<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 Blau syndrome and can you explain it in depth? [/INST] Blau syndrome is an autosomal dominant genetic inflammatory disorder which affects the skin, eyes, and joints. It is caused by a mutation in the NOD2 (CARD15) gene. Symptoms usually begin before the age of four, and the disease manifests as early onset cutaneous sarcoidosis, granulomatous arthritis, and uveitis.

Presentation
Cause
The elucidation that the gene defect in Blau syndrome (BS) involves the CARD15/NOD2 gene has stimulated many investigators to define how this gene operates as part of the innate immune system. The innate immune system recognizes pathogen-associated molecular patterns (PMAPs), including bacterial polysaccharides such as muramyl dipeptide, via its pattern recognition receptors (PRRs), such as NOD2, to induce signaling pathways that activate cytokine responses and protect the organism. In BS the genetic defect seems to lead to over activation and poor control of the inflammatory response leading to widespread granulomatous inflammation and tissue damage.

Diagnosis
Treatment
Treatment has included the usual anti-inflammatory drugs such as adrenal glucocorticoids, anti-metabolites and also biological agents such as anti-TNF and infliximab all with varying degrees of success.

History
In 1981, Malleson et al. reported a family that had autosomal dominant synovitis, camptodactyly, and iridocyclitis. One member died of granulomatous arteritis of the heart and aorta.
In 1982, Rotenstein reported a family with granulomatous arteritis, rash, iritis, and arthritis transmitted as an autosomal dominant trait over three generations.In 1985, Edward Blau, a pediatrician in Marshfield, Wisconsin, reported a family that over four generations had granulomatous inflammation of the skin, eyes and joints. The condition was transmitted as an autosomal dominant trait. In the same year Jabs et al. reported a family that over two generations had granulomatous synovitis, uveitis and cranial neuropathies. The condition was transmitted in an autosomal dominant fashion.Then in 1990 Pastores et al. reported a kindred with a phenotype very similar to what Blau described and suggested that the condition be called Blau Syndrome (BS). They also pointed out the similarities in the families noted above to BS but also pointed out the significant differences in the phenotypes.In 1996 Tromp et al. conducted a genome wide search using affected and non affected members of the original family. A marker, D16S298, gave a maximum logarithm of odds (LOD) score of 3.75 and put the BS susceptibility locus within the 16p12-q21 interval.  Hugot et al. found a susceptibility locus for Crohn disease, a granulomatous inflammation of the bowel, on chromosome 16 close to the locus for BS. Based on the above information Blau suggested in 1998 that the genetic defect in BS and Crohn Disease might be the same or similar.
Finally in 2001 Miceli-Richard et al. found the defect in BS to be in the nucleotide-binding domain of CARD15/NOD2. They commented in their article that mutations in CARD15 had also been found in Crohns disease. Confirmation of the defect in BS being in the CARD15 gene was made by Wang et al. in 2002 using the BS family and others. With that information the diagnosis of BS was not only determined by phenotype but now by genotype.Early onset sarcoidosis is BS without a family history,  BS has been diagnosed in patients who have not only the classic triad but granuloma in multiple organs.

See also
List of cutaneous conditions

References
Further reading
Wouters CH, Maes A, Foley KP, Bertin J, and Rose CD: Blau Syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatric Rheumatology 2014;12:33. PMID 25136265.  PMC 4136643.  doi:10.1186/1546-0096-12-33.
Blau EB : Familial Granulomatous Arthritis, Iritis, and Rash. The Journal of Pediatrics 1985; 107: 689-693.  PMID 4056967.  doi:10.1016/s0022-3476(85)80394-2.
Jabs DA, Houk JL, Bias WB, and Arnett FC: Familial Granulomatous Synovitis, Uveitis, and Cranial Neuropathies. The American Journal of Medicine 1985; 78: 801–804.  PMID 3993660.  doi:10.1016/0002-9343(85)90286-4.
Malleson P, Schaller JG, Dega F, Cassidy SB, and Pagon RA : Familial Arthritis and Camplodactyly. Arthritis and Rheumatism 1981; 24: 1199–1204.  PMID 7306244.  doi:10.1002/art.1780240915.
Rotenstein D, Gibbas DL, Majmudar B, and Chastain EA: Familial Granulomatous Arteritis with Polyarthritis of Juvenile Onset. The New England Journal of Medicine 1982; 306: 85–90. PMID 7053492.  doi:10.1056/NEJM198201143060208.
Pastores GM, Michels VV, Stickler GB, Su WP, Nelson AM, and Bovenmyer DA: Autosomal dominant granulomatous arthritis, uveitis, skin rash, and synovial cysts. The Journal of Pediatrics 1990; 117: 403–408.  PMID 2391595.  doi:10.1016/s0022-3476(05)81080-7.
Tromp G, Kuivaniemi H, Raphael S, et al.: Genetic Linkage of Familial Granulomatous Inflammatory Arthritis, Skin Rash, and Uveitis to Chromosome 16. The American Journal of Human Genetics 1996; 59: 1097-1107.  PMID 8900239.  PMC 1914842.
Hugot JP, Chamaillard M, Zouali H, et al.: Association of NOD2 leucine-rich repeat variants with susceptibility to Crohns disease. Nature 2001; 411:599-603.  PMID 11385576.  doi:10.1038/35079107.
Blau EB : Autosomal dominant granulomatous disease of childhood: The naming of things. The Journal of Pediatrics 1998; 133: 322–323.  PMID 9738710.  doi:10.1016/s0022-3476(98)70263-x.
Miceli-Richard C, Lesage S, Rybojad M, Prieur A-M, Manouvrier-Hanu S, Häfner R, Chamaillard M, Zouali H, Thomas G, and Hugot J-P: CARD15 mutations in Blau syndrome </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 Bagassosis 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 Growth hormone deficiency and can you explain it in depth? [/INST] Growth hormone deficiency (GHD), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also present low blood sugar or a small penis size. In adults there may be decreased muscle mass, high cholesterol levels, or poor bone density.GHD can be present at birth or develop later in life. Causes may include genetics, trauma, infections, tumors, or radiation therapy. Genes that may be involved include GH1, GHRHR, or BTK. In a third of cases no cause is apparent. The underlying mechanism generally involves problems with the pituitary gland. Some cases are associated with a lack of other pituitary hormones, in which case it is known as combined pituitary hormone deficiency. Diagnosis involves blood tests to measure growth hormone levels.Treatment is by growth hormone replacement using synthetic human growth hormone. The frequency of the condition is unclear. Most cases are initially noticed in children. The genetic forms of this disease are estimated to affect about 1 in 7,000 people. Most types occur equally in males and females though males are more often diagnosed.

Signs and symptoms
Child
Severe prenatal deficiency of GH, as occurs in congenital hypopituitarism, has little effect on fetal growth. However, prenatal and congenital deficiency can reduce the size of a males penis, especially when gonadotropins are also deficient. Besides micropenis in males, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyperbilirubinemia).Even congenital GH deficiency does not usually impair length growth until after the first few months of life. From late in the first year until mid-teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency is present from birth and never treated, adult heights can be as short as 48-65 inches (122–165 cm).Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone, muscle, and fat) is affected in many children with severe deficiency, so that mild to moderate chubbiness is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence.Other side effects in children include sparse hair growth and frontal recession, and pili torti and trichorrhexis nodosa are also sometimes present.: 501

Adults
Recognised effects include:
Increased 5-alpha-reductase
Reduced sex hormone-binding globulin (SHBG)
Reduced muscle mass and strength
Baldness in men
Reduced bone mass and osteoporosis (Decreased bone density)
Reduced energy
Impaired concentration and memory loss
Increased body fat, particularly around the waistline
Lipid abnormalities, particularly raised LDL cholesterol
Increased levels of fibrinogen and plasminogen activator inhibitor
Cardiac dysfunction, including a thickened intima media
Lack of well-being
Depression and anxiety
Social isolation
Fibromyalgia syndrome
Neuromuscular dysfunction
Central adiposity
Decreased muscle mass
Insulin resistance
Accelerated atherogenesis
Prothrombotic state
Decreased sweating and thermoregulation.

Causes
Growth hormone deficiency in childhood commonly has no identifiable cause (idiopathic), and adult-onset GHD is commonly due to pituitary tumours and their treatment or to cranial irradiation. A more complete list of causes includes:

mutations of specific genes (e.g., GHRHR, GH1)
congenital diseases such as Prader-Willi syndrome, Turner syndrome, or short-stature homeobox gene deficiency
congenital malformations involving the pituitary (e.g., septo-optic dysplasia, posterior pituitary ectopia)
chronic kidney disease
intracranial tumors in or near the sella turcica, especially craniopharyngioma
damage to the pituitary from radiation therapy to the head (e.g. for leukemia or brain tumors), from surgery, from trauma, or from intracranial disease (e.g. hydrocephalus)
autoimmune inflammation (hypophysitis)
ischemic or hemorrhagic infarction from low blood pressure (Sheehan syndrome) or hemorrhage pituitary apoplexyThere are a variety of rare diseases that resemble GH deficiency, including the childhood growth failure, facial appearance, delayed bone age, and low insulin-like growth factor-1 (IGF-1) levels. However, GH testing elicits normal or high levels of GH in the blood, demonstrating that the problem is not due to a deficiency of GH but rather to a reduced sensitivity to its action. Insensitivity to GH is traditionally termed Laron dwarfism, but over the last 15 years many different types of GH resistance have been identified, primarily involving mutations of the GH binding protein or receptors.Familial isolated growth hormone deficiency (IGHD) can be inherited as an autosomal recessive (type I), autosomal dominant (type II), or X-linked (type III) characteristic.

Pathophysiology
As an adult ages, it is normal for the pituitary to produce diminishing amounts of GH and many other hormones, particularly the sex steroids. Physicians, therefore, distinguish between the natural reduction in GH levels which comes with age, and the much lower levels of "true" deficiency. Such deficiency almost always has an identifiable cause, with adult-onset GHD without a definable cause ("idiopathic GH deficiency") extremely rare. GH does function in adulthood to maintain muscle and bone mass and strength, and has poorly understood effects on cognition and mood.

Diagnosis
Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians, therefore use a combination of indirect and direct criteria in assessing GHD, including:
Auxologic criteria (defined by body measurements)
Indirect hormonal criteria (IGF levels from a single blood sample)
Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:
Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours
Subnormal GH secretion in response to at least two provocative stimuli
Increased IGF1 levels after a few days of GH treatment
Response to GH treatment
Corroborative evidence of pituitary dysfunction"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15-minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine, levodopa, clonidine, epinephrine and propranolol, glucagon, and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults, and so is the test of choice.
Severe GH deficiency in childhood additionally has the following measurable characteristics:
Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency
Below-normal velocity of growth
Delayed physical maturation
Delayed bone age
Low levels of IGF1, IGF2, IGF binding protein 3
Increased growth velocity after a few months of GH treatmentIn childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.

Classification
Growth hormone deficiency can be congenital or acquired in childhood or adult life. It can be partial or complete. It is usually permanent, but sometimes transient. It may be an isolated deficiency or occur in association with deficiencies of other pituitary hormones.The term hypopituitarism is often used interchangeably with GH deficiency but more often denotes GH deficiency plus deficiency of at least one other anterior pituitary hormone. When GH deficiency (usually with other anterior pituitary deficiencies) is associated with posterior pituitary hormone deficiency (usually diabetes insipidus), the condition is termed panhypopituitarism.

Treatment
GH deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985, recombinant human growth hormone (rHGH) is a recombinant form of human GH produced by genetically engineered bacteria, manufactured by recombinant DNA technology. In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial.

Child
GH treatment is not recommended for children who are not growing despite having normal levels of growth hormone, and in the UK it is not licensed for this use. Children requiring treatment usually receive daily injections of growth hormone. Most pediatric endocrinologists monitor growth and adjust dose every 3–6 months and many of these visits involve blood tests and x-rays. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes, pen injectors, or a needle-free delivery system reduce the discomfort. Injection sites include the biceps, thigh, buttocks, and stomach. Injection sites should be rotated daily to avoid lipoatrophy. Treatment is expensive, costing as much as US$10,000 to $40,000 a year in the US.

Adults
GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion. It may be appropriate in diagnosed adult-onset deficiency, where a weekly dose of approximately 25% of that given to children is given. Lower doses again are called for in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-1.In many countries, including the UK, the majority view among endocrinologists is that the failure of treatment to provide any demonstrable, measurable benefits in terms of outcomes means treatment is not recommended for all adults with severe GHD, and national guidelines in the UK as set out by NICE suggest three criteria which all need to be met for treatment to be indicated:

Severe GH deficiency, defined as a peak GH response of <9mU/litre during an insulin tolerance test
Perceived impairment of quality of life, as assessed by questionnaire
They are already treated for other pituitary hormone disordersWhere treatment is indicated, duration is dependent upon indication.
Cost of adult treatment in the UK is 3000-4000 GBP annually.

Side effects
Headaches
Joint pain and muscle pain
Fluid retention, and carpal tunnel syndrome
Mild hypertension
Visual problems
Nausea and vomiting
Paraesthesiae
Antibody formation
Reactions at the injection site
Rarely, benign intracranial hypertension.

Prognosis
Child
When treated with GH, a severely deficient child will begin to grow faster within months </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 Maffucci syndrome and can you explain it in depth? [/INST] Maffucci syndrome is a very rare disorder in which multiple benign tumors of cartilage develop within the bones (such tumors are known as enchondromas). The tumors most commonly appear in the bones of the hands, feet, and limbs, causing bone deformities and short limbs.It is named for the Italian pathologist Angelo Maffucci who described it in 1881. Fewer than 200 cases of this syndrome have been reported.

Signs and symptoms
Patients are normal at birth and the syndrome manifests during childhood and puberty.The enchondromas affect the extremities and their distribution is asymmetrical. The most common sites of enchondromas are the metacarpal bones and phalanges of the hands. The feet are less commonly affected.
Disfigurations of the extremities are a result. Pathological fractures can arise in affected metaphyses and diaphyses of the long bones and are common (26%).
The risk for sarcomatous degeneration of enchondromas, hemangiomas, or lymphangiomas is 15–30% in the setting of Maffucci syndrome. Maffucci syndrome is associated with a higher risk of CNS, pancreatic, and ovarian malignancies. Multiple enchondromas may present in three disorders: Ollier disease, Maffucci syndrome, and metachondromatosis </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 Eumycetoma and can you explain it in depth? [/INST] Eumycetoma, also known as Madura foot, is a persistent fungal infection of the skin and the tissues just under the skin, affecting most commonly the feet, although it can occur in hands and other body parts.  It starts as a painless wet nodule, which may be present for years before ulceration, swelling, grainy discharge and weeping from sinuses and fistulae, followed by bone deformity.Several fungi can cause eumycetoma, including: Madurella mycetomatis, Madurella grisea, Leptosphaeria senegalensis, Curvularia lunata, Scedosporium apiospermum, Neotestudina rosatii, and Acremonium and Fusarium species. Diagnosis is by biopsy, visualising the fungi under the microscope and culture. Medical imaging may reveal extent of bone involvement. Other tests include ELISA, immunodiffusion, and DNA Barcoding.Treatment includes surgical removal of affected tissue and antifungal medicines. After treatment, recurrence is common. Sometimes, amputation is required.The infection occurs generally in the tropics, and is endemic in Sub-Saharan Africa, especially Sudan, India, parts of South America and Mexico. Few cases have been reported across North African. Mycetoma is probably low-endemic to Egypt with predilection for eumycetoma. In 2016, the World Health Organization recognised eumycetoma as a neglected tropical disease.

Signs and symptoms
The initial lesion is a small swelling under the skin following minor trauma. It appears as a painless wet nodule, which may be present for years before ulceration, swelling and weeping from sinuses, followed by bone deformity. The sinuses discharge a grainy liquid of fungal colonies. These grains are usually black or white. Destruction of deeper tissues, and deformity and loss of function in the affected limbs may occur in later stages. It tends to occur in one foot.  Mycetoma due to bacteria has similar clinical features.

Causes
Eumycetoma is a type of mycetoma caused by fungi. Mycetoma caused by bacteria from the phylum Actinomycetes is different.  Both have similar clinical features.The most common fungi causing white discharge is Pseudallescheria boydii. Other causative agents of non-black grain eumycetoma include Acremonium and Fusarium species.Black discharge tends to be caused by species from the genera Madurella, Pyrenochaeta, Exophiala, Leptosphaeria and Curvularia. The most common species are Madurella mycetomatis and Trematospheria grisea (previously called Madurella grisea).

Mechanism
The disease is acquired by entry of the fungal spores from the soil through a breach in the skin produced by minor trauma like a thorn prick. The disease then spreads to deeper tissues and also forms sinus tracts leading to skin surface. Mature lesions are characterised by a grainy discharge from these sinuses. These discharges contain fungal colonies and are infective. Spread of infection internally through blood or lymph is uncommon.Infections that produce a black discharge mainly spread subcutaneously. In the red and yellow varieties deep spread occurs early, infiltrating muscles and bones but sparing nerves and tendons, which are highly resistant to the invasion.Botryomycosis, also known as bacterial pseudomycosis, produces a similar clinical picture and is caused usually by Staphylococcus aureus. Other bacteria may also cause botryomycosis.

Diagnosis
Diagnosis is by biopsy, visualising the fungi under the microscope and culture, which show characteristic fungal filaments and vesicles characteristic of the fungi. Other tests include ELISA, immunodiffusion, and PCR with DNA sequencing (so-called DNA barcoding).X rays and ultrasonography may be carried out to assess the extent of the disease. X rays findings are extremely variable. The disease is most often observed at an advanced stage that exhibits extensive destruction of all bones of the foot </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 Histrionic personality disorder and can you explain it in depth? [/INST] Histrionic personality disorder (HPD) is defined by the American Psychiatric Association as a personality disorder characterized by a pattern of excessive attention-seeking behaviors, usually beginning in early childhood, including inappropriate seduction and an excessive desire for approval. People diagnosed with the disorder are said to be lively, dramatic, vivacious, enthusiastic, extroverted and flirtatious.

HPD lies in the dramatic cluster of personality disorders. People with HPD have a high desire for attention, make loud and inappropriate appearances, exaggerate their behaviors and emotions, and crave stimulation. They may exhibit sexually provocative behavior, express strong emotions with an impressionistic style, and can be easily influenced by others. Associated features include egocentrism, self-indulgence, continuous longing for appreciation, and persistent manipulative behavior to achieve their own wants.

Signs and symptoms
People diagnosed with HPD may be dramatic. They often fail to see their own personal situation realistically, instead dramatizing and exaggerating their difficulties. Patients with this disorder can have rapidly shifting emotions and a decreased ability to recognize others emotions. Their emotions may appear superficial or exaggerated to others. This disorder is associated with extraversion, a lower tolerance for frustration or delayed gratification, and openness to new experiences. People with HPD may have little self-doubt and often appear egocentric.Research has also shown those with histrionic personality have a greater desire for social approval and reassurance and will constantly seek it out, making those with HPD more vulnerable to social media addiction. People with this disorder often display excessive sensitivity to criticism or disapproval. They will work hard to get others to pay attention to them, possibly as a method of testing the stability of relationships. They may enjoy situations in which they can be the center of attention, and may feel uncomfortable when people are not paying attention to them. It is common for people with this disorder to wear flamboyant clothing, try body modifications, and fake medical conditions in an attempt to draw others attention. They may display inappropriately sexually provocative, flirtatious, or exploitative behavior. Sexting and exhibitionist behavior are also behaviors people with this condition sometimes exhibit. Some people with histrionic traits or personality disorder change their seduction technique into a more maternal or paternal style as they age. When their desire for attention is not met, it can heighten the severity of their symptoms. They tend to be impressionable and easily manipulatable, especially by those they respect.Patients with HPD are usually high-functioning, both socially and professionally. They usually have good social skills, despite tending to use them to make themselves the center of attention. HPD may also affect a persons social and romantic relationships, as well as their ability to cope with losses or failures. People with HPD tend to consider relationships closer than they usually are. They may seek treatment for clinical depression when romantic (or other close personal) relationships end. Substance disorders, such as Alcohol Use Disorder or Opioid use disorder, are all common in patients with Histrionic Personality Disorder. They are also at higher risks of suicide, body dysmorphia, and divorce. They may go through frequent job changes, as they become easily bored and may prefer withdrawing from frustration (instead of facing it). Because they tend to crave novelty and excitement, they may place themselves in risky situations. All of these factors may lead to greater risk of developing clinical depression. People with this condition can have an impressionistic and undetailed style of speech.Despite these traits they can be prideful of their own personality, and may be unwilling to change, viewing any change as a threat. They may even blame their personal failures or disappointments on others.

Causes
Little research has been done to find evidence of what causes histrionic personality disorder. Although direct causes are inconclusive, various theories and studies suggest multiple possible causes, of a neurochemical, genetic, psychoanalytic, or environmental nature. Traits such as extravagance, vanity, and seductiveness of hysteria have similar qualities to women diagnosed with HPD. HPD symptoms typically do not fully develop until the age of 15, while the onset of treatment only occurs, on average, at approximately 40 years of age.

Neurochemical/physiological
Studies have shown that there is a strong correlation between the function of neurotransmitters and the Cluster B personality disorders such as HPD. Individuals diagnosed with HPD have a highly responsive noradrenergic system, which is responsible for the synthesis, storage, and release of the neurotransmitter norepinephrine. High levels of norepinephrine lead to anxiety-proneness, dependency, and high sociability.

Genetic
Twin studies have aided in breaking down the genetic vs. environment debate. A twin study conducted by the Department of Psychology at Oslo University attempted to establish a correlation between genetics and Cluster B personality disorders. With a test sample of 221 twins, 92 monozygotic and 129 dizygotic, researchers interviewed the subjects using the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and concluded that there was a correlation of 0.67 that histrionic personality disorder is hereditary.

Psychoanalytic theory
Though criticised as being unsupported by scientific evidence, psychoanalytic theories incriminate authoritarian or distant attitudes by one (mainly the mother) or both parents, along with conditional love based on expectations the child can never fully meet. Using psychoanalysis, Freud believed that lustfulness was a projection of the patients lack of ability to love unconditionally and develop cognitively to maturity, and that such patients were overall emotionally shallow. He believed the reason for being unable to love could have resulted from a traumatic experience, such as the death of a close relative during childhood or divorce of ones parents, which gave the wrong impression of committed relationships. Exposure to one or multiple traumatic occurrences of a close friend or family members leaving (via abandonment or mortality) would make the person unable to form true and affectionate attachments towards other people.

HPD and antisocial personality disorder
Another theory suggests a possible relationship between histrionic personality disorder and antisocial personality disorder. Research has found 2/3 of patients diagnosed with histrionic personality disorder also meet criteria similar to those of the antisocial personality disorder, which suggests both disorders based towards sex-type expressions may have the same underlying cause.
Some family history studies have found that histrionic personality disorder, as well as borderline and antisocial personality disorders, tend to run in families, but it is unclear how much is due to genetic versus environmental factors. Both examples suggest that predisposition could be a factor as to why certain people are diagnosed with histrionic personality disorder, however little is known about whether or not the disorder is influenced by any biological compound or is genetically inheritable. Little research has been conducted to determine the biological sources, if any, of this disorder.

Diagnosis
The persons appearance, behavior and history, along with a psychological evaluation, are usually sufficient to establish a diagnosis. There is no test to confirm this diagnosis. Because the criteria are subjective, some people may be wrongly diagnosed.

DSM 5
The current edition of the Diagnostic and Statistical Manual of Mental Disorders, DSM 5, defines histrionic personality disorder (in Cluster B) as:
A pervasive pattern of excessive emotionality and attention-seeking, beginning by early adulthood and present in a variety of contexts, as indicated by five (or more) of the following:
is uncomfortable in situations in which he or she is not the center of attention
interaction with others is often characterized by inappropriate sexually seductive or provocative behavior
displays rapidly shifting and shallow expression of emotions
consistently uses physical appearance to draw attention to self
has a style of speech that is excessively impressionistic and lacking in detail
shows self-dramatization, theatricality, and exaggerated expression of emotion
is suggestible, i.e., easily influenced by others or circumstances
considers relationships to be more intimate than they actually are
The DSM 5 requires that a diagnosis for any specific personality disorder also satisfies a set of general personality disorder criteria.

ICD-10
The World Health Organizations ICD-10 lists histrionic personality disorder as:
A personality disorder characterized by:
shallow and labile affectivity,
self-dramatization,
theatricality,
exaggerated expression of emotions,
suggestibility,
egocentricity,
self-indulgence,
lack of consideration for others,
easily hurt feelings, and
continuous seeking for appreciation, excitement and attention.
It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria.

Comorbidity
Most histrionics also have other mental disorders. Comorbid conditions include: antisocial, dependent, borderline, and narcissistic personality disorders, as well as depression, anxiety disorders, panic disorder, somatoform disorders, anorexia nervosa, substance use disorder and attachment disorders, including reactive attachment disorder.

Millons subtypes
Theodore Millon identified six subtypes of histrionic personality disorder. Any individual histrionic may exhibit one or more of the following:

Treatment
Treatment is often prompted by depression associated with dissolved romantic relationships. Medication does little to affect the personality disorder, but may be helpful with symptoms such as depression. Treatment for HPD itself involves psychotherapy, including cognitive therapy.

Interviews and self-report methods
In general clinical practice with assessment of personality disorders, one form of interview is the most popular: an unstructured interview. The actual preferred method is a semi-structured interview but there is reluctance to use this type of interview because they can seem impractical or superficial. The reason that a semi-structured interview is preferred over an unstructured interview is that semi-structured interviews tend to be more objective, systematic, replicable, and comprehensive. Unstructured interviews, despite their popularity, tend to have problems with unreliability and are susceptible to errors leading to false assumptions of the patient.One of the single most successful methods for assessing personality disorders by researchers of normal personality functioning is the self-report inventory following up with a semi-structured interview. There are some disadvantages with the self-report inventory method that with histrionic personality disorder there is a distortion in character, self-presentation, and self-image. This cannot be assessed simply by asking most clients if they match the criteria for the disorder. Most projective testing depend less on the ability or willingness of the person to provide an accurate description of the self, but there is currently limited empirical evidence on projective testing to assess histrionic personality disorder.

Functional analytic psychotherapy
Another way to treat histrionic personality disorder after identification is through functional analytic psychotherapy. The job of a Functional Analytic Psychotherapist is to identify the interpersonal problems with the patient as they happen in session or out of session. Initial goals of functional analytic psychotherapy are set by the therapist and include behaviors that fit the clients needs for improvement. Functional analytic psychotherapy differs from the traditional psychotherapy due to the fact that the therapist directly addresses the patterns of behavior as they occur in-session.The in-session behaviors of the patient or client are considered to be examples of their patterns of poor interpersonal communication and to adjust their neurotic defenses. To do this, the therapist must act on the clients behavior as it happens in real time and give feedback on how the clients behavior is affecting their relationship during therapy. The therapist also helps the client with histrionic personality disorder by denoting behaviors that happen outside of treatment; these behaviors are termed "Outside Problems" and "Outside Improvements". This allows the therapist to assist in problems and improvements outside of session and to verbally support the client and condition optimal patterns of behavior". This then can reflect on how they are advancing in-session and outside of session by generalizing their behaviors over time for changes or improvement".

Coding client and therapist behaviors
In these sessions there is a certain set of dialogue or script that can be forced by the therapist for the client to give insight on their behaviors and reasoning". Here is an example from" the conversation is hypothetical. T = therapist C = Client This coded dialogue can be transcribed as:

ECRB – Evoking clinically relevant behavior
T: Tell me how you feel coming in here today (CRB2) C: Well, to be honest, I was nervous. Sometimes I feel worried about how things will go, but I am really glad I am here.
CRB1 – In-session problems
C: Whatever, you always say that. (becomes quiet). I dont know what I am doing talking so much.
CRB2 – In-session improvements
TCRB1 – Clinically relevant response to client problems
T: Now you seem to be withdrawing from me. That makes it hard for me to give you what you might need from me right now. What do you think you want from me as we are talking right now?".
TCRB2 – Responses to client improvement
T: Thats great. I am glad youre here, too. I look forward to talking to you.

Functional ideographic assessment template
Another example of treatment besides coding is functional ideographic assessment template. The functional ideographic assessment template, also known as FIAT, was used as a way to generalize the clinical processes of functional analytic psychotherapy. The template was made by a combined effort of therapists and can be used to represent the behaviors that are a focus for this treatment. Using the FIAT therapists can create a common language to get stable and accurate communication results through functional analytic psychotherapy at the ease of the client; as well as the therapist.

Epidemiology
The survey data from the National epidemiological survey from 2001 to 2002 suggests a prevalence of HPD of 1.84 percent. Major character traits may be inherited, while other traits may be due to a combination of genetics and environment, including childhood experiences </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 Lepromatous leprosy and can you explain it in depth? [/INST] Lepromatous leprosy is a form of leprosy characterized by pale macules in the skin.: 346 It results from the failure of Th1 cell activation which is necessary to eradicate the mycobacteria (Th1 response is required to activate macrophages that engulf and contain the disease). In lepromatous leprosy, TH2 response is turned on, and because of reciprocal inhibition (IL-4; IL-10), the cell-mediated response (TH1) is depressed. Lepromatous leprosy,  in contrast to the tuberculoid form of leprosy,  is characterized by the absence of epithelioid cells in the lesions </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Reactive perforating collagenosis 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 Bone fracture and can you explain it in depth? [/INST] A bone fracture  (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of a bone. In more severe cases, the bone may be broken into several fragments, known as a comminuted fracture. A bone fracture may be the result of high force impact or stress, or a minimal trauma injury as a result of certain medical conditions that weaken the bones, such as osteoporosis, osteopenia, bone cancer, or osteogenesis imperfecta, where the fracture is then properly termed a pathologic fracture.

Signs and symptoms
Although bone tissue contains no pain receptors, a bone fracture is painful for several reasons:
Breaking in the continuity of the periosteum, with or without similar discontinuity in endosteum, as both contain multiple pain receptors.
Edema and hematoma of nearby soft tissues caused by ruptured bone marrow evokes pressure pain.
Involuntary muscle spasms trying to hold bone fragments in place.Damage to adjacent structures such as nerves, muscles or blood vessels, spinal cord, and nerve roots (for spine fractures), or cranial contents (for skull fractures) may cause other specific signs and symptoms.

Complications
Some fractures may lead to serious complications including a condition known as compartment syndrome. If not treated, eventually, compartment syndrome may require amputation of the affected limb. Other complications may include non-union, where the fractured bone fails to heal or mal-union, where the fractured bone heals in a deformed manner. One form of malunion is the malrotation of a bone, which is especially common after femoral and tibial fractures.
Complications of fractures may be classified into three broad groups, depending upon their time of occurrence. These are as follows –

Immediate complications – occurs at the time of the fracture.
Early complications – occurring in the initial few days after the fracture.
Late complications – occurring a long time after the fracture.

Pathophysiology
The natural process of healing a fracture starts when the injured bone and surrounding tissues bleed, forming a fracture hematoma. The blood coagulates to form a blood clot situated between the broken fragments. Within a few days, blood vessels grow into the jelly-like matrix of the blood clot. The new blood vessels bring phagocytes to the area, which gradually removes the non-viable material. The blood vessels also bring fibroblasts in the walls of the vessels and these multiply and produce collagen fibres. In this way, the blood clot is replaced by a matrix of collagen. Collagens rubbery consistency allows bone fragments to move only a small amount unless severe or persistent force is applied.At this stage, some of the fibroblasts begin to lay down bone matrix in the form of collagen monomers. These monomers spontaneously assemble to form the bone matrix, for which bone crystals (calcium hydroxyapatite) are deposited in amongst, in the form of insoluble crystals. This mineralization of the collagen matrix stiffens it and transforms it into bone. In fact, bone is a mineralized collagen matrix; if the mineral is dissolved out of bone, it becomes rubbery. Healing bone callus on average is sufficiently mineralized to show up on X-ray within 6 weeks in adults and less in children. This initial "woven" bone does not have the strong mechanical properties of mature bone. By a process of remodelling, the woven bone is replaced by mature "lamellar" bone. The whole process may take up to 18 months, but in adults, the strength of the healing bone is usually 80% of normal by 3 months after the injury.Several factors may help or hinder the bone healing process. For example, tobacco smoking hinders the process of bone healing, and adequate nutrition (including calcium intake) will help the bone healing process. Weight-bearing stress on bone, after the bone has healed sufficiently to bear the weight, also builds bone strength.
Although there are theoretical concerns about NSAIDs slowing the rate of healing, there is not enough evidence to warrant withholding the use of this type analgesic in simple fractures.

Effects of smoking
Smokers generally have lower bone density than non-smokers, so they have a much higher risk of fractures. There is also evidence that smoking delays bone healing.

Diagnosis
A bone fracture may be diagnosed based on the history given and the physical examination performed. Radiographic imaging often is performed to confirm the diagnosis. Under certain circumstances, radiographic examination of the nearby joints is indicated in order to exclude dislocations and fracture-dislocations. In situations where projectional radiography alone is insufficient, Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) may be indicated.

Classification
In orthopedic medicine, fractures are classified in various ways. Historically they are named after the physician who first described the fracture conditions, however, there are more systematic classifications as well.They may be divided into stable versus unstable depending on the likelihood that they may shift further.

Mechanism
Traumatic fracture – a fracture due to sustained trauma. e.g., fractures caused by a fall, road traffic accident, fight, etc.
Pathologic fracture – a fracture through a bone that has been made weak by some underlying disease is called pathological fracture. e.g., a fracture through a bone weakened by metastasis. Osteoporosis is the most common cause of pathological fracture.
Periprosthetic fracture – a fracture at the point of mechanical weakness at the end of an implant

Soft-tissue involvement
Closed/simple fractures are those in which the overlying skin is intact
Open/compound fractures involve wounds that communicate with the fracture, or where fracture hematoma is exposed, and may thus expose bone to contamination. Open injuries carry a higher risk of infection. Reports indicate an incidence of infection after internal fixation of closed fracture of 1-2%, rising to 30% in open fractures.Clean fracture
Contaminated fracture

Displacement
Non-displaced
Displaced
Translated, or ad latus, with sideways displacement.
Angulated
Rotated
Shortened, a reduction in overall bone length when displaced fracture fragments overlap

Fracture pattern
Linear fracture – a fracture that is parallel to the bones long axis
Transverse fracture – a fracture that is at a right angle to the bones long axis
Oblique fracture – a fracture that is diagonal to a bones long axis (more than 30°)
Spiral fracture – a fracture where at least one part of the bone has been twisted
Compression fracture/wedge fracture – usually occurs in the vertebrae, for example when the front portion of a vertebra in the spine collapses due to osteoporosis (a medical condition which causes bones to become brittle and susceptible to fracture, with or without trauma)
Impacted fracture – a fracture caused when bone fragments are driven into each other
Avulsion fracture – a fracture where a fragment of bone is separated from the main mass

Fragments
Incomplete fracture – a fracture in which the bone fragments are still partially joined, in such cases, there is a crack in the osseous tissue that does not completely traverse the width of the bone.
Complete fracture – a fracture in which bone fragments separate completely.
Comminuted fracture – a fracture in which the bone has broken into several pieces.

Anatomical location
An anatomical classification may begin with specifying the involved body part, such as the head or arm, followed by more specific localization. Fractures that have additional definition criteria than merely localization often may be classified as subtypes of fractures, such as a Holstein-Lewis fracture being a subtype of a humerus fracture. Most typical examples in an orthopaedic classification given in the previous section cannot be classified appropriately into any specific part of an anatomical classification, however, as they may apply to multiple anatomical fracture sites.

Skull fracture
Basilar skull fracture
Blowout fracture – a fracture of the walls or floor of the orbit
Mandibular fracture
Nasal fracture
Le Fort fracture of skull – facial fractures involving the maxillary bone and surrounding structures in a usually bilateral and either horizontal, pyramidal, or transverse way.
Spinal fracture
Cervical fracture
Fracture of C1, including Jefferson fracture
Fracture of C2, including Hangmans fracture
Flexion teardrop fracture – a fracture of the anteroinferior aspect of a cervical vertebral
Clay-shoveler fracture – fracture through the spinous process of a vertebra occurring at any of the lower cervical or upper thoracic vertebrae
Burst fracture – in which a vertebra breaks from a high-energy axial load
Compression fracture – a collapse of a vertebra, often in the form of wedge fractures due to larger compression anteriorly
Chance fracture – compression injury to the anterior portion of a vertebral body with concomitant distraction injury to posterior elements
Holdsworth fracture – an unstable fracture dislocation of the thoraco lumbar junction of the spine
Rib fracture
Sternal fracture
Shoulder fracture
Clavicle fracture
Scapular fracture
Arm fracture
Humerus fracture (fracture of upper arm)
Supracondylar fracture
Holstein-Lewis fracture – a fracture of the distal third of the humerus resulting in entrapment of the radial nerve
Forearm fracture
Ulnar fracture
Monteggia fracture – a fracture of the proximal third of the ulna with the dislocation of the head of the radius
Hume fracture – a fracture of the olecranon with an associated anterior dislocation of the radial head
Radius fracture
Essex-Lopresti fracture – a fracture of the radial head with concomitant dislocation of the distal radio-ulnar joint with disruption of the interosseous membrane
Distal radius fracture
Galeazzi fracture – a fracture of the radius with dislocation of the distal radioulnar joint
Colles fracture – a distal fracture of the radius with dorsal (posterior) displacement of the wrist and hand
Smiths fracture – a distal fracture of the radius with volar (ventral) displacement of the wrist and hand
Bartons fracture – an intra-articular fracture of the distal radius with dislocation of the radiocarpal joint
Hand fracture
Scaphoid fracture
Rolando fracture – a comminuted intra-articular fracture through the base of the first metacarpal bone
Bennetts fracture – a fracture of the base of the first metacarpal bone which extends into the carpometacarpal (CMC) joint
Boxers fracture – a fracture at the neck of a metacarpal
Broken finger – a fracture of the carpal phalanges
Pelvic fracture
Fracture of the hip bone
Duverney fracture – an isolated pelvic fracture involving only the iliac wing
Femoral fracture
Hip fracture (anatomically a fracture of the femur bone and not the hip bone)
Patella fracture
Crus fracture
Tibia fracture
Pilon fracture
Tibial plateau fracture
Bumper fracture – a fracture of the lateral tibial plateau caused by a forced valgus applied to the knee
Segond fracture – an avulsion fracture of the lateral tibial condyle
Gosselin fracture – a fractures of the tibial plafond into anterior and posterior fragments
Toddlers fracture – an undisplaced and spiral fracture of the distal third to distal half of the tibia
Fibular fracture
Maisonneuve fracture – a spiral fracture of the proximal third of the fibula associated with a tear of the distal tibiofibular syndesmosis and the interosseous membrane
Le Fort fracture of ankle – a vertical fracture of the antero-medial part of the distal fibula with avulsion of the anterior tibiofibular ligament
Bosworth fracture – a fracture with an associated fixed posterior dislocation of the distal fibular fragment that becomes trapped behind the posterior tibial tubercle; the injury is caused by severe external rotation of the ankle
Combined tibia and fibula fracture
Trimalleolar fracture – involving the lateral malleolus, medial malleolus, and the distal posterior aspect of the tibia
Bimalleolar fracture – involving the lateral malleolus and the medial malleolus
Potts fracture
Foot fracture
Lisfranc fracture – in which one or all of the metatarsals are displaced from the tarsus
Jones fracture – a fracture of the proximal end of the fifth metatarsal
March fracture – a fracture of the distal third of one of the metatarsals occurring because of recurrent stress
Cuneiform fracture – a fracture of one of the three cuneiform bones typically due to direct blow, axial load, or avulsion
Calcaneal fracture – a fracture of the calcaneus (heel bone)
Broken toe – a fracture of the pedal phalanges

OTA/AO classification
The Orthopaedic Trauma Association Committee for Coding and Classification published its classification system  in 1996, adopting a similar system to the 1987 AO Foundation system. In 2007, they extended their system, unifying the two systems regarding wrist, hand, foot, and ankle fractures.

Classifications named after people
A number of classifications are named after the person (eponymous) who developed it.

"Denis classification" for spinal fractures
"Frykman classification" for forearm fractures (fractures of radius and ulna)
"Gustilo open fracture classification"
"Letournel and Judet Classification" for Acetabular fractures
"Neer classification" for humerus fractures
Seinsheimer classification, Evans-Jensen classification, Pipkin classification, and Garden classification for hip fractures

Prevention
Both high- and low-force trauma can cause bone fracture injuries. Preventive efforts to reduce motor vehicle crashes, the most common cause of high-force trauma, include reducing distractions while driving. Common distractions are driving under the influence and texting or calling while driving, both of which lead to an approximate 6-fold increase in crashes. Wearing a seatbelt can also reduce the likelihood of injury in a collision. 30 km/h or 20 mph speed limits (as opposed to the more common intracity 50 km/h / 30 mph) also drastically reduce the risk of accident, serious injury and even death in crashes between motor vehicles and humans. Vision Zero aims to reduce traffic deaths to zero through better traffic design and other measures and to drastically reduce traffic injuries which would prevent many bone fractures.
A common cause of low-force trauma is an at-home fall. When considering preventative efforts, the National Institute of Health (NIH) examines ways to reduce the likelihood of falling, the force of the fall, and bone fragility. To prevent at-home falls they suggest keeping cords out of high-traffic areas where someone could trip, installing handrails and keeping stairways well-lit, and installing an assistive bar near the bathtub in the washroom for support. To reduce the impact of a fall the NIH recommends to try falling straight down on your buttocks or onto your hands.Some sports have a relatively high risk of bone fractures as a common sports injury. Preventive measures depend to some extent on the specific sport, but learning proper technique, wearing  protective gear and having a realistic estimation of ones own capabilities and limitations can all help reduce the risk of bone fracture. In contact sports rules have been put in place to protect athlete health, such as the prohibition of unnecessary roughness in American football.
Taking calcium and vitamin D supplements can help strengthen your bones. Vitamin D supplements combined with additional calcium marginally reduces the risk of hip fractures and other types of fracture in older adults; however, vitamin D supplementation alone did not reduce the risk of fractures.

Patterns
Treatment
Treatment of bone fractures are broadly classified as surgical or conservative, the latter basically referring to any non-surgical procedure, such as pain management, immobilization or other non-surgical stabilization. A similar classification is open versus closed treatment, in which open treatment refers to any treatment in which the fracture site is opened surgically, regardless of whether the fracture is an open or closed fracture.

Pain management
In arm fractures in children, ibuprofen has been found to be as effective as a combination of paracetamol and codeine. In the ems setting it might be applicable to administer 1mg/kg of iv ketamine to achieve a dissociated state.

Immobilization
Since bone healing is a natural process that will occur most often, fracture treatment aims to ensure the best possible function of the injured part after healing. Bone fractures typically are treated by restoring the fractured pieces of bone to their natural positions (if necessary), and maintaining those positions while the bone heals. Often, aligning the bone, called reduction, in a good position and verifying the improved alignment with an X-ray is all that is needed. This process is extremely painful without anaesthesia, about as painful as breaking the bone itself. To this end, a fractured limb usually is immobilized with a plaster or fibreglass cast or splint that holds the bones in position and immobilizes the joints above and below the fracture. When the initial post-fracture oedema or swelling goes down, the fracture may be placed in a removable brace or orthosis. If being treated with surgery, surgical nails, screws, plates, and wires are used to hold the fractured bone together more directly. Alternatively, fractured bones may be treated by the Ilizarov method which is a form of an external fixator.
Occasionally smaller bones, such as phalanges of the toes and fingers, may be treated without the cast, by buddy wrapping them, which serves a similar function to making a cast. A device called a Suzuki frame may be used in cases of deep, complex intra-articular digit fractures. By allowing only limited movement, immobilization helps preserve anatomical alignment while enabling callus formation, toward the target of achieving union.
Splinting results in the same outcome as casting in children who have a distal radius fracture with little shifting.

Surgery
Surgical methods of treating fractures have their own risks and benefits, but usually, surgery is performed only if conservative treatment has failed, is very likely to fail, or is likely to result in a poor functional outcome. With some fractures such as hip fractures (usually caused by osteoporosis), surgery is offered routinely because non-operative treatment results in prolonged immobilisation, which commonly results in complications including chest infections, pressure sores, deconditioning, deep vein thrombosis (DVT), and pulmonary embolism, which are more dangerous than surgery. When a joint surface is damaged by a fracture, surgery is also commonly recommended to make an accurate anatomical reduction and restore the smoothness of the joint.
Infection is especially dangerous in bones, due to the recrudescent nature of bone infections. Bone tissue is predominantly extracellular matrix, rather than living cells, and the few blood vessels needed to support this low metabolism are only able to bring a limited number of immune cells to an injury to fight infection. For this reason, open fractures and osteotomies call for very careful antiseptic procedures and prophylactic use of antibiotics.
Occasionally, bone grafting is used to treat a fracture.Sometimes bones are reinforced with metal. These implants must be designed and installed with care. Stress shielding occurs when plates or screws carry too large of a portion of the bones load, causing atrophy </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 Siti 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 Aggressive angiomyxoma 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 Trigger finger and can you explain it in depth? [/INST] Trigger finger, also known as stenosing tenosynovitis, is  a disorder characterized by catching or locking of the involved finger in full or near full flexion, typically with force. There may be tenderness in the palm of the hand near the last skin crease (distal palmar crease). The name "trigger finger" may refer to the motion of "catching" like a trigger on a gun. The ring finger and thumb are most commonly affected.The problem is generally idiopathic (no known cause). There may be an association with diabetes. The pathophysiology is enlargement of the flexor tendon and the A1 pulley of the tendon sheath.  While often referred to as a type of stenosing tenosynovitis (which implies inflammation) the pathology is mucoid degeneration. Mucoid degeneration is when fibrous tissue such as tendon has less organized collagen, more abundant extra-cellular matrix, and changes in the cells (fibrocytes) to act and look more like cartilage cells (chondroid metaplasia). Diagnosis is typically based on symptoms and signs after excluding other possible causes.Trigger digits can resolve without treatment. Treatment options that are disease modifying include steroid injections and surgery. Splinting immobilization of the finger may or may not be disease modifying.

Signs and symptoms
Symptoms include catching or locking of the involved finger when it is forcefully flexed. There may be tenderness in the palm of the hand near the last skin crease (distal palmar crease). Often a nodule can be felt in this area. There is some evidence that idiopathic trigger finger behaves differently in people with diabetes.

Causes
It is important to distinguish association and causation. The vast majority of trigger digits are idiopathic, meaning there is no known cause.
Some speculate that repetitive forceful use of a digit leads to narrowing of the fibrous digital sheath in which it runs, but there is little scientific data to support this theory. The relationship of trigger finger to work activities is debatable and there are arguments for and against a relationship to hand use with no experimental evidence supporting a relationship.

Diagnosis
Diagnosis is made on interview and physical examination. More than one finger may be affected at a time. It is most common in the thumb and ring finger. The triggering more often occurs while gripping an object firmly or during sleep when the palm of the subject’s hand remains closed for an extended period of time. Upon waking, the affected person may have to force the triggered fingers open with their other hand. In some, this can be a daily occurrence.

Treatment
Corticosteroid injections can cure trigger digits.
Treatment consists of injection of a corticosteroid such as methylprednisolone often combined with a local anesthetic (lidocaine) at the A1 pulley in the palm. The infiltration of the affected site is straightforward using standard anatomic landmarks. There is evidence that the steroid does not need to enter the sheath. The role of sonographic guidance is therefore debatable.
Injection of the tendon sheath with a corticosteroid is effective over weeks to months in more than half of people </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 Epiretinal membrane and can you explain it in depth? [/INST] Epiretinal membrane or macular pucker is a disease of the eye in response to changes in the vitreous humor or more rarely, diabetes. Sometimes, as a result of immune system response to protect the retina, cells converge in the macular area as the vitreous ages and pulls away in posterior vitreous detachment (PVD). PVD can create minor damage to the retina, stimulating exudate, inflammation, and leucocyte response. These cells can form a transparent layer gradually and, like all scar tissue, tighten to create tension on the retina which may bulge and pucker, or even cause swelling or macular edema. Often this results in distortions of vision that are clearly visible as bowing and blurring when looking at lines on chart paper (or an Amsler grid) within the macular area, or central 1.0 degree of visual arc. Usually it occurs in one eye first, and may cause binocular diplopia or double vision if the image from one eye is too different from the image of the other eye. The distortions can make objects look different in size (usually larger = macropsia), especially in the central portion of the visual field, creating a localized or field dependent aniseikonia that cannot be fully corrected optically with glasses. Partial correction often improves the binocular vision considerably though. In the young (under 50 years of age), these cells occasionally pull free and disintegrate on their own; but in the majority of those affected (over 60 years of age) the condition is permanent. The underlying photoreceptor cells, rod cells and cone cells, are usually not damaged unless the membrane becomes quite thick and hard; so usually there is no macular degeneration.

Cause
The source of the cells in epiretinal membranes (ERM) has been found to comprise glial cells, retinal pigment epithelial (RPE) cells, macrophages, fibrocytes, and collagen cells. These cells are found in varying proportions. Those from retinal breaks, previous retinal detachments, or cryopexy are composed mainly of dispersed RPE cells, while cells of glial origin predominate in idiopathic pathology. Laminocytes are the fundamental cell type in idiopathic ERMs. These cells are frequently found in small and dispersed numbers in eyes containing a PVD. The presence of retinal pigment cells invariably indicates proliferative retinopathy and is only seen in association with a retinal detachment or tear.
The incidence of associated PVD range from 75 to 93%, and PVD is present in virtually all eyes with retinal breaks or retinal detachments and subsequent ERM formation. PVD can lead to retinal breaks that may liberate RPE cells that initiate membrane formation. Small breaks in the internal limiting membrane (ILM) after PVD also may provide retinal astrocytes access to the vitreous cavity, where they may subsequently proliferate. Many ERM also have ILM fragments that may be peeled separately. Finally, vitreous hemorrhage, inflammation, or both associated with a PVD also may stimulate ERM formation.
Both sexes appear to be affected equally frequently.

Diagnosis
Epiretinal membrane is typically diagnosed by appearance with optical coherence tomography (OCT) of the macula. Features include a thickening of the nerve fiber layer, a serrated appearance to the surface of the retina just beneath a thickened layer of glial tissue at the retinal-vitreous interface.

Prevention
There is no good evidence for any preventive actions, since it appears this is a natural response to aging changes in the vitreous. It has been estimated that Posterior vitreous detachment (PVD) occurs in over 75 percent of the population over age 65, that PVD is essentially a harmless condition (although with some disturbing symptoms), and that it does not normally threaten sight. However, since epiretinal membrane appears to be a protective response to PVD, where inflammation, exudative fluid, and scar tissue is formed, it is possible that NSAIDs may reduce the inflammation response. Usually there are flashing light experiences and the emergence of floaters in the eye that herald changes in the vitreous before the epiretinal membrane forms.

Treatment
Surgeons can remove or peel the membrane through the sclera and improve vision by 2 or more Snellen lines. Usually the vitreous is replaced at the same time with clear (BSS) fluid, in a vitrectomy. Surgery is not usually recommended unless the distortions are severe enough to interfere with daily living, since there are the usual hazards of surgery, infections, and a possibility of retinal detachment. More common complications are high intraocular pressure, bleeding in the eye, and cataracts, which are the most frequent complication of vitrectomy surgery. Many patients will develop a cataract within the first few years after surgery. In fact, the visual distortions and diplopia created by cataracts may sometimes be confused with epiretinal membrane.

Epidemiology
This ocular pathology was first described by Iwanoff in 1865, and it has been shown to occur in about 7% of the population. It can occur more frequently in the older population with postmortem studies showing it in 2% of those aged 50 years and 20% in those aged 75 years.

Culture
In 1996, Spalding Gray (June 5, 1941 – ca. January 10, 2004), an American actor, screenwriter and playwright, released Grays Anatomy, a film monologue describing his experiences dealing with a macular pucker and his decision to undergo surgery.
In the 2011 film Paul, Ruth had Epiretinal membrane complicated by macular edema in her left vitreous cavity.

See also
Eye surgery

References
Additional references
de Wit GC (2007). "Retinally-induced aniseikonia". Binocul Vis Strabismus Q. 22 (2): 96–101. PMID 17688418.
Benson WE, Brown GC, Tasman W, McNamara JA (1988). "Complications of vitrectomy for non-clearing vitreous hemorrhage in diabetic patients". Ophthalmic Surg. 19 (12): 862–4. PMID 3231410.
Suami M, Mizota A, Hotta Y, Tanaka M (2007). "Pattern VEPs before and after idiopathic epiretinal membrane removal". Doc Ophthalmol. 114 (2): 67–73. doi:10.1007/s10633-006-9039-4. PMID 17216518. S2CID 22039065.
Dev S, Mieler WF, Pulido JS, Mittra RA (1999) </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 Combined malonic and methylmalonic aciduria and can you explain it in depth? [/INST] Combined malonic and methylmalonic aciduria (CMAMMA), also called combined malonic and methylmalonic acidemia is an inherited metabolic disease characterized by elevated levels of malonic acid and methylmalonic acid. Some researchers have hypothesized that CMAMMA might be one of the most common forms of methylmalonic acidemia, and possibly one of the most common inborn errors of metabolism. Due to being infrequently diagnosed, it most often goes undetected.

Symptoms and signs
The clinical phenotypes of CMAMMA are highly heterogeneous and range from asymptomatic, mild to severe symptoms. The underlying pathophysiology is not yet understood. The following symptoms are reported in the literature:

metabolic acidosis
coma
hypoglycemia
seizures
gastrointestinal disease
developmental delay
speech delay
failure to thrive
psychiatric disease
memory problems
cognitive decline
encephalopathy
cardiomyopathy
dysmorphic featuresWhen the first symptoms appear in childhood, they are more likely to be intermediary metabolic disorders, whereas in adults they are usually neurological symptoms.

Causes
CMAMMA can be divided by causation into two separate inherited disorders: one is a deficiency of the mitochondrial enzyme acyl-CoA synthetase family member 3, encoded by the ACSF3 gene (OMIM#614265); the other disorder is a malonyl-CoA decarboxylase deficiency encoded by the MLYCD gene (OMIM#248360).

ACSF3 deficiency
CMAMMA due to ACSF3 is inherited in an autosomal recessive manner. The ACSF3 gene is located on chromosome 16 locus q24.3 and consists of 11 exons and encodes a 576-amino-acid protein. CMAMMA can be caused by homozygous or compound heterozygous variants in the ACSF3 gene. Based on minor allele frequency (MAF), a population incidence of ~ 1: 30 000 can be predicted for CMAMMA due to ACSF3.

Malonyl-CoA decarboxylase deficiency
CMAMMA due to malonyl-CoA decarboxylase is also inherited in an autosomal recessive manner. The MLYCD gene is located on chromosome 16 locus q23.3.

Pathophysiology
ACSF3
ACSF3 encodes an acyl-CoA synthetase, which is localized in the mitochondria and has a high specificity for malonic acid and methylmalonic acid. Thus, the synthetase catalyzes the synthesis of malonyl-CoA as well as methylmalonyl-CoA.

Malonic acid
The conversion of malonic acid to malonyl-CoA by acyl-CoA synthetase represents the first step in the mitochondrial fatty acid synthesis (mtFASII) pathway, which plays an important role in the regulation of energy metabolism and which should not be confused with the more familiar fatty acid synthesis that occurs in the cytoplasm. The dysfunctional mtFASII pathway leads to an accumulation of malonic acid, which has a competitive inhibitory effect on complex II, and also leads to a deficiency of malonyl-CoA. These deficiencies can be continued to the end-product of the mtFASII pathway, octanoyl-ACP. The consequences of this are diminished oxidative phosphorylation and major alterations in complex lipids, such as increased levels of sphingomyelins and cardiolipins and lower levels of phosphatidylcholines, phosphatidylglycerol and ceramides. Since octanoyl-ACP is the direct precursor in lipoic acid synthesis, this results in diminished lipoylation, since lipoic acid acts as an essential cofactor for several mitochondrial multienzyme complexes, such as pyruvate dehydrogenase complex (PDHC) and α-ketoglutarate dehydrogenase complex (α-KGDHC), among others. This diminished lipoylation also leads to a reduced glycolytic flux. To likely compensate for the cells energy demand, an upregulation of fatty acid β-oxidation and a decreased concentration of certain amino acids that feed anaplerotically into the citrate cycle, such as glutamine (via the fifth site of the citrate cycle), leucine, isoleucine, threonine (all via the sixth site of the citrate cycle) and aspartate (via the 10th site of the citrate cycle), could be detected. In summary, this reduced mitochondrial respiration and glycolytic flux results in impaired mitochondrial flexibility with a large dependence on fatty acid β-oxidation.However, neurons, with the exception of hypothalamic neurons, are not capable of satisfying their large energy demands by degrading fatty acids. It is speculated that an upregulation of β-oxidation also occurs in brain cells due to the hypofunctional mtFASII pathway. The consequence would be an increased risk for hypoxia and oxidative stress, which may contribute to neurological symptoms in the long term.

Methylmalonic acid
Methylmalonic acid is formed from the essential amino acids valine, methionine, threonine and isoleucine, from odd-chained fatty acids, from propionate and from cholesterol side chain, on the degradation path into the citrate cycle. In this process, the last intermediate methylmalony-CoA can be converted to methymalonic acid by a deacylase before incorporation at the succinyl-CoA site of the citrate cycle. At this point, the acyl-CoA synthease encoded by ACSF3 could convert the methylmalonic acid back to methylmalonyl-CoA and then feed it to the citrate cycle with the help of the methylmalonyl-CoA mutase and its cofactor vitamin B12. However, intracellular esterases are also capable of cleaving the methyl group of methylmalonic acid and generating the parent molecule malonic acid.Bacterial fermentation in the gut is a quantitatively significant source of propionate, which is a precursor for methylmalonic acid. Alongside this, propionic acid is also absorbed through the diet, as it is naturally present in certain foods or is added as a preservative by the food industry, especially in baked goods and dairy products. In addition, methylmalonate is formed during catabolism of thymine.In a study with fibroblasts, increased accumulations of triglycerides, an altered profile of fatty acid chain length and the presence of odd chain fatty acids were detected. A partial degradation due to accumulated methylmalonic acid and the use of propionyl-CoA as a starter unit for fatty acid synthesis is suggested as a possible cause, supported by the observation of a higher expression of CD36, which imports fatty acids into the cell.In vitro, a connection between free methylmalonic acid and malonic acid to neurotoxicity could be established.

Malonyl-CoA decarboxylase deficiency
Malonyl-CoA decarboxylase acts as a catalyst in the conversion of malonyl-CoA to acetyl-CoA and CO2. It is speculated that in MCD deficiency, the excess of mitochondrial malonyl-CoA increases methylmalonic acid levels, as a result of an inhibitory effect on methylmalonyl-CoA mutase. In the cytoplasm, malonyl-CoA acts as an inhibitor of the mitochondrial outer membrane enzyme carnitine palmitoyltransferase I (CPT1), which consequently inhibits fatty acid oxidation. The inhibitory effect of cytoplastic malonyl-CoA on CPT1 varies, so it inhibits roughly 100-fold greater in cardiac and skeletal muscles than in the liver.

Diagnosis
Due to a wide range of clinical symptoms and largely slipping through newborn screening programs, CMAMMA is thought to be an under-recognized condition.

Newborn screening programs
Because CMAMMA due to ACSF3 does not result in accumulation of methylmalonyl-CoA, malonyl-CoA, or propionyl-CoA, nor are abnormalities seen in the acylcarnitine profile, CMAMMA is not detected by standard blood-based newborn screening programs.A special case is the province of Quebec, which, in addition to the blood test, also screens urine on the 21st day after birth with the Quebec Neonatal Blood and Urine Screening Program. This makes Quebec province interesting for CMAMMA research, as it represents the only patient cohort in the world without selection bias. Between 1975 and 2010, an estimated 2 695 000 newborns were thus screened, with 3 detections of CMAMMA due to ACSF3. However, based on this lower detection rate to the predicted rate by heterozygous frequencies, it is likely that not all newborns with this biochemical phenotype were detected by the screening program. A 2019 study then identified as many as 25 CMAMMA due to ACSF3 patients in the province of Quebec. All but one came to clinical attention through the Provincial Neonatal Urine Screening Program, 20 of them directly and 4 after the diagnosis of an older sibling.

Malonic acid to methylmalonic acid ratio
The use of plasma rather than urine is recommended for determining the ratio of malonic acid to methylmalonic acid. Since even with an increase in sensitivity for malonic acid (MA), concentrations in urine samples can be so subtle that they are easily missed. In contrast, if only urinary methylmalonic acid (MAA) is used as the sole matrix, then CMAMMA due to ACSF3 may be misdiagnosed as classic methylmalonic acidemia. Also the calculation of the MA/MAA ratio in urine is not useful, because due to overlapping, healthy individuals cannot be clearly distinguished from CMAMMA affected individuals. Whereas, by calculating the MA/MMA ratio in plasma, a CMAMMA can be clearly distinguished from a classic methylmalonic acidemia </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 Adult polyglucosan body disease and can you explain it in depth? [/INST] Adult polyglucosan body disease (APBD) is a rare genetic glycogen storage disorder caused by an inborn error of metabolism.  Symptoms can emerge any time after the age of 30; early symptoms include trouble controlling urination, trouble walking, and lack of sensation in the legs. People eventually develop dementia.
A person inherits loss-of-function mutations in the GBE1 gene from each parent, and the lack of glycogen branching enzyme (the protein encoded by GBE1) leads to buildup of unbranched glycogen in cells, which harms neurons more than other kinds of cells.
Most people first go to the doctor due to trouble with urination.  The condition is diagnosed by gathering symptoms, a neurological examination, laboratory tests including genetic testing, and medical imaging.  As of 2015 there was no cure or treatment, but the symptoms could be managed.  People diagnosed with APBD can live a long time after diagnosis, but will probably die earlier than people without the condition.

Signs and symptoms
Adult polyglucosan body disease is a condition that affects the nervous system. People with this condition have problems walking due to reduced sensation in their legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). Damage to the nerves that control bladder function (neurogenic bladder) causes progressive difficulty in controlling the flow of urine. About half of people with adult polyglucosan body disease experience dementia.  Most people with the condition first complain of bladder issues.People with adult polyglucosan body disease typically first experience signs and symptoms related to the condition between ages 30 and 60.

Causes
APBD is an autosomal recessive disorder that is caused when a person inherits genes from both parents containing one or more loss-of-function mutations in the gene GBE1 which encodes for glycogen branching enzyme, also called 1,4-alpha-glucan-branching enzyme.

Mechanism
The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Most GBE1 gene mutations result in a shortage (deficiency) of the glycogen branching enzyme, which leads to the production of abnormal glycogen molecules. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Neurons appear to be particularly vulnerable to the accumulation of polyglucosan bodies in people with this disorder, leading to impaired neuronal function.Some mutations in the GBE1 gene that cause adult polyglucosan body disease do not result in a shortage of glycogen branching enzyme. In people with these mutations, the activity of this enzyme is normal. How mutations cause the disease in these individuals is unclear. Other people with adult polyglucosan body disease do not have identified mutations in the GBE1 gene </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 Bezoar and can you explain it in depth? [/INST] A bezoar is a mass often found trapped in the gastrointestinal system, though it can occur in other locations. A pseudobezoar is an indigestible object introduced intentionally into the digestive system.There are several varieties of bezoar, some of which have inorganic constituents and others organic. The term has both a modern (medical, scientific) and traditional usage.

Types
By content
Food boluses (or boli; singular bolus) have the archaic and positive meaning of bezoar, and are composed of loose aggregates of food items such as seeds, fruit pith, or pits, as well as other types of items such as shellac, bubble gum, soil, and concretions of some medications.
Lactobezoars are a specific type of food bezoar comprising inspissated milk. It is most commonly seen in premature infants receiving formula foods.
Pharmacobezoars (or medication bezoars) are mostly tablets or semiliquid masses of drugs, normally found following overdose of sustained-release medications.
Phytobezoars are composed of indigestible plant material (e.g., cellulose), and are frequently reported in patients with impaired digestion and decreased gastric motility.
Diospyrobezoar is a type of phytobezoar formed from unripe persimmons. Coca-Cola has been used to treat them.
Trichobezoar is a bezoar formed from hair – an extreme form of hairball. Humans who frequently consume hair sometimes require these to be removed. In cases of Rapunzel syndrome, surgery may be required.

By location
A bezoar in the esophagus is common in young children and in horses; in horses, it is known as choke.
A bezoar in the large intestine is known as a fecalith.
A bezoar in the trachea is called a tracheobezoar.

Cause
Esophageal bezoars discovered in nasogastrically fed patients on mechanical ventilation and sedation are reported to be due to precipitation of certain food types rich in casein, which are precipitated with gastric acid reflux to form esophageal bezoars. Bezoars can also be caused by gastroparesis due to the slowing of gastric emptying, which allows food to form a bolus.

History
The word bezoar is derived from the Persian pād-zahr (پادزهر), literally "antidote". The myth of the bezoar as an antidote was introduced to Europe from the Middle East in the 11th century and remained popular until the 18th century. It was believed to have the power of a universal antidote, would work against any poison, and that a drinking glass which contained a bezoar could neutralize any poison poured into it.

Ox bezoars are used in Chinese herbology, also known as niu-huang (牛黃) or calculus bovis. They are gallstones or gallstone substitutes created from ox or cattle bile. In some products, they claim to remove toxins from the body.
The Andalusian physician Ibn Zuhr (d. 1161), known in the West as Avenzoar, is thought to have made the earliest description of bezoar stones as medicinal items. Extensive reference to bezoars also appears in the Picatrix.
In 1567, French surgeon Ambroise Paré did not believe that it was possible for the bezoar to cure the effects of any poison, and described an experiment to test the properties of the stone. A cook in the Kings court was sentenced to death, and chose to be poisoned. Paré administered the bezoar stone to the cook, but it had no effect, and the cook died in agony seven hours after taking the poison, proving that contrary to popular belief, the bezoar could not cure all poisons.Modern examinations of the properties of bezoars by Gustaf Arrhenius and Andrew A. Benson of the Scripps Institution of Oceanography show that when bezoars are immersed in an arsenic-laced solution, they can remove the poison. The toxic compounds in arsenic are arsenate and arsenite; each is acted upon differently by the bezoars: arsenate is removed by being exchanged for phosphate in brushite found in the stones, while arsenite is bound to sulfur compounds in the protein of degraded hair, which is a key component in bezoars.A famous case in the common law of England (Chandelor v Lopus, 79 Eng Rep. 3, Cro. Jac. 4, Eng. Ct. Exch. 1603) announced the rule of caveat emptor ("let the buyer beware") if the goods they purchased are not in fact genuine and effective. The case concerned a purchaser who sued for the return of the purchase price of an allegedly fraudulent bezoar.
Bezoars were important objects in cabinets of curiosity and natural history collections, mainly for their use in early modern pharmacy and the study of animal health.The Merck Manual of Diagnosis and Therapy notes that consumption of unripened persimmons has been identified as the main cause of epidemics of intestinal bezoars, and that up to 90 percent of bezoars that occur from excessive consumption require surgery for removal.A 2013 review of three databases identified 24 publications presenting 46 patients treated with Coca-Cola for phytobezoars. The cola was administered in doses of 500 ml (18 imp fl oz; 17 US fl oz) to up to 3,000 ml (110 imp fl oz; 100 US fl oz) over 24 hours, orally or by gastric lavage. A total of 91.3% of patients had complete resolution after treatment with Coca-Cola: 50% after a single treatment, with others requiring the cola plus endoscopic removal. Doctors resorted to surgical removal in four cases.

See also
Bezoardicum
Coca-Cola treatment of phytobezoars
Enterolith
Fecalith
Gastrolith
Goa stone
Gorochana
List of English words of Persian origin
Regurgitalith
Snake-stones
Toadstone

References
Bibliography
Barry Levine. 1999. Principles of Forensic Toxicology. Amer. Assoc. for Clinical Chemistry. ISBN 1-890883-87-5.
Martín-Gil FJ, Blanco-Ávarez JI, Barrio-Arredondo MT, Ramos-Sanchez MC, Martin-Gil J. Jejunal bezoar caused by a piece of apple peel – Presse Med, 1995 Feb. 11; 24(6):326.
The Poison Sleuths: Arsenic – The King of Poisons.  Retrieved March 10, 2007 </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 Salpingitis and can you explain it in depth? [/INST] Salpingitis is an infection causing inflammation in the Fallopian tubes (also called salpinges). It is often included in the umbrella term of pelvic inflammatory disease (PID), along with endometritis, oophoritis, myometritis, parametritis, and peritonitis.

Signs and symptoms
The symptoms usually appear after a menstrual period. The most common are:
an abnormal smell and colour of vaginal discharge, fever, nausea, vomiting, bloating, and frequent urination.
Pain may be felt during ovulation, during periods, during sexual intercourse, on both sides of the abdomen, and lower back.

Causes
The infection usually has its origin in the vagina and ascends to the Fallopian tube from there. Because the infection can spread via the lymph vessels, infection in one Fallopian tube usually leads to infection of the other.

Risk factors
Its been theorized that retrograde menstrual flow and the cervix opening during menstruation allows the infection to reach the Fallopian tubes.
Other risk factors include surgical procedures that break the cervical barrier, such as:

endometrial biopsy
curettage
hysteroscopyAnother risk is factors that alter the microenvironment in the vagina and cervix, allowing infecting organisms to proliferate and eventually ascend to the Fallopian tube:

antibiotic treatment
ovulation
menstruation
sexually transmitted disease (STD)Finally, sexual intercourse may facilitate the spread of disease from the vagina to the Fallopian tube. Coital risk factors are:

Uterine contractions
Sperm, carrying organisms upward

Bacterial species
The bacteria most associated with salpingitis are:
N. gonorrhoeae
Chlamydia trachomatis
Mycoplasma
Staphylococcus
StreptococcusHowever, salpingitis is usually polymicrobial, involving many kinds of pathogens such as Ureaplasma urealyticum, and anaerobic and aerobic bacteria.

Diagnosis
Salpingitis may be diagnosed by pelvic examination, blood tests, and/or a vaginal or cervical swab.

Types
Salpingitis can be acute, chronic, or subclinical.

Epidemiology
Approximately one in fourteen untreated Chlamydia infections will result in salpingitis.Over one million cases of acute salpingitis are reported every year in the US, but the number of incidents is probably larger, due to incomplete and untimely reporting methods and that many cases are reported first when the illness has gone so far that it has developed chronic complications. For women age 16–25, salpingitis is the most common serious infection. It affects approximately 11% of females of reproductive age.Salpingitis has a higher incidence among members of lower socioeconomic classes. However, this is thought of being an effect of earlier sexual debut, multiple partners, and decreased ability to receive proper health care rather than any independent risk factor for salpingitis.
As an effect of an increased risk due to multiple partners, the prevalence of salpingitis is highest for people age 15–24 years. Decreased awareness of symptoms and less will to use contraceptives are also common in this group, raising the occurrence of salpingitis.

Complications
For those affected, 20% need hospitalization </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 Progressive rubella panencephalitis 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 Sandifer syndrome and can you explain it in depth? [/INST] Sandifer syndrome (or Sandifers syndrome) is an eponymous paediatric medical disorder, characterised by gastrointestinal symptoms and associated neurological features </s>