyperbaric exposure, and aetiology is uncertain.

Diagnosis
The diagnosis is made by x-ray/MRI appearance and has five juxta-articular classifications and forehead, neck, and shaft classifications indicating early radiological signs.Early on there is flattening of articular surfaces, thinning of cartilage with osteophyte (spur) formation. In juxta-articular lesions without symptoms, there is dead bone and marrow separated from living bone by a line of dense collagen. Microscopic cysts form, fill with necrotic material and there is massive necrosis with replacement by cancellous bone with collapse of the lesions.The following staging system is sometimes useful when managing lesions.
Stage 0 - Intravascular coagulation
Stage 1 - Dead bone without repair
Stage 2 - Dead bone with repair but without collapse
Stage 3 - Dead bone with repair and with collapse
Stage 4 - Secondary degenerative arthritisIn a study of bone lesions in 281 compressed air workers done by Walder in 1969, 29% of the lesions were in the humeral head (shoulder), 16% in the femoral head (hip), 40% in the lower end of the femur (lower thigh at the knee) and 15% in the upper tibia (knee below the knee cap).
Worsening of the condition from continued decompression in an asymptomatic x-ray finding may occur.

Prevention
Prevention is a more successful strategy than treatment.  By using the most conservative decompression schedule reasonably practicable, and by minimizing the number of major decompression exposures, the risk of DON may be reduced.  Prompt treatment of any symptoms of decompression sickness (DCS) with recompression and hyperbaric oxygen also reduce the risk of subsequent DON.

Treatment
Treatment is difficult, often requiring a joint replacement. Spontaneous improvement occasionally happens and some juxta-articular lesions do not progress to collapse </s>