<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 Tooth impaction and can you explain it in depth? [/INST] An impacted tooth is one that fails to erupt into the dental arch within the expected developmental window.
Because impacted teeth do not erupt, they are retained throughout the individuals lifetime unless extracted or exposed surgically. Teeth may become impacted because of adjacent teeth, dense overlying bone, excessive soft tissue or a genetic abnormality. Most often, the cause of impaction is inadequate arch length and space in which to erupt. That is the total length of the alveolar arch is smaller than the tooth arch (the combined mesiodistal width of each tooth). The wisdom teeth (third molars) are frequently impacted because they are the last teeth to erupt in the oral cavity. Mandibular third molars are more commonly impacted than their maxillary counterparts.
Some dentists believe that impacted teeth should be removed except, in certain cases, canine teeth: canines may just remain buried and give no further problems, thus not requiring surgical intervention. However, removal of asymptomatic, pathology-free, impacted teeth isnt a medical consensus: watchful monitoring may be a more prudent and cost-effective strategy and make the future placement of a dental implant through such impacted tooth a feasible approach.

Classification
Classifications enable the oral surgeon to determine the difficulty in removal of the impacted tooth. The primary factor determining the difficulty is accessibility, which is determined by adjacent teeth or other structures that impair access or delivery pathway. The majority of classification schemes are based on analysis on a radiograph. The most frequently considered factors are discussed below.

Angulation of tooth
Most commonly used classification system with respect to treatment planning. Depending on the angulation the tooth might be classified as:

Mesioangular
Horizontal
Vertical
Distoangular
Palatal
Buccal
Lingual

Relationship of tooth to anterior border of ramus
This type of classification is based on the amount of impacted tooth that is covered with the mandibular ramus. It is known as the Pell and Gregory classification, classes 1, 2, and 3.

Relationship of tooth to occlusal plane
The depth of the impacted tooth compared with the adjacent second molar gives the basis for this type of classification. This was also given by Pell and Gregory and is called as Pell and Gregory A, B and C classification.
Relationship to occlusal plane Class A-C

Complications
Erupted teeth that are adjacent to impacted teeth are predisposed to periodontal disease. Since the most difficult tooth surface to be cleaned is the distal surface of the last tooth, in the presence of an impacted tooth there is always gingival inflammation around the second molar that is invariably present. Even this minor amount of inflammation can provide bacteria access to a larger portion of the root surface that results in early formation of periodontitis compromising the tooth.
Even in situations in which no obvious communication exists between the mouth and the impacted third molar there may be enough communication to initiate dental caries (tooth decay).

Pericoronitis
Pericoronitis is an infection of the soft tissue that covers the crown of an impacted tooth and is usually caused by the normal oral microbiota. For most people there exists a balance between the host defenses and the oral micriobiota but if the host defenses are compromised like during minor illness such as influenza or an upper respiratory tract infection, pericoronitis results. Another common cause is entrapment of food beneath the gum flap (also called an operculum) </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 Gestational pemphigoid and can you explain it in depth? [/INST] Gestational pemphigoid (GP)  is a rare autoimmune variant of the skin disease bullous pemphigoid, and first appears in pregnancy. It presents with tense blisters, small bumps, hives and intense itching, usually starting around the navel before spreading to limbs in mid-pregnancy or shortly after delivery. The head, face and mouth are not usually affected.It may flare after delivery before resolving around three to six months after the pregnancy. It can be triggered by subsequent pregnancies, menstrual periods and oral contraceptive pill. A molar pregnancy and choriocarcinoma can provoke it. In some people, it persists long-term. It is associated with premature delivery of a small baby, a few who may be born with blisters and urticaria, which generally resolves within six weeks. It does not spread from one person to another, and does not run in families.Diagnosis is by visulaization, biopsy and immunofluorescence. It can resemble pruritic urticarial papules and plaques of pregnancy, erythema multiforme, drug reactions and blistering scabies.Around 1 in 20,000 to 50,000 pregnancies are affected. It was originally called herpes gestationis because of the blistering appearance, although it is not associated with the herpes virus.

Signs and symptoms
Diagnosis of GP becomes clear when skin lesions progress to tense blisters during the second or third trimester. The face and mucous membranes are usually spared. GP typically starts as a blistering rash in the navel area and then spreads over the entire body. It is sometimes accompanied by raised, hot, painful welts called plaques. After one to two weeks, large, tense blisters typically develop on the red plaques, containing clear or blood-stained fluid. GP creates a histamine response that causes extreme relentless itching (pruritus). GP is characterized by flaring and remission during the gestational and sometimes post partum period. Usually after delivery, lesions will heal within months, but may reoccur during menstruation.

Causes
Pathogenically, it is a type II hypersensitivity reaction where circulating complement-fixing IgG antibodies bind to an antigen (a 180-kDa protein, BP-180) in the hemidesmosomes (attach basal cells of epidermis to the basal lamina and hence to dermis) of the dermoepidermal junction, leading to blister formation as loss of hemidesmosomes causes the epidermis to separate from dermis. The immune response is even more highly restricted to the NC16A domain. The primary site of autoimmunity seems not to be the skin, but the placenta, as antibodies bind not only to the basement membrane zone of the epidermis, but also to that of chorionic and amniotic epithelia. Aberrant expression of MHC class II molecules on the chorionic villi suggests an allogenic immune reaction to a placental matrix antigen, thought to be of paternal origin. Recently, both IgA22 and IgE24 antibodies to either BP180 or BP230 have also been detected in pemphigoid gestationis.

Risk
Pregnant women with GP should be monitored for conditions that may affect the fetus, including, but not limited to, low or decreasing volume of amniotic fluid, preterm labor, and intrauterine growth retardation. Onset of GP in the first or second trimester and presence of blisters may lead to adverse pregnancy outcomes including decreased gestational age at delivery, preterm birth, and low birth weight children. Such pregnancies should be considered high risk and appropriate obstetric care should be provided. Systemic corticosteroid treatment, in contrast, does not substantially affect pregnancy outcomes, and its use for GP in pregnant women is justified. GP typically reoccurs in subsequent pregnancies. Passive transfer of the mother’s antibodies to the fetus causes some (about 10%) newborns to develop mild skin lesions, but these typically will resolve within weeks of parturition.

Diagnosis
Differential diagnosis
GP often is confused with pruritic urticarial papules and plaques of pregnancy (PUPPP), especially if it occurs in a first pregnancy.  PUPPP typically begins in stretch mark areas of the abdomen and usually ends within two weeks after delivery </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 Ulnar neuropathy and can you explain it in depth? [/INST] Ulnar neuropathy is a disorder involving the ulnar nerve. Ulnar neuropathy may be caused by entrapment of the ulnar nerve with resultant numbness and tingling. It may also cause weakness or and paralysis of the muscles supplied by the nerve.

Signs and symptoms
In terms of the signs/symptoms of ulnar neuropathy trauma and pressure to the arm and wrist, especially the elbow, the medial side of the wrist, and other sites close to the course of the ulnar nerve are of interest in this condition.  Many people complain of sensory changes in the fourth and fifth digits. Rarely, an individual actually notices that the unusual sensations are mainly in the medial side of the ring finger (fourth digit). Sometimes the third digit is also involved, especially on the ulnar (medial) side. The sensory changes can be a feeling of numbness or a tingling, pain rarely occurs in the hand. Complaints of pain tend to be more common in the arm, up to and including the elbow area, which is probably the most common site of pain in an ulnar neuropathy.

Causes
Among the causes of ulnar neuropathy are the following-

Much more commonly, ulnar neuropathy is caused by overuse of the triceps muscle and repetitive stress combined with poor ergonomics. Overused and hypertonic triceps muscle causes inflammation in the tendon and adhesions with the connective tissue surrounding that tendon and muscle. These in turn impinge on or trap the ulnar nerve. Ulnar neuropathy resulting from repetitive stress is amenable to massage and can usually be fully reversed without cortisone or surgery.
Center for Occupational and Environmental Neurology, Baltimore, MD has this to say:
“Repetitive Strain Injuries (RSI) refers to many different diagnoses of the neck/shoulder, arm, and wrist/hand area usually associated with work-related ergonomic stressors.  Other terms used for Repetitive Strain Injuries are overuse syndrome, musculoskeletal disorders, and cumulative trauma disorders.  Some of the more common conditions under these headings include:
Cubital Tunnel Syndrome-compression of the ulnar nerve in the cubital tunnel at the elbow.”

Pathophysiology
In regards to the pathophysiology of ulnar neuropathy:the axon, and myelin can be affected. Within the axon, fascicles to individual muscles could be involved, with subsequent motor unit loss and amplitude decrease. Conduction block means impaired transmission via a part of the nerve. Conduction block can mean myelin damage to the involved area, slowing of conduction or significant spreading out of the temporal profile of the response with axonal integrity is a hallmark of demyelination.

Diagnosis
Among the diagnostic procedures done to determine if the individual has ulnar neuropathy are (but may not be limited to the following):
Nerve conduction exam/study (Nerve Conduction Velocity is a measurements made in a nerve conduction exam)
Physical exam
Medical history
X-ray
CBC
Urinalysis
MRI
Ultrasound
Histology studyUlnar nerve neuropathy at the elbow or the wrist can be assessed by testing for a positive Froments sign. Little finger abduction and adduction can be tested as well.

Treatment
Treatment for ulnar neuropathy can entail:
NSAID (non-steroidal anti-inflammatory) medicines. there is also the option of a cortisone injection. Another possible option is splinting, to secure the elbow, a conservative procedure endorsed by some. In cases where surgery is needed, cubital tunnel release, where the ligament of the cubital tunnel is cut, thereby alleviating pressure on nerve can be performed.Treatment for the common occurrence of ulnar neuropathy resulting from overuse, with no fractures or structural abnormalities, is treatment massage, ice, and anti-inflammatories. Specifically, deep tissue massage to the triceps, myofascial release for the upper arm connective tissue, and cross-fiber friction to the triceps tendon.

Prognosis
In terms of the prognosis of ulnar neuropathy early decompression of the nerve sees a return to normal ability (function), which should be immediate. Severe cubital tunnel syndrome tends to have a faster recovery process in individuals below the age of 70, as opposed to those above such an age. Finally, revisional surgery for cubital tunnel syndrome does not result well for those individuals over 50 years of age.

References
Further reading
"NIOSHTIC-2 Publications Search - 20045060 - Do comorbid ulnar symptoms or ulnar neuropathy affect the prognosis of workers with carpal tunnel syndrome?". www.cdc.gov. Retrieved 2016-07-22.
Yoon, Joon Shik; Walker, Francis O.; Cartwright, Michael S. (1 February 2010). "Ulnar Neuropathy With Normal Electrodiagnosis and Abnormal Nerve Ultrasound". Archives of Physical Medicine and Rehabilitation. 91 (2): 318–320. doi:10.1016/j.apmr.2009.10.010. ISSN 0003-9993 </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 Hepatotoxicity and can you explain it in depth? [/INST] Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins), and herbal remedies (two prominent examples being kava, mechanism unknown, and comfrey, through its pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins.
More than 900 drugs have been implicated in causing liver injury (see LiverTox, external link, below) and it is the most common reason for a drug to be withdrawn from the market. Hepatotoxicity and drug-induced liver injury also account for a substantial number of compound failures, highlighting the need for toxicity prediction models (e.g. DTI), and drug screening assays, such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process. Chemicals often cause subclinical injury to the liver, which manifests only as abnormal liver enzyme tests.
Drug-induced liver injury is responsible for 5% of all hospital admissions and 50% of all acute liver failures.

Causes
Adverse drug reactions are classified as type A (intrinsic or pharmacological) or type B (idiosyncratic). Type A drug reaction accounts for 80% of all toxicities.Drugs or toxins that have a pharmacological (type A) hepatotoxicity are those that have predictable dose-response curves (higher concentrations cause more liver damage) and well characterized mechanisms of toxicity, such as directly damaging liver tissue or blocking a metabolic process. As in the case of paracetamol overdose, this type of injury occurs shortly after some threshold for toxicity is reached. Carbon tetrachloride is commonly used to induce acute type A liver injury in animal models.
Idiosyncratic (type B) injury occurs without warning, when agents cause non-predictable hepatotoxicity in susceptible individuals, which is not related to dose and has a variable latency period. This type of injury does not have a clear dose-response nor temporal relationship, and most often does not have predictive models. Idiosyncratic hepatotoxicity has led to the withdrawal of several drugs from market even after rigorous clinical testing as part of the FDA approval process; Troglitazone (Rezulin) and trovafloxacin (Trovan) are two prime examples of idiosyncratic hepatotoxins pulled from market.
The herb kava has caused a number of cases of idiosyncratic liver injury, ranging everywhere from asymptomatic to fatal.
Oral use of the antifungal ketoconazole has been associated with hepatic toxicity, including some fatalities; however, such effects appear to be limited to doses taken over a period longer than 7 days.

Paracetamol
Paracetamol also known as acetaminophen, and by the brand names of Tylenol and Panadol, is usually well-tolerated in prescribed dose, but overdose is the most common cause of drug-induced liver disease and acute liver failure worldwide.  Damage to the liver is not due to the drug itself but to a toxic metabolite (N-acetyl-p-benzoquinone imine (NAPQI)) produced by cytochrome P-450 enzymes in the liver. In normal circumstances, this metabolite is detoxified by conjugating with glutathione in phase 2 reaction. In an overdose, a large amount of NAPQI is generated, which overwhelms the detoxification process and leads to liver cell damage.   Nitric oxide also plays a role in inducing toxicity. The risk of liver injury is influenced by several factors including the dose ingested, concurrent alcohol or other drug intake, interval between ingestion and antidote, etc. The dose toxic to the liver is quite variable from person to person and is often thought to be lower in chronic alcoholics. Measurement of blood level is important in assessing prognosis, higher levels predicting a worse prognosis. Administration of Acetylcysteine, a precursor of glutathione, can limit the severity of the liver damage by capturing the toxic NAPQI. Those that develop acute liver failure can still recover spontaneously,  but may require transplantation if poor prognostic signs such as encephalopathy or coagulopathy is present (see Kings College Criteria).

Nonsteroidal anti-inflammatory drugs
Although individual analgesics rarely induce liver damage due to their widespread use, NSAIDs have emerged as a major group of drugs exhibiting hepatotoxicity. Both dose-dependent and idiosyncratic reactions have been documented. Aspirin and phenylbutazone are associated with intrinsic hepatotoxicity; idiosyncratic reaction has been associated with ibuprofen, sulindac,  phenylbutazone, piroxicam, diclofenac and indomethacin.

Glucocorticoids
Glucocorticoids are so named due to their effect on the carbohydrate mechanism. They promote glycogen storage in the liver. An enlarged liver is a rare side-effect of long-term steroid use in children. The classical effect of prolonged use both in adult and paediatric population is steatosis.

Isoniazid
Isoniazide (INH) is one of the most commonly used drugs for tuberculosis; it is associated with mild elevation of liver enzymes in up to 20% of patients and severe hepatotoxicity in 1-2% of patients.

Other hydrazine derivative drugs
There are also cases where other hydrazine derivative drugs, such as the MAOI antidepressant iproniazid, are associated with liver damage. Phenelzine has been associated with abnormal liver tests. Toxic effects can develop from antibiotics.

Natural products
Examples include alpha-Amanitin containing mushrooms, kava, and aflatoxin producing molds. Pyrrolizidine alkaloids, which occur in some plants, can be toxic. Green tea extract is a growing cause of liver failure due to its inclusion in more products.

Alternative remedies
Examples include: Ackee fruit, Bajiaolian, Camphor, Copaltra, Cycasin, Garcinia, Kava leaves, pyrrolizidine alkaloids, Horse chestnut leaves, Valerian, Comfrey. Chinese herbal remedies: Jin Bu Huan, Ephedra, Shou Wu Pian, Bai Xian Pi.

Industrial toxin
Examples include arsenic, carbon tetrachloride, and vinyl chloride.

Mechanism
Drugs continue to be taken off the market due to late discovery of hepatotoxicity. Due to its unique metabolism and close relationship with the gastrointestinal tract, the liver is susceptible to injury from drugs and other substances. 75% of blood coming to the liver arrives directly from gastrointestinal organs and the spleen via portal veins that bring drugs and xenobiotics in near-undiluted form. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process.
Many chemicals damage  mitochondria, an intracellular organelle that produces energy. Its dysfunction releases excessive amount of oxidants that, in turn, injure hepatic cells. Activation of some enzymes in the cytochrome P-450 system such as  CYP2E1 also lead to oxidative stress. Injury to hepatocyte and bile duct cells lead to accumulation of bile acid inside the liver. This promotes further liver damage. Non-parenchymal cells such as Kupffer cells, collagen-producing stellate cells, and leukocytes (i.e. neutrophil and monocyte) also have a role in the mechanism.

Drug metabolism in liver
The human body subjects most, but not all, compounds to various chemical processes (i.e. metabolism) to make them suitable for elimination. This involves chemical transformations to (a) reduce fat solubility and (b) to change biological activity. Although almost all tissues in the body have some ability to metabolize chemicals, smooth endoplasmic reticulum in the liver is the principal "metabolic clearing house" for both endogenous chemicals (e.g., cholesterol, steroid hormones,  fatty acids, proteins) and exogenous substances (e.g., drugs, alcohol). The central role played by liver in the clearance and transformation of chemicals makes it susceptible to drug-induced injury.
Drug metabolism is usually divided into two phases: phase 1 and phase 2. Phase 1 reaction is generally speaking to prepare a drug for phase 2. However, many compounds can be metabolized by phase 2 directly or be excreted without any phase 2 reactions occurring. Phase 1 reaction involves oxidation, reduction, hydrolysis, hydration and many other rare chemical reactions. These processes tend to increase water solubility of the drug and can generate metabolites that are more chemically active and/or potentially toxic. Most of phase 2 reactions take place in  cytosol and involve conjugation with endogenous compounds via transferase enzymes. Phase 1 are typically more suitable for elimination.
A group of enzymes located in the endoplasmic reticulum, known as cytochrome P-450, is the most important family of metabolizing enzymes in the liver. Cytochrome P-450 is not a single enzyme, but rather consists of a closely related family of 50 isoforms; six of them metabolize 90% of drugs. There is a tremendous diversity of individual P-450 gene products, and this heterogeneity allows the liver to perform oxidation on a vast array of chemicals (including most drugs) in phase 1. Three important characteristics of the P-450 system have roles in drug-induced toxicity:

1. Genetic diversity:Each of the P-450 proteins is unique and accounts (to some extent) for the variation in drug metabolism between individuals. Genetic variations (polymorphism) in P-450 metabolism should be considered when patients exhibit unusual sensitivity or resistance to drug effects at normal doses. Such polymorphism is also responsible for variable drug response among patients of differing ethnic backgrounds.

2. Change in enzyme activity:Many substances can influence the P-450 enzyme mechanism. Drugs interact with the enzyme family in several ways. Drugs that modify cytochrome P-450 enzyme are referred to as either inhibitors or inducers. Enzyme inhibitors block the metabolic activity of one or several P-450 enzymes. This effect usually occurs immediately. On the other hand, inducers increase P-450 activity by increasing enzyme production, or, in the case of CYP2E1, preventing degradation in the proteasome. There is usually a delay before enzyme activity increases.
3. Competitive inhibition:Some drugs may share the same P-450 specificity and thus competitively block their biotransformation. This may lead to accumulation of drugs metabolized by the enzyme. This type of drug interaction may also reduce the rate of generation of toxic metabolites.

Patterns of injury
Chemicals produce a wide variety of clinical and pathological hepatic injury. Biochemical markers (e.g. alanine transferase, alkaline phosphatase and bilirubin) are often used to indicate liver damage. Liver injury is defined as a rise in either (a) ALT level more than three times of upper limit of normal (ULN), (b) ALP level more than twice ULN, or (c) total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular (predominantly initial Alanine transferase elevation) and cholestatic (initial alkaline phosphatase rise) types. However they are not mutually exclusive and mixed types of injuries are often encountered.
Specific histo-pathological patterns of liver injury from drug-induced damage are discussed below.

Zonal Necrosis
This is the most common type of drug-induced liver cell necrosis where the injury is largely confined to a particular zone of the liver lobule. It may manifest as a very high level of ALT and severe disturbance of liver function leading to acute liver failure.

Causes include:
Paracetamol, carbon tetrachloride

Hepatitis
In this pattern, hepatocellular necrosis is associated with infiltration of inflammatory cells. There can be three types of drug-induced hepatitis. (A) viral hepatitis is the most common, where histological features are similar to acute viral hepatitis. (B) in focal or non-specific hepatitis, scattered foci of cell necrosis may accompany lymphocytic infiltration. (C) chronic hepatitis is very similar to autoimmune hepatitis clinically, serologically, and histologically.

Causes:
(a) Viral hepatitis: Halothane, isoniazid, phenytoin
(b) Focal hepatitis: Aspirin
(c) Chronic hepatitis: Methyldopa, diclofenac

Cholestasis
Liver injury leads to impairment of bile flow and cases are predominated by itching and jaundice. Histology may show inflammation (cholestatic hepatitis) or it can be bland (without any parenchymal inflammation). On rare occasions, it can produce features similar to primary biliary cirrhosis due to progressive destruction of small bile ducts (vanishing duct syndrome).

Causes:
(a) Bland: Oral contraceptive pills, anabolic steroid, androgens
(b) Inflammatory: Allopurinol, co-amoxiclav, carbamazepine
(c) Ductal: Chlorpromazine, flucloxacillin

Steatosis
Hepatotoxicity may manifest as triglyceride accumulation, which leads to either small-droplet (microvesicular) or large-droplet (macrovesicular) fatty liver. There is a separate type of steatosis by which phospholipid accumulation leads to a pattern similar to the diseases with inherited phospholipid metabolism defects (e.g., Tay–Sachs disease)

Causes:
(a) Microvesicular: Aspirin (Reyes syndrome), ketoprofen, tetracycline (especially if expired)
(b) Macrovesicular: Acetaminophen, methotrexate
(c) Phospholipidosis: Amiodarone, total parenteral nutrition
(d) Antiviral: nucleoside analogues
(e) Corticosteroid
(f) Hormonal: Tamoxifen

Granuloma
Drug-induced hepatic granulomas are usually associated with granulomas in other tissues and patients typically have features of systemic vasculitis and hypersensitivity. More than 50 drugs have been implicated.

Causes:
Allopurinol, phenytoin, isoniazid, quinine, penicillin, quinidine

Vascular lesions
These result from injury to the vascular endothelium.

Causes:
Venoocclusive disease: Chemotherapeutic agents, bush tea
Peliosis hepatis: Anabolic steroids
Hepatic vein thrombosis: Oral contraceptives

Neoplasm
Neoplasms have been described with prolonged exposure to some medications or toxins. Hepatocellular carcinoma, angiosarcoma, and liver adenomas are the ones usually reported.

Causes:
Vinyl chloride, combined oral contraceptive pill, anabolic steroid, arsenic, thorotrast

Diagnosis
This remains a  challenge in clinical practice due to a lack of reliable markers. Many other conditions lead to similar clinical as well as pathological pictures. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected. Simultaneous use of multiple drugs may add to the complexity. As in acetaminophen toxicity, well established, dose-dependent, pharmacological hepatotoxicity is easier to spot. Several clinical scales such as CIOMS/RUCAM scale and Maria and Victorino criteria have been proposed to establish causal relationship between offending drug and liver damage. CIOMS/RUCAM scale involves a scoring system that categorizes the suspicion into "definite or highly probable" (score > 8), "probable" (score 6–8), "possible" (score 3–5), "unlikely" (score 1–2) and "excluded" (score ≤ 0). In clinical practice, physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity (e.g., cholestatic damage in  amoxycillin-clauvonic acid ).

Treatment
In most cases, liver function will return to normal if the offending drug is stopped early. Additionally, the patient may require supportive treatment. In acetaminophen toxicity, however, the initial insult can be fatal. Fulminant hepatic failure from drug-induced hepatotoxicity may require liver transplantation. In the past, glucocorticoids in allergic features and ursodeoxycholic acid in cholestatic cases had been used, but there is no good evidence to support their effectiveness.

Prognosis
An elevation in serum bilirubin level of more than 2 times ULN with associated transaminase rise is an ominous sign. This indicates severe hepatotoxicity and is likely to lead to mortality in 10% to 15% of patients, especially if the offending drug is not stopped (Hys Law). This is because it requires significant damage to the liver to impair bilirubin excretion, hence minor impairment (in the absence of biliary obstruction or Gilbert syndrome) would not lead to jaundice. Other poor predictors of outcome are old age, female sex, high AST.

Drugs withdrawn
The following therapeutic drugs were withdrawn from the market primarily because of hepatotoxicity: Troglitazone, bromfenac, trovafloxacin, ebrotidine, nimesulide, nefazodone, ximelagatran and pemoline.

See also
Hepatoprotection
Reyes syndrome

Notes
References
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Mitsuda, H.; Yasumoto, K.; Iwami, K </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 Cardiac asthma and can you explain it in depth? [/INST] Cardiac asthma is the medical condition of intermittent wheezing, coughing, and shortness of breath that is associated with underlying congestive heart failure (CHF). Symptoms of cardiac asthma are related to the hearts inability to effectively and efficiently pump blood in a CHF patient. This can lead to accumulation of fluid in and around the lungs (pulmonary congestion), disrupting the lungs ability to oxygenate blood.Cardiac asthma carries similar symptoms to bronchial asthma, but is differentiated by lacking inflammatory origin. Because of the similarity in symptoms, diagnosis of cardiac versus bronchial asthma relies on full cardiac workup and pulmonary function testing.Treatment is centered on improving cardiac function, maintaining blood oxygen saturation levels, and stabilizing total body water volume and distribution.

Signs and symptoms
The most common findings of cardiac asthma are the presence of wheeze, cough, or shortness of breath (predominantly occurring at night or when laying down) in a patient that possesses signs of congestive heart failure.Additional findings consist of production of frothy or watery sputum and presence of water in the lungs that can be heard via stethoscope. In severe cases, a patient can experience multiple night time episodes of breathlessness, changes in skin coloration, and episodes of bloody sputum.

Pathophysiology
The underlying causes for cardiac asthma stem from the eventual back up of fluid into the pulmonary vasculature as a result of the hearts, particularly left sided, inability to effectively and efficiently pump blood. The accumulation of fluid in the heart creates a higher than normal pressure system that places increasing pressure demands on the pulmonary venous system in order for appropriate oxygenation of blood to occur. This results in what is called pulmonary venous hypertension (PVH), and results in distention and recruitment of pulmonary capillaries to help distribute the increased pressure gradient. At the capillary, there is a microvascular barrier that helps regulate fluid status via molecular pressure forces such as forces that push outward from vessels and pressures that pull or attract into vessels. With increasing PVH, pressure outward overcomes pressure inward, and fluid is distributed to the lung interstitium, preserving oxygen exchange at the capillary. Fluid is transported to the hilum and pleural space, and removed via the lymphatic system. At first, the body is capable of handling excess water. Later, the capillary vasculature is overwhelmed by increased pressure and fluid backs up into the alveolar sac, resulting in pulmonary edema and decreased oxygenation capability. Additionally, increased pressure demands on capillary vasculature result in increases in vascular tone to include remodeling of pre-capillary vessels such as medial wall hypertrophic changes. Overtime, the remodeling efforts of the vessels can progress to hyperplastic changes of the vessels wall construction, and results in increased pulmonary vascular resistance.There is ongoing interest into establishing connections of cardiac asthma to abnormalities in bronchiole anatomy </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 Hwabyeong and can you explain it in depth? [/INST] Hwabyeong or Hwapyŏng (hangul: 화병, hanja: 火病) is a Korean somatization disorder, a mental illness which arises when people are unable to confront their anger as a result of conditions which they perceive to be unfair. Hwabyeong is known as a Korean culture-bound syndrome.
Hwabyeong is a colloquial name, and it refers to the etiology of the disorder rather than its symptoms or apparent characteristics. In one survey, 4.1% of the general population in a rural area in Korea were reported as having hwabyeong. Hwabyeong is similar to Amuk.
The word hwabyeong is composed of hwa (the Sino-Korean word 火 for "fire" which can also contextually mean "anger") and byeong (the Sino-Korean word 病 for "syndrome" or "illness"). It may also be called ulhwabyeong (鬱火病), literally "depression anger illness".

Symptoms
Physical symptoms include:

palpitations
anorexia
dry mouth
insomnia
thoracic/chest pressure
respiratory difficulties
epigastric mass
headache
a whole-body sensation of heat (distinct from heat intolerance, a symptom of hyperthyroidism)Psychological symptoms include:

being easily startled
externalization of anger, also known in Korean as "bun" (憤, "eruption of anger"), a Korean culture-related sentiment related to social unfairness
generally sad mood
frequent sighing
a feeling of "eok-ul" (抑鬱, [feeling of] unfairness)
being easily agitated
feelings of guilt
feelings of impending doomDiagnosed patients may also have a medical history of prior major depressive disorder, dysthymic disorder, anxiety disorders, somatoform disorders, or adjustment disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria.Diagnosed patients are most likely to be middle-aged, post-menopausal women with low socio-economic status.

Causes
Underlying causes may include:

amuk
prior instances of major depressive disorder
prior instances of anxiety disorder
prior instances of adjustment disorder
prior instances of other somatoform disorders
repression of feelings of anger/resentment arising from past eventsTriggering causes are typically external events, including:

familial stressors, e.g. spousal infidelity or conflict with in-laws
witnessing acts/actions/phenomena that conflict with ones own moral and/or ethical principlesThe syndrome itself is believed to be the result of the continued repression of feelings of anger without addressing their source. In holistic medicine the containment of anger in hwabyung disturbs the balance of the five bodily elements, resulting in the development of psychosomatic symptoms such as panic, insomnia, and depression after a long period of repressed feelings.
It is possible that hormonal imbalances such as those around the time of menopause may also be an underlying cause of hwabyung in middle-aged women, the most often-diagnosed demographic.

Treatment
Western doctors are more likely to diagnose it as a kind of stress or depression. The Diagnostic and Statistical Manual of Mental Disorders currently lists hwabyeong among its culture-bound illnesses. Outside of Korea, informally hwabyeong may be mistaken as a reference to a psychological profile marked by a short temper, or explosive, generally bellicose behavior. To the contrary, hwabyeong is a traditional psychological term used to refer to a condition characterized by passive suffering, is roughly comparable to depression, and is typically associated with older women </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 Hypercementosis 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 Prurigo pigmentosa 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 T-cell acute lymphoblastic leukemia 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 Eosinophilic cystitis 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 Diastrophic dysplasia and can you explain it in depth? [/INST] Diastrophic dysplasia is an autosomal recessive dysplasia which affects cartilage and bone development </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 Craniotabes 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 Byssinosis and can you explain it in depth? [/INST] Byssinosis is an occupational lung disease caused by inhalation of cotton or jute dust in inadequately ventilated working environments and can develop over time with repeated exposure. Byssinosis commonly occurs in textile workers who are employed in yarn and fabric manufacture industries. It is now thought that the cotton dust directly causes the disease and some believe that the causative agents are endotoxins that come from the cell walls of gram-negative bacteria that grow on the cotton. Although bacterial endotoxin is a likely cause, the absence of similar symptoms in workers in other industries exposed to endotoxins makes this uncertain. Current smokers are also at risk for developing byssinosis or having complications relating to byssinosis.Of the 81 byssinosis-related fatalities reported in the United States between 1990 and 1999, 48% included an occupation in the yarn, thread, and fabric industry on their death certificate. This disease often occurred in the times of the Industrial Revolution. Most commonly young girls working in mills or other textile factories would be affected by this disease. In the United States, from 1996 to 2005, North Carolina accounted for about 37% of all deaths caused by byssinosis, with 31, followed by South Carolina (8) and Georgia (7).There is a lack of information regarding the prevalence and impact of byssinosis in low and middle income countries (LMIC) despite the fact that of the 25 million tons of cotton produced worldwide, about two thirds of this production comes from LMICs like India, Pakistan, and China. Many textile mills and fiber producing factories located in LMICs have high rates of chronic respiratory disease caused by byssinosis.The term "brown lung" is a misnomer, as the lungs of affected individuals are not brown. Byssinosis is also referred to as cotton workers lung, mill fever, brown lung disease, and Monday fever.

History
In 1971, the Occupational Safety and Health Administration (OSHA) set a permissible exposure limit (PEL) of  1-mg/m3 (total dust) for cotton dust in work places. Later in the 1978 OSHA developed the Cotton Dust Standard which aimed to prevent occupational respiratory disease, such as byssinosis, through medical monitoring of employees. The PEL of cotton dust was set to 0.2 mg/m3 of airborne dust. This was considered the lowest level that could be measured by the vertical elutriator cotton dust sampler.OSHA regulators hoped that the Cotton Dust Standard Act would help decrease the impact of dust exposure of employees and reduce occupational respiratory diseases. However, a NISOH sponsored committee remained apprehensive about this standard as an earlier study conducted by NIOSH found that byssinosis diagnoses were brought on by cotton dust levels as low as 0.1 mg/m3 meaning that there is still a risk for the development of byssinosis for cotton dust exposure under the PEL. Today, NIOSH has set a recommended exposure limit (REL) of cotton dust to less than 0.2 mg/m3 for up to a 10-hour workday.

Symptoms
Symptoms of byssinosis can include:
Cough with sputum
Dyspnea
Breathing difficulties
Chest tightness
Wheezing
CoughPatients can develop these symptoms after a few hours of exposure at minimum. For this reason, patients who develop and report these symptoms, and subsequently byssinosis, are one of the reasons why the term Monday Fever exists. Byssinosis can become chronic in a patient if they are continually exposed to cotton, jute, or yarn dust over time. Byssinosis can be misdiagnosed as COPD, or asthma however the difference in these lung diseases and byssinosis comes from the etiology. Byssinosis can ultimately result in narrowing of the airways, lung scarring and death from infection or respiratory failure. Extended exposure to cotton or jute dust can lead to impaired lung function and further respiratory complications. Patients may require oxygen to assist with breathing and may also have difficulty exercising.

Diagnosis
It can be difficult to accurately diagnose a patient with byssinosis due to symptoms that are similar to other respiratory diseases such as chronic obstructive pulmonary diseases (COPD), asthma, or bronchitis. Byssinosis can be misdiagnosed as other pneumoconioses therefore a chest x-ray and/or lung function test is needed to accurately diagnose a patient who may have byssinosis. The main distinction of byssinosis from other respiratory diseases comes from the initial exposure. Patients who have byssinosis have typically been exposed to cotton or just dust for an extended period of time and experience symptoms of chest tightness and coughing.Patient history should reveal exposure to cotton, flax, hemp, or jute dust. Measurable change in lung function before and after working shifts is key to diagnosis. Patients with byssinosis show a significant drop in FEV1 over the course of work shift.
Chest radiographs show areas of opacity due to fibrosis of the pulmonary parenchyma.Another form of diagnosis is observing patient symptoms throughout their work shift. Patients with byssinosis due to dust inhalation will experience adverse symptoms when they being their work shift on Monday which is where the term Monday Fever comes in.

Treatment
There is currently no official form of diagnosing an individual with byssinosis </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 Functional symptom and can you explain it in depth? [/INST] A functional symptom is a medical symptom with no known physical cause.  In other words, there is no structural or pathologically defined disease to explain the symptom. The use of the term functional symptom does not assume psychogenesis, only that the body is not functioning as expected. Functional symptoms are increasingly viewed within a framework in which biological, psychological, interpersonal and healthcare factors should all be considered to be relevant for determining the aetiology and treatment plans.Historically, there has often been fierce debate about whether certain problems are predominantly related to an abnormality of structure (disease) or are psychosomatic in nature, and what are at one stage posited to be functional symptoms are sometimes later reclassified as organic, as investigative techniques improve. It is well established that psychosomatic symptoms are a real phenomenon, so this potential explanation is often plausible, however the commonality of a range of psychological symptoms and functional weakness does not imply that one causes the other. For example, symptoms associated with migraine, epilepsy, schizophrenia, multiple sclerosis, stomach ulcers, chronic fatigue syndrome, Lyme disease and many other conditions have all tended historically at first to be explained largely as physical manifestations of the patients psychological state of mind; until such time as new physiological knowledge is eventually gained. Another specific example is functional constipation, which may have psychological or psychiatric causes </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 Conjunctivochalasis and can you explain it in depth? [/INST] Conjunctivochalasis, also known as Mechanical Dry Eye (MDE), is a common eye surface condition characterized by the presence of excess folds of the conjunctiva located between the globe of the eye and the eyelid margin.

Symptoms
Symptoms range from dry eye, epiphora and irritation to localized pain, foreign body sensation, subconjunctival hemorrhage and ulceration. Symptoms are often made worse by vigorous blinking.

Causes
Most Conjunctivochalasis is thought to be caused by both a gradual thinning and stretching of the conjunctiva that accompanies age and a loss of adhesion between the conjunctiva and underlying sclera as the result of dissolution of Tenons capsule. The resulting loose, excess conjunctiva may mechanically irritate the eye and disrupt the tear film and its outflow, leading to dry eye and excess tearing. A correlation may also exist between inflammation in the eye and conjunctivochalasis, though it is unclear whether this correlation is causal. Conjunctivochalasis may be associated with previous surgery, blepharitis, meibomian gland disorder (MGD), Ehlers-Danlos Syndrome and aqueous tear deficiency.

Diagnosis
Because the disorder often occurs in people with typical dry eye symptoms, it can be difficult to readily distinguish the discomfort caused by the dry eye from that directly related to the redundant conjunctiva.
Mechanical dry eye should not be confused with aqueous tear deficiency dry eye or delayed tear clearance. Mechanical dry eye patients complain of blurry vision and pain that tend to be worse when looking down such as while reading. Dryness in aqueous tear deficiency dry eye patients tends to be worse as the day progresses due to progressive exposure. Frequent blinking exacerbates mechanical dry eye symptoms, while increasing blinking improves symptoms of aqueous tear deficiency dry eye.
Diagnosis can be further made under a slit lamp upon the observation of redundant conjunctival folds. These folds can be made more apparent by staining with fluorescein dye and by applying gentle upward pressure with a finger to the eyeball through the lower lid. In pure aqueous tear deficiency dry eye patients, fluorescein stains in the interpalpebral exposure zone </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 Candidiasis and can you explain it in depth? [/INST] Candidiasis is a fungal infection due to any type of Candida (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers along with other symptoms depending on the parts involved.More than 20 types of Candida can cause infection with Candida albicans being the most common. Infections of the mouth are most common among children less than one month old, the elderly, and those with weak immune systems. Conditions that result in a weak immune system include HIV/AIDS, the medications used after organ transplantation, diabetes, and the use of corticosteroids. Other risks include dentures, following antibiotic therapy, and breastfeeding. Vaginal infections occur more commonly during pregnancy, in those with weak immune systems, and following antibiotic use. Individuals at risk for invasive candidiasis include low birth weight babies, people recovering from surgery, people admitted to intensive care units, and those with an otherwise compromised immune system.Efforts to prevent infections of the mouth include the use of chlorhexidine mouthwash in those with poor immune function and washing out the mouth following the use of inhaled steroids. Little evidence supports probiotics for either prevention or treatment, even among those with frequent vaginal infections. For infections of the mouth, treatment with topical clotrimazole or nystatin is usually effective. Oral or intravenous fluconazole, itraconazole, or amphotericin B may be used if these do not work. A number of topical antifungal medications may be used for vaginal infections, including clotrimazole. In those with widespread disease, an echinocandin such as caspofungin or micafungin is used. A number of weeks of intravenous amphotericin B may be used as an alternative. In certain groups at very high risk, antifungal medications may be used preventatively.Infections of the mouth occur in about 6% of babies less than a month old. About 20% of those receiving chemotherapy for cancer and 20% of those with AIDS also develop the disease. About three-quarters of women have at least one yeast infection at some time during their lives. Widespread disease is rare except in those who have risk factors.

Signs and symptoms
Signs and symptoms of candidiasis vary depending on the area affected. Most candidal infections result in minimal complications such as redness, itching, and discomfort, though complications may be severe or even fatal if left untreated in certain populations. In healthy (immunocompetent) persons, candidiasis is usually a localized infection of the skin, fingernails or toenails (onychomycosis), or mucosal membranes, including the oral cavity and pharynx (thrush), esophagus, and the genitalia (vagina, penis, etc.); less commonly in healthy individuals, the gastrointestinal tract, urinary tract, and respiratory tract are sites of candida infection.
In immunocompromised individuals, Candida infections in the esophagus occur more frequently than in healthy individuals and have a higher potential of becoming systemic, causing a much more serious condition, a fungemia called candidemia. Symptoms of esophageal candidiasis include difficulty swallowing, painful swallowing, abdominal pain, nausea, and vomiting.

Mouth
Infection in the mouth is characterized by white discolorations in the tongue, around the mouth, and throat. Irritation may also occur, causing discomfort when swallowing.Thrush is commonly seen in infants. It is not considered abnormal in infants unless it lasts longer than a few weeks.

Genitals
Infection of the vagina or vulva may cause severe itching, burning, soreness, irritation, and a whitish or whitish-gray cottage cheese-like discharge.  Symptoms of infection of the male genitalia (balanitis thrush) include red skin around the head of the penis, swelling, irritation, itchiness and soreness of the head of the penis, thick, lumpy discharge under the foreskin, unpleasant odour, difficulty retracting the foreskin (phimosis), and pain when passing urine or during sex.

Skin
Signs and symptoms of candidiasis in the skin include itching, irritation, and chafing or broken skin.

Invasive infection
Common symptoms of gastrointestinal candidiasis in healthy individuals are anal itching, belching, bloating, indigestion, nausea, diarrhea, gas, intestinal cramps, vomiting, and gastric ulcers. Perianal candidiasis can cause anal itching; the lesion can be red, papular, or ulcerative in appearance, and it is not considered to be a sexually transmissible disease. Abnormal proliferation of the candida in the gut may lead to dysbiosis. While it is not yet clear, this alteration may be the source of symptoms generally described as the irritable bowel syndrome, and other gastrointestinal diseases.

Causes
Candida yeasts are generally present in healthy humans, frequently part of the human bodys normal oral and intestinal flora, and particularly on the skin; however, their growth is normally limited by the human immune system and by competition of other microorganisms, such as bacteria occupying the same locations in the human body.Candida requires moisture for growth, notably on the skin. For example, wearing wet swimwear for long periods of time is believed to be a risk factor. Candida can also cause diaper rashes in babies. In extreme cases, superficial infections of the skin or mucous membranes may enter the bloodstream and cause systemic Candida infections.Factors that increase the risk of candidiasis include HIV/AIDS, mononucleosis, cancer treatments, steroids, stress, antibiotic usage, diabetes, and nutrient deficiency. Hormone replacement therapy and infertility treatments may also be predisposing factors. Use of inhaled corticosteroids increases risk of candidiasis of the mouth. Inhaled corticosteroids with other risk factors such as antibiotics, oral glucocorticoids, not rinsing mouth after use of inhaled corticosteroids or high dose of inhaled corticosteroids put people at even higher risk. Treatment with antibiotics can lead to eliminating the yeasts natural competitors for resources in the oral and intestinal flora, thereby increasing the severity of the condition. A weakened or undeveloped immune system or metabolic illnesses are significant predisposing factors of candidiasis. Almost 15% of people with weakened immune systems develop a systemic illness caused by Candida species. Diets high in simple carbohydrates have been found to affect rates of oral candidiases.C. albicans was isolated from the vaginas of 19% of apparently healthy people, i.e., those who experienced few or no symptoms of infection. External use of detergents or douches or internal disturbances (hormonal or physiological) can perturb the normal vaginal flora, consisting of lactic acid bacteria, such as lactobacilli, and result in an overgrowth of Candida cells, causing symptoms of infection, such as local inflammation. Pregnancy and the use of oral contraceptives have been reported as risk factors. Diabetes mellitus and the use of antibiotics are also linked to increased rates of yeast infections.In penile candidiasis, the causes include sexual intercourse with an infected individual, low immunity, antibiotics, and diabetes. Male genital yeast infections are less common, but a yeast infection on the penis caused from direct contact via sexual intercourse with an infected partner is not uncommon.Breast-feeding mothers may also develop candidiasis on and around the nipple as a result of moisture created by excessive milk-production.Vaginal candidiasis can cause congenital candidiasis in newborns.

Diagnosis
In oral candidiasis, simply inspecting the persons mouth for white patches and irritation may make the diagnosis. A sample of the infected area may also be taken to determine what organism is causing the infection.Symptoms of vaginal candidiasis are also present in the more common bacterial vaginosis; aerobic vaginitis is distinct and should be excluded in the differential diagnosis. In a 2002 study, only 33% of women who were self-treating for a yeast infection actually had such an infection, while most had either bacterial vaginosis or a mixed-type infection.Diagnosis of a yeast infection is done either via microscopic examination or culturing.  For identification by light microscopy, a scraping or swab of the affected area is placed on a microscope slide. A single drop of 10% potassium hydroxide (KOH) solution is then added to the specimen. The KOH dissolves the skin cells, but leaves the Candida cells intact, permitting visualization of pseudohyphae and budding yeast cells typical of many Candida species.For the culturing method, a sterile swab is rubbed on the infected skin surface. The swab is then streaked on a culture medium. The culture is incubated at 37 °C (98.6 °F) for several days, to allow development of yeast or bacterial colonies. The characteristics (such as morphology and colour) of the colonies may allow initial diagnosis of the organism causing disease symptoms.
Respiratory, gastrointestinal, and esophageal candidiasis require an endoscopy to diagnose. For gastrointestinal candidiasis, it is necessary to obtain a 3–5 milliliter sample of fluid from the duodenum for fungal culture. The diagnosis of gastrointestinal candidiasis is based upon the culture containing in excess of 1,000 colony-forming units per milliliter.

Classification
Candidiasis may be divided into these types:

Mucosal candidiasis
Oral candidiasis (thrush, oropharyngeal candidiasis)Pseudomembranous candidiasis
Erythematous candidiasis
Hyperplastic candidiasis
Denture-related stomatitis — Candida organisms are involved in about 90% of cases
Angular cheilitis — Candida species are responsible for about 20% of cases, mixed infection of C. albicans and Staphylococcus aureus for about 60% of cases.
Median rhomboid glossitis
Candidal vulvovaginitis (vaginal yeast infection)
Candidal balanitis — infection of the glans penis, almost exclusively occurring in uncircumcised males
Esophageal candidiasis (candidal esophagitis)
Gastrointestinal candidiasis
Respiratory candidiasis
Cutaneous candidiasis
Candidal folliculitis
Candidal intertrigo
Candidal paronychia
Perianal candidiasis, may present as pruritus ani: 309
Candidid
Chronic mucocutaneous candidiasis
Congenital cutaneous candidiasis
Diaper candidiasis: an infection of a childs diaper area: 309
Erosio interdigitalis blastomycetica
Candidal onychomycosis (nail infection) caused by Candida
Systemic candidiasisCandidemia, a form of fungemia which may lead to sepsis
Invasive candidiasis (disseminated candidiasis) — organ infection by Candida
Chronic systemic candidiasis (hepatosplenic candidiasis) — sometimes arises during recovery from neutropenia
Antibiotic candidiasis (iatrogenic candidiasis)

Prevention
A diet that supports the immune system and is not high in simple carbohydrates contributes to a healthy balance of the oral and intestinal flora. While yeast infections are associated with diabetes, the level of blood sugar control may not affect the risk. Wearing cotton underwear may help to reduce the risk of developing skin and vaginal yeast infections, along with not wearing wet clothes for long periods of time. For women who experience recurrent yeast infections, there is limited evidence that oral or intravaginal probiotics help to prevent future infections. This includes either as pills or as yogurt.Oral hygiene can help prevent oral candidiasis when people have a weakened immune system. For people undergoing cancer treatment, chlorhexidine mouthwash can prevent or reduce thrush. People who use inhaled corticosteroids can reduce the risk of developing oral candidiasis by rinsing the mouth with water or mouthwash after using the inhaler. People with dentures should also disinfect their dentures regularly to prevent oral candidiasis.

Treatment
Candidiasis is treated with antifungal medications; these include clotrimazole, nystatin, fluconazole, voriconazole, amphotericin B, and echinocandins.  Intravenous fluconazole or an intravenous echinocandin such as caspofungin are commonly used to treat immunocompromised or critically ill individuals.The 2016 revision of the clinical practice guideline for the management of candidiasis lists a large number of specific treatment regimens for Candida infections that involve different Candida species, forms of antifungal drug resistance, immune statuses, and infection localization and severity. Gastrointestinal candidiasis in immunocompetent individuals is treated with 100–200 mg fluconazole per day for 2–3 weeks.

Localized infection
Mouth and throat candidiasis are treated with antifungal medication. Oral candidiasis usually responds to topical treatments; otherwise, systemic antifungal medication may be needed for oral infections. Candidal skin infections in the skin folds (candidal intertrigo) typically respond well to topical antifungal treatments (e.g., nystatin or miconazole). For breastfeeding mothers topical miconazole is the most effective treatment for treating candidiasis on the breasts. Gentian violet can be used for thrush in breastfeeding babies. Systemic treatment with antifungals by mouth is reserved for severe cases or if treatment with topical therapy is unsuccessful. Candida esophagitis may be treated orally or intravenously; for severe or azole-resistant esophageal candidiasis, treatment with amphotericin B may be necessary.Vaginal yeast infections are typically treated with topical antifungal agents. Penile yeast infections are also treated with antifungal agents, but while an internal treatment may be used (such as a pessary) for vaginal yeast infections, only external treatments – such as a cream – can be recommended for penile treatment. A one-time dose of fluconazole by mouth is 90% effective in treating a vaginal yeast infection. For severe nonrecurring cases, several doses of fluconazole is recommended. Local treatment may include vaginal suppositories or medicated douches. Other types of yeast infections require different dosing.  C. albicans can develop resistance to fluconazole, this being more of an issue in those with HIV/AIDS who are often treated with multiple courses of fluconazole for recurrent oral infections.For vaginal yeast infection in pregnancy, topical imidazole or triazole antifungals are considered the therapy of choice owing to available safety data. Systemic absorption of these topical formulations is minimal, posing little risk of transplacental transfer. In vaginal yeast infection in pregnancy, treatment with topical azole antifungals is recommended for seven days instead of a shorter duration.For vaginal yeast infections, many complementary treatments are proposed, however a number have side effects. No benefit from probiotics has been found for active infections.

Blood infection
Treatment typically consists of oral or intravenous antifungal medications. In candidal infections of the blood, intravenous fluconazole or an echinocandin such as caspofungin may be used. Amphotericin B is another option.

Prognosis
Among individuals being treated in intensive care units, the mortality rate is about 30–50% when systemic candidiasis develops.

Epidemiology
Oral candidiasis is the most common fungal infection of the mouth, and it also represents the most common opportunistic oral infection in humans. Infections of the mouth occur in about 6% of babies less than a month old. About 20% of those receiving chemotherapy for cancer and 20% of those with AIDS also develop the disease.It is estimated that 20% of women may be asymptomatically colonized by vaginal yeast. In the United States there are approximately 1.4 million doctor office visits every year for candidiasis. About three-quarters of women have at least one yeast infection at some time during their lives.Esophageal candidiasis is the most common esophageal infection in persons with AIDS and accounts for about 50% of all esophageal infections, often coexisting with other esophageal diseases. About two-thirds of people with AIDS and esophageal candidiasis also have oral candidiasis.Candidal sepsis is rare. Candida is the fourth most common cause of bloodstream infections among hospital patients in the United States. The incidence of bloodstream candida in intensive care units varies widely between countries.

History
Descriptions of what sounds like oral thrush go back to the time of Hippocrates circa 460–370 BCE.The first description of a fungus as the causative agent of an oropharyngeal and oesophageal candidosis was by Bernhard von Langenbeck in 1839.Vulvovaginal candidiasis was first described in 1849 by Wilkinson. In 1875, Haussmann demonstrated the causative organism in both vulvovaginal and oral candidiasis is the same.With the advent of antibiotics following World War II, the rates of candidiasis increased. The rates then decreased in the 1950s following the development of nystatin.The colloquial term "thrush" refers to the resemblance of the white flecks present in some forms of candidiasis (e.g., pseudomembranous candidiasis) with the breast of the bird of the same name. The term candidosis is largely used in British English, and candidiasis in American English. Candida is also pronounced differently; in American English, the stress is on the "i", whereas in British English the stress is on the first syllable.The genus Candida and species C. albicans were described by botanist Christine Marie Berkhout in her doctoral thesis at the University of Utrecht in 1923. Over the years, the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).The genus Candida includes about 150 different species. However, only a few are known to cause human infections. C. albicans is the most significant pathogenic species. Other species pathogenic in humans include C. auris, C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, 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 Cat-scratch disease and can you explain it in depth? [/INST] Cat-scratch disease (CSD) or felinosis is an infectious disease that most often results from a scratch or bite of a cat. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen lymph nodes. People may feel tired, have a headache, or a fever. Symptoms typically begin within 3–14 days following infection.Cat-scratch disease is caused by the bacterium Bartonella henselae which is believed to be spread by the cats saliva. Young cats pose a greater risk than older cats. Occasionally dog scratches or bites may be involved. Diagnosis is generally based on symptoms. Confirmation is possible by blood tests.The primary treatment is supportive. Antibiotics speed healing and are recommended in those with severe disease or immune problems. Recovery typically occurs within 4 months but can require a year. About 1 in 10,000 people are affected. It is more common in children.

Signs and symptoms
Cat-scratch disease commonly presents as tender, swollen lymph nodes near the site of the inoculating bite or scratch or on the neck, and is usually limited to one side. This condition is referred to as regional lymphadenopathy and occurs 1–3 weeks after inoculation. Lymphadenopathy most commonly occurs in the axilla, arms, neck, or jaw, but may also occur near the groin or around the ear. A vesicle or an erythematous papule may form at the site of initial infection.Most people also develop systemic symptoms such as malaise, decreased appetite, and aches. Other associated complaints include headache, chills, muscular pains, joint pains, arthritis, backache, and abdominal pain. It may take 7 to 14 days, or as long as two months, for symptoms to appear. Most cases are benign and self-limiting, but lymphadenopathy may persist for several months after other symptoms disappear. The disease usually resolves spontaneously, with or without treatment, in one month.
In rare situations, CSD can lead to the development of serious neurologic or cardiac sequelae such as meningoencephalitis, encephalopathy, seizures, or endocarditis. Endocarditis associated with Bartonella infection has a particularly high mortality. Parinauds oculoglandular syndrome is the most common ocular manifestation of CSD, and is a granulomatous conjunctivitis with concurrent swelling of the lymph node near the ear. Optic neuritis or neuroretinitis is one of the atypical presentations.People who are immunocompromised are susceptible to other conditions associated with B. henselae and B. quintana, such as bacillary angiomatosis or bacillary peliosis. Bacillary angiomatosis is primarily a vascular skin lesion that may extend to bone or be present in other areas of the body. In the typical scenario, the patient has HIV or another cause of severe immune dysfunction. Bacillary peliosis is caused by B. henselae that most often affects people with HIV and other conditions causing severe immune compromise. The liver and spleen are primarily affected, with findings of blood-filled cystic spaces on pathology.

Cause
Bartonella henselae is a fastidious, intracellular, Gram-negative bacterium.

Transmission
The cat was recognized as the natural reservoir of the disease in 1950 by Robert Debré. Kittens are more likely to carry the bacteria in their blood, so may be more likely to transmit the disease than adult cats. However, fleas serve as a vector for transmission of B. henselae among cats, and viable B. henselae are excreted in the feces of Ctenocephalides felis, the cat flea. Cats could be infected with B. henselae through intradermal inoculation using flea feces containing B. henselae.As a consequence, a likely means of transmission of B. henselae from cats to humans may be inoculation with flea feces containing B. henselae through a contaminated cat scratch wound or by cat saliva transmitted in a bite. Ticks can also act as vectors and occasionally transmit the bacteria to humans. Combined clinical and PCR-based research has shown that other organisms can transmit Bartonella, including spiders. Cryptic Bartonella infection may be a much larger problem than previously thought, constituting an unrecognized occupational health hazard of veterinarians.

Diagnosis
The best diagnostic method available is polymerase chain reaction, which has a sensitivity of 43-76% and a specificity (in one study) of 100%. The Warthin–Starry stain can be helpful to show the presence of B. henselae, but is often difficult to interpret. B. henselae is difficult to culture and can take 2–6 weeks to incubate.

Histology
Cat-scratch disease is characterized by granulomatous inflammation on histological examination of the lymph nodes. Under the microscope, the skin lesion demonstrates a circumscribed focus of necrosis, surrounded by histiocytes, often accompanied by multinucleated giant cells, lymphocytes, and eosinophils. The regional lymph nodes demonstrate follicular hyperplasia with central stellate necrosis with neutrophils, surrounded by palisading histiocytes (suppurative granulomas) and sinuses packed with monocytoid B cells, usually without perifollicular and intrafollicular epithelioid cells. This pattern, although typical, is only present in a minority of cases.

Prevention
Cat-scratch disease can be primarily prevented by taking effective flea control measures; since cats are mostly exposed to fleas when they are outside, keeping cats inside can help prevent infestation. Strictly-indoor cats without exposure to indoor-outdoor animals are generally at negligible risk of infestation.  Cats which are carrying the bacterium, B. henselae, are asymptomatic, thus thoroughly washing hands after handling a cat or cat feces is an important factor in preventing potential cat-scratch disease transmission from possibly infected cats to humans.

Treatment
Most healthy people clear the infection without treatment, but in 5 to 14% of individuals, the organisms disseminate and infect the liver, spleen, eye, or central nervous system. Although some experts recommend not treating typical CSD in immunocompetent people with mild to moderate illness, treatment of all people with antimicrobial agents (Grade 2B) is suggested due to the probability of disseminated disease. The preferred antibiotic for treatment is azithromycin, since this agent is the only one studied in a randomized controlled study.Azithromycin is preferentially used in pregnancy to avoid the teratogenic side effects of doxycycline. However, doxycycline is preferred to treat B. henselae infections with optic neuritis due to its ability to adequately penetrate the tissues of the eye and central nervous system.

Epidemiology
Cat-scratch disease has a worldwide distribution, but it is a nonreportable disease in humans, so public health data on this disease are inadequate. Geographical location, present season, and variables associated with cats (such as exposure and degree of flea infestation) all play a factor in the prevalence of CSD within a population. In warmer climates, the CSD is more prevalent during the fall and winter, which may be attributed to the breeding season for adult cats, which allows for the birth of kittens. B henselae, the bacterium responsible for causing CSD, is more prevalent in younger cats (less than one year old) than it is in adult cats.To determine recent incidence of CSD in the United States, the Truven Health MarketScan Commercial Claims and Encounters database was analyzed in a case control study from 2005 to 2013. The database consisted of healthcare insurance claims for employees, their spouses, and their dependents. All participants were under 65 years of age, from all 50 states. The length of the study period was 9 years and was based on 280,522,578 person-years; factors such as year, length of insurance coverage, region, age, and sex were used to calculate the person-years incidence rate to eliminate confounding variables among the entire study population.A total of 13,273 subjects were diagnosed with CSD, and both in- and outpatient cases were analyzed. The study revealed an incidence rate of 4.5/100,000 outpatient cases of cat-scratch disease. For inpatient cases, the incidence rate was much lower at 0.19/100,000 population. Incidence of CSD was highest in 2005 among outpatient cases and then slowly declined. The Southern states had the most significant decrease of incidence over time. Mountain regions have the lowest incidence of this disease because fleas are not commonly found in these areas.Distribution of CSD among children aged 5–9 was of the highest incidence in the analyzed database, followed by women aged 60–64. Incidence among females was higher than that among males in all age groups. According to data on social trends, women are more likely to own a cat over men; which supports higher incidence rates of this disease in women. Risk of contracting CSD increases as the number of cats residing in the home increases. The number of pet cats in the United States is estimated to be 57 million. Due to the large population of cats residing in the United States, the ability of this disease to continue to infect humans is vast. Laboratory diagnosis of CSD has improved in recent years, which may support an increase in incidence of the disease in future populations.

Outbreaks
Historically, the number of reported cases of CSD has been low, there has been a significant increase in reports in urban and suburban areas in the northeast region of United States. An example of the increased incidence can be found in Essex County, New Jersey </s>