<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 Neurasthenia and can you explain it in depth? [/INST] Neurasthenia (from the Ancient Greek νεῦρον neuron "nerve" and ἀσθενής asthenés "weak") is a term that was first used at least as early as 1829 for a mechanical weakness of the nerves and became a major diagnosis in North America during the late nineteenth and early twentieth centuries after neurologist George Miller Beard reintroduced the concept in 1869.
As a psychopathological term, the first to publish on neurasthenia was Michigan alienist E. H. Van Deusen of the Kalamazoo asylum in 1869, followed a few months later by New York neurologist George Beard, also in 1869, to denote a condition with symptoms of fatigue, anxiety, headache, heart palpitations, high blood pressure, neuralgia, and depressed mood. Van Deusen associated the condition with farm wives made sick by isolation and a lack of engaging activity, while Beard connected the condition to busy society women and overworked businessmen.
Neurasthenia was a diagnosis in the World Health Organizations ICD-10, but is no more diagnosed in ICD-11, marked as deprecated. It also is no longer included as a diagnosis in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders. The condition is, however, described in the Chinese Society of Psychiatrys Chinese Classification of Mental Disorders.
Americans were said to be particularly prone to neurasthenia, which resulted in the nickname "Americanitis" (popularized by William James). Another, rarely used, term for neurasthenia is nervosism.

Symptoms
The condition was explained as being a result of exhaustion of the central nervous systems energy reserves, which Beard attributed to modern civilization. Physicians in the Beard school of thought associated neurasthenia with the stresses of urbanization and with stress suffered as a result of the increasingly competitive business environment. Typically, it was associated with upper class people and with professionals working in sedentary occupations, but really can apply to anyone who lives within the monetary system.
Freud included a variety of physical symptoms into this category, including fatigue, dyspepsia with flatulence, and indications of intra-cranial pressure and spinal irritation. In common with some other people of the time, he believed this condition to be due to "non-completed coitus" or the non-completion of the higher cultural correlate thereof, or to  "infrequency of emissions" or the infrequent practice of the higher cultural correlate thereof. Later, Freud formulated that in cases of coitus interruptus as well as in cases of masturbation, there was "an insufficient libidinal discharge" that had a poisoning effect on the organism, in other words, neurasthenia was the result of (auto‑)intoxication. Eventually he separated it from anxiety neurosis, though he believed that a combination of the two conditions existed in many cases.In 19th-century Britain and, by extension, across the British Empire, neurasthenia was also used to describe mental exhaustion or fatigue in “brain workers” or in the context of “overstudy”. This use was often synonymous with the term “brain fag”.

Diagnosis
From 1869, neurasthenia became a "popular" diagnosis, expanding to include such symptoms as weakness, dizziness and fainting.  A common treatment promoted by neurologist S. Weir Mitchell was the rest cure, especially for women. Data from this period gleaned from the Annual Reports of Queen Square Hospital, London, indicates that the diagnosis was balanced between the sexes and had a presence within Europe. Virginia Woolf was known to have been forced to have rest cures, which she describes in her book On Being Ill. Charlotte Perkins Gilmans protagonist in The Yellow Wallpaper also suffers under the auspices of rest cure doctors, much as Gilman herself did. Marcel Proust was said to suffer from neurasthenia. To capitalize on this epidemic, the Rexall drug company introduced a medication called Americanitis Elixir which claimed to be a soother for any bouts related to neurasthenia.

Treatment
Beard, with his partner A.D. Rockwell, advocated first electrotherapy and then increasingly experimental treatments for people with neurasthenia, a position that was controversial. An 1868 review posited that Beards and Rockwells knowledge of the scientific method was suspect and did not believe their claims to be warranted.
William James was diagnosed with neurasthenia, which he nicknamed Americanitis, and was quoted as saying, "I take it that no man is educated who has never dallied with the thought of suicide."In 1895, Sigmund Freud reviewed electrotherapy and declared it a "pretense treatment." He emphasized the example of Elizabeth von Rs note that "the stronger these were the more they seemed to push her own pains into the background."
Nevertheless, neurasthenia was a common diagnosis during World War I for "shell shock", but its use declined a decade later. Soldiers who deserted their post could be executed even if they had a medical excuse, but officers who had neurasthenia were not executed.

Current opinion
This concept remained popular well into the 20th century, eventually coming to be seen as a behavioural rather than physical condition, with a diagnosis that excluded postviral syndromes. Neurasthenia has largely been abandoned as a medical diagnosis. The ICD-10 system of the World Health Organization categorizes neurasthenia under "F48 - Other neurotic disorders".One modern opinion of neurasthenia is that it was actually dysautonomia, an "imbalance" of the autonomic nervous system.Barbara Ehrenreich, restating Jamess view, considers that neurasthenia was caused by the Calvinist gloom, and it was helped by the New Thought, through replacing the "puritanical demand for perpetual effort and self-examination to the point of self-loathing" with a more hopeful faith.

In Asia
The medical term neurasthenia is translated as Chinese shenjing shuairuo (simplified Chinese: 神经衰弱; traditional Chinese: 神經衰弱; pinyin: shénjīng shuāiruò; Cantonese Yale: sàhngīng sēuiyeuhk) or Japanese shinkei-suijaku (神経衰弱), both of which also translate the common term nervous breakdown. This loanword combines shenjing (神經) or shinkei (神経)  "nerve(s); nervous" and shuairuo or suijaku (衰弱) "weakness; feebleness; debility; asthenia".
Despite being omitted by the American Psychiatric Associations DSM in 1980, neurasthenia is listed in an appendix as the culture-bound syndrome shenjing shuairuo as well as appearing in the ICD-10.  The condition is thought to persist in Asia as a culturally acceptable diagnosis that avoids the social stigma of a diagnosis of mental disorder.
In Japan, shinkei-suijaku is treated with Morita therapy involving mandatory rest and isolation, followed by progressively more difficult work, and a resumption of a previous social role. The diagnosis is sometimes used as a disguise for serious mental illnesses such as schizophrenia and mood disorders.In China, traditional Chinese medicine describes shenjingshuairuo as a depletion of qi "vital energy" and reduction of functioning in the  wuzang "five internal organs" (heart, liver, spleen, lungs, kidneys). The modern CCMD classifies it as a persistent mental disorder diagnosed with three of these five symptoms: "weakness symptoms, emotional symptoms, excitement symptoms, tension-induced pain, and sleep disturbances" not caused by other conditions. Arthur Kleinman described Chinese neurasthenia as a "biculturally patterned illness experience (a special form of somatization), related to depression or other diseases or to culturally sanctioned idioms of distress and psychosocial coping."

See also
Combat stress reaction
Newyorkitis
Placebo effect
Psychogenic disease

References
Further reading
Brown, EM (1980). "An American Treatment for the American Nervousness". American Association of the History of Medicine. Archived from the original on 2008-09-07. Retrieved 2008-09-11.
Gijswijt-Hofstra, Marijke (2001). Cultures of Neurasthenia: From Beard to the First World War (Clio Medica 63) (Clio Medica). Rodopi Bv Editions. ISBN 978-90-420-0931-8.
Gosling, F. G. Before Freud: Neurasthenia and the American Medical Community, 1870-1910. Urbana: University of Illinois Press, 1987.
Weir Mitchell, S (1884). Fat and Blood: an essay on the treatment of certain types of Neurasthenia and hysteria. Philadelphia: J. D. Lippincott & Co. Retrieved 2008-09-11.
Farmer A, Jones I, Hillier J, Llewelyn M, Borysiewicz L, Smith A (October 1995) </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 Orthostatic purpura 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 Congenital stationary night blindness and can you explain it in depth? [/INST] Congenital stationary night blindness (CSNB) is a rare non-progressive retinal disorder. People with CSNB often have difficulty adapting to low light situations due to impaired photoreceptor transmission. These patients may also have reduced visual acuity, myopia, nystagmus, and strabismus. CSNB has two forms -- complete, also known as type-1 (CSNB1), and incomplete, also known as type-2 (CSNB2), which are distinguished by the involvement of different retinal pathways. In CSNB1, downstream neurons called  bipolar cells are unable to detect neurotransmission from photoreceptor cells. CSNB1 can be caused by mutations in various genes involved in neurotransmitter detection, including NYX. In CSNB2, the photoreceptors themselves have impaired neurotransmission function; this is caused primarily by mutations in the gene CACNA1F, which encodes a voltage-gated calcium channel important for neurotransmitter release. CSNB has been identified in horses and dogs as the result of mutations in  TRPM1 (Horse, "LP"), GRM6 (Horse, "CSNB2"), and LRIT3 (Dog, CSNB).
Congenital stationary night blindness (CSNB) can be inherited in an X-linked, autosomal dominant, or autosomal recessive pattern, depending on the genes involved.
Two forms of CSNB can also affect horses, one linked to the leopard complex of equine coat colors and the other found in certain horse breeds. Both are autosomal recessives.

Symptoms and signs
The X-linked varieties of congenital stationary night blindness (CSNB) can be differentiated from the autosomal forms by the presence of myopia, which is typically absent in the autosomal forms. Patients with CSNB often have impaired night vision, myopia, reduced visual acuity, strabismus and nystagmus. Individuals with the complete form of CSNB (CSNB1) have highly impaired rod sensitivity (reduced ~300x) as well as cone dysfunction. Patients with the incomplete form can present with either myopia or hyperopia.

Cause
CSNB is caused by malfunctions in neurotransmission from rod and cone photoreceptors to  bipolar cells in the retina. At this first synapse, information from photoreceptors is divided into two channels: ON and OFF. The ON pathway detects light onset, while the OFF pathway detects light offset. The malfunctions in CSNB1 specifically affect the ON pathway, by hindering the ability of ON-type bipolar cells to detect neurotransmitter released from photoreceptors. Rods, which are responsible for low-light vision, make contacts with ON-type bipolar cells only, while, cones, which are responsible for bright-light vision, make contacts with bipolar cells of both ON an OFF subtypes.  Because the low-light sensing rods feed only into the ON pathway, individuals with CSNB1 typically have problems with night vision, while vision in well-lit conditions is spared. In CSNB2, release of neurotransmitter from photoreceptors is impaired, leading to involvement of both ON and OFF pathways.
The electroretinogram (ERG) is an important tool for diagnosing CSNB. The ERG a-wave, which reflects the function of the  phototransduction cascade in response to a light flashes, is typically normal in CSNB patients, although in some cases phototransduction is also affected, leading to a reduced a-wave. The ERG b-wave, which primarily reflects the function of ON-bipolar cells, is greatly reduced in CSNB2 cases, and completely absent in CSNB1 cases.

Genetics
Only three rhodopsin mutations have been found associated with congenital stationary night blindness (CSNB). Two of these mutations are found in the second transmembrane helix of rhodopsin at Gly-90 and Thr-94. Specifically, these mutations are the Gly90Asp  and the Thr94Ile, which has been the most recent one reported. The third mutation is Ala292Glu, and it is located in the seventh transmembrane helix, in proximity to the site of retinal attachment at Lys-296. Mutations associated with CSNB affect amino acid residues near the protonated Schiff base (PSB) linkage. They are associated with changes in conformational stability and the protonated status of the PSB nitrogen.

Pathophysiology
CSNB1
The complete form of X-linked congenital stationary night blindness, also known as nyctalopia, is caused by mutations in the NYX gene (Nyctalopin on X-chromosome), which encodes a small leucine-rich repeat (LRR) family protein of unknown function. This protein consists of an N-terminal signal peptide and 11 LRRs (LRR1-11) flanked by cysteine-rich LRRs (LRRNT and LRRCT). At the C-terminus of the protein there is a putative GPI anchor site. Although the function of NYX is yet to be fully understood, it is believed to be located extracellularly. A naturally occurring deletion of 85 bases in NYX in some mice leads to the "nob" (no b-wave) phenotype, which is highly similar to that seen in CSNB1 patients. NYX is expressed primarily in the rod and cone cells of the retina. There are currently almost 40 known mutations in NYX associated with CSNB1, Table 1., located throughout the protein </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 Exencephaly and can you explain it in depth? [/INST] Exencephaly is a type of cephalic disorder wherein the brain is located outside of the skull. This condition is usually found in embryos as an early stage of anencephaly </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 Lymphangiosarcoma and can you explain it in depth? [/INST] Lymphangiosarcoma is a rare cancer which occurs in long-standing cases of primary or secondary lymphedema. It involves either the upper or lower lymphedematous extremities but is most common in upper extremities. Although its name implies lymphatic origin, it is believed to arise from endothelial cells and may be more accurately referred to as  angiosarcoma.

Signs and symptoms
Lymphangiosarcoma may present as a purple discoloration or a tender skin nodule in the extremity, typically on the anterior surface. It progresses to an ulcer with crusting to an extensive necrotic focus involving the skin and subcutaneous tissue. It metastasizes quickly.

Causes
It was previously a relatively common complication of the massive lymphedema of the arm which followed removal of axillary (arm pit) lymph nodes and lymphatic channels as part of the classical Halstedian radical mastectomy, as a treatment for breast cancer </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 Familial male-limited precocious puberty 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 Vulvodynia and can you explain it in depth? [/INST] Vulvodynia is a chronic pain syndrome that affects the vulvar area and occurs without an identifiable cause. Symptoms typically include a feeling of burning or irritation. It has been established by the ISSVD that for the diagnosis to be made symptoms must last at least three months.The exact cause is unknown but is believed to involve a number of factors, including genetics, immunology, and possibly diet. Diagnosis is by ruling out other possible causes. This may or may not include a biopsy of the area.Treatment may involve a number of different measures; however, none is universally effective, and the evidence to support their effectiveness is often poor. Some of these measures include improved vulvar care, dietary changes, medications, counselling, and, if conservative treatment is not effective, surgery. It is estimated to affect up to 16% of women.

Signs and symptoms
Pain is the most notable symptom of vulvodynia, and can be characterized as a burning, stinging, irritation or sharp pain that occurs in the vulva and entrance to the vagina. It may be constant, intermittent or happen only when the vulva is touched, but vulvodynia usually has a long duration.Symptoms may occur in one place or the entire vulvar area. It can occur during or after sexual activity, when tampons are inserted, or when prolonged pressure is applied to the vulva, such as during sitting, bike riding, or horseback riding. Some cases of vulvodynia are idiopathic where no particular cause can be determined.

Vulvar vestibulitis
Vulvar vestibulitis syndrome (VVS), vestibulodynia, or simply vulvar vestibulitis or "localized (to the vestibule) provoked vulvodynia" refers to pain localized to the vestibular region. It tends to be associated with a highly localized "burning" or "cutting" type of pain. The pain of vulvodynia may extend into the clitoris; this is referred to as clitorodynia.Vulvar vestibulitis syndrome is the most common subtype of vulvodynia that affects premenopausal women – the syndrome has been cited as affecting about 10%–15% of women seeking gynecological care.

Causes
A wide variety of possible causes and treatments for vulvodynia are currently being explored. Moreover, there are probably several causes of vulvodynia, and some may be individual to the patient.Possible causes include Sjögren syndrome, the symptoms of which include chronic vaginal dryness. Others include genetic predisposition to inflammation, allergy or other sensitivity (for example: oxalates in the urine), an autoimmune disorder similar to lupus erythematosus or to eczema or to lichen sclerosus, infection (e.g., yeast infections, bacterial vaginosis, HPV, HSV), injury, and neuropathy—including an increased number of nerve endings in the vaginal area. Some cases seem to be negative outcomes of genital surgery, such as a labioplasty.  Initiation of hormonal contraceptives that contain low- dose estrogen before the age of 16 could predispose women to vulvar vestibulitis syndrome. A significantly lower pain threshold, especially in the posterior vestibulum, has also been associated with the use of hormonal contraceptives in women without vulvar vestibulitis syndrome. Pelvic floor dysfunction may be the underlying cause of some womens pain.

Diagnosis
The condition is one of exclusion and other vulvovaginal problems should be ruled out. The diagnosis is based on the typical complaints of the patient, essentially normal physical findings, and the absence of identifiable causes per the differential diagnosis. Cotton swab testing is used to differentiate between generalized and localized pain and delineate the areas of pain and categorize their severity. Patients often will describe the touch of a cotton ball as extremely painful, like the scraping of a knife. A diagram of pain locations may be helpful in assessing the pain over time. The vagina should be examined, and tests, including wet mount, vaginal pH, fungal culture, and Gram stain, should be performed as indicated. Fungal culture may identify resistant strains.It is estimated that only half of affected women will seek medical help, among whom many will see several doctors before a correct diagnosis is made. Only 2% of the people that seek help do obtain a diagnostic. Many gynecologists are not familiar with this family of conditions, but awareness has spread with time. Affected women are also often hesitant to seek treatment for chronic vulvar pain, especially since many women begin experiencing symptoms around the same time they become sexually active. Moreover, the absence of any visible symptoms means that before being successfully diagnosed many patients have been told that the pain is "in their head" (a medical stance more associated with the 1970s than with modern medicine).

Differential diagnosis
Infections: urinary tract infection, candidiasis, herpes, HPV
Inflammation: lichen planus
Neoplasm: Pagets disease, vulvar carcinoma
Neurologic disorder: neuralgia secondary to herpes virus, spinal nerve injury

Treatment
There are a number of possible treatments with none being uniformly effective. Treatments include:

Lifestyle
A number of lifestyle changes are often recommended such as using cotton underwear, not using substances that may irritate the area, and using lubricant during sex. The use of alternative medicine has not been sufficiently studied to make recommendations.

Counseling
Education and accurate information about vestibulodynia: Gynaecologist-led educational seminars delivered in a group format have a significant positive impact on psychological symptoms and sexual functioning in women who have provoked (caused by a stimulus such as touch or sexual activity) vestibulodynia. Provoked vestibulodynia, whilst similar in some respects, is different to vulvodynia which this article refers to.
Biofeedback, physical therapy and relaxation: Biofeedback, often done by physical therapists, involves inserting a vaginal sensor to get a sense of the strength of the muscles and help a patient get greater control of her muscles to feel the difference between contraction and relaxation </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 Amnesic shellfish poisoning and can you explain it in depth? [/INST] Amnesic shellfish poisoning (ASP) is an illness caused by consumption of shellfish that contain the marine biotoxin called domoic acid.  In mammals, including humans, domoic acid acts as a neurotoxin, causing permanent short-term memory loss, brain damage, and death in severe cases.
This toxin is produced naturally by marine diatoms belonging to the genus Pseudo-nitzschia and the species Nitzschia navis-varingica.  When accumulated in high concentrations by shellfish during filter feeding, domoic acid can then be passed on to birds, marine mammals, and humans by consumption of the contaminated shellfish.Although human illness due to domoic acid has only been associated with shellfish, the toxin can bioaccumulate in many marine organisms that consume phytoplankton, such as anchovies and sardines.  Intoxication by domoic acid in nonhuman organisms is frequently referred to as domoic acid poisoning.

Symptoms and treatment
In the brain, domoic acid especially damages the hippocampus and amygdaloid nucleus. It damages the neurons by activating AMPA and kainate receptors, causing an influx of calcium. Although calcium flowing into cells is a normal event, the uncontrolled increase of calcium causes the cell to degenerate.Gastrointestinal symptoms can appear 24 hours after ingestion of affected molluscs. They may include vomiting, nausea, diarrhea, abdominal cramps, and haemorrhagic gastritis. In more severe cases, neurological symptoms can take several hours or up to 3 days to develop. These include headache, dizziness, disorientation, vision disturbances, loss of short-term memory, motor weakness, seizures, profuse respiratory secretions, hiccups, unstable blood pressure, abnormal heart rhythms, and coma.
People poisoned with very high doses of the toxin or displaying risk factors such as old age and kidney failure can die. Death has occurred in four of 107 confirmed cases. In a few cases, permanent sequelae included short-term memory loss and peripheral polyneuropathy.
No antidote for domoic acid is known, so if symptoms fit the description, immediate medical attention is advised. Cooking or freezing affected fish or shellfish tissue does not lessen the toxicity. Domoic acid is a heat-resistant and very stable toxin which can damage kidneys at concentrations that are 1/100th of those that cause neurological effects.

Discovery
ASP was first discovered in humans late in 1987, when a serious outbreak of food poisoning occurred in eastern Canada </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 Neutrophil immunodeficiency syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Camptocormia and can you explain it in depth? [/INST] Camptocormia, also known as bent spine syndrome (BSS), is a symptom of a multitude of diseases that is most commonly seen in the elderly. It is identified by an abnormal thoracolumbar spinal flexion, which is a forward bending of the lower joints of the spine, occurring in a standing position. In order to be classified as BSS, the anterior flexion (the lower back bending) must be of 45 degrees anteriorly. This classification differentiates it from a similar syndrome known as kyphosis. Although camptocormia is a symptom of many diseases, there are two common origins: neurological and muscular. Camptocormia is treated by alleviating the underlying condition causing it through therapeutic measures or lifestyle changes.

History and society
Camptocormia comes from two Greek words, meaning "to bend" (κάμπτω, kamptō) and "trunk" (κόρμος, kormos), and was coined by Alexandre-Achille Souques and B. Rosanoff-Saloff. These two men also created the definition of the disease that is widely accepted today.When the disorder was first clinically studied around the time of First World War, it was believed to be a psychogenic conversion disorder that resulted from the severe trauma of war. Souques and others treated patients with psychological therapy and early versions of electrotherapy. Samuel A. Sandler used a similar approach to treat soldiers during the Second World War. The view of BSS as a conversion disorder led to a lack of awareness about the conditions and few diagnoses by physicians.
As time progressed and advances were made in knowledge of neuroscience and physiology, biological mechanisms behind the irregular bending were identified. The current medically preferred term for the condition is bent spine syndrome, because of the psychological origin associated with camptocormia.

Camptocormia in the elderly
BSS is not limited to the elderly but has an average age of onset of 66 years and is more common amongst men. This late age of onset is largely due to the increased preponderance of the conditions causing the symptom in older individuals – such as muscular weakness and neurological disorders like Parkinsons disease. While BSS does not have any negative stigma in and of itself, those affected by it may be perceived differently due to the condition. For example, an elderly individual with the condition may be viewed as very physically weak, because of the severe bending of the back caused by the condition.

Symptoms
The primary symptom of camptocormia is abnormal forward bending of the torso. This bending becomes worse while walking but does not appear when the affected individual is lying down in a horizontal position. This alleviation of the condition indicates that it is a manifestation of another disease or ailment and is not due to a spine that is actually bent. This is somewhat ironic, since the medically accepted name for the condition is bent spine syndrome.
In an affected individual, the abnormal bending consists of an anterior flexion greater than 45 degrees. Because of this bending and the physical limitations caused by the conditions associated with the disease, it is usually impossible for an affected person to achieve a fully erect position. In addition, patients with camptocormia often experience low back pain as a result of the condition. BSS often appears in individuals with Parkinsons disease, muscular dystrophies, endocrine disorders, inflammatory conditions (myositis), or mitochondrial myopathies. As previously mentioned, the disease is more common in older individuals.

Pathology
When initially identified, camptocormia was classified as a psychogenic disease. Although the condition is sometimes a psychogenic manifestation, camptocormia typically originates from either muscular or neurological diseases. However, due to the wide variety of pathologies resulting in camptocormia, there is no singular cause that is most influential for the condition.

Muscular origin
Myopathic origin BSS can be secondary to various muscular disorders or occur as a primary idiopathy. These etiologies are termed secondary and primary BSS respectively. Idiopathic primary BSS is a late-onset myopathy with progressive muscular weakness that is detected on the spinal extensor muscles in elderly patients and is more predominant in females. The pathogenesis of primary BSS is typically related to fibrosis and fatty infiltration of muscular tissues and to mitochondrial changes due to the aging process. Specifically, weakening occurs in the paravertebral muscles of patients. These paravertebral muscles have a great influence over the walking stance and gait of a patient, so fatty infiltration and degradation of these muscle lead to the characteristics that easily define BSS, such as the anterior flexion of the back combined with an ability to keep upright with any kind of support (e.g., holding onto a table).Secondary BSS can have a multitude of causes, making it hard to pinpoint to a specific muscular disorder. Some examples of diseases that have secondary BSS as a symptom are myopathies caused by muscular dystrophies, neuromuscular disorders, and inflammatory muscle diseases; metabolic or endocrine disorders; and mitochondrial myopathies. A muscle biopsy can clearly demonstrate whether primary BSS or secondary BSS is affecting a patient, because primary BSS is much more identifiable.

Neurological origin
A multitude of neurological disorders cause BSS, including motor neuron disease, CNS disorders, and early amyotrophic lateral sclerosis. Usually, the bent spine is caused by dysfunctioning extensor spinal muscles with a neurological cause.
Neurological origin BSS may also result from damage to the basal ganglia nuclei that are a part of the cerebral cortex, which play a major role in bodily positioning. Damage to this part of the brain can inhibit proper flexion and extension in the muscles necessary for maintaining an upright position. Additionally, the neurotransmitter dopamine plays a key role in the operation of basal ganglia. An abnormally low dopamine concentration, such as that associated with Parkinsons disease, causes dysfunction in the basal ganglia and the associated muscle groups, leading to BSS. Studies have estimated the prevalence of BSS in people affected by Parkinsons to be between 3% and 18%.

Gene mutations
Several gene mutations have been identified in patients with camptocormia. These include the RYR1 gene in axial myopathy, the DMPK gene in myotonic dystrophy, and genes related to dysferlinopathy and Parkinsons disease. These genes could serve as targets for gene therapy to treat the condition in the years to come.

Diagnosis
In order to qualify a patients condition as BSS, the bending angle must be greater than 45 degrees. While the presence of the condition is very easy to note, the cause of the condition is much more difficult to discern. Conditions not considered to be BSS include vertebral fractures, previously existing conditions, and ankylosing spondylitis. Lower-back CT scans and MRIs can typically be used to visualize the cause of the disease. Further identification of the cause can be done by histochemical or cellular analysis of muscle biopsy.

Camptocormia is becoming progressively found in patients with Parkinsons disease.
The diagnosis of Parkinsons-associated camptocormia includes the use of imaging of the brain and the spinal cord, along with electromyography or muscle biopsies.
Muscle biopsies are also a useful tool to diagnose camptocormia. Muscle biopsies found to have variable muscle fiber sizes and even endomysial fibrosis may be markers of bent spine syndrome. In addition, disorganized internal architecture and little necrosis or regeneration is a marker of camptocormia.
Patients with camptocormia present with reduced strength and stooped posture when standing due to weakened paraspinous muscles (muscles parallel to the spine). Clinically, limb muscles show fatigue with repetitive movements. Paraspinous muscles undergo fat infiltration. Electromyography may be used as well in diagnosis. On average, the paraspinous muscles of affected individuals were found to be 75% myopathic, while limb muscles were 50% percent myopathic. Creatine kinase activity levels in skeletal muscle are a diagnostic indicator that can be identifiable through blood tests.

Treatment
Treatment and management
Due to the wide range of causes of camptocormia, there is no one treatment that suits all patients. In addition, there is no specific pharmacological treatment for primary BSS. The use of analgesic drugs depends entirely on the intensity of the back pain.  Muscular-origin BSS can be alleviated by positive lifestyle changes, including physical activity, walking with a cane, a nutritious diet, and weight loss. Worsening of symptoms is possible but rare in occurrence.Treatment of the underlying cause of the disease can alleviate the condition in some individuals with secondary BSS. Other treatment options include drugs, injections of botulinum toxin, electroconvulsive therapy, deep brain stimulation, and surgical correction. Unfortunately, many of the elderly individuals affected by the BSS are not treated surgically due to age-related physical ailments and the long postoperative recovery period.

Prognosis
This condition can lead to excess pressure on the spine, causing pain and discomfort. If the spine is bent too far, a patient may have difficulties breathing because of the pressure of the spine pressed against the lungs </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 Leiomyoma and can you explain it in depth? [/INST] A leiomyoma, also known as a fibroid, is a benign smooth muscle tumor that very rarely becomes cancer (0.1%). They can occur in any organ, but the most common forms occur in the uterus, small bowel, and the esophagus. Polycythemia may occur due to increased erythropoietin production as part of a paraneoplastic syndrome.
The word is from leio- + myo- + -oma, "smooth-muscle tumor". The plural form can be either the English leiomyomas or the classical leiomyomata.

Uterus
Uterine fibroids are leiomyomata of the uterine smooth muscle. As other leiomyomata, they are benign, but may lead to excessive menstrual bleeding (menorrhagia), often cause anemia and may lead to infertility.
A rare form of these tumors is uterine lipoleiomyoma—benign tumors consisting of a mixture of adipocytes and smooth muscle cells. Uterine lipoleiomyomata have been observed together with ovarian and other pathologies and some of them may develop into liposarcoma. These tumors are monoclonal, and non-random chromosomal abnormalities have been seen in 40% of the tumors.

Gallbladder
Mesenchymal neoplasms of the gallbladder are rare and in particular leiomyomas of the gallbladder have been rarely reported, all of them in patients with immune system disorders. However, a case was reported in absence of associated immunodeficiency at Monash Hospital in Melbourne, Australia, in a healthy 39-year-old woman with no symptoms.

Skin
Leiomyomas of the skin are generally (1) acquired, and (2) divided into several categories:
Solitary cutaneous leiomyoma
Multiple cutaneous (or pilar) leiomyomas arising from the arrectores pilorum muscles
Angioleiomyomas (vascular leiomyomas) that are thought to arise from vascular smooth muscle
Dartoic (or genital) leiomyomas originating in the dartos muscles of the genitalia, areola, and nipple
Angiolipoleiomyoma

Esophagus, stomach and small intestines
Leiomyoma is the most common benign mesenchymal tumor of esophagus and second most common benign tumor of the small bowel (with gastrointestinal stromal tumor as most common). Although leiomyoma is the most common benign esophageal tumor, malignant carcinoma is still 50 times more likely. Approximately 50% of cases are found in the jejunum, followed by the ileum in 31% of cases </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Myocardial stunning and can you explain it in depth? [/INST] Myocardial stunning or  transient post-ischemic myocardial dysfunction is a state of mechanical cardiac dysfunction that can occur in a portion of myocardium without necrosis after a brief interruption in perfusion, despite the timely restoration of normal coronary blood flow. In this situation, even after ischemia has been relieved (by for instance angioplasty or coronary artery bypass surgery) and myocardial blood flow (MBF) returns to normal, myocardial function is still depressed for a variable period of time, usually days to weeks. This reversible reduction of function of heart contraction after reperfusion is not accounted for by tissue damage or reduced blood flow, but rather, its thought to represent a perfusion-contraction "mismatch". Myocardial stunning was first described in laboratory canine experiments in the 1970s where LV wall abnormalities were observed following coronary artery occlusion and subsequent reperfusion.

Cause
Clinical situations associated with myocardial stunning include:
acute myocardial infarction (AMI) with early reperfusion
unstable angina
after percutaneous transluminal coronary angioplasty (PTCA)
after cardiac surgery
neurogenic stunned myocardium following an acute cerebrovascular event such as a subarachnoid hemorrhage
in patients undergoing chronic hemodialysis, chronic myocardial stunning may lead to heart failureMyocardial stunning has been implicated in the development of Takotsubo (Stress) cardiomyopathy.

Pathophysiology
The underlying mechanisms of myocardial stunning have remained the subject of debate for several decades. Two leading hypotheses implicate reperfusion-induced oxygen free-radical damage and altered calcium flux resulting in intracellular hypercalcemia and desensitization of myofilaments. After total ischemia occurs, the myocardium switches immediately from aerobic glycolysis to anaerobic glycolysis resulting in the reduced ability to produce high energy phosphates such as ATP and Creatinine Phosphate. At this point, the lack of the energy and lactate accumulation results in cessation of contraction within 60 seconds of ischemia (i.e. Vessel Occlusion).  Subsequent to this is a period of "myocardial stunning," in which reversible ischemic damage is taking place.  At approximately 30 minutes after the onset of total ischemia the damage becomes irreversible, thereby ending the phase of myocardial stunning. The generation of oxygen-derived [free radicals] during the initial period of reperfusion after ischemia is believed to contribute to the pathogenesis of myocardial stunning.Some evidence suggests that brief, repetitive episodes of myocardial ischemia may result in chronic myocardial stunning and ventricular contractile impairment.

Diagnosis
Imaging techniques such as echocardiography, ventriculography, and nuclear imaging can be used to detect a contractile dysfunction following reperfusion after an episode of ischemia. The area of dysfunction should also maintain normal perfusion, detected via Positron Emission Tomography, echocardiography with contrast, and/or thallium scintigraphy in order for a diagnosis of myocardial stunning to be considered. However, there are many practical challenges to diagnosing myocardial stunning using these methods. Accurate detection of regional myocardial blood flow and contraction function abnormalities must be detected at levels of high sensitivity.  The diagnosis of myocardial stunning must also be differentiated from other conditions such as hibernating myocardium and persistent (silent) subendocardial ischemia, which can also co-exist with superimposed stunning.

Management
Treatment considerations for myocardial stunning should be determined based on the clinical judgment of the cardiologist or physician, the degree of LV impairment and symptoms, and the wishes of the person.Some evidence supports the use of inotropic drugs in the case of severe myocardial dysfunction.Results from canine experimental trials investigating the oxygen free-radical hypothesis for myocardial stunning have shown a reduction in free radical generation and improvement in myocardial function following anti-oxidant infusion.

References
Further reading
"Myocardial “stunning” in man"
Baker C, Rimoldi O, Camici P, Barnes E, Chacon M, Huehns T, Haskard D, Polak J, Hall R (1999). "Repetitive myocardial stunning in pigs is associated with the increased expression of inducible and constitutive nitric oxide synthases". Cardiovasc. Res. 43 (3): 685–97. doi:10.1016/S0008-6363(99)00149-2 </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 Paracoccidioidomycosis and can you explain it in depth? [/INST] Paracoccidioidomycosis (PCM), also known as South American blastomycosis, is a fungal infection that can occur as a mouth and skin type, lymphangitic type, multi-organ involvement type (particularly lungs), or mixed type. If there are mouth ulcers or skin lesions, the disease is likely to be widespread. There may be no symptoms, or it may present with fever, sepsis, weight loss, large glands, or a large liver and spleen.The cause is fungi in the genus Paracoccidioides, including Paracoccidioides brasiliensis and Paracoccidioides lutzii, acquired by breathing in fungal spores.Diagnosis is by sampling of blood, sputum, or skin. The disease can appear similar to tuberculosis, leukaemia, and lymphoma Treatment is with antifungals; itraconazole. For severe disease, treatment is with amphotericin B followed by itraconazole, or trimethoprim/sulfamethoxazole as an alternative.It is endemic to Central and South America, and is considered a type of neglected tropical disease. In Brazil, the disease causes around 200 deaths per year.

Signs and symptoms
Asymptomatic lung infection is common, with fewer than 5% of infected individuals developing clinical disease.It can occur as a mouth and skin type, lymphangitic type, multi-organ involvement type (particularly lungs), or mixed type. If there are mouth ulcers or skin lesions, the disease is likely to be widespread. There may be no symptoms, or it may present with fever, sepsis, weight loss, large glands, or a large liver and spleen. If there are mouth ulcers or skin lesions, the disease is likely to be widespread.Two presentations are known, firstly the acute or subacute form, which predominantly affects children and young adults, and the chronic form, predominantly affecting adult men. Most cases are infected before age 20, although symptoms may present many years later.

Juvenile (acute/subacute) form
The juvenile, acute form is characterised by symptoms, such as fever, weight loss and feeling unwell together with enlarged lymph nodes and enlargement of the liver and spleen. This form is most often disseminated, with symptoms manifesting depending on the organs involved. Skin and mucous membrane lesions are often present, and bone involvement may occur in severe cases. This acute, severe presentation may mimic tuberculosis, lymphoma or leukaemia.

Adult (chronic) form
The chronic form presents months to years after the initial infection occurs and most frequently presents with dry cough and shortness of breath. Other symptoms include excess salivation, difficulty swallowing, and difficulties with voice control. Upper respiratory tract mucosal lesions may be present, as well as increased mucus production and coughing up blood. Both pulmonary and extrapulmonary involvement is common.Up to 70% of cases have mucosal involvement, with lesions often found in the mouth, oropharynx, larynx, and palate. Classic lesions are superficial painful granular ulcers, with small spots of bleeding.

Cause
Paracoccidioidomycosis is caused by two species of fungi that can exist as a mold or yeast depending on temperature, P. brasiliensis and P. lutzii. In protected soil environments, near water sources, that are disturbed either naturally or by human activity, P. brasiliensis has been epidemiologically observed (although not isolated). A known animal carrier is the armadillo. In the natural environment, the fungi are found as filamentous structures, and they develop infectious spores known as conidia.Human to human transmission has never been proven.

Mechanism
Primary infection, although poorly understood due to lack of data, is thought to occur through inhalation of the conidia through the respiratory tract, after inhaling fungal conidia produced by the mycelial form of P. brasiliensis. This occurs predominantly in childhood and young adulthood, after exposure to agricultural activity. Infection may occur through direct skin inoculation, although this is rare.After inhalation into the alveoli, there is rapid multiplication of the organism in the lung tissue, sometimes spreading via the venous and lymphatic systems. Approximately 2% of people develop clinical features after the initial asymptomatic infection.The type of immune response determines the clinical manifestation of the infection, with children and HIV co-infected individuals most commonly developing the acute/subacute disseminated disease. Most of those infected develop a Type 1 T-cell (Th1) mediated immune response, resulting in fibrosing alveolitis and compact granuloma formation that control fungal replication, and latent or asymptomatic infection. It then is thought to remain dormant in residual lung lesions and mediastinal lymph nodes. A deficient Th1 cell response results in the severe forms of the disease. In these individuals, granulomas do not form, and the affected person develops Th2 and Th9 responses, resulting in activation of B lymphocytes, high levels of circulating antibodies, eosinophilia, and hypergammaglobulinemia.Lung involvement subsequently occurs after a dormant phase, manifesting in upper respiratory tract symptoms, and lung infiltrates on imaging. The commonest, chronic form, is almost certainly a reactivation of the disease, and may develop into progressive scarring of the lungs (pulmonary fibrosis).It can cause disease in those with normal immune function, although immunosuppression increases the aggressiveness of the fungus. It rarely causes disease in fertile-age women, probably due to a protective effect of estradiol.

Diagnosis
More than 90% of cases can be diagnoses with direct histological examination of tissue, such as sputum, bronchial lavage fluid, exudates and biopsies. Histopathological study with Gomori methenamine silver (GMS) stain or hematoxylin and eosin (H&E) stain revealing large yeast cells with translucent cell walls with multiple buds.In the juvenile form, lung abnormalities are shown in high-resolution CT scans of the lungs, whereas in the chronic form plain X-rays may show interstitial and alveolar infiltrates in the central and lower lung fields.Culture of P. brasiliensis takes between 20 and 30 days, requiring multiple samples and culture media. Initial culture can occur at room temperature, however after growth is noted, confirmation occurs by incubating at to 36-37 degrees to transform the fungus into yeast cells.Antibody detection is useful both for acute diagnosis and monitoring. Gel immunodiffusion is commonly used in endemic areas, diagnoses 95% of cases with high specificity. Complement fixation allows for a measure of severity of cases by quantifying the antibody level, and is thus useful for monitoring treatment response. It is however only sensitive for 85% of cases, and cross-reacts with H. capsulatum.

Differential diagnosis
The disease can appear similar to tuberculosis, leukaemia, and lymphoma

Treatment
Both P. brasiliensis and P. lutzii are in-vitro susceptible to most antifungal agents, unlike other systemic fungal infections. Mild and moderate forms are treated with itraconazole for 9 to 18 months, as this has been shown to be more effective, has a shorter treatment duration and is more tolerated. Acidic beverages have been shown to reduce absorption of itraconazole. Co-trimoxazole is a second line agent, and is preferred for those with brain involvement, and during pregnancy. For severe cases, intravenous treatment with amphotericin B is indicated, for an average of 2 to 4 weeks.Prednisolone prescribed at the same time may reduce inflammation during treatment. Patients should be treated until stabilisation of symptoms, and increase in body weight. Advice in regards to nutritional support, as well as smoking and alcohol intake should be provided. Adrenal insufficiency, if found, is treated with corticosteroids. Clinical criteria for cure includes the absence or healing of lesions, stabilisation of body weight, negative as well as negative autoantibody tests. There is insufficient data to support the benefits of above drugs to treat the disease.

Epidemiology
Paracoccidioidomycosis is endemic in rural areas of Latin America, from southern Mexico to Argentina, and is also found in Brazil, Colombia, Venezuela, Ecuador and Paraguay. An epidemic outbreak has never been observed </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Congenital disorder of glycosylation and can you explain it in depth? [/INST] A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants. The most common sub-type is PMM2-CDG (formally known as CDG-Ia) where the genetic defect leads to the loss of phosphomannomutase 2 (PMM2), the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate.

Presentation
The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver disease; coagulopathies; failure to thrive (FTT); dysmorphic features (e.g., inverted nipples and subcutaneous fat pads), pericardial effusion, and hypotonia. If an MRI is obtained; cerebellar hypoplasia is a common finding.Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, peripheral neuropathy (PN), strabismus, nystagmus, optic disc pallor, and reduced rod function on electroretinography.Three subtypes PMM2-CDG, PMI-CDG, ALG6-CDG can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

N-Glycosylation and known defects
A biologically very important group of carbohydrates is the asparagine (Asn)-linked, or N-linked, oligosaccharides. Their biosynthetic pathway is very complex and involves a hundred or more glycosyltransferases, glycosidases, transporters and synthases. This plethora allows for the formation of a multitude of different final oligosaccharide structures, involved in protein folding, intracellular transport/localization, protein activity, and degradation/half-life. A vast amount of carbohydrate binding molecules (lectins) depend on correct glycosylation for appropriate binding; the selectins, involved in leukocyte extravasation, is a prime example. Their binding depends on a correct fucosylation of cell surface glycoproteins. Lack thereof leads to leukocytosis and increase sensitivity to infections as seen in SLC35C1-CDG(CDG-IIc); caused by a GDP-fucose (Fuc) transporter deficiency.All N-linked oligosaccharides originate from a common lipid-linked oligosaccharide (LLO) precursor, synthesized in the ER on a dolichol-phosphate (Dol-P) anchor. The mature LLO is transferred co-translationally to consensus sequence Asn residues in the nascent protein, and is further modified by trimming and re-building in the Golgi.
Deficiencies in the genes involved in N-linked glycosylation constitute the molecular background to most of the CDGs.
Type I defects involve the synthesis and transfer of the LLO
Type II defects impair the modification process of protein-bound oligosaccharides.

Type I
Type II
The mature LLO chain is next transferred to the growing protein chain, a process catalysed by the oligosaccharyl transferase (OST) complex.
Once transferred to the protein chain, the oligosaccharide is trimmed by specific glycosidases. This process is vital since the lectin chaperones calnexin and calreticulin, involved in protein quality, bind to the Glc1Man9GlcNAc-structure and assure proper folding. Lack of the first glycosidase (GCS1) causes CDG-IIb.
Removal of the Glc residues and the first Man residue occurs in the ER.
The glycoprotein then travels to the Golgi, where a multitude of different structures with different biological activities are formed.
Mannosidase I creates a Man5GlcNAc2-structure on the protein, but note that this has a different structure than the one made on LLO.
Next, a GlcNAc residue forms GlcNAc1Man5GlcNAc2, the substrate for a-mannosidase II (aManII).
aManII then removes two Man residues, creating the substrate for GlcNAc transferase II, which adds a GlcNAc to the second Man branch. This structure serves as substrate for additional galactosylation, fucosylation and sialylation reactions. Additionally, substitution with more GlcNAc residues can yield tri- and tetra-antennary molecules.Not all structures are fully modified, some remain as high-mannose structures, others as hybrids (one unmodified Man branch and one modified), but the majority become fully modified complex type oligosaccharides.In addition to glycosidase I, mutations have been found:
in MGAT2, in GlcNAc transferase II (CDG-IIa)
in SLC35C1, the GDP-Fuc transporter (CDG-IIc)
in B4GALT1, a galactosyltransferase (CDG-IId)
in COG7, the conserved oligomeric Golgi complex-7 (CDG-IIe)
in SLC35A1, the CMP-sialic acid (NeuAc) transporter (CDG-IIf)However, the use of >100 genes in this process, presumably means that many more defects are to be found.

Diagnosis
Classification
Historically, CDGs are classified as Types I and II (CDG-I and CDG-II), depending on the nature and location of the biochemical defect in the metabolic pathway relative to the action of oligosaccharyltransferase. The most commonly used screening method for CDG, analysis of transferrin glycosylation status by isoelectric focusing, ESI-MS, or other techniques, distinguish between these subtypes in so called Type I and Type II patterns.Currently, twenty-two CDG Type-I and fourteen Type-II subtypes of CDG have been described.Since 2009, most researchers use a different nomenclature based on the gene defect (e.g. CDG-Ia = PMM2-CDG, CDG-Ib = PMI-CDG, CDG-Ic = ALG6-CDG etc.). The reason for the new nomenclature was the fact that proteins not directly involved in glycan synthesis (such as members of the COG-family and vesicular H+-ATPase) were found to be causing the glycosylation defect in some CDG patients.
Also, defects disturbing other glycosylation pathways than the N-linked one are included in this classification. Examples are the α-dystroglycanopathies (e.g. POMT1/POMT2-CDG (Walker-Warburg syndrome and Muscle-Eye-Brain syndrome)) with deficiencies in O-mannosylation of proteins; O-xylosylglycan synthesis defects (EXT1/EXT2-CDG (hereditary multiple exostoses) and B4GALT7-CDG (Ehlers-Danlos syndrome, progeroid variant)); O-fucosylglycan synthesis (B3GALTL-CDG (Peters plus syndrome) and LFNG-CDG (spondylocostal dysostosis III)).

Type I
Type I disorders involve disrupted synthesis of the lipid-linked oligosaccharide precursor (LLO) or its transfer to the protein.Types include:

Type II
Type II disorders involve malfunctioning trimming/processing of the protein-bound oligosaccharide chain.Types include:

Disorders of O-mannosylation
Disorders with deficient α-dystroglycan O-mannosylation.Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild) </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 First-degree atrioventricular block and can you explain it in depth? [/INST] First-degree atrioventricular block (AV block) is a disease of the electrical conduction system of the heart in which electrical impulses conduct from the cardiac atria to the ventricles through the atrioventricular node (AV node) more slowly than normal. First degree AV block does not generally cause any symptoms, but may progress to more severe forms of heart block such as second- and third-degree atrioventricular block. It is diagnosed using an electrocardiogram, and is defined as a PR interval greater than 200 milliseconds. First degree AV block affects 0.65-1.1% of the population with 0.13 new cases per 1000 persons each year.

Causes
The most common causes of first-degree heart block are AV nodal disease, enhanced vagal tone (for example in athletes), myocarditis, acute myocardial infarction (especially acute inferior MI), electrolyte disturbances and medication.  The medications that most commonly cause first-degree heart block are those that increase the refractory time of the AV node, thereby slowing AV conduction. These include calcium channel blockers, beta-blockers, cardiac glycosides, and anything that increases cholinergic activity such as cholinesterase inhibitors.

Diagnosis
In normal individuals, the AV node slows the conduction of electrical impulses through the heart.  This is manifest on a surface electrocardiogram (ECG) as the PR interval.  The normal PR interval is from 120 ms to 200 ms in length.  This is measured from the initial deflection of the P wave to the beginning of the QRS complex.In first-degree heart block, the diseased AV node conducts the electrical activity more slowly </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 Cerebral atrophy and can you explain it in depth? [/INST] Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means a decrement in the size of the cell, which can be due to progressive loss of cytoplasmic proteins. In brain tissue, atrophy describes a loss of neurons and the connections between them. Brain atrophy can be classified into two main categories: generalized and focal atrophy. Generalized atrophy occurs across the entire brain whereas focal atrophy affects cells in a specific location. If the cerebral hemispheres (the two lobes of the brain that form the cerebrum) are affected, conscious thought and voluntary processes may be impaired.
Some degree of cerebral shrinkage occurs naturally with the dynamic process of aging. The human brain completes growth and attains its full maturity at 25 years of age. Structural changes continue during adulthood as brain shrinkage commences after the age of 35, at a rate of 0.2% per year. The rate of decline is accelerated when individuals reach 70 years old. By the age of 90, the human brain will have experienced a 15% loss of its initial peak weight. Besides brain atrophy, aging has also been associated with cerebral microbleeds.

Symptoms
Many diseases that cause cerebral atrophy are associated with dementia, seizures, and a group of language disorders called the aphasias. Dementia is characterized by a progressive impairment of memory and intellectual function that is severe enough to interfere with social and work skills. Memory, orientation, abstraction, ability to learn, visual-spatial perception, and higher executive functions such as planning, organizing and sequencing may also be impaired. Seizures can take different forms, appearing as disorientation, strange repetitive movements, loss of consciousness, or convulsions. Aphasias are a group of disorders characterized by disturbances in speaking and understanding language. Receptive aphasia causes impaired comprehension. Expressive aphasia is reflected in odd choices of words, the use of partial phrases, disjointed clauses, and incomplete sentences.

Causes
The pattern and rate of progression of cerebral atrophy depends on the disease involved.

Injury
Stroke, loss of brain function due to a sudden interruption of blood supply in the brain
Moderate-to-severe traumatic brain injury

Diseases and disorders
Alzheimers disease (High resolution MRI scans have shown the progression of cerebral atrophy in Alzheimers disease)
Cerebral palsy, in which lesions (damaged areas) may impair motor coordination
Senile dementia, fronto-temporal dementia, and vascular dementia
Picks disease, causes progressive destruction of nerve cells in the brain
Huntingtons disease, and other genetic disorders that cause build-up of toxic levels of proteins in neurons
Leukodystrophies, such as Krabbe disease, which destroy the myelin sheath that protects axons
Multiple sclerosis, which causes inflammation, myelin damage, and lesions in cerebral tissue
Epilepsy, in which lesions cause abnormal electrochemical discharges that result in seizures
Anorexia nervosa, bulimia nervosa, and other eating disorders
Malnutrition, caused by lack or excess of nutrition from foods
Type II diabetes, where the body does not use insulin properly resulting in high blood sugar
Bipolar disorder, significant loss of brain tissue during manic episodes; however its not verified whether the episodes cause brain tissue loss or vice versa
Schizophrenia
Mitochondrial encephalomyopathies, such as Kearns–Sayre syndrome, which interfere with the basic functions of neurons
Posterior cortical atrophy:  In the most posterior area of the brain lies the visual cortex, the area of the brain where visual information is received and processed.  When cortical atrophy occurs in this brain area due to neurodegeneration, the first symptom is impairment in vision.  A common vision impairment seen in patients with posterior cortical atrophy is simultanagnosia, where a person is unable to see multiple locations at once or to quickly shift attention between these locations.  When looking at images of a brain with posterior cortical atrophy, one can see a loss in volume of the dorsal and ventral visual pathways, where visual stimuli is brought to the visual cortex and integrated information is sent back out to other areas of the brain.  Because this disorder results in visual impairments, there is often a missed or delayed diagnosis, as the assumption is that there is a problem is in the eyes when the reality is that the problem is all the way in the back of the brain.
Prion diseases, a group of invariably fatal encephalopathies that cause the progressive death of neurons.

Infections
Where an infectious agent or the inflammatory reaction to it destroys neurons and their axons, these include...

Encephalitis, acute inflammation in the brain
Neurosyphilis, an infection in the brain or spinal chord
AIDS, disease of the immune system

Drug-induced
Alcohol (partially reversible): Standardized MRI evidence suggest chronic alcoholism (alcohol use disorder) is associated with widespread cortical atrophy and major brain changes. In contrast to healthy controls, macrostructural findings indicate alcoholic brains are smaller in mass and volume. Neuroimaging studies also show that cortical shrinkage in "uncomplicated alcoholism" is most severe in the frontal lobe in comparison to the other divisions of the cerebral cortex. In addition, neurological diseases that co-occur with excessive alcohol consumption—such as Wernicke-Korsakoff syndrome (WKS)—are characterized by substantial volume deficits of the diencephalon structures. In comparison to unaffected, non-alcoholic participants, tissue degeneration in WKS patients is found in specific white matter structures including the corpus callosum, the hippocampus, the subcortical basal ganglia (hypothalamus, thalamus, putamen), and the mammillary bodies.
Antipsychotic
Corticosteroid use (There appears to be correlations between degree of dosing with corticosteroids and cerebral atrophy)

Diagnosis
Neurofilament light chain
Cerebrospinal fluid (CSF) is a fluid that is found exclusively in the brain and spinal cord that circulates between sections of the brain offering an extra layer of protection.  Studies have shown that biomarkers in the CSF and plasma can be tracked for their presence in different parts of the brain—and their presence can tell us about cerebral atrophy.  One study took advantage of biomarkers, namely one called neurofilament light chain (NFL), in patients with Alzheimers Disease. Neurofilament light chain is a protein that is important in the growth and branching of neurons—cells found in the brain. In Alzheimers Disease, neurons will stop working or die in a process called neurodegeneration. By tracking NFL, researchers can see this neurodegeneration, which this study showed was associated with brain atrophy and later cognitive decline in Alzheimers patients. Other biomarkers like Ng – a protein important in long-term potentiation and memory – have been tracked for their associations with brain atrophy as well, but NFL had the greatest association.

Measures
CT and MRI are most commonly used to observe the brain for cerebral atrophy. A CT scan takes cross sectional images of the brain using X-rays, while an MRI uses a magnetic field. With both measures, multiple images can be compared to see if there is a loss in brain volume over time.

Difference from hydrocephalus
Cerebral atrophy can be hard to distinguish from hydrocephalus because both cerebral atrophy and hydrocephalus involve an increase in cerebrospinal fluid (CSF) volume. In cerebral atrophy, this increase in CSF volume comes as a result of the decrease in cortical volume. In hydrocephalus, the increase in volume happens due to the CSF itself.

Treatment
Cerebral atrophy is not usually preventable </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 Essential fructosuria and can you explain it in depth? [/INST] Essential fructosuria, caused by a deficiency of the enzyme hepatic fructokinase, is a clinically benign condition characterized by the incomplete metabolism of fructose in the liver, leading to its excretion in urine </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 Myoma 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 Methylmalonic acidemia and can you explain it in depth? [/INST] Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. It is a classical type of organic acidemia. The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood.Methylmalonic acidemia stems from several genotypes, all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated. It is estimated that this disorder has a frequency of 1 in 48,000 births, though the high mortality rate in diagnosed cases make exact determination difficult. Methylmalonic acidemias are found with an equal frequency across ethnic boundaries.

Symptoms and signs
Depending on the affected gene(s), this disorder may present symptoms that range from mild to life-threatening.

Stroke
Progressive encephalopathy
Seizure
Kidney failure
Vomiting
Dehydration
Failure to thrive and developmental delays
Lethargy
Repeated yeast infections
Acidosis
Hepatomegaly
Hypotonia
Pancreatitis
Respiratory distress

Cause
Genetic
The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.Vitamin B12 is also needed for the conversion of methylmalonyl-CoA to succinyl-CoA.  Mutations leading to defects in vitamin B12 metabolism or in its transport frequently result in the development of methylmalonic acidemia.This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene—one from each parent—must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Nutritional
Though not always grouped together with the inherited versions, a severe nutritional deficiency of vitamin B12 can also result in syndrome with identical symptoms and treatments as the genetic methylmalonic acidemias. Methylmalonyl-CoA requires vitamin B12 to form succinyl-CoA. When the amount of B12 is insufficient for the conversion of cofactor methylmalonyl-CoA into succinyl-CoA, the buildup of unused methylmalonyl-CoA eventually leads to methylmalonic acidemia. This diagnosis is often used as an indicator of vitamin B12 deficiency in serum.

Mechanism
Pathophysiology
In methylmalonic acidemia, the body is unable to break down the amino acids methionine, threonine, isoleucine and valine; as a result methylmalonic acid builds up in the blood and tissues. Those afflicted with this disorder are either lacking functional copies or adequate levels of one or more of the following enzymes: methylmalonyl-CoA mutase, methylmalonyl-CoA epimerase, or those involved in adenosylcobalamin synthesis.

Methylmalonyl-CoA mutase
It is estimated that as many as 60% of cases are the result of a mutated MUT gene which encodes the protein methylmalonyl-CoA mutase. This enzyme is responsible for the digestion of potentially toxic derivatives of the breakdown of the above-mentioned amino acids and fats, primarily cholesterol, particularly this enzyme converts methylmalonyl-CoA into succinyl-CoA. Without this enzyme, the body has no means to neutralize or remove methylmalonic acid and related compounds. The action of this enzyme can also be crippled by mutations in the MMAA, MMAB, and MMADHC genes, each of which encodes a protein required for normal functioning of methylmalonyl-CoA mutase.

Methylmalonyl-CoA epimerase
Mutations in the MCEE gene, which encodes the methylmalonyl-CoA epimerase protein, also referred to as methylmalonyl racemase, will cause a much more mild form of the disorder than the related methylmalonyl-CoA mutase variant. Like the mutase, the epimerase also functions in breaking down the same substances, but to a significantly lesser extent than the mutase does. The phenotypic differences caused by a deficiency of the epimerase as opposed to the mutase are so mild that there is debate within the medical community as to whether or not this genetic deficiency can be considered a disorder or clinical syndrome.

Adenosylcobalamin
Also known as vitamin B12, this form of cobalamin is a required cofactor of methylmalonyl-CoA mutase. Even with a functional version of the enzyme at physiologically normal levels, if B12 cannot be converted to this active form, the mutase will be unable to function.

Progression
Though there are not distinct stages of the disease, methylmalonic acidemia is a progressive condition; the symptoms of this disorder are compounded as the concentration of methylmalonic acid increases. If the triggering proteins and fats are not removed from the diet, this buildup can lead to irreparable kidney or liver damage and eventually death.

Diagnosis
One of, if not the most common form of organic acidemia, methylmalonic acidemia is not apparent at birth as symptoms usually do not present themselves until proteins are added to the infants diet. Because of this, symptoms typically manifest anytime within the first year of life. Due to the severity and rapidity in which this disorder can cause complications when left undiagnosed, screening for methylmalonic acidemia is often included in the newborn screening exam.Because of the inability to properly break down amino acids completely, the byproduct of protein digestion, the compound methylmalonic acid, is found in a disproportionate concentration in the blood and urine of those afflicted. These abnormal levels are used as the main diagnostic criteria for diagnosing the disorder. This disorder is typically determined through the use of a urine analysis or blood panel. The presence of methylmalonic acidemia can also be suspected through the use of a CT or MRI scan or ammonia test, however these tests are by no means specific and require clinical and metabolic/correlation. Elevated levels of ammonia, glycine, and ketone bodies may also be present in the blood and urine.

Types
Methylmalonic acidemia has varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder. The following are the known genotypes responsible for methylmalonic acidemia:

The mut type can further be divided into mut0 and mut- subtypes, with mut0 characterized by a complete lack of methylmalonyl-CoA mutase and more severe symptoms and mut- characterized by a decreased amount of mutase activity.Mut-, cblB, and cblA versions of methylmalonic acidemia have been found to be cobalamin responsive. Mut0 is a nonresponsive variant.

Treatment
Dietary
Treatment for all forms of this condition primarily relies on a low-protein diet, and depending on what variant of the disorder the individual suffers from, various dietary supplements. All variants respond to the levo isomer of carnitine as the improper breakdown of the affected substances results in sufferers developing a carnitine deficiency. The carnitine also assists in the removal of acyl-CoA, buildup of which is common in low-protein diets by converting it into acyl-carnitine which can be excreted in urine. Some forms of methylmalonyl acidemia are responsive to cobalamin although cyanocobalamin supplements could prove detrimental to some forms.  If the individual proves responsive to both cobalamin and carnitine supplements, then it may be possible for them to ingest substances that include small amounts of the problematic amino acids isoleucine, threonine, methionine, and valine without causing an attack.

Surgical
A more extreme treatment includes kidney or liver transplant from a donor without the condition. The foreign organs will produce a functional version of the defective enzymes and digest the methylmalonic acid, however all of the disadvantages of organ transplantation are of course applicable in this situation. There is evidence to suggest that the central nervous system may metabolize methylmalonyl-CoA in a system isolated from the rest of the body. If this is the case, transplantation may not reverse the neurological effects of methylmalonic acid previous to the transplant or prevent further damage to the brain by continued build up.

Prognosis
The prognosis will vary depending on the severity of the condition and the individuals response to treatment. Prognosis is typically better for those with cobalamin-responsive variants and not promising in those suffering from noncobalamin-responsive variants. Milder variants have a higher frequency of appearance in the population than the more severe ones. Even with dietary modification and continued medical care, it may not be possible to prevent neurological damage in those with a nonresponsive acidemia. Without proper treatment or diagnosis, it is not uncommon for the first acidemic attack to be fatal.Despite these challenges, since it was first identified in 1967, treatment and understanding of the condition has improved to the point where it is not unheard of for even those with unresponsive forms of methylmalonic acidemia to be able to reach adulthood and even carry and deliver children safely.

Research
Nosologic history
MMA was first characterized by Oberholzer et al. in 1967.

Neurologic effects
That MMA can have disastrous effects on the nervous system has been long reported; however, the mechanism by which this occurs has never been determined </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 Hemopericardium and can you explain it in depth? [/INST] Hemopericardium refers to blood in the pericardial sac of the heart. It is clinically similar to a pericardial effusion, and, depending on the volume and rapidity with which it develops, may cause cardiac tamponade.The condition can be caused by full-thickness necrosis (death) of the myocardium (heart muscle) after myocardial infarction, chest trauma, and by over-prescription of anticoagulants. Other causes include ruptured aneurysm of sinus of Valsalva and other aneurysms of the aortic arch.Hemopericardium can be diagnosed with a chest X-ray or a chest ultrasound, and is most commonly treated with pericardiocentesis.  While hemopericardium itself is not deadly, it can lead to cardiac tamponade, a condition that is fatal if left untreated.

Symptoms and signs
Symptoms of hemopericardium often include difficulty breathing, abnormally rapid breathing, and fatigue, each of which can be a sign of a serious medical condition not limited to hemopericardium. In many cases, patients also report feeling chest pressure and have an abnormally elevated heart rate.

Cause
Hemopericardium has been reported to result from various afflictions including chest trauma, free wall rupture after a myocardial infarction, bleeding into the pericardial sac following a type A aortic dissection, and as a complication of invasive cardiac procedures. Acute leukemia has also been reported as a cause of the condition. Several cases of hemopericardium have also been reported as a side-effect of anticoagulants. Patients should be made aware of this fact when prescribed these drugs.

Mechanism
Hemopericardium is a condition that affects the cardiovascular system. It typically begins with blood accumulating in the pericardial sac posterior to the heart, and eventually expands to surround the entire heart. The fluid build-up then causes pressure within the pericardial sac to increase. If the pressure becomes greater than the intracardiac pressure of the heart, compression of the adjacent cardiac chambers can occur.  This compression, called cardiac tamponade, is often associated with hemopericardium and can be fatal if not diagnosed and treated promptly </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 Autoimmune polyendocrine syndrome and can you explain it in depth? [/INST] Autoimmune polyendocrine syndromes (APSs), also called polyglandular autoimmune syndromes (PGASs) or polyendocrine autoimmune syndromes (PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. There are three types of APS, and there are a number of other diseases which involve endocrine autoimmunity.

Types
Autoimmune polyendocrine syndrome type 1, an autosomal recessive syndrome due to mutation of the AIRE gene resulting in hypoparathyroidism, adrenal insufficiency, hypogonadism, vitiligo, candidiasis and others.
Autoimmune polyendocrine syndrome type 2, an autosomal dominant syndrome due to multifactorial gene involvement resulting in adrenal insufficiency plus hypothyroidism and/or type 1 diabetes.
Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX syndrome) is X-linked recessive due to mutation of the FOXP3 gene on the X chromosome. Most patients develop diabetes and diarrhea and many die due to autoimmune activity against many organs. Boys are affected, while girls are carriers and might experience mild disease.

Cause
Each "type" of this condition has a different genetic cause. IPEX syndrome is inherited in males by an X-linked recessive process. The FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in the mechanism of the IPEX condition.

Diagnosis
Diagnosis for type 1 of this condition for example, sees that the following methods/tests are available:
Endoscopic
CT scan
Histologic test

Differential diagnosis
For this condition, differential diagnosis sees that the following should be considered:
CD25 deficiency
STAT5B deficiency
Severe combined immunodeficiency
X linked thrombocytopenia

Management
Immunosuppressive therapy may be used in type I of this condition. Ketoconazole can also be used for type I under certain conditions.The component diseases are managed as usual; the challenge is to detect the possibility of any of the syndromes and to anticipate other manifestations. For example, in a person with known type 2 autoimmune polyendocrine syndrome but no features of Addisons disease, regular screening for antibodies against 21-hydroxylase may prompt early intervention and hydrocortisone replacement to prevent characteristic crises

See also
Immunosuppression

References
Further reading
Improda, Nicola; Capalbo, Donatella; Cirillo, Emilia; Cerbone, Manuela; Esposito, Andrea; Pignata, Claudio; Salerno, Mariacarolina (1 November 2014). "Cutaneous vasculitis in patients with autoimmune polyendocrine syndrome type 1: report of a case and brief review of the literature" </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 Vesicouterine fistula and can you explain it in depth? [/INST] Vesicouterine fistula refers to an abnormal communication between the bladder and uterus. The first case of vesicouterine fistula was reported in 1908. It was however first described in 1957 by Abdel Fattah Youssef, an obstetrician and gynaecologist in Kasr el-Aini hospital, Cairo, Egypt. It is characterized by a vesicouterine fistula above the level of the internal os, absence of menstrual bleeding, cyclical presence of blood in urine and absence of urinary incontinence with a patent cervical canal following a lower segment caesarean section </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 Cyclic vomiting syndrome and can you explain it in depth? [/INST] Cyclic vomiting syndrome (CVS) is a chronic functional condition of unknown pathogenesis. CVS is characterized as recurring episodes lasting a single day to multiple weeks. Each episode is divided into four phases: inter-episodic, prodrome, vomiting, and recovery. Inter-episodic phase (symptom free phase), is characterized as no discernible symptoms, normal everyday activities can occur, and this phase typically lasts one week to one month. The prodrome phase is known as the pre-emetic phase, characterized by the initial feeling of an approaching episode, still able to keep down oral medication. Emetic or vomiting phase is characterized as intense persistent nausea, and repeated vomiting typically lasting hours to days. Recovery phase is typically the phase where vomiting ceases, nausea diminishes or is absent, and appetite returns. This syndrome is most commonly seen in children usually between ages 3 and 7, however adult diagnosis is quite common. This disorder is thought to be closely related to migraines and family history of migraines.

Signs and symptoms
Affected individuals may vomit or retch 6–12 times in an hour and an episode may last from a few hours to over three weeks and in some cases months, with a median episode duration of 41 hours.  Stomach acid, bile and, if the vomiting is severe, blood may be vomited. Some with the condition will ingest water to reduce the irritation of bile and acid on the esophagus during emesis. Between episodes, the affected individual is usually normal and healthy otherwise but can be in a weak state of fatigue or experience muscle pain. In approximately half of cases the attacks, or episodes, occur in a time-related manner. Each attack is stereotypical; that is, in any given individual, the timing, frequency and severity of attacks is similar. Some affected people experience episodes that progressively get worse when left untreated, occurring more frequently with reduced symptom free phase.Episodes may happen every few days, every few weeks or every few months, for some happening at common uniform times, typically mornings. For other affected people, there is not a pattern in time that can be recognized. Some with the condition have a warning of an episodic attack; they may experience a prodrome, some documented prodromal symptoms include: unusually intense nausea and pallor, excess salivation, sweating, flushing, rapid/irregular heartbeat, diarrhea, anxiety/panic, food aversion, restlessness/insomnia, irritability, depersonalization, fatigue/listlessness, intense feelings of being hot or chilled, intense thirst, shivering/shaking, retching, tachypnea, abdominal pain/cramping, limb paresthesias, hyperesthesia, photophobia, phonophobia, headache, and dyspnea, heightened sensitivity, especially to light, though sensitivity to smell, sound, pressure, and temperature, as well as oncoming muscle pain and fatigue, are also reported by some patients. Many experiences a full panic attack when nausea begins and continue to panic once the vomiting has begun. Medications like Lorazepam, Alprazolam, and other benzodiazepines are prescribed by their doctors and instructed to take immediately at the onset of any of their CVS symptoms and/or triggers. Some prodromal symptoms are present inter-episodically as well as during acute phases of illness. The majority of affected people can identify triggers that may precede an attack. The most common are various foods, infections (such as colds), menstruation, extreme physical exertion, lack of sleep, and psychological stresses, both positive and negative.An affected person may also be light-sensitive (photophobic), sound-sensitive (phonophobic) or, less frequently, temperature- or pressure-sensitive during an attack.  Some people also have a strong urge to bathe in warm or cold water. In fact, many people with CVS experience a compulsion to be submerged in hot water, and end up taking several baths during the duration of an episode. For some the psychological compulsion to be in hot water is so extreme that they cannot stop themselves from taking very long baths in near scalding hot water several times per day. For some of these people, they may have just finished taking a lengthy bath in extremely hot water and immediately feel this compulsion again and end up taking another bath right after drying off. Some people with the condition experience insomnia, diarrhea (GI complications), hot and cold flashes, and excessive sweating before an episode. Some report that they experience a restless sensation or stinging pain along the spine, hands, and feet followed by weakness in both legs. Some of these symptoms may be due to dehydration or hypokalemia from excessive vomiting, rather than the underlying cause of CVS.

Genetics
There is no known genetic pathogenesis for CVS. Recent studies suggest many affected individuals have a family history of related conditions, such as migraines, psychiatric disorders and gastrointestinal disorders. Inheritance is thought to be maternal, a possible genetic mitochondrial inheritance. Adolescents show higher possible mitochondrial inheritance and maternal inheritance than found in adults. Single base-pair and DNA rearrangements in the mitochondrial DNA (mtDNA) have been associated with these traits.

Diagnosis
The cause of CVS has not been determined and there are no diagnostic tests for CVS. Several other medical conditions, such as cannabinoid hyperemesis syndrome (CHS), can mimic the same symptoms, and it is important to rule these out. If all other possible causes have been excluded, a diagnosis of CVS using Rome criteria by a physician may be appropriate.Once formal investigations to rule out gastrointestinal or other causes have been conducted, these tests do not need to be repeated in the event of future episodes.

Diagnostic criteria
Due to the lack of specific biomarkers available for the disorder, and if all other possible causes can be ruled out (such as intestinal malrotation), physicians rely on the Rome IV process criteria in order to diagnose patients. Patients must meet all three of the following criteria to receive diagnosis:

Stereotypical episodes of acute vomiting each with a duration of less than 1 week
A history of at least three discrete episodes in the prior year and at least two episodes in the past 6 months, each occurring at least 1 week apart
An absence of vomiting between episodes, but other milder symptoms can be present between cyclesCriteria must be fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. A history of family history of migraine headaches can also be used in facilitating diagnosis.

Treatment
Treatment for cyclic vomiting syndrome depends on the evident phase of the disorder.Because the symptoms of CVS are similar (or perhaps identical) to those of the disease well-identified as "abdominal migraine,"  prophylactic migraine medications, such as topiramate and amitriptyline, have seen recent success in treatment for the prodrome and vomiting phases, reducing the duration, severity, and frequency of episodes.Therapeutic treatment for the prodromal phase, characterized by the anticipation of an episode, consists of sumatriptan (nasal or oral) an anti-migraine medication, anti-inflammatory drugs to reduce abdominal pain, and possible anti-emetic drugs. These options may be helpful in preventing an episode or reducing the severity of an attack.The most common therapeutic strategies for those already in the vomiting phase are maintenance of salt balance by appropriate intravenous fluids and, in some cases, sedation. Having vomited for a long period prior to attending a hospital, patients are typically severely dehydrated. For a number of patients, potent anti-emetic drugs such as ondansetron (Zofran) or granisetron (Kytril), and dronabinol (Marinol) may be helpful in either preventing an attack, aborting an attack, or reducing the severity of an attack. Many patients seek comfort during episodes by taking prolonged showers and baths typically quite hot. The use of a heating pad may also help reduce abdominal pain.Lifestyle changes may be recommended, such as extended rest, reduction of stress, frequent small meals, and to abstain from fasting. A diet change may be recommended avoid food allergens, eliminating trigger foods such as chocolates, cheese, beer, and red wine.Some patients experience relief from inhaled isopropyl alcohol.

Prognosis
Fitzpatrick et al. (2007) identified 41 children with CVS. The mean age of the sample was 6 years at the onset of the syndrome, 8 years at first diagnosis, and 13 years at follow-up. As many as 39% of the children had resolution of symptoms immediately or within weeks of the diagnosis. Vomiting had resolved at the time of follow-up in 61% of the sample. Many children, including those in the remitted group, continued to have somatic symptoms such as headaches (in 42%) and abdominal pain (in 37%).Most children who have this disorder miss on average 24 school days a year.  The frequency of episodes is higher for some people during times of excitement.  Charitable organizations to support affected people and their families and to promote knowledge of CVS exist in several countries.
A 2005 study by Fleisher et al. identified 41 adults who had been previously seen for complaints compatible with CVS </s>