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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pigeon toe and explain in detail? [/INST] Pigeon toe, also known as in-toeing, is a condition which causes the toes to point inward when walking. It is most common in infants and children under two years of age and, when not the result of simple muscle weakness, normally arises from underlying conditions, such as a twisted shin bone or an excessive anteversion (femoral head is more than 15° from the angle of torsion) resulting in the twisting of the thigh bone when the front part of a persons foot is turned in.

Causes
The cause of in-toeing can be differentiated based on the location of the misalignment. The variants are:
Curved foot (metatarsus adductus)
Twisted shin (tibial torsion)
Twisted thighbone (femoral anteversion)

Metatarsus adductus
The most common form of being pigeon toed, when the feet bend inward from the middle part of the foot to the toes. This is the most common congenital foot abnormality, occurring every 1 in 5,000 births. The rate of metatarsus adductus is higher in twin pregnancies and preterm deliveries.  Most often self-resolves by one year of age and 90% of cases will resolve spontaneously (without treatment) by age 4.Signs and Symptoms
C-shaped lateral border of foot
Intoeing gait
Pressure sites during shoe wear

Tibial torsion
The tibia or lower leg slightly or severely twists inward when walking or standing.  Usually seen in 1-3 year olds, internal tibial torsion is the most common cause of intoeing in toddlers.  It is usually bilateral (both legs) condition that typically self-resolves by 4 to 5 years of age.Signs and Symptoms
Frequent tripping and clumsiness
Intoeing gait

Femoral anteversion
The neck of the femur is angled forward compared to the rest of the bone, causing a compensatory internal rotation of the leg. As a result, all structures downstream of the hip including the thigh, knee, and foot will turn in toward mid-line. Femoral anteversion is the most common cause of in toeing in children older than 3 years of age. It is most commonly bilateral, affects females twice as much as males, and in some families can show a hereditary pattern. This condition may progressively worsen from years 4 to 7, yet the majority of case still spontaneously resolve by 8 years of age.Signs and Symptoms
W-Sitting and inability to sit cross-legged
Intoeing gait
Circumduction Gait (legs swing around one another)
Frequent tripping and clumsiness

Diagnosis
Pigeon toe can be diagnosed by physical examination alone. This can classify the deformity into "flexible", when the foot can be straightened by hand, or otherwise "nonflexible". Still, X-rays are often done in the case of nonflexible pigeon toe. On X-ray, the severity of the condition can be measured with a "metatarsus adductus angle", which is the angle between the directions of the metatarsal bones, as compared to the lesser tarsus (the cuneiforms, the cuboid and the navicular bone). Many variants of this measurement exist, but Sgarlatos angle has been found to at least have favorable correlation with other measurements. Sgarlatos angle is defined as the angle between:
A line through the longitudinal axis of the second metatarsal bone.
The longitudinal axis of the lesser tarsal bones. For this purpose, one line is drawn between the lateral limits of the fourth tarsometatarsal joint and the calcaneocuboid joint, and another line is drawn between the medial limits of the talonavicular joint and the 1st tarsometatarsal joint. The transverse axis is defined as going through the middle of those lines, and hence the longitudinal axis is perpendicular to this axis.This angle is normally up to 15°, and an increased angle indicates pigeon toe. Yet, it becomes more difficult to infer the locations of the joints in younger children due to incomplete ossification of the bones, especially when younger than 3–4 years.
Internal Tibial Torsion
Internal tibial torsion is diagnosed by physical exam. The principle clinical exam is an assessment of the thigh-foot angle.  The affected individual is placed in prone position with the knees flexed to 90 degrees.  An imaginary line is drawn along the longitudinal axis of the thigh, and of the sole of the foot from a birds-eye view and the angle at the intersection of these two lines is measured.  A value greater than 10 degrees of internal rotation is considered internal tibial torsion.  A thigh-foot angle less than 10 degrees internal, and up to 30 degrees of external rotation is considered normal.Femoral Anteversion
Femoral anteversion is diagnosed by physical exam.  The principle physical exam maneuver is an assessment of hip mobility. The child is evaluated in the prone position with knees flexed to 90 degrees. Using the tibia as a lever arm the femur is rotated both internally and externally.  A positive exam demonstrates internal rotation of greater than 70 degrees and external rotation reduced to less than 20 degrees. Normal values for internal rotation are between 20 and 60 degrees and normal values for external rotation are between 30 and 60 degrees.

Treatment
In those less than eight years old with simple in-toeing and minor symptoms, no specific treatment is needed.Metatarsus Adductus
Nonoperative management:  Non operative treatment of metatarsus adductus is dictated by the flexibility of the forefoot.  If the child can actively correct the forefoot to midline no treatment is indicated.  If the adduction cannot be corrected actively but is flexible in passive correction by an examiner, at-home stretching that mimics this maneuver can be performed by parents. In the case of a rigid deformity serial casting can straighten the foot.Surgical Management:  Most cases of metatarsus adductus that does not resolve is asymptomatic in adulthood and does not require surgery.  Occasionally, persistent rigid metatarsus adductus can produce difficulty and significant pain associated with inability to find accommodating footwear </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Chronic neutrophilic leukemia and explain in detail? [/INST] Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.

Signs and symptoms
The most common clinical finding is hepatosplenomegaly </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Serrated polyposis syndrome and explain in detail? [/INST] Serrated polyposis syndrome (SPS), previously known as hyperplastic polyposis syndrome, is a disorder characterized by the appearance of serrated polyps in the colon. While serrated polyposis syndrome does not cause symptoms, the condition is associated with a higher risk of colorectal cancer (CRC). The lifelong risk of CRC is between 25 and 40%. SPS is the most common polyposis syndrome affecting the colon, but is under recognized due to a lack of systemic long term monitoring. Diagnosis requires colonoscopy, and is defined by the presence of either of two criteria: ≥5 serrated lesions/polyps proximal to the rectum (all ≥ 5 mm in size, with two lesions ≥10 mm), or >20 serrated lesions/polyps of any size distributed throughout the colon with 5 proximal to the rectum.A family history of SPS and smoking tobacco are associated with a higher risk of serrated polyposis syndrome, whereas the use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a lower risk. While the only validated genetic cause of SPS is RNF43, additional important genetic abnormalities include BRAF mutations, abnormal CpG island methylator phenotype, and microsatellite instability. However, most individuals with the syndrome do not have an associated germline mutation. The types of polyps found in SPS include sessile serrated adenomas/polyps, traditional serrated adenomas, and hyperplastic polyps. SPS occurs in 2 phenotypes: proximal and distal.  Proximal SPS has a greater risk of CRC than distal SPS.
The vast majority of cases may be managed with colonoscopy with removal polyps (polypectomy). Polyp removal is recommended to decrease the risk of colorectal cancer.  Repeat colonoscopy should be performed every 1–2 years.  If polyps are very large, numerous, or increase in number rapidly, then surgery may be necessary. Surgery may also be warranted if CRC is suspected or confirmed. First-degree relatives of people with SPS have an increased risk of CRC, and should undergo early screening with colonoscopy.

Types
SPS may occur with one of two phenotypes: distal or proximal. The distal phenotype may demonstrate numerous small polyps in the distal colon (sigmoid) and rectum, whereas the proximal phenotype may be characterized by relatively fewer, but larger polyps in the proximal colon (cecum, ascending colon, etc.). Individuals meeting only criterion 3 from 2010 criteria, or only criterion 2 from the 2019 classification, have a distal phenotype have a lower risk of CRC compared with the proximal phenotype.

Signs and symptoms
Serrated polyposis syndrome often does not cause symptoms. The risk of colon cancer is between 25 and 40%.Sessile serrated polyps, as seen during endoscopy or colonoscopy, are flat (rather than raised) and are easily overlooked. Serrated lesions range in size from small (<5 mm) to large, and often have a "mucous cap" overlying the polyp. Serrated lesions are frequently located on the folds of the colon (haustral folds).

Pathophysiology
SPS is not caused by a single gene mutation. Several genetic abnormalities are associated with the condition, and a familial or inherited pattern may occur. Key genetic abnormalities include mutations in BRAF, abnormal CpG island methylator phenotype, and microsatellite instability. Additional implicated genes include: SMAD4, BMPR1A, PTEN, GREM1, and MUTYH. The only validated genetic cause of SPS is RNF43. However, most individuals with SPS do not have a germline mutation in any of the associated genes, including RNF43. As the underlying genetic risks for SPS are not fully understood, genetic testing is not recommended. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported, as well as sporadic. Individuals with SPS have serrated polyps, which include hyperplastic polyps, traditional serrated adenomas, and sessile serrated polyps. In addition to serrated polyps, adenomas are often identified.

Diagnosis
The diagnosis of serrated polyposis syndrome is achieved when either one of two criteria are met: ≥5 serrated lesions/polyps proximal to the rectum (all ≥ 5 mm in size, with two lesions ≥10 mm), or >20 serrated lesions/polyps of any size distributed throughout the large bowel with 5 proximal to the rectum. Any serrated polyp is counted towards the diagnosis, including sessile serrated lesions, hyperplastic polyps, and traditional serrated adenomas. In addition, the cumulative number of serrated lesions is cumulative over time and includes multiple colonoscopies. The diagnosis of SPS is often overlooked, and requires lifelong tracking of cumulative serrated polyps.

Treatment
Colonoscopy is the mainstay of treatment for SPS, which allows for the identification of polyps and removal. Polyp removal is recommended to prevent the development of colorectal cancer.  If polyps are relatively few, then removal may be achieved with colonoscopy. After polyps are removed, repeat colonoscopy is recommended in 1 to 3 year intervals. On average, about 2.8 colonscopies are necessary to achieve control of disease. The majority of cases may be managed with colonoscopy alone. Narrow-band imaging, an imaging technique used to enhance features of mucosa seen during colonoscopy, may improve detection of serrated lesions; however, one multicenter trial did not show improved detection.If polyps are very numerous, very large, or their growth cannot be controlled with colonoscopy, then surgery may be necessary. When surgery is necessary, a total abdominal colectomy with ileorectal anastomosis should be considered to minimize the risk of colon cancer.  If surgery is necessary and involvement of polyps is focal or largely confined to a particular section of bowel, then segmental resection may be considered. Segmental resection is also recommended for cancer. In most cases, the rectum is left in place. Any remaining segments of colon or rectum require annual surveillance with colonoscopy.First degree relatives of people with SPS are at a higher risk of colorectal cancer and SPS. As such, these individuals should undergo screening with colonoscopy beginning at the earliest of the following: 40 years of age, the age of the youngest diagnosis of SPS in the family, or 10 years younger than the earliest CRC related to SPS. Repeat colonoscopy should be performed at 5 year intervals.

Prognosis
The overall risk of colorectal cancer is about 19.9%. However, the risk of cancer varies widely and depends on age, polyp burden, phenotype and the presence of dysplasia on histology. Endoscopic surveillance can decrease the risk of progression to cancer.

History
The condition was originally known as hyperplastic polyposis syndrome. When the syndrome was first recognized, only hyperplastic polyps were included in its definition, and the syndrome was believed to not be associated with a higher risk of colorectal cancer. In 1996, a case series revealed an association of the syndrome with cancer and serrated adenomas. Subsequently, other types of serrated polyps were found to occur in this condition, so the name was adjusted to the present "serrated polyposis syndrome."The World Health Organization released diagnostic criteria in 2010, which were updated in 2010 and again in 2019. The 2010 classification defined SPS as meeting any of the following criteria: 1) five or more serrated polyps proximal to the sigmoid colon with 2 larger than 10 mm in size, 2) any serrated polyps found proximal to the sigmoid colon in a person with a first-degree relative with serrated polyposis, or 3) more than 20 serrated colon polyps. The updated 2019 classification revised the first criterion to include lesions in the sigmoid colon, and excluded very small polyps (<5 mm). The updated 2019 classification also removed the criterion that included any serrated lesions proximal to the sigmoid colon in a person with a first degree relative with SPS.

Epidemiology
Data regarding overall prevalence of SPS is lacking, but it is estimated to occur in roughly 1 in 100,000. SPS is equally common among men and women. Most individuals with SPS are diagnosed between 40 and 60 years of age, with an average age of 55 years. Nearly half of individuals with SPS have a family member with colorectal cancer </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Legius syndrome and explain in detail? [/INST] Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I (NF-1). It is caused by mutations in the SPRED1 gene. It is also known as neurofibromatosis type 1-like syndrome (NFLS).

Symptoms and signs
Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin.
Symptoms may include:
Freckles in the axillary and inguinal skin fold
Lipomas, developing in adulthood
Macrocephaly
Learning disabilities
ADHD
Developmental delayFeatures common in neurofibromatosis – like Lisch nodules (iris hamartomas diagnosed on slit lamp exam), bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors – are absent in Legius syndrome.

Cause
Legius syndrome is a phakomatosis and a RASopathy, a developmental syndrome due to germline mutations in genes. The condition is autosomal dominant in regards to inheritance and caused by mutations to the SPRED1 gene at chromosome 15, specifically 15q14 (or (GRCh38): 15:38,252,086-38,357,248). The gene in question demonstrates almost 100 mutations.

Mechanism
A mutated SPRED1 protein adversely regulates Ras-MAPK signaling, which is a chain of proteins in a cell that sends signals from the surface of a cell to the nucleus which in turn causes the symptoms of this condition.

Diagnosis
Genetic testing is necessary to identify the syndrome. The DNA test is necessary sometimes, because symptoms may not be sufficient to definitely diagnose this condition.

Differential diagnosis
The symptoms of Legius syndrome and NF-1 are very similar; An important difference between Legius syndrome and NF-1 is the absence of tumor growths Lisch nodules and neurofibromas which are common in NF-1.A genetic test is often the only way to make sure a person has LS and not NF-1; the similarity of symptoms stem from the fact that the different genes affected in the two syndromes code for proteins that carry out a similar task in the same reaction pathway.

Treatment
Management of Legius syndrome is done via the following:
Physical therapy
Speech therapy
Pharmacologic therapy (e.g. methylphenidate for ADHD)The prognosis of this condition is generally considered good with appropriate treatment.

See also
List of cutaneous conditions
List of genes mutated in cutaneous conditions

References
Further reading
MD, Robert P. Erickson; PhD, Anthony J. Wynshaw-Boris MD (2016). Epsteins Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Marshall syndrome and explain in detail? [/INST] Marshall syndrome is a genetic disorder of the connective tissue which can cause hearing loss. The three most common areas to be affected are the eyes which are uncommonly large, joints and the mouth and facial structures. Marshall syndrome and Stickler syndrome closely resemble each other; in fact they are so similar, some say they are the same.

Presentation
Eyes
Myopia is the most common eye problem in Marshall syndrome. Cataracts also occur more frequently and detached retina less frequently than in Stickler syndrome. Myopia also is the most common problem with the eyes in Stickler syndrome. In the latter syndrome, extreme myopia may lead to severe eye problems such as detached retina more frequently than in Marshall syndrome.

Joints
The joint changes include hyperextensibility (double-jointedness) and arthritis. Babies and young children with Stickler syndrome usually have very hyperextensible joints. As an affected child gets older, they may experience pain and stiffness from overuse of a joint. Osteoarthritis of the large joints often develops during the third or fourth decade. The joint changes in Marshall syndrome are of the same type but to a lesser degree. There also may be changes in the bones that show up on X-ray but generally are not a problem.

Orofacial Structure
The most severe problem associated with Stickler syndrome is Pierre Robin syndrome. This refers to a cleft palate resulting from a very small lower jaw. During early fetal life, the roof of the mouth is normally open and the sides of the palate have to come together to close. If the jaw is too small, there is not enough room for the tongue which is then pushed up and gets in the way of the closing palate. Sometimes the chin is so small the baby has problems with eating and breathing if the tongue blocks the back of the throat. Cleft palate is found less frequently in Marshall Syndrome than in Stickler syndrome but still more frequently than in the general population.The facial features of Marshall Syndrome include a flat midface, the appearance of large eyes, short upturned nose, and a round face. The facial features of Stickler syndrome are less prominent but include a rather long flat face, and depressed nasal bridge.

Hearing loss
The hearing loss associated with Stickler syndrome can be progressive and usually involves the high frequencies. Sensorineural hearing loss has been reported in as many as 100% and as low as 20% of affected individuals. A conductive loss due to otitis can magnify an existing sensorineural loss and is a frequent problem for children with Stickler or Marshall Syndrome.

Genetics
Stickler syndrome and Marshall syndrome have an autosomal dominant pattern of inheritance </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hailey–Hailey disease and explain in detail? [/INST] Hailey–Hailey disease, or familial benign chronic pemphigus: 559  or familial benign pemphigus,: 622  was originally described by the Hailey brothers (Hugh Edward and William Howard) in 1939. It is a genetic disorder that causes blisters to form on the skin.

Signs and symptoms
HHD is characterized by outbreaks of rashes and blisters on the skin. Affected areas of skin undergo repeated blistering and inflammation, and may be painful to the touch. Areas where the skin folds, as well as the armpits, groin, neck, buttocks and under the breasts are most commonly affected </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Periodontal abscess and explain in detail? [/INST] A periodontal abscess (also termed lateral abscess, or parietal abscess), is a localized collection of pus (i.e. an abscess) within the tissues of the periodontium. It is a type of dental abscess. A periodontal abscess occurs alongside a tooth, and is different from the more common periapical abscess, which represents the spread of infection from a dead tooth (i.e. which has undergone pulpal necrosis). To reflect this, sometimes the term "lateral (periodontal) abscess" is used. In contrast to a periapical abscess, periodontal abscesses are usually associated with a vital (living) tooth. Abscesses of the periodontium are acute bacterial infections classified primarily by location.

Signs and symptoms
The main symptom is pain, which often suddenly appears, and is made worse by biting on the involved tooth, which may feel raised and prominent in the bite. The tooth may be mobile, and the lesion may contribute to destruction of the periodontal ligament and alveolar bone. The pain is deep and throbbing. The oral mucosa covering an early periodontal abscess appears erythematous (red), swollen and painful to touch. The surface may be shiny due to stretching of the mucosa over the abscess. Before pus has formed, the lesion will not be fluctuant, and there will be no purulent discharge. There may be regional lymphadenitis.
When pus forms, the pressure increases, with increasing pain, until it spontaneously drains and relieves the pain. When pus drains into the mouth, a bad taste and smell are perceived. Usually drainage occurs via the periodontal pocket, or else the infection may spread as a cellulitis or a purulent odontogenic infection. Local anatomic factors determine the direction of spread (see fascial spaces of the head and neck). There may be systemic upset, with an onset of pain and fever.

Causes
A periodontal abscess most commonly occurs as a complication of advanced periodontal disease (which is normally painless). A periodontal pocket contains dental plaque, bacteria and subgingival calculus. Periodontal pathogens continually find their way into the soft tissues, but normally they are held in check by the immune system. A periodontal abscess represents a change in this balance, related to decreased local or systemic resistance of the host. An inflammatory response occurs when bacteria invade and multiply within the soft tissue of the gingival crevice/periodontal pocket. A pus-filled abscess forms when the immune system responds and attempts to isolate the infection from spreading.
Communication with the oral environment is maintained via the opening of the periodontal pocket. However, if the opening of a periodontal pocket becomes obstructed, as may occur if the pocket has become very deep (e.g. with furcation involvement), then plaque and calculus are trapped inside. Food packing may also obstruct a periodontal pocket. Food packing is usually caused by failure to accurately reproduce the contact points when dental restorations are placed on the interproximal surfaces of teeth. Another potential cause occurs when a periodontal pocket is scaled incompletely. Following this procedure, the gingival cuff tightens around the tooth, which may be enough to trap the bacteria left in the pocket. A gingival retraction cord which is accidentally left in situ is an occasional cause of a periodontal abscess.
Penetrating injury to the gingiva--for example, with a toothbrush bristle, fishbone, toothpick or periodontal instrument--may inoculate bacteria into the tissues. Trauma to the tissues, such as serious impact on a tooth or excessive pressure exerted on teeth during orthodontic treatment, can be a possible cause as well. Occlusal overload may also be involved in the development of a periodontal abscess, but this is rare and usually occurs in combination with other factors. Bruxism is a common cause of excessive occlusal forces.
Systemic immune factors such as diabetes can predispose a person to the formation of periodontal abscesses.
Perforation of a root canal during endodontic therapy can also lead to a periodontal abscess which if left untreated could become "prolonged" ultimately rupture then enter the blood stream and could lead to serious situations such as endocarditis.

Diagnosis
Periodontal abscesses may be difficult to distinguish from periapical abscesses. Since the management of a periodontal abscess is different from a periapical abscess, this differentiation is important to make (see Dental abscess#Diagnostic approach) For example, root canal therapy is unnecessary and has no impact on pain in a periodontal abscess.

Classification
There are four types of abscesses that can involve the periodontal tissues:
Gingival abscess—a localized, purulent infection involves only the soft gum tissue near the marginal gingiva or the interdental papilla.
Periodontal abscess—a localized, purulent infection involving a greater dimension of the gum tissue, extending apically and adjacent to a periodontal pocket.
Pericoronal abscess—a localized, purulent infection within the gum tissue surrounding the crown of a partially or fully erupted tooth </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Ketoacidosis and explain in detail? [/INST] Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in blood pH and requires medical attention. The most common cause of ketoacidosis is diabetic ketoacidosis but can also be caused by alcohol, medications, toxins, and rarely starvation.

Signs and symptoms
The symptoms of ketoacidosis are variable depending on the underlying cause. The most common symptoms include nausea, vomiting, abdominal pain, and weakness. Breath may also develop the smell of acetone as it is a volatile ketone that can be exhaled. Rapid deep breathing, or Kussmaul breathing, may be present to compensate for the metabolic acidosis. Altered mental status is more common in diabetic than alcoholic ketoacidosis.

Causes
Ketoacidosis is caused by the uncontrolled production of ketone bodies. Usually the production of ketones is carefully controlled by several hormones, most importantly insulin. If the mechanisms that control ketone production fail, ketone levels may become dramatically elevated and cause dangerous changes in physiology such as a metabolic acidosis.

Diabetes
The most common cause of ketoacidosis is a deficiency of insulin in type 1 diabetes or late-stage type 2 diabetes. This is called diabetic ketoacidosis and is characterized by hyperglycemia, dehydration and metabolic acidosis. Other electrolyte disturbances such as hyperkalemia and hyponatremia may also be present. A lack of insulin in the bloodstream allows unregulated fatty acid release from adipose tissue which increases fatty acid oxidation to acetyl CoA, some of which is diverted to ketogenesis. This raises ketone levels significantly above what is seen in normal physiology.

Alcohol
Alcoholic ketoacidosis is caused by complex physiology that is usually the result of prolonged and heavy alcohol intake in the setting of poor nutrition. Chronic alcohol use can cause depleted hepatic glycogen stores and ethanol metabolism further impairs gluconeogenesis. This can reduce glucose availability and lead to hypoglycemia and increased reliance on fatty acid and ketone metabolism. An additional stressor such as vomiting or dehydration can cause an increase in counterregulatory hormones such as glucagon, cortisol and growth hormone which may further increase free fatty acid release and  ketone production. Ethanol metabolism can also increase blood lactic acid levels which may also contribute to a metabolic acidosis.

Starvation
Starvation is a rare cause of ketoacidosis, usually instead causing physiologic ketosis without ketoacidosis. Ketoacidosis from starvation most commonly occurs in the setting of an additional metabolic stressor such as pregnancy, lactation, or acute illness.

Medications
Certain medications can also cause elevated ketones, such as SGLT2 inhibitors causing euglycemic ketoacidosis. Overdose of salicylates or isoniazid can also cause ketoacidosis.

Toxins
Ketoacidosis can be the result of ingestion of methanol, ethylene glycol, isopropyl alcohol, and acetone.

Pathophysiology
Ketones are primarily produced from free fatty acids in the mitochondria of liver cells. The production of ketones is strongly regulated by insulin and an absolute or relative lack of insulin underlies the pathophysiology of ketoacidosis. Insulin is a potent inhibitor of fatty acid release, so insulin deficiency can cause an uncontrolled release of fatty acids from adipose tissue </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Achondroplasia and explain in detail? [/INST] Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected have an average adult height of 131 centimetres (4 ft 4 in) for males and 123 centimetres (4 ft) for females. Other features can include an enlarged head and prominent forehead. Complications can include sleep apnea or recurrent ear infections. Achondroplasia includes short-limb skeletal dysplasia with severe combined immunodeficiency.
Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that results in its protein being overactive. Achondroplasia results in impaired endochondral bone growth (bone growth within cartilage). The disorder has an autosomal dominant mode of inheritance, meaning only one mutated copy of the gene is required for the condition to occur. About 80% of cases occur in children of parents of average stature and result from a new mutation, which most commonly originates as a spontaneous change during spermatogenesis. The rest are inherited from a parent with the condition. The risk of a new mutation increases with the age of the father. In families with two affected parents, children who inherit both affected genes typically die before birth or in early infancy from breathing difficulties. The condition is generally diagnosed based on the clinical features but may be confirmed by genetic testing.Treatments may include support groups and growth hormone therapy. Efforts to treat or prevent complications such as obesity, hydrocephalus, obstructive sleep apnea, middle ear infections or spinal stenosis may be required. Achondroplasia is the most common cause of dwarfism and affects about 1 in 27,500 people.

Signs and symptoms
Disproportionate dwarfism
Shortening of the proximal limbs (called rhizomelic shortening)
Short fingers and toes, with "trident hands" (short hands with stubby fingers, and a separation between the middle and ring fingers – reminiscent of a trident on fetal ultrasound )
Large head with prominent forehead frontal bossing
Small midface with a flattened nasal bridge
Spinal kyphosis (convex curvature) or lordosis (concave curvature)
Varus (bowleg) or valgus (knock knee) deformities
Frequent ear infections (due to Eustachian tube blockages), sleep apnea (which can be central or obstructive), and hydrocephalus

Complications
Children
Children with achondroplasia often have less muscle tone; because of this it is common for them to have delayed walking and motor skills. It is also common for children to have bowed legs, scoliosis, lordosis, arthritis, issues with joint flexibility, breathing problems, ear infections, and crowded teeth. These issues can be treated with surgery, braces, or physical therapy.
Hydrocephalus is a severe effect associated with achondroplasia in children. This condition occurs when cerebrospinal fluid is not able to flow in and out of the skull because of how the spine narrows. This fluid build up is associated with an enlarged head, vomiting, lethargy, headaches, and irritability. A shunt surgery is commonly performed to treat this condition, but an endoscopic third ventriculostomy can also be done.

Adults
Adults with achondroplasia often face issues with obesity and sleep apnea. It is also typical for adults to experience numbness or tingling in their legs because of nerve compression.
Some research has found that adults with achondroplasia may also experience psychosocial complications, usually associated with short stature.Pregnancy in women with achondroplasia is considered higher risk. Women with achondroplasia generally have their babies delivered through C-sections to prevent complications that could occur with a natural birth. The life expectancy of people with achondroplasia is approximately 10 years less than average.

Causes
Achondroplasia is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3) gene. This gene encodes a protein called fibroblast growth factor receptor 3, which contributes to the production of collagen and other structural components in tissues and bones. When the FGFR3 gene is mutated it interferes with how this protein interacts with growth factors leading to complications with bone production. Cartilage is not able to fully develop into bone, causing the individual to be disproportionately shorter in height.In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal (recessive lethal) before or shortly after birth (known as a lethal allele). This occurs due to respiratory failure from an underdeveloped ribcage. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring. People with achondroplasia are often born to parents that do not have the condition due to spontaneous mutation.Achondroplasia can be inherited through autosomal dominance. In couples where one partner has achondroplasia there is a 50% chance of passing the disorder on to their child every pregnancy. In situations where both parents have achondroplasia there is a 50% chance the child will have achondroplasia, 25% chance the child will not, and a 25% chance that the child will inherit the gene from both parents resulting in double dominance and leading to severe or lethal bone dysplasia.Studies have demonstrated that new gene mutations for achondroplasia are exclusively inherited from the father and occur during spermatogenesis; it has been theorized that sperm carrying the mutation in FGFR3 have a selective advantage over sperm with normal FGFR3. The frequency of mutations in sperm leading to achondroplasia increases in proportion to paternal age, as well as in proportion to exposure to ionizing radiation. The occurrence rate of achondroplasia in the children of fathers over 50 years of age is 1 in 1,875, compared to 1 in 15,000 in the general population. Research by urologist Harry Fisch of the Male Reproductive Center at Columbia Presbyterian Hospital in 2013 indicated that in humans this defect may be exclusively inherited from the father and becomes increasingly probable with paternal age, specifically males reproducing after 35.There are two other syndromes with a genetic basis similar to achondroplasia: hypochondroplasia and thanatophoric dysplasia.

Diagnosis
Achondroplasia can be detected before birth by prenatal ultrasound, although signs are often subtle and not apparent before the 24th week of pregnancy. A DNA test can be performed before birth to detect homozygosity, wherein two copies of the mutant gene are inherited, a lethal condition leading to stillbirths. Postnatal diagnosis of achondroplasia is typically uncomplicated, involving an assessment of physical and radiographic features.  Clinical features include megalocephaly, short limbs, prominent forehead, thoracolumbar kyphosis and mid-face hypoplasia. Complications like dental malocclusion, hydrocephalus and repeated otitis media can be observed. The risk of death in infancy is increased due to the likelihood of compression of the spinal cord with or without upper airway obstruction.

Radiologic findings
A skeletal survey is useful to confirm the diagnosis of achondroplasia. The skull is large, with a narrow foramen magnum, and relatively small skull base. The vertebral bodies are short and flattened with relatively large intervertebral disk height, and there is congenitally narrowed spinal canal. The iliac wings are small and squared, with a narrow sciatic notch and horizontal acetabular roof. The tubular bones are short and thick with metaphyseal cupping and flaring and irregular growth plates. Fibular overgrowth is present. The hand is broad with short metacarpals and phalanges, and a trident configuration. The ribs are short with cupped anterior ends. If the radiographic features are not classic, a search for a different diagnosis should be entertained. Because of the extremely deformed bone structure, people with achondroplasia are often "double jointed". The diagnosis can be made by fetal ultrasound by progressive discordance between the short femur length and biparietal diameter by age. The trident hand configuration can be seen if the fingers are fully extended.Another common characteristic of the syndrome is thoracolumbar gibbus in infancy.

Treatment
There is no known cure for achondroplasia even though the cause of the mutation in the growth factor receptor has been found. Although used by those without achondroplasia to aid in growth, human growth hormone does not help people with achondroplasia, which involve a different hormonal pathway. Usually, the best results appear within the first and second year of therapy. After the second year of growth hormone therapy, beneficial bone growth decreases, so the therapy is not a satisfactory long-term treatment. As of December 2020, the treatment of achondroplasia with human growth hormone was approved only in Japan.An experimental drug called vosoritide has shown promise in stage 3 human trials, although its long-term effects are unknown.Limb-lengthening will increase the length of the legs and arms of someone with achondroplasia,  but little medical consensus exists regarding this practice. The age of surgery can vary from early childhood to adulthood.Research has also shown that introducing parents of children with achondroplasia to support and advocacy groups at the time of diagnosis can improve outcomes. Several patient advocacy groups exist to support people with achondroplasia and their families.

Epidemiology
Achondroplasia is one of several congenital conditions with similar presentations, such as osteogenesis imperfecta, multiple epiphyseal dysplasia tarda, achondrogenesis, osteopetrosis, and thanatophoric dysplasia. This makes estimates of prevalence difficult, with changing and subjective diagnostic criteria over time. One detailed and long-running study in the Netherlands found that the prevalence determined at birth was only 1.3 per 100,000 live births. Another study at the same time found a rate of 1 per 10,000. A 2020 review and meta-analysis estimated a worldwide prevalence of 4.6 per 100,000.

Research
As of 2019, tentative evidence has found that the experimental peptide drug vosoritide increases growth velocity in those with achondroplasia. The drug inhibits the activity of FGFR3.

Animals
Based on their disproportionate dwarfism, some dog breeds traditionally have been classified as "achondroplastic". This is the case for the dachshund, basset hound, corgi and bulldog breeds. Data from whole genome association studies in short-limbed dogs reveal a strong association of this trait with a retro-gene coding for fibroblast growth factor 4 (FGF4). Therefore, it seems unlikely that dogs and humans are achondroplastic for the same reasons. However, histological studies in some achondroplastic dog breeds have shown altered cell patterns in cartilage that are very similar to those observed in humans exhibiting achondroplasia.A similar form of achondroplasia was found in a litter of piglets from a phenotypically normal Danish sow. The dwarfism was inherited dominant in the offspring from this litter. The piglets were born phenotypically normal, but became more and more symptomatic as they reached maturity </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Mortons neuroma and explain in detail? [/INST] Mortons neuroma  is a benign neuroma of an intermetatarsal plantar nerve, most commonly of the second and third intermetatarsal spaces (between the second/third and third/fourth metatarsal heads; the first is of the big toe), which results in the entrapment of the affected nerve. The main symptoms are pain and/or numbness, sometimes relieved by ceasing to wear footwear with tight toe boxes and high heels (which have been linked to the condition). The condition is named after Thomas George Morton, though it was first correctly described by a chiropodist named Durlacher.Some sources claim that entrapment of the plantar nerve resulting from compression between the metatarsal heads, as originally proposed by Morton, is highly unlikely, because the plantar nerve is on the plantar side of the transverse metatarsal ligament and thus does not come into contact with the metatarsal heads. It is more likely that the transverse metatarsal ligament is the cause of the entrapment.Though the condition is labeled as a neuroma, many sources do not consider it a true tumor, but rather a perineural fibroma (fibrous tissue formation around nerve tissue).

Signs and symptoms
Symptoms include pain on weight bearing, frequently after only a short time. The nature of the pain varies widely among individuals. Some people experience shooting pain affecting the contiguous halves of two toes. Others describe a feeling akin to having a pebble in the shoe or walking on razor blades. Burning, numbness, and paresthesia may also be experienced. The symptoms progress over time, often beginning as a tingling sensation in the ball of the foot.Mortons neuroma lesions have been found using MRI in patients without symptoms.

Diagnosis
Negative signs include a lack of obvious deformities, erythema, signs of inflammation, or limitation of movement. Direct pressure between the metatarsal heads will replicate the symptoms, as will compression of the forefoot between the finger and thumb so as to compress the transverse arch of the foot. This is referred to as Mulders sign.There are other causes of pain in the forefoot that often lead to miscategorization as neuroma, such as capsulitis, which is an inflammation of ligaments that surround two bones at the level of the joint. If the ligaments that attach the phalanx (bone of the toe) to the metatarsal bone are impacted, the resulting inflammation may put pressure on an otherwise healthy nerve and produce neuroma-type symptoms. Additionally, an intermetatarsal bursitis between the third and fourth metatarsal bones will also give neuroma-type symptoms because it too puts pressure on the nerve. Freiberg disease, which is an osteochondritis of the metatarsal head, causes pain on weight-bearing or compression. Other conditions that could be clinically confused with a neuroma include stress fractures/reactions and plantar plate disruption.

Histopathology
Microscopically, the affected nerve is markedly distorted, with extensive concentric perineural fibrosis. The arterioles are thickened and occlusion by thrombi are occasionally present.

Imaging
Though a neuroma is a soft-tissue abnormality and will not be visualized by standard radiographs, the first step in the assessment of forefoot pain is an X-ray to detect the presence of arthritis and exclude stress fractures/reactions and focal bone lesions, which may mimic the symptoms of a neuroma. Ultrasound (sonography) accurately demonstrates thickening of the interdigital nerve within the web space of greater than 3mm, diagnostic of a Morton’s neuroma. This typically occurs at the level of the intermetatarsal ligament. Frequently, intermetatarsal bursitis coexists with the diagnosis. MRI can distinguish conditions that mimic the symptoms of Mortons neuroma, but when more than one abnormality exists, ultrasound has the added advantage of determining the precise source of the patient’s pain by applying direct pressure with the probe. Ultrasound may also be used to guide treatment such as cortisone injections into the webspace, as well as alcohol ablation of the nerve.

Treatment
Conservative
Orthotics and improved footwear are the first-line treatments for Morton’s neuroma. In addition to traditional orthotic arch supports, a small foam or fabric pad may be positioned under the space between the two affected metatarsals, immediately behind the bone ends. This pad helps to splay the metatarsal bones and create more space for the nerve so as to relieve pressure and irritation. However, it may also elicit mild uncomfortable sensations of its own, such as the feeling of having an awkward object under ones foot. Toe spreaders are another form of conservative orthotic treatment that may yield relief for Mortons neuroma symptoms. Footwear and orthotics are most effective in neuromas that have existed less than four and a half months and are smaller than 4–5 millimetres (0.16–0.20 in). To prevent or treat Mortons neuroma, comfortable shoes that are sufficiently long and have a wide toe box, flat heel, and thick sole are recommended.Corticosteroid injections can relieve inflammation in some patients and help end the symptoms. For some patients, however, the inflammation and pain recur after some weeks or months, and corticosteroids may only be used a limited number of times because they cause progressive degeneration of ligamentous and tendinous tissues. About 30% of people who receive steroid injections go on to have surgery. According to a 2021 review, it is most effective in neuromas smaller than 6.3 millimetres (0.25 in).Sclerosing alcohol injections are an increasingly available treatment alternative if other management approaches fail. Dilute alcohol (4%) is injected directly into the area of the neuroma, causing toxicity to the fibrous nerve tissue. Frequently, treatment must be performed two to four times, with one to three weeks between interventions. A 60–80% success rate has been achieved in clinical studies, equal to or exceeding the success rate for surgical neurectomy, with fewer risks and less significant recovery. If done with more concentrated alcohol under ultrasound guidance, the success rate is considerably higher and fewer repeat procedures are needed.Radiofrequency ablation is also used in the treatment of Mortons neuroma. The outcomes appear to be similar to, or even more reliable than, alcohol injections, especially if the procedure is performed under ultrasound guidance.A 2019 systematic review of randomised controlled trials found that corticosteroid injections or manipulation/mobilisation reduced pain more than control, extracorporeal shockwave therapy or varus/valgus foot wedges (which did not reduce pain more than control or comparison treatment, and pain reduction was not reported in any wider foot/metatarsal padding studies). The review also found no randomised controlled trials for sclerosing alcohol injections, radiofrequency ablations, cryoneurolysis or botulinum toxin injections. These treatments have only been assessed with pre-test/post-test case series, which do not measure the benefit of treatment beyond any placebo effect, sham treatment or any natural improvement over time.

Surgery
If non-surgical interventions fail, patients are commonly offered neurectomy, a surgery that involves removing the affected piece of nerve tissue. Postoperative scar tissue formation (known as stump neuroma) can occur in approximately 20–30% of cases, causing a return of neuroma symptoms. Neurectomy may be performed using one of two general methods. Making the incision from the dorsal side (the top of the foot) is the more common method but requires cutting the deep transverse metatarsal ligament that connects the third and fourth metatarsals in order to access the nerve beneath it. This results in exaggerated postoperative splaying of the third and fourth digits (toes) resulting from the loss of the supporting ligamentous structure </s>


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Carotid-cavernous fistula and explain in detail? [/INST] A carotid-cavernous fistula results from an abnormal communication between the arterial and venous systems within the cavernous sinus in the skull. It is a type of arteriovenous fistula. As arterial blood under high pressure enters the cavernous sinus, the normal venous return to the cavernous sinus is impeded and this causes engorgement of the draining veins, manifesting most dramatically as a sudden engorgement and redness of the eye of the same side.

Presentation
CCF symptoms include bruit (a humming sound within the skull due to high blood flow through the arteriovenous fistula), progressive visual loss, and pulsatile proptosis or progressive bulging of the eye due to dilatation of the veins draining the eye </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pantothenic acid and explain in detail? [/INST] Pantothenic acid, also called vitamin B5 is a water-soluble B vitamin and therefore an essential nutrient. All animals require pantothenic acid in order to synthesize coenzyme A (CoA) – essential for fatty acid metabolism – as well as to, in general, synthesize and metabolize proteins, carbohydrates, and fats.Pantothenic acid is the combination of pantoic acid and β-alanine. Its name derives from the Greek pantos, meaning "from everywhere", as minimally, at least small quantities of pantothenic acid are found in nearly every food.  Human deficiency is very rare. As a dietary supplement or animal feed ingredient, the form commonly used is calcium pantothenate because of chemical stability, and hence long product shelf life, compared to sodium pantothenate or free pantothenic acid.

Definition
Pantothenic acid is a water-soluble vitamin, one of the B vitamins. It is synthesized from the amino acid β-alanine and pantoic acid (see biosynthesis and structure of coenzyme A figures). Unlike vitamin E or vitamin K, which occurs in several chemically related forms known as vitamers, pantothenic acid is only one chemical compound. It is a starting compound in the synthesis of coenzyme A (CoA), a cofactor for many enzyme processes.

Use in biosynthesis of coenzyme A
Pantothenic acid is a precursor to CoA via a five-step process.  The biosynthesis requires pantothenic acid, cysteine, four equivalents of ATP (see figure).
Pantothenic acid is phosphorylated to 4′-phosphopantothenate by the enzyme pantothenate kinase. This is the committed step in CoA biosynthesis and requires ATP.
A cysteine is added to 4′-phosphopantothenate by the enzyme phosphopantothenoylcysteine synthetase to form 4-phospho-N-pantothenoylcysteine (PPC). This step is coupled with ATP hydrolysis.
PPC is decarboxylated to 4′-phosphopantetheine by phosphopantothenoylcysteine decarboxylase
4′-Phosphopantetheine is adenylated (or more properly, AMPylated) to form dephospho-CoA by the enzyme phosphopantetheine adenylyl transferase
Finally, dephospho-CoA is phosphorylated to coenzyme A by the enzyme dephosphocoenzyme A kinase. This final step also requires ATP.This pathway is suppressed by end-product inhibition, meaning that CoA is a competitive inhibitor of pantothenate kinase, the enzyme responsible for the first step.Coenzyme A is necessary in the reaction mechanism of the citric acid cycle. This process is the bodys primary catabolic pathway and is essential in breaking down the building blocks of the cell such as carbohydrates, amino acids and lipids, for fuel. CoA is important in energy metabolism for pyruvate to enter the tricarboxylic acid cycle (TCA cycle) as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction, and various enzyme functions. In addition to functioning as CoA, this compound can act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. CoA is also required in the formation of acyl carrier protein (ACP), which is required for fatty acid synthesis. Its synthesis also connects with other vitamins such as thiamin and folic acid.

Dietary recommendations
The US Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for B vitamins in 1998. At that time there was not sufficient information to establish EARs and RDAs for pantothenic acid. In instances such as this, the Board sets Adequate Intakes (AIs), with the understanding that at some later date, AIs may be replaced by more exact information.The current AI for teens and adults ages 14 and up is 5 mg/day. This was based in part on the observation that for a typical diet, urinary excretion was approximately 2.6 mg/day, and that bioavailability of food-bound pantothenic acid was roughly 50%. AI for pregnancy is 6 mg/day. AI for lactation is 7 mg/day. For infants up to 12 months the AI is 1.8 mg/day. For children ages 1–13 years the AI increases with age from 2 to 4 mg/day.  Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).
While for many nutrients, the US Department of Agriculture uses food composition data combined with food consumption survey results to estimate average consumption, the surveys and reports do not include pantothenic acid in the analyses. Less formal estimates of adult daily intakes report about 4 to 7 mg/day.The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in the US. For women and men over age 11 the Adequate Intake (AI) is set at 5 mg/day. AI for pregnancy is 5 mg/day, for lactation 7 mg/day. For children ages 1–10 years the AI is 4 mg/day. These AIs are similar to the US AIs.

Safety
As for safety, the IOM sets Tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of pantothenic acid there is no UL, as there is no human data for adverse effects from high doses. The EFSA also reviewed the safety question and reached the same conclusion as in United States – that there was not sufficient evidence to set a UL for pantothenic acid.

Labeling requirements
For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For pantothenic acid labeling purposes 100% of the Daily Value was 10 mg, but as of 27 May 2016 it was revised to 5 mg to bring it into agreement with the AI.
Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales. A table of the old and new adult daily values is provided at Reference Daily Intake.

Sources
Dietary
Food sources of pantothenic acid include animal-sourced foods, including dairy foods and eggs. Potatoes, tomato products, oat-cereals, sunflower seeds, avocado and mushrooms are good plant sources. Whole grains are another source of the vitamin, but milling to make white rice or white flour removes much of the pantothenic acid, as it is found in the outer layers of whole grains. In animal feeds, the most important sources are alfalfa, cereal, fish meal, peanut meal, molasses, rice bran, wheat bran, and yeasts.

Supplements
Dietary supplements of pantothenic acid commonly use pantothenol (or panthenol), a shelf-stable analog, which is converted to pantothenic acid once consumed. Calcium pantothenate – a salt – may be used in manufacturing because it is more resistant than pantothenic acid to factors that deteriorate stability, such as acid, alkali or heat. The amount of pantothenic acid in dietary supplement products may contain up to 1,000 mg (200 times the Adequate Intake level for adults), without evidence that such large amounts provide any benefit. According to WebMD, pantothenic acid supplements have a long list of claimed uses, but there is insufficient scientific evidence to support any of them.As a dietary supplement, pantothenic acid is not the same as pantethine, which is composed of two pantothenic acid molecules linked by a disulfide bridge. Sold as a high-dose supplement (600 mg), pantethine may be effective for lowering blood levels of LDL cholesterol – a risk factor for cardiovascular diseases – but its long-term effects are unknown, requiring that its use be supervised by a physician. Dietary supplementation with pantothenic acid does not have the same effect on LDL.

Fortification
According to the Global Fortification Data Exchange, pantothenic acid deficiency is so rare that no countries require that foods be fortified.

Absorption, metabolism and excretion
When found in foods, most pantothenic acid is in the form of CoA or bound to acyl carrier protein (ACP).  For the intestinal cells to absorb this vitamin, it must be converted into free pantothenic acid.  Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4-phosphopantetheine. The 4-phosphopantetheine is then dephosphorylated into pantetheine.  Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid. Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system. At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be additionally absorbed via passive diffusion. As a whole, when intake increases 10-fold, absorption rate decreases to 10%.Pantothenic acid is excreted in urine. This occurs after its release from CoA. Urinary amounts are on the order of 2.6 mg/day, but decreased to negligible amounts when subjects in multi-week experimental situations were fed diets devoid of the vitamin.

Deficiency
Pantothenic acid deficiency in humans is very rare and has not been thoroughly studied. In the few cases where deficiency has been seen (prisoners of war during World War II, victims of starvation, or limited volunteer trials), nearly all symptoms were reversed with orally administered pantothenic acid. Symptoms of deficiency are similar to other vitamin B deficiencies. There is impaired energy production, due to low CoA levels, which could cause symptoms of irritability, fatigue, and apathy. Acetylcholine synthesis is also impaired; therefore, neurological symptoms can also appear in deficiency; they include sensation of numbness in hands and feet, paresthesia and muscle cramps. Additional symptoms could include restlessness, malaise, sleep disturbances, nausea, vomiting and abdominal cramps.In animals, symptoms include disorders of the nervous, gastrointestinal, and immune systems, reduced growth rate, decreased food intake, skin lesions and changes in hair coat, and alterations in lipid and carbohydrate metabolism. In rodents, there can be loss of hair color, which led to marketing of pantothenic acid as a dietary supplement which could prevent or treat graying of hair in humans (despite the lack of any human trial evidence).Pantothenic acid status can be assessed by measuring either whole blood concentration or 24-hour urinary excretion. In humans, whole blood values less than 1 μmol/L are considered low, as is urinary excretion of less than 4.56 mmol/day.

Animal nutrition
Calcium pantothenate and dexpanthenol (D-panthenol) are European Food Safety Authority (EFSA) approved additives to animal feed. Supplementation is on the order of 8–20 mg/kg for pigs, 10–15 mg/kg for poultry, 30–50 mg/kg for fish and 8–14 mg/kg feed for pets. These are recommended concentrations, designed to be higher than what are thought to be requirements. There is some evidence that feed supplementation increases pantothenic acid concentration in tissues, i.e., meat, consumed by humans, and also for eggs, but this raises no concerns for consumer safety.No dietary requirement for pantothenic acid has been established in ruminant species. Synthesis of pantothenic acid by ruminal microorganisms appears to be 20 to 30 times more than dietary amounts. Net microbial synthesis of pantothenic acid in the rumen of steer calves has been estimated to be 2.2 mg/kg of digestible organic matter consumed per day. Supplementation of pantothenic acid at 5 to 10 times theoretical requirements did not improve growth performance of feedlot cattle.

Synthesis
Biosynthesis
Bacteria synthesize pantothenic acid from the amino acids aspartate and a precursor to the amino acid valine. Aspartate is converted to β-alanine. The amino group of valine is replaced by a keto-moiety to yield α-ketoisovalerate, which, in turn, forms α-ketopantoate following transfer of a methyl group, then D-pantoate (also known as pantoic acid) following reduction. β-alanine and pantoic acid are then condensed to form pantothenic acid (see figure).

Industrial synthesis
The industrial synthesis of pantothenic acid starts with the aldol condensation of isobutyraldehyde and formaldehyde. The resulting hydroxypivaldehyde is converted to its cyanohydrin derivative. which is cyclised to give racemic pantolactone </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hyperpituitarism and explain in detail? [/INST] Hyperpituitarism is a condition due to the primary hypersecretion of pituitary hormones; it typically results from a pituitary adenoma. In children with hyperpituitarism, disruption of growth regulation is rare, either because of hormone hypersecretion or because of manifestations caused by local compression of the adenoma.

Symptoms and signs
Symptoms caused by hormone excess and associated mass effects include:

Cause
The cause of hyperpituitarism in most cases is due to pituitary adenomas. They usually come from the anterior lobe, are functional and secrete the hormone, GH and prolactin.

Mechanism
Evidence indicates that the mechanism of hyperpituitarism can originate from genetic disruption causing pituitary tumorigenesis, most pituitary adenomas are monoclonal, which in turn indicates their origin from an event in a single cell. There are three hormones that are oversecreted resulting in the pituitary adenoma: prolactin, adrenocorticotropic hormone (ACTH), and growth hormone (GH).Excess prolactin may result in a prolactinoma Excess GH results in gigantism, the severity of gigantism depends on whether the epiphyseal plate is open. The four most common types of hyperpituitarism are caused by 4 types of pituitary adenoma, as follows: prolactinoma, corticotropinoma (Cushings disease), somatotropinoma (gigantism), and thyrotropinoma .

Diagnosis
For the diagnosis of hyperpituitarism it depends on the cell type(s) affected, clinical manifestations of hormone excess may include, gigantism or acromegaly, which can be identified by clinical and radiographic results. Cushings disease diagnosis is done with a physical examination, laboratory tests and X rays of the pituitary glands (to locate tumors) For prolactinoma, diagnosis comes in the form of the measurement of serum prolactin levels and x-ray of pituitary gland.

Treatment
Treatment (for hyperpituitarism) in the case of prolactinoma consists of long-term medical management. Dopamine agonists are strong suppressors of PRL secretion and establish normal gonadal function. It also inhibits tumor cell replication (in some cases causes tumor shrinkage) Treatment for gigantism begins with establishing target goals for IGF-1, transsphenoidal surgery (somatostatin receptor ligands- preoperatively) and postoperative imaging assessment. For Cushings disease there is surgery to extract the tumor; after surgery, the gland may slowly start to work again, though not always.

See also
Hypopituitarism

References
Further reading
Handbook of Medical-surgical Nursing. Lippincott Williams & Wilkins. 2006-01-01 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Small fiber peripheral neuropathy and explain in detail? [/INST] Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated and myelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, peripheral nerves, and organs. The role of these nerves is to innervate the skin (somatic fibers) and help control autonomic function (autonomic fibers). It is estimated that 15–20 million people in the United States have some form of peripheral neuropathy.

Signs and symptoms
Small fiber neuropathy is a condition characterized by severe pain. Symptoms typically begin in the feet or hands but can start in other parts of the body. Some people initially experience a more generalized, whole-body pain. The pain is often described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy can occur at any point in life depending on the underlying cause.
Individuals with small fiber neuropathy often cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (allodynia). People affected with this condition may also have a reduced ability to differentiate between hot and cold.
Sudomotor dysfunction is one of the most common and earliest neurophysiological manifestations of small fiber neuropathies.In some instances, the small fibers of the autonomic nervous system can be affected, leading to urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting.
Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. Insensitivity to pain can be particularly problematic. One may be bleeding or have a skin injury without even knowing it.

Topographic pattern
Like many polyneuropathies, the symptoms are typically length-dependent, starting in the longer nerves and progressively attacking shorter nerves. This means that symptoms often start in the hands and feet before progressing upwards, and that symptoms are usually more severe in the extremities. Some patients have a widespread, non-length dependent, or "patchy", presentation which is sporadic and can affect many nerves.
Patients with Fabry disease have isolated small fiber engagement, and can have a more widespread small fiber disruption.

Causes
Mutations in the SCN9A or SCN10A gene can cause small fiber neuropathy. These genes provide instructions for making pieces (the alpha subunits) of sodium channels. The SCN9A gene instructs the production of the alpha subunit for the NaV1.7 sodium channel and the SCN10A gene instructs the production of the alpha subunit for the NaV1.8 sodium channel. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cells ability to generate and transmit electrical signals. The NaV1.7 and NaV1.8 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.
The SCN9A gene mutations that cause small fiber neuropathy result in NaV1.7 sodium channels that do not close completely when the channel is turned off. Many SCN10A gene mutations result in NaV1.8 sodium channels that open more easily than usual. The altered channels allow sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, causing individuals to be more sensitive to stimulation that might otherwise not cause pain. In this condition, the small fibers that extend from the nociceptors through which pain signals are transmitted (axons) degenerate over time. The cause of this degeneration is unknown, but it likely accounts for signs and symptoms such as the loss of temperature differentiation and pinprick sensation. The combination of increased pain signaling and degeneration of pain-transmitting fibers leads to a variable condition with signs and symptoms that can change over time.
SCN9A gene mutations have been found in approximately 30 percent of individuals with small fiber neuropathy; SCN10A gene mutations are responsible for about 5 percent of cases. In some instances, other health conditions cause this disorder. Diabetes mellitus and impaired glucose tolerance are the most common diseases that lead to this disorder, with 6 to 50 percent of diabetics or pre-diabetics developing small fiber neuropathy. Other causes of this condition include a metabolic disorder called Fabry disease, immune disorders such as celiac disease or Sjogren syndrome, an inflammatory condition called sarcoidosis, and human immunodeficiency virus (HIV) infection.Recently several studies have suggested an association between autonomic small fiber neuropathy and postural orthostatic tachycardia syndrome. Other notable studies have shown a link between erythromelalgia, fibromyalgia, and Ehlers–Danlos Syndrome.

Diagnosis
The diagnosis of small fiber neuropathy often requires ancillary testing </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Abruzzo–Erickson syndrome and explain in detail? [/INST] Abruzzo–Erickson syndrome is an extremely rare disorder characterized by deafness, protruding ears, coloboma, a cleft palate or palatal rugosity, radial synostosis, and short stature. It was first characterized by Abruzzo and Erickson in 1977 as a CHARGE like syndrome as variably expressed among a family of two brothers, their mother, and their maternal uncle. Members of this family exhibited many of the CHARGE symptoms, but notably did not have choanal atresia and the brothers experienced typical genital development. Due to the recent discovery of this disorder, its etiology is not fully known but it is understood that it arises from mutations on the TBX22 gene on the X-chromosome. The disorder is inherited in an X-linked recessive manner. There is currently no known cure but its symptoms can be treated.

Signs and Symptoms
Abruzzo-Erikson syndrome is characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis. There are also additional symptoms that are very similar to CHARGE syndrome such as large and protruding ears, wide spacing between the second and third fingers, ulnar deviation, facial asymmetry, dental abnormalities, and congenital heart malformation. However, in contrast to CHARGE syndrome, patients with Abruzzo-Erikson syndrome do not display intellectual disability, choanal atresia, or genital hypoplasia. As with most diseases, the symptoms will vary from person to person.

Genetics
While the complete etiology is not fully known, Abruzzo-Erickson Syndrome arises in part due to mutations on the TBX22 gene, a gene that is located on the X-chromosome (around 80,014,753 to 80,031,774 bp), and is inherited in an X-linked recessive manner. The T-box transcription factor TBX22 plays an essential role in normal craniofacial development. Nonsense, frameshift, splice-site and missense mutations in this region can result in patients with X-linked cleft palate (CPX) and ankyloglossia phenotypes. The CPX phenotype observed in individuals with Abruzzo-Erickson Syndrome most likely results from a loss of protein function as severely truncated proteins can result from the introduction of a premature stop codon can result from nonsense, splice-site, or frame shift sequence changes, while missense mutations in this region have less of a structural effect on the protein, but instead interferes with DNA binding and transcriptional activity.

Diagnosis
Abruzzo–Erickson syndrome can be diagnosed on the basis of a complete physical examination (as patients with the syndrome often possess noticeable physical characteristics such as a cleft palate, large protruding ears, and facial asymmetry) </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anemia of prematurity and explain in detail? [/INST] Anemia of prematurity (AOP) refers to a form of anemia affecting preterm infants with decreased hematocrit. AOP is a normochromic, normocytic hypoproliferative anemia. The primary mechanism of AOP is a decrease in erythropoietin (EPO), a red blood cell growth factor.

Pathophysiology
Preterm infants are often anemic and typically experience heavy blood losses from frequent laboratory testing in the first few weeks of life.  Although their anemia is multifactorial, repeated blood sampling and reduced erythropoiesis with extremely low serum levels of erythropoietin (EPO) are major causative factors. Blood sampling done for laboratory testing can easily remove enough blood to produce anemia. Obladen, Sachsenweger and Stahnke (1987) studied 60 very low birth weight infants during the first 28 days of life.  Infants were divided into 3 groups, group 1 (no ventilator support, 24 ml/kg blood loss), group 2(minor ventilated support, 60 ml/kg blood loss), and group 3(ventilated support for respiratory distress syndrome, 67 ml/kg blood loss).  Infants were checked for clinical symptoms and laboratory signs of anemia 24 hours before and after the blood transfusion.  The study found that groups 2 and 3 who had significant amount of blood loss, showed poor weight gain, pallor and distended abdomen.  These reactions are the most frequent symptoms of anemia in very low birth weight infants.During the first weeks of life, all infants experience a decline in circulating red blood cell (RBC) volume generally expressed as blood hemoglobin concentration (Hb). As anemia develops, there is even more of a significant reduction in the concentration of hemoglobin. Normally this stimulates a significant increased production of erythropoietin (EPO), but this response is diminished in premature infants.  Dear, Gill, Newell, Richards and Schwarz (2005) conducted a study to show that there is a weak negative correlation between EPO and Hb.  The researchers recruited 39 preterm infants from 10 days of age or as soon as they could manage without respiratory support.  They estimated total EPO and Hb weekly and 2 days after a blood transfusion.  The study found that when Hb>10, EPO mean was 20.6 and when Hb≤10, EPO mean was 26.8.  As Hb goes down, EPO goes up. While the reason for this decreased response is not fully understood, Strauss (n.d.) states that it results from both physiological factors (e.g., the rapid rate of growth and need for a commensurate increase in RBC mass to accompany the increase in blood volume) and, in sick premature infants, from phlebotomy blood losses.  In premature infants this decline occurs earlier and more pronounced that it does in healthy term infants.  Healthy term infants Hb rarely falls below 9 g/dL at an age of approximately 10–12 weeks, while in premature infants, even in those without complicating illnesses, the mean Hb falls to approximately 8g/dL in infants of 1.0-1.5 kg birth weight and to 7g/dL in infants <1.0 kg.  Because this postnatal drop in hemoglobin level is universal and is well tolerated in term infants, it is commonly referred to as the “physiologic” anemia of infancy.  However, in premature infants the decline in Hb may be associated with abnormal clinical signs severe enough to prompt transfusions.

Treatment
Transfusion
AOP is usually treated by blood transfusion but the indications for this are still unclear.  Blood transfusions have both infectious and non-infectious risks associated with them.  Also, blood transfusions are costly and may add to parental anxiety.  The best treatment for AOP is prevention of worsening of anemia by minimizing the amount of blood drawn from the infant (ie, anemia from phlebotomy). It is found that since blood loss attributable to laboratory testing is the primary cause of anemia among preterm infants during the first weeks of life, it would be useful to quantify blood loss attributable to phlebotomy overdraw (ie, blood collected in excess than what is strictly required for the requested lab tests).  Lin and colleagues performed a study to see when and if phlebotomy overdraw was actually a significant problem.  They recorded all of the data that could be of influence such as the test performed, the blood collection container used, the infants location (neonatal intensive care unit (NICU) and intermediate intensive care unit), the infant’s weight sampling and the phlebotomist’s level of experience, work shift, and clinical role.  Infants were classified by weight into 3 groups: <1 kg, 1 to 2 kg, and >2 kg.  The volume of blood removed was calculated by subtracting the weight of the empty collection container from that of the container filled with blood.  They found that the mean volume of blood drawn for the 578 tests exceeded that requested by the hospital laboratory by 19.0% ± 1.8% per test.  The main factors of overdraw was: collection in blood containers without fill-lines, lighter weight infants and critically ill infants being cared for in the NICU.

EPO
Recombinant EPO (r-EPO) may be given to premature infants to stimulate red blood cell production. Brown and Keith studied two groups of 40 very low birth weight (VLBW) infants to compare the erythropoietic response between two and five times a week dosages of recombinant human erythropoietin (r-EPO) using the same dose.  They established that more frequent dosing of the same weekly amount of r-EPO generated a significant and continuous increase in Hb in VLBW infants.  The infants that received five dosages had higher absolute reticulocyte counts (219,857 mm³) than those infants that received only two dosages (173,361 mm³).  However, it was noted that the response to r-EPO typically takes up to two weeks. This study also showed responses between two dosage schedules (two times a week and five times a week).  Infants were recruited for gestational age—age since conception—≤27 weeks and 28 to 30 weeks and then randomized into the two groups, each totaling 500 U/kg a week.  Brown and Keith found that after two weeks of r-EPO administration, Hb counts had increased and leveled off; the infants who received r-EPO five times a week had significantly higher Hb counts.  This was present at four weeks for all infants ≤30 weeks gestation and at 8 weeks for infants ≤27 weeks gestation.To date, studies of r-EPO use in premature infants have had mixed results. Ohls et al. examined the use of early r-EPO plus iron and found no short-term benefits in two groups of infants (172 infants less than 1000 g and 118 infants 1000–1250 g).  All r-EPO treated infants received 400 U/g three times a week until they reached 35 weeks gestational age.  The use of r-EPO did not decrease the average number of transfusions in the infants born at less than 1000 g, or the percentage of infants in the 1000 to 1250 group.  A multi-center European trial studied early versus late r-EPO in 219 infants with birth weights between 500 and 999 g.  An r-EPO close of 750 U/kg/week was given to infants in both the early (1–9 weeks) and late (4–10 weeks) groups.  The two r-EPO groups were compared to a control group who did not receive r-EPO.  Infants in all three groups received 3 to 9 mg/kg of enteral iron.  These investigators reported a slight decrease in transfusion and donor exposures in the early r-EPO group (1–9 weeks): 13% early, 11% late and 4% control group.  It is likely that only a carefully selected subpopulation of infants may benefit from its use </s>