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Neutrophilic eccrine hidradenitis	Neutrophilic eccrine hidradenitis (NEH) usually is a cutaneous complication of chemotherapy, but it can also occur for other reasons. It consists of fever and non specific skin lesions. It is rare, and self-limited. Signs and symptoms Fever and a non specific skin eruption – with reddening (erythema) and swelling (oedema) of the skin – are the most common symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis. Generalised lesions resembling erythema multiforme have been reported. Cause The overwhelming majority of neutrophilic eccrine hidradenitis (NEH) is seen in people with cancer, especially leukaemia, who receive chemotherapy with a cytotoxic drug. These include: Bleomycin, chlorambucil, cyclophosphamide, cytarabine, doxorubicin, lomustine, mitoxantrone, topotecan, and vincristine.NEH was first described in 1982 in a patient with acute myeloid leukaemia (AML) who had received cytarabine as chemotherapy.Cancer itself, infections, and other medicinal drugs also can lead to NEH. NEH has been reported in patients with cancer who have not received any form of chemotherapy (i.e., as a paraneoplastic syndrome), in patients with HIV and/or AIDS, and after the use of paracetamol (acetaminophen). Also the use of targeted agents can lead to NEH, e.g. imatinib, a tyrosine kinase inhibitor.NEH has also been described without any known reason (idiopathic cases), including idiopathic cases in children.The exact cause of NEH is unknown. In patients receiving chemotherapy, it has been postulated that a high concentration of the cytotoxic drug in sweat has a direct toxic effect on the eccrine glands. Diagnosis In all cases of suspected NEH, a skin biopsy should be performed, because the clinical symptoms are non specific, but the histopathological findings on the biopsy are specific. The biopsy shows characteristic changes of the eccrine glands, the major sweat glands of the body.In NEH, eccrine gland necrosis, and neutrophils surroundings the eccrine glands, are typical findings on biopsy. If the chemotherapy has recently been administered, chemotherapy induced neutropenia may be present, and, as a result, the neutrophils may be absent. But the other characteristic finding, i.e. eccrine gland necrosis, can still be seen. A vacuolar interface dermatitis also is visible in glands and ducts, along with necrosis of the lining cells. In addition, in patients receiving chemotherapy, keratinocyte atypia can be seen. Prevention A single case report suggested that oral dapsone may be useful for prevention. However, the efficacy of oral dapsone as prevention has not been demonstrated very clearly until now. Treatment NEH is self-limited and usually resolves without treatment. In the overwhelming majority of the cases, spontaneous resolution occurs within 1–2 weeks. However, if the patient developed NEH after chemotherapy, the offending cytotoxic drug has to be discontinued, and the patient must avoid this particular cytotoxic drug in the future, because NEH usually re occurs upon re exposure to the same cytotoxic drug.Despite the fact that NEH is self limited and usually resolves without treatment, some researchers use treatment, mainly systemic corticosteroids, although the efficacy of such a therapy has not been demonstrated in a large randomised controlled clinical trial until now. See also Skin lesion List of cutaneous conditions References == External links ==
Spermatocele	Spermatocele is a fluid-filled cyst that develops at the top of the testicle of the epididymis. The fluid is usually a clear or milky white color and may contain sperm. Spermatoceles are typically filled with spermatozoa and they can vary in size from several millimeters to many centimeters. Small spermatoceles are relatively common, occurring in an estimated 30 percent of males. They are generally not painful. However, some people may experience discomfort such as a dull pain in the scrotum from larger spermatoceles. They are not cancerous, nor do they cause an increased risk of testicular cancer. Additionally, unlike varicoceles, they do not reduce fertility. History "Spermatocele" is originally derived from the Greek term spermatos (sperm) and kele (cavity or mass). Oftentimes, "epididymal cyst" has been used interchangeably with "spermatocele." However, it is important to note their differences. Epididymal cysts may appear anywhere along or within the epididymis and do not contain sperm, whereas spermatoceles may contain sperm. Epididymal cysts have been shown to occur more frequently in children before reaching puberty. Epidemiology Spermatoceles usually affect men who are middle-aged and can, although rarely, affect children during puberty. The incidence rate is around 5-20% for children. It is estimated that approximately 30 percent of men have been diagnosed with small spermatoceles while less have larger spermatoceles. The incidence of spermatoceles increases as men age. Before puberty, children from the male sex may develop a similar benign mass called epididymis cyst. Although both epididymis cyst and spermatocele may be referred as the same, the epididymis cyst does not contain sperm and it can occur anywhere within the epididymis. It can be differentiated through an ultrasound imagining. Epididymis cysts larger than 10mm in diameter are recommended for surgery but if there is no problem then surgery is discouraged as it can affect fertility in the future. Chronic infectious epididymitis Chronic infectious epididymitis is rare. Some signs and symptoms include localized tenderness and swelling in the epididymis, which are different from any tenderness/abnormality present in the testis, these are usually not found in lower urinary tract. Chronic infectious epididymitis may be diagnosed in healthy adolescents as well as men. Some factors that predispose individuals to chronic infectious epididymitis include sexual activity, heavy physical exertion, and bicycle or motorcycle riding. Those diagnosed with chronic or recurrent epididymitis should receive a CT scan with contrast and a prostate ultrasonography to rule out structural abnormality of the urinary tract. If suspected to have chronic infectious epididymitis, consider getting a urinalysis, urine culture, and urine nucleic acid amplification tests for presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Management of chronic infectious epididymitis is similar to management of acute infectious epididymitis, rarely does treatment extend to surgical management. Chronic noninfectious epididymitis Chronic noninfectious epididymitis – Trauma, autoimmune disease, or vasculitis can cause chronic noninfectious epididymitis, but no clear cause or origin of the disease is found in most cases. Noninfectious epididymitis that happen spontaneously might be caused by the reflux of urine through the ejaculatory ducts and vas deferens into the epididymis, producing inflammation that leads to swelling and ductal obstruction. Men with history of vasectomy are also predisposed to chronic nonifectious epididymitis. Typical inciting factors include prolonged periods of sitting (long plane or car travel, sedentary desk jobs) or vigorous exercise (heavy lifting). Acute infectious epididymitis are often associated with more tenderness and swelling, whereas chronic noninfectious epididymitis tend to have less tenderness and swelling upon examination. Thorough past medical history and physical examination can help with determining the diagnosis. It is often that individuals with chronic noninfectious epididymitis will present with a history of a lack of symptom improvement while on antibiotic therapy. Management of chronic noninfectious epididymitis includes scrotal elevation, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (unless unable to take for medical reasons), and it is recommended that individuals avoid physical activities that may cause said symptoms. Those with sedentary jobs or often experience prolonged periods of time sitting should practice physical mobility more frequently. Risk Factors It is not well known what may be causing the growth of a spermatocele. It has been observed that pregnant women who were prescribed diethylstilbestro (DES) to prevent pregnancy complications, such as miscarriage, and gave birth to a son most likely increased the risk of the son to develop a spermatocele in the future. However, doctors stopped prescribing this medication in 1971 since it increased the risk of women developing a rare vaginal cancer. Causes Spermatoceles can originate as diverticulum from the tubules found in the head of the epididymis. Sperm accumulation gradually causes the diverticulum to increase in size, causing a spermatocele. Since there are many tubules connecting the epididymis to the testis, a blockage in one of the tubules may lead to formation of a cyst. In many instances they appear to occur spontaneously without any preceding instances of injury.Scarring of any part of the epididymis due to trauma or inflammation can cause it to become obstructed and in turn form a spermatocele. Diagnosis Spermatoceles can be discovered as incidental scrotal masses found on physical examination by a physician or by self-inspection of the scrotum and testicles. The various types of diagnosis for spermatocele types include hydrocele, varicocele, hernia, simple epididymal cyst, and neoplasm.The primary care physician may diagnose and manage benign causes of scrotal masses such as hydrocele, varicocele and spermatocele. However, if a "must not miss" diagnoses related to testicular masses such as testicular torsion, epididymitis, acute orchitis, strangulated hernia and testicular cancer is suspected, the family physician must refer to a urologist. Finding a painless, cystic mass at the head of the epididymis that is clearly separate from the testicle can indicate a spermatocele. Shining a light through the mass through a process known as transillumination can also help differentiate between a fluid-filled cyst and a tumor, which would not allow as much light to pass. If uncertainty exists, ultrasonography of the scrotum can confirm the presence of a spermatocele. The location and history of any scrotal masses are crucial in determining whether or not the mass is benign or malignant. Lab tests such as a complete blood count (CBC test) or urine test can also be conducted to check for any possible infection or signs of inflammation.Spermatoceles come in varying sizes and shapes. Some spermatoceles are very small and can only be detected through an ultrasound. More commonly seen are spermatoceles that are a pea-sized lump. They tend to form above or behind a testicle and have a shape and size that looks like a pea. Larger growths have been reported to look similar to a third testicle and can be very discomforting. For those who are affected with large spermatoceles, some have reported feeling pain, heaviness, and fullness in the affected testicle. When to see a doctor If a person is experiencing pain and/or swelling in the scrotum or if a person notices a physical difference such as a mass during a testicular self-exam then they must seek medical attention quickly to help rule out any other causes and begin treatment. Special Populations Spermatoceles in Children Epididymal cysts may arise in children due to numerous different reasons. They may even originate from a disturbance in endocrine factors during the development of the embryo. The incidence of these cysts are possibly linked to boys who are exposed to diethylstilbestrol, an estrogen medication, while in the fetus.Although the evidence and information for incidence of spermatoceles in children is lacking, there are general management guidelines for caregivers who may encounter spermatoceles in their children. Epididymal cysts are typically benign in nature. However, caregivers should take note of any discomfort and symptoms in children, including but not limited to, erythema, scrotal edema or swelling. Epididymal cysts appear in approximately 70% of boys who present as asymptomatic. The diagnosis of epididymal cysts in children can be discovered upon physical examination and eventually confirmed via ultrasound. Treatment Small cysts as well as asymptomatic larger cysts are better left alone and carefully observed. However, treatment can be considered if the cysts are causing discomfort/pain, enlarging in size, or per patient request. There are a few different treatment options, ranging in levels of invasiveness. Medications Certain drugs such as oral analgesics or anti-inflammatory medications can be taken by mouth to decrease spermatocele-related symptoms such as pain and/or swelling. At the moment, there is no medication that can inhibit the production of a spermatocele or cure it. Common medications recommended by doctors are acetaminophen (Tylenol) that can treat pain. To treat the inflammation and pain, non-steroidal anti-inflammatory drugs (NSAIDs) are recommended such as ibuprofen (Motrin, Advil), naproxen (Aleve), and others. Antibiotics may also be prescribed in cases where risk of infection and discomfort is indicated. Medical Procedures Aspiration and sclerotherapy are treatments that remove fluid from the spermatocele and seal the spermatocele sac closed from further fluid build-up, respectively. Due to a higher risk of epididymis damage, fertility problems, and further recurrences, these procedures are not recommended and not commonly used. Surgical Treatments Surgical treatments must be thoroughly discussed with people prior to any final decisions. Different types of surgical procedures may be chosen based on the extent of risk.A short procedure called a spermatocelectomy can be performed for spermatoceles that cause irritating symptoms. This standard procedure can be performed in an outpatient setting with the use of local or general anesthesia. This procedure typically consists of removing the spermatocele and a portion of the epididymis. The risk of epididymal injury is 17.12%. This incident may happen when the spermatocele is being dissected from the head of the epididymis. Spermatocelectomy can cause complications such as hematoma, wound infection, scrotal abscess as well as recurrence. After surgery, the doctor may recommend to apply ice packs for several days to help reduce swelling. Oral pain medications can also be taken for a few days to reduce discomfort. In addition, the patient returns 2–6 weeks after to inspect any progress/complications. If received a vasectomy, then two semen samples must be collected and analyzed after 6–12 weeks post-operation and several ejaculations. The centrifuged semen samples are used to look for the absence of viable sperm in the semen. Risk of Complications After surgical removal, it is possible that the pain will persist and recurrence can occur. Fertility may be compromised with these surgical procedures, so people may consider postponing surgery until after having children. If the pain is intolerable and the person would like to get the spermatocele removed immediately, the person should talk to his doctor about the possibility of freezing or donating sperm in case infertility occurs. Male Reproductive System Spermatoceles are important to not be ignored as it can affect the male reproductive system. The testes are organs inside the scrotum that create sperm as well as sex hormones and testosterone. The sperm in the testes move to the epididymis which is a long, coiled tube behind the testes. The primary function is to store and mature sperm so it can fertilize the egg. However, if the epididymis becomes injured, then there is a chance that the sperm will not mature and a man will not be able to reproduce with a woman. Therefore, serious thought must be considered when undergoing spermatocelectomy. Prevention and Screening There is no way to prevent a spermatocele from forming, but there are routines that can be established to help identify any changes in a persons scrotum such as masses, abnormalities, or discomfort. Performing a monthly testicular self-exam can improve the persons chances of identifying spermatoceles or any abnormalities quickly. It is best to perform a testicular self-exam after a warm shower to help the scrotum relax. To properly exam the scrotum, look for any swelling on the skin and examine each testicle by rolling the testicle between the thumbs and the fingers. A normal testicle is oval-shaped and will usually feel smooth and firm. It is also not uncommon for the testicles to be different sizes.Upon physical examination, if a lump is found during the testicular exam, further screening may be performed via ultrasound to eliminate testicular cancer. See also hydrocele orchitis rete tubular ectasia testicular torsion tumor varicocele References == External links ==
Cutis laxa	Cutis laxa or pachydermatocele is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds. Signs and symptoms It is characterised by skin that is loose, hanging, wrinkled, and lacking in elasticity. The loose skin can be either generalised or localised. Biopsies have shown reduction and degeneration of dermal elastic fibres in the affected areas of skin. The loose skin is often most noticeable on the face, resulting in a prematurely aged appearance. The affected areas of skin may be thickened and dark. In addition, the joints may be loose (hypermobile) because of lax ligaments and tendons. When cutis laxa is severe, it can also affect the internal organs. The lungs, heart (supravalvular pulmonary stenosis), intestines, or arteries may be affected with a variety of severe impairments. In some cases, hernias and outpouching of the bladder can be observed. Patients can also present with whites of the eyes that are blue. Causes In many cases, cutis laxa is inherited. Autosomal dominant, autosomal recessive, and X-linked recessive forms have been described, but acquired forms also occur.Cutis laxa is associated with deficient or absent elastin fibers in the extracellular matrix. This can be related to decreased elastin synthesis or structural defects in the extracellular matrix.Cutis laxa may be caused by mutations in the genes: ELN, ATP6V0A2,ATP7A, FBLN4, FBLN5, and PYCR1. A related neurocutaneous syndrome may be caused by mutations in the gene ALDH18A1 (P5CS). Cutis laxa may also be seen in association with inherited connective tissue disorders such as Ehlers–Danlos syndromes. Another syndrome associated with cutis laxa is Lenz-Majewski syndrome which is due to a mutation in the phosphatidylserine synthase 1 (PTDSS1) gene.In contrast, acquired cutis laxa often has a triggering event such as urticaria, drugs (such as penicillin) or neoplasms. Acquired cutis laxa may also be immunologically mediated, as it can involve dermal deposit of immunoglobulins and it can occur with autoimmune diseases. Acquired cutis laxa has been associated with granular immunoglobulin A deposits as well as abundant neutrophils. One hypothesis for the cause is excessive elastase release from neutrophils and macrophages. It has also been considered that mutations in elastin (ELN) and fibulin-5 (FBLN5) genes can increase susceptibility of elastic fibres to inflammatory degradation in acquired cutis laxa.Acquired cutis laxa has also been seen in conjunction with a number of conditions including: rheumatoid arthritis, systemic lupus erythematosus, celiac disease, and monoclonal gammopathies. It can also occur as a postinflammatory response after urticaria. Urticarial skin fibroblasts have shown a 2- to 3- fold increase in elastase activity in a patient with acquired cutis laxa. Diagnosis Treatment As of 2019, there is no treatment for cutis laxa. Procedures aimed at mitigating symptoms and identifying subsequent conditions are often advised. No pharmacological agent has been able to stop the progression of the disease. However, cosmetic surgeries are potentially an option as cutis laxa does not generally involve vascular fragility. See also Occipital horn syndrome List of cutaneous conditions References Further reading External links Medscape entry on Cutis Laxa
Primary cutaneous coccidioidomycosis	Primary cutaneous coccidioidomycosis is a skin condition caused by Coccidioides immitis following a definite history of inoculation or a colonized splinter found in the skin lesion.: 315 See also Coccidioidomycosis List of cutaneous conditions == References ==
Sonoda syndrome	Sonoda syndrome is a rare genetic disorder characterized by cranio-facial dysmorphisms, fingerprint abnormalities, intellectual disability, and congenital cardiopathy. It has been described in a Japanese family. History This condition has only been described once in history in three siblings from Japan (1987).This trio of siblings was born in Miyazaki Prefecture, Japan to healthy, non-consanguineous Japanese parents who were in their mid-20s (25 years old, to be exact). The parents height (the father was 170 cm tall and the mother was 153 cm tall), skin color (light), and craniofacial appearance were normal and average for their Japanese background, the mother did not have any history of miscarriage or stillbirth. While the both of them denied parental consanguinity, both of their familial lineages had lived in the same small isolated village for various years.The proband was a 6-year-old toddler girl, she was born weighing 2664 grams. Measurements taken in March 1983 (nearly 2 years after her birth) showed a height of 73.1 cm, a weight of 7.1 kg, and a head circumference of 46 cm. Physical examination done in 87 detailed her dark skin tone and light brown hair (which the authors described as uncommon among the Japanese), a round face, flat nasal bridge, small nose, nostril anteversion, and the presence of whorls and loops in her fingerprints (3 and 7, respectively). Routine laboratory tests and a 550-band level karyotype gave normal results. She was noted to have a heart murmur which was then discovered to be caused by a ventricular septal defect (a type of congenital heart defect), but it disappeared on its own few years after the physical examination that discovered said defect (thought to be caused by a spontaneous closure of said defect).The second case was her younger, 4-year-old toddler brother. He was born weighing 3042 grams, and was noted to have cyanosis at birth, which was an indicator for a possible heart anomaly. He learned how to control his head at 3 months of age and learned how to walk when he was 20 months old, at the age of 2 he was found to have a speech delay and could only say a handful of words. Physical examination done on him in July 1984 showed a height of 72.7 cm, a weight of 7.7 km, and a head circumference of 44.5 cm. He had the same skin tone, hair color, and facial characteristics as his proband sister. A systolic ejection murmur (grade 4/6) could be heard at his second left intercostal face, this same murmur was later discovered to be caused by pulmonary valve stenosis. Like his sister, he also had whorls and loops in his fingerprints (4 and 6, respectively), and he had routine laboratory tests and a karyotype which turned back normal. Physical examination done in him again in May 1987 showed a height of 94.3 cm, a weight of 45.2 kg, and a head circumference of 49.7 cm. His bone age was appropriate for his age.The third and final case was the youngest brother of the three, a 2-year old infant boy. He weighed 2962 grams at birth and he was found to have heart murmur when he was 3 months old. Physical examination done on him in May 1986 showed a height of 63 cm, a weight of 5.3 kg, and a head circumference of 41.5 cm. His skin color, hair color and facial features were the same as his siblings. His heart murmur was found to be a grade 3/6 systolic murmur that could be heard in his lower left sternal border, after cardiac echography and other tests, the murmur was ruled out to be benign and harmless. He was noted to have ankyloglossia and hypospadias. He was also found to have whorls and loops in his fingerprints just like his siblings (5 and 5, respectively). A karyotype done on him gave back normal results. Physical examination done on him a year later in May 1987 showed a height of 73.9 cm, a weight of 8.8 kg, and a head circumference of 47.4 cm. He could control his head at the age of 6 months but even at the age of 18 months he was found to have a walking delay and a speech delay. Routine laboratory tests and bone age examination turned back normal.The authors of the condition concluded that this combination of symptoms was probably inherited in an autosomal recessive manner. == References ==
Classic autism	Kanner autism, or classic autism, is an outdated neurodevelopmental diagnosis which is now considered part of autism spectrum disorder. The term autism was historically used to refer specifically to classic autism, but it is now more commonly used for the spectrum at large.Parents often noticed signs of autism during the first three years of their childs life.Autism was hypothesized to be caused by a combination of genetic and environmental factors, with genetic factors thought to heavily predominate. Controversies surround other proposed environmental causes; for example, the vaccine hypothesis, which although disproven, continues to hold sway in certain communities. Contemporary diagnostic manuals include only one diagnosis - autism spectrum disorder (ASD) - which includes classic autism along with Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS).Globally, classic autism was estimated to affect 24.8 million people as of 2015. Characteristics Classic autism is a highly variable neurodevelopmental disorder whose symptoms first appear during infancy or childhood, and generally follows a steady course without remission. Autistic people may be severely impaired in some respects but average, or even superior, in others. Overt symptoms gradually begin after the age of six months and become established by age two or three years. Some autistic children experience regression in their communication and social skills after reaching developmental milestones at a normal pace. It was said to be distinguished by a characteristic triad of symptoms: impairments in social interaction, impairments in communication, and repetitive behavior. Other aspects, such as atypical eating, are also common but are not essential for diagnosis. Individual symptoms of autism occur in the general population and appear not to associate highly, without a sharp line separating pathologically severe from common traits. Social development Autistic people have social impairments and often lack the intuition about others that many people take for granted. Unusual social development becomes apparent early in childhood. Autistic infants show less attention to social stimuli, smile and look at others less often, and respond less to their own name. Autistic toddlers differ more strikingly from social norms; for example, they have less eye contact and turn-taking, and do not have the ability to use simple movements to express themselves, such as pointing at things. Three- to five-year-old autistic children are less likely to exhibit social understanding, approach others spontaneously, imitate and respond to emotions, communicate nonverbally, and take turns with others. However, they do form attachments to their primary caregivers. Most autistic children displayed moderately less attachment security than neurotypical children, although this difference disappears in children with higher mental development or less pronounced autistic traits. Children with high-functioning autism have more intense and frequent loneliness compared to non-autistic peers, despite the common belief that autistic children prefer to be alone. Making and maintaining friendships often proves to be difficult for autistic people. For them, the quality of friendships, not the number of friends, predicts how lonely they feel. Functional friendships, such as those resulting in invitations to parties, may affect the quality of life more deeply. Communication Differences in communication may be present from the first year of life, and may include delayed onset of babbling, unusual gestures, diminished responsiveness, and vocal patterns that are not synchronized with the caregiver. In the second and third years, autistic children have less frequent and less diverse babbling, consonants, words, and word combinations; their gestures are less often integrated with words. Autistic children are less likely to make requests or share experiences, and are more likely to simply repeat others words (echolalia) or reverse pronouns. Deficits in joint attention may be present - for example, they may look at a pointing hand instead of the object to which the hand is pointing. Autistic children may have difficulty with imaginative play and with developing symbols into language. Repetitive behavior Autistic individuals can display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R) categorizes as follows. Stereotyped behaviors: Repetitive movements, such as hand flapping, head rolling, or body rocking. Compulsive behaviors: Time-consuming behaviors intended to reduce the anxiety that an individual feels compelled to perform repeatedly or according to rigid rules, such as placing objects in a specific order, checking things, or handwashing. Sameness: Resistance to change; for example, insisting that the furniture not be moved or refusing to be interrupted. Ritualistic behavior: Unvarying pattern of daily activities, such as an unchanging menu or a dressing ritual. Restricted interests: Interests or fixations that are abnormal in theme or intensity of focus, such as preoccupation with a single television program, toy, or game.No single repetitive or self-injurious behavior seems to be specific to autism, but autism appears to have an elevated pattern of occurrence and severity of these behaviors. Other symptoms Autistic individuals may have symptoms that are independent of the diagnosis. An estimated 0.5% to 10% of individuals with classic autism show unusual abilities, ranging from splinter skills such as the memorization of trivia to the extraordinarily rare talents of prodigious autistic savants. Sensory abnormalities are found in over 90% of autistic people, and are considered core features by some, although there was no good evidence that sensory symptoms differentiate autism from other developmental disorders. An estimated 60–80% of autistic people have motor signs that include poor muscle tone, poor motor planning, and toe walking. Causes It was presumed initially that there was a common cause at the genetic, cognitive, and neural levels for classic autisms characteristic triad of symptoms. However, over time, there was increasing evidence that autism was instead a complex and highly heritable disorder whose core aspects have distinct causes which often often co-occur. Although theories regarding vaccines lack convincing scientific evidence, are biologically implausible, and originated from a fraudulent study, parental concern about a potential vaccine link with autism (and subsequent concern about ASD) has led to lower rates of childhood immunizations, outbreaks of previously controlled childhood diseases in some countries, and the preventable deaths of several children. Diagnosis Diagnosis of classic autism was based on behavioral symptoms, not cause or mechanism. Classification Classic autism was listed as autistic disorder in the fourth edition of the American Psychiatric Associations diagnostic manual, as one of the five pervasive developmental disorders (PDDs). However, the PDDs were collapsed into the single diagnosis of Autism Spectrum Disorder in 2013, and the WHOs diagnostic manual ICD-11 (which had listed it as childhood autism in its previous edition) followed suit a few years later. Classic autism was said to be characterized by widespread abnormalities of social interactions and communication, severely restricted interests, and highly repetitive behavior.Of the PDDs, Asperger syndrome was closest to classic autism in signs and likely causes; Rett syndrome and childhood disintegrative disorder share several signs with it, but were understood to potentially have unrelated causes; PDD not otherwise specified (PDD-NOS; also called atypical autism) was diagnosed when the criteria are not met for one of the other four PDDs. People would usually attract a diagnosis of Asperger syndrome rather than classic autism if they showed no substantial delay in language development, but early language ability was found to be a poor predictor of outcomes in adulthood. Prognosis and management There is no known cure for autism, and very little research addressed long-term prognosis for classic autism. Many autistic children lack social support, future employment opportunities or self-determination.The main goals when treating autistic children are to lessen associated deficits and family distress, and to increase quality of life and functional independence. In general, higher IQs are correlated with greater responsiveness to treatment and improved treatment outcomes. Services should be carried out by behavior analysts, special education teachers, speech pathologists, and licensed psychologists. Intensive, sustained special education programs and behavior therapy early in life often improves functioning and decreases symptom severity and maladaptive behaviors; claims that intervention by around age three years is crucial are not substantiated.No known medication relieves autisms core symptoms of social and communication impairments. Education Early, intensive ABA therapy has demonstrated effectiveness in enhancing communication and adaptive functioning in preschool children; it is also well-established for improving the intellectual performance of that age group. It is not known whether treatment programs for children lead to significant improvements after the children grow up, and the limited research on the effectiveness of adult residential programs shows mixed results. Alternative medicine Although many alternative therapies and interventions were used, few are supported by scientific studies. Treatment approaches have little empirical support in quality-of-life contexts, and many programs focus on success measures that lack predictive validity and real-world relevance. Some alternative treatments placed autistic individuals at risk. For example, in 2005, a five-year-old child with autism was killed by botched chelation therapy (which is not recommended for autism as risks outweigh any potential benefits). Epidemiology Globally, classic autism was understood to affect an estimated 24.8 million people as of 2015. After it was recognised as a distinct disorder, reports of autism cases substantially increased, which was largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, and public awareness (particularly among women).Several other conditions were commonly seen in children with autism. They include: Intellectual disability. The percentage of autistic individuals who also met criteria for intellectual disability has been reported as anywhere from 25% to 70%, a wide variation illustrating the difficulty of assessing intelligence of individuals on the autism spectrum. In comparison, for PDD-NOS the association with intellectual disability was much weaker, and by definition, the diagnosis of Aspergers excluded intellectual disability. Minor physical anomalies are significantly increased in the autistic population. Preempted diagnoses. Although the DSM-IV ruled out the concurrent diagnosis of many other conditions along with autism, the full criteria for Attention deficit hyperactivity disorder (ADHD), Tourette syndrome, and other of these conditions were often present. As a result, modern ASD allows for these diagnoses. History The New Latin word autismus (English translation autism) was coined by the Swiss psychiatrist Eugen Bleuler in 1910 as he was defining symptoms of schizophrenia. He derived it from the Greek word autós (αὐτός, meaning "self"), and used it to mean morbid self-admiration, referring to "autistic withdrawal of the patient to his fantasies, against which any influence from outside becomes an intolerable disturbance". The word autism first took its modern sense in 1938 when Hans Asperger of the Vienna University Hospital adopted Bleulers terminology autistic psychopaths in a lecture in German about child psychology. Asperger was investigating Asperger syndrome which, for various reasons, was not widely considered a separate diagnosis until 1981, although both are now considered part of ASD. Leo Kanner of the Johns Hopkins Hospital first used autism in English to refer to classic autism when he introduced the label early infantile autism in a 1943 report. Almost all the characteristics described in Kanners first paper on the subject, notably "autistic aloneness" and "insistence on sameness", are still regarded as typical of the autistic spectrum of disorders. Starting in the late 1960s, classic autism was established as a separate syndrome.It took until 1980 for the DSM-III to differentiate autism from childhood schizophrenia. In 1987, the DSM-III-R provided a checklist for diagnosing autism. In May 2013, the DSM-5 was released, updating the classification for pervasive developmental disorders. The grouping of disorders, including PDD-NOS, autism, Asperger syndrome, Rett syndrome, and CDD, has been removed and replaced with the general term of Autism Spectrum Disorder. References == External links ==
Transient erythroblastopenia of childhood	Transient erythroblastopenia of childhood (TEC) is a slowly developing anemia of early childhood characterized by gradual onset of pallor. Signs and symptoms Individuals with TEC have a median age of presentation of 18–26 months; however, the disorder may occur in infants younger than 6 months and in children as old as age 10 years. Because of the gradual onset of the anemia, children are often healthier than expected from their low hemoglobin levels. Cause The cause of TEC is unknown, but it thought to be triggered by a viral infection. While rare cases have been attributed to infection with Parvovirus B19, the majority of cases are not related to Parvovirus infection. This is in contrast to transient aplastic crisis, seen in patients with hemoglobinopathies such as sickle cell disease, which is usually caused by Parvovirus infection. Diagnosis Children typically present with a moderate normocytic anemia (usual range: Hemoglobin 5-8 g/dL) and reticulocytopenia. Mean corpuscular volume (MCV) is usually normal for age. Hemoglobin F levels are also typically normal. Prognosis Most patients recover completely within 1–2 months. However many reported cases have lasted 18–24 months and longer. References External links ped/2279 at eMedicine
Malignant acrospiroma	A malignant acrospiroma is a sweat gland carcinoma of the hand, which may recur locally in 50% of patients after excision, with distant metastases occurring in 60% of patients. See also Acrospiroma Syringoma Hidrocystoma List of cutaneous conditions References == External links ==
Hamartoma	A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended from a single mutated cell (monoclonality), as would typically define a benign neoplasm/tumor. Despite this, many hamartomas are found to have clonal chromosomal aberrations that are acquired through somatic mutations, and on this basis the term hamartoma is sometimes considered synonymous with neoplasm. Hamartomas are by definition benign, slow-growing or self-limiting, though the underlying condition may still predispose the individual towards malignancies. Hamartomas are usually caused by a genetic syndrome that affects the development cycle of all or at least multiple cells. Many of these conditions are classified as overgrowth syndromes or cancer syndromes. Hamartomas occur in many different parts of the body and are most often asymptomatic incidentalomas (undetected until they are found incidentally on an imaging study obtained for another reason). Additionally, the definition of hamartoma versus benign neoplasm is often unclear, since both lesions can be clonal. Lesions such as adenomas, developmental cysts, hemangiomas, lymphangiomas and rhabdomyomas within the kidneys, lungs or pancreas are interpreted by some experts as hamartomas while others consider them true neoplasms. Moreover, even though hamartomas show a benign histology, there is a risk of some rare but life-threatening complications such as those found in neurofibromatosis type I and tuberous sclerosis.It is different from choristoma, a closely related form of heterotopia. The two can be differentiated as follows: a hamartoma is an excess of normal tissue in a normal situation (e.g., a birthmark on the skin), while a choristoma is an excess of tissue in an abnormal situation (e.g., pancreatic tissue in the duodenum). The term hamartoma is from the Greek ἁμαρτία, hamartia ("error"), and was introduced by D.P.G. Albrecht in 1904. Causes Hamartomas result from an abnormal formation of normal tissue, although the underlying reasons for the abnormality are not fully understood. They grow along with, and at the same rate as, the organ from whose tissue they are made, and, unlike cancerous tumors, only rarely invade or compress surrounding structures significantly. Diagnosis Types Lung About 5–8% of all solitary lung nodules and about 75% of all benign lung tumors, are hamartomas. They almost always arise from connective tissue and are generally formed of cartilage, connective tissue, and fat cells, although they may include many other types of cells. The great majority of them form in the connective tissue on the outside of the lungs, although about 10% form deep in the linings of the bronchi. They can be worrisome, especially if situated deep in the lung, as it is sometimes difficult to make the important distinction between a hamartoma and a lung malignancy. An X-ray will often not provide a definitive diagnosis, and even a CT scan may be insufficient if the hamartoma lacks the typical cartilage and fat cells. Lung hamartomas may have popcorn-like calcifications on chest xray or computed tomography (CT scan). Lung hamartomas are more common in men than in women, and may present additional difficulties in smokers. Some lung hamartomas can compress surrounding lung tissue to a degree, but this is generally not debilitating and is often asymptomatic, especially for the more common peripheral growths. They are treated, if at all, by surgical resection, with an excellent prognosis: generally, the only real danger is the inherent possibility of surgical complications. Heart Cardiac rhabdomyomas are hamartomas composed of altered cardiac myocytes that contain large vacuoles and glycogen. They are the most common tumor of the heart in children and infants. There is a strong association between cardiac rhabdomyomas and tuberous sclerosis (characterized by hamartomas of the central nervous system, kidneys, and skin, as well as pancreatic cysts); 25-50% of patients with cardiac rhabdomyomas will have tuberous sclerosis, and up to 100% of patients with tuberous sclerosis will have cardiac masses by echocardiography. Symptoms depend on the size of the tumor, its location relative to the conduction system, and whether or not it obstructs blood flow. Symptoms are usually from congestive heart failure; in utero heart failure may occur. If patients survive infancy, their tumors may regress spontaneously; resection in symptomatic patients has good results. Nerves Sometimes nerves can also be affected. The most common nerve to be affected by hamartoma is reported to be median nerve. Hypothalamus One of the most troublesome hamartomas occurs on the hypothalamus. Unlike most such growths, a hypothalamic hamartoma is symptomatic; it most often causes gelastic seizures, and can cause visual problems, other seizures, rage disorders associated with hypothalamic diseases, and early onset of puberty. The symptoms typically begin in early infancy and are progressive, often into general cognitive and/or functional disability. Moreover, resection is usually difficult, as the growths are generally adjacent to, or even intertwined with, the optic nerve. Symptoms tend to be resistant to medical control; however, surgical techniques are improving and can result in immense improvement of prognosis. Kidneys, stomach, spleen and other vascular organs One general danger of hamartomas is that they may impinge into blood vessels, resulting in a risk of serious bleeding. Because a hamartoma typically lacks elastic tissue, it may lead to the formation of aneurysms and thus possible hemorrhage. Where a hamartoma impinges into a major blood vessel, such as the renal artery, hemorrhage must be considered life-threatening. Angiomyolipoma of the kidney was previously considered to be a hamartoma or choristoma. A myoepithelial hamartoma, also known as a pancreatic rest, is ectopic pancreatic tissue found in the stomach, duodenum, or proximal jejunum. When seen on upper gastrointestinal series, a pancreatic rest may appear to be a submucosal mass or gastric neoplasm. Most are asymptomatic, but they can cause dyspepsia or upper gastrointestinal bleeding.A hamartoma has been identified as a cause of partial outflow obstruction in the abomasum (true gastric stomach) of a dairy goat.Hamartomas of the spleen are uncommon but can be dangerous. About 50% of such cases manifest abdominal pain, and they are often associated with hematologic abnormalities and spontaneous rupture. Cowden syndrome Cowden syndrome is a serious genetic disorder characterized by multiple hamartomas. Usually skin hamartomas exist, and commonly (in about 66% of cases) hamartoma of the thyroid gland exists. Additional growths can form in many parts of the body, especially in bones, CNS, the eyes, the genitourinary tract, the GI tract, and mucosa. The hamartomas themselves may cause symptoms or even death, but morbidity is more often associated with increased occurrence of malignancies, usually in the breast or thyroid. Cowden syndrome is considered a PTEN hamartoma tumor syndrome (PHTS), which also includes Bannayan–Riley–Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome. Prognosis Hamartomas, while generally benign, can cause problems due to their location. For example, when located on the skin, especially on the face or neck, they can be very disfiguring. Cases have been reported of hamartomas the size of a small orange. They may obstruct practically any organ in the body, such as the colon, eye, etc. They are particularly likely to cause major health issues when located in the hypothalamus, kidneys, lips, or spleen. They can be removed surgically if necessary, and are not likely to recur. Prognosis will depend upon the location and size of the lesion, as well as the overall health of the patient. See also Hamartia (medical term) List of cutaneous conditions References External links "Topic 28: Angiomyolipoma". eMedicine.com Radio. 2019-04-05. "Topic 316: Lung Hamartoma". eMedicine.com Radio. 2018-12-17.
Asperger syndrome	Asperger syndrome (AS), also known as Aspergers, was the name of a neurodevelopmental disorder no longer recognised as a diagnosis in itself, having been merged into autism spectrum disorder (ASD). It was characterized by significant difficulties in social interaction and nonverbal communication, along with restricted and repetitive patterns of behaviour and interests. It was said to differ from other diagnoses that were merged into ASD by relatively unimpaired language and intelligence. The syndrome was named after the Austrian pediatrician Hans Asperger, who, in 1944, described children in his care who struggled to form friendships, did not understand others gestures or feelings, engaged in one-sided conversations about their favourite interests, and were clumsy.The exact cause of Aspergers is poorly understood. While it has high heritability, the underlying genetics have not been determined conclusively. Environmental factors are also believed to play a role. Brain imaging has not identified a common underlying condition.In 1994, the diagnosis of Aspergers was included in the fourth edition (DSM-IV) of the American Diagnostic and Statistical Manual of Mental Disorders; with the publication of DSM-5 in 2013 the diagnosis was removed, and the symptoms are now included within autism spectrum disorder along with classic autism and pervasive developmental disorder not otherwise specified (PDD-NOS). It was similarly merged into autism spectrum disorder in the International Classification of Diseases (ICD-11) as of 2021.There is no single treatment, and the UKs National Health Service (NHS) guidelines suggest that treatment of any form of autism should not be a goal, since autism is not a disease that can be removed or cured. According to the Royal College of Psychiatrists, while co-occurring conditions might require treatment, management of autism itself is chiefly about the provision of the education, training and social support/care required to improve the persons ability to function in the everyday world. The effectiveness of particular interventions for autism is supported by only limited data. Interventions may include social skills training, cognitive behavioral therapy, physical therapy, speech therapy, parent training, and medications for associated problems, such as mood or anxiety. Autistic characteristics tend to become less obvious in adulthood, but social and communication difficulties usually persist.Some autistic people, as well as a number of researchers, have advocated a shift in attitudes toward the view that autism spectrum disorder is a difference, rather than a disease that must be treated or cured. Critics have bemoaned the entrenchment of some of these groups opinions.In 2015, Aspergers was estimated to affect 37.2 million people globally, or about 0.5% of the population. The exact percentage of people affected is not firmly established. Autism spectrum disorder is diagnosed in males more often than females, and females are typically diagnosed at a later age. The modern conception of Asperger syndrome came into existence in 1981, and went through a period of popularization. It became a standardized diagnosis in the 1990s, and was retired as a diagnosis in 2013. Many questions and controversies about the condition remain. Classification The extent of the overlap between Asperger syndrome and high-functioning autism (HFA – autism unaccompanied by intellectual disability) is unclear. The ASD classification is to some extent an artifact of how autism was discovered, and may not reflect the true nature of the spectrum; methodological problems have beset Asperger syndrome as a valid diagnosis from the outset. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in May 2013, Asperger syndrome, as a separate diagnosis, was eliminated and folded into autism spectrum disorder. Like the diagnosis of Asperger syndrome, the change was controversial and thus Asperger syndrome was subsequently not removed from the WHOs ICD-10; however, it was removed from the ICD-11.The World Health Organization (WHO) previously defined Asperger syndrome (AS) as one of the autism spectrum disorders (ASD) or pervasive developmental disorders (PDD), which are a spectrum of psychological conditions that are characterized by abnormalities of social interaction and communication that pervade the individuals functioning, and by restricted and repetitive interests and behavior. Like other neurodevelopment disorders, ASD begins in infancy or childhood, has a steady course without remission or relapse, and has impairments that result from maturation-related changes in various systems of the brain. ASD, in turn, is a subset of the broader autism phenotype, which describes individuals who may not have ASD but do have autistic-like traits, such as social deficits. Characteristics As a pervasive developmental disorder, Asperger syndrome is distinguished by a pattern of symptoms rather than a single symptom. It is characterized by qualitative impairment in social interaction, by stereotyped and restricted patterns of behavior, activities, and interests, and by no clinically significant delay in cognitive development or general delay in language. Intense preoccupation with a narrow subject, one-sided verbosity, restricted prosody, and physical clumsiness are typical of the condition, but are not required for diagnosis. Suicidal behavior appears to occur at rates similar to those without ASD. Social interaction A lack of demonstrated empathy affects aspects of social relatability for persons with Asperger syndrome. Individuals with Asperger syndrome experience difficulties in basic elements of social interaction, which may include a failure to develop friendships or to seek shared enjoyments or achievements with others (e.g., showing others objects of interest); a lack of social or emotional reciprocity (social "games" give-and-take mechanic); and impaired nonverbal behaviors in areas such as eye contact, facial expression, posture, and gesture.People with Asperger syndrome may not be as withdrawn around others, compared with those with other forms of autism; they approach others, even if awkwardly. For example, a person with Asperger syndrome may engage in a one-sided, long-winded speech about a favorite topic, while misunderstanding or not recognizing the listeners feelings or reactions, such as a wish to change the topic of talk or end the interaction. This social awkwardness has been called "active but odd". Such failures to react appropriately to social interaction may appear as disregard for other peoples feelings and may come across as rude or insensitive. However, not all individuals with Asperger syndrome will approach others. Some may even display selective mutism, not speaking at all to most people and excessively to specific others. Some may choose only to talk to people they like.The cognitive ability of children with AS often allows them to articulate social norms in a laboratory context, where they may be able to show a theoretical understanding of other peoples emotions; however, they typically have difficulty acting on this knowledge in fluid, real-life situations. People with AS may analyze and distill their observations of social interaction into rigid behavioral guidelines and apply these rules in awkward ways, such as forced eye contact, resulting in a demeanor that appears rigid or socially naïve. Childhood desire for companionship can become numbed through a history of failed social encounters. Violent or criminal behavior The hypothesis that individuals with AS are predisposed to violent or criminal behavior has been investigated but is not supported by data. More evidence suggests that children diagnosed with Asperger syndrome are more likely to be victims, rather than offenders.A 2008 review found that an overwhelming number of reported violent criminals with Asperger syndrome also had other coexisting psychotic psychiatric disorders such as schizoaffective disorder. This coexistence of psychotic disorders is referred to as comorbid disorders. Comorbid disorders can be completely independent of one another or can have overlap in symptoms and how they express themselves. Empathy People with an Asperger profile might not be recognized for their empathetic qualities, due to variation in the ways empathy is felt and expressed. Some people feel deep empathy, but do not outwardly communicate these sentiments through facial expressions or language. Some people come to empathy through intellectual processes, using logic and reasoning to arrive at the feelings. It is also important to keep in mind that many people with Asperger profiles have been bullied or excluded by peers in the past and might therefore be guarded around people, which could appear as lack of empathy. People with Asperger profiles can be and are extremely caring individuals; in fact, it is particularly common for those with the profile to feel and exhibit deep concern for human welfare, animal rights, environmental protection, and other global and humanitarian causes.Evidence suggests that in the "double empathy problem model, autistic people have a unique interaction style which is significantly more readable by other autistic people, compared to non-autistic people." Restricted and repetitive interests and behavior People with Asperger syndrome can display behavior, interests, and activities that are restricted and repetitive and are sometimes abnormally intense or focused. They may stick to inflexible routines, move in stereotyped and repetitive ways, preoccupy themselves with parts of objects, or engage in compulsive behaviors like lining objects up to form patterns.The pursuit of specific and narrow areas of interest is one of the most striking among possible features of AS. Individuals with AS may collect volumes of detailed information on a relatively narrow topic such as weather data or star names without necessarily having a genuine understanding of the broader topic. For example, a child might memorize camera model numbers while caring little about photography. This behavior is usually apparent by age five or six. Although these special interests may change from time to time, they typically become more unusual and narrowly focused and often dominate social interaction so much that the entire family may become immersed. Because narrow topics often capture the interest of children, this symptom may go unrecognized.Stereotyped and repetitive motor behaviors are a core part of the diagnosis of AS and other ASDs. They include hand movements such as flapping or twisting, and complex whole-body movements. These are typically repeated in longer bursts and look more voluntary or ritualistic than tics, which are usually faster, less rhythmical, and less often symmetrical. However, in addition to this, various studies have reported a consistent comorbidity between AS and Tourette syndrome in the range of 8–20%, with one figure as high as 80% for tics of some kind or another, for which several explanations have been put forward, including common genetic factors and dopamine, glutamate, or serotonin abnormalities.According to the Adult Asperger Assessment (AAA) diagnostic test, a lack of interest in fiction and a positive preference towards non-fiction is common among adults with AS. Speech and language Although individuals with Asperger syndrome acquire language skills without significant general delay and their speech typically lacks significant abnormalities, language acquisition and use is often atypical. Abnormalities include verbosity; abrupt transitions; literal interpretations and miscomprehension of nuance; use of metaphor meaningful only to the speaker; auditory perception deficits; unusually pedantic, formal, or idiosyncratic speech; and oddities in loudness, pitch, intonation, prosody, and rhythm. Echolalia has also been observed in individuals with AS.Three aspects of communication patterns are of clinical interest: poor prosody, tangential and circumstantial speech, and marked verbosity. Although inflection and intonation may be less rigid or monotonic than in classic autism, people with AS often have a limited range of intonation: speech may be unusually fast, jerky, or loud. Speech may convey a sense of incoherence; the conversational style often includes monologues about topics that bore the listener, fails to provide context for comments, or fails to suppress internal thoughts. Individuals with AS may fail to detect whether the listener is interested or engaged in the conversation. The speakers conclusion or point may never be made, and attempts by the listener to elaborate on the speechs content or logic, or to shift to related topics, are often unsuccessful.Children with AS may have a sophisticated vocabulary at a young age and such children have often been colloquially called "little professors" but have difficulty understanding figurative language and tend to use language literally. Children with AS appear to have particular weaknesses in areas of nonliteral language that include humor, irony, teasing, and sarcasm. Although individuals with AS usually understand the cognitive basis of humor, they seem to lack understanding of the intent of humor to share the enjoyment with others. Despite strong evidence of impaired humor appreciation, anecdotal reports of humor in individuals with AS seem to challenge some psychological theories of AS and autism. Motor and sensory perception Individuals with Asperger syndrome may have signs or symptoms that are independent of the diagnosis but can affect the individual or the family. These include differences in perception and problems with motor skills, sleep, and emotions. Individuals with AS often have excellent auditory and visual perception. Children with ASD often demonstrate enhanced perception of small changes in patterns such as arrangements of objects or well-known images; typically this is domain-specific and involves processing of fine-grained features. Conversely, compared with individuals with high-functioning autism, individuals with AS have deficits in some tasks involving visual-spatial perception, auditory perception, or visual memory. Many accounts of individuals with AS and ASD report other unusual sensory and perceptual skills and experiences. They may be unusually sensitive or insensitive to sound, light, and other stimuli; these sensory responses are found in other developmental disorders and are not specific to AS or to ASD. There is little support for increased fight-or-flight response or failure of habituation in autism; there is more evidence of decreased responsiveness to sensory stimuli, although several studies show no differences.Hans Aspergers initial accounts and other diagnostic schemes include descriptions of physical clumsiness. Children with AS may be delayed in acquiring skills requiring dexterity, such as riding a bicycle or opening a jar, and may seem to move awkwardly or feel "uncomfortable in their own skin". They may be poorly coordinated or have an odd or bouncy gait or posture, poor handwriting, or problems with motor coordination. They may show problems with proprioception (sensation of body position) on measures of developmental coordination disorder (motor planning disorder), balance, tandem gait, and finger-thumb apposition. There is no evidence that these motor skills problems differentiate AS from other high-functioning ASDs.Children with AS are more likely to have sleep problems, including difficulty in falling asleep, frequent nocturnal awakenings, and early morning awakenings. AS is also associated with high levels of alexithymia, which is difficulty in identifying and describing ones emotions. Although AS, lower sleep quality, and alexithymia are associated with each other, their causal relationship is unclear. Causes Hans Asperger described common traits among his patients family members, especially fathers, and research supports this observation and suggests a genetic contribution to Asperger syndrome. Although no specific genetic factor has yet been identified, multiple factors are believed to play a role in the expression of autism, given the variability in symptoms seen in children. Evidence for a genetic link is that AS tends to run in families where more family members have limited behavioral symptoms similar to AS (for example, some problems with social interaction, or with language and reading skills). Most behavioral genetic research suggests that all autism spectrum disorders have shared genetic mechanisms, but AS may have a stronger genetic component than autism. There may be shared genes in which particular alleles make an individual vulnerable, and varying combinations result in differing severity and symptoms in each person with AS.A few ASD cases have been linked to exposure to teratogens (agents that cause birth defects) during the first eight weeks from conception. Although this does not exclude the possibility that ASD can be initiated or affected later, it is strong evidence that ASD arises very early in development. Many environmental factors have been hypothesized to act after birth, but none has been confirmed by scientific investigation. Mechanism Asperger syndrome appears to result from developmental factors that affect many or all functional brain systems, as opposed to localized effects.Although the specific underpinnings of AS or factors that distinguish it from other ASDs are unknown, and no clear pathology common to individuals with AS has emerged, it is still possible that ASs mechanism is separate from other ASDs.Neuroanatomical studies and the associations with teratogens strongly suggest that the mechanism includes alteration of brain development soon after conception. Abnormal fetal development may affect the final structure and connectivity of the brain, resulting in altered neural circuits controlling thought and behavior. Several theories of mechanism are available; none are likely to provide a complete explanation. General-processing theories One general-processing theory is weak central coherence theory, which hypothesizes that a limited ability to see the big picture underlies the central disturbance in ASD. A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals. Mirror neuron system (MNS) theory The mirror neuron system (MNS) theory hypothesizes that alterations to the development of the MNS interfere with imitation and lead to Aspergers core feature of social impairment. One study found that activation is delayed in the core circuit for imitation in individuals with AS. This theory maps well to social cognition theories like the theory of mind, which hypothesizes that autistic behavior arises from impairments in ascribing mental states to oneself and others; or hyper-systemizing, which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at empathizing when handling events generated by other agents. Diagnosis Standard diagnostic criteria require impairment in social interaction and repetitive and stereotyped patterns of behavior, activities, and interests, without significant delay in language or cognitive development. Unlike the international standard, the DSM-IV-TR criteria also required significant impairment in day-to-day functioning; DSM-5 eliminated AS as a separate diagnosis in 2013, and folded it into the umbrella of autism spectrum disorders. Other sets of diagnostic criteria have been proposed by Szatmari et al. and by Gillberg and Gillberg.Diagnosis is most commonly made between the ages of four and eleven. A comprehensive assessment involves a multidisciplinary team that observes across multiple settings, and includes neurological and genetic assessment as well as tests for cognition, psychomotor function, verbal and nonverbal strengths and weaknesses, style of learning, and skills for independent living. The "gold standard" in diagnosing ASDs combines clinical judgment with the Autism Diagnostic Interview-Revised (ADI-R), a semistructured parent interview; and the Autism Diagnostic Observation Schedule (ADOS), a conversation and play-based interview with the child. Delayed or mistaken diagnosis can be traumatic for individuals and families; for example, misdiagnosis can lead to medications that worsen behavior.Underdiagnosis and overdiagnosis may be problems. The cost and difficulty of screening and assessment can delay diagnosis. Conversely, the increasing popularity of drug treatment options and the expansion of benefits has motivated providers to overdiagnose ASD. There are indications AS has been diagnosed more frequently in recent years, partly as a residual diagnosis for children of normal intelligence who are not autistic but have social difficulties.There are questions about the external validity of the AS diagnosis. That is, it is unclear whether there is a practical benefit in distinguishing AS from HFA and from PDD-NOS; different screening tools render different diagnoses depending in the same person. Differential diagnosis Many children with AS are initially misdiagnosed with attention deficit hyperactivity disorder (ADHD). Diagnosing adults is more challenging, as standard diagnostic criteria are designed for children and the expression of AS changes with age. Adult diagnosis requires painstaking clinical examination and thorough medical history gained from both the individual and other people who know the person, focusing on childhood behavior.Conditions that must be considered in a differential diagnosis along with ADHD include other ASDs, the schizophrenia spectrum, personality disorders, obsessive–compulsive disorder, major depressive disorder, semantic pragmatic disorder, nonverbal learning disorder, social anxiety disorder, Tourette syndrome, stereotypic movement disorder, bipolar disorder, social-cognitive deficits due to brain damage from alcohol use disorder, and obsessive–compulsive personality disorder (OCPD). Screening Parents of children with Asperger syndrome can typically trace differences in their childrens development to as early as 30 months of age. Developmental screening during a routine check-up by a general practitioner or pediatrician may identify signs that warrant further investigation. The United States Preventive Services Task Force in 2016 found it was unclear if screening was beneficial or harmful among children in whom there are no concerns.Different screening instruments are used to diagnose AS, including the Asperger Syndrome Diagnostic Scale (ASDS); Autism Spectrum Screening Questionnaire (ASSQ); Childhood Autism Spectrum Test (CAST), previously called the Childhood Asperger Syndrome Test; Gilliam Aspergers disorder scale (GADS); Krug Aspergers Disorder Index (KADI); and the autism-spectrum quotient (AQ), with versions for children, adolescents, and adults. None have been shown to reliably differentiate between AS and other ASDs. Management Asperger syndrome treatment attempts to manage distressing symptoms and to teach age-appropriate social, communication, and vocational skills that are not naturally acquired during development, with intervention tailored to the needs of the individual based on multidisciplinary assessment. Although progress has been made, data supporting the efficacy of particular interventions are limited. Therapies Managing AS ideally involves multiple therapies that address core symptoms of the disorder. While most professionals agree that the earlier the intervention, the better, there is no treatment combination that is recommended above others. AS treatment resembles that of other high-functioning ASDs, except that it takes into account the linguistic capabilities, verbal strengths, and nonverbal vulnerabilities of individuals with AS. A typical program generally includes: Applied behavior analysis (ABA) procedures, including positive behavior support (PBS)—or training and support of parents and school faculty in behavior management strategies to use in the home and school, and social skills training for more effective interpersonal interactions; Cognitive behavioral therapy to improve stress management relating to anxiety or explosive emotions and to help reduce obsessive interests and repetitive routines; Medication for coexisting conditions such as major depressive disorder and anxiety disorders; Occupational or physical therapy to assist with poor sensory processing and motor coordination; and, Social communication intervention, which is specialized speech therapy to help with the pragmatics and give-and-take of normal conversation.Of the many studies on behavior-based early intervention programs, most are case reports of up to five participants and typically examine a few problem behaviors such as self-injury, aggression, noncompliance, stereotypies, or spontaneous language; unintended side effects are largely ignored. Despite the popularity of social skills training, its effectiveness is not firmly established. A randomized controlled study of a model for training parents in problem behaviors in their children with AS showed that parents attending a one-day workshop or six individual lessons reported fewer behavioral problems, while parents receiving the individual lessons reported less intense behavioral problems in their AS children. Vocational training is important to teach job interview etiquette and workplace behavior to older children and adults with AS, and organization software and personal data assistants can improve the work and life management of people with AS. Medications No medications directly treat the core symptoms of AS. Although research into the efficacy of pharmaceutical intervention for AS is limited, it is essential to diagnose and treat comorbid conditions. Deficits in self-identifying emotions or in observing effects of ones behavior on others can make it difficult for individuals with AS to see why medication may be appropriate. Medication can be effective in combination with behavioral interventions and environmental accommodations in treating comorbid symptoms such as anxiety disorders, major depressive disorder, inattention, and aggression. The atypical antipsychotic medications risperidone, olanzapine and aripiprazole have been shown to reduce the associated symptoms of AS; risperidone can reduce repetitive and self-injurious behaviors, aggressive outbursts, and impulsivity, and improve stereotypical patterns of behavior and social relatedness. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine, and sertraline have been effective in treating restricted and repetitive interests and behaviors, while stimulant medication, such as methylphenidate, can reduce inattention.Care must be taken with medications, as side effects may be more common and harder to evaluate in individuals with AS, and tests of drugs effectiveness against comorbid conditions routinely exclude individuals from the autism spectrum. Abnormalities in metabolism, cardiac conduction times, and an increased risk of type 2 diabetes have been raised as concerns with antipsychotic medications, along with serious long-term neurological side effects. SSRIs can lead to manifestations of behavioral activation such as increased impulsivity, aggression, and sleep disturbance. Weight gain and fatigue are commonly reported side effects of risperidone, which may also lead to increased risk for extrapyramidal symptoms such as restlessness and dystonia and increased serum prolactin levels. Sedation and weight gain are more common with olanzapine, which has also been linked with diabetes. Sedative side-effects in school-age children have ramifications for classroom learning. Individuals with AS may be unable to identify and communicate their internal moods and emotions or to tolerate side effects that for most people would not be problematic. Prognosis There is some evidence that children with AS may see a lessening of symptoms; up to 20% of children may no longer meet the diagnostic criteria as adults, although social and communication difficulties may persist. As of 2006, no studies addressing the long-term outcome of individuals with Asperger syndrome are available and there are no systematic long-term follow-up studies of children with AS. Individuals with AS appear to have normal life expectancy, but have an increased prevalence of comorbid psychiatric conditions, such as major depressive disorder and anxiety disorders that may significantly affect prognosis. Although social impairment may be lifelong, the outcome is generally more positive than with individuals with lower-functioning autism spectrum disorders; for example, ASD symptoms are more likely to diminish with time in children with AS or HFA. Most students with AS and HFA have average mathematical ability and test slightly worse in mathematics than in general intelligence. However, mathematicians are at least three times more likely to have autism-spectrum traits than the general population, and are more likely to have family members with autism.Although many attend regular education classes, some children with AS may attend special education classes such as separate classroom and resource room because of their social and behavioral difficulties. Adolescents with AS may exhibit ongoing difficulty with self-care or organization, and disturbances in social and romantic relationships. Despite high cognitive potential, most young adults with AS remain at home, yet some do marry and work independently. The "different-ness" adolescents experience can be traumatic. Anxiety may stem from preoccupation over possible violations of routines and rituals, from being placed in a situation without a clear schedule or expectations, or from concern with failing in social encounters; the resulting stress may manifest as inattention, withdrawal, reliance on obsessions, hyperactivity, or aggressive or oppositional behavior. Depression is often the result of chronic frustration from repeated failure to engage others socially, and mood disorders requiring treatment may develop. Clinical experience suggests the rate of suicide may be higher among those with AS, but this has not been confirmed by systematic empirical studies.Education of families is critical in developing strategies for understanding strengths and weaknesses; helping the family to cope improves outcomes in children. Prognosis may be improved by diagnosis at a younger age that allows for early interventions, while interventions in adulthood are valuable but less beneficial. There are legal implications for individuals with AS as they run the risk of exploitation by others and may be unable to comprehend the societal implications of their actions. Epidemiology Frequency estimates vary enormously. In 2015, it was estimated that 37.2 million people globally are affected. A 2003 review of epidemiological studies of children found autism rates ranging from 0.03 to 4.84 per 1,000, with the ratio of autism to Asperger syndrome ranging from 1.5:1 to 16:1; combining the geometric mean ratio of 5:1 with a conservative prevalence estimate for autism of 1.3 per 1,000 suggests indirectly that the prevalence of AS might be around 0.26 per 1,000. Part of the variance in estimates arises from differences in diagnostic criteria. For example, a relatively small 2007 study of 5,484 eight-year-old children in Finland found 2.9 children per 1,000 met the ICD-10 criteria for an AS diagnosis, 2.7 per 1,000 for Gillberg and Gillberg criteria, 2.5 for DSM-IV, 1.6 for Szatmari et al., and 4.3 per 1,000 for the union of the four criteria. Boys seem to be more likely to have AS than girls; estimates of the sex ratio range from 1.6:1 to 4:1, using the Gillberg and Gillberg criteria. Females with autism spectrum disorders may be underdiagnosed. Comorbidities Anxiety disorders and major depressive disorder are the most common conditions seen at the same time; comorbidity of these in persons with AS is estimated at 65%. Reports have associated AS with medical conditions such as aminoaciduria
Asperger syndrome	and ligamentous laxity, but these have been case reports or small studies and no factors have been associated with AS across studies. One study of males with AS found an increased rate of epilepsy and a high rate (51%) of nonverbal learning disorder. AS is associated with tics, Tourette syndrome and bipolar disorder. The repetitive behaviors of AS have many similarities with the symptoms of obsessive–compulsive disorder and obsessive–compulsive personality disorder, and 26% of a sample of young adults with AS were found to meet the criteria for schizoid personality disorder (which is characterised by severe social seclusion and emotional detachment), more than any other personality disorder in the sample. However many of these studies are based on clinical samples or lack standardized measures; nonetheless, comorbid conditions are relatively common. History Named after the Austrian pediatrician Hans Asperger (1906–1980), Asperger syndrome is a relatively new diagnosis in the field of autism, though a syndrome like it was described as early as 1925 by Soviet child psychiatrist Grunya Sukhareva (1891–1981), leading some of those diagnosed with Aspergers Syndrome to instead refer to their condition as Sukharevas Syndrome, in opposition to Hans Aspergers association with Nazism. As a child, Asperger appears to have exhibited some features of the very condition named after him, such as remoteness and talent in language. In 1944, Asperger described four children in his practice who had difficulty in integrating themselves socially and showing empathy towards peers. They also lacked nonverbal communication skills and were physically clumsy. Asperger described this "autistic psychopathy" as social isolation. Fifty years later, several standardizations of AS as a medical diagnosis were tentatively proposed, many of which diverge significantly from Aspergers original work.Unlike todays AS, autistic psychopathy could be found in people of all levels of intelligence, including those with intellectual disability. Asperger defended the value of so-called "high-functioning" autistic individuals, writing: "We are convinced, then, that autistic people have their place in the organism of the social community. They fulfill their role well, perhaps better than anyone else could, and we are talking of people who as children had the greatest difficulties and caused untold worries to their care-givers." Asperger also believed some would be capable of exceptional achievement and original thought later in life.Aspergers paper was published during World War II and in German, so it was not widely read elsewhere. Lorna Wing used the term Asperger syndrome in 1976, and popularized it to the English-speaking medical community in her February 1981 publication of case studies of children showing the symptoms described by Asperger, and Uta Frith translated his paper to English in 1991. Sets of diagnostic criteria were outlined by Gillberg and Gillberg in 1989 and by Szatmari et al. in the same year. In 1992, AS became a standard diagnosis when it was included in the tenth edition of the World Health Organizations diagnostic manual, International Classification of Diseases (ICD-10). It was added to the fourth edition of the American Psychiatric Associations diagnostic reference, Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), published in 1994.Hundreds of books, articles, and websites now describe AS and prevalence estimates have increased dramatically for ASD, with AS recognized as an important subgroup. Whether it should be seen as distinct from high-functioning autism is a fundamental issue requiring further study, and there are questions about the empirical validation of the DSM-IV and ICD-10 criteria. In 2013, DSM-5 eliminated AS as a separate diagnosis, folding it into the autism spectrum on a severity scale. Society and culture People identifying with Asperger syndrome may refer to themselves in casual conversation as aspies (a term first used in print in the Boston Globe in 1998). Some autistic people have advocated a shift in perception of autism spectrum disorders as complex syndromes rather than diseases that must be cured. Proponents of this view reject the notion that there is an "ideal" brain configuration and that any deviation from the norm is pathological; they promote tolerance for what they call neurodiversity. These views are the basis for the autistic rights and autistic pride movements. There is a contrast between the attitude of adults with self-identified AS, who typically do not want to be cured and are proud of their identity; and parents of children with AS, who typically seek assistance and a cure for their children.Some researchers have argued that AS can be viewed as a different cognitive style, not a disorder, and that it should be removed from the standard Diagnostic and Statistical Manual, much as homosexuality was removed. In a 2002 paper, Simon Baron-Cohen wrote of those with AS: "In the social world, there is no great benefit to a precise eye for detail, but in the worlds of maths, computing, cataloging, music, linguistics, engineering, and science, such an eye for detail can lead to success rather than failure." Baron-Cohen cited two reasons why it might still be useful to consider AS to be a disability: to ensure provision for legally required special support, and to recognize emotional difficulties from reduced empathy. Baron-Cohen argues that the genes for Aspergers combination of abilities have operated throughout recent human evolution and have made remarkable contributions to human history.By contrast, Pier Jaarsma and Welin wrote in 2011 that the "broad version of the neurodiversity claim, covering low-functioning as well as high-functioning autism, is problematic. Only a narrow conception of neurodiversity, referring exclusively to high-functioning autists, is reasonable." They say that "higher functioning" individuals with autism may "not [be] benefited with such a psychiatric defect-based diagnosis... some of them are being harmed by it, because of the disrespect the diagnosis displays for their natural way of being", but "think that it is still reasonable to include other categories of autism in the psychiatric diagnostics. The narrow conception of the neurodiversity claim should be accepted but the broader claim should not." Jonathan Mitchell, an autistic author and blogger who advocates a cure for autism, has described autism as having "prevented me from making a living or ever having a girlfriend. Its given me bad fine motor coordination problems where I can hardly write. I have an impaired ability to relate to people. I cant concentrate or get things done." He describes neurodiversity as a "tempting escape valve". References Further reading Autistic Empire, Are you Autistic? Take the test – an online version of the Adult Aspergers Assessment developed by Cohen, S. et al. (2005) (see Woodbury-Smith MR, "Screening adults for Asperger Syndrome using the AQ: a preliminary study of its diagnostic validity in clinical practice", in §References). Hus, Vanessa; Lord, Catherine (2014). "The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores". Journal of Autism and Developmental Disorders. 44 (8): 1996–2012. doi:10.1007/s10803-014-2080-3. PMC 4104252. PMID 24590409. A public paper re-calibrating the Autism Diagnostic Observation Schedule for appropriate assessment of autistic adults, who typically score lower on measures of impairment than autistic children due to compensatory strategies. Royal College of Psychiatrists (2017), Interview Guide for the Diagnostic Assessment of Able Adults with Autistic Spectrum Disorder – based on the Autism Diagnostic Interview-Revised (ADI-R)
Supravalvular aortic stenosis	Supravalvular aortic stenosis is a congenital obstructive narrowing of the aorta just above the aortic valve and is the least common type of aortic stenosis. It is often associated with other cardiovascular anomalies and is one of the characteristic findings of Williams syndrome. The diagnosis can be made by echocardiography or MRI. Genetics Supravalvular aortic stenosis is associated with genetic damage at the Elastin gene locus on chromosome 7q11.23. Fluorescent in situ hybridisation techniques have revealed that 96% of patients with Williams syndrome, where supravalvular aortic stenosis is characteristic, have a hemizygous deletion of the Elastin gene. Further studies have shown that patients with less extensive deletions featuring the Elastin gene also tend to develop supravalvular aortic stenosis Pathophysiology Supravalvular aortic stenosis is due to diffuse or discrete narrowing of ascending aorta. The murmur associated with it is systolic murmur and is similar in character to valvular aortic stenosis murmur but commonly present at 1st Intercostal space (ICS) on the right. Individuals with this anomaly may have unequal carotid pulses, differential blood pressure in upper extremities and a palpable thrill in Suprasternal notch. Individuals with significant supravalvular AS chronically may develop left ventricular hypertrophy and also are at risk of developing coronary artery stenosis. With increased metabolic demands (e.g. exercise) such individuals may develop subendocardial or myocardial ischemia due to increased myocardial oxygen demand and seek medical help with symptoms of exercise induced angina. Diagnosis Treatment == References ==
Hereditary nonpolyposis colorectal cancer	Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. It is a type of cancer syndrome. Because patients with Lynch syndrome can have polyps, the term HNPCC has fallen out of favor. Signs and symptoms Risk of cancer Lifetime risk and mean age at diagnosis for Lynch syndrome associated cancers In addition to the types of cancer found in the chart above, it is understood that Lynch syndrome also contributes to an increased risk of small bowel cancer, pancreatic cancer, ureter/renal pelvis cancer, biliary tract cancer, brain cancer, and sebaceous neoplasms. Increased risk of prostate cancer and breast cancer has also been associated with Lynch syndrome, although this relationship is not entirely understood.Two-thirds of colon cancers occur in the proximal colon and common signs and symptoms include blood in the stool, diarrhea or constipation, and unintended weight loss. The mean age of colorectal cancer diagnosis is 44 for members of families that meet the Amsterdam criteria. The average age of diagnosis of endometrial cancer is about 46 years. Among women with HNPCC who have both colon and endometrial cancer, about half present first with endometrial cancer, making endometrial cancer the most common sentinel cancer in Lynch syndrome. The most common symptom of endometrial cancer is abnormal vaginal bleeding. In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40.Significant variation in the rate of cancer has been found depending on the mutation involved. Up to the age of 75 years the risks of different cancers by the mutations are in the table below. Genetics HNPCC is inherited in an autosomal dominant fashion. The hallmark of HNPCC is defective DNA mismatch repair, which causes an elevated rate of single nucleotide changes and microsatellite instability, also known as MSI-H (the H is "high"). MSI is identifiable in cancer specimens in the pathology laboratory. Most cases result in changes in the lengths of dinucleotide repeats of the nucleobases cytosine and adenine (sequence: CACACACACA...).The 4 main genes involved in HNPCC normally encode for proteins that form dimers to function: MLH1 protein dimerizes with PMS2 protein to form MutLα, which coordinates the binding of other proteins involved with mismatch repair like DNA helicase, single-stranded-DNA binding-protein (RPA), and DNA polymerases. MSH2 protein dimerizes with MSH6 protein, which identifies mismatches via a sliding clamp model, a protein for scanning for errors.The impairment of either gene for the protein dimer impairs the protein function. These 4 genes are involved in error correction (mismatch repair), so dysfunction of the genes can lead to the inability to fix DNA replication errors and cause HNPCC. HNPCC is known to be associated with other mutations in genes involved in the DNA mismatch repair pathway: People with MSH6 mutations are more likely to be Amsterdam criteria II-negative. The presentation with MSH6 is slightly different from with MLH1 and MSH2, and the term "MSH6 syndrome" has been used to describe this condition. In one study, the Bethesda guidelines were more sensitive than the Amsterdam Criteria in detecting it.Up to 39% of families with mutations in an HNPCC gene do not meet the Amsterdam criteria. Therefore, families found to have a deleterious mutation in an HNPCC gene should be considered to have HNPCC regardless of the extent of the family history. This also means that the Amsterdam criteria fail to identify many people who are at risk for Lynch syndrome. Improving the criteria for screening is an active area of research, as detailed in the Screening Strategies section of this article. Most people with HNPCC inherit the condition from a parent. However, due to incomplete penetrance, variable age of cancer diagnosis, cancer risk reduction, or early death, not all people with an HNPCC gene mutation have a parent who had cancer. Some people develop HNPCC de-novo in a new generation, without inheriting the gene. These people are often only identified after developing an early-life colon cancer. Parents with HNPCC have a 50% chance of passing the genetic mutation on to each child. It is also important to note, that deleterious mutation in one of MMR genes alone is not sufficient to cause cancer, but that rather further mutations in other tumour suppressor genes need to occur. Diagnosis A diagnosis of Lynch syndrome is applied to people with a germline DNA mutation in one of the MMR genes (MLH1, MSH2, MSH6, and PMS2) or the EPCAM gene, identified by genetic testing. Candidates for germline genetic testing can be identified by clinical criteria such as the Amsterdam Clinical Criteria and Bethesda Guidelines, or through tumor analysis by immunohistochemistry(IHC), or microsatellite instability (MSI) testing. In the US, professional societies recommend testing every colon cancer for MSI or IHC as screening for Lynch syndrome, but this is not always performed because of cost and resource limitations. Genetic testing is commercially available and consists of a blood test. Immunohistochemistry Immunohistochemistry (IHC) is a method that can be used to detect abnormal mismatch repair (MMR) protein expression in tumours that are associated with Lynch syndrome. While it is not diagnostic of a Lynch syndrome, it can play a role in identifying people who should have germline testing. Two methods of implementation of IHC testing includes age-based testing and universal testing for all people. Currently, there is no widespread agreement regarding which screening method should be used. Age-based testing for IHC has been suggested in part due to cost-benefit analyses, whereas universal testing for all people with colorectal cancer ensures people with Lynch Syndrome are not missed. To address the costs, researchers are trying to predict MSI or IHC directly from the way the tumor looks under the microscope, without doing any molecular testing. Microsatellite Instability Mutations in DNA mismatch repair systems can lead to difficulty transmitting regions within the DNA which contain repeating patterns of two or three nucleotides (microsatellites), otherwise known as microsatellite instability (MSI). MSI is identified through DNA extraction from both a tumor tissue sample and a normal tissue sample followed by PCR analysis of microsatellite regions. MSI analysis can be used to identify people who may have Lynch syndrome and direct them for further testing. Classification Three major groups of MSI-H (microsatellite instability – MSI) cancers can be recognized by histopathological criteria: right-sided poorly differentiated cancers right-sided mucinous cancers adenocarcinomas in any location showing any measurable level of intraepithelial lymphocyte (TIL)The histopathological criteria are not sensitive enough to detect MSI from histology but researchers are trying to use artificial intelligence to predict MSI from histology.In addition, HNPCC can be divided into Lynch syndrome I (familial colon cancer) and Lynch syndrome II (HNPCC associated with other cancers of the gastrointestinal tract or reproductive system). Prevention After reporting a null finding from their randomized controlled trial of aspirin (acetylsalicylic acid – ASA) to prevent the colorectal neoplasia of Lynch syndrome, Burn and colleagues have reported new data, representing a longer follow-up period than reported in the initial NEJM paper. These new data demonstrate a reduced incidence in people with Lynch syndrome who were exposed to at least four years of high-dose aspirin, with a satisfactory risk profile. These results have been widely covered in the media; future studies will look at modifying (lowering) the dose (to reduce risk associated with the high dosage of ASA). Screening Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer. Colon cancer Colonoscopies are recommended as a preventative method of surveillance for individuals who have Lynch syndrome, or LS-associated genes. Specifically, it is recommended that colonoscopies begin at ages 20–25 for MLH1 and MSH2 mutation carriers and 35 years for MSH6 and PMS2 mutation carriers. Colonoscopic surveillance should then be performed at a 1-2 year interval for Lynch Syndrome patients.Endometrial/Ovarian cancer A transvaginal ultrasound with or without endometrial biopsy is recommended annually for ovarian and endometrial cancer screening. For women with Lynch syndrome, a yearly CA-125 blood test can be used to screen for ovarian cancer, however there is limited data on the efficacy of this test in reducing mortality.Other cancers There are also strategies for detecting other cancers early or reducing the chances of developing them that people with Lynch syndrome can discuss with their doctor, however their effectiveness is not clear. These options include: Upper endoscopies to detect stomach and small bowel cancer every 3–5 years, starting at age 30 at the earliest (preferably in a research setting) Annual urinalysis to detect bladder cancer, starting at age 30 at the earliest (preferably in a research setting) Annual physical and neurological exams to detect cancer in the central nervous system (brain or spinal cord), starting at age 25 at the earliest Amsterdam criteria The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:Amsterdam I Criteria (all bullet points must be fulfilled): The Amsterdam I criteria were published in 1990; however, were felt to be insufficiently sensitive. Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two Two successive affected generations One or more colon cancers diagnosed under age 50 years Familial adenomatous polyposis (FAP) has been excludedThe Amsterdam II criteria were developed in 1999 and improved the diagnostic sensitivity for Lynch syndrome by including cancers of the endometrium, small bowel, ureter and renal pelvis.Amsterdam Criteria II (all bullet points must be fulfilled): Three or more family members with HNPCC-related cancers, one of whom is a first-degree relative of the other two Two successive affected generations One or more of the HNPCC-related cancers diagnosed under age 50 years Familial adenomatous polyposis (FAP) has been excludedThe Bethesda criteria were developed in 1997 and later updated in 2004 by the National Cancer Institute to identify persons requiring further testing for Lynch syndrome through MSI. In contrast to the Amsterdam Criteria, the Revised Bethesda Guidelines use pathological data in addition to clinical information to help health care providers identify persons at high risk.Revised Bethesda Guidelines If a person meets any 1 of 5 criteria the tumour(s) from the person should be tested for MSI:1. Colorectal cancer diagnosed before age 50 2. Presence of synchronous or metachronous colorectal or other Lynch syndrome associated cancers (e.g. cancers of endometrium, ovary, stomach, small bowel, pancreas, biliary tract, ureter, renal pelvis, brain, sebaceous glands, keratoacanthomas) 3. Colorectal cancer with MSI-high pathology in a person who is younger than 60 years of age 4. Colorectal cancer diagnosed in a person with one or more first-degree relative with colorectal cancer or Lynch syndrome associated tumour diagnosed under age 50 5. Person with colorectal cancer and two or more first- or second-degree relatives with colorectal cancer or Lynch syndrome associated cancer diagnosed at any age.It is important to note that these clinical criteria can be difficult to use in practice and clinical criteria used alone misses between 12 and 68 percent of Lynch syndrome cases. Surgery Prophylactic hysterectomy and salpingo-oophorectomy (removal of the uterus, Fallopian tubes, and ovaries to prevent cancer from developing) can be performed before ovarian or endometrial cancer develops. Treatment Surgery remains the front-line therapy for HNPCC. Patients with Lynch syndrome who develop colorectal cancer may be treated with either a partial colectomy or total colectomy with ileorectal anastomosis. Due to increased risk of colorectal cancer following partial colectomy and similar quality of life after both surgeries, a total colectomy may be a preferred treatment for HNPCC, especially in younger patients.There is an ongoing controversy over the benefit of 5-fluorouracil-based adjuvant therapies for HNPCC-related colorectal tumours, particularly those in stages I and II. Anti-PD-1 antibody therapy can be effective.Checkpoint blockade with anti-PD-1 therapy is now preferred first line therapy for advanced Microsatellite-Instability–High colorectal cancer. Epidemiology Though the exact prevalence of Lynch syndrome-causing mutations in the general population remain unknown, recent studies estimate the prevalence to be 1 in 279 individuals, or 0.35%. Certain populations are known to have a higher prevalence of founder mutations, including, but not limited to, French Canadians, Icelanders, African Americans, and Ashkenazi Jews. Lynch syndrome-causing mutations are found in approximately 3% of all diagnosed colorectal cancers, and 1.8% of all diagnosed endometrial cancers. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome. Terminology Henry T. Lynch, Professor of Medicine at Creighton University Medical Center, characterized the syndrome in 1966. In his earlier work, he described the disease entity as "cancer family syndrome." The term "Lynch syndrome" was coined in 1984 by other authors; Lynch named the condition HNPCC in 1985. Since then the two terms have been used interchangeably, until later advances in the understanding of the genetics of the disease led to the term HNPCC falling out of favor.Other sources reserve the term "Lynch syndrome" when there is a known DNA mismatch repair defect, and use the term "familial colorectal cancer type X" when the Amsterdam criteria are met but there is no known DNA mismatch repair defect. The putative "type X" families appear to have a lower overall incidence of cancer and lower risk for non-colorectal cancers than families with documented DNA mismatch repair deficiency. About 35% of people who meet Amsterdam criteria do not have a DNA-mismatch-repair gene mutation.Complicating matters is the presence of an alternative set of criteria, known as the "Bethesda Guidelines." Society There are a number of non-profit organisations providing information and support, including Lynch Syndrome International, AliveAndKickn, Lynch Syndrome UK and Bowel Cancer UK. In the US, National Lynch Syndrome Awareness Day is March 22. References Further reading Books McKay, Ami (2019). Daughter of Family G. : a memoir of cancer genes, love and fate. Toronto: Alfred A. Knopf Canada. ISBN 978-0-345-80946-9. OCLC 1089450897. Paperback version retitled Before My Time. External links FAQs on HNPCC Archived 2007-08-15 at the Wayback Machine from the National Institute of Health GeneReviews/NCBI/NIH/UW entry on Lynch syndrome hnpcc at NIH/UW GeneTests National Cancer Institute: Genetics of Colorectal Cancer information summary
Portal hypertensive gastropathy	Portal hypertensive gastropathy refers to changes in the mucosa of the stomach in patients with portal hypertension; by far the most common cause of this is cirrhosis of the liver. These changes in the mucosa include friability of the mucosa and the presence of ectatic blood vessels at the surface. Patients with portal hypertensive gastropathy may experience bleeding from the stomach, which may uncommonly manifest itself in vomiting blood or melena; however, portal hypertension may cause several other more common sources of upper gastrointestinal bleeding, such as esophageal varices and gastric varices. On endoscopic evaluation of the stomach, this condition shows a characteristic mosaic or "snake-skin" appearance to the mucosa of the stomach. Signs and symptoms Most patients with portal hypertensive gastropathy have either a stable or improving course in the appearance of the gastropathy on endoscopy. However, according to retrospective data, roughly one in seven patients with portal hypertensive gastropathy will develop bleeding (either acute or chronic) attributable to the gastropathy. Patients with chronic bleeding will usually come to the attention of the medical system because of anemia. The diagnosis of portal hypertensive gastropathy is usually made on endoscopy. The usual appearance of portal hypertensive gastropathy on endoscopy is a mosaic-like or reticular pattern in the mucosa. Red spots may or may not be present. The pattern is usually seen throughout the stomach. A similar pattern can be seen with a related condition called gastric antral vascular ectasia (GAVE), or watermelon stomach. However, in GAVE, the ectatic blood vessels are more commonly found in the antrum or lower part of the stomach. Pathogenesis Several studies have found that patients with portal hypertension develop increased blood flow to the stomach. The physiological findings that correlate with worsening portal hypertensive gastropathy include an increased portal venous pressure gradient and decreased hepatic blood flow. Biopsies of the stomach in patients with portal hypertensive gastropathy show ectatic (or dilated) blood vessels, evidence of bleeding by means of red blood cells in the lamina propria, and edema in the stomach wall. Treatment Medications Several treatment options have been developed for portal hypertensive gastropathy. The first is the use of beta-blockers, which reduce portal pressures. Non-selective beta blockers (such as propranolol and nadolol) have been used to decrease the pressure of the portal vein in patients with esophageal varices, and have been shown to regress portal hypertensive gastropathy that has been worsened by medical treatment of varices. Propranolol has also been evaluated in patients with chronic cirrhosis and portal hypertensive gastropathy. Other medications that primarily treat bleeding, including anti-fibrinolytic medications such as tranexamic acid have also been used in case reports of patients with portal hypertensive gastropathy. These medications work by stabilizing deposits of fibrin at sites that ordinarily would bleed. Finally, octreotide, an analogue of somatostatin that leads to vasoconstriction of the portal circulation, can be used for active bleeding due to portal hypertensive gastropathy. Sucralfate, a coating medication has also been used, but evidence is from animal models. Procedural Portal hypertensive gastropathy can also be treated with endoscopic treatment delivered through a fibre-optic camera into the stomach. Argon plasma coagulation and electrocautery have both been used to stop bleeding from ectatic vessels, and to attempt to obliterate the vessels, but have limited utility if the disease is diffuse.Transjugular intrahepatic portosystemic shunt procedures, or TIPS involve decompressing the portal vein by shunting a portal venule to a lower pressure systemic venule, under guidance with fluoroscopy. Since it treats the root cause of portal hypertension gastropathy, it has been putatively used for the condition. The literature reports suggest both regression of portal hypertensive gastropathy on endoscopic images and improvement in bleeding after TIPS.Finally, cryotherapy involves the use of pressurized carbon dioxide administered through the endoscope to freeze and destroy tissue in a focal area. It is being studied for the treatment of portal hypertensive gastropathy. Similar conditions Congestion of the mucosa in other parts of the gastrointestinal tract can also be seen in portal hypertension. When the condition involves the colon, it is termed portal hypertensive colopathy. References == External links ==
Potassium-aggravated myotonia	Potassium-aggravated myotonia is a rare genetic disorder that affects skeletal muscle. Beginning in childhood or adolescence, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness, often painful, that worsens after exercise and may be aggravated by eating potassium-rich foods such as bananas and potatoes. Stiffness occurs in skeletal muscles throughout the body. Potassium-aggravated myotonia ranges in severity from mild episodes of muscle stiffness to severe, disabling disease with frequent attacks. Potassium-aggravated myotonia may, in some cases, also cause paradoxical myotonia, in which myotonia becomes more severe at the time of movement instead of after movement has ceased. Unlike some other forms of myotonia, potassium-aggravated myotonia is not associated with episodes of muscle weakness.Mutations in the SCN4A gene cause potassium-aggravated myotonia. The SCN4A gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles contract and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged ions, including sodium, into skeletal muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells. Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot properly regulate ion flow, increasing the movement of sodium ions into skeletal muscle cells. The influx of extra sodium ions triggers prolonged muscle contractions, which are the hallmark of myotonia.Potassium-aggravated myotonia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the SCN4A gene from one affected parent. Other cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. References == External links ==
Dermatitis	Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can vary from small to covering the entire body. Dermatitis is often called eczema, and the difference between those terms is not standardized. The exact cause of the condition is often unclear. Cases may involve a combination of allergy and poor venous return. The type of dermatitis is generally determined by the persons history and the location of the rash. For example, irritant dermatitis often occurs on the hands of those who frequently get them wet. Allergic contact dermatitis occurs upon exposure to an allergen, causing a hypersensitivity reaction in the skin.Prevention of atopic dermatitis is typically with essential fatty acids, and may be treated with moisturizers and steroid creams. The steroid creams should generally be of mid- to high strength and used for less than two weeks at a time, as side effects can occur. Antibiotics may be required if there are signs of skin infection. Contact dermatitis is typically treated by avoiding the allergen or irritant. Antihistamines may help with sleep and decrease nighttime scratching.Dermatitis was estimated to affect 245 million people globally in 2015, or 3.34% of the world population. Atopic dermatitis is the most common type and generally starts in childhood. In the United States, it affects about 10–30% of people. Contact dermatitis is twice as common in females as males. Allergic contact dermatitis affects about 7% of people at some point in their lives. Irritant contact dermatitis is common, especially among people with certain occupations; exact rates are unclear. Types Dermatitis includes: Atopic dermatitis Allergic contact dermatitis Irritant contact dermatitis Seborrhoeic dermatitis Stasis dermatitis Signs and symptoms Dermatitis symptoms vary with all different forms of the condition. Although every type of dermatitis has different symptoms, there are certain signs that are common for all of them, including redness of the skin, swelling, itching and skin lesions with sometimes oozing and scarring. Also, the area of the skin on which the symptoms appear tends to be different with every type of dermatitis, whether on the neck, wrist, forearm, thigh or ankle. Although the location may vary, the primary symptom of this condition is itchy skin. More rarely, it may appear on the genital area, such as the vulva or scrotum. Symptoms of this type of dermatitis may be very intense and may come and go. Irritant contact dermatitis is usually more painful than itchy. Although the symptoms of atopic dermatitis vary from person to person, the most common symptoms are dry, itchy, red skin. Typical affected skin areas include the folds of the arms, the back of the knees, wrists, face and hands. Perioral dermatitis refers to a red bumpy rash around the mouth.Dermatitis herpetiformis symptoms include itching, stinging and a burning sensation. Papules and vesicles are commonly present. The small red bumps experienced in this type of dermatitis are usually about 1 cm in size, red in color and may be found symmetrically grouped or distributed on the upper or lower back, buttocks, elbows, knees, neck, shoulders and scalp. The symptoms of seborrhoeic dermatitis, on the other hand, tend to appear gradually, from dry or greasy scaling of the scalp (dandruff) to scaling of facial areas, sometimes with itching, but without hair loss. In newborns, the condition causes a thick and yellowish scalp rash, often accompanied by a diaper rash. In severe cases, symptoms may appear along the hairline, behind the ears, on the eyebrows, on the bridge of the nose, around the nose, on the chest, and on the upper back. Complications People with eczema should not receive the smallpox vaccination due to risk of developing eczema vaccinatum, a potentially severe and sometimes fatal complication. Other major health risks for people with dermatitis are viral and bacterial infections because atopic dermatitis patients have deficiencies in their proteins and lipids that have barrier functions along with defects in dendritic cells and as a result are unable to keep foreign invaders out leading to recurring infections. If left untreated, these infections may be life-threatening, so skin barrier improvement (such as daily moisturizing to minimize transepidermal water loss) and anti-inflammatory therapy are recommended as preventative measures. Cause The cause of dermatitis is unknown but is presumed to be a combination of genetic and environmental factors. Environmental The hygiene hypothesis postulates that the cause of asthma, eczema, and other allergic diseases is an unusually clean environment in childhood which leads to an insufficient human microbiota. It is supported by epidemiologic studies for asthma. The hypothesis states that exposure to bacteria and other immune system modulators is important during development, and missing out on this exposure increases the risk for asthma and allergy. One systematic review of literature on eczema found that urban areas have an increased prevalence of eczema compared to rural areas. While it has been suggested that eczema may sometimes be an allergic reaction to the excrement from house dust mites, with up to 5% of people showing antibodies to the mites, the overall role this plays awaits further corroboration. Malnutrition Essential fatty acid deficiency results in a dermatitis similar to that seen in zinc or biotin deficiency. Genetic A number of genes have been associated with eczema, one of which is filaggrin. Genome-wide studies found three new genetic variants associated with eczema: OVOL1, ACTL9 and IL4-KIF3A.Eczema occurs about three times more frequently in individuals with celiac disease and about two times more frequently in relatives of those with celiac disease, potentially indicating a genetic link between the conditions. Prevention Exclusive breastfeeding of infants during at least the first few months may decrease the risk. There is no good evidence that a mothers diet during pregnancy or breastfeeding affects the risk, nor is there evidence that delayed introduction of certain foods is useful. There is tentative evidence that probiotics in infancy may reduce rates but it is insufficient to recommend its use. There is moderate certainty evidence that the use of skin care interventions such as emollients within the first year of life of an infants life is not effective in preventing eczema. In fact, it may increase the risk of skin infection and of unwanted effects such as allergic reaction to certain moisturizers and a stinging sensation. Healthy diet There has not been adequate evaluation of changing the diet to reduce eczema. There is some evidence that infants with an established egg allergy may have a reduction in symptoms if eggs are eliminated from their diets. Benefits have not been shown for other elimination diets, though the studies are small and poorly executed. Establishing that there is a food allergy before dietary change could avoid unnecessary lifestyle changes. Fatty acids Oils with fatty acids that has been studied to prevent dermatitis includes: Corn oil: Linoleic acid (LA) Fish oil: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) Hemp seed oil: Linoleic acid (LA), and alpha-Linolenic acid (ALA)In the 1950s Arild Hansen showed that in humans: infants fed skimmed milk developed the essential fatty acid deficiency. It was characterized by an increased food intake, poor growth, and a scaly dermatitis, and was cured by the administration of corn oil. Management There is no known cure for some types of dermatitis, with treatment aiming to control symptoms by reducing inflammation and relieving itching. Contact dermatitis is treated by avoiding what is causing it. Lifestyle Bathing once or more a day is recommended, usually for five to ten minutes in warm water. Soaps should be avoided, as they tend to strip the skin of natural oils and lead to excessive dryness. The American Academy of Dermatology suggests using a controlled amount of bleach diluted in a bath to help with atopic dermatitis.People can wear clothing designed to manage the itching, scratching and peeling.House dust mite reduction and avoidance measures have been studied in low quality trials and have not shown evidence of improving eczema. Moisturizers Low-quality evidence indicates that moisturizing agents (emollients) may reduce eczema severity and lead to fewer flares. In children, oil–based formulations appear to be better, and water–based formulations are not recommended. It is unclear if moisturizers that contain ceramides are more or less effective than others. Products that contain dyes, perfumes, or peanuts should not be used. Occlusive dressings at night may be useful.Some moisturizers or barrier creams may reduce irritation in occupational irritant hand dermatitis, a skin disease that can affect people in jobs that regularly come into contact with water, detergents, chemicals or other irritants. Some emollients may reduce the number of flares in people with dermatitis. Medications Corticosteroids If symptoms are well controlled with moisturizers, steroids may only be required when flares occur. Corticosteroids are effective in controlling and suppressing symptoms in most cases. Once daily use is generally enough. For mild-moderate eczema a weak steroid may be used (e.g., hydrocortisone), while in more severe cases a higher-potency steroid (e.g., clobetasol propionate) may be used. In severe cases, oral or injectable corticosteroids may be used. While these usually bring about rapid improvements, they have greater side effects. Long term use of topical steroids may result in skin atrophy, stria, telangiectasia. Their use on delicate skin (face or groin) is therefore typically with caution. They are, however, generally well tolerated. Red burning skin, where the skin turns red upon stopping steroid use, has been reported among adults who use topical steroids at least daily for more than a year. Antihistamines There is little evidence supporting the use of antihistamine medications for the relief of dermatitis. Sedative antihistamines, such as diphenhydramine, may be useful in those who are unable to sleep due to eczema. Second generation antihistamines have minimal evidence of benefit. Of the second generation antihistamines studied, fexofenadine is the only one to show evidence of improvement in itching with minimal side effects. Immunosuppressants Topical immunosuppressants like pimecrolimus and tacrolimus may be better in the short term and appear equal to steroids after a year of use. Their use is reasonable in those who do not respond to or are not tolerant of steroids. Treatments are typically recommended for short or fixed periods of time rather than indefinitely. Tacrolimus 0.1% has generally proved more effective than pimecrolimus, and equal in effect to mid-potency topical steroids. There is no link to increased risk of cancer from topical use of 1% pimecrolimus cream.When eczema is severe and does not respond to other forms of treatment, systemic immunosuppressants are sometimes used. Immunosuppressants can cause significant side effects and some require regular blood tests. The most commonly used are ciclosporin, azathioprine, and methotrexate. Dupilumab is a new medication that improves eczema lesions, especially moderate to severe eczema. Dupilumab, a monoclonal antibody, suppresses inflammation by targeting the interleukin-4 receptor. Others In September 2021, ruxolitinib cream (Opzelura) was approved by the U.S. Food and Drug Administration (FDA) for the topical treatment of mild to moderate atopic dermatitis. It is a topical Janus kinase inhibitor. Light therapy Narrowband UVB Atopic dermatitis (AD) may be treated with narrowband UVB, which increases 25-hydroxyvitamin D3 in persons in individuals with AD.Light therapy using heliotherapy, balneophototherapy, psoralen plus UVA (PUVA), light has tentative support but the quality of the evidence is not very good compared with narrowband UVB, and UVA1. However, UVB is more effective than UVA1 for treatment of atopical dermatitis.Overexposure to ultraviolet light carries its own risks, particularly that of skin cancer. Alternative medicine Topical Limited evidence suggests that acupuncture may reduce itching in those affected by atopic dermatitis.Chiropractic spinal manipulation lacks evidence to support its use for dermatitis. There is little evidence supporting the use of psychological treatments. While dilute bleach baths have been used for infected dermatitis there is little evidence for this practice. Supplements Sulfur: There is currently no scientific evidence for the claim that sulfur treatment relieves eczema. Chinese herbs: It is unclear whether Chinese herbs help or harm. Dietary supplements are commonly used by people with eczema. Neither evening primrose oil nor borage seed oil taken orally have been shown to be effective. Both are associated with gastrointestinal upset. Probiotics are likely to make little to no difference in symptoms. Pathophysiology Eczema can be characterized by spongiosis which allows inflammatory mediators to accumulate. Different dendritic cells sub types, such as Langerhans cells, inflammatory dendritic epidermal cells and plasmacytoid dendritic cells have a role to play. Diagnosis Diagnosis of eczema is based mostly on the history and physical examination. In uncertain cases, skin biopsy may be taken for a histopathologic diagnosis of dermatitis. Those with eczema may be especially prone to misdiagnosis of food allergies.Patch tests are used in the diagnosis of allergic contact dermatitis. Classification The term eczema refers to a set of clinical characteristics. Classification of the underlying diseases has been haphazard with numerous different classification systems, and many synonyms being used to describe the same condition.A type of dermatitis may be described by location (e.g., hand eczema), by specific appearance (eczema craquele or discoid) or by possible cause (varicose eczema). Further adding to the confusion, many sources use the term eczema interchangeably for the most common type: atopic dermatitis.The European Academy of Allergology and Clinical Immunology (EAACI) published a position paper in 2001, which simplifies the nomenclature of allergy-related diseases, including atopic and allergic contact eczemas. Non-allergic eczemas are not affected by this proposal. Histopathologic classification By histopathology, superficial dermatitis (in the epidermis, papillary dermis, and superficial vascular plexus) can basically be classified into either of the following groups: Vesiculobullous lesions Pustular dermatosis Non vesicullobullous, non-pustularWith epidermal changes Without epidermal changes. These characteristically have a superficial perivascular inflammatory infiltrate and can be classified by type of cell infiltrate:Lymphocytic (most common) Lymphoeosinophilic Lymphoplasmacytic Mast cell Lymphohistiocytic Neutrophilic Terminology There are several types of dermatitis including atopic dermatitis, contact dermatitis, stasis dermatitis and seborrhoeic dermatitis. Many authors use the terms dermatitis and eczema synonymously, and various dictionaries that treat the terms as differentiable nonetheless do not provide explicit criteria for differentiating them, as the aspects of inflammation, pruritus, and either exogenous or endogenous provoking agent all can apply to either term, and thus autoimmune components are not excluded from either. Others use the term eczema to specifically mean atopic dermatitis. Atopic dermatitis is also known as atopic eczema. In some languages, dermatitis and eczema mean the same thing, while in other languages dermatitis implies an acute condition and eczema a chronic one. Common types Diagnosis of types may be indicated by codes defined according to International Statistical Classification of Diseases and Related Health Problems (ICD). Atopic Atopic dermatitis is an allergic disease believed to have a hereditary component and often runs in families whose members have asthma. Itchy rash is particularly noticeable on the head and scalp, neck, inside of elbows, behind knees, and buttocks. It is very common in developed countries and rising. Irritant contact dermatitis is sometimes misdiagnosed as atopic dermatitis. Stress can cause atopic dermatitis to worsen. Contact Contact dermatitis is of two types: allergic (resulting from a delayed reaction to an allergen, such as poison ivy, nickel, or Balsam of Peru), and irritant (resulting from direct reaction to a detergent, such as sodium lauryl sulfate, for example). Some substances act both as allergen and irritants (wet cement, for example). Other substances cause a problem after sunlight exposure, bringing on phototoxic dermatitis. About three-quarters of cases of contact eczema are of the irritant type, which is the most common occupational skin disease. Contact eczema is curable, provided the offending substance can be avoided and its traces removed from ones environment. (ICD-10 L23; L24; L56.1; L56.0) Seborrhoeic Seborrhoeic dermatitis or seborrheic dermatitis is a condition sometimes classified as a form of eczema that is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk. In newborns, it causes a thick, yellow, crusty scalp rash called cradle cap, which seems related to lack of biotin and is often curable. (ICD-10 L21; L21.0) Less common types Dyshidrosis Dyshidrosis (dyshidrotic eczema, pompholyx, vesicular palmoplantar dermatitis) only occurs on palms, soles, and sides of fingers and toes. Tiny opaque bumps called vesicles, thickening, and cracks are accompanied by itching, which gets worse at night. A common type of hand eczema, it worsens in warm weather. (ICD-10 L30.1) Discoid Discoid eczema (nummular eczema, exudative eczema, microbial eczema) is characterized by round spots of oozing or dry rash, with clear boundaries, often on lower legs. It is usually worse in winter. The cause is unknown, and the condition tends to come and go. (ICD-10 L30.0) Venous Venous eczema (gravitational eczema, stasis dermatitis, varicose eczema) occurs in people with impaired circulation, varicose veins, and edema, and is particularly common in the ankle area of people over 50. There is redness, scaling, darkening of the skin, and itching. The disorder predisposes to leg ulcers. (ICD-10 I83.1) Herpetiformis Dermatitis herpetiformis (Duhrings disease) causes an intensely itchy and typically symmetrical rash on arms, thighs, knees, and back. It is directly related to celiac disease, can often be put into remission with an appropriate diet, and tends to get worse at night. (ICD-10 L13.0) Neurodermatitis Neurodermatitis (lichen simplex chronicus, localized scratch dermatitis) is an itchy area of thickened, pigmented eczema patch that results from habitual rubbing and scratching. Usually, there is only one spot. Often curable through behaviour modification and anti-inflammatory medication. Prurigo nodularis is a related disorder showing multiple lumps. (ICD-10 L28.0; L28.1) Autoeczematization Autoeczematization (id reaction, auto sensitization) is an eczematous reaction to an infection with parasites, fungi, bacteria, or viruses. It is completely curable with the clearance of the original infection that caused it. The appearance varies depending on the cause. It always occurs some distance away from the original infection. (ICD-10 L30.2) Viral There are eczemas overlaid by viral infections (eczema herpeticum or vaccinatum), and eczemas resulting from underlying disease (e.g., lymphoma). Eczemas originating from ingestion of medications, foods, and chemicals, have not yet been clearly systematized. Other rare eczematous disorders exist in addition to those listed here. Prognosis Most cases are well managed with topical treatments and ultraviolet light. About 2% of cases are not. In more than 60% of young children, the condition subsides by adolescence. Epidemiology Globally dermatitis affected approximately 230 million people as of 2010 (3.5% of the population). Dermatitis is most commonly seen in infancy, with female predominance of eczema presentations occurring during the reproductive period of 15–49 years. In the UK about 20% of children have the condition, while in the United States about 10% are affected.Although little data on the rates of eczema over time exists prior to the 1940s, the rate of eczema has been found to have increased substantially in the latter half of the 20th century, with eczema in school-aged children being found to increase between the late 1940s and 2000. In the developed world there has been rise in the rate of eczema over time. The incidence and lifetime prevalence of eczema in England has been seen to increase in recent times.Dermatitis affected about 10% of U.S. workers in 2010, representing over 15 million workers with dermatitis. Prevalence rates were higher among females than among males and among those with some college education or a college degree compared to those with a high school diploma or less. Workers employed in healthcare and social assistance industries and life, physical, and social science occupations had the highest rates of reported dermatitis. About 6% of dermatitis cases among U.S. workers were attributed to work by a healthcare professional, indicating that the prevalence rate of work-related dermatitis among workers was at least 0.6%. History The term "atopic dermatitis" was coined in 1933 by Wise and Sulzberger. Sulfur as a topical treatment for eczema was fashionable in the Victorian and Edwardian eras.The word dermatitis is from the Greek δέρμα derma "skin" and -ῖτις -itis "inflammation" and eczema is from Greek: ἔκζεμα ekzema "eruption". Society and culture Some cosmetics are marketed as hypoallergenic to imply that their use is less likely to lead to an allergic reaction than other products. However, the term "hypoallergenic" is not regulated, and no research has been done showing that products labeled "hypoallergenic" are less problematic than any others. In 1977, courts overruled the U.S. Food and Drug Administrations regulation of the use of the term hypoallergenic. In 2019, the European Union on released a document about claims made concerning cosmetics, but this was issued as "guidance" not a regulation. Research Monoclonal antibodies are under preliminary research to determine their potential as treatments for atopic dermatitis, with only dupilumab showing evidence of efficacy, as of 2018. See also Dyshidrosis Noxzema Urticaria References External links Dermatitis at Curlie
Macropsia	Macropsia is a neurological condition affecting human visual perception, in which objects within an affected section of the visual field appear larger than normal, causing the person to feel smaller than they actually are. Macropsia, along with its opposite condition, micropsia, can be categorized under dysmetropsia. Macropsia is related to other conditions dealing with visual perception, such as aniseikonia and Alice in Wonderland Syndrome (AIWS, also known as Todds syndrome). Macropsia has a wide range of causes, from prescription and illicit drugs, to migraines and (rarely) complex partial epilepsy, and to different retinal conditions, such as epiretinal membrane. Physiologically, retinal macropsia results from the compression of cones in the eye. It is the compression of receptor distribution that results in greater stimulation and thus a larger perceived image of an object. Signs and symptoms The most obvious symptom of macropsia is the presence of exceptionally enlarged objects throughout the visual field. For example, a young girl might see her sisters books as the same size as her sister. Stemming from this symptom, someone with macropsia may feel undersized in relation to his or her surrounding environment. Patients with macropsia have also noted the cessation of auditory function prior to the onset of visual hallucination, indicating possible seizure either before or after the hallucination. A buzzing sound in the ears has also been reported immediately before macropsia development. Some patients claim that symptoms may be eased if an attempt is made to physically touch the object which appears enormous in size. It is important to note, however, that patients typically remain lucid and alert throughout episodes, being able to recount specific details. A person with macropsia may have no psychiatric conditions. Symptoms caused chemically by drugs such as cannabis, magic mushrooms, or cocaine tend to dissipate after the chemical compound has been excreted from the body. Those who acquire macropsia as a symptom of a virus usually experience complete recovery and restoration of normal vision.Dysmetropsia in one eye, a case of aniseikonia, can present with symptoms such as headaches, asthenopia, reading difficulties, depth perception problems, or double vision. The visual distortion can cause uncorrelated images to stimulate corresponding retinal regions simultaneously impairing fusion of the images. Without suppression of one of the images symptoms from mild poor stereopsis, binocular diplopia and intolerable rivalry can occur. Psychological effects There are a broad range of psychological and emotional effects that a person with macropsia may experience. One competing theory has radically stated that macropsia may be an entirely psychological pathological phenomenon without any structural defect or definite cause. They may be in an irritable or angry state, or in contrast, a euphoric state. There is evidence that those who experience Alice in Wonderland Syndrome and associated macropsia are able to recount their experiences with thorough detail. There may be no evidence of psychiatric disturbance and, as a result, no psychiatric therapy may be required. Psychological conditions often arise from macropsia, but the general consensus is that they do not cause macropsia. Those affected may experience extreme anxiety both during and after episodes as a result of the overwhelming nature of his or her distorted visual field. Due to the fear and anxiety associated with the condition, those who have previously had an episode hesitate to recount the episode, although retain the ability to do so. Psychologically, a person with macropsia may feel separation and dissociation from the outside world and even from immediate family. This feeling of dissociation has mostly been noted in child or adolescent patients. The patient may feel that he or she must unfairly contend with hostile and aggressive forces due to the gigantic nature of the surrounding environment. The defense against said forces is usually expressed verbally. The patient may falsely present an outgoing or flamboyant persona, while remaining fearful of people internally. He or she, in an attempt to balance the size distortion, may try to make others feel small in size through insult or hostile behavior. The psychological impact of macropsia on long-time people who have had the condition since childhood may be greater and lead to severe ego-deficiencies. An alternative interpretation of the condition is that macropsia is a response to biophysiological contraction and has no psychological roots. Thus, when a patient reaches for an enlarged object, he or she is overcoming that physiological contraction. However, this theory has been under much scrutiny. Causes Structural defects In cases where macropsia affects one eye resulting in differences in the way the two eyes perceive the size or shape of images, the condition is known as aniseikonia. Aniseikonia is known to be associated with certain retinal conditions. Epiretinal membrane has been found to cause metamorphopsia and aniseikonia. Vitreomacular traction caused by the excessive adhesion of vitreous fluid to the retina is related to aniseikonia due to the separation and compression of photoreceptor cells. Macular edema and surgical re-attachment for macula-off rhegmatogenous retinal detachment can also cause an increased separation of macular photoreceptor cells resulting in dysmetropsia. Retinoschisis is another eye disease that has been shown to cause aniseikonia.There is evidence that a lesion appearing in the posterior area of the ventral occipitotemporal visual pathway can cause macropsia. This lesion can be due to an ischemic cell death after an acute posterior cerebral infarction. Medications The most prevalent research on prescription drugs with side effects of macropsia deals with zolpidem and citalopram. Zolpidem is a drug prescribed for insomnia, and although it has proven beneficial effects, there have been numerous reported cases of adverse perceptual reactions. One of these cases discusses an anorexic womans episode of macropsia, which occurred twenty minutes after taking 10 mg zolpidem. The same woman later had two more episodes of zolpidem-induced macropsia, after taking 5 mg and 2.5 mg zolpidem, respective to each episode. The intensity of the macropsia episodes decreased with the decreasing amount of zolpidem administered; it is implied in the article that the level of intensity was based on the patients accounts of her macropsia episodes, and that no external diagnosis was used. Hoyler points out notable similarities among the different reported cases of zolpidem-induced disorganization. The similarities were that all the cases were reported by women, the disorganization and agitation followed the first administration of zolpidem, and once zolpidem was discontinued, there were no lasting residual effects. It is believed that zolpidem-related macropsia is more prevalent in women because plasma zolpidem concentration is 40% higher in women, a concentration that further increases in anorexic women.Citalopram-induced macropsia is similar to zolpidem-induced macropsia since both types have been observed in relatively few cases, and neither of the drugs side effects can be supported by experimental evidence. Citalopram is an antidepressant that inhibits serotonin reuptake. The first case of macropsia thought to be induced by citalopram involves a woman who experienced macropsia after her first administration of 10 mg citalopram. Just as with zolpidem, after the immediate discontinuation of citalopram, there were no further episodes of macropsia. Illicit drugs There are suggestions that visual distortions, such as macropsia, can be associated with cocaine use. Episodes of temporary drug-induced macropsia subside as the chemicals leave the body. Migraine Past research has linked macropsia to migraine. One of these studies was conducted on Japanese adolescents who reported visual episodic illusions with macropsia and showed that illusions are three times more likely to occur in association with migraine. The illusions were most prevalent among girls between the ages of 16 and 18. It is unlikely that macropsia in Japanese adolescents could be due to epileptic seizure since only 0.3% of Japanese adolescents have epilepsy. No evidence of drugs was found, which eliminates the possibility of the macropsia in the adolescents being drug-induced. It is also unlikely for macropsia in adolescent children to be associated with a serious disease. It is usually the macropsia or other visual disturbance which precedes the painful migrainous headaches. The episodes of macropsia can occur as part of the aura in a migraine. These episodes are often brief, lasting only a few minutes. Adolescents who are deemed to have multiple distortions per episode, such as slow motion vision and macropsia, are even more likely to be people with migraine. The macropsia episodes associated with migraine are typically equivalent to the duration of the aura, which can range from moments to 15 minutes. Non-migrainous headaches are not known to be associated with episodic illusions. Even in the absence of a migraine, a fever or a hypnogogic state can provoke visual illusions, which one might claim to be macropsia. A person with macropsia may fail to see the connection between the migraine and the macropsia, since the conditions may not elicit symptoms at the same time. The pathophysiology of the condition is not fully understood, but the timing of some episodic occurrences with the headaches suggests that there is a connection between macropsia and the vasoconstrictive phase of a migraine. The differences in visual phenomena, such as macropsia with slow motion versus macropsia without slow motion, may result from different areas of the brain being affected by migraine. Epilepsy Macropsia may present itself as a symptom of both frontal lobe epilepsy and temporal lobe epilepsy, which may actually help in the diagnosis of those diseases. Children who experience nocturnal hallucinations accompanied by macropsia may seek medical care for panic attack disorders and instead are diagnosed with forms of epilepsy. Epilepsy patients may have no memory of the seizure, but can remember the hallucinations and aura which proceed the attack. Electroencephalography, or EEG imaging, can then be utilized while the patient experiences the episode. It may be subsequently concluded that the EEG is congruent with temporal or frontal lobe seizure. Anxiety and headaches accompany the episodes of visual distortion associated with epilepsy. While Valproic acid has been used to treat this type of seizure, anti-seizure medications appropriate for focal-onset seizures, like oxcarbazapine, have also been used successfully in the treatment of epilepsy-related macropsia. Hypoglycaemia Endogenous hypoglycaemia can result in number of visual disturbances and sometimes macropsia. This kind of hypoglycaemia is defined as having an abnormally low blood-sugar level due to anything other than the exogenous administration of insulin. Macropsia has been observed in experimental hypoglycaemia and in patients receiving insulin therapy. Viruses Patients with both Epstein-Barr virus and infectious mononucleosis have cited an increase in the sizes of perceived objects, coinciding with other symptoms of Alice in Wonderland Syndrome. Additionally, it has been observed that Epstein-Barr patients who cite hallucinations display abnormal MRI scans. The MRI may show swelling of the cerebral cortex, transient T2 prolongation, and transient lesions. Unlike in MRIs, no abnormalities have been reported in CT scans. It is thus recommended that an Epstein-Barr patient who cites visual hallucinations have an MRI scan. Macropsia may appear either before the onset, or after the resolution, of all clinical symptoms associated with the illness. The duration of the disturbances have been shown to range between two weeks and seven months. Almost all patients with macropsia due to infectious mononucleosis make full recoveries. Patients with Coxsackievirus B1 have reported numerous symptoms of Alice in Wonderland Syndrome, the most common of which being macropsia and micropsia. Pathophysiology Macropsia may be a result of optical magnification differences between the eyes, retinal receptor distribution, or the cortical processing of the sampled image. The current hypothesis for the occurrence of dysmetropsia is due to the stretching or compression of the retina leading to the displacement of receptors. Macropsia arises from a compressed receptor distribution leading to a larger perceived image size and conversely, micropsia results from stretching of the retina leading to a more sparse receptor distribution that gives a smaller perceived image size. In the case of macropsia, the greater density of photoreceptor cells leads to greater stimulation making the object seem larger. In some cases, the effects of macropsia have been shown to be field dependent, in that the degree of visual distortion is related to the visual field angle. Non-uniform stretching or compression of the receptor distribution could explain the field dependency of the macropsia. If the compression forces were closer to the fovea the resulting compression would cause a greater amount of macropsia at lower field angles with little effect at higher field angles where the receptor distribution is not as compressed. Alterations in receptor distribution can be the result of epiretinal membrane, neuroretina detachment and/or re-attachment, or retinoschisis. Macropsia caused by surgical re-attachment of macula-off rhegmatogenous retinal detachment is not symmetrical around the fovea, resulting in differences size changes in the horizontal and vertical meridians. Asymmetry has also been observed with retinoschisis, in which macropsia generally results in the vertical direction while micropsia presents in the horizontal direction. Diagnosis Macropsia is generally diagnosed once a patient complains of the characteristic symptoms, such as disproportionally large objects in their visual field. The Amsler Grid test can be used to diagnose macropsia, along with other visual maladies depending on the subjective disturbance reported by the patient after looking at the Amsler Grid. Outward bulging of the lines on an Amsler Grid is consistent with patients experiencing macropsisa. The New Aniseikonia Test (NAT) can quantify the degree of macropsia or micropsia independently in the vertical and horizontal meridians. The test consists of red and green semicircles on a black background with a white round fixation target. The size of the red semicircle is held constant while the green semicircle is varied in size in 1% increments. The patient wears a pair of red/green goggles so that one eye is tested at a time, and the patient attempts to determine when the semicircles are the same size. This is termed the reversal threshold and the size difference between the semicircles is reported as the degree of aniseikonia. A positive value indicates that the object was perceived bigger and thus corresponds to macropsia, and conversely a negative value indicates micropsia. The Aniseikonia Inspector contains an aniseikonia test based on the same principles as the NAT, but the test is run on a computer screen, it is based on a forced choice method, and it can measure the size difference as a function of the size of the objects. The functionality of being able to measure the size difference as function of the size (i.e. field dependent testing) is especially important when the macropsia (or micropsia) has a retinal origin. Treatment The most common way to treat forms of aniseikonia, including macropsia, is through the use of auxiliary optics to correct for the magnification properties of the eyes. This method includes changing the shape of spectacle lenses, changing the vertex distances with contact lenses, creating a weak telescope system with contact lenses and spectacles, and changing the power of one of the spectacle lenses. Computer software, such as the Aniseikonia Inspector, has been developed to determine the prescription needed to correct for a certain degree of aniseikonia. The problem with correction through optical means is that the optics do not vary with field angle and thus cannot compensate for non-uniform macropsia. Patients have reported significantly improved visual comfort associated with a correction of 5-10% of the aniseikonia.With regard to drug-induced or virus-induced macropsia, once the underlying problem, either drug abuse or viral infection, is treated, the induced macropsia ceases. Research Future research may focus on ways to limit the occurrence of retinally-induced macropsia due to surgery. In terms of treatment, the most effective optical correction is still being researched with respect to visual field angles and direction to a target. The susceptibility of certain age demographics to macropsia is a subject that requires further validation. Overall, there have not been very many reports of macropsia induced by certain drugs, specifically zolpidem and citalopram. Once a larger effort is made to compile such reports, there will inevitably be more research on the subject of macropsia. References == External links ==
Rolandic epilepsy	Benign Rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes (BCECTS) is the most common epilepsy syndrome in childhood. Most children will outgrow the syndrome (it starts around the age of 3–13 with a peak around 8–9 years and stops around age 14–18), hence the label benign. The seizures, sometimes referred to as sylvian seizures, start around the central sulcus of the brain (also called the centrotemporal area, located around the Rolandic fissure, after Luigi Rolando). Signs and symptoms The cardinal features of Rolandic epilepsy are infrequent, often single, focal seizures consisting of: a. unilateral facial sensorimotor symptoms (30% of patients) b. oropharyngolaryngeal manifestations (53% of patients) c. speech arrest (40% of patients), and d. hypersalivation (30% of patients)Hemifacial sensorimotor seizures are often entirely localised in the lower lip or spread to the ipsilateral hand. Motor manifestations are sudden, continuous or bursts of clonic contractions, usually lasting from a few seconds to a minute. Ipsilateral tonic deviation of the mouth is also common. Hemifacial sensory symptoms consist of unilateral numbness mainly in the corner of the mouth. Hemifacial seizures are often associated with an inability to speak and hypersalivation: The left side of my mouth felt numb and started jerking and pulling to the left, and I could not speak to say what was happening to me. Negative myoclonus can be observed in some cases, as an interruption of tonic muscular activity Oropharyngolaryngeal ictal manifestations are unilateral sensorimotor symptoms inside the mouth. Numbness, and more commonly paraesthesias (tingling, prickling, freezing), are usually diffuse on one side or, exceptionally, may be highly localised even to one tooth. Motor oropharyngolaryngeal symptoms produce strange sounds, such as death rattle, gargling, grunting and guttural sounds, and combinations: In his sleep, he was making guttural noises, with his mouth pulled to the right, ‘as if he was chewing his tongue’. We heard her making strange noises ‘like roaring’ and found her unresponsive, head raised from the pillow, eyes wide open, rivers of saliva coming out of her mouth, rigid. Arrest of speech is a form of anarthria. The child is unable to utter a single intelligible word and attempts to communicate with gestures. My mouth opened and I could not speak. I wanted to say I cannot speak. At the same time, it was as if somebody was strangling me. Hypersalivation, a prominent autonomic manifestation, is often associated with hemifacial seizures, oro-pharyngo-laryngeal symptoms and speech arrest. Hypersalivation is not just frothing: Suddenly my mouth is full of saliva, it runs out like a river and I cannot speak. Syncope-like epileptic seizures may occur, probably as a concurrent symptom of Panayiotopoulos syndrome: She lies there, unconscious with no movements, no convulsions, like a wax work, no life. Consciousness and recollection are fully retained in more than half (58%) of Rolandic seizures. I felt that air was forced into my mouth, I could not speak and I could not close my mouth. I could understand well everything said to me. Other times I feel that there is food in my mouth and there is also a lot of salivation. I cannot speak. In the remainder (42%), consciousness becomes impaired during the ictal progress and in one third there is no recollection of ictal events. Progression to hemiconvulsions or generalised tonic-clonic seizures occurs in around half of children and hemiconvulsions may be followed by postictal Todds hemiparesis. Duration and circadian distribution: Rolandic seizures are usually brief, lasting for 1–3 minutes. Three-quarters of seizures occur during nonrapid eye movement sleep, mainly at sleep onset or just before awakening. Status epilepticus: Although rare, focal motor status or hemiconvulsive status epilepticus is more likely to occur than secondarily generalised convulsive status epilepticus, which is exceptional. Opercular status epilepticus usually occurs in children with atypical evolution or may be induced by carbamazepine or lamotrigine. This state lasts for hours to months and consists of ongoing unilateral or bilateral contractions of the mouth, tongue or eyelids, positive or negative subtle perioral or other myoclonus, dysarthria, speech arrest, difficulties in swallowing, buccofacial apraxia and hypersalivation. These are often associated with continuous spikes and waves on an EEG during NREM sleep. Other seizure types: Despite prominent hypersalivation, focal seizures with primarily autonomic manifestations (autonomic seizures) are not considered part of the core clinical syndrome of Rolandic epilepsy. However, some children may present with independent autonomic seizures or seizures with mixed Rolandic-autonomic manifestations including emesis as in Panayiotopoulos syndrome.Atypical forms: Rolandic epilepsy may present with atypical manifestations such early age at onset, developmental delay or learning difficulties at inclusion, other seizure types, atypical EEG abnormalities.These children usually have normal intelligence and development. Learning can remain unimpaired while a child is afflicted with Rolandic epilepsy. Cause Benign epilepsy with centrotemporal spikes is thought to be a genetic disorder. An autosomal dominant inheritance with age dependency and variable penetrance has been reported, although not all studies support this theory. Linkage studies have pointed to a possible susceptibility region on chromosome 15q14, in the vicinity of the alpha-7 subunit of the acetylcholine receptor. Most studies show a slight male predominance. Because of the benign course and age-specific occurrence, it is thought to represent a hereditary impairment of brain maturation.An association with ELP4 has been identified. Diagnosis The diagnosis can be confirmed when the characteristic centrotemporal spikes are seen on electroencephalography (EEG). Typically, high-voltage spikes followed by slow waves are seen. Given the nocturnal activity, a sleep EEG can often be helpful. Technically, the label "benign" can only be confirmed if the childs development continues to be normal during follow-up. Neuroimaging, usually with an MRI scan, is only advised for cases with atypical presentation or atypical findings on clinical examination or EEG. The disorder should be differentiated from several other conditions, especially centrotemporal spikes without seizures, centrotemporal spikes with local brain pathology, central spikes in Rett syndrome and fragile X syndrome, malignant Rolandic epilepsy, temporal lobe epilepsy and Landau-Kleffner syndrome. Treatment Given the benign nature of the condition and the low seizure frequency, treatment is often unnecessary. If treatment is warranted or preferred by the child and his or her family, antiepileptic drugs can usually control the seizures easily. Carbamazepine is the most frequently used first-line drug, but many other antiepileptic drugs, including valproate, phenytoin, gabapentin, levetiracetam and sultiame have been found effective as well. Bedtime dosing is advised by some. Treatment can be short and drugs can almost certainly be discontinued after two years without seizures and with normal EEG findings, perhaps even earlier. Parental education about Rolandic epilepsy is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant.It is unclear if there are any benefits to clobazam over other seizure medications. Prognosis The prognosis for Rolandic seizures is invariably excellent, with probably less than 2% risk of developing absence seizures and less often GTCS in adult life. Remission usually occurs within 2–4 years from onset and before the age of 16 years. The total number of seizures is low, the majority of patients having fewer than 10 seizures; 10–20% have just a single seizure. About 10–20% may have frequent seizures, but these also remit with age. Children with Rolandic seizures may develop usually mild and reversible linguistic, cognitive and behavioural abnormalities during the active phase of the disease. These may be worse in children with onset of seizures before 8 years of age, high rate of occurrence and multifocal EEG spikes. The development, social adaptation and occupations of adults with a previous history of Rolandic seizures were found normal. Epidemiology The age of onset ranges from 1 to 14 years with 75% starting between 7–10 years. There is a 1.5 male predominance, prevalence is around 15% in children aged 1–15 years with non-febrile seizures and incidence is 10–20/100,000 of children aged 0–15 years See also Generalized epilepsy with febrile seizures plus References == External links ==
Horizontal gaze palsy	A gaze palsy is the paresis of conjugate eye movements. Horizontal gaze palsy may be caused by lesions in the cerebral hemispheres, which cause paresis of gaze away from the side of the lesion, or from brain stem lesions, which, if they occur below the crossing of the fibers from the frontal eye fields in the caudal midbrain, will cause weakness of gaze toward the side of the lesion. These will result in horizontal gaze deviations from unopposed action of the unaffected extraocular muscles. Another way to remember this is that patients with hemisphere lesions look towards their lesion, while patients with pontine gaze palsies look away from their lesions. Note that patients with gaze palsy still have conjugate eye movements and therefore do not complain of diplopia. The human Robo gene acts as a receptor for a midline repulsive cue. When Robo is mutated, the longitudinal tract formation is disrupted and therefore normal neuronal connections cannot form. This leads to the reduced hindbrain volume and scoliosis, which are common symptoms of horizontal gaze palsy. References "Altered Levels of Consciousness - Nursing Link". Nursinglink.monster.com. Retrieved 2017-04-18.
Meiges syndrome	Meiges syndrome is a type of dystonia. It is also known as Brueghels syndrome and oral facial dystonia. It is actually a combination of two forms of dystonia, blepharospasm and oromandibular dystonia (OMD). When OMD is combined with blepharospasm, it may be referred to as Meiges Syndrome named after Henri Meige, the French neurologist who first described the symptoms in detail in 1910. The symptoms usually begin between the ages of 30 and 70 years old and appear to be more common in women than in men (2:1 ratio). The combination of upper and lower dystonia is sometimes called cranial-cervical dystonia. The incidence is about one case in 20,000 people. Presentation The main symptoms involve involuntary blinking and chin thrusting. Some patients may experience excessive tongue protrusion, squinting, light sensitivity, muddled speech, or uncontrollable contraction of the platysma muscle. Some Meiges patients also have "laryngeal dystonia" (spasms of the larynx). Blepharospasm may lead to embarrassment in social situations, and oromandibular dystonia can affect speech, making it difficult to carry on the simplest conversations. This can cause difficulty in both personal and professional contexts, and in some cases may cause patients to withdraw from social situations.The condition tends to affect women more frequently than men. Symptoms Oromandibular Symptoms difficulty opening the mouth (trismus) clenching or grinding of the teeth (bruxism) spasms of jaw opening sideways deviation or protrusion of the jaw lip tightening and pursing drawing back (retraction) of the corners of the mouth deviation or protrusion of the tongue. jaw pain difficulties eating and drinking difficulties speaking (dysarthria)Blepharospasm symptoms the first symptom to appear is an increased rate of blinking uncontrollable squinting/closing of eyes light sensitivity (photophobia) squinting/eyes closing during speech uncontrollable eyes closing shut (rare instances completely causing blindness)In addition, in some patients, the dystonic spasms may sometimes be provoked by certain activities, such as talking, chewing, or biting. Particular activities or sensory tricks may sometimes temporarily alleviate OMD symptoms, including chewing gum, talking, placing a toothpick in the mouth, lightly touching the lips or chin, or applying pressure beneath the chin. Diagnosis Meiges is commonly misdiagnosed and most doctors will not be familiar with this condition due to its rare incidence. Usually, a neurologist specializing in psychomotor disorders can detect Meiges. There are currently no technological diagnostic tools to detect Meiges, as it cannot be identified using blood chemistry analysis or radiological imaging, such as MRI or CT scans. A patient presenting with signs of OMD alone may be misdiagnosed with TMJD.Patients with idiopathic Meiges syndrome do not quickly respond to anticholinergic drug treatments, a diagnostic sign that can help differentiate it from acute dystonia, which does respond to anticholinergic drugs. Upper and lower dystonia types The Greek word blepharon means "eyelid". Spasm means "uncontrolled muscle contraction". The term blepharospasm [blef-a-ro-spaz-m] can be applied to any abnormal blinking or eyelid tic or twitch resulting from any cause, ranging from dry eyes to Tourettes syndrome to tardive dyskinesia. The blepharospasm referred to here is officially called benign essential blepharospasm (BEB) to distinguish it from the less serious secondary blinking disorders. "Benign" indicates the condition is not life-threatening, and "essential" is a medical term meaning "of unknown cause". It is both a cranial and a focal dystonia. Cranial refers to the head and focal indicates confinement to one part. The word dystonia describes abnormal involuntary sustained muscle contractions and spasms. Patients with blepharospasm have normal eyes. The visual disturbance is due solely to the forced closure of the eyelids.Oromandibular dystonia (OMD) is a form of focal dystonia that affects varying areas of the head and neck including the lower face, jaw, tongue and larynx. The spasms may cause the mouth to pull open, shut tight, or move repetitively. Speech and swallowing may be distorted. It is often associated with dystonia of the cervical muscles (Spasmodic Torticollis), eyelids (Blepharospasm), or larynx (Spasmodic Dysphonia).In patients with OMD, involuntary contractions may involve the muscles used for chewing (masticatory muscles). These may include the thick muscle in the cheek that closes the jaw (masseter muscle) and the broad muscle that draws back the lower jaw and closes the mouth (temporalis muscle). Some patients may also experience involuntary contractions of the wide muscle at the side of the neck (platysmal muscle). This muscle draws down the corner of the mouth and lower lip or other muscle groups. Treatment In some cases Meiges syndrome can be reversed when it is caused by medication. Botulinum toxin injections can be helpful for the blepharospasm and for masseter spasm. See also Mogigraphia References Paulson, George W. (December 13, 1997). "Meiges Syndrome". Blepharospasm.org. Archived from the original on 2012-02-06. "Oromandibular". Dystonia.org.za. 2006. Archived from the original on 2009-03-24. "Focal Dystonias: Oromandibular Dystonia". WeMove.org. 2009. Archived from the original on 2009-02-28. == External links ==
Mastitis	Mastitis is inflammation of the breast or udder, usually associated with breastfeeding. Symptoms typically include local pain and redness. There is often an associated fever and general soreness. Onset is typically fairly rapid and usually occurs within the first few months of delivery. Complications can include abscess formation.Risk factors include poor latch, cracked nipples, use of a breast pump, and weaning. The bacteria most commonly involved are Staphylococcus and Streptococci. Diagnosis is typically based on symptoms. Ultrasound may be useful for detecting a potential abscess.Prevention is by proper breastfeeding techniques. When infection is present, antibiotics such as cephalexin may be recommended. Breastfeeding should typically be continued, as emptying the breast is important for healing. Tentative evidence supports benefits from probiotics. About 10% of breastfeeding women are affected. Types When it occurs in breastfeeding mothers, it is known as puerperal mastitis, lactation mastitis, or lactational mastitis. When it occurs in non breastfeeding women it is known as non-puerperal or nonlactational. Mastitis can, in rare cases, occur in men. Inflammatory breast cancer has symptoms very similar to mastitis and must be ruled out. The symptoms are similar for puerperal and nonpuerperal mastitis but predisposing factors and treatment can be very different. Pregnancy related Puerperal mastitis is the inflammation of the breast in connection with pregnancy, breastfeeding or weaning. Since one of the most prominent symptoms is tension and engorgement of the breast, it is thought to be caused by blocked milk ducts or milk excess. It is relatively common; estimates range depending on methodology between 5–33%. However, only about 0.4–0.5% of breastfeeding mothers develop an abscess.Some predisposing factors are known but their predictive value is minimal. It appears that proper breastfeeding technique, frequent breastfeeding and avoidance of stress are the most important factors that can be influenced. Light cases of mastitis are often called breast engorgement; the distinction is overlapping and possibly arbitrary or subject to regional variations. Non pregnancy related The term nonpuerperal mastitis describes inflammatory lesions of the breast occurring unrelated to pregnancy and breastfeeding. This article includes description of mastitis as well as various kinds of mammary abscesses. Skin related conditions like dermatitis and foliculitis are a separate entity. Names for non-puerperal mastitis are not used very consistently and include mastitis, subareolar abscess, duct ectasia, periductal inflammation, Zuskas disease and others. Periductal mastitis is a form of nonlactational mastitis, and is characterized by inflammation of the subareolar ducts. Although the cause of periductal mastitis is currently unknown, it is predicted that smoking may be related. This condition is mainly seen in young women but can also be seen in men. Signs and symptoms Lactation mastitis usually affects only one breast and the symptoms can develop quickly. It develops into three stages, from the initial stage, the pus formation stage, to the restoration stage. The signs and symptoms usually appear suddenly and they include: Breast tenderness or warmth to the touch General malaise or feeling ill Swelling of the breast Pain or a burning sensation continuously or while breast-feeding Skin redness, often in a wedge-shaped pattern Fever of 101 F (38.3 C) or greater The affected breast can then start to appear lumpy and red.Some women may also experience flu-like symptoms such as: Aches Shivering and chills Feeling anxious or stressed FatigueContact should be made with a health care provider with special breastfeeding competence as soon as the patient recognizes the combination of signs and symptoms. Most of the women first experience the flu-like symptoms and just after they may notice a sore red area on the breast. Also, women should seek medical care if they notice any abnormal discharge from the nipples, if breast pain is making it difficult to function each day, or they have prolonged, unexplained breast pain. Breast abscess A breast abscess is a collection of pus that develops in the breast with various causes. During lactation, breast abscess develops only rarely, most sources cite about 0.4–0.5% of breastfeeding women. Known risk factors are age over 30, primiparous and late delivery. No correlation was found with smoking status; however, this may be in part because far fewer smoking women choose to breastfeed. Antibiotics were not shown effective in prevention of lactation abscess but are useful to treat a secondary infection (see the section on the treatment of breast abscess in this article). Keratinizing squamous metaplasia of lactiferous ducts may play a similar role in the pathogenesis of nonpuerperal subareolar abscess. Causes Since the 1980s mastitis has often been divided into non-infectious and infectious sub-groups. However, recent research suggests that it may not be feasible to make divisions in this way. It has been shown that types and amounts of potentially pathogenic bacteria in breast milk are not correlated to the severity of symptoms. Moreover, although only 15% of women with mastitis in Kvist et al.s study were given antibiotics, all recovered and few had recurring symptoms. Many healthy breastfeeding women wishing to donate breast milk have potentially pathogenic bacteria in their milk but have no symptoms of mastitis. Risk factors Mastitis typically develops when the milk is not properly removed from the breast. Milk stasis can lead to the milk ducts in the breasts becoming blocked, as the breast milk is not being properly and regularly expressed. It has also been suggested that blocked milk ducts can occur as a result of pressure on the breast, such as tight-fitting clothing or an over-restrictive bra, although there is sparse evidence for this supposition. Mastitis may occur when the baby is not appropriately attached to the breast while feeding, when the baby has infrequent feeds or has problems suckling the milk out of the breast. The presence of cracks or sores on the nipples increases the likelihood of infection. Tight clothing or ill-fitting bras may also cause problems as they compress the breasts. There is a possibility that infants carrying infectious pathogens in their noses can infect their mothers; the clinical significance of this finding is still unknown. Mastitis and breast abscesses can also be caused by direct trauma to the breast. Such injury can occur for example during sports activities or due to seat belt injury. Mastitis can also develop due to contamination of a breast implant or any other foreign body, for example after nipple piercing. In such cases, the removal of the foreign body is indicated.Women who are breastfeeding are at risk for developing mastitis especially if they have sore or cracked nipples or have had mastitis before while breastfeeding another baby. Also, the chances of getting mastitis increases if women use only one position to breastfeed or wear a tight-fitting bra, which may restrict milk flow Difficulties in getting a nursing infant to latch on to the breast can also increase the risk for mastitis.Women with diabetes, chronic illness, AIDS, or an impaired immune system may be more susceptible to the development of mastitis. Infection Some women (approximately 15%) will require antibiotic treatment for infection which is usually caused by bacteria from the skin or the babys mouth entering the milk ducts through skin lesions of the nipple or through the opening of the nipple. Infection is usually caused by Staphylococcus aureus. Infectious pathogens commonly associated with mastitis are Staphylococcus aureus, Streptococcus spp. and Gram-negative bacilli such as Escherichia coli. Salmonella spp., mycobacteria, and fungi such as Candida and Cryptococcus have been identified in rare instances.Recent research suggests that infectious pathogens play a much smaller role in the pathogenesis than was commonly assumed only a few years ago. Most detected pathogens are very common species that are natural part of the breast fauna and simple detection of their presence is not sufficient to prove a causative role. Furthermore, there are indications that treatment with antibiotics may have minimal impact, and over-all there is insufficient evidence to confirm or refute the effectiveness of antibiotic therapy for treating lactational mastitis. Diagnosis The diagnosis of mastitis and breast abscess can usually be made based on a physical examination. The doctor will also take into account the signs and symptoms of the condition. However, if the doctor is not sure whether the mass is an abscess or a tumor, a breast ultrasound may be performed. The ultrasound provides a clear image of the breast tissue and may be helpful in distinguishing between simple mastitis and abscess or in diagnosing an abscess deep in the breast. The test consists of placing an ultrasound probe over the breast. In cases of infectious mastitis, cultures may be needed in order to determine what type of organism is causing the infection. Cultures are helpful in deciding the specific type of antibiotics that will be used in curing the disease. These cultures may be taken either from the breast milk or of the material aspirated from an abscess. Mammograms or breast biopsies are normally performed on women who do not respond to treatment or on non-breastfeeding women. This type of tests is sometimes ordered to exclude the possibility of a rare type of breast cancer which causes symptoms similar to those of mastitis. Differential diagnosis Breast cancer may coincide with or mimic symptoms of mastitis. Only full resolution of symptoms and careful examination are sufficient to exclude the diagnosis of breast cancer. Lifetime risk for breast cancer is significantly reduced for women who were pregnant and breastfeeding. Mastitis episodes do not appear to influence lifetime risk of breast cancer. Mastitis does however cause great difficulties in diagnosis of breast cancer and delayed diagnosis and treatment can result in worse outcome. Breast cancer may coincide with mastitis or develop shortly afterwards. All suspicious symptoms that do not completely disappear within 5 weeks must be investigated. Breast cancer incidence during pregnancy and lactation is assumed to be the same as in controls. Course and prognosis are also very similar to age matched controls. However diagnosis during lactation is particularly problematic, often leading to delayed diagnosis and treatment. Some data suggest that noninflammatory breast cancer incidence is increased within a year following episodes of nonpuerperal mastitis and special care is required for follow-up cancer prevention screening. So far only data from short term observation is available and total risk increase can not be judged. Because of the very short time between presentation of mastitis and breast cancer in this study it is considered very unlikely that the inflammation had any substantial role in carcinogenesis, rather it would appear that some precancerous lesions may increase the risk of inflammation (hyperplasia causing duct obstruction, hypersensitivity to cytokines or hormones) or the lesions may have common predisposing factors. A very serious type of breast cancer called inflammatory breast cancer presents with similar symptoms as mastitis (both puerperal and nonpuerperal). It is the most aggressive type of breast cancer with the highest mortality rate. The inflammatory phenotype of IBC is thought to be mostly caused by invasion and blocking of dermal lymphatics, however it was recently shown that NF-κB target genes activation may significantly contribute to the inflammatory phenotype. Case reports show that inflammatory breast cancer symptoms can flare up following injury or inflammation making it even more likely to be mistaken for mastitis. Symptoms are also known to partially respond to progesterone and antibiotics, reaction to other common medications can not be ruled out at this point. Treatment In lactation mastitis, frequent emptying of both breasts by breastfeeding is essential. Also essential is adequate fluid supply for the mother and baby. For breastfeeding women with light mastitis, massage and application of heat prior to feeding can help as this may aid unblocking the ducts. However, in more severe cases of mastitis heat or massage could make the symptoms worse and cold compresses are better suited to contain the inflammation. Nonpuerperal mastitis is treated by medication and possibly aspiration or drainage (see in particular treatment of subareolar abscess and treatment of granulomatous mastitis). According to a BMJ best practice report, antibiotics are generally to be used in all nonpuerperal mastitis cases, with replacement of the antibiotics by an antifungal agent such as fluconazole in cases of deep fungal infections, and corticosteroids are to be used in case of granulomatous mastitis (with differential diagnosis to tuberculosis infection of the breast).In idiopathic granulomatous mastitis, successful treatment includes invasive surgical procedures or less invasive treatment with steroid medications. Antibiotics In lactational mastitis, antibiotics are not needed in the overwhelming majority of cases and should be used only for bacterial infections. For people with nonsevere infections, dicloxacillin or cephalexin are recommended. For people with severe infections, vancomycin is recommended. The length of antibiotic treatment ranges anywhere from 5–14 days. The effects of antibiotics has not been well studied as of 2013. Breast abscess An abscess (or suspected abscess) in the breast may be treated by ultrasound-guided fine-needle aspiration (percutaneous aspiration) or by surgical incision and drainage; each of these approaches is performed under antibiotic coverage. In case of puerperal breast abscess, breastfeeding from the affected breast should be continued where possible.For small breast abscesses, ultrasound-guided fine needle aspiration such as to completely drain the abscess is widely recognized as a preferred initial management.One recommended treatment includes antibiotics, ultrasound evaluation and, if fluid is present, ultrasound-guided fine needle aspiration of the abscess with an 18 gauge needle, under saline lavage until clear. The exudate is then sent for microbiological analysis for identification of the pathogen and determination of its antibiotic sensitivity profile, which may in turn give an indication for changing the antibiotics. At follow-up, a mammography is performed if the condition has resolved; otherwise the ultrasound-guided fine-needle aspiration with lavage and microbiological analysis is repeated. If three to five aspirations still do not resolve the condition, percutaneous drainage in combination with placement of an indwelling catheter is indicated, and only if several attempts at ultrasound-guided drainage fail, surgical resection of the inflamed lactiferous ducts (preferably performed after the acute episode is over). It is noted, however, that even the excision of the affected ducts does not necessarily prevent recurrence.Nonpuerperal breast abscesses have a higher rate of recurrence compared to puerperal breast abscesses. There is a high statistical correlation of nonpuerperal breast abscess with diabetes mellitus (DM). On this basis, it has recently been suggested that diabetes screening should be performed on patients with such abscess.Although there are a number of recommendations regarding the treatment of breast abscesses, a 2015 review found insufficient evidence of whether needle aspiration is comparable to incision and drainage, or whether antibiotics should generally be given to women undergoing incision and drainage. Prognosis Temperature and severity of symptoms at presentation do not predict outcome; women with sore or damaged nipples may need special attention. Epidemiology Mastitis is quite common among breastfeeding women. The WHO estimates that although incidences vary between 2.6% and 33%, the prevalence globally is approximately 10% of breastfeeding women. Most mothers who develop mastitis usually do so within the first few weeks after delivery. Most breast infections occur within the first or second month after delivery or at the time of weaning. However, in rare cases it affects women who are not breastfeeding. Terminology Popular usage of the term mastitis varies by geographic region. Outside the US it is commonly used for puerperal and nonpuerperal cases, in the US the term nonpuerperal mastitis is rarely used and alternative names such as duct ectasia, subareolar abscess and plasma cell mastitis are more frequently used. Chronic cystic mastitis is an older name for fibrocystic disease. American usage: mastitis usually refers to puerperal (occurring to breastfeeding mothers) mastitis with symptoms of systemic infection. Lighter cases of puerperal mastitis are often called breast engorgement. In this article, "mastitis" is used in the original sense of the definition as inflammation of the breast with additional qualifiers where appropriate. Etymology and pronunciation The word mastitis () uses combining forms of mast- + -itis. The word mammitis () uses combining forms of mamm- + -itis. They are synonymous in modern usage, and mastitis is the more commonly used synonym. Other animals Mastitis occurs in other animals as in humans, and is especially a concern in livestock, since milk from the affected udders of livestock may enter the food supply and pose a health risk. It is a major condition in some species, like dairy cows. It is the cause of much unwanted suffering for the dairy cows. It is of tremendous economic importance for the dairy industry, and it is also of concern for public health. The same considerations apply to mastitis in sheep and goats and other milk-producing females. It is also of economic importance in the sow, but, in this species, it is not related to public health. In other domestic females (queen, mare, etc.), it is more an individual illness dealt with by veterinary practitioners. References External links Mastitis on mayoclinic.com Australian Breastfeeding Association
Congenital trigger thumb	Congenital trigger thumb is a trigger thumb in infants and young children. Triggering, clicking or snapping is observed by flexion or extension of the interphalangeal joint (IPJ). In the furthest stage, no extension is possible and there is a fixed flexion deformity of the thumb in the IPJ. Cause, natural history, prognosis and recommended treatment are controversial. Signs and symptoms Besides the clicking, snapping or triggering, a characteristic Notta nodule is commonly found on the palmar side at the metacarpophalangeal (MCP) joint. This nodule can be found by palpation. Children can also present a thumb which they cannot extend actively due to entrapment of the nodule to the A1 pulley. Some may even present with a fixed flexion deformity of the IPJ where no extension is possible. Cause It is unclear whether the cause of the trigger thumb is congenital or acquired. The occurrence of bilateral incidence and trigger thumbs in both children of twins are an indication for a congenital cause. Trigger thumb in children is also associated with trisomy of chromosome 13. For these reasons it was assumed that trigger thumbs in children are to be of congenital cause. However, more and more evidence which point towards an acquired cause have been found in recent studies. Therefore, the name pediatric trigger thumb is also widely used (and currently preferred by some) for the same disorder. Diagnosis Diagnosis of a trigger thumb is solely made by these clinical observations and further classified into four stages: Treatment There are several types of treatment for congenital trigger thumb, conservative and surgical. Conservative The conservative treatment consists of observation in time. Studies show that the trigger thumb spontaneously resolves in 49 months. According to Leung et al., trigger thumbs in infants resolve spontaneously in 63% of the cases. No residual deformities were found and there is no recurrence once resolved. Residual deformity is defined as persistent flexion deformities of the thumb and radial deviation at the IPJ. Extension exercises and splinting can be added to the observation. These two elements have favourable results in improvement in flexion impairment of the thumb. However, compared to observation, the benefit of merely extension exercises and splinting are still unclear.It has been recommended to attempt conservative treatment first, before attempting surgical treatment. Surgical Surgical treatment should be considered when the patient has a trigger thumb bilaterally and when the patient has a severe trigger thumb. Severe is defined as when the thumb is locked so that the thumb cannot be flexed or extended either passively or actively. Surgical treatment should also be considered when observation and/or splint therapy has not achieved sufficient results after 49 months. Unlike the surgical treatment given for adults, which is unambiguously a surgical release of the A1 pulley of the thumb, the optimum surgical treatment for infants has not yet been discerned. In case of infants, research has shown that only in 15% of the cases A1 pulley release alone is sufficient. In most of the cases there was an additional annular pulley structure distal to the A1 to be released resolving the triggering: the so-called Av pulley or variable pulley. Therefore, infants and adults need to be treated differently as the main problem is different. Open vs. percutaneous There are two types of surgery: open surgery which is mentioned above and percutaneous surgery. Unlike open surgery percutaneous surgery is done without exposing the anatomical structures beneath the skin. Research has shown that percutaneous surgery is a good alternative to open surgery. Percutaneous surgery is done with a needle that is inserted in the flexor sheath at the level of the A1 pulley. Before the needle insertion the thumb is placed in extension, whereas when the needle is already inserted the thumb will be put into semi-flexion, so that the needle can be moved and the palmar skin is movable. The A1 pulley will then be cut with the needle longitudinally and parallel to the fibers of the tendon of the flexor pollicis longus muscle. When the release with the needle is done according to the pivot maneuver the chances of incomplete release and damage to the digital nerve nearby will be increased. To prevent any postoperative hematoma and swelling, pressure should be applied for at least 10 minutes after the procedure. Percutaneous surgery has also been proven to be without residual deformities and recurrence after surgery. When the A1 pulley is too thick and long to be released at once, open surgery still can be a solution. The advantages over open surgery are that percutaneous surgery is simpler, more straightforward and shorter concerning the duration. It can also be done in every other examination room unlike the open surgery, which is done in an operation room. The risk nonetheless is that the digital nerve of the thumb nearby can be damaged. Epidemiology Not much research has been done on the epidemiology of congenital trigger thumbs. There are a few reports on the incidence in their respective studies. The most recent data comes from a Japanese study by Kukichi and Ogino where they found an incidence 3.3 trigger thumbs per 1,000 live births in 1-year-old children. References == External links ==
Brain tumor	A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondary tumors, which most commonly have spread from tumors located outside the brain, known as brain metastasis tumors. All types of brain tumors may produce symptoms that vary depending on the size of the tumor and the part of the brain that is involved. Where symptoms exist, they may include headaches, seizures, problems with vision, vomiting and mental changes. Other symptoms may include difficulty walking, speaking, with sensations, or unconsciousness.The cause of most brain tumors is unknown. Uncommon risk factors include exposure to vinyl chloride, Epstein–Barr virus, ionizing radiation, and inherited syndromes such as neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau Disease. Studies on mobile phone exposure have not shown a clear risk. The most common types of primary tumors in adults are meningiomas (usually benign) and astrocytomas such as glioblastomas. In children, the most common type is a malignant medulloblastoma. Diagnosis is usually by medical examination along with computed tomography (CT) or magnetic resonance imaging (MRI). The result is then often confirmed by a biopsy. Based on the findings, the tumors are divided into different grades of severity.Treatment may include some combination of surgery, radiation therapy and chemotherapy. Since the brain is the bodys only non-fungible organ, surgery carries a risk of the tumor returning. If seizures occur, anticonvulsant medication may be needed. Dexamethasone and furosemide are medications that may be used to decrease swelling around the tumor. Some tumors grow gradually, requiring only monitoring and possibly needing no further intervention. Treatments that use a persons immune system are being studied. Outcomes for malignant tumors vary considerably depending on the type of tumor and how far it has spread at diagnosis. Although benign tumors only grow in one area, they may still be life-threatening depending on their size and location. Malignant glioblastomas usually have very poor outcomes, while benign meningiomas usually have good outcomes. The average five-year survival rate for all (malignant) brain cancers in the United States is 33%.Secondary, or metastatic, brain tumors are about four times as common as primary brain tumors, with about half of metastases coming from lung cancer. Primary brain tumors occur in around 250,000 people a year globally, and make up less than 2% of cancers. In children younger than 15, brain tumors are second only to acute lymphoblastic leukemia as the most common form of cancer. In NSW Australia in 2005, the average lifetime economic cost of a case of brain cancer was AU$1.9 million, the greatest of any type of cancer. Signs and symptoms The signs and symptoms of brain tumors are broad. People may experience symptoms regardless of whether the tumor is benign (not cancerous) or cancerous. Primary and secondary brain tumors present with similar symptoms, depending on the location, size, and rate of growth of the tumor. For example, larger tumors in the frontal lobe can cause changes in the ability to think. However, a smaller tumor in an area such as Wernickes area (small area responsible for language comprehension) can result in a greater loss of function. Headaches Headaches as a result of raised intracranial pressure can be an early symptom of brain cancer. However, isolated headache without other symptoms is rare, and other symptoms including visual abnormalities may occur before headaches become common. Certain warning signs for headache exist which make the headache more likely to be associated with brain cancer. These are, as defined by the American Academy of Neurology: "abnormal neurological examination, headache worsened by Valsalva maneuver, headache causing awakening from sleep, new headache in the older population, progressively worsening headache, atypical headache features, or patients who do not fulfill the strict definition of migraine". Other associated signs are headaches that are worse in the morning or that subside after vomiting. Location-specific symptoms The brain is divided into lobes and each lobe or area has its own function. A tumor in any of these lobes may affect the areas performance. The symptoms experienced are often linked to the location of the tumor, but each person may experience something different. Frontal lobe: Tumors may contribute to poor reasoning, inappropriate social behavior, personality changes, poor planning, lower inhibition, and decreased production of speech (Brocas area). Temporal lobe: Tumors in this lobe may contribute to poor memory, loss of hearing, and difficulty in language comprehension (Wernickes area is located in this lobe). Parietal lobe: Tumors here may result in poor interpretation of languages, difficulty with speaking, writing, drawing, naming, and recognizing, and poor spatial and visual perception. Occipital lobe: Damage to this lobe may result in poor vision or loss of vision. Cerebellum: Tumors in this area may cause poor balance, muscle movement, and posture. Brain stem: Tumors on the brainstem can cause seizures, endocrine problems, respiratory changes, visual changes, headaches and partial paralysis. Behavior changes A persons personality may be altered due to the tumor damaging lobes of the brain. Since the frontal, temporal, and parietal lobes control inhibition, emotions, mood, judgement, reasoning, and behavior, a tumor in those regions can cause inappropriate social behavior, temper tantrums, laughing at things which merit no laughter, and even psychological symptoms such as depression and anxiety. More research is needed into the effectiveness and safety of medication for depression in people with brain tumors.Personality changes can have damaging effects such as unemployment, unstable relationships, and a lack of control. Cause Epidemiological studies are required to determine risk factors. Aside from exposure to vinyl chloride or ionizing radiation, there are no known environmental factors associated with brain tumors. Mutations and deletions of tumor suppressor genes, such as P53, are thought to be the cause of some forms of brain tumor. Inherited conditions, such as Von Hippel–Lindau disease, tuberous sclerosis, multiple endocrine neoplasia, and neurofibromatosis type 2 carry a high risk for the development of brain tumors. People with celiac disease have a slightly increased risk of developing brain tumors. Smoking has been suggested to increase the risk but evidence remains unclear.Although studies have not shown any link between cell phone or mobile phone radiation and the occurrence of brain tumors, the World Health Organization has classified mobile phone radiation on the IARC scale into Group 2B – possibly carcinogenic. The claim that cell phone usage may cause brain cancer is likely based on epidemiological studies which observed a slight increase in glioma risk among heavy users of wireless and cordless phones. When those studies were conducted, GSM (2G) phones were in use. Modern, third-generation (3G) phones emit, on average, about 1% of the energy emitted by those GSM (2G) phones, and therefore the finding of an association between cell phone usage and increased risk of brain cancer is not based upon current phone usage. Pathophysiology Meninges Human brains are surrounded by a system of connective tissue membranes called meninges that separate the brain from the skull. This three-layered covering is composed of (from the outside in) the dura mater, arachnoid mater, and pia mater. The arachnoid and pia are physically connected and thus often considered as a single layer, the leptomeninges. Between the arachnoid mater and the pia mater is the subarachnoid space which contains cerebrospinal fluid (CSF). This fluid circulates in the narrow spaces between cells and through the cavities in the brain called ventricles, to support and protect the brain tissue. Blood vessels enter the central nervous system through the perivascular space above the pia mater. The cells in the blood vessel walls are joined tightly, forming the blood–brain barrier which protects the brain from toxins that might enter through the blood.Tumors of the meninges are meningiomas and are often benign. Though not technically a tumor of brain tissue, they are often considered brain tumors since they protrude into the space where the brain is, causing symptoms. Since they are usually slow-growing tumors, meningiomas can be quite large by the time symptoms appear. Brain matter The brains of humans and other vertebrates are composed of very soft tissue and have a gelatin-like texture. Living brain tissue has a pink tint in color on the outside (gray matter), and nearly complete white on the inside (white matter), with subtle variations in color. The three largest divisions of the brain are: Cerebral cortex Brainstem CerebellumThese areas are composed of two broad classes of cells: neurons and glia. These two types are equally numerous in the brain as a whole, although glial cells outnumber neurons roughly 4 to 1 in the cerebral cortex. Glia come in several types, which perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development. Primary tumors of the glial cells are called gliomas and often are malignant by the time they are diagnosed.The thalamus and hypothalamus are major divisions of the diencephalon, with the pituitary gland and pineal gland attached at the bottom; tumors of the pituitary and pineal gland are often benign.The brainstem lies between the large cerebral cortex and the spinal cord. It is divided into the midbrain, pons, and medulla oblongata. Spinal cord The spinal cord is considered a part of the central nervous system. It is made up of the same cells as the brain: neurons and glial cells. Diagnosis Although there is no specific or singular symptom or sign, the presence of a combination of symptoms and the lack of corresponding indications of other causes can be an indicator for investigation towards the possibility of a brain tumor. Brain tumors have similar characteristics and obstacles when it comes to diagnosis and therapy with tumors located elsewhere in the body. However, they create specific issues that follow closely to the properties of the organ they are in.The diagnosis will often start by taking a medical history noting medical antecedents, and current symptoms. Clinical and laboratory investigations will serve to exclude infections as the cause of the symptoms. Examinations in this stage may include the eyes, otolaryngological (or ENT) and electrophysiological exams. The use of electroencephalography (EEG) often plays a role in the diagnosis of brain tumors.Brain tumors, when compared to tumors in other areas of the body, pose a challenge for diagnosis. Commonly, radioactive tracers are uptaken in large volumes in tumors due to the high activity of tumor cells, allowing for radioactive imaging of the tumor. However, most of the brain is separated from the blood by the blood-brain barrier (BBB), a membrane that exerts a strict control over what substances are allowed to pass into the brain. Therefore, many tracers that may reach tumors in other areas of the body easily would be unable to reach brain tumors until there was a disruption of the BBB by the tumor. Disruption of the BBB is well imaged via MRI or CT scan, and is therefore regarded as the main diagnostic indicator for malignant gliomas, meningiomas, and brain metastases.Swelling or obstruction of the passage of cerebrospinal fluid (CSF) from the brain may cause (early) signs of increased intracranial pressure which translates clinically into headaches, vomiting, or an altered state of consciousness, and in children changes to the diameter of the skull and bulging of the fontanelles. More complex symptoms such as endocrine dysfunctions should alarm doctors not to exclude brain tumors.A bilateral temporal visual field defect (due to compression of the optic chiasm) or dilation of the pupil, and the occurrence of either slowly evolving or the sudden onset of focal neurologic symptoms, such as cognitive and behavioral impairment (including impaired judgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, or more severe symptoms such as tremors, paralysis on one side of the body hemiplegia, or (epileptic) seizures in a patient with a negative history for epilepsy, should raise the possibility of a brain tumor. Imaging Medical imaging plays a central role in the diagnosis of brain tumors. Early imaging methods – invasive and sometimes dangerous – such as pneumoencephalography and cerebral angiography have been abandoned in favor of non-invasive, high-resolution techniques, especially magnetic resonance imaging (MRI) and computed tomography (CT) scans, though MRI is typically the reference standard used. Neoplasms will often show as differently colored masses (also referred to as processes) in CT or MRI results. Benign brain tumors often show up as hypodense (darker than brain tissue) mass lesions on CT scans. On MRI, they appear either hypodense or isointense (same intensity as brain tissue) on T1-weighted scans, or hyperintense (brighter than brain tissue) on T2-weighted MRI, although the appearance is variable. Contrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either CT or MRI scans in most malignant primary and metastatic brain tumors. Pressure areas where the brain tissue has been compressed by a tumor also appear hyperintense on T2-weighted scans and might indicate the presence a diffuse neoplasm due to an unclear outline. Swelling around the tumor known as peritumoral edema can also show a similar result.This is because these tumors disrupt the normal functioning of the BBB and lead to an increase in its permeability. More recently, advancements have been made to increase the utility of MRI in providing physiological data that can help to inform diagnosis and prognosis. Perfusion Weighted Imaging (PWI) and Diffusion Weighted Imaging (DWI) are two MRI techniques that reviews have been shown to be useful in classifying tumors by grade, which was not previously viable using only structural imaging. However, these techniques cannot alone diagnose high- versus low-grade gliomas, and thus the definitive diagnosis of brain tumor should only be confirmed by histological examination of tumor tissue samples obtained either by means of brain biopsy or open surgery. The histological examination is essential for determining the appropriate treatment and the correct prognosis. This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and follow-up examination of prepared tissues after immunohistochemical staining or genetic analysis. Pathology Tumors have characteristics that allow the determination of malignancy and how they will evolve, and determining these characteristics will allow the medical team to determine the management plan.Anaplasia or dedifferentiation: loss of differentiation of cells and of their orientation to one another and blood vessels, a characteristic of anaplastic tumor tissue. Anaplastic cells have lost total control of their normal functions and many have deteriorated cell structures. Anaplastic cells often have abnormally high nuclear-to-cytoplasmic ratios, and many are multinucleated. Additionally, the nucleus of anaplastic cells is usually unnaturally shaped or oversized. Cells can become anaplastic in two ways: neoplastic tumor cells can dedifferentiate to become anaplasias (the dedifferentiation causes the cells to lose all of their normal structure/function), or cancer stem cells can increase their capacity to multiply (i.e., uncontrollable growth due to failure of differentiation).Atypia: an indication of abnormality of a cell (which may be indicative of malignancy). Significance of the abnormality is highly dependent on context.Neoplasia: the (uncontrolled) division of cells. As such, neoplasia is not problematic but its consequences are: the uncontrolled division of cells means that the mass of a neoplasm increases in size, and in a confined space such as the intracranial cavity this quickly becomes problematic because the mass invades the space of the brain pushing it aside, leading to compression of the brain tissue and increased intracranial pressure and destruction of brain parenchyma. Increased intracranial pressure (ICP) may be attributable to the direct mass effect of the tumor, increased blood volume, or increased cerebrospinal fluid (CSF) volume, which may, in turn, have secondary symptoms.Necrosis: the (premature) death of cells, caused by external factors such as infection, toxin or trauma. Necrotic cells send the wrong chemical signals which prevent phagocytes from disposing of the dead cells, leading to a buildup of dead tissue, cell debris and toxins at or near the site of the necrotic cellsArterial and venous hypoxia, or the deprivation of adequate oxygen supply to certain areas of the brain, occurs when a tumor makes use of nearby blood vessels for its supply of blood and the neoplasm enters into competition for nutrients with the surrounding brain tissue. More generally a neoplasm may cause release of metabolic end products (e.g., free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (e.g., cytokines) that disrupt normal parenchymal function. Classification Tumors can be benign or malignant, can occur in different parts of the brain, and may be classified as primary or secondary. A primary tumor is one that has started in the brain, as opposed to a metastatic tumor, which is one that has spread to the brain from another area of the body. The incidence of metastatic tumors is approximately four times greater than primary tumors. Tumors may or may not be symptomatic: some tumors are discovered because the patient has symptoms, others show up incidentally on an imaging scan, or at an autopsy.Grading of the tumors of the central nervous system commonly occurs on a 4-point scale (I-IV) created by the World Health Organization in 1993. Grade I tumors are the least severe and commonly associated with long-term survival, with severity and prognosis worsening as the grade increases. Low-grade tumors are often benign, while higher grades are aggressively malignant and/or metastatic. Other grading scales do exist, many based upon the same criteria as the WHO scale and graded from I-IV. Primary The most common primary brain tumors are: Gliomas (50.4%) Meningiomas (20.8%) Pituitary adenomas (15%) Nerve sheath tumors (10%)These common tumors can also be organized according to tissue of origin as shown below: Secondary Secondary tumors of the brain are metastatic and have invaded the brain from cancers originating in other organs. This means that a cancerous neoplasm has developed in another organ elsewhere in the body and that cancer cells have leaked from that primary tumor and then entered the lymphatic system and blood vessels. They then circulate through the bloodstream, and are deposited in the brain. There, these cells continue growing and dividing, becoming another invasive neoplasm of primary cancers tissue. Secondary tumors of the brain are very common in the terminal phases of patients with an incurable metastasized cancer; the most common types of cancers that bring about secondary tumors of the brain are lung cancer, breast cancer, malignant melanoma, kidney cancer, and colon cancer (in decreasing order of frequency).Secondary brain tumors are more common than primary ones; in the United States, there are about 170,000 new cases every year. Secondary brain tumors are the most common cause of tumors in the intracranial cavity. The skull bone structure can also be subject to a neoplasm that by its very nature reduces the volume of the intracranial cavity, and can damage the brain. By behavior Brain tumors or intracranial neoplasms can be cancerous (malignant) or non-cancerous (benign). However, the definitions of malignant or benign neoplasms differ from those commonly used in other types of cancerous or non-cancerous neoplasms in the body. In cancers elsewhere in the body, three malignant properties differentiate benign tumors from malignant forms of cancer: benign tumors are self-limited and do not invade or metastasize. Characteristics of malignant tumors include: uncontrolled mitosis (growth by division beyond the normal limits) anaplasia: the cells in the neoplasm have an obviously different form (in size and shape). Anaplastic cells display marked pleomorphism. The cell nuclei are characteristically extremely hyperchromatic (darkly stained) and enlarged; the nucleus might have the same size as the cytoplasm of the cell (nuclear-cytoplasmic ratio may approach 1:1, instead of the normal 1:4 or 1:6 ratio). Giant cells – considerably larger than their neighbors – may form and possess either one enormous nucleus or several nuclei (syncytia). Anaplastic nuclei are variable and bizarre in size and shape. invasion or infiltration (medical literature uses these terms as synonymous equivalents. However, for clarity, the articles that follow adhere to a convention that they mean slightly different things; this convention is not followed outside these articles): Invasion or invasiveness is the spatial expansion of the tumor through uncontrolled mitosis, in the sense that the neoplasm invades the space occupied by adjacent tissue, thereby pushing the other tissue aside and eventually compressing the tissue. Often these tumors are associated with clearly outlined tumors in imaging. Infiltration is the behavior of the tumor either to grow (microscopic) tentacles that push into the surrounding tissue (often making the outline of the tumor undefined or diffuse) or to have tumor cells "seeded" into the tissue beyond the circumference of the tumorous mass; this does not mean that an infiltrative tumor does not take up space or does not compress the surrounding tissue as it grows, but an infiltrating neoplasm makes it difficult to say where the tumor ends and the healthy tissue starts. metastasis (spread to other locations in the body via lymph or blood).Of the above malignant characteristics, some elements do not apply to primary neoplasms of the brain: Primary brain tumors rarely metastasize to other organs; some forms of primary brain tumors can metastasize but will not spread outside the intracranial cavity or the central spinal canal. Due to the BBB, cancerous cells of a primary neoplasm cannot enter the bloodstream and get carried to another location in the body. (Occasional isolated case reports suggest spread of certain brain tumors outside the central nervous system, e.g. bone metastasis of glioblastoma multiforme.) Primary brain tumors generally are invasive (i.e. they will expand spatially and intrude into the space occupied by other brain tissue and compress those brain tissues); however, some of the more malignant primary brain tumors will infiltrate the surrounding tissue. By genetics In 2016, the WHO restructured their classifications of some categories of gliomas to include distinct genetic mutations that have been useful in differentiating tumor types, prognoses, and treatment responses. Genetic mutations are typically detected via immunohistochemistry, a technique that visualizes the presence or absence of a targeted protein via staining. Mutations in IDH1 and IDH2 genes are commonly found in low-grade gliomas Loss of both IDH genes combined with loss of chromosome arms 1p and 19q indicates the tumor is an oligodendroglioma Loss of TP53 and ATRX characterizes astrocytomas Genes EGFR, TERT, and PTEN, are commonly altered in gliomas and are useful in differentiating tumor grade and biology Specific types Anaplastic astrocytoma, Anaplastic oligodendroglioma, Astrocytoma, Central neurocytoma, Choroid plexus carcinoma, Choroid plexus papilloma, Choroid plexus tumor, Colloid cyst, Dysembryoplastic neuroepithelial tumour, Ependymal tumor, Fibrillary astrocytoma, Giant-cell glioblastoma, Glioblastoma multiforme, Gliomatosis cerebri, Gliosarcoma, Hemangiopericytoma, Medulloblastoma, Medulloepithelioma, Meningeal carcinomatosis, Neuroblastoma, Neurocytoma, Oligoastrocytoma, Oligodendroglioma, Optic nerve sheath meningioma, Pediatric ependymoma, Pilocytic astrocytoma, Pinealoblastoma, Pineocytoma, Pleomorphic anaplastic neuroblastoma, Pleomorphic xanthoastrocytoma, Primary central nervous system lymphoma, Sphenoid wing meningioma, Subependymal giant cell astrocytoma, Subependymoma, Trilateral retinoblastoma. Treatment A medical team generally assesses the treatment options and presents them to the person affected and their family. Various types of treatment are available depending on tumor type and location, and may be combined to produce the best chances of survival: Surgery: complete or partial resection of the tumor with the objective of removing as many tumor cells as possible. Radiotherapy: the most commonly used treatment for brain tumors; the tumor is irradiated with beta, x rays or gamma rays. Chemotherapy: a treatment option for cancer, however, it is not always used to treat brain tumors as the blood-brain barrier can prevent some drugs from reaching the cancerous cells. A variety of experimental therapies are available through clinical trials.Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical removal and other factors specific to each case.Standard care for anaplastic oligodendrogliomas and anaplastic oligoastrocytomas is surgery followed by radiotherapy. One study found a survival benefit for the addition of chemotherapy to radiotherapy after surgery, compared with radiotherapy alone. Surgery The primary and most desired course of action described in medical literature is surgical removal (resection) via craniotomy. Minimally invasive techniques are becoming the dominant trend in neurosurgical oncology. The main objective of surgery is to remove as many tumor cells as possible, with complete removal being the best outcome and cytoreduction ("debulking") of the tumor otherwise. A Gross Total Resection (GTR) occurs when all visible signs of the tumor are removed, and subsequent scans show no apparent tumor. In some cases access to the tumor is impossible and impedes or prohibits surgery. Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically. Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenomas require a craniotomy (opening of the skull) for their removal. Radiotherapy, including stereotactic approaches, is reserved for inoperable cases.Several current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with 5-aminolevulinic acid that causes them to fluoresce. Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors.Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy rather than surgery and the prognosis in such cases is determined by the primary tumor, and is generally poor. Radiation therapy The goal of radiation therapy is to kill tumor cells while leaving normal brain tissue unharmed. In standard external beam radiation therapy, multiple treatments of standard-dose "fractions" of radiation are applied to the brain. This process is repeated for a total of 10 to 30 treatments, depending on the type of tumor. This additional treatment provides some patients with improved outcomes and longer survival rates.Radiosurgery is a treatment method that uses computerized calculations to focus radiation at the site of the tumor while minimizing the radiation dose to the surrounding brain. Radiosurgery may be an adjunct to other treatments, or it may represent the primary treatment technique for some tumors. Forms used include stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery.Radiotherapy is the most common treatment for secondary brain tumors. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam "whole-brain radiotherapy treatment" (WBRT) or "whole-brain irradiation" may be suggested if there is a risk
Brain tumor	that other secondary tumors will develop in the future. Stereotactic radiotherapy is usually recommended in cases involving fewer than three small secondary brain tumors. Radiotherapy may be used following, or in some cases in place of, resection of the tumor. Forms of radiotherapy used for brain cancer include external beam radiation therapy, the most common, and brachytherapy and proton therapy, the last especially used for children. People who receive stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone. Results of a 2021 systematic review found that when using SRS as the initial treatment, survival or death related to brain metastasis was not greater than alone versus SRS with WBRT.Postoperative conventional daily radiotherapy improves survival for adults with good functional well-being and high grade glioma compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma. Chemotherapy Patients undergoing chemotherapy are administered drugs designed to kill tumor cells. Although chemotherapy may improve overall survival in patients with the most malignant primary brain tumors, it does so in only about 20 percent of patients. Chemotherapy is often used in young children instead of radiation, as radiation may have negative effects on the developing brain. The decision to prescribe this treatment is based on a patients overall health, type of tumor, and extent of cancer. The toxicity and many side effects of the drugs, and the uncertain outcome of chemotherapy in brain tumors puts this treatment further down the line of treatment options with surgery and radiation therapy preferred.UCLA Neuro-Oncology publishes real-time survival data for patients with a diagnosis of glioblastoma multiforme. They are the only institution in the United States that displays how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high-grade glioma tumors.Genetic mutations have significant effects on the effectiveness of chemotherapy. Gliomas with IDH1 or IDH2 mutations respond better to chemotherapy than those without the mutation. Loss of chromosome arms 1p and 19q also indicate better response to chemoradiation. Other A shunt may be used to relieve symptoms caused by intracranial pressure, by reducing the build-up of fluid (hydrocephalus) caused by the blockage of the free flow of cerebrospinal fluid. Prognosis The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma multiforme has a median survival of only 12 months even with aggressive chemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type, focal brainstem gliomas in children, seems open to exceptional prognosis and long-term survival has frequently been reported.Prognosis is also affected by presentation of genetic mutations. Certain mutations provide better prognosis than others. IDH1 and IDH2 mutations in gliomas, as well as deletion of chromosome arms 1p and 19q, generally indicate better prognosis. TP53, ATRX, EGFR, PTEN, and TERT mutations are also useful in determining prognosis. Glioblastoma multiforme Glioblastoma multiforme (GBM) is the most aggressive (grade IV) and most common form of a malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer, then by chemotherapy, such as temozolomide. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to relieve symptoms. Experimental treatments include targeted therapy, gamma knife radiosurgery, boron neutron capture therapy, gene therapy also chemowafer implants. Oligodendrogliomas Oligodendrogliomas are incurable but slowly progressive malignant brain tumors. They can be treated with surgical resection, chemotherapy, radiotherapy or a combination. For some suspected low-grade (grade II) tumors, only a course of watchful waiting and symptomatic therapy is opted for. These tumors show a high frequency of co-deletions of the p and q arms of chromosome 1 and chromosome 19 respectively (1p19q co-deletion) and have been found to be especially chemosensitive with one report claiming them to be one of the most chemosensitive tumors. A median survival of up to 16.7 years has been reported for grade II oligodendrogliomas. Acoustic neuroma Acoustic neuromas are non-cancerous tumors. They can be treated with surgery, radiation therapy, or observation. Early intervention with surgery or radiation is recommended to prevent progressive hearing loss. Epidemiology Figures for incidences of cancers of the brain show a significant difference between more- and less-developed countries (the less-developed countries have lower incidences of tumors of the brain). This could be explained by undiagnosed tumor-related deaths (patients in extremely poor situations do not get diagnosed, simply because they do not have access to the modern diagnostic facilities required to diagnose a brain tumor) and by deaths caused by other poverty-related causes that preempt a patients life before tumors develop or tumors become life-threatening. Nevertheless, statistics suggest that certain forms of primary brain tumors are more common among certain populations.The incidence of low-grade astrocytoma has not been shown to vary significantly with nationality. However, studies examining the incidence of malignant central nervous system (CNS) tumors have shown some variation with national origin. Since some high-grade lesions arise from low-grade tumors, these trends are worth mentioning. Specifically, the incidence of CNS tumors in the United States, Israel, and the Nordic countries is relatively high, while Japan and Asian countries have a lower incidence. These differences probably reflect some biological differences as well as differences in pathologic diagnosis and reporting. Worldwide data on incidence of cancer can be found at the WHO (World Health Organisation) and is handled by the IARC (International Agency for Research on Cancer) located in France. United States In the United States in 2015, approximately 166,039 people were living with brain or other central nervous system tumors. Over 2018, it was projected that there would be 23,880 new cases of brain tumors and 16,830 deaths in 2018 as a result, accounting for 1.4 percent of all cancers and 2.8 percent of all cancer deaths. Median age of diagnosis was 58 years old, while median age of death was 65. Diagnosis was slightly more common in males, at approximately 7.5 cases per 100 000 people, while females saw 2 fewer at 5.4. Deaths as a result of brain cancer were 5.3 per 100 000 for males, and 3.6 per 100 000 for females, making brain cancer the 10th leading cause of cancer death in the United States. Overall lifetime risk of developing brain cancer is approximated at 0.6 percent for men and women. UK Brain, other CNS or intracranial tumors are the ninth most common cancer in the UK (around 10,600 people were diagnosed in 2013), and it is the eighth most common cause of cancer death (around 5,200 people died in 2012). White British patients with brain tumour are 30% more likely to die within a year of diagnosis than patients from other ethnicities. The reason for this is unknown. Children In the United States more than 28,000 people under 20 are estimated to have a brain tumor. About 3,720 new cases of brain tumors are expected to be diagnosed in those under 15 in 2019. Higher rates were reported in 1985–1994 than in 1975–1983. There is some debate as to the reasons; one theory is that the trend is the result of improved diagnosis and reporting, since the jump occurred at the same time that MRIs became available widely, and there was no coincident jump in mortality. Central nervous system tumors make up 20–25 percent of cancers in children.The average survival rate for all primary brain cancers in children is 74%. Brain cancers are the most common cancer in children under 19, are result in more death in this group than leukemia. Younger people do less well.The most common brain tumor types in children (0-14) are: pilocytic astrocytoma, malignant glioma, medulloblastoma, neuronal and mixed neuronal-glial tumors, and ependymoma.In children under 2, about 70% of brain tumors are medulloblastomas, ependymomas, and low-grade gliomas. Less commonly, and seen usually in infants, are teratomas and atypical teratoid rhabdoid tumors. Germ cell tumors, including teratomas, make up just 3% of pediatric primary brain tumors, but the worldwide incidence varies significantly.In the UK, 429 children aged 14 and under are diagnosed with a brain tumour on average each year, and 563 children and young people under the age of 19 are diagnosed. Research Immunotherapy Cancer immunotherapy is being actively studied. For malignant gliomas no therapy has been shown to improve life expectancy as of 2015. Vesicular stomatitis virus In 2000, researchers used the vesicular stomatitis virus, or VSV, to infect and kill cancer cells without affecting healthy cells. Retroviral replicating vectors Led by Prof. Nori Kasahara, researchers from USC, who are now at UCLA, reported in 2001 the first successful example of applying the use of retroviral replicating vectors towards transducing cell lines derived from solid tumors. Building on this initial work, the researchers applied the technology to in vivo models of cancer and in 2005 reported a long-term survival benefit in an experimental brain tumor animal model. Subsequently, in preparation for human clinical trials, this technology was further developed by Tocagen (a pharmaceutical company primarily focused on brain cancer treatments) as a combination treatment (Toca 511 & Toca FC). This has been under investigation since 2010 in a Phase I/II clinical trial for the potential treatment of recurrent high-grade glioma including glioblastoma multiforme (GBM) and anaplastic astrocytoma. No results have yet been published. Non-invasive detection Efforts to detect and monitor development and treatment response of brain tumors by liquid biopsy from blood, cerebrospinal fluid or urine, are in the early stages of development. See also Brain Tumor Nervous system neoplasm List of brain tumor cases References External links Brain and CNS cancers at Curlie Brain tumour information from Cancer Research UK Neuro-Oncology: Cancer Management Guidelines MedPix Teaching File MR Scans of Primary Brain Lymphoma, etc.
Hiccup	A hiccup (scientific name singultus, from a Latin word meaning "to catch ones breath while sobbing"; also spelled hiccough) is an involuntary contraction (myoclonic jerk) of the diaphragm that may repeat several times per minute. The hiccup is an involuntary action involving a reflex arc. Once triggered, the reflex causes a strong contraction of the diaphragm followed about a quarter of a second later by closure of the vocal cords, which results in the "hic" sound. Hiccups may occur individually, or they may occur in bouts. The rhythm of the hiccup, or the time between hiccups, tends to be relatively constant. A bout of hiccups generally resolves itself without intervention, although many home remedies are often used to attempt to shorten the duration. Medical treatment is occasionally necessary in cases of chronic hiccups. Incidence Hiccups affect people of all ages, even being observed in utero. They become less frequent with advancing age. Intractable hiccups, lasting more than a month, are more common in adults. While males and females are affected equally often, men are more likely to develop hiccups lasting more than 48 hours. Dogs may also get hiccups. Signs and symptoms A hiccup consists of a single or a series of breathing diaphragm spasms, of variable spacing and duration, and a brief (less than one half second), unexpected, shoulder, abdomen, throat, or full body tremor. Hiccups may present as an audible chirp, squeak, "hupp", or if controlled, a quick inhaling gasp, sigh, or sniff. They may also present as brief but distracting or painful interruptions in normal breathing, with sudden momentary pain of the throat, chest, or abdomen. Causes Pathophysiological causes Swallowing air excessively Gastroesophageal reflux Hiatal hernia Rapid eating Carbonated beverages, alcohol, dry breads, and some spicy foods Opiate drug use Laughing vigorously or for a long timeHiccups may be triggered by a number of common human conditions. In rare cases, they can be a sign of serious medical problems. In rare cases, hiccups can be the sole symptom of myocardial infarction. Pre-phrenic nucleus irritation of medulla Kidney failure CNS disorders Stroke Multiple sclerosis Meningitis Nerve damage Damage to the vagus nerve after surgery Other known associations Although no clear pathophysiological mechanism has been described, hiccups is known to have been the initial symptom of Plasmodium vivax malaria in at least one documented case. Evolutionary theories The burping reflex hypothesis A leading hypothesis is that hiccups evolved to facilitate greater milk consumption in young mammals. The coordination of breathing and swallowing during suckling is a complicated process. Some air inevitably enters the stomach, occupying space that could otherwise be optimally used for calorie rich milk.The hypothesis suggests that the presence of an air bubble in the stomach stimulates the sensory (afferent) limb of the reflex through receptors in the stomach, esophagus and along the underside of the diaphragm. This triggers the active part of the hiccup (efferent limb), sharply contracting the muscles of breathing and relaxing the muscles of the esophagus, then closing the vocal cords to prevent air from entering the lungs. This creates suction in the chest, pulling air from the stomach up into the esophagus. As the respiratory muscles relax the air is expelled through the mouth, effectively "burping" the animal.There are a number of characteristics of hiccups that support this theory. The burping of a suckling infant may increase its capacity for milk by more than 15-25%, bringing a significant survival advantage. There is a strong tendency for infants to get hiccups, and although the reflex persists throughout life it decreases in frequency with age. The location of the sensory nerves that trigger the reflex suggests it is a response to a condition in the stomach. The component of the reflex that suppresses peristalsis in the esophagus while the airway is being actively blocked suggests the esophagus is involved. Additionally, hiccups are only described in mammals - the group of animals that share the trait of suckling their young. Phylogenetic hypothesis An international respiratory research group composed of members from Canada, France, and Japan proposed that the hiccup is an evolutionary remnant of earlier amphibian respiration. Amphibians such as tadpoles gulp air and water across their gills via a rather simple motor reflex akin to mammalian hiccuping. The motor pathways that enable hiccuping form early during fetal development, before the motor pathways that enable normal lung ventilation form. Thus, the hiccup is evolutionarily antecedent to modern lung respiration. Additionally, this group (C. Straus et al.) points out that hiccups and amphibian gulping are inhibited by elevated CO2 and may be stopped by GABAB receptor agonists, illustrating a possible shared physiology and evolutionary heritage. These proposals may explain why premature infants spend 2.5% of their time hiccuping, possibly gulping like amphibians, as their lungs are not yet fully formed.The phylogenetic hypothesis may explain hiccups as an evolutionary remnant, held over from our amphibious ancestors. This hypothesis has been questioned because of the complexity of the mammalian hiccup reflex compared to the amphibian breathing reflex, the fact that it does not explain the reason for glottic closure, and because the very short contraction of the hiccup is unlikely to have a significant strengthening effect on the slow-twitch muscles of respiration.Fetal intrauterine hiccups are of two types. The physiological type occurs prior to twenty-eight weeks after conception and tends to last five to ten minutes. These hiccups are part of fetal development and are associated with the myelination of the phrenic nerve, which primarily controls the thoracic diaphragm.The phylogenetic and the burping hypotheses are not mutually exclusive. The phylogeny hypothesis could explain how the hiccup reflex might have evolved, while the "Burping Hypothesis" could explain why it would offer enough of an evolutionary advantage to persist and increase in complexity. Duration Episodes of hiccups usually last just a few minutes, doing nothing worse than annoying those affected and amusing bystanders, but prolonged attacks can be serious, with a cause difficult to diagnose. Such attacks can cause significant morbidity and even death. An episode lasting more than a few minutes is termed a bout; a bout of over 48 hours is termed persistent or protracted. Hiccups lasting longer than a month are termed intractable. In many cases, only a single hemidiaphragm, usually the left one, is affected, although both may be involved. Treatment Hiccups are normally waited out, as any fit of them will usually pass quickly. Folk cures for hiccups are common and varied, but no effective standard for stopping hiccups has been documented. Hiccups are treated medically only in severe and persistent (termed "intractable") cases.Numerous medical remedies exist but no particular treatment is known to be especially effective, generally because of a lack of high-quality evidence. Many drugs have been used, such as baclofen, chlorpromazine, metoclopramide, gabapentin, and various proton-pump inhibitors. Hiccups that are secondary to some other cause, like gastroesophageal reflux disease or esophageal webs, are dealt with by treating the underlying disorder. The phrenic nerve can be blocked temporarily with injection of 0.5% procaine, or permanently with bilateral phrenicotomy or other forms of surgical destruction. Even this rather drastic treatment does not cure some cases, however.Haloperidol, metoclopramide, and chlorpromazine are used in cases of intractable hiccups. Effective treatment with sedatives often requires a dose that renders the person either unconscious or highly lethargic. Hence, medicating with sedatives is only appropriate short-term, as the affected individual cannot continue with normal life activities while under their effect.A vagus nerve stimulator has been used with an intractable case of hiccups. "It sends rhythmic bursts of electricity to the brain by way of the vagus nerve, which passes through the neck. The Food and Drug Administration approved the vagus nerve stimulator in 1997 as a way to control seizures in some patients with epilepsy."Persistent digital rectal massage has also been proven effective in terminating intractable hiccups. Folk remedies There are many superstitious and folk remedies for hiccups, including headstanding, drinking a glass of water upside-down, being frightened by someone, breathing into a bag, eating a large spoonful of peanut butter and placing sugar on or under the tongue.Acupressure, either through actual function or placebo effect, may cure hiccups in some people. For example, one technique is to relax the chest and shoulders and find the deepest points of the indentations directly below the protrusions of the collarbones. The index or middle fingers are inserted into the indents and pressed firmly for sixty seconds as long, deep breaths are taken.A simple treatment involves increasing the partial pressure of CO2 and inhibiting diaphragm activity by holding ones breath or rebreathing into a paper bag. Other potential remedies suggested by NHS Choices include pulling the knees up to the chest and leaning forward, sipping ice-cold water and swallowing some granulated sugar.Drinking through a straw with the ears plugged is a folk remedy that can be successful. In 2021 a scientific tool with a similar basis was tested on 249 hiccups subjects; the results were published in the Journal of the American Medical Association (JAMA). This device is named FISST (Forced Inspiratory Suction and Swallow Tool) and branded as "HiccAway". This study supports the use of FISST as an option to stop transient hiccups, with more than 90% of participants reporting better results than home remedies. HiccAway stops hiccups by forceful suction that is being generated by diaphragm contraction (phrenic nerve activity), followed by swallowing the water, which requires epiglottis closure. Society and culture The word hiccup itself was created through imitation. The alternative spelling of hiccough results from the association with the word cough. American Charles Osborne (December 14, 1892 – May 1, 1991) had hiccups for 68 years, from 1922 to February 1990, and was entered in the Guinness World Records as the man with the longest attack of hiccups, an estimated 430 million hiccups. In 2007, Florida teenager Jennifer Mee gained media fame for hiccuping around 50 times per minute for more than five weeks. Christopher Sands, a Briton, hiccupped an estimated 10 million times in a 27-month period from February 2007 to May 2009. His condition, which meant that he could hardly eat or sleep, was eventually discovered to be caused by a tumor on his brain stem pushing on nerves causing him to hiccup every two seconds, 12 hours a day. His hiccups stopped in 2009 following surgery.In Baltic, German, Hungarian, Indian, Romanian, Slavic, Turkish, Greek, Albanian and among some Tribes in Kenya, for example the Luos folklore, it is said that hiccups occur when the person experiencing them is being talked about by someone not present. See also Getting the wind knocked out of you Mr. Hiccup Sneeze Thumps, a more serious form of hiccups found in equines Yawn Vocal hiccup References Further reading External links BBC News: Why we hiccup WIRED: The Best Cure for Hiccups: Remind Your Brain Youre Not a Fish Cymet TC (June 2002). "Retrospective analysis of hiccups in patients at a community hospital from 1995–2000". J Natl Med Assoc. 94 (6): 480–3. PMC 2594386. PMID 12078929. WebMD: Hiccups
Papillary hidradenoma	A papillary hidradenoma, also termed hidradenoma papilliferum or mammary-like gland adenoma of the vulva, is a rare, but nonetheless most common benign tumor that occurs in and between anal and genital regions (i.e. anogenital area) of females. These hidradenomas are sharply circumscribed, nodular tumors that usually develop in womens anogenital area (particularly the vulva) but uncommonly occur in other sites in women and men. Papillary hidradenomas that develop outside of the anogenital region are termed ecctopic papillary hidradenomas or ectopic hidradenoma papilliferums.Anogenital papillary hidradenomas are regarded as tumors that form in anogenital mammary–like glands (MLAGs); MLAGs are a type of apocrine gland. MLAGs were once classified as abnormally located breast tissue glands (see accessory breast tissue@ https://doi.org/10.53347/rID-11125) but are now considered to be normal components of the anogenital region. Microscopically, papillary hidradenomas often resemble certain types of breast tumors. Ectopic papillary hidradenomas are thought to be tumors of apocrine glands which have an as yet unclear relationship to MLAGs.Typically, papillary hidradenomas are solitary, slow-growing, small tumors that may have been present for months to many years before the time of diagnosis. The tumors are usually symptomless but may be intermittently or constantly painful, become ulcerated, and exhibit minor levels of bleeding. The pain resulting from these tumors may be simple tenderness, more or less constant usually mild pain, or, in females, dyspareunia, i.e. pain during and just after sexual intercourse.Rarely, papillary hidradenomas have progressed to what appear to be 1) in situ malignancies (i.e. malignancies that have neither metastasized nor invaded beyond the layer of tissue where they arose); 2) locally invasive malignancies; or 3) complex tumors intermixed with other malignancies such as extramammary Paget disease, melanoma, and squamous cell carcinoma. Furthermore, benign papillary hidradenoma tumors may be confused clinically with cancerous tumors and recent studies have indicated that other types of tumors have often been mistakenly diagnosed as papillary hidradenomas. Papillary hidradenomas, particularly ectopic papillary hidradenomas, require further study to better define the criteria for their diagnosis. Presentation In a review of 264 women diagnosed with anogenital papillary hidradenomas, patients ranged in age from 25 to 82 years (median: 49 years); in 25 cases where the information was available, the tumors had been present for 2–120 months (median: 12 months) with 13 patients reporting their tumors presence for less than 1 year before diagnosis. All patients had a solitary tumor in the anogenital area except for one patient who presented with four clustered tumors. Most tumors involved the vulva (71.6%) and areas around the anus (14%) or space between the anus and vulva, i.e. the perineum (3.8%). Their lesions ranged in size from 0.2 to 2 centimeters (cm.) in largest dimension (median: 0.7 cm.). Smaller studies on one or a few females with anogenital papillary hidradenomas found that the tumors commonly presented as asymptomatic, well-confined, skin-colored, red, or bluish nodules in women of Caucasian origin between the ages of 25–66 years. The nodules were solid or cystic; 0.4 to 2.5 cm. in widest dimension; and usually located in the grooves (termed interlabial sulci or interlabial folds) between the labia majora and labia minora, the clitoris, or the region between the vulva and anus (i.e. Frenulum of labia minora). Ectopic papillary hidradenomas in women have been reported to occur on the scalp, eyelid, cheek, forehead, face, ear canal, and back. Nearly 50% of ectopic papillary hidradenoma have been diagnosed in men; these have occurred on the thigh, arm, armpit, face and eyelid. While usually symptomless, patients may complain that the tumor is ulcerated, bleeds, or is painful. This pain may be simple tenderness, more or less constant but usually mild, or, in females with anogenital lesions, dyspareunia. The rare cases of ectopic papillary hidradenoma in the external auditory canal have presented with unilateral conductive hearing loss sometimes associated with ear pain, drainage of ear fluid, or weakness of a facial muscle(s). Histopathology Microscopic histopathological analyses of papillary hidradenoma tumors typically reveal a nodule in the dermis, i.e. layer of skin between the epidermis and subcutaneous tissue. The tumor consists of complex patterns of interconnecting tubular and papillary (i.e. thin finger-like or frond-like) structures. These structures are lined with glandular epithelial and myoepithelial cells. The glandular epithelial cells appear to be excessively proliferating in the ducts leading to the epidermis and show oxyphilic changes, (i.e. cytoplasm filled with large mitochondria, glycogen, and ribosomes) while the myoepithelial cells often appear clear cell-like, i.e. have uncolored cytoplasm when stained with hematoxylin and eosin. The histopathology of anogenital and ectopic papillary hidradenomas are similar to each other. Immunohistochemistry Immunohistochemical analyses of anogenital papillary hidradenoma tumors have detected the expression of both the estrogen and progesterone receptors in 18 and the androgen receptor in 4 of 20 cases. In another study of anogenital papillary hidradenomas, expression of the estrogen receptor was restricted to the tumors glandular epithelial cells while the tumors myoepithelial cells expressed tumor protein p63 and alpha-smooth muscle actin protein. Presence of the estrogen and progesterone receptors may underlie the female prevalence of anogenital papillary hidradenomas as well as their development in females only after puberty. The anogenital tumor cells may also express vimentin, various cytokeratin proteins, and in a minority of cases the DNA of human papillomavirus (infection by this virus and the presence of its DNA does not appear involved in the development of papillary hidradenoma). These immunohistochemistry findings have not as yet been reported in atypical papillary hidradenomas. Gene and signaling pathway abnormalities Several studies have reported the presence in anogenital papillary hidradenoma tumor cells of mutations in one or multiple genes that lead to the production of proteins that directly or indirectly stimulate the PI3K/AKT/mTOR intracellular signaling pathway. The mutated genes include PIK3CA, AKT1, PIK3CA, MAGI1, SYNE1, USP9X, KLNI (also termed CASC5), RNF213, FLCN, PDGFRB, AR (i.e. the androgen receptor gene), BTK, MLL3, KAT6A, BRD3, EP400, TET2, IL6, and IL7R. The PI3K/AKT/mTOR pathway promotes the grow (i.e. proliferation) and survival of cells and is abnormally activated in, and appears to contribute to the development and or progression of, a wide range of tumors. While further studies are needed, these findings suggest that the cited mutations lead to stimulation of the PI3K/AKT/mTOR pathway and thereby promote the development and/or progression of anogenital papillary hidradenoma in the majority of cases. These abnormalities have not yet been reported in ectopic papillary hidradenomas. Diagnosis The diagnosis of anogenital papillary hidradenoma lesions, while often suggested based on their clinical presentations, must be differentiated from a wide range of other similarly presenting anogenital lesions such as hemorrhoidal disease, anorectal abscesses, virus-related wart-like lesions, sebaceous cysts, mucous cysts, lipomas, neurofibromas, metastatic carcinomas with papillary histopathology, syringocystoadenocarcinoma papilliferum (i.e. malignant syringocystadenoma papilliferum), syringocystadenoma papilliferum, melanomas, eccrine porocarcinomas, squamous cell carcinomas, nodular lesions in extramammary Paget disease, dermatofibroma, focal areas of mucinosis, colloid milium, and sebaceous adenomas. This differentiation is made by finding that a lesion has the histopathological features typical of papillary hidradenomas. However, some cases diagnosed as ectopic papillary hidradenomas, particularly those occurring in men, have subsequently been found to be syringocystadenoma papilliferums or trichoepitheliomas. Further studies are required to better define the criteria for ectopic papillary hidradenomas. Treatment and prognosis The treatment of choice for anogenital and ectopic papillary hidradenomas, regardless of their locations, is similar: resection of the tumor while preserving the surrounding structures. Recurrence of these tumors is rare and usually due to incomplete removal of the primary lesion. As of 2021, there has been no reported recurrence of ectopic papillary hidradenomas. Prognosis after complete surgical removal of anogenital and ectopic papillary hidradenomas is excellent. Malignant transformation of papillary hidradenomas Transformations of papillary hidradenomas into malignant forms are extremely rare. Two cases progressed to in situ (malignant cells present in the tumor but have neither metastasized, i.e. spread to distant tissues nor invaded beyond the layer of tissue from where they arose) cancers; two cases appeared to have infiltrated locally but not metastasized; and one case was a rapidly fatal lesion that appeared to be an adenosquamous carcinoma that arose in a papillary hidradenoma. It is not clear that these cases actually represent true progression of papillary hidradenoma into a cancer. See also Hidroacanthoma simplex List of cutaneous conditions References == External links ==
Lown–Ganong–Levine syndrome	Lown–Ganong–Levine syndrome (LGL) is a pre-excitation syndrome of the heart. Those with LGL syndrome have episodes of abnormal heart racing with a short PR interval and normal QRS complexes seen on their electrocardiogram when in a normal sinus rhythm. LGL syndrome was originally thought to be due to an abnormal electrical connection between the atria and the ventricles, but is now thought to be due to accelerated conduction through the atrioventricular node in the majority of cases. The syndrome is named after Bernard Lown, William Francis Ganong, Jr., and Samuel A. Levine. Signs and symptoms Pathophysiology LGL syndrome was originally thought to involve a rapidly conducting accessory pathway (bundle of James) that connects the atria directly to the bundle of His, bypassing the slowly conducting atrioventricular node. However, the majority of those with LGL in whom electrophysiological studies have been performed do not have any evidence of an accessory pathway or structural abnormality. Whilst in a minority of cases some form of intranodal or paranodal fibers that bypass all or part of the atrioventricular node can be found with subsequent conduction down the normal His-Purkinje system, in most cases the short PR interval is caused by accelerated conduction through the atrioventricular node. LGL syndrome is therefore felt to represent a clinical syndrome with multiple different underlying causes. Diagnosis LGL syndrome is diagnosed in a person who has experienced episodes of abnormal heart racing (arrhythmias) who has a PR interval less than or equal to 0.12 second (120 ms) with normal QRS complex configuration and duration on their resting ECG. A short PR interval found incidentally on an ECG without episodes of tachycardia is simply a benign ECG variant.LGL can be distinguished from WPW syndrome because the delta waves seen in WPW syndrome are not seen in LGL syndrome. The QRS complex will also be narrow in LGL syndrome, as opposed to WPW, because ventricular conduction is via the His-Purkinje system. Lown–Ganong–Levine syndrome is a clinical diagnosis that came about before the advent of electrophysiology studies. It is important to be aware that not all WPW ECGs have a delta wave; the absence of a delta wave does not conclusively rule out WPW. Prognosis Individuals with LGL syndrome do not carry an increased risk of sudden death. The only morbidity associated with the syndrome is the occurrence of paroxysmal episodes of tachycardia which may be of several types, including sinus tachycardia, atrioventricular nodal re-entrant tachycardia, atrial fibrillation, or atrial flutter. See also Cardiac electrophysiology Electrocardiogram Electrophysiology study Premature ventricular contraction Wolff–Parkinson–White syndrome References == External links ==
Vossius ring	Vossius ring (also called Vossiuss ring or Vossius ring) is due to blunt trauma to the eye. When the eye is injured, a circular ring of fainted or stippled opacity is seen on the anterior surface of the lens due to brown amorphous granules of pigment lying on the capsule. It has the same diameter as the contracted pupil, and is due to impression of the iris on the lens as a result of the force of a concussion injury, which drives the cornea and iris backward. It is named after German ophthalmologist Adolf Vossius, who first described the condition in 1906. References External links NIH website
Neonatal hypoglycemia	Neonatal hypoglycemia occurs when the neonates blood glucose level is less than the newborns body requirements for factors such as cellular energy and metabolism. There is inconsistency internationally for diagnostic thresholds. In the US, hypoglycemia is when the blood glucose level is below 30 mg/dL within the first 24 hours of life and below 45 mg/dL thereafter. In the UK, however, lower and more variable thresholds are used (<18 mg/dL at any time OR baby with abnormal clinical signs and a single value <45 mg/dL OR baby at risk of impaired metabolic adaptation but without abnormal clinical signs and a measurement <36 mg/dL and remaining <36 mg/dL at next measurement). The neonates gestational age, birth weight, metabolic needs, and wellness state of the newborn has a substantial impact on the neonates blood glucose level. There are known risk factors that can be both maternal and neonatal. This is a treatable condition. Its treatment depends on the cause of the hypoglycemia. Though it is treatable, it can be fatal if gone undetected. Hypoglycemia is the most common metabolic problem in newborns.Neonatal hypoglycemia occurs in between 1 in 3 births out of every 1,000 births but is hard to quantify internationally due to lack of consensus about diagnostic thresholds. It often occurs in premature babies, small full-term babies, babies of diabetic mothers, and is more common in neonatal hypoxic asphyxia, sclerosis, and infected sepsis. Severe hypoglycaemia with persistent or repeated episodes can cause damage to the central nervous system. Neonatal hypoglycaemia can be a stand-alone condition or a clinical manifestation of other conditions. Signs and symptoms The way in which neonatal hypoglycemia symptoms may be presented is vague or hard to tell apart from other conditions. The symptoms can be confused with: hypocalcemia Sepsis CNS disorders Cardiorespiratory problemsNeonatal hypoglycemia can also show no symptoms in some newborns or may be life-threatening.Some observed symptoms are (these symptoms may be transient but reoccurring): Jitteriness hypothermia irritability pallor tremors twitching weak or high pitched cry lethargy hypotonia generalized seizures coma cyanosis apnea rapid and irregular respirations diaphoresis eye rolling refusal to feed hunger Causes Risk Factors Mother Risk factors in the mother that increased the risk of developing hypoglycemia shortly after birth include: Type 1 diabetes Gestational diabetes mellitus (Transient) Intrapartum glucose administration (Transient) Gestational hypertension Preeclampsia Terbutaline administration (Transient) Intrauterine growth restriction (Transient) Perinatal stress or asphyxia (Transient) Baby Babies which have an increased risk of developing hypoglycemia shortly after birth are: hypothermia (Transient) polycythemia (Transient) hyperinsulinism (Recurrent) IEMs (Recurrent) Beckwith-Wiedmann syndrome (Recurrent) nesidioblastosis (Recurrent) Rh isoimmunization (Recurrent) Certain endocrine disorders (Recurrent) fetal hydrops Prematurity (Transient) congenital malformations small for gestational age (Transient) Large for gestational age (Transient) Hyperinsulinism The most common cause on neonatal hypoglycemia is hyperinsulinism. Hyperinsulinism is also called persistent hyperinsulemic hypoglycemia of infancy (PHHI). This is seen very frequently to the neonates born from mothers with diabetes. Congenital hyperinsulinism is correlated with the abnormality of beta-cell regulation within the pancreas. Isolated islet adenoma, which is a focal disease, is often the cause of congenital hyperinsulism. Drug-induced hyperinsulisim is correlated with the administration insulin or use of hypoglycemic medication. In critical cases, a drug called Diazoxide is availed to stop any secretion of insulin. Limited glycogen stores Limited glycogen storage occurs in premature newborns or newborns that had intrauterine growth retardation. Increased glucose use Major causes of increased glucose use in a newborn include hyperthermia, polycythemia, sepsis, and growth hormone deficiency. Decreased gluconeogenesis Two major issues that cause decreased gluconogeneis are inborn errors of metabolism and adrenal insufficiency. Depeleted glycogen stores Most common causes of depleted glycogen stores are starvation and asphyxia-perinatal stress. Mechanism There are many types of hypoglycemia, including transient and reoccurring. Each is associated with different risk factors and may have many underlying causes. Neonatal hypoglycemia occurs because an infants brain is dependent on a healthy supply of glucose. During the last trimester of pregnancy, glucose is stored in the liver, heart, and skeletal muscles. All newborns experience a physiological and transient fall in blood glucose, reaching a nadir at 2–3 hours of age before slowly rising over the next 24 hours. Newborns do have the ability to use an alternative form of energy, especially if breastfed. However, some newborns are only able to compensate this glucose deficiency up to a certain limit. Infants who have hyperinsulinism may increase the risk to develop hypoglycemia. There are other conditions that can increase the risk of an infant becoming hypoglycemic (See Risks). Diagnosis Screening for hypoglycemia is done on every neonate on admission in the USA but this is not recommended practice in all developed countries. One way of screening includes a heel stick to test the blood glucose level at the bedside. Diagnosing hypoglycemia in neonates requires two consecutive blood glucose readings of less than 40 mg/dL to properly diagnose hypoglycemia. Bedside glucose monitoring is only effective if the equipment is accurate, rapid, and reliable. This form of testing is often faster and more cost effective. Laboratory serum glucose testing is the most accurate way of testing blood glucose levels. These specimens are either taken from the heel, arterial, or venous punctures and must be store immediately on ice in order to prevent glycolysis, further altering the results. USA guidelines recommended that the hypoglycemic neonate should have a glucose test every 2–4 hours for the first 24 hours of life. Guidelines in the UK, however, recommend pre-feed screening of at-risk infants at 2–4 hours of age (to avoid false positives when blood glucose is, ordinarily, at its lowest at 2–3 hours of age) and at the subsequent feed until a blood glucose level of >2.0 mmol/L (36 mg/dL) on at least two consecutive occasions and is feeding well. 1. Medical history Maternal diabetes mellitus, gestational hypertension, neonatal erythrocytosis, neonatal haemolysis of incompatible blood groups, perinatal asphyxia, severe infection, sclerosis, neonatal respiratory distress syndrome, etc., especially in premature babies, babies younger than gestational age and those who are underfed in the early stages of life are at risk of neonatal hypoglycaemia. 2. Clinical manifestations Neonatal hypoglycemia should be considered if there are atypical clinical manifestations, if the symptoms improve after glucose infusion, or if there are neurological symptoms and signs that cannot be easily explained. 3. Blood glucose measurement Postnatal glucose monitoring is the main method of early detection of neonatal hypoglycaemia. In particular, children at risk of neonatal hypoglycaemia should have their blood glucose monitored within one hour of birth. Management Some infants are treated with 40% dextrose (a form of sugar) gel applied directly to the infants mouth. There are two main ways that neonatal hypoglycemia is treated. The first way includes intravenous infusion of glucose. For less severe, borderline, asymptomatic hypoglycemic neonates early introduction of breast milk can be effective for raising glucose levels to a healthy level. Any infant at risk of hypoglycemia should have their blood sugar taken again one hour after birth. Oral glucose is another option to restore normal glucose levels if the newborn is having difficulty latching to the breast or breastfeeding is not an option, however, breast milk is proven to be a better source as it includes glucose and carbohydrates. It is recommended by The American Academy of Pediatrics that infants feed within the first hour of life with the glucose reading being 30 minutes after this feeding for an accurate result. If the initial feeding does not raise the newborns blood glucose above 40 mg/dL then the newborn must receive an IV infusion of 10% dextrose in water as a mini bolus as 2 mL/kg over 1 minute. Following the mini bolus a continuous infusion of 10% dextrose in water at 80-100 mL/kg/day in order to maintain a healthy serum glucose level between 40 and 50 mg/dL. Maintaining newborn thermoregulation is a large part in preventing further hypoglycemia as well. Nursing care management The biggest nursing concern for a neonate experiencing hypoglycemia is the physical assessment to potentially find the cause. It is also essential to prevent environmental factors such as cold stress that may predispose the newborn for further decreasing blood sugar. Within the physical assessment, comorbidities of hypoglycemia should also be assessed such as intolerance of feeding, or respiratory distress. Another important nursing intervention is assisting the mother in successful breastfeeding as this can prevent and treat hypoglycemia.If an IV infusion of 10% dextrose in water is initiated then the nurse must monitor for: •Circulatory overload•Hyperglycemia•Glycosuria•Intracellular dehydration Outcomes Infants that experienced hypoglycemic episodes requiring treatment within the first few days of life have a higher chance of developing neurological or neurodevelopmental diagnoses than normoglycemic infants. The severity of the effects resulting from the hypoglycemic episode depend on the length of the hypoglycemic episode and how low the neonates blood glucose levels drop during the episode. Because glucose is an essential nutrient for the brain, untreated neonatal hypoglycemia causes irreversible damage to both the posterior occipital and cortex regions of the brain. These areas function in cognition, adaptability, and visual skills. Long term complications of neonatal hypoglycemia may include: Neurologic damage that results in mental retardation Developmental delay Personality disorders Recurrent seizure activity Impaired cardiovascular function Research Continuous glucose monitoring devices have been suggested to be helpful for improving blood glucose monitoring in neonatal infants, however, the devices have not been approved for use in this age group and the potential benefits and risks are not clear from available studies.The taḥnīk also exercises the muscles of the mouth and helps with the circulation of blood in the mouth - this may help the baby to be able to suck and take mothers milk. It is also credited to prevent neonatal hypoglycemia in newborn babies. See also Congenital hyperinsulinism Hyperinsulinemic hypoglycemia References Bibliography Walker, Marsha (2011). Breastfeeding management for the clinician : using the evidence. Sudbury, Mass: Jones and Bartlett Publishers. ISBN 9780763766511.
Spindle cell lipoma	Spindle cell lipoma is an asymptomatic, slow-growing subcutaneous tumor that has a predilection for the posterior back, neck, and shoulders of older men.: 625 See also Intradermal spindle cell lipoma List of cutaneous conditions References == External links ==
Congenital hyperinsulinism	Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and most become apparent in early infancy. Mild cases can be treated by frequent feedings, more severe cases can be controlled by medications that reduce insulin secretion or effects. Signs and symptoms Hypoglycemia in early infancy can cause jitteriness, lethargy, unresponsiveness, or seizures. The most severe forms may cause macrosomia in utero, producing a large birth weight, often accompanied by abnormality of the pancreas. Milder hypoglycemia in infancy causes hunger every few hours, with increasing jitteriness or lethargy. Milder forms have occasionally been detected by investigation of family members of infants with severe forms, adults with the mildest degrees of congenital hyperinsulinism have a decreased tolerance for prolonged fasting.Other presentations are: Dizziness Intellectual disability Hypoglycemic coma CardiomegalyThe variable ages of presentations and courses suggest that some forms of congenital hyperinsulinism, especially those involving abnormalities of KATP channel function, can worsen or improve with time. The potential harm from hyperinsulinemic hypoglycemia depends on the severity, and duration. Children who have recurrent hyperinsulinemic hypoglycemia in infancy can suffer harm to the brain. Cause The cause of congenital hyperinsulinism has been linked to anomalies in nine genes. The diffuse form of this condition is inherited via the autosomal recessive manner (though sometimes in autosomal dominant). Pathophysiology In terms of the mechanism of congenital hyperinsulinism one sees that channel trafficking requires KATP channels need the shielding of ER retention signal.E282K prevents the KATP channel surface expression, the C-terminus (SUR1 subunit) is needed in KATP channel mechanism.R1215Q mutations (ABCC8 gene) affect ADP gating which in turn inhibits KATP channel. Diagnostic In terms of the investigation of congenital hyperinsulinism, valuable diagnostic information is obtained from a blood sample drawn during hypoglycemia, detectable amounts of insulin during hypoglycemia are abnormal and indicate that hyperinsulinism is likely to be the cause. Inappropriately low levels of free fatty acids and ketones provide additional evidence of insulin excess. An additional piece of evidence indicating hyperinsulinism is a usually high requirement for intravenous glucose to maintain adequate glucose levels, the minimum glucose required to maintain a plasma glucose above 70 mg/dl. A GIR above 8 mg/kg/minute in infancy suggests hyperinsulinism. A third form of evidence suggesting hyperinsulinism is a rise of the glucose level after injection of glucagon at the time of the low glucose.Diagnostic efforts then shift to determining the type- elevated ammonia levels or abnormal organic acids can indicate specific, rare types. Intrauterine growth retardation and other perinatal problems raise the possibility of transience, while large birthweight suggests one of the more persistent conditions. Genetic screening is now available within a useful time frame for some of the specific conditions. It is worthwhile to identify the minority of severe cases with focal forms of hyperinsulinism because these can be completely cured by partial pancreatectomy. A variety of pre-operative diagnostic procedures have been investigated but none has been established as infallibly reliable. Positron emission tomography is becoming the most useful imaging technique. Differential diagnosis The differential diagnosis of congenital hyperinsulinism is consistent with PMM2-CDG, as well as several syndromes. Among other diagnoses, the following are listed: MPI-CDG Beckwith-Wiedemann syndrome Sotos syndrome Usher 1 syndromes Types Congenital hyperinsulinism has two types, diffuse and focal, as indicated below: Treatment In terms of treatment, acute hypoglycemia is reversed by raising the blood glucose, but in most forms of congenital hyperinsulinism hypoglycemia recurs and the therapeutic effort is directed toward preventing falls and maintaining a certain glucose level. Some of the following measures are often tried: Corn starch can be used in feeding; unexpected interruptions of continuous feeding regimens can result in sudden hypoglycemia, gastrostomy tube insertion (requires a minor surgical procedure) is used for such feeding. Prolonged glucocorticoid use incurs the many unpleasant side effects of Cushings syndrome, while diazoxide can cause fluid retention requiring concomitant use of a diuretic, and prolonged use causes hypertrichosis. Diazoxide works by opening the KATP channels of the beta cells. Octreotide must be given by injection several times a day or a subcutaneous pump must be inserted every few days, octreotide can cause abdominal discomfort and responsiveness to octreotide often wanes over time. Glucagon requires continuous intravenous infusion, and has a very short half-life.Nifedipine is effective only in a minority, and dose is often limited by hypotension. Pancreatectomy (removal of a portion or nearly all of the pancreas) is usually a treatment of last resort when the less-drastic medical measures fail to provide prolonged normal blood sugar levels. For some time, the most common surgical procedure was removal of almost all of the pancreas; this cured some infants but not all. Insulin-dependent diabetes mellitus commonly develops, though in many cases it occurs many years after the pancreatectomy. Later it was discovered that a sizeable minority of cases of mutations were focal, involving overproduction of insulin by only a portion of the pancreas. These cases can be cured by removing much less of the pancreas, resulting in excellent outcomes with fewer long-term problems. History This condition has been referred to by a variety of names in the past 50 years; nesidioblastosis and islet cell adenomatosis were favored in the 1970s, beta cell dysregulation syndrome or dysmaturation syndrome in the 1980s, and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the 1990s. See also Hyperammonemia List of congenital disorders References Further reading Hoyme, Louanne Hudgins; Toriello, Helga V.; Enns, Gregory M.; Hoyme, H. Eugene (2014). Signs and symptoms of genetic disease : a handbook. Oxford: Oxford University Press. ISBN 9780199930975. Hertz, David E., ed. (2005). Care of the newborn a handbook for primary care. Philadelphia: Lippincott Williams & Wilkins. ISBN 9780781755856. External links PubMed
Hypocalciuria	Hypocalciuria is a low level of calcium in the urine. It is a significant risk factor for predicting eclampsia in pregnancy. The most common causes for hypocalciuria is either thiazide diuretics or reduced dietary intake of calcium. The other cause is Familial hypocalciuric hypercalcemia (FHH). Low dietary sodium causes hypocalciuria. It is also common in patients with Gitelman syndrome. == References ==
Acute fatty liver of pregnancy	Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy that occurs in the third trimester or the immediate period after delivery. It is thought to be caused by a disordered metabolism of fatty acids by mitochondria in the fetus, caused by long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. This leads to decreased metabolism of long chain fatty acids by the feto-placental unit, causing subsequent rise in hepatotoxic fatty acids in maternal plasma. The condition was previously thought to be universally fatal, but aggressive treatment by stabilizing the mother with intravenous fluids and blood products in anticipation of early delivery has improved prognosis. Signs and symptoms Acute fatty liver of pregnancy (or hepatic lipidosis of pregnancy) usually manifests in the third trimester of pregnancy, but may occur any time in the second half of pregnancy, or in the puerperium, the period immediately after delivery. On average, the disease presents during the 35th or 36th week of pregnancy. The usual symptoms in the mother are non-specific including nausea, vomiting, anorexia (or lack of desire to eat) and abdominal pain; excessive thirst may be the earliest symptom without overlap with otherwise considered normal pregnancy symptoms; however, jaundice and fever may occur in as many as 70% of patients.In patients with more severe disease, pre-eclampsia may occur, which involves elevation of blood pressure and accumulation of fluid (termed oedema). This may progress to involvement of additional systems, including acute kidney failure, hepatic encephalopathy, and pancreatitis. There have also been reports of diabetes insipidus complicating this condition.Many laboratory abnormalities are seen in acute fatty liver of pregnancy. Liver enzymes are elevated, with the AST and ALT enzymes ranging from minimal elevation to 1000 IU/L, but usually staying in the 300-500 range. Bilirubin is almost universally elevated. Alkaline phosphatase is often elevated in pregnancy due to production from the placenta, but may be additionally elevated. Other abnormalities may include an elevated white blood cell count, hypoglycemia, elevated coagulation parameters, including the international normalized ratio, and decreased fibrinogen. Frank disseminated intravascular coagulation, or DIC, may occur in as many as 70% of people.Abdominal ultrasound may show fat deposition in the liver, but, as the hallmark of this condition is microvesicular steatosis (see pathology below), this is not seen on ultrasound. Rarely, the condition can be complicated by rupture or necrosis of the liver, which may be identified by ultrasound. Pathophysiology The understanding of the causes of acute fatty liver of pregnancy has been improved by advances in mitochondrial biochemistry. Deficiency of LCHAD (3-hydroxyacyl-CoA dehydrogenase) leads to an accumulation of medium and long chain fatty acids. When this occurs in the foetus, the unmetabolized fatty acids will re-enter the maternal circulation through the placenta, and overwhelm the beta-oxidation enzymes of the mother. The gene responsible for LCHAD has been isolated, and the most common mutation found in acute fatty liver of pregnancy is the E474Q missense mutation. LCHAD deficiency is autosomal recessive in inheritance and mothers are often found to be heterozygous for the affected mutation. Diagnosis The diagnosis of acute fatty liver of pregnancy is usually made on clinical grounds by the treating physician, but differentiation from other conditions affecting the liver may be difficult. The diagnosis of acute fatty liver of pregnancy is suggested by jaundice with a lesser elevation of liver enzymes, elevated white blood cell count, disseminated intravascular coagulation, and a clinically unwell patient.A liver biopsy can provide a definitive diagnosis, but is not always done, due to the increased chance of bleeding in acute fatty liver of pregnancy. Often testing will be done to exclude more common conditions that present in a similar fashion, including viral hepatitis, pre-eclampsia, HELLP syndrome, intrahepatic cholestasis of pregnancy, and autoimmune hepatitis. Pathology If a liver biopsy is needed for diagnosis of the condition, the mother should be appropriately stabilized and treated to reduce bleeding related complications. The diagnosis can be made by a frozen-section (as opposed to a specimen in formalin) that is stained with the Oil red O stain, that shows microvesicular steatosis (or small collections of fat within the liver cells). The microvesicular steatosis usually spares zone one of the liver, which is the area closest to the hepatic artery. On the regular trichrome stain, the liver cell cytoplasm shows a foamy appearance due to the prominence of fat. Necrosis is rarely seen. The diagnosis can be enhanced by electron microscopy which can be used to confirm the presence of microvesicular steatosis, and specifically the presence of megamitochondria and paracrystalline inclusions. Liver diseases with similar appearances include Reyes syndrome, drug-induced hepatitis from agents with mitochondrial toxicity, including nucleoside reverse transcriptase inhibitors used to treat HIV, and a rare condition known as Jamaican vomiting sickness which is caused by the eating of the unripened Ackee fruit. Treatment Acute fatty liver of pregnancy is best treated in a centre with expertise in hepatology, high-risk obstetrics, maternal-fetal medicine and neonatology. The physicians who treat this condition will often consult with experts in liver transplantation in severe cases. Admission to the intensive care unit is recommended.Initial treatment involves supportive management with intravenous fluids, intravenous glucose and blood products, including fresh frozen plasma and cryoprecipitate to correct DIC. The foetus should be monitored with cardiotocography. After the mother is stabilized, arrangements are usually made for delivery. This may occur vaginally, but, in cases of severe bleeding or compromise of the mothers status, a caesarian section may be needed. Often AFLP is not diagnosed until the mother and baby are in trouble, so it is most likely that an emergency C-section is needed.The complications of acute fatty liver of pregnancy may require treatment after delivery, especially if pancreatitis occurs. Liver transplantation is rarely required for treatment of the condition, but may be needed for mothers with severe DIC, those with rupture of the liver, or those with severe encephalopathy. Epidemiology Acute fatty liver of pregnancy is a rare condition and occurs in approximately one in 7,000 to one in 15,000 pregnancies. The mortality from acute fatty liver of pregnancy has been reduced significantly to 18%, and is now related primarily to complications, particularly DIC (Disseminated Intravascular Coagulation) and infections. After delivery, most mothers do well, as the stimulus for fatty acid overload is removed. The disease can recur in future pregnancies, with a calculated genetic chance of 25%; the actual rate is lower, however. Mortality of the foetus has also diminished significantly, but still remains 23%, and may be related to the need for premature delivery. History The disease was first described in 1940 by H. L. Sheehan as an "acute yellow atrophy" of the liver, then thought to be related to delayed chloroform poisoning. See also Fatty liver References == External links ==
Angiolipoma	Angiolipoma is a subcutaneous nodule with vascular structure, having all other features of a typical lipoma. They are commonly painful.: 624 Pathology Histopathology Diagnosis Differential diagnosis Kaposi sarcoma Angiosarcoma See also Lipoma Skin lesion List of cutaneous conditions References == External links ==
Supraspinatus muscle	The supraspinatus (plural supraspinati) is a relatively small muscle of the upper back that runs from the supraspinous fossa superior portion of the scapula (shoulder blade) to the greater tubercle of the humerus. It is one of the four rotator cuff muscles and also abducts the arm at the shoulder. The spine of the scapula separates the supraspinatus muscle from the infraspinatus muscle, which originates below the spine. Structure The supraspinatus muscle arises from the supraspinous fossa, a shallow depression in the body of the scapula above its spine. The supraspinatus muscle tendon passes laterally beneath the cover of the acromion. Research in 1996 showed that the postero-lateral origin was more lateral than classically described.The supraspinatus tendon is inserted into the superior facet of the greater tubercle of the humerus. The distal attachments of the three rotator cuff muscles that insert into the greater tubercle of the humerus can be abbreviated as SIT when viewed from superior to inferior (for supraspinatus, infraspinatus, and teres minor), or SITS when the subscapularis muscle, which attaches to the lesser tubercle of the humerus, is included. Nerve supply The suprascapular nerve (C5) innervates the supraspinatus muscle as well as the infraspinatus muscle. It comes from the upper trunk of the brachial plexus. This nerve can be damaged along its course in fractures of the overlying clavicle, which can reduce the persons ability to initiate the abduction. Function The supraspinatus muscle performs abduction of the arm, and pulls the head of the humerus medially towards the glenoid cavity. It independently prevents the head of the humerus from slipping inferiorly. The supraspinatus works in cooperation with the deltoid muscle to perform abduction, including when the arm is in an adducted position. Beyond 15 degrees the deltoid muscle becomes increasingly more effective at abducting the arm and becomes the main propagator of this action. Clinical significance The supraspinatus forms part of the rotator cuff and is one of its most frequently damaged components, whether from acute injury or gradual degeneration. Bad posture and age are leading risk factors, with a high prevalence of unsymptomatic partial and full tears, as well as symptomatic syndromes with chronic pain. Connected pathologies include acromial impingement, frozen shoulder, and poor sleep, especially on the side. Both ultrasound and MRI are now effective methods of diagnosis. Tear DiagnosisAntero-posterior projectional radiography of the shoulder may demonstrate a high-riding humeral head, with an acromiohumeral distance of less than 7 mm. RepairOne study has indicated that arthroscopic surgery for full-thickness supraspinatus tears is effective for improving shoulder functionality.A comparative effectiveness review of nonoperative and operative treatments for rotator cuff tears was performed at the University of Alberta Evidence-based Practice Center in 2010. The review identified one study which reported that, "Patients receiving early surgery had superior function compared with the delayed surgical group". The review noted that the level of significance of the study was not reported, and the review chose not to include it as one of their conclusions. Instead it concluded that "The paucity of evidence related to early versus delayed surgery is of particular concern, as patients and providers must decide whether to attempt initial nonoperative management or proceed immediately with surgical repair". In terms of operative techniques, differences in neither cuff integrity nor shoulder function were reported in studies comparing single-row versus double-row suture anchor fixation and mattress locking versus absorbable sutures. Postoperatively, a slight advantage was evident in patients who performed continuous passive motion alongside physical therapy, as opposed to those who solely performed physical therapy. There is insufficient evidence to adequately compare the effects of operative against nonoperative interventions. Complications were reported very seldom, or were not determined to be clinically significant.A 2016 study evaluating the effectiveness of arthroscopic treatment of rotator cuff calcification firmly supported surgical intervention. Calcification of the supraspinatus tendon is a major contributor to shoulder pain in the general population and is often worsened following a supraspinatus tear. The results of the study included the return to sports and original functionality of 95.8% of the patients after a mean of 5.3 post-operative months. A significant decrease in pain was observed over time following removal of the calcification. The study showed the overall effectiveness of arthroscopic procedures on shoulder repair, and the lack of risk experienced. Before surgery, supraspinatus tendonitis should be ruled out as the cause of pain. Additional images References External links GoogleBody - Supraspinatus muscle
Short anagen syndrome	Short anagen syndrome is a condition where hair does not grow beyond a short length, due to an unusually short duration of active hair growth (anagen phase). Most cases are associated with fine blond hair. See also List of cutaneous conditions == References ==
Accommodative excess	In ophthalmology, accommodative excess (also known as excessive accommodation or accommodation excess) occurs when an individual uses more than normal accommodation (focusing on close objects) for performing certain near work. Accommodative excess has traditionally been defined as accommodation that is persistently higher than expected for the patients age. Modern definitions simply regard it as an inability to relax accommodation readily. Excessive accommodation is seen in association with excessive convergence also. Symptoms and signs Blurring of vision due to pseudomyopia Headache Eye strain Asthenopia Trouble concentrating when reading Causes Causes related to refractive errors Accommodative excess may be seen in the following conditions: Hypermetropia: Young hypermetropes use excessive accommodation as a physiological adaptation in the interest of clear vision. Myopia: Young myopes performing excessive near work may also use excessive accommodation in association with excessive convergence. Astigmatism: Astigmatic eye may also be associated with accommodative excess. Presbyopia: Early presbyopic eye may also induce excessive accommodation. Improper or ill fitting spectacles: Use of improper or ill fitting spectacles may also cause use of excessive accommodation. Causes related to systemic drugs Use of systemic drugs like Morphine, Digitalis, Sulfonamides, Carbonic anhydrase inhibitors may cause accommodative excess. Causes related to diseases Unilateral excessive accommodation-Trigeminal neuralgia, and head trauma may cause ciliary spasm and may cause accommodative excess. Bilateral excessive accommodation-Diseases like Encephalitis, Syphilis, Head trauma, Influenza, Meningitis may cause ciliary spasm and bilateral excessive accommodation. Secondary to Convergence insufficiency Accommodative excess may occur secondary to convergence insufficiency also. In convergence insufficiency near point of convergence will recede, and positive fusional vergence (PFV) will reduce. So, the patient uses excessive accommodation to stimulate accommodative convergence to overcome reduced PFV. Risk factors A large amount of near work is the main precipitating factor of accommodative excess. Pseudomyopia Pseudomyopia also known as artificial myopia refers to an intermittent and temporary shift in refractive error of the eye towards myopia. It may occur due to excessive accommodation or spasm of accommodation. Diagnosis Differential diagnosis Parinaud’s syndrome, which can mimic some aspects of spasm of the near reflex, such as excessive accommodation and convergence; however, pupillary near-light dissociation, not miosis, is a feature of Parinaud’s syndrome. Treatment Optical: Cycloplegic refraction, and correction of Refractive errors if any Vision therapy General: Relax from near work See also Spasm of accommodation Convergence excess == References ==
Hypersensitivity pneumonitis	Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis (EAA) is a syndrome caused by the repetitive inhalation of antigens from the environment in susceptible or sensitized people. Common antigens include molds, bacteria, bird droppings, bird feathers, agricultural dusts, bioaerosols and chemicals from paints or plastics. People affected by this type of lung inflammation (pneumonitis) are commonly exposed to the antigens by their occupations, hobbies, the environment and animals. The inhaled antigens produce a hypersensitivity immune reaction causing inflammation of the airspaces (alveoli) and small airways (bronchioles) within the lung. Hypersensitivity pneumonitis may eventually lead to interstitial lung disease. Signs and symptoms Hypersensitivity pneumonitis (HP) can be categorized as acute, subacute, and chronic based on the duration of the illness. Acute In the acute form of HP dose of antigen exposure tends to be very high but only for a short duration. Symptoms may develop 4–6 hours following heavy exposure to the provoking antigen. Symptoms include fever, chills, malaise, cough, chest tightness, dyspnea, rash, swelling and headache. Symptoms resolve within 12 hours to several days upon cessation of exposure. Subacute Patients with subacute HP gradually develop a productive cough, dyspnea, fatigue, anorexia, weight loss, and pleurisy. Symptoms are similar to the acute form of the disease, but are less severe and last longer. Findings may be present in patients who have experienced repeated acute attacks. Chronic In chronic HP, dose of the antigen tends to be low volume but for a longer duration. Patients often lack a history of acute episodes. They have an insidious onset of cough, progressive dyspnea, fatigue, and weight loss. This is associated with partial to complete but gradual reversibility. Avoiding any further exposure is recommended. Clubbing is observed in 50% of patients. Tachypnea, respiratory distress, and inspiratory crackles over lower lung fields often are present. In fact, hypersensitivity pneumonitis can often resemble (IPF) in terms of pulmonary fibrosis and that many patients experience hypoxemia. Epidemiology Although the prevalence of hypersensitivity pneumonitis is not established it is thought to be low. Data collection limitations are a result of difficulty in diagnosis, sub-clinical presentations that go undetected and variability in climate, region and proximity to local industries. The most common types are bird fanciers and farmers lung. Interestingly, cigarette smoking appears to be protective against the disease. Pathophysiology Hypersensitivity pneumonitis is caused by an exaggerated immune response (hypersensitivity). Type III hypersensitivity and type IV hypersensitivity can both occur depending on the cause. In general, acute HP is suspected to be attributed to a type III hypersensitivity while the subacute and chronic types are suspected to be caused by T cell infiltration and granuloma formation. Because different people react variably to antigen exposure, the exact mechanism is unclear but genetic and host factors are likely at play. The two hit hypothesis is often toted in the literature to explain why some people have a normal reaction to an antigenic exposure without clinical findings while others experience an exaggerated immune response. The "first hit" in the hypothesis is proposed to be genetic susceptibility and surrounding environmental factors and the "second hit" would be the introduction of the antigen into the respiratory system which causes the exaggerated immune response. Diagnosis The diagnosis is made through clinical judgement using a combination of findings because there does not exist a single, universal diagnostic criteria for the disease. The diagnosis is most commonly ascertained first with a detailed exposure history followed by a battery of clinical tests including: imaging, histopathology, pulmonary function testing, serology, bronchoscopy, and more. In 2020, official guidelines were published by American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax which provides a systematic approach to the diagnosis of HP that relies on high-resolution computed tomography. Exposure History A detailed occupational, home and environmental exposure history is the first step in diagnosis. Unfortunately, only 60% of inciting antigens are identified in exposure assessment. Re-exposure to the antigen can help aid in diagnosis. Standardized questionnaires have been created to help in obtaining an exposure history although no official questionnaire has been purported. It has been recommended that the questionnaire administered should be relevant to the region in which the exposure has potentially occurred.Detailed exposure assessments are warranted in the cause of damp indoor environments which have the potential to propagate mold throughout the dwelling. The decision to enlist an industrial hygienist should be made based on the answers to evidence based questions during the environmental assessment. The industrial hygeinst or environmental scientist will make the decision to conduct additional sampling. Types Hypersensitivity pneumonitis may also be called many different names, based on the provoking antigen. These include: Of these types, Farmers Lung and Bird-Breeders Lung are the most common. "Studies document 8-540 cases per 100,000 persons per year for farmers and 6000-21,000 cases per 100,000 persons per year for pigeon breeders. High attack rates are documented in sporadic outbreaks. Prevalence varies by region, climate, and farming practices. HP affects 0.4–7% of the farming population. Reported prevalence among bird fanciers is estimated to be 20-20,000 cases per 100,000 persons at risk." Imaging No single imaging finding is singularly definitive of a diagnosis rather clinicians rely on a constellation of findings. Both chest radiographs and high resolution CT scans can be normal. Chest Radiographs Acute presentation may reveal poorly defined a micro-nodular interstitial pattern and ground-glass opacities in the lower and mid lung zones. In addition to this, subacute presentations may show reticular nodular opacities in mid-to-lower lung zones. Chronic forms may show fibrotic changes and appear like Idiopathic pulmonary fibrosis. High-Resolution Computed Tomography This has become a common diagnostic imaging for the diagnosis and is the modality used in the Official ATS/JRS/ALAT Clinical Practice Guideline. Two forms of hypersensitivity pneumonitis are fibrotic and non-fibrotic findings on chest CT. The two differ in terms of their diagnostic work up and management although there is overall between them. The non-fibrotic form is typically characterized by ground glass opacities, mosaic attenuation, ill-defined centrilobular nodules (<5 mm), and air trapping. The fibrotic form is typically characterized by irregular linear opacities/coarse reticulations, traction bronchiectasis, and honeycombing, patchy ground-glass attenuation, centrilobular nodules, and mosaic attenuation. Three-density pattern (head cheese sign) is radiological sign which shows a region of the lung with three or more different types of attenuation which can be typical for the fibrotic type. Histopathology The acute form can be characterized by poorly formed noncaseating interstitial granulomas and mononuclear cell infiltration in a peribronchial distribution with prominent giant cells. The subacute, or intermittent, form produces more well-formed noncaseating granulomas, bronchiolitis with or without organizing pneumonia, and interstitial fibrosis. Much like the pathogenesis of idiopathic pulmonary fibrosis (IPF), chronic HP is related to increased expression of Fas antigen and Fas ligand, leading to increased epithelial apoptosis activation in the alveoli. Cholesterol clefts or asteroid bodies are present within or outside granulomas. Pulmonary Function Testing Pulmonary function tests (PFTs) can generally reveal a restrictive pattern however, either a restrictive or obstructive pattern (or both) may emerge on PFTs. PFTs, therefore, are less useful in making a diagnosis but rather tracking improvement or deterioration in lung function following removal or addition of suspected antigens. They may also demonstrate reduced diffusion capacity of lungs for carbon monoxide (DLCO). Bronchoscopy Bronchoalveolar lavage (BAL) is a reliable way to detect inflammation in the lung airways. Fluid analysis from the lavage extracted from the airways on bronchoscopy often reveals a total elevation in cell count in addition to an elevation in the percentage of T lymphocytes. This is a good way to help exclude other similar lung diseases like sarcoidosis, infection and Idiopathic pulmonary fibrosis. Lung biopsy Lung biopsies can be diagnostic in cases of chronic hypersensitivity pneumonitis, or may help to suggest the diagnosis and trigger or intensify the search for an allergen. The main feature of chronic hypersensitivity pneumonitis on lung biopsies is expansion of the interstitium by lymphocytes accompanied by an occasional multinucleated giant cell or loose granuloma.When fibrosis develops in chronic hypersensitivity pneumonitis, the differential diagnosis in lung biopsies includes the idiopathic interstitial pneumonias. This group of diseases includes usual interstitial pneumonia, non-specific interstitial pneumonia and cryptogenic organizing pneumonia, among others.The prognosis of some idiopathic interstitial pneumonias, e.g. idiopathic usual interstitial pneumonia (i.e. idiopathic pulmonary fibrosis), are very poor and the treatments of little help. This contrasts the prognosis (and treatment) for hypersensitivity pneumonitis, which is generally fairly good if the allergen is identified and exposures to it significantly reduced or eliminated. Thus, a lung biopsy, in some cases, may make a decisive difference. Serum Precipitins Assays for serum IgGs can aid in identifying possible antigenic exposures and are used as markers of exposure However, there use is limited in making a definitive diagnosis because serum antibody levels are often elevated in those people who are exposed to an antigen but do not have the disease. Up to 90% of people exposed to the antigen have precipitins but only 50% of similarly exposed people who are asymptomatic have the same precipitins. False negatives are often common with serum precipitins because of lack of testing reagents for many antigens.Precipitating IgG antibodies against fungal or avian antigens can be detected in the laboratory using the traditional Ouchterlony immunodiffusion method wherein precipitin lines form on agar plate. The ImmunoCAP technology has replaced this time-consuming, labor-intensive method with their automated CAP assays and FEIA (Fluorescence enzyme immunoassay) that can detect IgG antibodies against Aspergillus fumigatus (Farmers lung or for ABPA) or avian antigens (Bird Fanciers Lung). Differential Diagnosis Organic dust toxic syndrome presents similarly with fevers, chills a few hours after exposure to bioaerosols with toxins from fungi, however this is not a true hypersensitivity reaction because it occurs on initial exposure without a preceding sensitization In chronic disease, HP must be differentiated from very similarly presenting idiopathic pulmonary fibrosis.Although overlapping in many cases, hypersensitivity pneumonitis may be distinguished from occupational asthma in that it is not restricted to only occupational exposure, and that asthma generally is classified as a type I hypersensitivity. Unlike asthma, hypersensitivity pneumonitis targets lung alveoli rather than bronchi.Similarly, sarcoidosis has noncaseating granuloma formation, however hilar adenopathy is often seen on chest radiographs. Treatment The best treatment is to avoid the provoking allergen, as chronic exposure can cause permanent damage and acute disease is often self-limiting. The identification of the provoking antigen and its location must be ascertained by conducting an exposure assessment. Home cleaning is one method of antigen avoidance. If avoidance is not possible, such as in the case of some workplace exposures, minimizing exposure can be accomplished through various means including the implementation of PPE or proper ventilation of a workplace. Corticosteroids such as prednisolone may help to control symptoms but may produce side-effects. In the case of severe, end-stage pulmonary fibrosis arising from chronic exposure, lung transplant may be the only viable option. In addition to steroids for fibrotic disease, other immunosuppressants (Azathioprine, Mycophenolic acid) and anti-fibrotic agents (Nintedanib) may be used although their effectiveness is unclear Prognosis There are few studies examining longitudinal outcomes in patients diagnosed with hypersensitivity pneumonitis. One study in the US showed about a 0.09 to 0.29 per million increase in mortality rates although the cause specific cause was unclear. Most of the outcomes collected are from patients diagnosed with farmers or bird breeders lung and thus the degree to which this data can be extrapolated to other types of HP is uncertain. Generally outcomes for HP in those with acute disease are very good if exposure is avoided. However, those with subacute or chronic type, especially with biopsy proven fibrosis fair much poorer death rates comparable to people diagnosed with Interstitial pulmonary fibrosis. Additional images See also Dust pneumonia Pneumonitis References == External links ==
Bruise	A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises are not very deep under the skin so that the bleeding causes a visible discoloration. The bruise then remains visible until the blood is either absorbed by tissues or cleared by immune system action. Bruises which do not blanch under pressure can involve capillaries at the level of skin, subcutaneous tissue, muscle, or bone. Bruises are not to be confused with other similar-looking lesions. (Such lesions include petechia (less than 3 mm (0.12 in), resulting from numerous and diverse etiologies such as adverse reactions from medications such as warfarin, straining, asphyxiation, platelet disorders and diseases such as cytomegalovirus), purpura (3–10 mm (0.12–0.39 in), classified as palpable purpura or non-palpable purpura and indicates various pathologic conditions such as thrombocytopenia), and ecchymosis (more than 1 cm (0.39 in), caused by blood dissecting through tissue planes and settled in an area remote from the site of trauma or pathology such as periorbital ecchymosis, e.g. "raccoon eyes", arising from a basilar skull fracture or from a neuroblastoma).As a type of hematoma, a bruise is always caused by internal bleeding into the interstitial tissues which does not break through the skin, usually initiated by blunt trauma, which causes damage through physical compression and deceleration forces. Trauma sufficient to cause bruising can occur from a wide variety of situations including accidents, falls, and surgeries. Disease states such as insufficient or malfunctioning platelets, other coagulation deficiencies, or vascular disorders, such as venous blockage associated with severe allergies can lead to the formation of purpura which is not to be confused with trauma-related bruising/contusion. If the trauma is sufficient to break the skin and allow blood to escape the interstitial tissues, the injury is not a bruise but bleeding, a different variety of hemorrhage. Such injuries may be accompanied by bruising elsewhere. Signs and symptoms Bruises often induce pain immediately after the trauma that results in their formation, but small bruises are not normally dangerous alone. Sometimes bruises can be serious, leading to other more life-threatening forms of hematoma, such as when associated with serious injuries, including fractures and more severe internal bleeding. The likelihood and severity of bruising depends on many factors, including type and healthiness of affected tissues. Minor bruises may be easily recognized in people with light skin color by characteristic blue or purple appearance (idiomatically described as "black and blue") in the days following the injury. Hematomas can be subdivided by size. By definition, ecchymoses are 1 centimetres in size or larger, and are therefore larger than petechiae (less than 3 millimetres in diameter) or purpura (3 to 10 millimetres in diameter). Ecchymoses also have a more diffuse border than other purpura. A broader definition of ecchymosis is the escape of blood into the tissues from ruptured blood vessels. The term also applies to the subcutaneous discoloration resulting from seepage of blood within the injured tissue. Bruise colors vary from red, blue, or almost black, depending on the severity of broken capillaries or blood vessels within the bruise site. Broken venules or arterioles often result in a deep blue or dark red bruise, respectively. Darker colored bruises may result from a more severe bleeding from both blood vessels. Older bruises may appear yellow, green or brown. Cause There are many causes of subcutaneous hematomas including ecchymoses. Coagulopathies such as Hemophilia A may cause ecchymosis formation in children. The medication betamethasone can have the adverse effect of causing ecchymosis.The presence of bruises may be seen in patients with platelet or coagulation disorders, or those who are being treated with an anticoagulant. Unexplained bruising may be a warning sign of child abuse, domestic abuse, or serious medical problems such as leukemia or meningoccocal infection. Unexplained bruising can also indicate internal bleeding or certain types of cancer. Long-term glucocorticoid therapy can cause easy bruising. Bruising present around the navel (belly button) with severe abdominal pain suggests acute pancreatitis. Connective tissue disorders such as Ehlers-Danlos syndrome may cause relatively easy or spontaneous bruising depending on the severity. Spontaneous bruising or bruising with minimal trauma in the absence of other explanations and together with other minor or major criteria suggestive of Vascular Ehlers-Danlos Syndrome (vEDS) suggests genetic testing for the condition.During an autopsy, bruises accompanying abrasions indicate the abrasions occurred while the individual was alive, as opposed to damage incurred post mortem. Size and shape Bruise shapes may correspond directly to the instrument of injury or be modified by additional factors. Bruises often become more prominent as time lapses, resulting in additional size and swelling, and may grow to a large size over the course of the hours after the injury that caused the bruise was inflicted. Condition and type of tissue: In soft tissues, a larger area is bruised than would be in firmer tissue due to ease of blood to invade tissue. Age: elderly skin and other tissues are often thinner and less elastic and thus more prone to bruising. Gender: More bruising occurs in females due to increased subcutaneous fat. Skin tone: Discoloration caused by bruises is more prominent in lighter complexions. Diseases: Coagulation, platelet and blood vessel diseases or deficiencies can increase bruising due to more bleeding. Location: More extensive vascularity causes more bleeding. Areas such as the arms, knees, shins and the facial area are especially common bruise sites. Forces: Greater striking forces cause greater bruising. Genes: Despite having completely normal coagulation factors, natural redheads have been shown to bruise more, although this may just be due to greater visibility on commonly associated lighter complexion. Severity Bruises can be scored on a scale from 0–5 to categorize the severity and danger of the injury. The harm score is determined by the extent and severity of the injuries to the organs and tissues causing the bruising, in turn depending on multiple factors. For example, a contracted muscle will bruise more severely, as will tissues crushed against underlying bone. Capillaries vary in strength, stiffness and toughness, which can also vary by age and medical conditions. Low levels of damaging forces produce small bruises and generally cause the individual to feel minor pain straight away. Repeated impacts worsen bruises, increasing the harm level. Normally, light bruises heal nearly completely within two weeks, although duration is affected by variation in severity and individual healing processes; generally, more severe or deeper bruises take somewhat longer. Severe bruising (harm score 2–3) may be dangerous or cause serious complications. Further bleeding and excess fluid may accumulate causing a hard, fluctuating lump or swelling hematoma. This has the potential to cause compartment syndrome in which the swelling cuts off blood flow to the tissues. The trauma that induced the bruise may also have caused other severe and potentially fatal harm to internal organs. For example, impacts to the head can cause traumatic brain injury: bleeding, bruising and massive swelling of the brain with the potential to cause concussion, coma and death. Treatment for brain bruising may involve emergency surgery to relieve the pressure on the brain. Damage that causes bruising can also cause bones to be broken, tendons or muscles to be strained, ligaments to be sprained, or other tissue to be damaged. The symptoms and signs of these injuries may initially appear to be those of simple bruising. Abdominal bruising or severe injuries that cause difficulty in moving a limb or the feeling of liquid under the skin may indicate life-threatening injury and require the attention of a physician. Mechanism Increased distress to tissue causes capillaries to break under the skin, allowing blood to escape and build up. As time progresses, blood seeps into the surrounding tissues, causing the bruise to darken and spread. Nerve endings within the affected tissue detect the increased pressure, which, depending on severity and location, may be perceived as pain or pressure or be asymptomatic. The damaged capillary endothelium releases endothelin, a hormone that causes narrowing of the blood vessel to minimize bleeding. As the endothelium is destroyed, the underlying von Willebrand factor is exposed and initiates coagulation, which creates a temporary clot to plug the wound and eventually leads to restoration of normal tissue. During this time, larger bruises may change color due to the breakdown of hemoglobin from within escaped red blood cells in the extracellular space. The striking colors of a bruise are caused by the phagocytosis and sequential degradation of hemoglobin to biliverdin to bilirubin to hemosiderin, with hemoglobin itself producing a red-blue color, biliverdin producing a green color, bilirubin producing a yellow color, and hemosiderin producing a golden-brown color. As these products are cleared from the area, the bruise disappears. Often the underlying tissue damage has been repaired long before this process is complete. Treatment Treatment for light bruises is minimal and may include RICE (rest, ice, compression, and elevation), painkillers (particularly NSAIDs) and, later in recovery, light stretching exercises. Particularly, immediate application of ice while elevating the area may reduce or completely prevent swelling by restricting blood flow to the area and preventing internal bleeding. Rest and preventing re-injury is essential for rapid recovery. Very gently massaging the area and applying heat may encourage blood flow and relieve pain according to the Gate control theory of pain, although causing additional pain may indicate the massage is exacerbating the injury. As for most injuries, these techniques should not be applied until at least three days following the initial damage to ensure all internal bleeding has stopped, because although increasing blood flow will allow more healing factors into the area and encourage drainage, if the injury is still bleeding this will allow more blood to seep out of the wound and cause the bruise to become worse. In most cases hematomas spontaneously revert, but in cases of large hematomas or those localized in certain organs (e.g., the brain), the physician may perform a puncture of the hematoma to allow blood to exit. History Folk medicine, including ancient medicine of Egyptians, Greeks, Celts, Turks, Slavs, Mayans, Aztecs and Chinese, has used bruising as a treatment for some health problems. The methods vary widely and include cupping, scraping, and slapping. Fire cupping uses suction which causes bruising in patients. Scraping (Gua Sha) uses a small hand device with a rounded edge to gently scrape the scalp or the skin. Another ancient device that creates mild bruising is a strigil, used by Greeks and Romans in the bath. Archaeologically there is no precedent for scraping tools before Greek archaeological evidence, not Chinese or Egyptian. Etymology and pronunciation The word ecchymosis (; plural ecchymoses, ), comes to English from New Latin, based on Greek ἐκχύμωσις ekchymōsis, from ἐκχυμοῦσθαι ekchymousthai "to extravasate blood", from ἐκ- ek- (elided to ἐ- e-) and χυμός chymos "juice". Compare enchyma, "tissue infused with organic juice"; elaboration from chyme, the formative juice of tissues. See also Blunt trauma Black eye Blister Burn Cerebral contusion – bruising of brain tissue Kissing contusion – contusions of both surfaces of the knee joint Love-bite – bruising created by excessive suction of a particular area of skin, associated with an individual kissing or sucking the affected area beforehand Myocardial contusion – bruising of the heart muscle Pulmonary contusion – bruising of lung tissue Ship foot – a bruise underneath the toenail Subconjunctival hemorrhage Welts Notes External links What is a bruise? for kids Bruises in sports
Omental infarction	Omental infarction, or omental torsion, is an acute vascular disorder which compromises tissue of the greater omentum—the largest peritoneal fold in the abdomen. Signs and symptoms Patients will present with a sudden onset of cramps/abdominal pain or a stitch. The pain localises in the area of the umbilicus and can radiate to the lumbar and surrounding regions. Causes Omental infarction is a rare cause of acute abdomen pain with reported incidence being less than 4 per 1000 cases of appendicitis. Omental infarction usually presents as right-sided abdominal pain although seldom causing left-sided abdominal pain and even epigastric pain. The dominion of right-sided abdominal pain in omental infarction has been attributed to right segmental infarction as a result of the tenuous blood vessels in this part of the omentum as well as its longer size and higher mobility in comparison to the left side which subjects it to torsion. Obesity is a known risk factor for omental infarction. The theory behind this is that fat accumulation within the omentum occludes blood supply to the distal parts of the omentum in addition to making it more susceptible to torsion. Other risk factors for omental infarction are polycythemia, hypercoagulability, and vasculitides plus other conditions which predispose to torsion such as trauma, sudden body movements, coughing, heavy food intake, and hyperperistalsis.Historically, omental infarction was diagnosed only intraoperatively during surgery for presumed appendicitis or other causes of acute abdomen. But with the increase in the use of imaging, especially abdominal computed tomography (CT) scan in the work-up for acute abdomen, more cases of omental infarction are being diagnosed preoperatively. This has also led to the observation that omental infarction is a self-limiting condition which can be managed conservatively. Currently, conservative management and surgery are the only treatment options for omental infarction with no consensus as to the best treatment modality. Having both acute appendicitis and omental infarction is extremely rare with only two cases reported in the literature: one in an adult female and the other in a 7-year-old girl. Diagnosis The diagnosis is usually inferred from abdominal CT scan which shows a localised inflammatory-appearing mass of omentum . Treatment Conservative treatment may include antibiotics, anti-inflammatory medication, and pain medication. See also Greater omentum References == External links ==
Exophthalmos	Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves disease) or unilateral (as is often seen in an orbital tumor). Complete or partial dislocation from the orbit is also possible from trauma or swelling of surrounding tissue resulting from trauma. In the case of Graves disease, the displacement of the eye results from abnormal connective tissue deposition in the orbit and extraocular muscles, which can be visualized by CT or MRI.If left untreated, exophthalmos can cause the eyelids to fail to close during sleep, leading to corneal dryness and damage. Another possible complication is a form of redness or irritation called superior limbic keratoconjunctivitis, in which the area above the cornea becomes inflamed as a result of increased friction when blinking. The process that is causing the displacement of the eye may also compress the optic nerve or ophthalmic artery, and lead to blindness. Causes Inflammatory/Infection: Graves ophthalmopathy due to Graves disease, usually causes bilateral proptosis. Orbital cellulitis – often with unilateral proptosis, severe redness, and moderate to severe pain, sinusitis and an elevated white blood cell count. Dacryoadenitis Erdheim–Chester disease Mucormycosis Orbital pseudotumor – presents with acute, usually unilateral proptosis with severe pain. High-altitude cerebral edema Granulomatosis with polyangiitisNeoplastic: Leukemias Meningioma, (of sphenoid wing) Nasopharyngeal angiofibroma Hand–Schüller–Christian disease Hemangioma, cavernousCystic: Dermoid cystVascular: Carotid-cavernous fistula Aortic insufficiency: manifests as a pulsatile pseudoproptosis, described by British cardiothoracic surgeon Hutan Ashrafian in 2006Others: Orbital fracture: apex, floor, medial wall, zygomatic Retrobulbar hemorrhage: trauma to the orbit can lead to bleeding behind the eye. The hemorrhage has nowhere to escape and the increased pressure pushes the eye out of the socket, leading to proptosis and can also cause blindness if not treated promptly. Cushings syndrome (due to fat in the orbital cave) Some forms of craniosynostosis: Crouzon syndrome Pfeiffer syndrome Pansynostosis Anatomy Proptosis is the anterior displacement of the eye from the orbit. Since the orbit is closed off posteriorly, medially and laterally, any enlargement of structures located within will cause the anterior displacement of the eye. Swelling or enlargement of the lacrimal gland causes inferior medial and anterior dislocation of the eye. This is because the lacrimal glands are located superiorly and laterally in the orbit. Diagnosis Measurement Measurement of the degree of exophthalmos is performed using an exophthalmometer. Most sources define exophthalmos/proptosis as a protrusion of the globe greater than 18 mm.The term exophthalmos is often used when describing proptosis associated with Graves disease. Animals Exophthalmos is commonly found in dogs. It is seen in brachycephalic (short-nosed) dog breeds because of the shallow orbit. It can lead to keratitis secondary to exposure of the cornea. Exophthalmos is commonly seen in the pug, Boston terrier, Pekingese, and shih tzu. It is a common result of head trauma and pressure exerted on the front of the neck too hard in dogs. In cats, eye proptosis is uncommon and is often accompanied by facial fractures.About 40% of proptosed eyes retain vision after being replaced in the orbit, but in cats very few retain vision. Replacement of the eye requires general anesthesia. The eyelids are pulled outward, and the eye is gently pushed back into place. The eyelids are sewn together in a procedure known as tarsorrhaphy for about five days to keep the eye in place. Replaced eyes have a higher rate of keratoconjunctivitis sicca and keratitis and often require lifelong treatment. If the damage is severe, the eye is removed in a relatively simple surgery known as enucleation of the eye. The prognosis for a replaced eye is determined by the extent of damage to the cornea and sclera, the presence or absence of a pupillary light reflex, and the presence of ruptured rectus muscles. The rectus muscles normally help hold the eye in place and direct eye movement. Rupture of more than two rectus muscles usually requires the eye to be removed, because significant blood vessel and nerve damage also usually occurs. Compared to brachycephalic breeds, dochilocephalic (long-nosed) breeds usually have more trauma to the eye and its surrounding structures, so the prognosis is worse. See also Bostons sign Carotid-cavernous fistula Enophthalmos Von Graefes sign References == External links ==
Char syndrome	Char syndrome is an autosomal dominant congenital disease caused by mutations in TFAP2B gene which affects the development of the bones of the face as well as the heart and limbs. During embryo development, TFAP2B regulates the production of the protein AP-2β, a transcription factor that is active in the neural crest and helps regulate genes that control cell division and apoptosis. There are at least 10 mutations of this gene that have been identified in people presenting Char syndrome, which alters specific regions of the gene preventing production of the transcription factor and disrupting normal development of embryo structures. People with this condition present a very distinct facial appearance with flattened cheek bones, flat and broad tip nose, shortened distance between the nose and upper lip, triangular-shaped mouth with tick lips and strabismus. It is also characterized by a patent ductus arteriosus, which is the failure to close the ductus that connects the aorta and pulmonary artery during pre-birth life and may cause many symptoms including breathing issues and heart failure. Abnormalities of hand and finger development have also been reported in people with this condition, including short or absent fifth finger. Other abnormal findings include supernumerary nipples. These conditions often affect multiple members of a family and there are no reports of non-genetic factors that might be related with incidence of this syndrome. It was first described by Florence Char in 1978. == References ==
Endometrioma	Endometrioma is the presence of tissue similar but distinct to the endometrium in and sometimes on the ovary. It is the most common form of endometriosis. Endometrioma is found in 17–44% patients with endometriosis. More broadly, endometriosis is the presence of tissue similar but distinct to endometrial tissue located outside the uterus. The presence of endometriosis can result in the formation of scar tissue, adhesions and an inflammatory reaction. It usually is a benign growth. An endometrioma is most often found in the ovary. This ovarian endometriosis forms dark, fluid-filled cysts. These fluid-filled sacs can vary greatly in size and are known as endometriomas, also called "chocolate cysts". The fluid inside the cysts is thick, dark, old blood, giving it a chocolate-like appearance. It can also develop in the cul-de-sac (the space behind the uterus), the surface of the uterus, and between the vagina and rectum. Pathophysiology Endometrial tissue is the mucous membrane that normally lines the uterus. The endometrium is richly supplied with blood and its growth is regulated by estrogen and progesterone. It consists of glandular and stroma tissue from the lining of the uterus. When the endometrial mucous membrane is found outside of the uterus in places such as the ovaries, it causes chronic pelvic pain with intercourse and menstrual cycles. Endometriomas can produce a toxic environment by producing estrogen, cytokines, interleukins, and other inflammatory substances, that could damage healthy endometriomal tissue. This toxic fluid content can cause dire alterations to the normal surrounding endometriotic cells, potentially impacting the embryo, the ability of an embryo to implant successfully, and the responsiveness of the endometrium. Endometrioma can potentially lead to premature ovarian failure, decreased ovarian function, or problems with ovulation. Studies have also found that endometriomas occur two times more frequently in the left ovary (67%) than in the right one (33%), possibly due to the presence of the sigmoid colon on the left side. Risks Endometriomas can increase the risk of ovarian cancer in reproductive women, decrease normal ovarian function, and cause pain in the pelvis during or after periods or during sexual intercourse. Although most endometriomas are found to be benign, the possibility of malignant tumors still exists, and surgery is needed to confirm malignancy and determine what future treatment must be administered. Another factor that endometrioma can impact is the ovarian reserve, or the number of quality follicles left in the ovary to produce viable eggs. Ovaries with endometriomas showed significantly less follicular density as compared to healthy ovaries, leading to a decrease in fertility. Treatment Medication Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used first in patients with pelvic pain, particularly if the diagnosis of endometriosis has not been definitively (excision and biopsy) established. The goal of directed medical treatment is to achieve an anovulatory state. Typically, this is achieved initially using hormonal contraception. This can also be accomplished with progestational agents (i.e., medroxyprogesterone acetate), danazol, gestrinone, or gonadotropin-releasing hormone agonists (GnRH), as well as other less well-known agents. These agents are generally used if oral contraceptives and NSAIDs are ineffective. GnRH can be combined with estrogen and progestogen (add-back therapy) without loss of efficacy but with fewer hypoestrogenic symptoms. These medications are often ineffective in treating endometriomas and any relief is short lived while taking the medications. Therapy with these agents has a large number of sometimes permanent side effects, such as hot flushes, loss of bone mass, deepening of voice, weight gain, and facial hair growth. Surgery Laparoscopic surgical approaches include excision of ovarian adhesions and of endometriomas. Endometriomas require surgical removal and excision is considered to be superior to cyst vaporization or coagulation in terms of permanent removal of the disease and pain relief. Surgery can sometimes have the effect of improving fertility but can have the adverse effect of leading to increases in cycle day 2 or 3 FSH for many patients. It can also pose the risk of diminishing the ovarian reserve, which could lead to post-surgery infertility. The removal of healthy ovarian tissue or compromising blood flow to the ovary are both risk factors of the surgery that could lead to detrimental affects on the ovarian reserve. However, despite the fact that there is a risk of loss of ovarian function, studies have shown the recurrence rate of endometrioma is reduced.Recurrence rate after the surgery varies from 5 to 20%. References Bibliography Tabers cyclopedic medical dictionary. Venes, Donald, 1952-, Taber, Clarence Wilbur, 1870-1968. (Ed. 22, illustrated in full color ed.). Philadelphia: F.A. Davis. 2013. ISBN 9780803629783. OCLC 808316462.{{cite book}}: CS1 maint: others (link) == External links ==
Autoimmune optic neuropathy	Autoimmune optic neuropathy (AON), sometimes called autoimmune optic neuritis, may be a forme fruste of systemic lupus erythematosus (SLE) associated optic neuropathy. AON is more than the presence of any optic neuritis in a patient with an autoimmune process, as it describes a relatively specific clinical syndrome. AON is characterized by chronically progressive or recurrent vision loss associated with serological evidence of autoimmunity. Specifically, this term has been suggested for cases of optic neuritis with serological evidence of vasculitis by positive ANA, despite the lack of meeting criteria for SLE. The clinical manifestations include progressive vision loss that tends to be steroid-responsive and steroid dependent. Patients with defined SLE that go on to develop optic neuritis should be better identified as lupus optic neuritis. Signs and symptoms AON was first described in 1982. It presents with visual loss and signs of optic nerve dysfunction, such as loss of color vision, afferent pupil defect, and sometimes abnormalities of the optic disc. The clinical features of AON can be variable and present in several unilateral or bilateral forms: Acute anterior or retrobulbar optic neuritis sometimes associated with pain. Anterior or retrobulbar ischemic optic neuropathy not associated with pain. Chronic progressive vision loss that mimics a compressive lesion.The main features that differentiate AON from the more common typical demyelinating optic neuritis is the poor recovery of vision and the chronic or recurrent or bilateral course of AON. Furthermore, the workup for multiple sclerosis including MRI, will be negative. Thus, it may be necessary to diagnose AON after a period of observation, noting the problem is not behaving as expected for demyelinative disease. Pathogenesis Approximately 1-2% of patients with defined SLE develop an optic neuropathy during the course of their disease. SLE-associated optic neuritis is rarely the presenting sign of the disease. The molecular pathogenesis is hypothesized, based on clinical features and the emerging understanding of mechanisms in SLE. Inflammation resulting from auto-antibodies, immune complexes, T-cells and complement, probably damages the components of the optic nerve, as well as the blood vessels (vasculitis). The resulting vasculitis causes a loss of blood supply to the nerve (ischemia). This combination of inflammation and ischemia may produce reversible changes such as demyelination alone, or more permanent damage axonal (necrosis), or a combination. The poor recovery of vision in AON despite anti-inflammatory treatment suggests that ischemia from the underlying vasculitis is an important component, but the details have not been established. It may be reasonable to consider that AON pathogenesis represents an incomplete expression of the SLE-associated optic neuropathy disease process. Diagnosis Treatment AON is a rare disease and the natural history of the disease process is not well defined. Unlike typical optic neuritis, there is no association with multiple sclerosis, but the visual prognosis for AON is worse than typical optic neuritis. Thus AON patients have different treatment, and often receive chronic immunosuppression. No formal recommendation can be made regarding the best therapeutic approach. However, the available evidence to date supports treatment with corticosteroids and other immunosuppressive agents.Early diagnosis and prompt treatment with systemic corticosteroids may restore some visual function but the patient may remain steroid dependent; vision often worsens when corticosteroids are tapered. As such, long-term steroid-sparing immunosuppressive agents may be required to limit the side-effects of steroids and minimize the risk of worsening vision. == References ==
Iminoglycinuria	Iminoglycinuria is an autosomal recessive disorder of renal tubular transport affecting reabsorption of the amino acid glycine, and the imino acids proline and hydroxyproline. This results in excess urinary excretion of all three acids (-uria denotes "in the urine").Iminoglycinuria is a rare and complex disorder, associated with a number of genetic mutations that cause defects in both renal and intestinal transport systems of glycine and imino acids.Imino acids typically contain an imine functional group, instead of the amino group found in amino acids. Proline is considered and usually referred to as an amino acid, but unlike others, it has a secondary amine. This feature, unique to proline, identifies proline also as an imino acid. Hydroxyproline is another imino acid, made from the naturally occurring hydroxylation of proline. Presentation The primary characteristic of iminoglycinuria is the presence of glycine and imino acids in the urine. Otherwise, it is thought to be a relatively benign disorder, although symptoms associated with disruptions of proline and glycine metabolism caused by malabsorption may be present with iminoglycinuria. These include encephalopathy, mental retardation, deafness, blindness, kidney stones, hypertension and gyrate atrophy.Gyrate atrophy is an inherited degenerative disorder of the retina and choroid, sometimes accompanying the metabolic condition hyperornithinemia. The presence of gyrate atrophy with iminoglycinuria stems from a deficiency of proline in chorioretinal tissues, while processes behind hyperornithinemia disrupt the metabolic pathway from ornithine to proline, which alters the catabolism of ornithine, and also results in reduced levels of proline. Thus, gyrate atrophy can be found with either disorder, with proline deficiency as an underlying feature.Hyperglycinuria is another disorder affecting reabsorption of glycine and imino acids, similar to iminoglycinuria and considered to be a heterozygous form. When accompanied by a specific type of kidney stone (nephrolithiasis), it is sometimes referred to as "iminoglycinuria, type II". Genetics Iminoglycinuria is believed to be inherited in an autosomal recessive manner. This means a defective gene responsible for the disorder is located on an autosome, and inheritance requires two copies of the defective gene—one from each parent. Parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.A non-inherited cause of excess urinary excretion of proline and glycine, similar to that found in iminoglycinuria, is quite common to newborn infants younger than six months. Sometimes referred to as neonatal iminoglycinuria, it is due to underdevelopment of high-affinity transport mechanisms within the renal circuit, specifically PAT2, SIT1 and SLC6A18. The condition corrects itself with age. In cases where this persists beyond childhood, however, inherited hyperglycinuria or iminoglycinuria may be suspected. Pathophysiology Glycine, proline and hydroxyproline share common renal tubular mechanisms of reabsorption, a function specific to the proximal tubule. Both reabsorption or absorption of glycine and imino acids takes place respectively at the proximal tubule or intestinal brush border epithelium. The more selective transport of proline and other imino acids is driven at the molecular level by a mammalian cellular transport mechanism aptly known as system IMINO. While no single genetic mutation has been established as the cause of iminoglycinuria; several mutations, affecting transport mechanisms shared by glycine, proline and hydroxyproline, as well as those that selectively transport either glycine or imino acids, including the IMINO system, are known to be associated with the disorder. When combined, these factors will result in a variable phenotype for iminoglycinuria depending on which mutations are present. However, despite the role that intestinal malabsorption of glycine and imino acids can play in iminoglycinuria, the primary defect disrupts their renal transport and reabsorption. This is evident, as inherited iminoglycinuria can be clinically present with no intestinal involvement.In mammals, including humans, the transport of amino and imino acids from the lumen (interior) of the intestine or the renal proximal tubule into the cells occurs at the brush border membrane of the epithelium (moist, tightly packed cellular lining of many tissues and organs of the body). Here, cotransporters such as sodium or chloride (part of the system of Na-K-Cl cotransporters) couple with the amino or imino acids on the molecular level and transport them through specific integral membrane proteins that form ion channels, which are located within the cell membrane. From the cells, the absorbed or reabsorbed amino and imino acids eventually reach the blood. Absorption refers to the overall process happening in the intestine in lieu of normal digestive breakdown of proteins, while reabsorption refers to the process occurring in the renal proximal tubule to reclaim amino and imino acids that have been filtered out of the blood via the glomerulus.These forms of transport require energy, as the products being transported are usually moving against a higher concentration gradient. This process, called active transport, get its energy from ATP and other ATP-related cotransport systems that produce energy, like the sodium-potassium pump. Mechanism The primary defect associated with iminoglycinuria is a homozygous (recessive) mutation of the SLC36A2 (PAT2) gene. One of several membrane transport proteins in the solute carrier family of amino acid transporters, PAT2 is the high-affinity renal transporter of glycine, proline and hydroxyproline found to be defective in both alleles when iminoglycinuria is present in an individual. This is in contrast to the fact that when only one PAT2 allele is defective, hyperglycinuria will be present instead of iminoglycinuria. These findings delineate iminoglycinuria as the homozygous form of hyperglycinuria, with the former having a higher degree of urinary excretion of glycine and imino acids correlating to mutations in both alleles.Another mutation suspected to convey the iminoglycinuria phenotype may be found in the SLC36A1 (PAT1) gene. Identified as the low-affinity intestinal transporter of glycine and imino acids, PAT1 works in cooperation with the renal sodium-hydrogen exchanger NHE3 (SLC9A3). As absorption and reabsorption of glycine, proline and hydroxyproline occurs through PAT1 as well, it is believed to play another role in expressing the malabsorptive iminoglycinuria phenotype. Recent reports, however, suggest a more diminished role from PAT1 in some cases of the disorder.While PAT2 is strongly indicated as the primary mutagen responsible for iminoglycinuria, the variability of the phenotype is found to be instituted by three modifying genetic mutations. The major one among these is believed to be system IMINO.Defined as the sodium-dependent proline transporter not inhibited by alanine, system IMINO, believed to be formed by the SLC6A20 (SIT1) gene, is a crucial mammalian transport mechanism responsible for both renal reabsorption and intestinal absorption of proline and other imino acids, such as hydroxyproline and pipecolate. The mRNA sequence for SIT1 is expressed in a great deal of the gastrointestinal tract, including the stomach, duodenum, jejunum, ileum, cecum and colon. It is also found in the kidney, optical choroid, and parts of the central nervous system such the brain and microglial cells.Reduced penetrance is a phenomenon where a fully inherited genetic trait, such as a disease or disorder, fails to exhibit the expected phenotype. This has been reported in some cases of iminoglycinuria. Here, system IMINO is thought to play a role in reduced penetrance of iminoglycinuria by compensating for imino acid malabsorption related specifically to mutations of PAT2. Conversely, SIT1 mutations are believed to result in full expression of iminoglycinuria in some cases where heterozygous mutations of PAT2 would otherwise have only been sufficient to cause hyperglycinuria.Two other transport systems are believed to play subsequent roles in iminoglycinuria, when mutations in them are present. The neutral amino acid transporter SLC6A19 (affecting glycine, proline, and other neutral amino acids like cysteine and tryptophan), associated with Hartnup disease, plays a role in iminoglycinuria as a modifier to PAT2 mutations and is also directly affected by the actions of SIT1. The glycine-specific transporter, SLC6A18, also has an effect on the iminoglycinuria phenotype by either compounding or compensating for failures of glycine transport.To summarize, iminoglycinuria is primarily expressed by homozygous mutations of the PAT2 renal transporter, while the overall iminoglycinuria phenotype may be modified by normal or defective activity of SIT1 (IMINO), SLC6A19 and SLC6A18. Diagnosis Treament See also Pipecolic acid Facilitated diffusion Oral rehydration therapy References == External links ==
Immersion	Immersion may refer to: The arts "Immersion", a 2012 story by Aliette de Bodard Immersion, a French comic book series by Léo Quievreux Immersion (album), the third album by Australian group Pendulum Immersion (film), a 2021 Chilean thriller film Immersion (series), a webseries which test the concepts of video games in real life, created by Rooster Teeth Productions Immersion journalism, a style of journalism Science and technology Immersion lithography or immersion microscopy, optical techniques in which liquid is between the objective and image plane in order to raise numerical aperture Immersion (mathematics), a smooth map whose differential is everywhere injective, related to the mathematical concept of an embedding Immersion (virtual reality), the perception of being physically present in a non-physical world, created by using VR Other uses Immersion baptism, a type of baptism whereby the subject is immersed in water Immersion Corporation, a haptic technology developer Immersion heater, a kind of water heater Immersion therapy, overcoming fears through confrontation Language immersion, a method of teaching a second language in which the target language is used for instruction
Malonyl-CoA decarboxylase deficiency	Malonyl-CoA decarboxylase deficiency (MCD) is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-CoA decarboxylase. This enzyme breaks down Malonyl-CoA (a fatty acid precursor and a fatty acid oxidation blocker) into acetyl-CoA and carbon dioxide. Signs and symptoms The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency. Some common symptoms in Malonyl-CoA decarboxylase deficiency, such as cardiomyopathy and metabolic acidosis, are triggered by the high concentrations of Malonyl-CoA in the cytoplasm. High levels of Malonyl-CoA will inhibit β-oxidation of fatty acids through deactivating the carrier of fatty acyl group, CPT1, and thus, blocking fatty acids from going into the mitochondrial matrix for oxidation.A research conducted in Netherlands has suggested that carnitine supplements and a low fat diet may help to reduce the level of malonic acid in our body. Genetics Malonyl-CoA decarboxylase deficiency is caused by mutations in the MLYCD gene, located on chromosome 16q24. The gene encodes the enzyme malonyl-CoA decarboxylase. Within cells, this enzyme helps regulate the formation and breakdown of a certain group of fats called fatty acids. Many tissues, including heart muscle, use fatty acids as a major source of energy. Mutations in the MLYCD gene reduce or eliminate the function of malonyl-CoA decarboxylase. A lack of this enzyme disrupts the normal balance of fatty acid formation and breakdown. As a result, fatty acids cannot be converted to energy, which can lead to characteristic features of this disorder, such as low blood sugar and cardiomyopathy. By-products of fatty acid processing build up in tissues, which also contributes to the signs and symptoms of malonyl-CoA decarboxylase deficiency. Malonyl-CoA decarboxylase deficiency is inherited in an autosomal recessive pattern. This means that the defective gene is located on an autosome (chromosome 16 is an autosome), and two copies of the defective gene - one inherited from each parent - are required to be born with the disorder. The parents of a child with an autosomal recessive disorder both carry one copy of the defective gene, but are usually not affected by the disorder. Malonyl-CoA decarboxylase deficiency is extremely rare, evidence suggests that it is caused by the abnormality in the protein transcription regulation. Looking at the molecular basis, two distinct homozygous mutations are found to cause Malonyl-CoA Decarboxylase deficiency in human. The first mutation is the transversion of gene from C to G causing a premature stop signal in the protein. The second mutation is a base pair insertion in the mature RNA that will eventually result in the protein truncation.A research has also confirmed that the homozygous mutation which eventually leads to MCD deficiency is caused by the isodisomy of maternal UPD. This indicates that such disease is likely to be inherited from mother’s gene profile, not from paternal source. Pathophysiology Without the enzymatic activity of Malonyl-CoA decarboxylase, cellular Mal-CoA increases so dramatically that at the end it is instead broken down by an unspecific short-chain acyl-CoA hydrolase, which produces malonic acid and CoA. Malonic acid is a Krebs cycle inhibitor, preventing the cells to make ATP through oxidation. In this condition, the cells, to make ATP, are forced to increase glycolysis, which produces lactic acid as a by-product. The increase of lactic and malonic acid drastically lowers blood pH, and causes both lactic and malonic aciduria (acidic urine). This condition is very rare, as fewer than 20 cases have been reported. By 1999, only seven cases of Malonyl- CoA decarboxylase deficiency had been reported in human in Australia; however, this deficiency predominately occurs during childhood. Patients from the seven reported cases of Malonyl- CoA decarboxylase deficiency have an age range between 4 days to 13 years, and they all have the common symptom of delayed neurological development. Similar study was conducted in Netherland, and found seventeen reported cases of Malonyl- CoA decarboxylase deficiency in children age range from 8 days to 12 years.Although we have not yet gained a clear understanding of the pathogenic mechanism of this deficiency, some researchers have suggested a brain-specific interaction between Malonyl-CoA and CTP1 enzyme which may leads to unexplained symptoms of the MCD deficiency.Research has found that large amount of MCD are detached in the hypothalamus and cortex of the brain where high levels of lipogenic enzymes are found, indicating that MCD plays a role in lipid synthesis in the brain. Disturbed interaction between Malonyl-CoA and CPT1 may also contributed to abnormal brain development.Malonyl-CoA decarboxylase plays an important role in the β-oxidation processes in both mitochondria and peroxisome. Some other authors have also hypothesized that it is the MCD deficiency induced inhibition of peroxisomal β-oxidation that contributes to the development delay. Diagnosis Treatment See also Combined malonic and methylmalonic aciduria (CMAMMA) References External links Malonyl-CoA decarboxylase deficiency at NLM Genetics Home Reference
Ross syndrome	Ross syndrome consists of Adies syndrome (myotonic pupils and absent deep tendon reflexes) plus segmental anhidrosis (typically associated with compensatory hyperhidrosis).It was characterized in 1958 by A.T. Ross.By 1992, eighteen cases had been documented.Signs and Symptoms Initial manifestations often include an abnormal segmental sweating response (described as hyperhidrosis or anhidrosis in some patients) and a tonic pupil. Other commonly reported symptoms included fatigue, chronic cough, and increased urinary frequency.Prognosis Ross syndrome is a non life-threatening benign condition but delay in diagnosis can result in slow progression of autonomic symptoms. Epidemiology Ross Syndrome is a progressive autonomic dysfunction that can occur in any age, ethnicity, or gender. The average age of diagnosis for Ross syndrome is 36 years and affects more females than males. See also Hypohidrosis List of cutaneous conditions References == External links ==
Renpennings syndrome	Renpennings syndrome is a neurodevelopmental disorder recognised in males that causes intellectual disability, mild growth retardation with examples in the testes and head, and a somewhat short stature. The condition only affects males, starting at birth. Presentation People with Renpennings typically begin learning language at an ordinary pace, but by the age of 3–4 they experience a regression in mental and physical development, such as mild low muscle tone resulting in elongated faces and rapid loss in the normal growth of the head (microcephaly). Small testes and short stature are also known to commonly occur. Genetics It is associated with mutations in the PQBP1 gene. The gene product is a polyglutamine-binding protein involved in transcription and pre-mRNA splicing. The gene itself is located on the short arm of the X chromosome (Xp11.23). The most common mutations causing this condition occur in exon 4. Diagnosis This diagnosis may be suspected on clinical grounds but should be confirmed by sequencing the PQBP1 gene. Treatment There is no specific or curative treatment for this condition at present. Management is supportive Epidemiology This condition normally only occurs in males but a case in a female has been reported. History This condition was first characterized in 1962. and later described by Hans Renpenning in 1963 after he documented these traits on many children in one family alone. See also Lujan-Fryns syndrome Fragile x syndrome References == External links ==
Blepharochalasis	Blepharochalasis is an inflammation of the eyelid that is characterized by exacerbations and remissions of eyelid edema, which results in a stretching and subsequent atrophy of the eyelid tissue, leading to the formation of redundant folds over the lid margins. It typically affects only the upper eyelids, and may be unilateral as well as bilateral. Signs and symptoms Complications Complications of blepharochalasis may include conjunctival hyperemia (excessive blood flow through the moist tissues of the orbit), chemosis, entropion, ectropion, and ptosis. Causes Blepharochalasis is idiopathic in most cases, i.e., the cause is unknown. Systemic conditions linked to blepharochalasis are renal agenesis, vertebral abnormalities, and congenital heart disease. Pathophysiology Blepharochalasis results from recurrent bouts of painless eyelid swelling, each lasting for several days. This is thought to be a form of localized angioedema, or rapid accumulation of fluid in the tissues. Recurrent episodes lead to thin and atrophic skin. Damage to the levator palpebrae superioris muscle causes ptosis, or drooping of the eyelid, when the muscle can no longer hold the eyelid up. Diagnosis Differential diagnosis Dermatochalasis is sometimes confused with blepharochalasis, but these are two different conditions. Treatment The following procedures have been described for blepharochalasis: External levator aponeurosis tuck Blepharoplasty Lateral canthoplasty Dermis fat graftsThese are used to correct atrophic blepharochalasis after the syndrome has run its course. Epidemiology It is encountered more commonly in younger rather than older individuals References == External links ==
Nephronophthisis	Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure. It is a form of ciliopathy. Its incidence has been estimated to be 0.9 cases per million people in the United States, and 1 in 50,000 births in Canada. Signs and symptoms Infantile, juvenile, and adolescent forms of nephronophthisis have been identified. Although the range of characterizations is broad, people affected by nephronophthisis typically present with polyuria (production of a large volume of urine), polydipsia (excessive liquid intake), and after several months to years, end-stage kidney disease, a condition necessitating either dialysis or a kidney transplant in order to survive. Some individuals with nephronophthisis also have so-called "extra-renal symptoms" which can include tapetoretinal degeneration, liver problems, oculomotor apraxia, and cone-shaped epiphysis (Saldino-Mainzer syndrome). Cause Nephronophthisis is characterized by fibrosis and the formation of cysts at the cortico-medullary junction, it is an autosomal recessive disorder which eventually leads to terminal kidney failure. Pathophysiology Mechanism of nephronophthisis indicates that all proteins mutated in cystic kidney diseases express themselves in primary cilia. NPHP gene mutations cause defects in signaling resulting in flaws of planar cell polarity. The ciliary theory indicates that multiple organs are involved in NPHP (retinal degeneration, cerebellar hypoplasia, liver fibrosis, and intellectual disability). Related rare genetic disorders Nephronophthisis is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, Alström syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration.NPHP2 is infantile type of nephropthisis and sometimes associated with situs inversus this can be explained by its relation with inversin gene. NPHP1, NPHP3, NPHP4, NPHP5, and NPHP6 are sometimes seen with retinitis pigmentosa, this particular association has a name, Senior-Loken syndrome. Diagnosis The diagnosis of nephronophthisis can be obtained via a kidney ultrasound, family history and clinical history of the affected individual according to Stockman, et al. Types Infantile NPH Juvenile NPH Adult NPH Management The management of this condition can be done via-improvement of any electrolyte imbalance, as well as, high blood pressure and low red blood cell counts (anemia) treatment as the individuals condition warrants. Epidemiology Nephronophthisis occurs equally in both sexes and has an estimate 9 in about 8 million rate in individuals. Nephronophthisis is the leading monogenic cause of end-stage kidney disease. References Further reading Simms, Roslyn J.; Hynes, Ann Marie; Eley, Lorraine; Sayer, John A. (2011). "Nephronophthisis: A Genetically Diverse Ciliopathy". International Journal of Nephrology. 2011: 1–10. doi:10.4061/2011/527137. PMC 3108105. PMID 21660307. Hildebrandt, Friedhelm; Attanasio, Massimo; Otto, Edgar (2009-01-01). "Nephronophthisis: Disease Mechanisms of a Ciliopathy". Journal of the American Society of Nephrology. 20 (1): 23–35. doi:10.1681/ASN.2008050456. ISSN 1046-6673. PMC 2807379. PMID 19118152. Murray, Karen F.; Larson, Anne M. (2010-07-23). Fibrocystic Diseases of the Liver. Springer Science & Business Media. ISBN 9781603275248. == External links ==
Familial multiple lipomatosis	Familial multiple lipomatosis is a hereditary adipose tissue disorder that is characterized by the formation of multiple lipomas that occur in a particular distribution. The lipomas are well-encapsulated, slow-growing, benign fatty tumors. The distribution is defined as being focused in the trunk of the body and extremities. Familial Multiple Lipomatosis can be identified when multiple lipomas occur in multiple family members that span different generations. Some people may have hundreds of lipomas present. Symptoms The source of this disease is from family history, and symptoms most often arise in middle age. Newly formed lipomas frequently present themselves as a bead-like lump under the skin, and become rubbery and movable. They may be seen throughout the body and in some areas more than others, however, it does not make an appearance on the head or shoulders of the individual. The size of those bumps may vary and could possibly get in the way of an individual living their life peacefully. There are usually no feelings of discomfort or pain unless a lipoma has been aggravated or is directly on a nerve. Lipomas that sit over bony areas such as the ribs and lower back can cause discomfort when lying down or receiving any kind of pressure. The age at which familial multiple lipomatosis begins to make an appearance on the individual’s body varies; for some it may be as early as 5 years of age. Diagnosis Familial multiple lipomatosis is usually diagnosed through a physical exam via palpation, medical history and imaging studies such as ultrasound, CT scan, or magnetic resonance imaging (MRI). A CT scan is an imaging method that uses x-rays to create images of cross sections of the body, while an MRI uses powerful magnets and radio waves to create images of lipomas and surrounding tissues. Both tests are useful to establish the diagnosis of multiple symmetric lipomatosis, although magnetic resonance imaging provides more details and may be used when lipomas are large, deep, or have infiltrated muscle fibers or nerves. In some cases, a biopsy of the lipomas may be necessary to confirm the diagnosis. Differential diagnoses Liposarcoma Dercum’s disease Benign symmetric lipomatosis Madelung’s disease Cyst Causes The exact cause of FML is not yet known, but there are several theories of different causes: Hormonal disorder due to the bodys inability to properly metabolize fat Increase in fat cells (adipocytes) Enzymatic defect or a change in the surface of the cells that could prevent the breakdown of fat Poor lymphatic drainage Defective regulation of mitochondria in brown fat. Brown fat is responsible for causing heat in times of stress or cold. For general callus tissue is stimulated by the sympathetic nervous system and this response is mediated by a substance called norepinephrine. This process occurs in the mitochondria In most families, the mode of inheritance has not been determined. However, changes (mutations) in mitochondrial DNA that involve the MT-TK gene have been identified in some families who have the disease and other conditions that affect many different body systems. Treatment The only effective treatments for lipomas caused by familial multiple lipomatosis are liposuction or surgical removal. Steroid injections may also be used to shrink the tumors by causing local fat atrophy. Patients with the condition often seek removal when the lipomas are large, disfiguring, or cause pain. This may be done by a dermatologist or other surgeon. In the majority of cases where one to a few subcutaneous lipomas are being excised, the procedure is done under local anaesthetic and the patient can resume most normal activities immediately afterward. Over-the-counter pain medications are generally sufficient in the following days and long-term scarring is minimal. Regrowth is rare because lipomas are usually well-encapsulated and are therefore removed entirely although more new lipomas may start to grow in the same area.Therapeutic treatments that are recommended for adipose tissue disorders include improving lymphatic flow through exercise and massage, following an anti-inflammatory diet, and reducing non-disordered fat tissue when necessary. Weight loss has not been shown to eliminate lipomas but may help reduce overall inflammation and influence hormone levels. While there is no total cure for FML to stop the growth of new lipomas, most of the growths can remain untreated and rarely cause medical complications. In the media April Wesson / Dr. Pimple Popper Season 2 Episode 1: “Nose No Bounds" on January 3, 2019 Olivia Buckland / Love Island 2016: After 4 years of building the courage to get it checked, the lump located near the star’s left armpit was discovered to be a lipoma, which was removed before her wedding == References ==
Hypochondrogenesis	Hypochondrogenesis is a severe genetic disorder causing malformations of bone growth. The condition is characterized by a short body and limbs and abnormal bone formation in the spine and pelvis. Hypochondrogenesis is a subtype of collagenopathy, types II and XI, and is similar to another skeletal disorder, achondrogenesis type 2, although the spinal changes seen in hypochondrogenesis tend to be somewhat milder. Signs and symptoms Symptoms of hypochondrogenesis include: edema, limb undergrowth, spondyloepiphyseal dysplasia, short ribs, respiratory failure, short chin, upper limb undergrowth, thoracic hypoplasia, hypertelorism, hydrops fetalis, pulmonary hypoplasia, and a cleft palate. Pathophysiology Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the COL2A1 gene. The protein made by this gene forms type II collagen, a molecule found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). Type II collagen is essential for the normal development of bones and other connective tissues (tissues that form the bodys supportive framework). Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones from developing properly. This condition is caused by new mutations in the COL2A1 gene. Hypochondrogenesis is considered an autosomal dominant disorder because the affected gene is located on an autosome, and only one copy of the altered gene is necessary to cause the condition. The disorder is not passed on to the next generation, however, because affected individuals do not live long enough to have children. Diagnosis Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped lungs. The spinal bones (vertebrae) in the neck and part of the pelvis (the sacrum) do not harden, or ossify, properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a cleft palate. The abdomen is enlarged, and excess fluid may build up in the body before birth (a condition called hydrops fetalis). As a result of these serious health problems, infants are usually premature and stillborn or die shortly after birth from respiratory failure. Some infants have lived for a time, however, with intensive medical support. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related disorder on the spectrum of abnormal bone growth. Treatment There is no cure or treatment for hypochondrogenesis. References External links This article incorporates public domain text from The U.S. National Library of Medicine
Ependymoma	An ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymomas is the fourth ventricle. Rarely, ependymomas can occur in the pelvic cavity. Syringomyelia can be caused by an ependymoma. Ependymomas are also seen with neurofibromatosis type II. Signs and symptoms Source: severe headache visual loss (due to papilledema) vomiting bilateral Babinski sign drowsiness (after several hours of the above symptoms) gait change (rotation of feet when walking) impaction/constipation back flexibility Morphology Ependymomas are composed of cells with regular, round to oval nuclei. There is a variably dense fibrillary background. Tumor cells may form gland-like round or elongated structures that resemble the embryologic ependymal canal, with long, delicate processes extending into the lumen; more frequently present are perivascular pseudorosettes in which tumor cells are arranged around vessels with an intervening zone consisting of thin ependymal processes directed toward the wall of the vessel.It has been suggested that ependymomas are derived from radial glia, despite their name suggesting an ependymal origin. Ependymoma tumors Ependymomas make up about 5% of adult intracranial gliomas and up to 10% of childhood tumors of the central nervous system (CNS). Their occurrence seems to peak at age 5 years and then again at age 35. They develop from cells that line both the hollow cavities of the brain and the canal containing the spinal cord, but they usually arise from the floor of the fourth ventricle, situated in the lower back portion of the brain, where they may produce headache, nausea and vomiting by obstructing the flow of cerebrospinal fluid. This obstruction may also cause hydrocephalus. They may also arise in the spinal cord, conus medullaris and supratentorial locations. Other symptoms can include (but are not limited to): loss of appetite, difficulty sleeping, temporary inability to distinguish colors, uncontrollable twitching, seeing vertical or horizontal lines when in bright light, and temporary memory loss. It should be remembered that these symptoms also are prevalent in many other illnesses not associated with ependymoma.About 10% of ependymomas are benign myxopapillary ependymoma (MPE). MPE is a localized and slow-growing low-grade tumor, which originates almost exclusively from the lumbosacral nervous tissue of young patients. On the other hand, it is the most common tumor of the lumbosacral canal comprising about 90% of all tumoral lesions in this region.Although some ependymomas are of a more anaplastic and malignant type, most of them are not anaplastic. Well-differentiated ependymomas are usually treated with surgery. For other ependymomas, total surgical removal is the preferred treatment in addition to radiation therapy. The malignant (anaplastic) varieties of this tumor, malignant ependymoma and the ependymoblastoma, are treated similarly to medulloblastoma but the prognosis is much less favorable. Malignant ependymomas may be treated with a combination of radiation therapy and chemotherapy. Ependymoblastomas, which occur in infants and children younger than 5 years of age, may spread through the cerebrospinal fluid and usually require radiation therapy. The subependymoma, a variant of the ependymoma, is apt to arise in the fourth ventricle but may occur in the septum pellucidum and the cervical spinal cord. It usually affects people over 40 years of age and more often affects men than women.Extraspinal ependymoma (EEP), also known as extradural ependymoma, may be an unusual form of teratoma or may be confused with a sacrococcygeal teratoma. Treatment Guidelines for initial management for ependymoma are maximum surgical resection followed by radiation. Chemotherapy is of limited use and reserved for special cases including young children and those with tumor present after resection. Prophylactic craniospinal irradiation is of variable use and is a source of controversy given that most recurrence occurs at the site of resection and therefore is of debatable efficacy. Confirmation of cerebrospinal infiltration warrants more expansive radiation fields.Prognosis of recurrence is poor and often indicates palliative care to manage symptoms. References External links Brain and Spinal Tumors: Hope Through Research (National Institute of Neurological Disorders and Stroke)
Primary pulmonary coccidioidomycosis	Primary pulmonary coccidioidomycosis is an infection caused by inhalation of Coccidioides immitis.: 314 Once pulmonary symptoms subside, about 30% of women and 15% of men will have allergic skin manifestations in the form of erythema nodosum.: 314 A coccidioidoma is a benign localized residual granulomatous lesion or scar that can remain in the lungs tissues following primary pulmonary coccidioidomycosis. See also Coccidioidomycosis List of cutaneous conditions == References ==
Chickenpox	Chickenpox, also known as varicella, is a highly contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms small, itchy blisters, which eventually scab over. It usually starts on the chest, back, and face. It then spreads to the rest of the body. The rash and other symptoms, such as fever, tiredness, and headaches, usually last five to seven days. Complications may occasionally include pneumonia, inflammation of the brain, and bacterial skin infections. The disease is usually more severe in adults than in children.Chickenpox is an airborne disease which spreads easily from one person to the next through the coughs and sneezes of an infected person. The incubation period is 10–21 days, after which the characteristic rash appears. It may be spread from one to two days before the rash appears until all lesions have crusted over. It may also spread through contact with the blisters. Those with shingles may spread chickenpox to those who are not immune through contact with the blisters. The disease can usually be diagnosed based on the presenting symptom; however, in unusual cases it may be confirmed by polymerase chain reaction (PCR) testing of the blister fluid or scabs. Testing for antibodies may be done to determine if a person is immune. People usually only get chickenpox once. Although reinfections by the virus occur, these reinfections usually do not cause any symptoms.Since its introduction in 1995, the varicella vaccine has resulted in a decrease in the number of cases and complications from the disease. It protects about 70–90 percent of people from disease with a greater benefit for severe disease. Routine immunization of children is recommended in many countries. Immunization within three days of exposure may improve outcomes in children. Treatment of those infected may include calamine lotion to help with itching, keeping the fingernails short to decrease injury from scratching, and the use of paracetamol (acetaminophen) to help with fevers. For those at increased risk of complications, antiviral medication such as aciclovir are recommended.Chickenpox occurs in all parts of the world. In 2013 there were 140 million cases of chickenpox and shingles worldwide. Before routine immunization the number of cases occurring each year was similar to the number of people born. Since immunization the number of infections in the United States has decreased nearly 90%. In 2015 chickenpox resulted in 6,400 deaths globally – down from 8,900 in 1990. Death occurs in about 1 per 60,000 cases. Chickenpox was not separated from smallpox until the late 19th century. In 1888 its connection to shingles was determined. The first documented use of the term chicken pox was in 1658. Various explanations have been suggested for the use of "chicken" in the name, one being the relative mildness of the disease. Signs and symptoms The early (prodromal) symptoms in adolescents and adults are nausea, loss of appetite, aching muscles, and headache. This is followed by the characteristic rash or oral sores, malaise, and a low-grade fever that signal the presence of the disease. Oral manifestations of the disease (enanthem) not uncommonly may precede the external rash (exanthem). In children the illness is not usually preceded by prodromal symptoms, and the first sign is the rash or the spots in the oral cavity. The rash begins as small red dots on the face, scalp, torso, upper arms and legs; progressing over 10–12 hours to small bumps, blisters and pustules; followed by umbilication and the formation of scabs.At the blister stage, intense itching is usually present. Blisters may also occur on the palms, soles, and genital area. Commonly, visible evidence of the disease develops in the oral cavity and tonsil areas in the form of small ulcers which can be painful or itchy or both; this enanthem (internal rash) can precede the exanthem (external rash) by 1 to 3 days or can be concurrent. These symptoms of chickenpox appear 10 to 21 days after exposure to a contagious person. Adults may have a more widespread rash and longer fever, and they are more likely to experience complications, such as varicella pneumonia.Because watery nasal discharge containing live virus usually precedes both exanthem (external rash) and enanthem (oral ulcers) by 1 to 2 days, the infected person actually becomes contagious one to two days before recognition of the disease. Contagiousness persists until all vesicular lesions have become dry crusts (scabs), which usually entails four or five days, by which time nasal shedding of live virus ceases. The condition usually resolves by itself within a week or two. The rash may, however, last for up to one month.Chickenpox is rarely fatal, although it is generally more severe in adult men than in women or children. Non-immune pregnant women and those with a suppressed immune system are at highest risk of serious complications. Arterial ischemic stroke (AIS) associated with chickenpox in the previous year accounts for nearly one third of childhood AIS. The most common late complication of chickenpox is shingles (herpes zoster), caused by reactivation of the varicella zoster virus decades after the initial, often childhood, chickenpox infection. Pregnancy and neonates During pregnancy the dangers to the fetus associated with a primary VZV infection are greater in the first six months. In the third trimester, the mother is more likely to have severe symptoms. For pregnant women, antibodies produced as a result of immunization or previous infection are transferred via the placenta to the fetus. Varicella infection in pregnant women could lead to spread via the placenta and infection of the fetus. If infection occurs during the first 28 weeks of gestation, this can lead to fetal varicella syndrome (also known as congenital varicella syndrome). Effects on the fetus can range in severity from underdeveloped toes and fingers to severe anal and bladder malformation. Possible problems include: Damage to brain: encephalitis, microcephaly, hydrocephaly, aplasia of brain Damage to the eye: optic stalk, optic cup, and lens vesicles, microphthalmia, cataracts, chorioretinitis, optic atrophy Other neurological disorder: damage to cervical and lumbosacral spinal cord, motor/sensory deficits, absent deep tendon reflexes, anisocoria/Horners syndrome Damage to body: hypoplasia of upper/lower extremities, anal and bladder sphincter dysfunction Skin disorders: (cicatricial) skin lesions, hypopigmentationInfection late in gestation or immediately following birth is referred to as "neonatal varicella". Maternal infection is associated with premature delivery. The risk of the baby developing the disease is greatest following exposure to infection in the period 7 days before delivery and up to 8 days following the birth. The baby may also be exposed to the virus via infectious siblings or other contacts, but this is of less concern if the mother is immune. Newborns who develop symptoms are at a high risk of pneumonia and other serious complications of the disease. Pathophysiology Exposure to VZV in a healthy child initiates the production of host immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies; IgG antibodies persist for life and confer immunity. Cell-mediated immune responses are also important in limiting the scope and the duration of primary varicella infection. After primary infection, VZV is hypothesized to spread from mucosal and epidermal lesions to local sensory nerves. VZV then remains latent in the dorsal ganglion cells of the sensory nerves. Reactivation of VZV results in the clinically distinct syndrome of herpes zoster (i.e., shingles), postherpetic neuralgia, and sometimes Ramsay Hunt syndrome type II. Varicella zoster can affect the arteries in the neck and head, producing stroke, either during childhood, or after a latency period of many years. Shingles After a chickenpox infection, the virus remains dormant in the bodys nerve tissues for about 50 years. This, however, does not mean that VZV cannot be contracted later in life. The immune system usually keeps the virus at bay, however it can still manifest itself at any given age between 1 and 60, causing a different form of the viral infection called shingles (also known as herpes zoster). Since the human immune system efficacy decreases with age, the United States Advisory Committee on Immunization Practices (ACIP) suggests that every adult over the age of 50 years get the herpes zoster vaccine.Shingles affects one in five adults infected with chickenpox as children, especially those who are immune-suppressed, particularly from cancer, HIV, or other conditions. Stress can bring on shingles as well, although scientists are still researching the connection. Adults over the age of 60 who had chickenpox but not shingles are the most prone age demographic. Diagnosis The diagnosis of chickenpox is primarily based on the signs and symptoms, with typical early symptoms followed by a characteristic rash. Confirmation of the diagnosis is by examination of the fluid within the vesicles of the rash, or by testing blood for evidence of an acute immunologic response.Vesicular fluid can be examined with a Tzanck smear, or by testing for direct fluorescent antibody. The fluid can also be "cultured", whereby attempts are made to grow the virus from a fluid sample. Blood tests can be used to identify a response to acute infection (IgM) or previous infection and subsequent immunity (IgG).Prenatal diagnosis of fetal varicella infection can be performed using ultrasound, though a delay of 5 weeks following primary maternal infection is advised. A PCR (DNA) test of the mothers amniotic fluid can also be performed, though the risk of spontaneous abortion due to the amniocentesis procedure is higher than the risk of the babys developing fetal varicella syndrome. Prevention Hygiene measures The spread of chickenpox can be prevented by isolating affected individuals. Contagion is by exposure to respiratory droplets, or direct contact with lesions, within a period lasting from three days before the onset of the rash, to four days after the onset of the rash. The chickenpox virus is susceptible to disinfectants, notably chlorine bleach (i.e., sodium hypochlorite). Like all enveloped viruses, it is sensitive to drying, heat and detergents. Vaccine Chickenpox can be prevented by vaccination. The side effects are usually mild, such as some pain or swelling at the injection site.A live attenuated varicella vaccine, the Oka strain, was developed by Michiaki Takahashi and his colleagues in Japan in the early 1970s. In 1981, Merck & Co. licensed the "Oka" strain of the varicella virus in the United States, and Maurice Hillemans team at Merck invented a varicella vaccine in the same year.The varicella vaccine is recommended in many countries. Some countries require the varicella vaccination or an exemption before entering elementary school. A second dose is recommended five years after the initial immunization. A vaccinated person is likely to have a milder case of chickenpox if they become infected. Immunization within three days following household contact reduces infection rates and severity in children. Being exposed to chickenpox as an adult (for example, through contact with infected children) may boosts immunity to shingles. So it was thought, that when the majority of children are vaccinated against chickenpox, adults might lose this natural boosting, so immunity would drop and more shingles cases would occur. On the other hand, current observations suggest that exposure to children with varicella is not a critical factor in the maintenance of immunity. Multiple subclinical reactivations of varicella zoster virus may occur spontaneously and, despite not causing clinical disease, may still provide an endogenous boost to immunity against zoster.It is part of the routine immunization schedule in the US. Some European countries include it as part of universal vaccinations in children, but not all countries provide the vaccine. In the UK as of 2014, the vaccine is only recommended in people who are particularly vulnerable to chickenpox. This is to keep the virus in circulation thereby exposing the population to the virus at an early age, when it is less harmful, and to reduce the occurrence of shingles in those who have already had chickenpox by repeated exposure to the virus later in life. In populations that have not been immunized or if immunity is questionable, a clinician may order an enzyme immunoassay. An immunoassay measures the levels of antibodies against the virus that give immunity to a person. If the levels of antibodies are low (low titer) or questionable, reimmunization may be done. Treatment Treatment mainly consists of easing the symptoms. As a protective measure, people are usually required to stay at home while they are infectious to avoid spreading the disease to others. Cutting the fingernails short or wearing gloves may prevent scratching and minimize the risk of secondary infections.Although there have been no formal clinical studies evaluating the effectiveness of topical application of calamine lotion (a topical barrier preparation containing zinc oxide, and one of the most commonly used interventions), it has an excellent safety profile. Maintaining good hygiene and daily cleaning of skin with warm water can help to avoid secondary bacterial infection; scratching may increase the risk of secondary infection.Paracetamol (acetaminophen) but not aspirin may be used to reduce fever. Aspirin use by someone with chickenpox may cause serious, sometimes fatal disease of the liver and brain, Reye syndrome. People at risk of developing severe complications who have had significant exposure to the virus may be given intra-muscular varicella zoster immune globulin (VZIG), a preparation containing high titres of antibodies to varicella zoster virus, to ward off the disease.Antivirals are sometimes used. Children If aciclovir by mouth is started within 24 hours of rash onset, it decreases symptoms by one day but has no effect on complication rates. Use of aciclovir therefore is not currently recommended for individuals with normal immune function. Children younger than 12 years old and older than one month are not meant to receive antiviral drugs unless they have another medical condition which puts them at risk of developing complications.Treatment of chickenpox in children is aimed at symptoms while the immune system deals with the virus. With children younger than 12 years, cutting fingernails and keeping them clean is an important part of treatment as they are more likely to scratch their blisters more deeply than adults.Aspirin is highly contraindicated in children younger than 16 years, as it has been related to Reye syndrome. Adults Infection in otherwise healthy adults tends to be more severe. Treatment with antiviral drugs (e.g. aciclovir or valaciclovir) is generally advised, as long as it is started within 24–48 hours from rash onset. Remedies to ease the symptoms of chickenpox in adults are basically the same as those used for children. Adults are more often prescribed antiviral medication, as it is effective in reducing the severity of the condition and the likelihood of developing complications. Adults are advised to increase water intake to reduce dehydration and to relieve headaches. Painkillers such as paracetamol (acetaminophen) are recommended, as they are effective in relieving itching and other symptoms such as fever or pains. Antihistamines relieve itching and may be used in cases where the itching prevents sleep, because they also act as a sedative. As with children, antiviral medication is considered more useful for those adults who are more prone to develop complications. These include pregnant women or people who have a weakened immune system. Prognosis The duration of the visible blistering caused by varicella zoster virus varies in children usually from 4 to 7 days, and the appearance of new blisters begins to subside after the fifth day. Chickenpox infection is milder in young children, and symptomatic treatment, with sodium bicarbonate baths or antihistamine medication may ease itching. In adults, the disease is more severe, though the incidence is much less common. Infection in adults is associated with greater morbidity and mortality due to pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), bronchitis (either viral bronchitis or secondary bacterial bronchitis), hepatitis, and encephalitis. In particular, up to 10% of pregnant women with chickenpox develop pneumonia, the severity of which increases with onset later in gestation. In England and Wales, 75% of deaths due to chickenpox are in adults. Inflammation of the brain, encephalitis, can occur in immunocompromised individuals, although the risk is higher with herpes zoster. Necrotizing fasciitis is also a rare complication.Varicella can be lethal to individuals with impaired immunity. The number of people in this high-risk group has increased, due to the HIV epidemic and the increased use of immunosuppressive therapies. Varicella is a particular problem in hospitals when there are patients with immune systems weakened by drugs (e.g., high-dose steroids) or HIV.Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most common complication in healthy children. Disseminated primary varicella infection usually seen in the immunocompromised may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, hepatitis, and glomerulonephritis.Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected. Five major clinical syndromes have been described: febrile purpura, malignant chickenpox with purpura, postinfectious purpura, purpura fulminans, and anaphylactoid purpura. These syndromes have variable courses, with febrile purpura being the most benign of the syndromes and having an uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a mortality rate of greater than 70%. The cause of these hemorrhagic chickenpox syndromes is not known. Epidemiology Primary varicella occurs in all countries worldwide. In 2015 chickenpox resulted in 6,400 deaths globally – down from 8,900 in 1990. There were 7,000 deaths in 2013. Varicella is highly transmissible, with an infection rate of 90% in close contacts.In temperate countries, chickenpox is primarily a disease of children, with most cases occurring during the winter and spring, most likely due to school contact. In such countries it is one of the classic diseases of childhood, with most cases occurring in children up to age 15; most people become infected before adulthood, and 10% of young adults remain susceptible. In the United States, a temperate country, the Centers for Disease Control and Prevention (CDC) do not require state health departments to report infections of chickenpox, and only 31 states volunteered this information as of 2013. A 2013 study conducted by the social media disease surveillance tool called Sickweather used anecdotal reports of chickenpox infections on social media systems Facebook and Twitter to measure and rank states with the most infections per capita, with Maryland, Tennessee and Illinois in the top three.In the tropics, chickenpox often occurs in older people and may cause more serious disease. In adults, the pock marks are darker and the scars more prominent than in children. Society and culture Etymology How the term chickenpox originated is not clear but it may be due to it being a relatively mild disease. It has been said to be derived from chickpeas, based on resemblance of the vesicles to chickpeas, or to come from the rash resembling chicken pecks. Other suggestions include the designation chicken for a child (i.e., literally child pox), a corruption of itching-pox, or the idea that the disease may have originated in chickens. Samuel Johnson explained the designation as "from its being of no very great danger". Intentional exposure Because chickenpox is usually more severe in adults than it is in children, some parents deliberately expose their children to the virus, for example by taking them to "chickenpox parties". Doctors say that children are safer getting the vaccine, which is a weakened form of the virus, than getting the disease, which can be fatal or lead to shingles later in life. Repeated exposure to chickenpox may protect against zoster. Other animals Humans are the only known species that the disease affects naturally. However, chickenpox has been caused in other primates, including chimpanzees and gorillas. Research Sorivudine, a nucleoside analog, has been reported to be effective in the treatment of primary varicella in healthy adults (case reports only), but large-scale clinical trials are still needed to demonstrate its efficacy. There was speculation in 2005 that continuous dosing of aciclovir by mouth for a period of time could eradicate VZV from the host, although further trials were required to discern whether eradication was actually viable. See also Measles References External links Chickenpox at Curlie Prevention of Varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 1996 Antiviral therapy of varicella-zoster virus infections, 2007 Epidemiology and Prevention of Vaccine-Preventable Diseases: Varicella, US CDCs "Pink Book" Chickenpox at MedlinePlus
Acute posthemorrhagic anemia	Acute posthemorrhagic anemia or acute blood loss anemia is a condition in which a person quickly loses a large volume of circulating hemoglobin. Acute blood loss is usually associated with an incident of trauma or a severe injury resulting in a large loss of blood. It can also occur during or after a surgical procedure. See also List of circulatory system conditions List of hematologic conditions References == External links ==
Secondary glaucoma	Secondary glaucoma is a collection of progressive optic nerve disorders associated with a rise in intraocular pressure (IOP) which results in the loss of vision. In clinical settings, it is defined as the occurrence of IOP above 21 mmHg requiring the prescription of IOP-managing drugs. It can be broadly divided into two subtypes: secondary open-angle glaucoma and secondary angle-closure glaucoma, depending on the closure of the angle between the cornea and the iris. Principal causes of secondary glaucoma include optic nerve trauma or damage, eye disease, surgery, neovascularization, tumours and use of steroid and sulfa drugs. Risk factors for secondary glaucoma include uveitis, cataract surgery and also intraocular tumours. Common treatments are designed according to the type (open-angle or angle-closure) and the underlying causative condition, in addition to the consequent rise in IOP. These include drug therapy, the use of miotics, surgery or laser therapy. Pathophysiology Secondary glaucoma has different forms based on the varying underlying ocular conditions. These conditions result in an increase in IOP that manifests as secondary glaucoma. Paediatric congenital cataract associated glaucoma Based on the onset of secondary glaucoma in paediatric patients, it can be classified into early-stage and late-stage glaucoma cases. Early-stage secondary glaucoma, observed as angle-closure glaucoma, results from the blockage and inflammation of the peripheral anterior synechiae structure. However, early-stage secondary glaucoma rarely occurs with the readily available prescription of anti-inflammatory medications. On the other hand, late-stage glaucoma is commonly associated with open-angle glaucoma but the mechanisms are currently unconfirmed. Yet, it is believed to be closely related to the onset of trabeculitis or vitreous toxicity.In paediatric congenital cataract patients under the age of two, cataract surgery is considered and frequently employed as the primary treatment. There are two types of therapeutic combination, primary and secondary lens implantation (IOL). In primary IOL, cataract surgery is performed alongside immediate implantation of IOL. However, in secondary IOL implantation, the patient is prescribed aphakic glasses or contact lenses till the implantation of IOL after a varied period of time between a few months or years. Primary IOL implantation is observed to significantly reduce and avoid the occurrence of secondary glaucoma in paediatric patients under the age of two. Herpetic anterior uveitis associated glaucoma In patients diagnosed with herpetic anterior uveitis, elevated IOP and secondary glaucoma are often detected. This is due to two main reasons, the blockage of vitreous flow resulting from inflammation in the structures of the trabecular meshwork, and the sedimentation of inflamed cells. Specifically for viral anterior uveitis, patients with IOP levels above 30 mmHg are often suffer from secondary glaucoma caused by cytomegalovirus. Other forms of secondary glaucoma Pigmentary glaucoma: In pigmentary glaucoma, the obstruction of the trabecular meshwork caused by iris pigment release results in increased IOP. This release in iris pigment occurs as a result of the interaction of a flaccid iris with the zonular fibres.Exfoliation syndrome: Exfoliation syndrome is a classic cause of secondary open-angle glaucoma, a common symptom of exfoliation syndrome is a cloudy layer on the anterior lens capsule.Aphakic and pseudophakic glaucoma: Aphakic glaucoma is a common side-effect of cataract surgery which causes an increase in IOP.Corticosteroid-induced glaucoma: Corticosteroids is a risk factor for the development of secondary glaucoma, as there had been increased IOP observed as a drug side-effect.Post-traumatic glaucoma: Trauma to the eye is often observed to cause secondary glaucoma. The incidence is notably higher in populations with increased levels of physical activity.Ghost-cell glaucoma: Ruptured red blood cells will release haemoglobin in the form of Heinz bodies, which are potent in increasing the IOP level.Inflammatory glaucoma: The inflammatory reaction will affect the drainage of aqueous humour in the eye, causing an increase in IOP.Glaucoma associated with ocular tumours: Although each tumour subtype has its own mechanism in causing secondary glaucoma, the general cause is the restriction of the meshwork resulting in the obstruction of aqueous humour flow.Increased episcleral venous pressure: According to the Goldmann equation, the relationship between episcleral venous pressure (EVP) is directly proportional to the IOP. Therefore, an increase in the EVP will result in an increase in IOP. Neovascular glaucoma: As a consequence of neovascularisation, or the formation of new blood vessels and supporting connective structures, there is blockage of the anterior chamber angle. This leads to elevation of IOP causing neovascular glaucoma. Epidemiology The overall prevalence of secondary glaucoma across China between 1990 and 2015 was reported to be 0.15%, lower than the overall estimates for East Asia (0.39%). Varying forms of secondary glaucoma Pigmentary glaucoma has lower incidence in Black and Asian populations, due to their characteristically thicker irises that result in a lower likelihood of pigment release, as compared to the White populations. Incidence of exfoliation syndrome-caused secondary glaucoma is estimated to be approximately 10% of the glaucoma patient population in the United States and over 20% of the patient population in Iceland and Finland.In populations above the age of 40, neovascular glaucoma has a prevalence of 0.4% worldwide. The incidence of pigmentary glaucoma decreases with age while in exfoliation syndrome the incidence increases with age. However, given the derived nature of secondary glaucoma, there may be no significant association between age, ethnicity or gender and the prevalence of the condition.Secondary glaucoma indicated after congenital cataract surgery is found between 6 and 24% of the cases noted, whereas, secondary glaucoma caused by primary IOL implantation was observed as 9.5%. Additionally, for patients with aphakia and secondary IOL implantation, 15.1% of the cases were determined. The incidence risk in primary IOL implantation in children with cataract in both eyes is lower than secondary IOL implantation and aphakic condition. However, this difference is not observed in the general population and populations with cataract in one eye.Due to lack of concrete and specific epidemiological evidence, further research is required to accurately estimate the prevalence of secondary glaucoma and its subtypes. Risk factors In general, elevated IOP is a major risk factor in the development of secondary glaucoma. However, there are several risk factors contributing to the fluctuation in IOP levels. Uveitis Secondary glaucoma is commonly associated with uveitis. Uveitis is the inflammation of the uvea, a middle layer tissue of the eye consisting of the ciliary body, choroid and iris. Various causes have been identified as potential risk factors contributing to the occurrence of secondary glaucoma. These include viral anterior uveitis due to cytomegalovirus infection, and herpetic anterior uveitis caused by herpes simplex virus. The observed pathophysiology of secondary glaucoma in uveitis is found to be linked to the increase and fluctuation of IOP. Inflammation of eye tissues contributes to the blockage of IOP produced in the ciliary body. This results in the accumulation of aqueous and thus elevated IOP, which is a common risk factor for the progression of secondary glaucoma. Paediatric congenital cataract surgery Paediatric congenital cataract surgery is also identified as a risk factor for the progression of secondary glaucoma. Cataract is an ocular disease, identified by the progressive clouding of the lens. Surgical procedures are often employed to replace the lens and allow for clear vision. However, there is an increased risk of secondary glaucoma development in children due to the secondary IOL implantation procedure. The increased inflammatory sensitivity in the anterior chamber angle may contribute to the risks of secondary glaucoma. Intraocular tumour Intraocular tumours (uveal and retinal tumours) are also found to be closely associated with the development of secondary glaucoma. The pathophysiology of secondary glaucoma in these cases is affected by the type of tumour, location and other tumour-associated factors. Among the many subtypes of uveal tumours, secondary glaucoma is the most prominent among patients with trabecular meshwork iris melanoma. The blockage of vitreous flow due to inflammation in the structures of the trabecular meshwork is also observed in herpetic anterior uveitis patients. In addition to this, angle invasion is a mechanism that is observed to contribute greatly to the development of secondary glaucoma in patients with iris tapioca melanoma, iris lymphoma, choroidal melanoma, and medulloepithelioma. Treatment and management Pharmacological interventions Miotic drugs are a class of cholinergic drugs that are frequently employed in the treatment and management of all types of glaucoma. These drugs stimulate the contraction of the pupil causing the iris to pull away from the trabecular meshwork. Consequently, the normal drainage of the aqueous humour is restored, relieving IOP. In addition to causing a direct effect on IOP, these drugs are applied to reduce pigment release (from the iris pigment epithelium) in the treatment of pigmentary glaucoma. Despite the advantages, the widespread use of miotic drugs is limited by its associated side effects. There is an increased risk of development of posterior synechiae in glaucoma secondary to exfoliation syndrome and ocular trauma. Other side effects include increased risk of miosis-induced headaches, blurred vision, retinal detachment and damage to the blood-aqueous barrier.Alternative drugs which can reduce the synthesis of aqueous humour, called aqueous suppressants, or increase the drainage of aqueous humour emerged as effective first-line treatments. Aqueous suppressants include beta-blockers, alpha-agonists and carbonic anhydrase inhibitors. They are particularly effective in treating corticosteroid, uveitic, aphakic, pseudophakic, ghost-cell and post-traumatic glaucoma. Prostaglandin analogues increase aqueous drainage and are thus used in the reduction of IOP. There are contradictory findings regarding the occurrence of prostaglandin analogue mediated side effects in the treatment of uveitic glaucoma. It was previously identified that the side effects comprise damage to the blood-aqueous barrier, cystoid macular oedema, risk of developing anterior uveitis and recurrence of keratitis caused by herpes simplex virus. However, current scientific evidence only supports the reactivation of herpes simplex keratitis among the other side effects.In uveitic and inflammatory glaucoma, reduction in inflammation is a critical step during the treatment and management process. This is commonly done using corticosteroids coupled with immunosuppressants. Steroidal treatment is also used in management of aphakic, pseudophakic, and post-traumatic glaucoma. Inflammatory glaucoma may further be treated using cycloplegics, a class of drugs that treats pain, ciliary spasm, uveoscleral tract blockage and disrupted blood-aqueous barrier linked with this form of glaucoma. While some studies recommend the use of anti-vascular endothelial growth factor drugs for inhibition of neovascularization in neovascular glaucoma, there is a lack of substantial evidence for the effectiveness of this treatment method. Laser therapy Among different laser therapies, laser peripheral iridotomy and laser trabeculoplasty are the most common procedures for secondary glaucoma. Both methods involve creating new outlets for the aqueous humour to flow out of, effectively reducing the IOP. In peripheral laser iridotomy, the opening is created in the iris tissue while in trabeculoplasty, this opening is made in the trabecular meshwork. Further, there are two types of laser trabeculoplasty: argon laser trabeculoplasty and selective laser trabeculoplasty.Laser peripheral iridotomy has high efficacy in the treatment of pigmentary glaucoma. Argon laser trabeculoplasty is effective in the management of corticosteroid and pigmentary glaucoma. However, this is often contraindicated due to high rates of failure in patients with uveitic glaucoma. For uveitic glaucoma, treatment with selective laser trabeculoplasty is associated with fewer adverse effects and risks of failure. Surgical treatment Surgical procedures are effective in cases where pharmacological management is not successful or suitable. Such methods work by facilitating aqueous outflow through the modification of the obstructing trabecular meshwork using trabeculectomy, goniotomy, non-penetrating deep sclerectomy or canaloplasty. Alternatively, introduction of new drainage pathways may also be achieved by the implantation of glaucoma shunts or glaucoma drainage devices.Trabeculectomy is held as the gold standard for surgical management of glaucoma. Studies indicate that treatment of uveitic glaucoma using trabeculectomy with antimetabolites administration has a high success rate of 62%-81%. Thus, it is also commonly used in the treatment of pigmentary glaucoma. Drainage tube implants are also implicated in treatment of uveitic and inflammatory glaucoma.Minimally invasive glaucoma surgery is performed in order to overcome the risks and adverse effects associated with conventional surgical procedures. However, there are limited studies testing the efficacy of utilising this type of surgery for the treatment of uveitic glaucoma.In addition to the direct reduction of IOP, surgical procedures are used to remove blood, viscoelastic fluid and debris in glaucoma caused by cataract extraction and ocular trauma. They may also be utilized to remove depot steroids in corticosteroid glaucoma and ghost cells from the vitreous humour in ghost-cell glaucoma through a procedure known as vitrectomy. == References ==
Phytobezoar	A phytobezoar is a type of bezoar, or trapped mass in the gastrointestinal system, that consists of components of indigestible plant material, such as fibres, skins and seeds. While phytobezoars may be discovered incidentally on barium x-ray or endoscopic testing of the stomach, individuals with phytobezoars may develop symptoms: nausea, vomiting, gastric outlet obstruction, perforation, abdominal pain, and bleeding have been reported. Conditions that lead to decreased motility in the stomach (gastroparesis) and surgeries on the stomach (such as vagotomy or gastric bypass) are associated with the development of phytobezoars. A specific type of phytobezoar, termed a diospyrobezoar, is associated with ingestion of unripe persimmons, which contain a soluble tannin called shibuol that polymerizes into a coagulative cellulose-protein compound in the acid environment of the stomach, to form the bezoar. In addition to their presence in human stomachs, phytobezoars have been documented in the stomachs of slaughtered plant-eating animals. Cause Gastric phytobezoars are a form of intestinal blockage and are seen in those with poor gastric motility. The preferred treatment of bezoars includes different therapies and/or fragmentation to avoid surgery. Phytobezoars are most common and consist of undigested lignin, cellulose, tannins, celery, pumpkin skin, grape skins, prunes, raisins, vegetables and fruits. Phytobezoars can form after eating persimmons and pineapples. These are more difficult to treat and are referred to as diospyrobezoars. Phytobezoars are more likely to form due to the ingestion of raw plant foods, even in persons without predisposing factors, as cooking softens them for easier digestion. Treatment Several treatments for phytobezoars have been described. Endoscopy involves using a fibre-optic flexible camera to identify the phytobezoar, that can be evacuated from the stomach using various assisted devices (such as Roth baskets, snares, or Dormia baskets). If the phytobezoar cannot be removed due to size, electrohydraulic lithotripsy, mechanical lithotripsy, snares, or Nd:YAG laser therapy may be used to fragment the mass. Papain (meat tenderizer) and cellulase enzymes have been used to help reduce the size of phytobezoars. Carbonated soda ingestion has also been found to be useful to decrease the size of diospyrobezoars. A systematic review regarding initial treatment of phytobezoars with Coca-Cola found that Coca-Cola alone completely dissolved phytobezoars in half of cases, and that Coca-Cola combined with other endoscopic methods (particularly endoscopic fragmentation) was successful more than 90% of the time. The same review found that diospyrobezoars (which are considered more difficult to dissolve because of their hard consistency) were successfully treated with Coca-Cola alone in only 23% of cases, but that follow-up endoscopic fragmentation was successful in 84.6% of cases in the publications reviewed. When all other measures have failed, surgical gastrectomy is required to evacuate the bezoar. Physical and chemical properties Generally, bezoars can be found in the stomach in less than 0.5% of patients having an esophagogastroduodenoscopy. The formation of phytobezoars from persimmons is due to a chemical reaction between stomach acid and phlobatannin contained in the persimmon. Tannin and shibuol found in the skin of unripe persimmons reacts with gastric acid and forms a coagulum. This structure then accumulates cellulose, hemicellulose and protein. References == External links ==
Trichotillomania	Trichotillomania (TTM), also known as hair-pulling disorder or compulsive hair pulling, is a mental disorder characterized by a long-term urge that results in the pulling out of ones own hair. A brief positive feeling may occur as hair is removed. Efforts to stop pulling hair typically fail. Hair removal may occur anywhere; however, the head and around the eyes are most common. The hair pulling is to such a degree that it results in distress and hair loss can be seen.The disorder may run in families. It occurs more commonly in those with obsessive compulsive disorder. Episodes of pulling may be triggered by anxiety. People usually acknowledge that they pull their hair, and broken hairs may be seen on examination. Other conditions that may present similarly include body dysmorphic disorder; however, in that condition people remove hair to try to improve what they see as a problem in how they look.Treatment is typically with cognitive behavioral therapy. The medication clomipramine may also be helpful, as will keeping fingernails clipped. Trichotillomania is estimated to affect one to four percent of people. Trichotillomania most commonly begins in childhood or adolescence. Women are affected about 10 times more often than men. The name was created by François Henri Hallopeau in 1889, from the Greek θριξ/τριχ; thrix (meaning hair), along with τίλλειν; tíllein (meaning to pull), and μανία; mania (meaning madness). Signs and symptoms Trichotillomania is usually confined to one or two sites, but can involve multiple sites. The scalp is the most common pulling site, followed by the eyebrows, eyelashes, face, arms, and legs. Some less common areas include the pubic area, underarms, beard, and chest. The classic presentation is the "Friar Tuck" form of vertex and crown alopecia. Children are less likely to pull from areas other than the scalp.People with trichotillomania often pull only one hair at a time and these hair-pulling episodes can last for hours at a time. Trichotillomania can go into remission-like states where the individual may not experience the urge to "pull" for days, weeks, months, or even years.Individuals with trichotillomania exhibit hair of differing lengths; some are broken hairs with blunt ends, some new growth with tapered ends, some broken mid-shaft, or some uneven stubble. Scaling on the scalp is not present, overall hair density is normal, and a hair pull test is negative (the hair does not pull out easily). Hair is often pulled out leaving an unusual shape. Individuals with trichotillomania may be secretive or shameful of the hair pulling behavior.An additional psychological effect can be low self-esteem, often associated with being shunned by peers and the fear of socializing, due to appearance and negative attention they may receive. Some people with trichotillomania wear hats, wigs, false eyelashes, eyebrow pencil, or style their hair in an effort to avoid such attention. There seems to be a strong stress-related component. In low-stress environments, some exhibit no symptoms (known as "pulling") whatsoever. This "pulling" often resumes upon leaving this environment. Some individuals with trichotillomania may feel they are the only person with this problem due to low rates of reporting.For some people, trichotillomania is a mild problem, merely a frustration. But for many, embarrassment about hair pulling causes isolation and results in a great deal of emotional distress, placing them at risk for a co-occurring psychiatric disorder, such as a mood or anxiety disorder. Hair pulling can lead to tension and strained relationships with family members and friends. Family members may need professional help in coping with this problem.Other medical complications include infection, permanent loss of hair, repetitive stress injury, carpal tunnel syndrome, and gastrointestinal obstruction as a result of trichophagia. In trichophagia, people with trichotillomania also ingest the hair that they pull; in extreme (and rare) cases this can lead to a hair ball (trichobezoar). Rapunzel syndrome, an extreme form of trichobezoar in which the "tail" of the hair ball extends into the intestines, can be fatal if misdiagnosed.Environment is a large factor which affects hair pulling. Sedentary activities such as being in a relaxed environment are conducive to hair pulling. A common example of a sedentary activity promoting hair pulling is lying in a bed while trying to rest or fall asleep. An extreme example of automatic trichotillomania is found when some patients have been observed to pull their hair out while asleep. This is called sleep-isolated trichotillomania. Causes Anxiety, depression and obsessive–compulsive disorder are more frequently encountered in people with trichotillomania. Trichotillomania has a high overlap with post traumatic stress disorder, and some cases of trichotillomania may be triggered by stress. Another school of thought emphasizes hair pulling as addictive or negatively reinforcing, as it is associated with rising tension beforehand and relief afterward. A neurocognitive model — the notion that the basal ganglia play a role in habit formation and that the frontal lobes are critical for normally suppressing or inhibiting such habits — sees trichotillomania as a habit disorder.Abnormalities in the caudate nucleus are noted in OCD, but there is no evidence to support that these abnormalities can also be linked to trichotillomania. One study has shown that individuals with trichotillomania have decreased cerebellar volume. These findings suggest some differences between OCD and trichotillomania. There is a lack of structural MRI studies on trichotillomania. In several MRI studies that have been conducted, it has been found that people with trichotillomania have more gray matter in their brains than those who do not have the disorder.It is likely that multiple genes confer vulnerability to trichotillomania. One study identified mutations in the SLITRK1 gene. Diagnosis Patients may be ashamed or actively attempt to disguise their symptoms. This can make diagnosis difficult as symptoms are not always immediately obvious, or have been deliberately hidden to avoid disclosure. If the patient admits to hair pulling, diagnosis is not difficult; if patients deny hair pulling, a differential diagnosis must be pursued. The differential diagnosis will include evaluation for alopecia areata, iron deficiency, hypothyroidism, tinea capitis, traction alopecia, alopecia mucinosa, thallium poisoning, and loose anagen syndrome. In trichotillomania, a hair pull test is negative.A biopsy can be performed and may be helpful; it reveals traumatized hair follicles with perifollicular hemorrhage, fragmented hair in the dermis, empty follicles, and deformed hair shafts. Multiple catagen hairs are typically seen. An alternative technique to biopsy, particularly for children, is to shave a part of the involved area and observe for regrowth of normal hairs. Classification Trichotillomania is defined as a self-induced and recurrent loss of hair. It includes the criterion of an increasing sense of tension before pulling the hair and gratification or relief when pulling the hair. However, some people with trichotillomania do not endorse the inclusion of "rising tension and subsequent pleasure, gratification, or relief" as part of the criteria because many individuals with trichotillomania may not realize they are pulling their hair, and patients presenting for diagnosis may deny the criteria for tension prior to hair pulling or a sense of gratification after hair is pulled.Trichotillomania may lie on the obsessive-compulsive spectrum, also encompassing obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), nail biting (onychophagia) and skin picking (dermatillomania), tic disorders and eating disorders. These conditions may share clinical features, genetic contributions, and possibly treatment response; however, differences between trichotillomania and OCD are present in symptoms, neural function and cognitive profile. In the sense that it is associated with irresistible urges to perform unwanted repetitive behavior, trichotillomania is akin to some of these conditions, and rates of trichotillomania among relatives of OCD patients is higher than expected by chance. However, differences between the disorder and OCD have been noted, including: differing peak ages at onset, rates of comorbidity, gender differences, and neural dysfunction and cognitive profile. When it occurs in early childhood, it can be regarded as a distinct clinical entity.Because trichotillomania can be present in multiple age groups, it is helpful in terms of prognosis and treatment to approach three distinct subgroups by age: preschool age children, preadolescents to young adults, and adults.In preschool age children, trichotillomania is considered benign. For these children, hair-pulling is considered either a means of exploration or something done subconsciously, similar to nail-biting and thumb-sucking, and almost never continues into further ages.The most common age of onset of trichotillomania is between ages 9 and 13. In this age range, trichotillomania is usually chronic, and continues into adulthood. Trichiotillomania that begins in adulthood most commonly arises from underlying psychiatric causes.Trichotillomania is often not a focused act, but rather hair pulling occurs in a "trance-like" state; hence, trichotillomania is subdivided into "automatic" versus "focused" hair pulling. Children are more often in the automatic, or unconscious, subtype and may not consciously remember pulling their hair. Other individuals may have focused, or conscious, rituals associated with hair pulling, including seeking specific types of hairs to pull, pulling until the hair feels "just right", or pulling in response to a specific sensation. Knowledge of the subtype is helpful in determining treatment strategies. Treatment Treatment is based on a persons age. Most pre-school age children outgrow the condition if it is managed conservatively. In young adults, establishing the diagnosis and raising awareness of the condition is an important reassurance for the family and patient. Non-pharmacological interventions, including behavior modification programs, may be considered; referrals to psychologists or psychiatrists may be considered when other interventions fail. When trichotillomania begins in adulthood, it is often associated with other mental disorders, and referral to a psychologist or psychiatrist for evaluation or treatment is considered best. The hair pulling may resolve when other conditions are treated. Psychotherapy Habit reversal training (HRT) has the highest rate of success in treating trichotillomania. HRT has also been shown to be a successful adjunct to medication as a way to treat trichotillomania. With HRT, the individual is trained to learn to recognize their impulse to pull and also teach them to redirect this impulse. In comparisons of behavioral versus pharmacologic treatment, cognitive behavioral therapy (including HRT) have shown significant improvement over medication alone. It has also proven effective in treating children. Biofeedback, cognitive-behavioral methods, and hypnosis may improve symptoms. Acceptance and commitment therapy (ACT) is also demonstrating promise in trichotillomania treatment. A systematic review from 2012 found tentative evidence for "movement decoupling". Medication The United States Food and Drug Administration (FDA) has not approved any medications for trichotillomania treatment.However, some medications have been used to treat trichotillomania, with mixed results. Treatment with clomipramine, a tricyclic antidepressant, was shown in a small double-blind study to improve symptoms, but results of other studies on clomipramine for treating trichotillomania have been inconsistent. Naltrexone may be a viable treatment. Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have limited usefulness in treating trichotillomania, and can often have significant side effects. Behavioral therapy has proven more effective when compared to fluoxetine. There is little research on the effectiveness of behavioral therapy combined with medication, and robust evidence from high-quality studies is lacking. Acetylcysteine treatment stemmed from an understanding of glutamates role in regulation of impulse control.Different medications, depending on the individual, may increase hair pulling. Devices Technology can be used to augment habit reversal training or behavioral therapy. Several mobile apps exist to help log behavior and focus on treatment strategies. There are also wearable devices that track the position of a users hands. They produce sound or vibrating notifications so that users can track rates of these events over time. Prognosis When it occurs in early childhood (before five years of age), the condition is typically self-limiting and intervention is not required. In adults, the onset of trichotillomania may be secondary to underlying psychiatric disturbances, and symptoms are generally more long-term.Secondary infections may occur due to picking and scratching, but other complications are rare. Individuals with trichotillomania often find that support groups are helpful in living with and overcoming the disorder. Epidemiology Although no broad-based population epidemiologic studies had been conducted as of 2009, the lifetime prevalence of trichotillomania is estimated to be between 0.6% and 4.0% of the overall population. With a 1% prevalence rate, 2.5 million people in the U.S. may have trichotillomania at some time during their lifetimes.Trichotillomania is diagnosed in all age groups; onset is more common during preadolescence and young adulthood, with mean age of onset between 9 and 13 years of age, and a notable peak at 12–13. Among preschool children the genders are equally represented; there appears to be a female predominance among preadolescents to young adults, with between 70% and 93% of patients being female. Among adults, females typically outnumber males by 3 to 1."Automatic" pulling occurs in approximately three-quarters of adult patients with trichotillomania. History Hair pulling was first mentioned by Aristotle in the fourth century B.C., was first described in modern literature in 1885, and the term trichotillomania was coined by the French dermatologist François Henri Hallopeau in 1889.In 1987, trichotillomania was recognized in the Diagnostic and Statistical Manual of the American Psychiatric Association, third edition-revised (DSM-III-R). Society and culture Support groups and internet sites can provide recommended educational material and help persons with trichotillomania in maintaining a positive attitude and overcoming the fear of being alone with the disorder. Media A documentary film exploring trichotillomania, Bad Hair Life, was the 2003 winner of the International Health & Medical Media Award for best film in psychiatry and the winner of the 2004 Superfest Film Festival Merit Award.Trichster is a 2016 documentary that follows seven individuals living with trichotillomania, as they navigate the complicated emotions surrounding the disorder, and the effect it has on their daily lives. Fiction The trichotillomania of a prominent character is a key plot element in the 1999 novel Whatever Love Means by David Baddiel.In the superhero fiction series The Boys character Ashley Barret, portrayed by Colby Minifie is shown suffering from it. Music On the 2017 album, 20s a Difficult Age by Marcus Orelias, there is a song called "Trichotillomania". See also Feather-plucking Noncicatricial alopecia Psychogenic alopecia, a form of baldness that is caused by excessive grooming in cats Self-harm == References ==
Antepartum bleeding	Antepartum bleeding, also known as antepartum haemorrhage (APH) or prepartum hemorrhage, is genital bleeding during pregnancy after the 28th week of pregnancy up to delivery.It can be associated with reduced fetal birth weight. Use of aspirin before 16 weeks of pregnancy to prevent pre-eclampsia also appears effective at preventing antepartum bleeding.In regard to treatment, it should be considered a medical emergency (regardless of whether there is pain), as if it is left untreated it can lead to death of the mother or baby. Classification The total amount of blood loss and signs of circulatory shock due to blood determine the severity of the antepartum haemorrhaging. There are 4 degrees of antepartum haemorrhaging: Causes Placenta praevia Placenta praevia refers to when the placenta of a growing foetus is attached abnormally low within the uterus. Intermittent antepartum haemorrhaging occurs in 72% of women living with placenta praevia. The severity of a patients placenta praevia depends on the location of placental attachment; Types 1 and 2 are classified as minor placental praevia as these typically result in minor antepartum haemorrhaging. Types 3 and 4 are referred to as major placental praevia due to the risk of heavy haemorrhaging in the case of a rupture due to the location of placental attachment. During the third trimester of pregnancy, thinning of the lower uterine segment or contractions caused by cervical dilation can increase the amount of stress placed on the placental attachment to the uterine wall. In patients with placenta praevia, these stresses can cause detachment of the placenta from the uterine wall causing haemorrhaging. To prevent further haemorrhaging patients with major placental praevia are recommended to have a caesarean delivery. Abnormal placentation During pregnancy the layer of endometrium that attaches directly to developing blastocyst becomes the maternal portion of the placenta, also known as the decidua basalis. In the absence of a decidua basalis, trophoblast cells on the developing blastocyst form an abnormally deep attachment to the uterine wall, this is known as abnormal placentation. Abnormal placentation can categorised into 3 types, depending on the depth of infiltration of the chorionic villi into the uterine wall: In placenta percreta, the chorionic villi have grow entirely through the myometrium and invade into the perimetrium. Placenta percreta results in the most intense haemorrhaging that can be expected caused by abnormal placentation. In the event of placental detachment from the uterine wall, the depth of chorionic villi attachment dictates the amount of haemorrhaging that can be expected. The chance of abnormal placentation increases in subsequent pregnancies, if there is scar tissue present from previous pregnancies. For example, previously undergoing a caesarean or placenta previa increases the likelihood of abnormal placentation, therefore increasing the chances of antepartum haemorrhaging. Placental abruption Placental abruption occurs when the placenta detaches from the endometrium. Detachment causes antepartum haemorrhaging at the location of abruption. Depending on the site of detachment, haemorrhaging may or may not be apparent. If abruption occurs behind the placenta where blood cannot escape through the cervix, blood will pool and form a retroplacental clot. Only when the site of detachment occurs on the side facing the cervical opening can the total amount of haemorrhaging be measured by vaginal bleeding. Using vaginal bleeding as a measurement of the severity of the placental abruption is therefore ineffective. The scale of haemorrhaging depends on the degree to which the placenta has separated from the uterine wall. In the case of partial placental separation, haemorrhaging can be minor. However, in the case of total placental separation haemorrhaging will be major and emergency delivery will typically be the course of action. Placental abruption causes blood loss from the mother and loss of oxygen and nutrients to the placenta occasionally leading to preterm labour. Other causes of placental abruption can be abdominal trauma or sudden decompression of amniotic fluid, however it is not uncommon for the cause of placental abruption to be unknown. Vasa praevia Vasa praevia is the presence of unprotected foetal blood vessels running along the placenta and over the internal cervical opening. Vasa praevia is a very rare, presenting only 4:10,000 cases from the largest study of the condition. Risks of antepartum bleeding due to vasa praevia greatly increase during the third trimester of pregnancy during cervical dilation or placenta praevia. Vessel rupture is very likely in the event of a membranous rupture as foetal blood vessels arent protected by the umbilical cord of the placenta. In the event of foetal vessel rupture, antepartum haemorrhaging occurs however blood is lost from the foetal blood supply. If the foetus is developed enough caesarean sections are often recommended. Abnormal placental shape Circumvallate placentaA circumvallate placenta refers to when the foetal membrane wraps twice around, over the foetal side around the edge of the placenta. This is to compensate for an undersized chorionic plate resulting in a decreased nutritional supply to the foetus. Thickening of the placental edge due to a circumvallate placenta can lead to placental abruption, causing antepartum haemorrhaging. Bilobed PlacentaA bilobed placenta has a cleavage in the middle dividing it into two lobes with membranous vessels branching in between. The exposed connecting membranous vessels present risk of rupturing due to limited protection from thrombosis and trauma. Bilobing of the placenta can be caused by placental implantation occurring over areas of uterine fibroid scarring, previous surgery, decreased blood supply or implantation occurring over the internal cervical orifice. Chances of vasa previa and placental abruption increase in the presence of a bilobed placenta due to decreased surface area for attachment to the uterine wall and the exposure of membranous vessels. Multilobed or Succenturiate PlacentaWhen a placenta has multiple lobes which are distal and not of equal size this is referred to as a succenturiate placenta. Distal lobes are connected by a placental artery and vein extending from the main placenta, which tends to be centrally located and is the largest in mass. At the time of contraction or delivery the connecting placental arteries and veins may rupture resulting in significant haemorrhaging. Incidences of vasa previa and haemorrhaging in the presence of a succenturiate placenta are highly increased. Fetal blood (can be distinguished with Apt test) Minor causes Cervical ectropion There are 2 types of epithelial cells present within the cervical canal. In the endocervix the epithelia is columnar glandular which transitions into stratified squamous towards the ectocervix and external cervical orifice. During cervical ectropion the epithelial transitional zone (also called the squamo-columnar junction) migrates from the endocervical canal towards the ectocervix exposing some columnar glandular cells on the external cervical orifice. Unlike stratified squamous epithelial cells, glandular cells are columnar and not used to external stresses such as abrasion. The translocation of these cells causes bleeding and mucus secretion. Cervical ectropion can be attributed to rises in oestrogen levels during foetal development. Antepartum haemorrhage caused by cervical ectropion can be expected and is typically harmless.Vaginal infection The presence of severe vaginal infections at the time of pregnancy may cause minor antepartum haemorrhaging. For example, the presence of chlamydia, thrush, cervicitis or other infections are all irritants to the vaginal and cervical lining, causing bleeding from those surfaces where the infection is severe.Cervical canal and distal genital tract Most cases of Antepartum haemorrhaging originate from within the cervical canal or vagina. The amount of bleeding in these areas are typically limited to spotting or minor antepartum haemorrhaging. Cervical ectropion, dysplasia, polyps or cervical carcinoma may cause lesions in the cervix leading to minor haemorrhaging or spotting. Abrasion or slight trauma caused by intercourse, clinical examinations and pap smear may also cause spotting from the cervix. Vaginal bleeding from atrophy, vaginitis, and ulcers also attribute to minor haemorrhaging. Similarly, varicosities, tumours or inflammation in the vulva can cause minor antepartum haemorrhaging. Non genital tract bleeding caused by haematuria or haemorrhoids can often be mistaken for antepartum haemorrhaging and are typically harmless. Diagnosis Differential diagnosis GI bleed - haemorrhoids, inflammatory bowel disease See also Obstetrical haemorrhage References == External links ==
Birth trauma	Birth trauma may refer to: Childbirth-related posttraumatic stress disorder, psychological trauma to the mother following childbirth Birth trauma (physical), physical trauma to the infant following childbirth, as described at ICD-10 codes P10-P15 Birth trauma (psychoanalysis), a concept in Freudian psychoanalysis described by Otto Rank
Spastic cerebral palsy	Spastic cerebral palsy is the type of cerebral palsy characterized by spasticity or high muscle tone often resulting in stiff, jerky movements. Cases of spastic CP are further classified according to the part or parts of the body that are most affected. Such classifications include spastic diplegia, spastic hemiplegia, spastic quadriplegia, and in cases of single limb involvement, spastic monoplegia.Spastic cerebral palsy affects the motor cortex of the brain, a specific portion of the cerebral cortex responsible for the planning and completion of voluntary movement. Spastic CP is the most common type of overall cerebral palsy, representing roughly 80% of cases. Spastic CP is a permanent condition and will affect an individual across the lifespan. The brain injury that causes spastic CP remains stable over time, but the way spasticity affects a person can change. For example, with age they may develop bone deformities from the pull of spastic muscles, muscular deterioration, and loss of range of motion in a joint. Thus, individuals with spastic CP often have different support needs with time. Signs and symptoms People with the spastic type of CP typically have muscles that are "tight" or stiff due to high muscle tone. Symptoms of spastic cerebral palsy vary as the disability can affect individuals differently. However, they typically appear in infancy and early childhood and most children are diagnosed in the first two years of life. The main indicator of spastic cerebral palsy is a delay in reaching motor milestones. The following are some common early signs, though the presence of a listed symptom does not definitively mean that a child has spastic CP:Prior to 6 months Legs crossing when a child is picked up, also called scissoring Stiffness Head "lagging" when the child is picked up6–10 months Fisting one hand Difficulty rolling Difficulty bringing hands togetherOlder than 12 months of age Difficulty crawling Difficulty standing even with support Walking with an unsteady, uneven, or stiff gaitSpastic CP is distinguished from other forms of cerebral palsy by its prominent symptom of spasticity or stiff, tight movements and gait patterns such as the scissor gait. However, spasticity as a symptom is also seen in other conditions such as stroke and multiple sclerosis. Thus, the presence of spasticity alone does not warrant a conclusive diagnosis of spastic cerebral palsy. Changes in spasticity and corresponding postures may also occur with other brain activity, such as excitement, fear or anxiety, or even pain, which increase muscle tension.A person with spastic CP will commonly show, in addition to higher muscle tone, persistent primitive reflexes, greater stretch reflexes, plantar reflex, and ankle clonus.A third of people with cerebral palsy have seizures - this is most common in spastic CP. Audiovisual, cognitive compromise and behavioral disorders can occur. Cause Spastic cerebral palsy is caused by malformation of or damage to the parts of the brain that control movement. What exactly makes some children susceptible to such brain damage is often unknown but it is believed that cerebral palsy may be the result of causal pathways, or chains of events that cause or increase the likelihood of brain injury. Most of the time, children are born with the brain damage resulting in spastic cerebral palsy, but a small percentage experience the damage shortly after birth following a stroke, head injury, or infection.The following are types of brain damage that can result in spastic cerebral palsy: cerebral dysgenesis periventricular leukomalacia brain bleeds Hypoxic ischaemic encephalopathy Risk factors The following medical conditions are associated with increased likelihood of spastic cerebral palsy, as well as with other types of cerebral palsy: Preterm birth/low birthweight Multiple births Incompatible blood type between mother and fetus Exposure to toxins Complicated labor Diagnosis There is no single test to diagnose spastic cerebral palsy. It is typically diagnosed by age 2, though milder cases may go undetected for a longer time. A doctor will typically use a series of tests to assess developmental progress in growth, muscle control, coordination, vision, hearing, and posture. Continuous loss of motor skills likely indicates a condition other than spastic CP such as a genetic muscle disease Some metabolic disorders mimic spastic cerebral palsy and can be ruled out using a Magnetic resonance imaging test (MRI).Some tests to assess a child suspected to have spastic cerebral palsy are: Cranial ultrasound CT scan Magnetic resonance imagingThese tests are imaging techniques used to produce pictures of the brain and to examine them for areas of damage that indicate a diagnosis of spastic cerebral palsy. A child with a spastic CP diagnosis will likely be referred to screening for other conditions associated with spastic cerebral palsy such as epilepsy (seizure disorder), intellectual disability, and visual impairment. Types Scientific classifications The types of spastic cerebral palsy are generally distinguished by the primary areas of the body that are affected. Spastic hemiplegia Hemiplegia is a type of cerebral palsy affecting one vertical half of the body (such as one arm and one leg). The affected side of the body is opposite the affected area of the brain in hemiplegia. For example, if the right side of the brain is damaged, the person will have weakness or paralysis on the left side of the body. People with hemiplegia typically favor an arm or hand and may keep the weaker hand in a fist. Typically, people that have spastic hemiplegia are the most ambulatory of all the forms, although they generally have dynamic equinus (a limping instability) on the affected side and are primarily prescribed ankle-foot orthoses to prevent said equinus. Spastic diplegia describes spastic CP in which muscle tightness predominantly occurs in the legs. The arms may be somewhat affected or not affected at all. Spastic monoplegia is one single limb being affected. Spastic triplegia is three limbs being affected. Spastic quadriplegia is all four limbs more or less equally affected. People with spastic quadriplegia are rarely able to ambulate without assistance and may not stand at all. Among the forms of spastic CP, quad CP is more likely to co-occur with seizures and mild to moderate intellectual disability.In spastic cerebral palsy in children with low birth weights, 25% of children had hemiplegia, 37.5% had quadriplegia, and 37.5% had diplegia. No one person with a particular type of spastic CP presents in exactly the same way. Treatment There is no cure for spastic cerebral palsy and no way to reverse the initial brain injury. However, various treatments and assistive devices can help mitigate pain and allow those affected to have a higher quality of life. Different combinations of treatments are right for each individual and are determined by individuals and their care team.Some common interventions are: Physical therapy- exercises to develop balance and strength and to learn skills such as walking, rolling, or driving a wheelchair. Occupational therapy- therapy to help an individual develop strategies to complete activities of daily living such as dressing, toileting, and bathing either independently or with a level of assistance that is safe and comfortable. Orthotics- braces and splints to improve posture and positioning (usually on legs or arms). Assistive devices- Wheelchairs, crutches, and walkers may help someone with spastic CP navigate safely. Different devices may be used in different settings or for longer distances. People with cerebral palsy may use up to 3-5 times the energy as those without when moving; thus, a device such as a wheelchair may reduce fatigue. Speech therapy- Therapy to help someone speak more clearly, swallow more safely, or use a communication device such as a DynaVox Medication- Certain medications can reduce stiffness from overactive muscles and decrease pain. Examples are botulinum toxin or baclofen, with the latter delivered orally or via an intrathecal pump. Surgery- In some cases, orthopedic and/or neurological surgeries are recommended when pain and stiffness interfere with participation in meaningful activities and other treatments are not effective. Prognosis Every case of spastic cerebral palsy is different. Some people with this type of CP can accomplish activities of daily living independently, while some need the assistance of a personal care aide for certain tasks, and others need 24-hour support. About 1/3 of people with cerebral palsy cannot walk, about 1/2 have intellectual disabilities, and 3/4 experience some level of chronic pain. There is limited research on adults with spastic CP. The brain injury causing CP does not progress or change, but the functional impact and thus, ones needs may change with age.Some issues specific to adults with spastic and other forms of cerebral palsy are: Premature aging Fatigue Pain Arthritis Depression and anxiety Post impairment syndromeRegardless of their particular expression of spastic cerebral palsy, affected individuals can lead fulfilling lives. Improved physical accessibility in society and increased social acceptance can increase community participation. Workforce participation of people with CP has almost doubled in the last four decades. Social inclusion and the presence or absence of policy to address discrimination, in addition to medical intervention, influences the outlook for people living with spastic cerebral palsy. See also General movements assessment References == External links ==
Chondroid lipoma	Chondroid lipomas are deep-seated, firm, yellow tumors that characteristically occur on the legs of women. They exhibit a characteristic genetic translocation t(11;16) with a resulting C11orf95-MKL2 fusion oncogene.: 625 See also Lipoma Skin lesion List of cutaneous conditions References == External links ==
Wound	A wound is a rapid onset of injury that involves lacerated or punctured skin (an open wound), or a contusion (a closed wound) from blunt force trauma or compression. In pathology, a wound is an acute injury that damages the epidermis of the skin. Classification According to level of contamination, a wound can be classified as: Clean wound – made under sterile conditions where there are no organisms present, and the skin is likely to heal without complications. Contaminated wound – usually resulting from accidental injury; there are pathogenic organisms and foreign bodies in the wound. Infected wound – the wound has pathogenic organisms present and multiplying, exhibiting clinical signs of infection (yellow appearance, soreness, redness, oozing pus). Colonized wound – a chronic situation, containing pathogenic organisms, difficult to heal (e.g. bedsore). Open Open wounds can be classified according to the object that caused the wound: Incisions or incised wounds – caused by a clean, sharp-edged object such as a knife, razor, or glass splinter. Lacerations – irregular tear-like wounds caused by some blunt trauma. Lacerations and incisions may appear linear (regular) or stellate (irregular). The term laceration is commonly misused in reference to incisions. Abrasions (grazes) – superficial wounds in which the topmost layer of the skin (the epidermis) is scraped off. Abrasions are often caused by a sliding fall onto a rough surface such as asphalt, tree bark or concrete. Avulsions – injuries in which a body structure is forcibly detached from its normal point of insertion. A type of amputation where the extremity is pulled off rather than cut off. When used in reference to skin avulsions, the term degloving is also sometimes used as a synonym. Puncture wounds – caused by an object puncturing the skin, such as a splinter, nail or needle. Penetration wounds – caused by an object such as a knife entering and coming out from the skin. Gunshot wounds – caused by a bullet or similar projectile driving into or through the body. There may be two wounds, one at the site of entry and one at the site of exit, generally referred to as a "through-and-through." Critical wounds- Including large burns that have been split. These wounds can cause serious hydroelectrolytic and metabolic alterations including fluid loss, electrolyte imbalances, and increased catabolism Closed Closed wounds have fewer categories, but are just as dangerous as open wounds: Hematomas (or blood tumor) – caused by damage to a blood vessel that in turn causes blood to collect under the skin. Hematomas that originate from internal blood vessel pathology are petechiae, purpura, and ecchymosis. The different classifications are based on size. Hematomas that originate from an external source of trauma are contusions, also commonly called bruises. Crush injury – caused by a great or extreme amount of force applied over a long period of time. Presentation Complications Bacterial infection of wound can impede the healing process and lead to life-threatening complications. Scientists at Sheffield University have used light to rapidly detect the presence of bacteria, by developing a portable kit in which specially designed molecules emit a light signal when bound to bacteria. Current laboratory-based detection of bacteria can take hours or days. Workup Wounds that are not healing should be investigated to find the causes; many microbiological agents may be responsible. The basic workup includes evaluating the wound, its extent and severity. Cultures are usually obtained both from the wound site and blood. X-rays are obtained and a tetanus shot may be administered if there is any doubt about prior vaccination. Chronic Non-healing wounds of the diabetic foot are considered one of the most significant complications of diabetes, representing a major worldwide medical, social, and economic burden that greatly affects patient quality of life. Almost 24 million Americans—one in every twelve—are diabetic and the disease is causing widespread disability and death at an epidemic pace, according to the Centers for Disease Control and Prevention. Of those with diabetes, 6.5 million are estimated to have chronic or non-healing wounds. Associated with inadequate circulation, poorly functioning veins, and immobility, non-healing wounds occur most frequently in the elderly and in people with diabetes—populations that are sharply rising as the nation ages and chronic diseases increase. Although diabetes can ravage the body in many ways, non-healing ulcers on the feet and lower legs are common outward manifestations of the disease. Also, diabetics often experience nerve damage in their feet and legs, allowing small wounds or irritations to develop without awareness. Given the abnormalities of the microvasculature and other side effects of diabetes, these wounds take a long time to heal and require a specialized treatment approach for proper healing. As many as 75% of diabetic patients will eventually develop foot ulcers, and recurrence within five years is 70%. If not aggressively treated, these wounds can lead to amputations. It is estimated that every 30 seconds a lower limb is amputated somewhere in the world because of a diabetic wound. Amputation often triggers a downward spiral of declining quality of life, frequently leading to disability and death. In fact, only about one third of diabetic amputees will live more than five years, a survival rate equivalent to that of many cancers. Many of these lower extremity amputations can be prevented through an interdisciplinary approach to treatment involving a variety of advanced therapies and techniques, such as debridement, hyperbaric oxygen treatment therapy, dressing selection, special shoes, and patient education. When wounds persist, a specialized approach is required for healing. Pathophysiology To heal a wound, the body undertakes a series of actions collectively known as the wound healing process. Diagnosis A wound may be recorded for follow-up and observing progress of healing with different techniques which include: Photographs, with subsequent area quantification using computer processing Wound tracings on acetate sheets Kundin wound gauge Management The overall treatment depends on the type, cause, and depth of the wound, and whether other structures beyond the skin (dermis) are involved. Treatment of recent lacerations involves examining, cleaning, and closing the wound. Minor wounds, like bruises, will heal on their own, with skin discoloration usually disappearing in 1–2 weeks. Abrasions, which are wounds with intact skin (non-penetration through dermis to subcutaneous fat), usually require no active treatment except keeping the area clean, initially with soap and water. Puncture wounds may be prone to infection depending on the depth of penetration. The entry of puncture wound is left open to allow for bacteria or debris to be removed from inside. Cleaning Evidence to support the cleaning of wounds before closure is scant. For simple lacerations, cleaning can be accomplished using a number of different solutions, including tap water and sterile saline solution. Infection rates may be lower with the use of tap water in regions where water quality is high. Cleaning of a wound is also known as wound toilet. It is not clear if delaying a shower following a surgery helps reduce complications related to wound healing. Wound cleansing solutions Evidence is insufficient to conclude whether cleaning wounds is beneficial or whether wound cleaning solutions (polyhexamethylene biguanide, aqueous oxygen peroxide, etc.) are better than sterile water or saline solutions to help venous leg ulcers heal. It is also uncertain whether the choice of cleaning solution or method of application makes any difference to venous leg ulcer healing. Closure If a person presents to a healthcare center within 6 hours of a laceration they are typically closed immediately after evaluating and cleaning the wound. After this point in time, however, there is a theoretical concern of increased risks of infection if closed immediately. Thus some healthcare providers may delay closure while others may be willing to immediately close up to 24 hours after the injury. Using clean non-sterile gloves is equivalent to using sterile gloves during wound closure.If closure of a wound is decided upon a number of techniques can be used. These include bandages, a cyanoacrylate glue, staples, and sutures. Absorbable sutures have the benefit over non absorbable sutures of not requiring removal. They are often preferred in children. Buffering the pH of lidocaine makes the injection less painful. Adhesive glue and sutures have comparable cosmetic outcomes for minor lacerations <5 cm in adults and children. The use of adhesive glue involves considerably less time for the doctor and less pain for the person. The wound opens at a slightly higher rate but there is less redness. The risk for infections (1.1%) is the same for both. Adhesive glue should not be used in areas of high tension or repetitive movements, such as joints or the posterior trunk. Split-thickness skin grafting (STSG) is also a surgical technique that features rapid wound closure, multiple possible donor sites with minimal morbidity. Dressings In the case of clean surgical wounds, there is no evidence that the use of topical antibiotics reduces infection rates in comparison with non-antibiotic ointment or no ointment at all. Antibiotic ointments can irritate the skin, slow healing, and greatly increase the risk of developing contact dermatitis and antibiotic resistance. Because of this, they should only be used when a person shows signs of infection and not as a preventative.The effectiveness of dressings and creams containing silver to prevent infection or improve healing is not currently supported by evidence. Alternative medicine There is moderate evidence that honey is more effective than antiseptic followed by gauze for healing wounds infected after surgical operations. There is a lack of quality evidence relating to the use of honey on other types of wounds, such as minor acute wounds, mixed acute and chronic wounds, pressure ulcers, Fourniers gangrene, venous leg ulcers, diabetic foot ulcers and Leishmaniasis.There is no good evidence that therapeutic touch is useful in healing. More than 400 species of plants are identified as potentially useful for wound healing. Only three randomized controlled trials, however, have been done for the treatment of burns. History From the Classical Period to the Medieval Period, the body and the soul were believed to be intimately connected, based on several theories put forth by the philosopher Plato. Wounds on the body were believed to correlate with wounds to the soul and vice versa; wounds were seen as an outward sign of an inward illness. Thus, a man who was wounded physically in a serious way was said to be hindered not only physically but spiritually as well. If the soul was wounded, that wound may also eventually become physically manifest, revealing the true state of the soul. Wounds were also seen as writing on the "tablet" of the body. Wounds acquired in war, for example, told the story of a soldier in a form which all could see and understand, and the wounds of a martyr told the story of their faith. Research In humans and mice it has been shown that estrogen might positively affect the speed and quality of wound healing. See also European Wound Management Association International Red Cross Wound Classification System Wound bed preparation References External links US based wound healing society Association for the Advancement of Wound Care AAWC European Wound Management Association – EWMA works to promote the advancement of education and research.
Cone dystrophy	A cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision. Presentation The most common symptoms of cone dystrophy are vision loss (age of onset ranging from the late teens to the sixties), sensitivity to bright lights, and poor color vision. Therefore, patients see better at dusk. Visual acuity usually deteriorates gradually, but it can deteriorate rapidly to 20/200; later, in more severe cases, it drops to "counting fingers" vision. Color vision testing using color test plates (HRR series) reveals many errors on both red-green and blue-yellow plates. Dystrophy of the rods and cones Dystrophy of the light-sensing cells of the eye may also occur in the rods as well, or in both the cones and the rods. A type of rod-cone dystrophy—where rod function decline is typically earlier or more pronounced than cone dystrophy—has been identified as a relatively common characteristic of Bardet–Biedl Syndrome.At least one type of autosomal dominant cone-rod dystrophy is caused by mutations in the guanylate cyclase 2D (not geometrical) gene (GUCY2D) on chromosome 17. Mechanism The pathogenesis of cone dystrophy has yet to be elucidated. It appears that the dystrophy is primary, since subjective and objective abnormalities of cone function are found before ophthalmoscopic changes can be seen. However, the retinal pigment epithelium (RPE) rapidly becomes involved, leading to a retinal dystrophy primarily involving the macula. The histological examination of the eyes of one such patient showed that the outer nuclear layer of cones and rods had disappeared completely, whereas the RPE showed pronounced pigment changes. There was also atrophy of the temporal disc. Diagnosis The fundus exam via ophthalmoscopy is essentially normal early on in cone dystrophy, and definite macular changes usually occur well after visual loss. Fluorescein angiography (FA) is a useful adjunct in the workup of someone suspected to have cone dystrophy, as it may detect early changes in the retina that are too subtle to be seen by ophthalmoscope. For example, FA may reveal areas of hyperfluorescence, indicating that the RPE has lost some of its integrity, allowing the underlying fluorescence from the choroid to be more visible. These early changes are usually not detected during the ophthalmoscopic exam. The most common type of macular lesion seen during ophthalmoscopic examination has a bulls-eye appearance and consists of a doughnut-like zone of atrophic pigment epithelium surrounding a central darker area. In another, less frequent form of cone dystrophy there is rather diffuse atrophy of the posterior pole with spotty pigment clumping in the macular area. Rarely, atrophy of the choriocapillaris and larger choroidal vessels is seen in patients at an early stage. The inclusion of fluorescein angiography in the workup of these patients is important since it can help detect many of these characteristic ophthalmoscopic features. In addition to the retinal findings, temporal pallor of the optic disc is commonly observed. As expected, visual field testing in cone dystrophy usually reveals a central scotoma. In cases with the typical bulls-eye appearance, there is often relative central sparing.Because of the wide spectrum of fundus changes and the difficulty in making the diagnosis in the early stages, electroretinography (ERG) remains the best test for making the diagnosis. Abnormal cone function on the ERG is indicated by a reduced single-flash and flicker response when the test is carried out in a well-lit room (photopic ERG). The relative sparing of rod function in cone dystrophy is evidenced by a normal scotopic ERG, i.e. when the test is carried out in the dark. In more severe or longer standing cases, the dystrophy involves a greater proportion of rods with resultant subnormal scotopic records. Since cone dystrophy is hereditary and can be asymptomatic early on in the disease process, ERG is an invaluable tool in the early diagnosis of patients with positive family histories. Cone dystrophy in general usually occurs sporadically. Hereditary forms are usually autosomal dominant, and instances of autosomal recessive and X-linked inheritance also occur. In the differential diagnosis, other macular dystrophies as well as the hereditary optic atrophies must be considered. Fluorescent angiography, ERG, and color vision tests are important tools to help facilitate diagnosis in early stages. Treatment Though there is no treatment for cone dystrophy, certain supplements may help in delaying the progression of the disease. The beta-carotenoids, lutein and zeaxanthin, have been evidenced to reduce the risk of developing age-related macular degeneration (AMD), and may therefore provide similar benefits to people with cone dystrophy.Consuming omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) has been correlated with a reduced progression of early AMD, and in conjunction with low glycemic index foods, with reduced progression of advanced AMD, and may therefore delay the progression of cone dystrophy. Dr. Randall Walker, who has a variation of the condition himself, invented a software to enable low vision people to read with greater ease.<ref>url= https://www.bizjournals.com/twincities/print-edition/2014/06/06/made-at-mayo-mayo-professor-doubles-as-founder-of.html <ref> Notes References Stephen J. Ryan et al., Retina, 3rd ed. (C.V. Mosby, 2001) ISBN 0-323-00804-6 Stephen J. Ryan et al., Retina, 4th ed. (C.V. Mosby, 2005) ISBN 0-323-02598-6 Carpentier S, Knaus M, Suh M (April 2009). "Associations between lutein, zeaxanthin, and age-related macular degeneration: an overview". Crit Rev Food Sci Nutr. 49 (4): 313–26. doi:10.1080/10408390802066979. PMID 19234943. S2CID 23524407.{{cite journal}}: CS1 maint: multiple names: authors list (link) "Abstract doesnt include conclusion" Chiu CJ, Klein R, Milton RC, Gensler G, Taylor A (September 2009). "Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?". Br J Ophthalmol. 93 (9): 1241–6. doi:10.1136/bjo.2008.143412. PMC 3033729. PMID 19508997.{{cite journal}}: CS1 maint: multiple names: authors list (link) "Conclusions: The findings show an association of consuming a diet rich in DHA with a lower progression of early AMD. In addition to the AREDS supplement, a lower dGI with higher intakes of DHA and EPA was associated with a reduced progression to advanced AMD." == External links ==
Lipid storage disorder	A lipid storage disorder (or lipidosis) is any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some body cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize and break down lipids or, they produce enzymes that do not work properly. Over time, the buildup of fats may cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen, and bone marrow. Inside cells under normal conditions, lysosomes convert, or metabolize, lipids and proteins into smaller components to provide energy for the body. Classification Disorders that store this intracellular material are part of the lysosomal storage diseases family of disorders. Sphingolipidoses Many lipid storage disorders can be classified into the subgroup of sphingolipidoses, as they relate to sphingolipid metabolism. Members of this group include Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease, metachromatic leukodystrophy, multiple sulfatase deficiency, and Farber disease. They are generally inherited in an autosomal recessive fashion, but Fabry disease is X-linked. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000. Enzyme replacement therapy is available mainly to treat Fabry disease and Gaucher disease and people with these types of sphingolipidoses may live well into adulthood. Generally, the other types are fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile-onset or adult-onset forms.Alternatively, some of the sphingolipidoses may be classified into either GM1 gangliosidoses or GM2 gangliosidoses. Tay–Sachs disease belongs to the latter. Other Other lipid storage disorders that generally are not classified as sphingolipidoses include fucosidosis, Schindler disease, and Wolman disease. Genetics Lipid storage diseases can be inherited two ways: Autosomal recessive inheritance occurs when both parents carry and pass on a copy of the faulty gene, but neither parent show signs and symptoms of the condition and is not affected by the disorder. Each child born to these parents have a 25 percent chance of inheriting both copies of the defective gene, a 50 percent chance of being a carrier, and a 25 percent chance of not inheriting either copy of the defective gene. Children of either gender may be affected by an autosomal recessive this pattern of inheritance.X-linked recessive (or sex linked) inheritance occurs when the mother carries the affected gene on the X chromosome that has determined the childs gender and passes it to her son. Sons of carriers have a 50 percent chance of inheriting the disorder. Daughters have a 50 percent chance of inheriting the X-linked chromosome, but usually are not severely affected by the disorder. Affected men do not pass the disorder to their sons, but their daughters will be carriers for the disorder. Diagnosis Diagnosis of the lipid storage disorders can be achieved through the use of several tests. These tests include clinical examination, biopsy, genetic testing, molecular analysis of cells or tissues, and enzyme assays. Certain forms of this disease also can be diagnosed through urine testing, which detects the stored material. Prenatal testing also is available to determine whether the fetus will have the disease or is a carrier. Treatment There are no specific treatments for lipid storage disorders; however, there are some highly effective enzyme replacement therapies for people with type 1 Gaucher disease and some patients with type 3 Gaucher disease. There are other treatments such as the prescription of certain drugs such as phenytoin and carbamazepine to treat pain for patients with Fabry disease. Furthermore, gene therapies and bone marrow transplantation may prove to be effective for certain lipid storage disorders.Diet restrictions do not help prevent the buildup of lipids in the tissues. See also Xanthomatosis Niemann–Pick disease References == External links ==
Acne	Acne, also known as acne vulgaris, is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and possible scarring. It primarily affects skin with a relatively high number of oil glands, including the face, upper part of the chest, and back. The resulting appearance can lead to anxiety, reduced self-esteem, and, in extreme cases, depression or thoughts of suicide.Susceptibility to acne is primarily genetic in 80% of cases. The roles of diet and cigarette smoking in the condition are unclear, and neither cleanliness nor exposure to sunlight appear to play a part. In both sexes, hormones called androgens appear to be part of the underlying mechanism, by causing increased production of sebum. Another common factor is the excessive growth of the bacterium Cutibacterium acnes, which is present on the skin.Treatments for acne are available, including lifestyle changes, medications, and medical procedures. Eating fewer simple carbohydrates such as sugar may minimize the condition. Treatments applied directly to the affected skin, such as azelaic acid, benzoyl peroxide, and salicylic acid, are commonly used. Antibiotics and retinoids are available in formulations that are applied to the skin and taken by mouth for the treatment of acne. However, resistance to antibiotics may develop as a result of antibiotic therapy. Several types of birth control pills help prevent acne in women. Medical professionals typically reserve isotretinoin pills for severe acne, due to greater potential side effects. Early and aggressive treatment of acne is advocated by some in the medical community to decrease the overall long-term impact on individuals.In 2015, acne affected approximately 633 million people globally, making it the eighth-most common disease worldwide. Acne commonly occurs in adolescence and affects an estimated 80–90% of teenagers in the Western world. Some rural societies report lower rates of acne than industrialized ones. Children and adults may also be affected before and after puberty. Although acne becomes less common in adulthood, it persists in nearly half of affected people into their twenties and thirties, and a smaller group continues to have difficulties in their forties. Classification The severity of acne vulgaris (Gr. ἀκµή, "point" + L. vulgaris, "common") can be classified as mild, moderate, or severe to determine an appropriate treatment regimen. There is no universally accepted scale for grading acne severity. The presence of clogged skin follicles (known as comedones) limited to the face with occasional inflammatory lesions defines mild acne. Moderate severity acne is said to occur when a higher number of inflammatory papules and pustules occur on the face, compared to mild cases of acne, and appear on the trunk of the body. Severe acne is said to occur when nodules (the painful bumps lying under the skin) are the characteristic facial lesions, and involvement of the trunk is extensive.Large nodules were previously called cysts. The term nodulocystic has been used in the medical literature to describe severe cases of inflammatory acne. True cysts are rare in those with acne, and the term severe nodular acne is now the preferred terminology.Acne inversa (L. invertō, "upside-down") and acne rosacea (rosa, "rose-colored" + -āceus, "forming") are not forms of acne and are alternate names that respectively refer to the skin conditions hidradenitis suppurativa (HS) and rosacea. Although HS shares certain overlapping features with acne vulgaris, such as a tendency to clog skin follicles with skin cell debris, the condition otherwise lacks the hallmark features of acne and is therefore considered a distinct skin disorder. Signs and symptoms Typical features of acne include increased secretion of oily sebum by the skin, microcomedones, comedones, papules, nodules (large papules), pustules, and often results in scarring. The appearance of acne varies with skin color. It may result in psychological and social problems. Scars Acne scars are caused by inflammation within the dermis and are estimated to affect 95% of people with acne vulgaris. Abnormal healing and dermal inflammation create the scar. Scarring is most likely to take place with severe acne but may occur with any form of acne vulgaris. Acne scars are classified based on whether the abnormal healing response following dermal inflammation leads to excess collagen deposition or loss at the site of the acne lesion.Atrophic acne scars have lost collagen from the healing response and are the most common type of acne scar (accounting for approximately 75% of all acne scars). Ice-pick scars, boxcar scars, and rolling scars are subtypes of atrophic acne scars. Boxcar scars are round or ovoid indented scars with sharp borders and vary in size from 1.5–4 mm across. Ice-pick scars are narrow (less than 2 mm across), deep scars that extend into the dermis. Rolling scars are broader than ice-pick and boxcar scars (4–5 mm across) and have a wave-like pattern of depth in the skin.Hypertrophic scars are uncommon and are characterized by increased collagen content after the abnormal healing response. They are described as firm and raised from the skin. Hypertrophic scars remain within the original margins of the wound, whereas keloid scars can form scar tissue outside of these borders. Keloid scars from acne occur more often in men and people with darker skin, and usually occur on the trunk of the body.In November 2021 a study was published exposing the consensus of twenty-four renowned international plastic surgeons and dermatologists about the most effective energy-based devices for the treatment of acne scars. Pigmentation After an inflamed nodular acne lesion resolves, it is common for the skin to darken in that area, which is known as postinflammatory hyperpigmentation (PIH). The inflammation stimulates specialized pigment-producing skin cells (known as melanocytes) to produce more melanin pigment, which leads to the skins darkened appearance. PIH occurs more frequently in people with darker skin color. Pigmented scar is a common term used for PIH, but is misleading as it suggests the color change is permanent. Often, PIH can be prevented by avoiding any aggravation of the nodule and can fade with time. However, untreated PIH can last for months, years, or even be permanent if deeper layers of skin are affected. Even minimal skin exposure to the suns ultraviolet rays can sustain hyperpigmentation. Daily use of SPF 15 or higher sunscreen can minimize such a risk. Causes Risk factors for the development of acne, other than genetics, have not been conclusively identified. Possible secondary contributors include hormones, infections, diet, and stress. Studies investigating the impact of smoking on the incidence and severity of acne have been inconclusive. Sunlight and cleanliness are not associated with acne. Genes Acne appears to be highly heritable; genetics explain 81% of the variation in the population. Studies performed in affected twins and first-degree relatives further demonstrate the strongly inherited nature of acne. Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic (Mendelian) inheritance pattern. These gene candidates include certain variations in tumor necrosis factor-alpha (TNF-alpha), IL-1 alpha, and CYP1A1 genes, among others. The 308 G/A single nucleotide polymorphism variation in the gene for TNF is associated with an increased risk for acne. Acne can be a feature of rare genetic disorders such as Aperts syndrome. Severe acne may be associated with XYY syndrome. Hormones Hormonal activity, such as occurs during menstrual cycles and puberty, may contribute to the formation of acne. During puberty, an increase in sex hormones called androgens causes the skin follicle glands to grow larger and make more oily sebum. The androgen hormones testosterone, dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) are all linked to acne. High levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are also associated with worsened acne. Both androgens and IGF-1 seem to be essential for acne to occur, as acne does not develop in individuals with complete androgen insensitivity syndrome (CAIS) or Laron syndrome (insensitivity to GH, resulting in very low IGF-1 levels).Medical conditions that commonly cause a high-androgen state, such as polycystic ovary syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors, can cause acne in affected individuals. Conversely, people who lack androgenic hormones or are insensitive to the effects of androgens rarely have acne. Pregnancy can increase androgen levels, and consequently, oily sebum synthesis. Acne can be a side effect of testosterone replacement therapy or anabolic steroid use. Over-the-counter bodybuilding and dietary supplements often contain illegally added anabolic steroids. Infections The anaerobic bacterial species Cutibacterium acnes (formerly Propionibacterium acnes) contributes to the development of acne, but its exact role is not well understood. There are specific sub-strains of C. acnes associated with normal skin and others with moderate or severe inflammatory acne. It is unclear whether these undesirable strains evolve on-site or are acquired, or possibly both depending on the person. These strains have the capability of changing, perpetuating, or adapting to the abnormal cycle of inflammation, oil production, and inadequate sloughing of dead skin cells from acne pores. Infection with the parasitic mite Demodex is associated with the development of acne. It is unclear whether eradication of the mite improves acne. Diet High-glycemic-load diets have been found to have different degrees of effect on acne severity. Multiple randomized controlled trials and nonrandomized studies have found a lower-glycemic-load diet to be effective in reducing acne. There is weak observational evidence suggesting that dairy milk consumption is positively associated with a higher frequency and severity of acne. Milk contains whey protein and hormones such as bovine IGF-1 and precursors of dihydrotestosterone. Studies suggest these components promote the effects of insulin and IGF-1 and thereby increase the production of androgen hormones, sebum, and promote the formation of comedones. Available evidence does not support a link between eating chocolate or salt and acne severity. Few studies have examined the relationship between obesity and acne. Vitamin B12 may trigger skin outbreaks similar to acne (acneiform eruptions), or worsen existing acne when taken in doses exceeding the recommended daily intake. Stress There are few high-quality studies to demonstrate that stress causes or worsens acne. Despite being controversial, some research indicates that increased acne severity is associated with high stress levels in certain contexts, such as hormonal changes seen in premenstrual syndrome. Other Some individuals experience severe intensification of their acne when they are exposed to hot humid climates; this is due to bacteria and fungus thriving in warm, moist environments. This climate induced acne exacerbation has been termed tropical acne. Mechanical obstruction of skin follicles with helmets or chinstraps can worsen pre-existing acne. However, when acne is caused by mechanical obstruction it is not considered a form of acne vulgaris when being very technical. It would be an other acneiform eruption known as Acne mechanica. Several medications can also worsen pre-existing acne; this condition is the acne medicamentosa form of acne. Examples of such medications include lithium, hydantoin, isoniazid, glucocorticoids, iodides, bromides, and testosterone. When acne medicamentosa is specifically caused by anabolic–androgenic steroids it can simply be referred to as steroid acne. Genetically susceptible individuals can get acne breakouts as a result of polymorphous light eruption; a condition triggered by sunlight and artificial UV light exposure. This form of acne is called Acne aestivalis and its specifically caused by intense UVA light exposure. Affected individuals usually experience seasonal acne breakouts on their upper arms, shoulder girdle, back, and chest. The breakouts typically occur one-to-three days after theyve been exposed to intese UVA radiation. Unlike other forms of acne the condition spares the face; this could possibly be a result of the pathogenesis of polymorphous light eruption, in which areas of the skin that are newly exposed to intense ultraviolet radiation are affected. Since faces are typically left uncovered at all stages of life theres little-to-no likelihood for an eruption to appear there. Studies show that both polymorphous light eruption outbreaks and the acne aestivalis breakout response can be prevented by topical antioxidants combined with the application of a broad spectrum sunscreen. Pathophysiology Acne vulgaris is a chronic skin disease of the pilosebaceous unit and develops due to blockages in the skins hair follicles. These blockages occur as a result of the following four abnormal processes: increased oily sebum production (influenced by androgens), excessive deposition of the protein keratin leading to comedo formation, colonization of the follicle by Cutibacterium acnes (C. acnes) bacteria, and the local release of pro-inflammatory chemicals in the skin.The earliest pathologic change is the formation of a plug (a microcomedone), which is driven primarily by excessive growth, reproduction, and accumulation of skin cells in the hair follicle. In healthy skin, the skin cells that have died come up to the surface and exit the pore of the hair follicle. In people with acne, the increased production of oily sebum causes the dead skin cells to stick together. The accumulation of dead skin cell debris and oily sebum blocks the pore of the hair follicle, thus forming the microcomedone. The C. acnes biofilm within the hair follicle worsens this process. If the microcomedone is superficial within the hair follicle, the skin pigment melanin is exposed to air, resulting in its oxidation and dark appearance (known as a blackhead or open comedo). In contrast, if the microcomedone occurs deep within the hair follicle, this causes the formation of a whitehead (known as a closed comedo).The main hormonal driver of oily sebum production in the skin is dihydrotestosterone. Another androgenic hormone responsible for increased sebaceous gland activity is DHEA-S. The adrenal glands secrete higher amounts of DHEA-S during adrenarche (a stage of puberty), and this leads to an increase in sebum production. In a sebum-rich skin environment, the naturally occurring and largely commensal skin bacterium C. acnes readily grows and can cause inflammation within and around the follicle due to activation of the innate immune system. C. acnes triggers skin inflammation in acne by increasing the production of several pro-inflammatory chemical signals (such as IL-1α, IL-8, TNF-α, and LTB4); IL-1α is essential to comedo formation.C. acnes ability to bind and activate a class of immune system receptors known as toll-like receptors (TLRs), especially TLR2 and TLR4, is a core mechanism of acne-related skin inflammation. Activation of TLR2 and TLR4 by C. acnes leads to increased secretion of IL-1α, IL-8, and TNF-α. The release of these inflammatory signals attracts various immune cells to the hair follicle, including neutrophils, macrophages, and Th1 cells. IL-1α stimulates increased skin cell activity and reproduction, which, in turn, fuels comedo development. Furthermore, sebaceous gland cells produce more antimicrobial peptides, such as HBD1 and HBD2, in response to the binding of TLR2 and TLR4.C. acnes also provokes skin inflammation by altering the fatty composition of oily sebum. Oxidation of the lipid squalene by C. acnes is of particular importance. Squalene oxidation activates NF-κB (a protein complex) and consequently increases IL-1α levels. Additionally, squalene oxidation increases 5-lipoxygenase enzyme activity, which catalyzes the conversion of arachidonic acid to leukotriene B4 (LTB4). LTB4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (PPARα) protein. PPARα increases the activity of activator protein 1 (AP-1) and NF-κB, thereby leading to the recruitment of inflammatory T cells. C. acnes ability to convert sebum triglycerides to pro-inflammatory free fatty acids via secretion of the enzyme lipase further explains its inflammatory properties. These free fatty acids spur increased production of cathelicidin, HBD1, and HBD2, thus leading to further inflammation.This inflammatory cascade typically leads to the formation of inflammatory acne lesions, including papules, infected pustules, or nodules. If the inflammatory reaction is severe, the follicle can break into the deeper layers of the dermis and subcutaneous tissue and cause the formation of deep nodules. The involvement of AP-1 in the aforementioned inflammatory cascade activates matrix metalloproteinases, which contribute to local tissue destruction and scar formation.Along with the bacteria C. acnes, the bacterial species Staphylococcus epidermidis (S. epidermidis) also takes a part in the physiopathology of acne vulgaris. The proliferation of S. epidermidis with C. acnes causes the formation of biofilms, which blocks the hair follicles and pores, creating an anaerobic environment under the skin. This enables for increased growth of both C. acnes and S. epidermidis under the skin. The proliferation of C. acnes causes the formation of biofilms and a biofilm matrix, making it even harder to treat the acne. Diagnosis Acne vulgaris is diagnosed based on a medical professionals clinical judgment. The evaluation of a person with suspected acne should include taking a detailed medical history about a family history of acne, a review of medications taken, signs or symptoms of excessive production of androgen hormones, cortisol, and growth hormone. Comedones (blackheads and whiteheads) must be present to diagnose acne. In their absence, an appearance similar to that of acne would suggest a different skin disorder. Microcomedones (the precursor to blackheads and whiteheads) are not visible to the naked eye when inspecting the skin and require a microscope to be seen. Many features may indicate that a persons acne vulgaris is sensitive to hormonal influences. Historical and physical clues that may suggest hormone-sensitive acne include onset between ages 20 and 30; worsening the week before a womans period; acne lesions predominantly over the jawline and chin; and inflammatory/nodular acne lesions.Several scales exist to grade the severity of acne vulgaris, but disagreement persists about the ideal one for diagnostic use. Cooks acne grading scale uses photographs to grade severity from 0 to 8, with higher numbers representing more severe acne. This scale was the first to use a standardized photographic protocol to assess acne severity; since its creation in 1979, the scale has undergone several revisions. The Leeds acne grading technique counts acne lesions on the face, back, and chest and categorizes them as inflammatory or non-inflammatory. Leeds scores range from 0 (least severe) to 10 (most severe) though modified scales have a maximum score of 12. The Pillsbury acne grading scale classifies the severity of the acne from grade 1 (least severe) to grade 4 (most severe). Differential diagnosis Many skin conditions can mimic acne vulgaris, and these are collectively known as acneiform eruptions. Such conditions include angiofibromas, epidermal cysts, flat warts, folliculitis, keratosis pilaris, milia, perioral dermatitis, and rosacea, among others. Age is one factor that may help distinguish between these disorders. Skin disorders such as perioral dermatitis and keratosis pilaris can appear similar to acne but tend to occur more frequently in childhood. Rosacea tends to occur more frequently in older adults. Facial redness triggered by heat or the consumption of alcohol or spicy food is also more suggestive of rosacea. The presence of comedones helps health professionals differentiate acne from skin disorders that are similar in appearance. Chloracne and occupational acne due to exposure to certain chemicals & industrial compounds, may look very similar to acne vulgaris. Management Many different treatments exist for acne. These include alpha hydroxy acid, anti-androgen medications, antibiotics, antiseborrheic medications, azelaic acid, benzoyl peroxide, hormonal treatments, keratolytic soaps, nicotinamide, retinoids, and salicylic acid. Acne treatments work in at least four different ways, including the following: reducing inflammation, hormonal manipulation, killing C. acnes, and normalizing skin cell shedding and sebum production in the pore to prevent blockage. Typical treatments include topical therapies such as antibiotics, benzoyl peroxide, and retinoids, and systemic therapies, including antibiotics, hormonal agents, and oral retinoids.Recommended therapies for first-line use in acne vulgaris treatment include topical retinoids, benzoyl peroxide, and topical or oral antibiotics. Procedures such as light therapy and laser therapy are not first-line treatments and typically have only an add on role due to their high cost and limited evidence. Blue light therapy is of unclear benefit. Medications for acne target the early stages of comedo formation and are generally ineffective for visible skin lesions; acne generally improves between eight and twelve weeks after starting therapy.People often view acne as a short-term condition, some expecting it to disappear after puberty. This misconception can lead to depending on self-management or problems with long-term adherence to treatment. Communicating the long-term nature of the condition and better access to reliable information about acne can help people know what to expect from treatments. Skin care In general, it is recommended that people with acne do not wash affected skin more than twice daily. The application of a fragrance-free moisturizer to sensitive and acne-prone skin may reduce irritation. Skin irritation from acne medications typically peaks at two weeks after onset of use and tends to improve with continued use. Dermatologists recommend using cosmetic products that specifically say non-comedogenic, oil-free, and wont clog pores.Acne vulgaris patients, even those with oily skin, should moisturize in order to support the skins moisture barrier since skin barrier dysfunction may contribute to acne. Moisturizers, especially ceramide-containing moisturizers, as an adjunct therapy are particularly helpful for the dry skin and irritation that commonly results from topical acne treatment. Studies show that ceramide-containing moisturizers are important for optimal skin care; they enhance acne therapy adherence and complement existing acne therapies. In a study where acne patients used 1.2% clindamycin phosphate / 2.5% benzoyl peroxide gel in the morning and applied a micronized 0.05% tretinoin gel in the evening the overwhelming majority of patients experienced no cutaneous adverse events throughout the study. It was concluded that using ceramide cleanser and ceramide moisturizing cream caused the favorable tolerability, did not interfere with the treatment efficacy, and improved adherence to the regimen. The importance of preserving the acidic mantle and its barrier functions is widely accepted in the scientific community. Thus, maintaining a pH in the range 4.5 - 5.5 is essential in order to keep the skin surface in its optimal, healthy conditions. Diet Causal relationship is rarely observed with diet/nutrition and dermatologic conditions. Rather, associations — some of them compelling — have been found between diet and outcomes including disease severity and the number of conditions experienced by a patient. Evidence is emerging in support of medical nutrition therapy as a way of reducing the severity and incidence of dermatologic diseases, including acne. Researchers observed a link between high glycemic index diets and acne. Dermatologists also recommend a diet low in simple sugars as a method of improving acne. As of 2014, the available evidence is insufficient to use milk restriction for this purpose. Medications Benzoyl peroxide Benzoyl peroxide (BPO) is a first-line treatment for mild and moderate acne due to its effectiveness and mild side-effects (mainly skin irritation). In the skin follicle, benzoyl peroxide kills C. acnes by oxidizing its proteins through the formation of oxygen free radicals and benzoic acid. These free radicals likely interfere with the bacteriums metabolism and ability to make proteins. Additionally, benzoyl peroxide is mildly effective at breaking down comedones and inhibiting inflammation. Combination products use benzoyl peroxide with a topical antibiotic or retinoid, such as benzoyl peroxide/clindamycin and benzoyl peroxide/adapalene, respectively. Topical benzoyl peroxide is effective at treating acne.Side effects include increased skin photosensitivity, dryness, redness, and occasional peeling. Sunscreen use is often advised during treatment, to prevent sunburn. Lower concentrations of benzoyl peroxide are just as effective as higher concentrations in treating acne but are associated with fewer side effects. Unlike antibiotics, benzoyl peroxide does not appear to generate bacterial antibiotic resistance. Retinoids Retinoids are medications that reduce inflammation, normalize the follicle cell life cycle, and reduce sebum production. They are structurally related to vitamin A. Studies show dermatologists and primary care doctors underprescribe them for acne. The retinoids appear to influence the cell life cycle in the follicle lining. This helps prevent the accumulation of skin cells within the hair follicle that can create a blockage. They are a first-line acne treatment, especially for people with dark-colored skin. Retinoids are known to lead to faster improvement of postinflammatory hyperpigmentation.Topical retinoids include adapalene, retinol, retinaldehyde, isotretinoin, tazarotene, trifarotene, and tretinoin. They often cause an initial flare-up of acne and facial flushing and can cause significant skin irritation. Generally speaking, retinoids increase the skins sensitivity to sunlight and are therefore recommended for use at night. Tretinoin is the least expensive of the topical retinoids and is the most irritating to the skin, whereas adapalene is the least irritating but costs significantly more. Most formulations of tretinoin are incompatible for use with benzoyl peroxide. Tazarotene is the most effective and expensive topical retinoid but is usually not as well tolerated. In 2019 a tazarotene lotion formulation, marketed to be a less irritating option, was approved by the FDA. Retinol is a form of vitamin A that has similar but milder effects and is present in many over-the-counter moisturizers and other topical products. Isotretinoin is an oral retinoid that is very effective for severe nodular acne, and moderate acne that is stubborn to other treatments. One to two months of use is typically adequate to see improvement. Acne often resolves completely or is much milder after a 4–6 month course of oral isotretinoin. After a single round of treatment, about 80% of people report an improvement, with more than 50% reporting complete remission. About 20% of people require a second course, but 80% of those report improvement, resulting in a cumulative 96% efficacy rate.There are concerns that isotretinoin is linked to adverse effects, like depression, suicidality, and anemia. There is no clear evidence to support some of these claims. Isotretinoin has been found in some studies to be superior to antibiotics or placebo in reducing acne lesions. However, a 2018 review comparing inflammatory lesions after treatment with antibiotics or isotretinoin found no difference. The frequency of adverse events was about twice as high with isotretinoin use, although these were mostly dryness-related events. No increased risk of suicide or depression was conclusively found.Medical authorities strictly regulate isotretinoin use in women of childbearing age due to its known harmful effects in pregnancy. For such a woman to be considered a candidate for isotretinoin, she must have a confirmed negative pregnancy test and use an effective form of birth control. In 2008, the United States started the iPLEDGE program to prevent isotretinoin use during pregnancy. iPledge requires the woman to have two negative pregnancy tests and to use two types of birth control for at least one month before isotretinoin therapy begins and one month afterward. The effectiveness of the iP
Acne	ledge program is controversial due to continued instances of contraception nonadherence. Antibiotics People may apply antibiotics to the skin or take them orally to treat acne. They work by killing C. acnes and reducing inflammation. Although multiple guidelines call for healthcare providers to reduce the rates of prescribed oral antibiotics, many providers do not follow this guidance. Oral antibiotics remain the most commonly prescribed systemic therapy for acne. Widespread broad-spectrum antibiotic overuse for acne has led to higher rates of antibiotic-resistant C. acnes strains worldwide, especially to the commonly used tetracycline (e.g., doxycycline) and macrolide antibiotics (e.g., topical erythromycin). Therefore, dermatologists prefer antibiotics as part of combination therapy and not for use alone.Commonly used antibiotics, either applied to the skin or taken orally, include clindamycin, erythromycin, metronidazole, sulfacetamide, and tetracyclines (e.g., doxycycline or minocycline). Doxycycline 40 milligrams daily (low-dose) appears to have similar efficacy to 100 milligrams daily and has fewer gastrointestinal side effects. However, low-dose doxycycline is not FDA-approved for the treatment of acne. Antibiotics applied to the skin are typically used for mild to moderately severe acne. Oral antibiotics are generally more effective than topical antibiotics and produce faster resolution of inflammatory acne lesions than topical applications. Topical and oral antibiotics are not recommended for use together.Oral antibiotics are recommended for no longer than three months as antibiotic courses exceeding this duration are associated with the development of antibiotic resistance and show no clear benefit over shorter durations. If long-term oral antibiotics beyond three months are used, then it is recommended that benzoyl peroxide or a retinoid be used at the same time to limit the risk of C. acnes developing antibiotic resistance.The antibiotic dapsone is effective against inflammatory acne when applied to the skin. It is generally not a first-line choice due to its higher cost and a lack of clear superiority over other antibiotics. Topical dapsone is sometimes a preferred therapy in women or for people with sensitive or darker-toned skin. It is not recommended for use with benzoyl peroxide due to the risk of causing yellow-orange skin discoloration with this combination. Minocycline is an effective acne treatment, but it is not a first-line antibiotic due to a lack of evidence that it is better than other treatments, and concerns about its safety compared to other tetracyclines.Sarecycline is the most recent oral antibiotic developed specifically for the treatment of acne, and is FDA-approved for the treatment of moderate to severe inflammatory acne in patients nine years of age and older. It is a narrow-spectrum tetracycline antibiotic that exhibits the necessary antibacterial activity against pathogens related to acne vulgaris and a low propensity for inducing antibiotic resistance. In clinical trials, sarecycline demonstrated clinical efficacy in reducing inflammatory acne lesions as early as three weeks and reduced truncal (back and chest) acne. Hormonal agents In women, the use of combined birth control pills can improve acne. These medications contain an estrogen and a progestin. They work by decreasing the production of androgen hormones by the ovaries and by decreasing the free and hence biologically active fractions of androgens, resulting in lowered skin production of sebum and consequently reduce acne severity. First-generation progestins such as norethindrone and norgestrel have androgenic properties and may worsen acne. Although oral estrogens decrease IGF-1 levels in some situations, which could theoretically improve acne symptoms, combined birth control pills do not appear to affect IGF-1 levels in fertile women. Cyproterone acetate-containing birth control pills seem to decrease total and free IGF-1 levels. Combinations containing third- or fourth-generation progestins, including desogestrel, dienogest, drospirenone, or norgestimate, as well as birth control pills containing cyproterone acetate or chlormadinone acetate, are preferred for women with acne due to their stronger antiandrogenic effects. Studies have shown a 40 to 70% reduction in acne lesions with combined birth control pills. A 2014 review found that oral antibiotics appear to be somewhat more effective than birth control pills at reducing the number of inflammatory acne lesions at three months. However, the two therapies are approximately equal in efficacy at six months for decreasing the number of inflammatory, non-inflammatory, and total acne lesions. The authors of the analysis suggested that birth control pills may be a preferred first-line acne treatment, over oral antibiotics, in certain women due to similar efficacy at six months and a lack of associated antibiotic resistance. In contrast to combined birth control pills, progestogen-only birth control forms that contain androgenic progestins have been associated with worsened acne.Antiandrogens such as cyproterone acetate and spironolactone can successfully treat acne, especially in women with signs of excessive androgen production, such as increased hairiness or skin production of sebum, or scalp hair loss. Spironolactone is an effective treatment for acne in adult women. Unlike combined birth control pills, it is not approved by the United States Food and Drug Administration for this purpose. Spironolactone is an aldosterone antagonist and is a useful acne treatment due to its ability to additionally block the androgen receptor at higher doses. Alone or in combination with a birth control pill, spironolactone has shown a 33 to 85% reduction in acne lesions in women. The effectiveness of spironolactone for acne appears to be dose-dependent. High-dose cyproterone acetate alone reportedly decreases acne symptoms in women by 75 to 90% within three months. It is usually combined with an estrogen to avoid menstrual irregularities and estrogen deficiency. The medication appears to be effective in the treatment of acne in males, with one study finding that a high dosage reduced inflammatory acne lesions by 73%. However, spironolactone and cyproterone acetates side effects in males, such as gynecomastia, sexual dysfunction, and decreased bone mineral density, generally make their use for male acne impractical.Pregnant and lactating women should not receive antiandrogens for their acne due to a possibility of birth disorders such as hypospadias and feminization of male babies. Women who are sexually active and who can or may become pregnant should use an effective method of contraception to prevent pregnancy while taking an antiandrogen. Antiandrogens are often combined with birth control pills for this reason, which can result in additive efficacy. The FDA added a black-box warning to spironolactone about possible tumor risks based on preclinical research with very high doses (>100-fold clinical doses) and cautioned that unnecessary use of the medication should be avoided. However, several large epidemiological studies subsequently found no greater risk of tumors in association with spironolactone in humans. Conversely, strong associations of cyproterone acetate with certain brain tumors have been discovered and its use has been restricted. The brain tumor risk with cyproterone acetate is due to its strong progestogenic actions and is not related to antiandrogenic activity nor shared by other antiandrogens.Flutamide, a pure antagonist of the androgen receptor, is effective in treating acne in women. It appears to reduce acne symptoms by 80 to 90% even at low doses, with several studies showing complete acne clearance. In one study, flutamide decreased acne scores by 80% within three months, whereas spironolactone decreased symptoms by only 40% in the same period. In a large long-term study, 97% of women reported satisfaction with the control of their acne with flutamide. Although effective, flutamide has a risk of serious liver toxicity, and cases of death in women taking even low doses of the medication to treat androgen-dependent skin and hair conditions have occurred. As such, the use of flutamide for acne has become increasingly limited, and it has been argued that continued use of flutamide for such purposes is unethical. Bicalutamide, a pure androgen receptor antagonist with the same mechanism as flutamide and with comparable or superior antiandrogenic efficacy but with a far lower risk of liver toxicity, is an alternative option to flutamide in the treatment of androgen-dependent skin and hair conditions in women.Clascoterone is a topical antiandrogen that has demonstrated effectiveness in the treatment of acne in both males and females and was approved for clinical use for this indication in August 2020. It has shown no systemic absorption or associated antiandrogenic side effects. In a small direct head-to-head comparison, clascoterone showed greater effectiveness than topical isotretinoin. 5α-Reductase inhibitors such as finasteride and dutasteride may be useful for the treatment of acne in both males and females but have not been adequately evaluated for this purpose. Moreover, 5α-reductase inhibitors have a strong potential for producing birth defects in male babies and this limits their use in women. However, 5α-reductase inhibitors are frequently used to treat excessive facial/body hair in women and can be combined with birth control pills to prevent pregnancy. There is no evidence as of 2010 to support the use of cimetidine or ketoconazole in the treatment of acne.Hormonal treatments for acne such as combined birth control pills and antiandrogens may be considered first-line therapy for acne under many circumstances, including desired contraception, known or suspected hyperandrogenism, acne during adulthood, acne that flares premenstrually, and when symptoms of significant sebum production (seborrhea) are co-present. Hormone therapy is effective for acne both in women with hyperandrogenism and in women with normal androgen levels. Azelaic acid Azelaic acid is effective for mild to moderate acne when applied topically at a 15–20% concentration. Treatment twice daily for six months is necessary, and is as effective as topical benzoyl peroxide 5%, isotretinoin 0.05%, and erythromycin 2%. Azelaic acid is an effective acne treatment due to its ability to reduce skin cell accumulation in the follicle and its antibacterial and anti-inflammatory properties. It has a slight skin-lightening effect due to its ability to inhibit melanin synthesis. Therefore, it is useful in treating individuals with acne who are also affected by post-inflammatory hyperpigmentation. Azelaic acid may cause skin irritation. It is less effective and more expensive than retinoids. Azelaic acid also led to worse treatment response when compared to benzoyl peroxide. When compared to tretinoin, azelaic acid makes little or no treatment response. Salicylic acid Salicylic acid is a topically applied beta-hydroxy acid that stops bacteria from reproducing and has keratolytic properties. It is less effective than retinoid therapy. Salicylic acid opens obstructed skin pores and promotes the shedding of epithelial skin cells. Dry skin is the most commonly seen side effect with topical application, though darkening of the skin can occur in individuals with darker skin types. Other medications Topical and oral preparations of nicotinamide (the amide form of vitamin B3) are alternative medical treatments. Nicotinamide reportedly improves acne due to its anti-inflammatory properties, its ability to suppress sebum production, and its wound healing properties. Topical and oral preparations of zinc are suggested treatments for acne; evidence to support their use for this purpose is limited. Zincs capacities to reduce inflammation and sebum production as well as inhibit C. acnes growth are its proposed mechanisms for improving acne. Antihistamines may improve symptoms among those already taking isotretinoin due to their anti-inflammatory properties and their ability to suppress sebum production.Hydroquinone lightens the skin when applied topically by inhibiting tyrosinase, the enzyme responsible for converting the amino acid tyrosine to the skin pigment melanin, and is used to treat acne-associated post-inflammatory hyperpigmentation. By interfering with the production of melanin in the epidermis, hydroquinone leads to less hyperpigmentation as darkened skin cells are naturally shed over time. Improvement in skin hyperpigmentation is typically seen within six months when used twice daily. Hydroquinone is ineffective for hyperpigmentation affecting deeper layers of skin such as the dermis. The use of a sunscreen with SPF 15 or higher in the morning with reapplication every two hours is recommended when using hydroquinone. Its application only to affected areas lowers the risk of lightening the color of normal skin but can lead to a temporary ring of lightened skin around the hyperpigmented area. Hydroquinone is generally well-tolerated; side effects are typically mild (e.g., skin irritation) and occur with the use of a higher than the recommended 4% concentration. Most preparations contain the preservative sodium metabisulfite, which has been linked to rare cases of allergic reactions, including anaphylaxis and severe asthma exacerbations in susceptible people. In extremely rare cases, the frequent and improper application of high-dose hydroquinone has been associated with a systemic condition known as exogenous ochronosis (skin discoloration and connective tissue damage from the accumulation of homogentisic acid). Combination therapy Combination therapy—using medications of different classes together, each with a different mechanism of action—has been demonstrated to be a more effective approach to acne treatment than monotherapy. The use of topical benzoyl peroxide and antibiotics together is more effective than antibiotics alone. Similarly, using a topical retinoid with an antibiotic clears acne lesions faster than the use of antibiotics alone. Frequently used combinations include the following: antibiotic and benzoyl peroxide, antibiotic and topical retinoid, or topical retinoid and benzoyl peroxide. Dermatologists generally prefer combining benzoyl peroxide with a retinoid over the combination of a topical antibiotic with a retinoid. Both regimens are effective, but benzoyl peroxide does not lead to antibiotic resistance. Pregnancy Although sebaceous gland activity in the skin increases during the late stages of pregnancy, pregnancy has not been reliably associated with worsened acne severity. In general, topically applied medications are considered the first-line approach to acne treatment during pregnancy, as they have little systemic absorption and are therefore unlikely to harm a developing fetus. Highly recommended therapies include topically applied benzoyl peroxide (pregnancy category C) and azelaic acid (category B). Salicylic acid carries a category C safety rating due to higher systemic absorption (9–25%), and an association between the use of anti-inflammatory medications in the third trimester and adverse effects to the developing fetus including too little amniotic fluid in the uterus and early closure of the babies ductus arteriosus blood vessel. Prolonged use of salicylic acid over significant areas of the skin or under occlusive (sealed) dressings is not recommended as these methods increase systemic absorption and the potential for fetal harm. Tretinoin (category C) and adapalene (category C) are very poorly absorbed, but certain studies have suggested teratogenic effects in the first trimester. The data examining the association between maternal topical retinoid exposure in the first trimester of pregnancy and adverse pregnancy outcomes is limited. A systematic review of observational studies concluded that such exposure does not appear to increase the risk of major birth defects, miscarriages, stillbirths, premature births, or low birth weight. Similarly, in studies examining the effects of topical retinoids during pregnancy, fetal harm has not been seen in the second and third trimesters. Nevertheless, since rare harms from topical retinoids are not ruled out, they are not recommended for use during pregnancy due to persistent safety concerns. Retinoids contraindicated for use during pregnancy include the topical retinoid tazarotene, and oral retinoids isotretinoin and acitretin (all category X). Spironolactone is relatively contraindicated for use during pregnancy due to its antiandrogen effects. Finasteride is not recommended as it is highly teratogenic.Topical antibiotics deemed safe during pregnancy include clindamycin, erythromycin, and metronidazole (all category B), due to negligible systemic absorption. Nadifloxacin and dapsone (category C) are other topical antibiotics that may be used to treat acne in pregnant women but have received less study. No adverse fetal events have been reported from the topical use of dapsone. If retinoids are used there is a high risk of abnormalities occurring in the developing fetus; women of childbearing age are therefore required to use effective birth control if retinoids are used to treat acne. Oral antibiotics deemed safe for pregnancy (all category B) include azithromycin, cephalosporins, and penicillins. Tetracyclines (category D) are contraindicated during pregnancy as they are known to deposit in developing fetal teeth, resulting in yellow discoloration and thinned tooth enamel. Their use during pregnancy has been associated with the development of acute fatty liver of pregnancy and is further avoided for this reason. Procedures Limited evidence supports comedo extraction, but it is an option for comedones that do not improve with standard treatment. Another procedure for immediate relief is the injection of a corticosteroid into an inflamed acne comedo. Electrocautery and electrofulguration are effective alternative treatments for comedones.Light therapy is a treatment method that involves delivering certain specific wavelengths of light to an area of skin affected by acne. Both regular and laser light have been used. The evidence for light therapy as a treatment for acne is weak and inconclusive. Various light therapies appear to provide a short-term benefit, but data for long-term outcomes, and outcomes in those with severe acne, are sparse; it may have a role for individuals whose acne has been resistant to topical medications. A 2016 meta-analysis was unable to conclude whether light therapies were more beneficial than placebo or no treatment, nor the duration of benefit.When regular light is used immediately following the application of a sensitizing substance to the skin such as aminolevulinic acid or methyl aminolevulinate, the treatment is referred to as photodynamic therapy (PDT). PDT has the most supporting evidence of all light therapy modalities. PDT treats acne by using various forms of light (e.g., blue light or red light) that preferentially target the pilosebaceous unit. Once the light activates the sensitizing substance, this generates free radicals and reactive oxygen species in the skin, which purposefully damage the sebaceous glands and kill C. acnes bacteria. Many different types of nonablative lasers (i.e., lasers that do not vaporize the top layer of the skin but rather induce a physiologic response in the skin from the light) have been used to treat acne, including those that use infrared wavelengths of light. Ablative lasers (such as CO2 and fractional types) have also been used to treat active acne and its scars. When ablative lasers are used, the treatment is often referred to as laser resurfacing because, as mentioned previously, the entire upper layers of the skin are vaporized. Ablative lasers are associated with higher rates of adverse effects compared with non-ablative lasers, with examples being post-inflammatory hyperpigmentation, persistent facial redness, and persistent pain. Physiologically, certain wavelengths of light, used with or without accompanying topical chemicals, are thought to kill bacteria and decrease the size and activity of the glands that produce sebum. Disadvantages of light therapy can include its cost, the need for multiple visits, the time required to complete the procedure(s), and pain associated with some of the treatment modalities. Typical side effects include skin peeling, temporary reddening of the skin, swelling, and post-inflammatory hyperpigmentation.Dermabrasion is an effective therapeutic procedure for reducing the appearance of superficial atrophic scars of the boxcar and rolling varieties. Ice-pick scars do not respond well to treatment with dermabrasion due to their depth. The procedure is painful and has many potential side effects such as skin sensitivity to sunlight, redness, and decreased pigmentation of the skin. Dermabrasion has fallen out of favor with the introduction of laser resurfacing. Unlike dermabrasion, there is no evidence that microdermabrasion is an effective treatment for acne.Dermal or subcutaneous fillers are substances injected into the skin to improve the appearance of acne scars. Fillers are used to increase natural collagen production in the skin and to increase skin volume and decrease the depth of acne scars. Examples of fillers used for this purpose include hyaluronic acid; poly(methyl methacrylate) microspheres with collagen; human and bovine collagen derivatives, and fat harvested from the persons own body (autologous fat transfer).Microneedling is a procedure in which an instrument with multiple rows of tiny needles is rolled over the skin to elicit a wound healing response and stimulate collagen production to reduce the appearance of atrophic acne scars in people with darker skin color. Notable adverse effects of microneedling include post-inflammatory hyperpigmentation and tram track scarring (described as discrete slightly raised scars in a linear distribution similar to a tram track). The latter is thought to be primarily attributable to improper technique by the practitioner, including the use of excessive pressure or inappropriately large needles.Subcision is useful for the treatment of superficial atrophic acne scars and involves the use of a small needle to loosen the fibrotic adhesions that result in the depressed appearance of the scar.Chemical peels can be used to reduce the appearance of acne scars. Mild peels include those using glycolic acid, lactic acid, salicylic acid, Jessners solution, or a lower concentration (20%) of trichloroacetic acid. These peels only affect the epidermal layer of the skin and can be useful in the treatment of superficial acne scars as well as skin pigmentation changes from inflammatory acne. Higher concentrations of trichloroacetic acid (30–40%) are considered to be medium-strength peels and affect the skin as deep as the papillary dermis. Formulations of trichloroacetic acid concentrated to 50% or more are considered to be deep chemical peels. Medium-strength and deep-strength chemical peels are more effective for deeper atrophic scars but are more likely to cause side effects such as skin pigmentation changes, infection, and small white superficial cysts known as milia. Alternative medicine Researchers are investigating complementary therapies as treatment for people with acne. Low-quality evidence suggests topical application of tea tree oil or bee venom may reduce the total number of skin lesions in those with acne. Tea tree oil appears to be approximately as effective as benzoyl peroxide or salicylic acid but is associated with allergic contact dermatitis. Proposed mechanisms for tea tree oils anti-acne effects include antibacterial action against C. acnes and anti-inflammatory properties. Numerous other plant-derived therapies have demonstrated positive effects against acne (e.g., basil oil; oligosaccharides from seaweed; however, few well-done studies have examined their use for this purpose. There is a lack of high-quality evidence for the use of acupuncture, herbal medicine, or cupping therapy for acne. Self-care Many over-the-counter treatments in many forms are available, which are often known as cosmeceuticals. Certain types of makeup may be useful to mask acne. In those with oily skin, a water-based product is often preferred. Prognosis Acne usually improves around the age of 20 but may persist into adulthood. Permanent physical scarring may occur. Rare complications from acne or its treatment include the formation of pyogenic granulomas, osteoma cutis, and acne with facial edema. Early and aggressive treatment of acne is advocated by some in the medical community to reduce the chances of these poor outcomes. Mental health impact There is good evidence to support the idea that acne and associated scarring negatively affect a persons psychological state, worsen mood, lower self-esteem, and are associated with a higher risk of anxiety disorders, depression, and suicidal thoughts.Misperceptions about acnes causative and aggravating factors are common, and people with acne often blame themselves, and others often blame those with acne for their condition. Such blame can worsen the affected persons sense of self-esteem. Until the 20th century, even among dermatologists, the list of causes was believed to include excessive sexual thoughts and masturbation. Dermatologys association with sexually transmitted infections, especially syphilis, contributed to the stigma.Another psychological complication of acne vulgaris is acne excoriée, which occurs when a person persistently picks and scratches pimples, irrespective of the severity of their acne. This can lead to significant scarring, changes in the affected persons skin pigmentation, and a cyclic worsening of the affected persons anxiety about their appearance. Epidemiology Globally, acne affects approximately 650 million people, or about 9.4% of the population, as of 2010. It affects nearly 90% of people in Western societies during their teenage years, but can occur before adolescence and may persist into adulthood. While acne that first develops between the ages of 21 and 25 is uncommon, it affects 54% of women and 40% of men older than 25 years of age and has a lifetime prevalence of 85%. About 20% of those affected have moderate or severe cases. It is slightly more common in females than males (9.8% versus 9.0%). In those over 40 years old, 1% of males and 5% of females still have problems.Rates appear to be lower in rural societies. While some research has found it affects people of all ethnic groups, acne may not occur in the non-Westernized peoples of Papua New Guinea and Paraguay.Acne affects 40–50 million people in the United States (16%) and approximately 3–5 million in Australia (23%). Severe acne tends to be more common in people of Caucasian or Amerindian descent than in people of African descent. History Historical records indicate Pharaohs had acne, which may be the earliest known reference to the disease. Sulfurs usefulness as a topical remedy for acne dates back to at least the reign of Cleopatra (69–30 BCE). The sixth-century Greek physician Aëtius of Amida reportedly coined the term "ionthos" (ίονθωξ,) or "acnae", which seems to be a reference to facial skin lesions that occur during "the acme of life" (puberty).In the 16th century, the French physician and botanist François Boissier de Sauvages de Lacroix provided one of the earlier descriptions of acne. He used the term "psydracia achne" to describe small, red, and hard tubercles that altered a persons facial appearance during adolescence and were neither itchy nor painful.The recognition and characterization of acne progressed in 1776 when Josef Plenck (an Austrian physician) published a book that proposed the novel concept of classifying skin diseases by their elementary (initial) lesions. In 1808 the English dermatologist Robert Willan refined Plencks work by providing the first detailed descriptions of several skin disorders using morphologic terminology that remains in use today. Thomas Bateman continued and expanded on Robert Willans work as his student and provided the first descriptions and illustrations of acne accepted as accurate by modern dermatologists. Erasmus Wilson, in 1842, was the first to make the distinction between acne vulgaris and rosacea. The first professional medical monograph dedicated entirely to acne was written by Lucius Duncan Bulkley and published in New York in 1885.Scientists initially hypothesized that acne represented a disease of the skins hair follicle, and occurred due to blockage of the pore by sebum. During the 1880s, they observed bacteria by microscopy in skin samples from people with acne. Investigators believed the bacteria caused comedones, sebum production, and ultimately acne. During the mid-twentieth century, dermatologists realized that no single hypothesized factor (sebum, bacteria, or excess keratin) fully accounted for the disease in its entirety. This led to the current understanding that acne could be explained by a sequence of related events, beginning with blockage of the skin follicle by excessive dead skin cells, followed by bacterial invasion of the hair follicle pore, changes in sebum production, and inflammation.The approach to acne treatment underwent significant changes during the twentieth century
Acne	. Retinoids became a medical treatment for acne in 1943. Benzoyl peroxide was first proposed as a treatment in 1958 and remains a staple of acne treatment. The introduction of oral tetracycline antibiotics (such as minocycline) modified acne treatment in the 1950s. These reinforced the idea amongst dermatologists that bacterial growth on the skin plays an important role in causing acne. Subsequently, in the 1970s, tretinoin (original trade name Retin A) was found to be an effective treatment. The development of oral isotretinoin (sold as Accutane and Roaccutane) followed in 1980. After its introduction in the United States, scientists identified isotretinoin as a medication highly likely to cause birth defects if taken during pregnancy. In the United States, more than 2,000 women became pregnant while taking isotretinoin between 1982 and 2003, with most pregnancies ending in abortion or miscarriage. Approximately 160 babies were born with birth defects due to maternal use of isotretinoin during pregnancy.Treatment of acne with topical crushed dry ice, known as cryoslush, was first described in 1907 but is no longer performed commonly. Before 1960, the use of X-rays was also a common treatment. Society and culture The costs and social impact of acne are substantial. In the United States, acne vulgaris is responsible for more than 5 million doctor visits and costs over US$2.5 billion each year in direct costs. Similarly, acne vulgaris is responsible for 3.5 million doctor visits each year in the United Kingdom. Sales for the top ten leading acne treatment brands in the US in 2015 amounted to $352 million.Acne vulgaris and its resultant scars are associated with significant social and academic difficulties that can last into adulthood. During the Great Depression, dermatologists discovered that young men with acne had difficulty obtaining jobs. Until the 1930s, many people viewed acne as a trivial problem among middle-class girls because, unlike smallpox and tuberculosis, no one died from it, and a feminine problem, because boys were much less likely to seek medical assistance for it. During World War II, some soldiers in tropical climates developed such severe and widespread tropical acne on their bodies that they were declared medically unfit for duty. Research Efforts to better understand the mechanisms of sebum production are underway. This research aims to develop medications that target and interfere with the hormones that are known to increase sebum production (e.g., IGF-1 and alpha-melanocyte-stimulating hormone). Other sebum-lowering medications such as topical antiandrogens, peroxisome proliferator-activated receptor modulators, and inhibitors of the stearoyl-CoA desaturase-1 enzyme are also a focus of research efforts. Particles that release nitric oxide into the skin to decrease skin inflammation caused by C. acnes and the immune system have shown promise for improving acne in early clinical trials. Another avenue of early-stage research has focused on how to best use laser and light therapy to selectively destroy sebum-producing glands in the skins hair follicles to reduce sebum production and improve acne appearance.The use of antimicrobial peptides against C. acnes is under investigation as a treatment for acne to overcoming antibiotic resistance. In 2007, scientists reported the first genome sequencing of a C. acnes bacteriophage (PA6). The authors proposed applying this research toward the development of bacteriophage therapy as an acne treatment to overcome the problems associated with long-term antibiotic use, such as bacterial resistance. Oral and topical probiotics are under evaluation as treatments for acne. Probiotics may have therapeutic effects for those affected by acne due to their ability to decrease skin inflammation and improve skin moisture by increasing the skins ceramide content. As of 2014, knowledge of the effects of probiotics on acne in humans was limited.Decreased levels of retinoic acid in the skin may contribute to comedo formation. Researchers are investigating methods to increase the skins production of retinoic acid to address this deficiency. A vaccine against inflammatory acne has shown promising results in mice and humans. Some have voiced concerns about creating a vaccine designed to neutralize a stable community of normal skin bacteria that is known to protect the skin from colonization by more harmful microorganisms. Other animals Acne can occur on cats, dogs, and horses. References Further reading External links Acne Support. Expert, impartial advice on acne by the BAD. "Acne". MedlinePlus. U.S. National Library of Medicine.
Crystal arthropathy	Crystal arthropathy is a class of joint disorder (called arthropathy) that is characterized by accumulation of tiny crystals in one or more joints. Polarizing microscopy and application of other crystallographic techniques have improved identification of different microcrystals including monosodium urate, calcium pyrophosphate dihydrate, calcium hydroxyapatite, and calcium oxalate. Types Causes Deposition of crystals in joints Calcium pyrophosphate dihydrate crystal formation: Increased production of inorganic pyrophosphate Decreased levels of pyrophosphatase in cartilage Decreased levels of cartilage glycosaminoglycans Hyperparathyroidism Hemochromatosis Hypophosphatasia Hypomagnesemia Hydroxyapatite deposition: Tissue damage Hyperparathyroidism Hypercalcemia Hyperphosphatemia Calcium oxalate deposition: Enhanced production of oxalic acid due to enzyme defect Poor excretion of oxalic acid in kidney failure Excessive ascorbic acid intake in kidney failure Risk factors Obesity Kidney failure Hyperphosphatemia Hyperparathyroidism Hypercalcemia Tissue damage (dystrophic calcification) Diagnosis Differential diagnosis Septic arthritis Type IIa hyperlipoproteinemia Amyloidosis Multicentric reticulohistiocytosis Hyperparathyroidism Spondyloarthropathy Rheumatoid arthritis Fibromyalgia Treatment References == External links ==
Heparin	Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given by injection into a vein or under the skin. Other uses for its anticoagulant properties include inside blood specimen test tubes and kidney dialysis machines.Common side effects include bleeding, pain at the injection site, and low blood platelets. Serious side effects include heparin-induced thrombocytopenia. Greater care is needed in those with poor kidney function.Heparin is contraindicated for suspected cases of vaccine-induced pro-thrombotic immune thrombocytopenia (VIPIT) secondary to SARS-CoV-2 vaccination, as heparin may further increase the risk of bleeding in an anti-PF4/heparin complex autoimmune manner, in favor of alternative anticoagulant medications (such as argatroban or danaparoid).Heparin appears to be relatively safe for use during pregnancy and breastfeeding. Heparin is produced by basophils and mast cells in all mammals.The discovery of heparin was announced in 1916. It is on the World Health Organizations List of Essential Medicines. A fractionated version of heparin, known as low molecular weight heparin, is also available. History Heparin was discovered by Jay McLean and William Henry Howell in 1916, although it did not enter clinical trials until 1935. It was originally isolated from dog liver cells, hence its name (hepar or "ήπαρ" is Greek for "liver"; hepar + -in). McLean was a second-year medical student at Johns Hopkins University, and was working under the guidance of Howell investigating pro-coagulant preparations, when he isolated a fat-soluble phosphatide anticoagulant in canine liver tissue. In 1918, Howell coined the term heparin for this type of fat-soluble anticoagulant. In the early 1920s, Howell isolated a water-soluble polysaccharide anticoagulant, which he also termed heparin, although it was different from the previously discovered phosphatide preparations. McLeans work as a surgeon probably changed the focus of the Howell group to look for anticoagulants, which eventually led to the polysaccharide discovery. In the 1930s, several researchers were investigating heparin. Erik Jorpes at Karolinska Institutet published his research on the structure of heparin in 1935, which made it possible for the Swedish company Vitrum AB to launch the first heparin product for intravenous use in 1936. Between 1933 and 1936, Connaught Medical Research Laboratories, then a part of the University of Toronto, perfected a technique for producing safe, nontoxic heparin that could be administered to patients, in a saline solution. The first human trials of heparin began in May 1935, and, by 1937, it was clear that Connaughts heparin was safe, easily available, and effective as a blood anticoagulant. Prior to 1933, heparin was available in small amounts, was extremely expensive and toxic, and, as a consequence, of no medical value.Heparin production experienced a break in the 1990s. Until then, heparin was mainly obtained from cattle tissue, which was a by-product of the meat industry, especially in North America. With the rapid spread of BSE, more and more manufacturers abandoned this source of supply. As a result, global heparin production became increasingly concentrated in China, where the substance was now procured from the expanding industry of breeding and slaughtering hog. The dependence of medical care on the meat industry assumed threatening proportions in the wake of the COVID-19 pandemic. In 2020, several studies demonstrated the efficacy of heparin in mitigating severe disease progression, as its anticoagulant effect counteracted the formation of immunothrombosis. However, the availability of heparin on the world market was decreased, because concurrently a renewed swine flu epidemic had reduced significant portions of the Chinese hog population. The situation was further exacerbated by the fact that mass slaughterhouses around the world became corona hotspots themselves and were forced to close temporarily. In less affluent countries, the resulting heparin shortage also led to worsened health care beyond the treatment of covid, for example through the cancellation of cardiac surgeries. Medical use Heparin acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While heparin itself does not break down clots that have already formed (unlike tissue plasminogen activator), it allows the bodys natural clot lysis mechanisms to work normally to break down clots that have formed. Heparin is generally used for anticoagulation for the following conditions: Acute coronary syndrome, e.g., NSTEMI Atrial fibrillation Deep-vein thrombosis and pulmonary embolism Cardiopulmonary bypass for heart surgery ECMO circuit for extracorporeal life support Hemofiltration Indwelling central or peripheral venous cathetersHeparin and its low-molecular-weight derivatives (e.g., enoxaparin, dalteparin, tinzaparin) are effective in preventing deep vein thromboses and pulmonary emboli in people at risk, but no evidence indicates any one is more effective than the other in preventing mortality.In angiography, 2 to 5 units/mL of unfractionated heparin saline flush is used to prevent the clotting of blood in guidewires, sheaths, and catheters, thus preventing thrombus from dislodging from these devices into the circulatory system.Unfractionated heparin is used in hemodialysis. Comparing to low-molecular-weight heparin, unfractionated heparin does not have prolonged anticoagulation action after dialysis, and low cost. However, the short duration of action for heparin would require it to maintain continuous infusion to maintain its action. Meanwhile, unfractionated heparin has higher risk of heparin-induced thrombocytopenia. Adverse effects A serious side-effect of heparin is heparin-induced thrombocytopenia (HIT), caused by an immunological reaction that makes platelets a target of immunological response, resulting in the degradation of platelets, which causes thrombocytopenia. This condition is usually reversed on discontinuation, and in general can be avoided with the use of synthetic heparins. Also, a benign form of thrombocytopenia is associated with early heparin use, which resolves without stopping heparin. Two non-hemorrhagic side-effects of heparin treatment are known. The first is elevation of serum aminotransferase levels, which has been reported in as many as 80% of patients receiving heparin. This abnormality is not associated with liver dysfunction, and it disappears after the drug is discontinued. The other complication is hyperkalemia, which occurs in 5 to 10% of patients receiving heparin, and is the result of heparin-induced aldosterone suppression. The hyperkalemia can appear within a few days after the onset of heparin therapy. More rarely, the side-effects alopecia and osteoporosis can occur with chronic use. As with many drugs, overdoses of heparin can be fatal. In September 2006, heparin received worldwide publicity when three prematurely born infants died after they were mistakenly given overdoses of heparin at an Indianapolis hospital. Contraindications Heparin is contraindicated in those with risk of bleeding (especially in people with uncontrolled blood pressure, liver disease, and stroke), severe liver disease, or severe hypertension. Antidote to heparin Protamine sulfate has been given to counteract the anticoagulant effect of heparin (1 mg per 100 units of heparin that had been given over the past 6 hours). It may be used in those who overdose on heparin or to reverse heparins effect when it is no longer needed. Physiological function Heparins normal role in the body is unclear. Heparin is usually stored within the secretory granules of mast cells and released only into the vasculature at sites of tissue injury. It has been proposed that, rather than anticoagulation, the main purpose of heparin is defense at such sites against invading bacteria and other foreign materials. In addition, it is observed across a number of widely different species, including some invertebrates that do not have a similar blood coagulation system. It is a highly sulfated glycosaminoglycan. It has the highest negative charge density of any known biological molecule. Evolutionary conservation In addition to the bovine and porcine tissue from which pharmaceutical-grade heparin is commonly extracted, it has also been extracted and characterized from: The biological activity of heparin within species 6–11 is unclear and further supports the idea that the main physiological role of heparin is not anticoagulation. These species do not possess any blood coagulation system similar to that present within the species listed 1–5. The above list also demonstrates how heparin has been highly evolutionarily conserved, with molecules of a similar structure being produced by a broad range of organisms belonging to many different phyla. Pharmacology In nature, heparin is a polymer of varying chain size. Unfractionated heparin (UFH) as a pharmaceutical is heparin that has not been fractionated to sequester the fraction of molecules with low molecular weight. In contrast, low-molecular-weight heparin (LMWH) has undergone fractionation for the purpose of making its pharmacodynamics more predictable. Often either UFH or LMWH can be used; in some situations one or the other is preferable. Mechanism of action Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop. The activated AT then inactivates thrombin, factor Xa and other proteases. The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of heparin. Heparin binds to AT via a specific pentasaccharide sulfation sequence contained within the heparin polymer: GlcNAc/NS(6S)-GlcA-GlcNS(3S,6S)-IdoA(2S)-GlcNS(6S)The conformational change in AT on heparin-binding mediates its inhibition of factor Xa. For thrombin inhibition, however, thrombin must also bind to the heparin polymer at a site proximal to the pentasaccharide. The highly negative charge density of heparin contributes to its very strong electrostatic interaction with thrombin. The formation of a ternary complex between AT, thrombin, and heparin results in the inactivation of thrombin. For this reason, heparins activity against thrombin is size-dependent, with the ternary complex requiring at least 18 saccharide units for efficient formation. In contrast, antifactor Xa activity via AT requires only the pentasaccharide-binding site. This size difference has led to the development of low-molecular-weight heparins (LMWHs) and fondaparinux as anticoagulants. Fondaparinux targets anti-factor Xa activity rather than inhibiting thrombin activity, with the aim of facilitating a more subtle regulation of coagulation and an improved therapeutic index. It is a synthetic pentasaccharide, whose chemical structure is almost identical to the AT binding pentasaccharide sequence that can be found within polymeric heparin and heparan sulfate. With LMWH and fondaparinux, the risk of osteoporosis and heparin-induced thrombocytopenia (HIT) is reduced. Monitoring of the activated partial thromboplastin time is also not required and does not reflect the anticoagulant effect, as APTT is insensitive to alterations in factor Xa. Danaparoid, a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate can be used as an anticoagulant in patients having developed HIT. Because danaparoid does not contain heparin or heparin fragments, cross-reactivity of danaparoid with heparin-induced antibodies is reported as less than 10%.The effects of heparin are measured in the lab by the partial thromboplastin time (aPTT), one of the measures of the time it takes the blood plasma to clot. Partial thromboplastin time should not be confused with prothrombin time, or PT, which measures blood clotting time through a different pathway of the coagulation cascade. Administration Heparin is given parenterally because it is not absorbed from the gut, due to its high negative charge and large size. It can be injected intravenously or subcutaneously (under the skin); intramuscular injections (into muscle) are avoided because of the potential for forming hematomas. Because of its short biologic half-life of about one hour, heparin must be given frequently or as a continuous infusion. Unfractionated heparin has a half-life of about one to two hours after infusion, whereas LMWH has a half-life of four to five hours. The use of LMWH has allowed once-daily dosing, thus not requiring a continuous infusion of the drug. If long-term anticoagulation is required, heparin is often used only to commence anticoagulation therapy until an oral anticoagulant e.g. warfarin takes effect. The American College of Chest Physicians publishes clinical guidelines on heparin dosing. Natural degradation or clearance Unfractionated heparin has a half-life of about one to two hours after infusion, whereas low-molecular-weight heparins half-life is about four times longer. Lower doses of heparin have a much shorter half-life than larger ones. Heparin binding to macrophage cells is internalized and depolymerized by the macrophages. It also rapidly binds to endothelial cells, which precludes the binding to antithrombin that results in anticoagulant action. For higher doses of heparin, endothelial cell binding will be saturated, such that clearance of heparin from the bloodstream by the kidneys will be a slower process. Chemistry Heparin structure Native heparin is a polymer with a molecular weight ranging from 3 to 30 kDa, although the average molecular weight of most commercial heparin preparations is in the range of 12 to 15 kDa. Heparin is a member of the glycosaminoglycan family of carbohydrates (which includes the closely related molecule heparan sulfate) and consists of a variably sulfated repeating disaccharide unit. The main disaccharide units that occur in heparin are shown below. The most common disaccharide unit* (see below) is composed of a 2-O-sulfated iduronic acid and 6-O-sulfated, N-sulfated glucosamine, IdoA(2S)-GlcNS(6S). For example, this makes up 85% of heparins from beef lung and about 75% of those from porcine intestinal mucosa.Not shown below are the rare disaccharides containing a 3-O-sulfated glucosamine (GlcNS(3S,6S)) or a free amine group (GlcNH3+). Under physiological conditions, the ester and amide sulfate groups are deprotonated and attract positively charged counterions to form a heparin salt. Heparin is usually administered in this form as an anticoagulant. GlcA = β-D-glucuronic acid, IdoA = α-L-iduronic acid, IdoA(2S) = 2-O-sulfo-α-L-iduronic acid, GlcNAc = 2-deoxy-2-acetamido-α-D-glucopyranosyl, GlcNS = 2-deoxy-2-sulfamido-α-D-glucopyranosyl, GlcNS(6S) = 2-deoxy-2-sulfamido-α-D-glucopyranosyl-6-O-sulfate One unit of heparin (the "Howell unit") is an amount approximately equivalent to 0.002 mg of pure heparin, which is the quantity required to keep 1 ml of cats blood fluid for 24 hours at 0 °C. Three-dimensional structure The three-dimensional structure of heparin is complicated because iduronic acid may be present in either of two low-energy conformations when internally positioned within an oligosaccharide. The conformational equilibrium is influenced by sulfation state of adjacent glucosamine sugars. Nevertheless, the solution structure of a heparin dodecasaccharide composed solely of six GlcNS(6S)-IdoA(2S) repeat units has been determined using a combination of NMR spectroscopy and molecular modeling techniques. Two models were constructed, one in which all IdoA(2S) were in the 2S0 conformation (A and B below), and one in which they are in the 1C4 conformation (C and D below). However, no evidence suggests that changes between these conformations occur in a concerted fashion. These models correspond to the protein data bank code 1HPN. In the image above: A = 1HPN (all IdoA(2S) residues in 2S0 conformation) Jmol viewer B = van der Waals radius space filling model of A C = 1HPN (all IdoA(2S) residues in 1C4 conformation) Jmol viewer D = van der Waals radius space filling model of CIn these models, heparin adopts a helical conformation, the rotation of which places clusters of sulfate groups at regular intervals of about 17 angstroms (1.7 nm) on either side of the helical axis. Depolymerization techniques Either chemical or enzymatic depolymerization techniques or a combination of the two underlie the vast majority of analyses carried out on the structure and function of heparin and heparan sulfate (HS). Enzymatic The enzymes traditionally used to digest heparin or HS are naturally produced by the soil bacterium Pedobacter heparinus (formerly named Flavobacterium heparinum). This bacterium is capable of using either heparin or HS as its sole carbon and nitrogen source. To do so, it produces a range of enzymes such as lyases, glucuronidases, sulfoesterases, and sulfamidases. The lyases have mainly been used in heparin/HS studies. The bacterium produces three lyases, heparinases I (EC 4.2.2.7), II (no EC number assigned) and III (EC 4.2.2.8) and each has distinct substrate specificities as detailed below. The lyases cleave heparin/HS by a beta elimination mechanism. This action generates an unsaturated double bond between C4 and C5 of the uronate residue. The C4-C5 unsaturated uronate is termed ΔUA or UA. It is a sensitive UV chromophore (max absorption at 232 nm) and allows the rate of an enzyme digest to be followed, as well as providing a convenient method for detecting the fragments produced by enzyme digestion. Chemical Nitrous acid can be used to chemically depolymerize heparin/HS. Nitrous acid can be used at pH 1.5 or at a higher pH of 4. Under both conditions, nitrous acid effects deaminative cleavage of the chain. At both high (4) and low (1.5) pH, deaminative cleavage occurs between GlcNS-GlcA and GlcNS-IdoA, albeit at a slower rate at the higher pH. The deamination reaction, and therefore chain cleavage, is regardless of O-sulfation carried by either monosaccharide unit. At low pH, deaminative cleavage results in the release of inorganic SO4, and the conversion of GlcNS into anhydromannose (aMan). Low-pH nitrous acid treatment is an excellent method to distinguish N-sulfated polysaccharides such as heparin and HS from non N-sulfated polysaccharides such as chondroitin sulfate and dermatan sulfate, chondroitin sulfate and dermatan sulfate not being susceptible to nitrous acid cleavage. Detection in body fluids Current clinical laboratory assays for heparin rely on an indirect measurement of the effect of the drug, rather than on a direct measure of its chemical presence. These include activated partial thromboplastin time (APTT) and antifactor Xa activity. The specimen of choice is usually fresh, nonhemolyzed plasma from blood that has been anticoagulated with citrate, fluoride, or oxalate. Other functions Blood specimen test tubes, vacutainers, and capillary tubes that use the lithium salt of heparin (lithium heparin) as an anticoagulant are usually marked with green stickers and green tops. Heparin has the advantage over EDTA of not affecting levels of most ions. However, the concentration of ionized calcium may be decreased if the concentration of heparin in the blood specimen is too high. Heparin can interfere with some immunoassays, however. As lithium heparin is usually used, a persons lithium levels cannot be obtained from these tubes; for this purpose, royal-blue-topped (and dark green-topped) vacutainers containing sodium heparin are used. Heparin-coated blood oxygenators are available for use in heart-lung machines. Among other things, these specialized oxygenators are thought to improve overall biocompatibility and host homeostasis by providing characteristics similar to those of native endothelium. The DNA binding sites on RNA polymerase can be occupied by heparin, preventing the polymerase from binding to promoter DNA. This property is exploited in a range of molecular biological assays. Common diagnostic procedures require PCR amplification of a patients DNA, which is easily extracted from white blood cells treated with heparin. This poses a potential problem, since heparin may be extracted along with the DNA, and it has been found to interfere with the PCR reaction at levels as low as 0.002 U in a 50 μL reaction mixture. Heparin has been used as a chromatography resin, acting as both an affinity ligand and an ion exchanger. Its polyanionic structure can mimic nucleic acids like DNA and RNA, making it useful for purification of nucleic acid-binding proteins including DNA and RNA polymerases and transcription factors. Heparins specific affinity for VSV-G, a viral envelope glycoprotein often used to pseudotype retroviral and lentiviral vectors for gene therapy, allows it to be used for downstream purification of viral vectors. Heparin is being trialed in a nasal spray form as prophylaxis against COVID-19 infection. Furthermore, its reported from trials that due to anti-viral, anti-inflammatory and its anti-clotting effects its inhalation could improve at a 70% rate on patients that were actively struck by a COVID-19 infection. Society and culture Contamination recalls Considering the animal source of pharmaceutical heparin, the numbers of potential impurities are relatively large compared with a wholly synthetic therapeutic agent. The range of possible biological contaminants includes viruses, bacterial endotoxins, transmissible spongiform encephalopathy (TSE) agents, lipids, proteins, and DNA. During the preparation of pharmaceutical-grade heparin from animal tissues, impurities such as solvents, heavy metals, and extraneous cations can be introduced. However, the methods employed to minimize the occurrence and to identify and/or eliminate these contaminants are well established and listed in guidelines and pharmacopoeias. The major challenge in the analysis of heparin impurities is the detection and identification of structurally related impurities. The most prevalent impurity in heparin is dermatan sulfate (DS), also known as chondroitin sulfate B. The building-block of DS is a disaccharide composed of 1,3-linked N-acetyl galactosamine (GalN) and a uronic acid residue, connected via 1,4 linkages to form the polymer. DS is composed of three possible uronic acid (GlcA, IdoA or IdoA2S) and four possible hexosamine (GalNAc, Gal- NAc4S, GalNAc6S, or GalNAc4S6S) building-blocks. The presence of iduronic acid in DS distinguishes it from chrondroitin sulfate A and C and likens it to heparin and HS. DS has a lower negative charge density overall compared to heparin. A common natural contaminant, DS is present at levels of 1–7% in heparin API, but has no proven biological activity that influences the anticoagulation effect of heparin.In December 2007, the US Food and Drug Administration (FDA) recalled a shipment of heparin because of bacterial growth (Serratia marcescens) in several unopened syringes of this product. S. marcescens can lead to life-threatening injuries and/or death. 2008 recall due to adulteration in drug from China In March 2008, major recalls of heparin were announced by the FDA due to contamination of the raw heparin stock imported from China. According to the FDA, the adulterated heparin killed nearly 80 people in the United States. The adulterant was identified as an "over-sulphated" derivative of chondroitin sulfate, a popular shellfish-derived supplement often used for arthritis, which was intended to substitute for actual heparin in potency tests.According to the New York Times: "Problems with heparin reported to the agency include difficulty breathing, nausea, vomiting, excessive sweating and rapidly falling blood pressure that in some cases led to life-threatening shock". Use in homicide In 2006, Petr Zelenka, a nurse in the Czech Republic, deliberately administered large doses to patients, killing seven, and attempting to kill ten others. Overdose issues In 2007, a nurse at Cedars-Sinai Medical Center mistakenly gave the 12-day-old twins of actor Dennis Quaid a dose of heparin that was 1,000 times the recommended dose for infants. The overdose allegedly arose because the labeling and design of the adult and infant versions of the product were similar. The Quaid family subsequently sued the manufacturer, Baxter Healthcare Corp., and settled with the hospital for $750,000. Prior to the Quaid accident, six newborn babies at Methodist Hospital in Indianapolis, Indiana, were given an overdose. Three of the babies died after the mistake.In July 2008, another set of twins born at Christus Spohn Hospital South, in Corpus Christi, Texas, died after an accidentally administered overdose of the drug. The overdose was due to a mixing error at the hospital pharmacy and was unrelated to the products packaging or labeling. As of July 2008, the exact cause of the twins death was under investigation.In March 2010, a two-year-old transplant patient from Texas was given a lethal dose of heparin at the University of Nebraska Medical Center. The exact circumstances surrounding her death are still under investigation. Production Pharmaceutical-grade heparin is derived from mucosal tissues of slaughtered meat animals such as porcine (pig) intestines or bovine (cattle) lungs. Advances to produce heparin synthetically have
Heparin	been made in 2003 and 2008. In 2011, a chemoenzymatic process of synthesizing low molecular weight heparins from simple disaccharides was reported. Research As detailed in the table below, the potential is great for the development of heparin-like structures as drugs to treat a wide range of diseases, in addition to their current use as anticoagulants. – indicates that no information is availableAs a result of heparins effect on such a wide variety of disease states, a number of drugs are indeed in development whose molecular structures are identical or similar to those found within parts of the polymeric heparin chain. References Further reading External links "Heparin". Drug Information Portal. U.S. National Library of Medicine. History of heparin
Nemaline myopathy	Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout ones life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy."Myopathy" means muscle disease. Muscle fibers from a person with nemaline myopathy contains thread-like rods, sometimes called nemaline bodies. While the rods are diagnostic of the disorder, they are more likely a byproduct of the disease process rather than causing any dysfunction on their own. People with nemaline myopathy (NM) usually experience delayed motor development, or no motor development in severe cases, and weakness may occur in all of the skeletal muscles, such as muscles in the arms, legs, torso, neck flexors, throat, and face. The weakness tends to be more severe in the proximal muscles rather than the distal muscles. The ocular muscles are normally spared. The disorder is often clinically categorized into groups with wide ranges of overlapping severity, from the most severe neonatal form which is incompatible with life, to a form so mild that it may not be diagnosed since the person appears to function at the lowest end of normal strength and breathing adequacy. Sporadic late onset nemaline myopathy (SLONM) is not a congenital disorder and is considered a different muscle disease from NM, which has its onset at birth or early childhood. Respiratory problems are usually a primary concern for people with all forms of NM, and respiratory infections are quite common. NM shortens life expectancy, particularly in the more severe forms, but aggressive and proactive care allows most individuals to survive and even lead active lives. Nemaline myopathy is one of the neuromuscular diseases covered by the Muscular Dystrophy Association in the United States. Signs and symptoms Signs vary from person to person. Young children and babies lack movement and have a difficult time eating and breathing. For young children not diagnosed immediately at birth, these are usually the first visible symptoms. One sign is a swollen face in disproportional areas. Other examples in newborns include swaying and a difficulty in moving. Other symptoms include feeble muscles in the neck and upper rib cage area. In adults, the most common symptom is respiratory problems. Other symptoms in adults could range from mild to severe speech impediments. It is common to be diagnosed with scoliosis in relations to nemaline myopathy. As babies that have NM develop and become of age when they should start walking, many take longer than average due to the lack of muscle, or just muscle fatigue.Since facial muscles are involved in NM takeover, elongated faces and a lower mandible are often observed in people with NM. People affected by NM usually will begin to feel muscle exhaustion between ages 20–50. NM is usually not progressive. Gastroesophageal reflux, although not common, is associated with NM. Heart abnormalities can occur as a result of NM, but the likelihood of that happening are not high. Mobility and orthopedics Most children with mild NM eventually walk independently, although often at a later age than their peers. Some use wheelchairs or other devices, such as walkers or braces, to enhance their mobility. Individuals with severe NM generally have limited limb movement and use wheelchairs full-time. Due to weakness in the trunk muscles, people with NM are prone to scoliosis, which usually develops in childhood and worsens during puberty. Many individuals with NM undergo spinal fusion surgery to straighten and stabilize their backs.Although patients early on often have mobility in their joints that is past the normal range, as they age, joint deformities and scoliosis usually occur. If the person with nemaline myopathy keeps an eye on his or her joints early on, the problems with them can be detected when they begin and their progression can be delayed. Treatment of joint problems ranges from stretching exercises with physical therapy to surgical introduction of braces. The benefits of exercise in people with nemaline myopathy are still being studied, however, researchers have seen improvements in muscle function from low-intensity exercise. Vigorous exercise and the use of heavy weights should be avoided. Respiratory involvement Attention to respiratory issues is critical to the health of many people with NM. Infants with severe NM frequently experience respiratory distress at or soon after birth, although this is only found in the rarest forms. Though respiratory compromise may not be immediately apparent in people with intermediate or mild NM, it often, but not always, exists to some extent. As in many neuromuscular disorders, hypoventilation can begin insidiously, and it may cause serious health problems if not remedied by the use of noninvasive mechanical devices to assist breathing, particularly at night. Communication and eating Bulbar (throat) muscle weakness is a main feature of nemaline myopathy. Individuals with the most severe forms of NM are unable to swallow and receive their nutrition through feeding tubes. Most people with intermediate and mild NM take some or all of their nutrition orally. Bulbar muscle impairment may also lead to difficulty with communication. People with NM often have hypernasal speech as a result of poor closure of the velopharyngeal port (between the soft palate and the back of the throat). This may be able to be surgically corrected. Communicative skills may be enhanced through speech therapy, oral prosthetic devices, surgery, and augmentative communication devices. NM does not have any impact on cognition or intelligence. Physical characteristics and effects Physical expression of nemaline myopathy varies greatly, but weakness is usually concentrated in the proximal muscles, particularly respiratory, bulbar and trunk muscles. People with severe NM show obvious symptoms at birth, while those with intermediate or mild NM may initially appear unaffected. Babies with NM are frequently observed to be "floppy" and hypotonic. Children born with NM often gain strength as they grow, though the effect of muscle weakness on body features may become more evident with time. Adults with NM typically have a very slender physique. Causes Nemaline myopathy is caused by mutations in one of at least 11 different genes. Nemaline myopathy is a clinically and genetically heterogeneous disorder and both autosomal dominant and autosomal recessive forms can occur. Diagnosis is made based upon clinical signs such as muscle weakness, absent or low deep tendon reflexes (hyporeflexia), and a high-arched palate, along with electron-dense aggregates, called nemaline rods, being observed at the microscopic level within muscle fibers. Genetic confirmation through identification of a known genetic mutation in the patient is also an important component of diagnosis.The two most common gene mutations causing nemaline myopathy are found on NEB or ACTA1. Mutations of the NEB gene usually result in symptoms present at birth or beginning in early childhood. This mutation results in about 50% of affected nemaline myopathy patients. The most common inheritance pathway for those with mutations in NEB is autosomal recessive in which each parent carries one mutated copy along with one normal functioning copy of the gene, and they pass the mutated copy to their offspring. In some cases, occasionally with ACTA1 mutations, NM can be caused by an inheritance pattern of autosomal dominance. This mutation results in about 15 to 25 percent of NM cases. One reason why this is lower is because NM is associated with de novo mutations in ACTA1, occurring spontaneously in the egg or sperm. When the condition is heritable, each pregnancy with the same partners has the same risk of passing the mutated genes to offspring. New mutations (de novo) can also occur causing NM and de novo mutations have been most often found to occur in the ACTA1 gene. MYPN is the last found gene related to NM The risk of all cases of nemaline myopathy is the same in males and females. The physical capabilities of a given person with NM do not correlate well either with genotype or with muscle pathology as observed in the biopsy. Mechanism Muscle cells contract in complex mechanical and chemical processes. If any part of the process or structure is disrupted, dysfunction will likely result, as in the case of those with genetic variations. In those with nemaline myopathy, muscle contraction is adversely affected. At the electron microscopic level, rod-shaped components can often be seen in some of the muscle cells, and when seen, are diagnostic for the condition called nemaline rod myopathy. The presence of these rods is not itself causing muscle weakness; rather they appear as a result of something going wrong within the muscle fiber. There is no connection between the number of rods found in the muscle cells and the amount of weakness a person has. All of the different gene mutations leading to the condition called nemaline myopathy that have been found so far are in genes that encode different components of the sarcomere. In normal muscle cells, the various parts of the muscle fibers that make up the sarcomere are distributed evenly in a pattern for effective muscle contraction. Evidence suggests that some kinds of NM affect the arrangement of these muscle fibers, causing the muscles to be unable to contract as efficiently or effectively. Nemaline myopathy is usually genetic and shows traits in the affected individual from birth or an early age. However, there are some cases of symptoms of nemaline myopathy not showing up until adulthood. These cases are usually not genetic. Of the genes that have been linked to nemaline myopathy, most are also involved in encoding proteins in the sarcomeres in the muscle cells. Respiratory muscles are often more affected than other skeletal muscle groups. Cardiac muscle is usually not affected in nemaline myopathy; however, in cases where it does, patients often present with dilated cardiomyopathy. The ocular muscles are usually spared.The different genes whose mutations lead to the different kinds of nemaline myopathies affect the cells and the persons body differently. The first kind of nemaline myopathy identified is due to the Slow α-Tropomyosin Gene TPM3 and varies from case to case with its severity. In this kind of nemaline myopathy, affected people are weaker and more affected in their lower limbs than their upper limbs.As stated above, the most common genetic form of NM is caused by a mutation in the nebulin gene, called Nebulin, and has a range of severity levels. All published cases up to this point where NM is thought to be caused by a mutation in the NEB gene have been autosomal recessive and are the most common cause of nemaline myopathy. Patients with this kind of NM are more affected in the muscles in their head, rather than their proximal muscles at the core of their body. Consequently, patients with this genetic mutation often cannot lift their heads and speak with a nasal voice. There have been cases that suggest this kind of NM may lead to patients having higher intellect.A third kind of nemaline myopathy in the Skeletal Muscle α-Actin Gene ACTA1 is due to a recessive null mutation. These patients do not always show the typical nemaline bodies in their muscle cells. The only abnormality they show is an abnormal distribution of muscle fibers. There are several other identified kinds of mutations that lead to Nemaline Myopathies. One affects slow skeletal muscles, one leads to the formation of both nemaline bodies and other abnormal, core-like, structures forming in the patients muscles. Diagnosis Electromyography or (EMG). This procedure determines if nerve or muscle cells are damaged. Since a common symptom of Nemaline Myopathy is muscle weakness this allows doctors to determine where and why the weakness is occurring. MRI of the Musculoskeletal System. MRI uses a magnetic field to take pictures of body structures and allows physicians to determine if a patient has a certain disease. Needle biopsy A needle biopsy allows a physician to test specific cells in the body. These cells are sent to a laboratory to undergo testing and can further determine why muscle weakness throughout the body could be occurring. This testing can confirm that muscle cells contain rod like structures. Treatment At present, Nemaline myopathy does not have a cure. Nemaline myopathy is a very rare disease that only affects 1 out of 50,000 on average, although recent studies show that this number is even smaller. There are a number of treatments to minimize the symptoms of the disease. The treatments and procedures to help patients with nemaline myopathy vary depending on the severity of the disease. A possible accommodation could be the use of a stabilizer, such as a brace. Other means include moderate stretching and moderate exercise to help target muscles maintain maximum health. As people with NM grow and develop throughout their lives, it is important for them to see a variety of health professionals regularly, including a neurologist, physical therapist, and others, such as speech therapists and psychologists, to help both the patient and family adjust to everyday life. Outcome Although there is no cure for NM, it is possible, and common for many people live healthy active lives even with moderate to severe cases. Research continues to seek ways to ameliorate debilitating symptoms and lengthen the life-span in quality ways for those affected. Some people have seen mild improvements in secretion handling, energy level, and physical functioning with supplemental L-tyrosine, an amino acid that is available through health centers. Some symptoms may worsen as the patient ages. Muscle loss increases with age naturally, but it is even more significant with nemaline myopathy. Current research New research resources have become available for the NM community, such as the CMDIR (registry) and the CMD-TR (biorepository). These two resources connect families and individuals interested in participating in research with the scientists that aim to treat or cure NM. Some research on NM seeks to better understand the molecular effects the gene mutations have on muscle cells and the rest of the body and to observe any connections NM may have to other diseases and health complications. History "Rod myopathy" was first identified by Douglas Reye, an Australian physician, in 1958. However, Reyes results were never published because another doctor dismissed his finding of rods in the muscle tissue as an artifact of the biopsy. Forty years later, Reyes "rod myopathy" patient was confirmed to have nemaline myopathy. Another group of Australian researchers has since published an article recognizing Reye for his work."Nemaline myopathy" was first named in a published paper in 1963 by North American researchers P.E. Cohen and G. M. Shy. Shy and his team discovered rod- like structures in muscle fibers of patients with muscle weakness by performing muscle biopsies on multiple patients. Laboratories performing research on NM are located around the world, notably in the United States, Canada, England, Finland, and Australia. Society and culture In 1999, the first website on nemaline myopathy was launched, and in October 2004, the first Nemaline Myopathy Convention was held in Toronto, Canada. Many more conferences and social events have been held since, and all events organized since 2008 have been co-sponsored by A Foundation Building Strength for Nemaline Myopathy (AFBS), the only foundation focused on supporting treatment development and social events for the NM community. In March 2006, Niki Shisler released a book, Fragile, in which she recounted her experiences surrounding the birth of twin sons with severe NM. In 2014, a team of experts collaborated with affected individuals and families caring for someone with a congenital myopathy to develop the first guidebook on managing life with a congenital myopathy References External links GeneReview/NCBI/NIH/UW entry on Nemaline Myo\
Selective immunoglobulin A deficiency	Selective immunoglobulin A (IgA) deficiency (SIgAD) is a genetic immunodeficiency, a type of hypogammaglobulinemia. People with this deficiency lack immunoglobulin A (IgA), a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract. It is defined as an undetectable serum IgA level in the presence of normal serum levels of IgG and IgM, in persons older than 4 years. It is the most common of the primary antibody deficiencies. Most such persons remain healthy throughout their lives and are never diagnosed. Signs and symptoms 85–90% of IgA-deficient individuals are asymptomatic, although the reason for lack of symptoms is relatively unknown and continues to be a topic of interest and controversy. Some patients with IgA deficiency have a tendency to develop recurrent sinopulmonary infections, gastrointestinal infections and disorders, allergies, autoimmune conditions, and malignancies. These infections are generally mild and would not usually lead to an in-depth workup except when unusually frequent. They rarely present with severe reactions, including anaphylaxis, to blood transfusions or intravenous immunoglobulin due to the presence of IgA in these blood products. Patients have an increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age.IgA deficiency and common variable immunodeficiency (CVID) feature similar B cell differentiation arrests, but it does not present the same lymphocyte subpopulation abnormalities. IgA-deficient patients may progress to panhypogammaglobulinemia characteristic of CVID. Selective IgA and CVID are found in the same family. Cause Selective IgA deficiency is inherited and has been associated with differences in chromosomes 18, 14 and 6. Selective IgA deficiency is often inherited, but has been associated with some congenital intrauterine infections. Pathophysiology Pathogenesis of IgA Deficiency ‘In IgA-deficient patients, the common finding is a maturation defect in B cells to produce IgA’. ‘In IgA deficiency, B cells express IgA; however, they are of immature phenotype with the coexpression of IgM and IgD, and they cannot fully develop into IgA-secreting plasma cells’. There is an inherited inability to produce immunoglobulin A (IgA), a part of the bodys defenses against infection at the bodys surfaces (mainly the surfaces of the respiratory and digestive systems). As a result, bacteria at these locations are somewhat more able to cause disease.Types include: Diagnosis When suspected, the diagnosis can be confirmed by laboratory measurement of IgA level in the blood. SIgAD is an IgA level < 7 mg/dL with normal IgG and IgM levels (reference range 70–400 mg/dL for adults; children somewhat less). Treatment The treatment consists of identification of co-morbid conditions, preventive measures to reduce the risk of infection, and prompt and effective treatment of infections. Infections in an IgA-deficient person are treated as usual (i.e., with antibiotics). There is no treatment for the underlying disorder. Use of IVIG as treatment There is a historical popularity in using intravenous immunoglobulin (IVIG) to treat SIgAD, but the consensus is that there is no evidence that IVIG treats this condition. In cases where a patient presents SIgAD and another condition which is treatable with IVIG, then a physician may treat the other condition with IVIG. The use of IVIG to treat SIgAD without first demonstrating an impairment of specific antibody formation is not recommended. Prognosis Prognosis is excellent, although there is an association with autoimmune disease. Of note, selective IgA deficiency can complicate the diagnosis of one such condition, celiac disease, as the deficiency masks the high levels of certain IgA antibodies usually seen in celiac disease.As opposed to the related condition CVID, selective IgA deficiency is not associated with an increased risk of cancer.Patients with Selective IgA deficiency rarely have severe reactions to blood transfusions. Although Selective IgA deficiency is common, severe reactions to blood transfusions are very rare. People with selective IgA deficiency do not require special blood products unless they have a history of a severe allergic reaction to a blood transfusion. Epidemiology Prevalence varies by population, but is on the order of 1 in 100 to 1 in 1000 people, making it relatively common for a genetic disease. SIgAD occurs in 1 in 39 to 1 in 57 people with celiac disease. This is much higher than the prevalence of selective IgA deficiency in the general population. It is also significantly more common in those with type 1 diabetes.It is more common in males than in females. See also B cell deficiency References == External links ==
Benign hypertension	Benign hypertension or benign essential hypertension are historical terms that are considered misleading, as hypertension is never benign, and consequently they have fallen out of use (see history of hypertension). The terminology persisted in the International Classification of Disease (ICD9), but is not included in the current ICD10. == References ==
Hidradenoma	Hidradenoma refers to a benign adnexal tumor of the apical sweat gland. These are 1–3 cm translucent blue cystic nodules. It usually presents as a single, small skin-colored lesion, and may be considered closely related to or a variant of poromas. Hidradenomas are often sub-classified based on subtle histologic differences, for example: Eccrine acrospiroma Clear-cell hidradenoma or acrospiroma Nodular hidradenoma or acrospiroma Solid-cystic hidradenomaDiscussion of sweat gland tumors can be difficult and confusing due to the complex classification and redundant terminology used to describe the same tumors. For example, acrospiroma and hidradenoma are synonymous, and sometimes the term acrospiroma is used to generally describe benign sweat gland tumors. In addition, a single lesion may contain a mixture of cell-types. There has also been a change in understanding about how tumors that were previously believed to strictly derive from specific sweat gland types may, in fact, derive from both eccrine or apocrine glands.Hidradenomas are by definition benign, with malignant transformation very rare. When tumors show malignant characteristics, they are known as hidradenocarcinoma. Surgical excision is usually curative and local recurrences are rare, although malignant tumors may metastasize. See also Spiroma List of cutaneous conditions List of cutaneous neoplasms associated with systemic syndromes References == External links ==
Acute flaccid myelitis	Acute flaccid myelitis (AFM) is a serious condition of the spinal cord. Symptoms include rapid onset of arm or leg weakness and decreased reflexes. Difficulty moving the eyes, speaking, or swallowing may also occur. Occasionally, numbness or pain may be present. Complications can include trouble breathing.The cause of most cases is unclear as of 2018. More than 90% of recent cases have followed a mild viral infection such as from enteroviruses. While polio can cause AFM, since 2014, it has not been involved in cases in the United States. The underlying mechanism involves damage to the spinal cords grey matter. Diagnosis may be supported by medical imaging of the spine, nerve conduction studies, and cerebrospinal fluid testing.Treatment involves supportive care. Physical therapy may be recommended. Occasionally, mechanical ventilation is required to support breathing. Outcomes are variable. The condition is rare and occurs most commonly in children. Fewer than one in 500,000 children is affected per year in the United States. Although the illness is not new, an increase in cases has been seen since 2014 in the United States. In 2018, 233 cases were confirmed in the United States. Signs and symptoms Symptoms include: Difficulty moving the eyes or drooping eyelids Facial droop or weakness Difficulty with swallowing or slurred speech Sudden arm or leg weaknessA summary of the condition by the Centers for Disease Control and Prevention (CDC) in 2014: Common features included acute focal limb weakness and specific findings on magnetic resonance imaging (MRI) of the spinal cord consisting of nonenhancing lesions largely restricted to the grey matter. In most cases, these lesions spanned more than one level of the spinal cord. Some also had acute cranial nerve dysfunction with correlating nonenhancing brainstem lesions on MRI. None of the children experienced altered mental status or seizures. None had any cortical, subcortical, basal ganglial, or thalamic lesions on MRI. Most children reported a febrile respiratory illness in the two weeks preceding development of neurologic symptoms. In most cases, cerebrospinal fluid (CSF) analyses demonstrated mild-moderate pleocytosis (increased cell count in the CSF) consistent with an inflammatory or infectious process. Causes As of October 2018, the U.S. CDC regarded the cause of AFM as having "a variety of possible causes such as viruses, environmental toxins, and genetic disorders", listing poliovirus, nonpolio enteroviruses, West Nile virus, and adenoviruses among the potential causes. More than 90% of people with AFM reported having symptoms consistent with a mild viral infection before the onset of AFM.Much research has focused on the nonpolio enteroviruses 68 (EV-D68) and 71 (EV-A71), a common cause of hand, foot, and mouth disease in infants and young children, members of the enterovirus D and enterovirus A species, respectively, as suspected causes. Some evidence supports a causal role of EV-D68. Coxsackievirus A16 may also play a role in some cases.A 2014 Morbidity and Mortality Weekly Report report noted the difficulty of establishing causation by the virus. Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke and president of the International Society for NeuroVirology, compared the situation to the prolonged investigations that led to confirmation of HIV as the cause of AIDS. In response to the suggestion that the enterovirus might be taking over the role of polio, Nath said that EV-D68 was far less virulent and spread much more slowly than polio, and that unlike in polio, only a few cases of paralysis were seen per thousand children infected. He also suggested that adults with respiratory diseases should also be evaluated for neurological deficits, and that infectious disease should be considered as a cause when patients presented with neurological symptoms.A subsequent report described 29 cases of EV-D68-associated AFM in Europe in 2016, noting, "these probably represent only the tip of the iceberg."CDC sees 2018 as a record year, annual documented cases of AFM reached a record 238 nationwide. The relatively lower circulation in 2020 may reflect the use of COVID-19 pandemic infection mitigation measures. Because of the EV-D68 surge in 2022 Health Alert Network (HAN) released a notice for Healthcare providers and hospitals. The CDC warned clinicians that EV-D68 detections have continued to be high. "Sentinel surveillance sites are reporting a higher proportion of EV-D68 positivity in children who are [rhinovirus and/or enterovirus] positive compared to previous years," the agency wrote. Clinicians should be aware of "the potential for an increase in AFM cases in the upcoming weeks." CDC urges healthcare providers to consider EV-D68 as a possible cause of acute, severe respiratory illness and a potential increase in AFM cases. Diagnosis AFM is diagnosed by examining a persons nervous system in combination with reviewing images of the spinal cord. A doctor can examine a persons nervous system and the places on the body where he or she has weakness, poor muscle tone, and decreased reflexes. In addition, a doctor can do magnetic resonance imaging to look at a persons brain and spinal cord, do laboratory tests on the cerebrospinal fluid (CSF, the fluid around the brain and spinal cord), and may check nerve conduction (impulse sent along a nerve fiber) and response.Diagnosis of AFM requires acute onset limb paralysis and at least one gray-matter spinal-cord lesion. CSF should show pleocytosis. Prevention The CDC recommends, "To prevent infections in general, persons should stay home if they are ill, wash their hands often with soap and water, avoid close contact (such as touching and shaking hands) with those who are ill, and clean and disinfect frequently touched surfaces." Treatment Treatment involves supportive care. Physical therapy may be recommended. Occasionally mechanical ventilation is required to support breathing.If immunoglobulin, corticosteroids, plasma exchange, or antiviral medication are useful is unclear. Outcomes Studies from 2014 to 2017 indicated a poor outcome for many cases. Seven of 61 cases with EVD68 detected and eight long‐term follow‐ups had full recovery; two deaths were described in severely immunocompromised people (one with EVD68 and one with both EVD68 and coxsackie A16 detected).Six of 10 children in Denver were sent home for outpatient treatment. Some of the children with mild and moderate cases have recovered partially from temporary limb weakness but still have permanent weakness, whereas those with more severe cases have not recovered as much. Intensive physical therapy and occupational therapy may be beneficial for recovery. Epidemiology A seasonal pattern is seen in outbreaks, with a marked increase in cases reported in the late summer and early fall.The CDC has determined and submitted to GenBank complete or nearly complete genomic sequences for three known strains of the virus, which are "genetically related to strains of EV-D68 virus that were detected in previous years in the United States, Europe, and Asia."While rates of paralytic symptoms appear to be correlated with the number of respiratory infections, in initial anecdotal reports, the cases are not clustered within a family or school, suggesting that the paralysis per se is not directly contagious, but arises as a very rare complication of the common respiratory infection.Cases of similar illnesses have been reported in Canada, Northern Europe, and Japan. Over 90% of reported cases are in children. History AFM has only been formally tracked since 2014, since the incidence has spiked in recent years.A group in Texas reported having observed a pattern in 2013 of one to four cases per year with similar polio-like characteristics.In 2014, the CDC Morbidity and Mortality Weekly Report and a CDC Clinician Outreach and Communication Activity (COCA) conference call, noted that many cases had neck, back, or extremity pain, but otherwise those affected generally had normal sensation in their limbs. A few participants in the conference call discussed whether pain, later abating, might precede the onset of paralysis.An October 2014 report described outbreaks in California and Colorado, suggesting that the number of cases might be 100 or more nationwide. Diagnosis included a detailed medical history, MRI imaging, and the elimination of transverse myelitis or Guillain–Barré syndrome as potential causes. Physicians were using an online mailing list to communicate about similar cases in Alabama and Kansas. The largest known cluster of cases was in Colorado, with 29 total, 12 of whom had been reported from August and onwards of that year. Three of four cases treated in Alabama involved a complete inability to move one arm, reminiscent of peripheral nerve injury: The three cases since August really look like each other. They have severe arm flaccidity and no mental status changes. All of them have similar spine MRIs showing gray-matter involvement. You could lay all three MRIs on top of each other and they look almost the same. Its pretty striking. ... It you lift the arm up, it literally drops. Sensation is usually intact. There might be slightly decreased sensation in the other arm, but these are younger kids, so theyre not always so cooperative in giving you a good sensory exam. Childrens Mercy Hospital, which had three or four cases in 2014, reported that the MRI images and symptoms closely mimicked polio. They reported: "The sudden onset of flaccid paralysis in single or multiple limbs with absolutely no sensory findings, the MRIs all showing uniformly a signal increase in the ventral horns of the spinal cord — this is exactly the same region of the spinal cord affected in polio ... Almost all of the patients have an increase in their white blood cells in the cerebrospinal fluid. Some of the patients have brainstem findings and cranial-nerve findings."Of 64 patients meeting the CDC criteria before October 29, 2014, 80% had had a preceding respiratory illness and 75% reported fever in the days leading up to limb weakness, the onset of which was generally abrupt. By November 20, the number of confirmed cases stood at 88 from 29 states.The CDC requested that physicians provide information about cases meeting these criteria: patients diagnosed after August 1, 2014, who are no older than 21 years of age, showing acute onset of focal limb weakness, with a spinal-cord lesion largely restricted to grey matter visualized by MRI.In November 2018, the CDC reported that they were investigating 286 cases, with at least 116 confirmed cases in 31 states. The CDC is setting up a task force to investigate the causes and to find treatments. == References ==
Pneumococcal pneumonia	Pneumococcal pneumonia is a type of bacterial pneumonia that is caused by Streptococcus pneumoniae (pneumococcus). It is the most common bacterial pneumonia found in adults, the most common type of community-acquired pneumonia, and one of the common types of pneumococcal infection. The estimated number of Americans with pneumococcal pneumonia is 900,000 annually, with almost 400,000 cases hospitalized and fatalities accounting for 5-7% of these cases. Symptoms The symptoms of pneumococcal pneumonia can occur suddenly, presenting as a severe chill, followed by a severe fever, cough, shortness of breath, rapid breathing, and chest pains. Other symptoms like nausea, vomiting, headache, fatigue, and muscle aches could also accompany initial symptoms. The coughing can occasionally produce rusty or blood-streaked sputum. In 25% of cases, a parapneumonic effusion may occur. Chest X-rays will typically show lobar consolidation or patchy infiltrates. Treatment In most cases, once pneumococcal pneumonia has been identified, doctors will prescribe antibiotics. These antibiotics usually help alleviate and eliminate symptoms between 12 and 36 hours after the initial dose. Despite most antibiotics effectiveness in treating the disease, sometimes the bacteria can resist the antibiotics, causing symptoms to worsen. Age and health of the infected patient can also contribute to the effectiveness of the antibiotics. A vaccine has been developed for the prevention of pneumococcal pneumonia, recommended to children under age five as well as adults over the age of 65. Research advancements in the field While it has been commonly known that the influenza virus increases ones chances of contracting pneumonia or meningitis caused by the streptococcus pneumonaie bacteria, new medical research in mice indicates that the flu is actually a necessary component for the transmission of the disease. Researcher Dimitri Diavatopoulo from the Radboud University Nijmegen Medical Centre in the Netherlands describes his observations in mice, stating that in these animals, the spread of the bacteria only occurs between animals already infected with the influenza virus, not between those without it. He says that these findings have only been inclusive in mice, however, he believes that the same could be true for humans. Mechanism of disease manifestation Three stages can be used to categorize the infection process of pneumococcal pneumonia: transmission, colonization, and invasion. The Streptococcus pneumoniae (S. pneumoniae) leave the colonized host via shedding in order to be transmissible to new hosts, and must survive in the environment until infection of a new host (unless direct transmission occurs). Animal models have allowed scientists to have an increased understanding of these stages of infection. Transmission In order for transmission to occur, there must be close contact with a carrier or amongst carriers. The likelihood of this increases during colder, dryer months of the year. The probability of transmission is shown to proliferate in coordination with other upper respiratory tract (URT) infections. Animal models have allowed for an increased understanding of the transmission stage during infection. A 2010 study examining co-infection of influenza in co-housed ferret pairs found that the influenza increased both incidence and severity of pneumococcal infection. These findings exhibited pneumococcal strain dependence. A separate 2010 study examining intra-litter transmission, with influenza co-infection in infant mice, found that the influenza co-infection is a facilitator for pneumococcal susceptibility, transmission, and disease via bacterial shedding. A third study of note, from 2016, was able to examine pneumococcal transmission without co-infection of an URT infection. This study utilized intra-litter transmission in infant mice during bacterial mono-infection with pneumococcus. The results of this study indicated higher rates of shedding for infections in younger mice. These studies, along with the animal models that they utilize have enhanced our understanding of the transmission of pneumococcus. Inflammation induced by Influenza A Virus (IAV) stimulates the flow of mucus through the expression of glycoproteins, prompts secretion, and increases shedding. Streptococcus is found in the inflammation-generated mucus layers covering the URT and increased pneumococci are observed in nasal secretions with IAV co-infection. Levels of shedding have correlations with IAV induced URT inflammation. Pro-inflammatory effects are exhibited by the single pneumococcal toxin, pneumolysin (Ply); use of anti-Ply antibodies result in decreased inflammation. Studies have found transmissible levels of bacterium only in young mice, exhibiting that shedding increases with incidences of contact and proximity. Shedding is shown to decrease in the presence of agglutinating antibodies such as IgG and IgA1 unless cleavage occurs via an IgA1-specific pneumococcal protease. Transmission via the secretions of carriers can result from direct interpersonal contact or contact with a contaminated surface. Bacteria on contaminated surfaces can be easily cultured. In conditions with sufficient nutrients, pneumococci can survive for 24 hours and avoid desiccation for multiple days. Reduced transmission has been observed amongst children with Pneumococcal conjugate vaccine (PCV) immunization as acquisition of a new strain of S. pneumoniae is inhibited by pre-existing colonization. Immunoglobulin G (IgG) immunization with high antibody concentration can also inhibit acquisition. These antibodies require the agglutinating function of the Fc fragment. For successful acquisition in a new host, pneumococcus must successfully adhere to the mucous membrane of the new host’s nasopharynx. Pneumococcus is able to evade detection by the mucous membrane when there is a higher proportion of negatively charged capsules. This clearance is mediated by Immunoglobulin A1 (IgA1) which is abundant on the URT mucosal surfaces. Colonization Transparent and opaque colony morphology has been observed for pneumococci. Airway colonization is observed in transparent phenotypes of serotypes, while survival in bloodstreams is observed for opaque phenotypes. Colonizable strains exhibit resistance against neutrophilic immune response. Successful colonization requires S. pnuemoniae to evade detection by the nasal mucus and attach to epithelial surface receptors. Asymptomatic colonization occurs when S. pneumoniae bind to N-acetyl-glucosamine on epithelium without inflammation. However, co-infection with a pre-existing inflammatory URT infection results in an over-expression of the epithelial receptors utilized by S. pneumoniae, thus increasing the likelihood of colonization. Neuraminidase also increases instances of epithelial binding through its cleavage of N-acetylneuraminic acid, glycolipids, glycoproteins, and oligosaccharides. Invasion Initial colonization of the nasopharynx is typically asymptomatic, but invasion occurs when the bacteria spreads to other parts of the body including the lungs, blood, and brain. Interactions between Phosphorylcholine (ChoP) components on colonized epithelial cells allow for docking of choline binding proteins (CBPs), most notably CbpA. Colonization of the respiratory tract, and thus pneumonia cannot occur without CpbA. The pneumococcus moves across the mucosal barrier by integrating itself with the polymeric immunoglobulin receptor (pIgR), which is used by mucosal epithelial cells to transport IgA and IgM to the apical surface. Following its cleavage at the apical surface, pIgR, and subsequently the pneumococcus, move back to the basolateral surface allowing invasion of the upper respiratory tract. The pneumococcus then moves to invade the lower respiratory tract, evading the mucociliary escalator with the assistance of neuraminidase. == References ==
Cerebroretinal microangiopathy with calcifications and cysts	Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is a rare genetic disorder, which affects multiple organs. Its hallmarks are widespread progressive calcifications, cysts and abnormalities of the white matter of the brain, usually occurring together with abnormalities of the blood vessels of the retina. Additional features include poor prenatal growth, preterm birth, anemia, osteopenia and bone fractures, and gastrointestinal bleeding. It is caused by compound heterozygous mutations in the conserved telomere maintenance component 1 (CTC1) gene, but its exact pathophysiology is still not well understood. Cerebroretinal microangiopathy with calcifications and cysts is alternatively known as the Coats plus syndrome, a reference to its most typical ocular phenotype. Signs and Symptoms Presentation Before birth A child who has inherited this disorder will grow slower than normal in the uterus before birth and typically will be born before term. The pregnancy can be complicated by gestational hypertension and pre-eclampsia. After birth The majority of affected children present with symptoms and signs relating to the eyes such as leukokoria, redness, irritation and impaired vision, which result from retinal detachment and glaucoma. A minority present with seizures or spasticity. The time of onset of symptoms varies from infancy to adolescence. Because a child born before term will need to undergo screening for retinopathy of prematurity, some will have abnormalities in their retinal blood vessels detected when they have no symptoms yet. Brain Neurologic symptoms and signs vary depending on the site of the brain abnormalities. Common symptoms are partial epilepsy, asymmetric spasticity, ataxia and cognitive impairment. The latter affects visuospatial and visuoconstructive skills first. The intracranial pressure can be elevated if cysts develop in the brain. Migraine-like headaches can occur. Eyes Smaller blood vessels of the retina are abnormally developed and appear tortuous and dilated to a variable extent, typically in one sector and mainly in the peripheral and temporal portions of the retina. This is known as telangiectasia. The vessel walls are weak and leak blood plasma and lipid within and underneath the retina. This leakage can lead to exudative retinal detachment, also known as exudative retinopathy in this context. The detachment typically has a yellowish tint because the fluid under the retina contains lipid. These findings mimic Coats disease. Characteristically, the abnormal vessels are localized and the retinal blood vessels peripheral to the abnormal ones seemingly have failed to develop and are thus not seen. In some eyes, retinal vessels form small nodules on the surface of the retina, known as angiomas. These can bleed and be attached to the vitreous humour. The attachment can cause traction retinal detachment. Gastrointestinal tract Recurrent intestinal bleeding is fairly common. It originates from telangiectatic small blood vessels in the intestinal mucosa. Additional findings in some individuals are portal hypertension and liver failure. Blood Many affected children develop anemia, which may be macrocytic in type. Some also develop thrombocytopenia. Bone marrow examinations may show megaloblasts and increased erythropoiesis or bone marrow suppression. Bones The long bones show osteopenia and pathologic fractures can occur. Skin, nails and hair Some children have sparse and greying hair, café au lait spots and nail dystrophy. General Most patients continue to grow poorly after birth. Genetics Typical childhood-onset cerebroretinal microangiopathy with calcifications and cysts is caused by compound heterozygous mutations in the conserved telomere maintenance component 1 (CTC1) gene located in chromosome 17p.31. A late-onset phenotype without abnormal eye findings from a CTC1 mutation has been reported.CTC1 is a component of the CST complex, which is additionally composed of oligonucleotide/oligosaccharide-binding fold containing 1 (coded by OBFC1, also known as STN1) and telomerase capping complex subunit homolog 1 (coded by TEN1). CST complex is evolutionarily conserved. It binds to single-stranded DNA and associates with a fraction of telomeres, potentially protecting them. Pathophysiology Angiomas and numerous abnormal, small, dilated telangiectatic vessels with thickened, sclerotic and calcified walls have been found in those brain areas which also show calcifications.By analogy to Coats disease, the exudative retinopathy is thought to result from breakdown of the blood-retinal barrier at the level of the vascular endothelial cell, resulting in leakage of blood plasma and lipid. Macrophages then migrate into the retina and subretinal space and digest the lipid. The accumulation of the proteinaceous exudate and macrophages thickens the retina, leading to exudative retinal detachment. Diagnosis Clinical The retinal changes are easily identified by ophthalmoscopy, which is performed under general anesthesia if the child is very young. The abnormal vessels are even better seen with fluorescein angiography. In advanced disease, glaucoma is diagnosed by measuring intraocular pressure and cataract by using slit lamp biomicroscopy. Imaging findings The most consistent finding are widespread calcifications, which involve the white matter of the cerebrum mostly adjacent to the junction with the grey matter, the thalami, the basal ganglia and the brainstem. The white matter of the cerebellum and the dentate nuclei are less often involved. However, the brain may appear normal in the neonatal period. The calcifications are visible both with computed tomography and with magnetic resonance imaging. Magnetic resonance imaging shows additionally diffuse or patchy white matter changes, especially in the periventricular region, the thalami and the internal capsule. Cerebellar and brainstem lesions are less common. Imaging also uncovers parenchymal cysts situated mainly in the thalamic region and more rarely in the brainstem, the parietal lobe and the frontal lobe. The long bones may be osteopenic and various skeletal changes are found in several patients, such as metaphyseal sclerosis and mild flaring, which is most pronounced in the femur and tibia. Laboratory findings The cerebrospinal fluid and blood tests are typically normal, except for anemia and thrombocytopenia in some children. Screening Because of the rarity of the syndrome, it is not routinely screened before birth. Prenatal diagnosis is possible in families in which a prior child has been diagnosed, because the responsible gene CTC1is known. Management Seizures are managed with anticonvulsive medications. Laser coagulation or cryoablation (freezing) of the retina can be used to destroy the abnormal blood vessels. Retinal detachment is repaired with a scleral buckle or with vitrectomy. Removal or enucleation of the eye is a last resort option if the eye already has become blind and painful.Repeated blood transfusions may be needed to control anemia, and thrombocytopenia can be managed with splenectomy. Prognosis The neurological symptoms are progressive and can lead to severe spasticity, bulbar symptoms and dysarthria within one to two decades. The life span is shorter than normal. Death occurs between 2 and 30 years of age, depending on the severity of the syndrome. The immediate cause of death is pneumonia, fulminant intestinal bleeding or multiple organ dysfunction.If not treated, the retinal detachment can lead to ischemia and growth of new blood vessels over the iris and anterior chamber angle. This in turn can cause secondary glaucoma, cataract and, ultimately, blindness of the eye. Epidemiology This syndrome is usually sporadic although families with two or more affected siblings of both sexes are known. History A child who was eventually diagnosed with cerebroretinal microangiopathy with calcifications and cysts was first described in the literature in 1987. The disorder was suspected of being allelic with either the Revesz syndrome or leukoencephalopathy with calcifications and cysts. However, Revesz syndrome, a severe variant of dyskeratosis congenita, was later shown to result from heterozygous dominant mutations in the TINF2 gene, which encodes TRF1-interacting nuclear factor 2, a major component of the telomere protecting shelterin complex, and individuals with the leukoencephalopathy with calcifications and cysts phenotype have not had mutations in the CTC1 gene.Before the causative mutation was identified, mutations were sought from the Wnt signalling pathway because its components were known to be responsible for Norrie disease and familial exudative vitreoretinopathy, which share features of the eye phenotype but not the brain or systemic abnormalities.Coats disease is named after George Coats. References == External links ==
Central cord syndrome	Central cord syndrome (CCS) is the most common form of cervical spinal cord injury. It is characterized by loss of motion and sensation in arms and hands. It usually results from trauma which causes damage to the neck, leading to major injury to the central corticospinal tract of the spinal cord. The syndrome is more common in people over the age of 50 because osteoarthritis in the neck region causes weakening of the vertebrae. CCS most frequently occurs among older persons with cervical spondylosis, however, it also may occur in younger individuals.CCS is the most common incomplete spinal cord injury syndrome. It accounts for approximately 9% of traumatic SCIs. After an incomplete injury, the brain still has the capacity to send and receive some signals below the site of injury. Sending and receiving of signals to and from parts of the body is reduced, not entirely blocked. CCS gives a greater motor loss in the upper limbs than in the lower limbs, with variable sensory loss. It was first described by Schneider in 1954. It is generally associated with favorable prognosis for some degree of neurological and functional recovery. However, factors such as age, preexisting conditions, and extent of injury will affect the recovery process. Presentation CCS is characterized by disproportionately greater motor impairment in upper compared to lower extremities, and variable degree of sensory loss below the level of injury in combination with bladder dysfunction and urinary retention. This syndrome differs from that of a complete lesion, which is characterized by total loss of all sensation and movement below the level of the injury. Causes In older patients, CCS most often occurs after acute hyperextension injury in an individual with long-standing cervical spondylosis. A slow, chronic cause in this age group is when the cord gets caught and squeezed between a posterior intervertebral disc herniation against the anterior cord and/or with posterior pressure on the cord from hypertrophy of the ligamentum flavum (Lhermittes sign may be the experience that causes the patient to seek medical diagnosis). However, CCS is not exclusive to older patients as younger individuals can also sustain an injury leading to CCS. Typically, younger patients are more likely to get CCS as a result of a high-force trauma or a bony instability in the cervical spine. Historically, spinal cord damage was believed to originate from concussion or contusion of the cord with stasis of axoplasmic flow, causing edematous injury rather than destructive hematomyelia. More recently, autopsy studies have demonstrated that CCS may be caused by bleeding into the central part of the cord, portending less favorable prognosis. Studies also have shown from postmortem evaluation that CCS probably is associated with selective axonal disruption in the lateral columns at the level of the injury to the spinal cord with relative preservation of the grey matter. Diagnosis Management Nonsurgical In many cases, individuals with CCS can experience a reduction in their neurological symptoms with conservative management. The first steps of these intervention strategies include admission to an intensive care unit (ICU) after initial injury. After entering the ICU, early immobilization of the cervical spine with a neck collar would be placed on the patient to limit the potential of further injury. Cervical spine restriction is maintained for approximately six weeks until the individual experiences a reduction in pain and neurological symptoms. Inpatient rehabilitation is initiated in the hospital setting, followed by outpatient physical therapy and occupational therapy to assist with recovery.An individual with a spinal cord injury may have many goals for outpatient occupational and physiotherapy. Their level of independence, self-care, and mobility are dependent on their degree of neurological impairment. Rehabilitation organization and outcomes are also based on these impairments. The physiatrist, along with the rehabilitation team, work with the patient to develop specific, measurable, action-oriented, realistic, and time-centered goals.With respect to physical therapy interventions, it has been determined that repetitive task-specific sensory input can improve motor output in patients with central cord syndrome. These activities enable the spinal cord to incorporate both supraspinal and afferent sensory information to help recover motor output. This occurrence is known as "activity dependent plasticity". Activity dependent plasticity is stimulated through such activities as: locomotor training, muscle strengthening, voluntary cycling, and functional electrical stimulation (FES) cycling Surgical Surgical intervention is usually given to those individuals who have increased instability of their cervical spine, which cannot be resolved by conservative management alone. Further indications for surgery include a neurological decline in spinal cord function in stable patients as well as those who require cervical spinal decompression. See also Spinal cord injury Anterior cord syndrome Posterior cord syndrome Brown-Séquard syndrome References External links NINDS Central Cord Syndrome Information Page
Gangrene	Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gangrene is caused by an infectious agent, it may present with a fever or sepsis.Risk factors include diabetes, peripheral arterial disease, smoking, major trauma, alcoholism, HIV/AIDS, frostbite, influenza, dengue fever, malaria, chickenpox, plague, hypernatremia, radiation injuries, meningococcal disease, Group B streptococcal infection and Raynauds syndrome. It can be classified as dry gangrene, wet gangrene, gas gangrene, internal gangrene, and necrotizing fasciitis. The diagnosis of gangrene is based on symptoms and supported by tests such as medical imaging.Treatment may involve surgery to remove the dead tissue, antibiotics to treat any infection, and efforts to address the underlying cause. Surgical efforts may include debridement, amputation, or the use of maggot therapy. Efforts to treat the underlying cause may include bypass surgery or angioplasty. In certain cases, hyperbaric oxygen therapy may be useful. How commonly the condition occurs is unknown. Signs and symptoms Symptoms may include a change in skin color to red or black, numbness, pain, skin breakdown, and coolness. The feet and hands are most commonly involved. Causes Gangrene is caused by a critically insufficient blood supply (e.g., peripheral vascular disease) or infection. It is associated with diabetes and long-term tobacco smoking. Dry gangrene Dry gangrene is a form of coagulative necrosis that develops in ischemic tissue, where the blood supply is inadequate to keep tissue viable. It is not a disease itself, but a symptom of other diseases. The term dry is used only when referring to a limb or to the gut (in other locations, this same type of necrosis is called an infarction, such as myocardial infarction). Dry gangrene is often due to peripheral artery disease, but can be due to acute limb ischemia. As a result, people with arteriosclerosis, high cholesterol, diabetes and smokers commonly have dry gangrene. The limited oxygen in the ischemic limb limits putrefaction and bacteria fail to survive. The affected part is dry, shrunken, and dark reddish-black. The line of separation usually brings about complete separation, with eventual falling off of the gangrenous tissue if it is not removed surgically, a process called autoamputation.Dry gangrene is the result of chronic ischemia without infection. If ischemia is detected early, when ischemic wounds rather than gangrene are present, the process can be treated by revascularization (via vascular bypass or angioplasty). However, once gangrene has developed, the affected tissues are not salvageable. Because dry gangrene is not accompanied by infection, it is not as emergent as gas gangrene or wet gangrene, both of which have a risk of sepsis. Over time, dry gangrene may develop into wet gangrene if an infection develops in the dead tissues.Diabetes mellitus is a risk factor for peripheral vascular disease, thus for dry gangrene, but also a risk factor for wet gangrene, particularly in patients with poorly controlled blood sugar levels, as elevated serum glucose creates a favorable environment for bacterial infection. Wet gangrene Wet, or infected, gangrene is characterized by thriving bacteria and has a poor prognosis (compared to dry gangrene) due to sepsis resulting from the free communication between infected fluid and circulatory fluid. In wet gangrene, the tissue is infected by saprogenic microorganisms (Clostridium perfringens or Bacillus fusiformis, for example), which cause tissue to swell and emit a foul odor. Wet gangrene usually develops rapidly due to blockage of venous (mainly) or arterial blood flow. The affected part is saturated with stagnant blood, which promotes the rapid growth of bacteria. The toxic products formed by bacteria are absorbed, causing systemic manifestation of sepsis and finally death. The affected part is edematous, soft, putrid, rotten, and dark.Because of the high mortality associated with infected gangrene (about 80% without treatment and 20% with treatment), an emergency salvage amputation, such as a guillotine amputation, is often needed to limit systemic effects of the infection. Such an amputation can be converted to a formal amputation, such as a below- or above-knee amputation. Gas gangrene Gas gangrene is a bacterial infection that produces gas within tissues. It can be caused by Clostridium, most commonly alpha toxin-producing C. perfringens, or various nonclostridial species. Infection spreads rapidly as the gases produced by the bacteria expand and infiltrate healthy tissue in the vicinity. Because of its ability to quickly spread to surrounding tissues, gas gangrene should be treated as a medical emergency. Gas gangrene is caused by bacterial exotoxin-producing clostridial species, which are mostly found in soil, and other anaerobes such as Bacteroides and anaerobic streptococci. These environmental bacteria may enter the muscle through a wound and subsequently proliferate in necrotic tissue and secrete powerful toxins that destroy nearby tissue, generating gas at the same time. A gas composition of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen was reported in one clinical case.Gas gangrene can cause necrosis, gas production, and sepsis. Progression to toxemia and shock is often very rapid. Other types Necrotizing fasciitis, also known as hemolytic streptococcal gangrene, is a very rare infection that spreads deep into the body along tissue planes. It is characterized by infection with S.pyogenes, a gram-positive cocci bacteria. Noma is a gangrene of the face common in Africa and Asia, with 99% of cases occurring there, whereas the disease is practically non-existent in other continents. Fournier gangrene is a type of necrotizing fasciitis that usually affects the genitals and groin. Venous limb gangrene may be caused by heparin-induced thrombocytopenia and thrombosis. Severe mesenteric ischemia may result in gangrene of the small intestine. Severe ischemic colitis may result in gangrene of the large intestine. Treatment Treatment varies based on the severity and type of gangrene. Lifestyle Exercises such as walking and massage therapy may be tried. Medication Medications may include pain management, medications that promote circulation in the circulatory system and antibiotics. Since gangrene is associated with periodic pain caused by too little blood flow, pain management is important so patients can continue doing exercises that promote circulation. Pain management medications can include opioids and opioid-like analgesics. Since gangrene is a result of ischemia, circulatory system management is important. These medications can include antiplatelet drug, anticoagulant, and fibrinolytics. As infection is often associated with gangrene, antibiotics are often a critical component of its treatment. The life-threatening nature of gangrene requires treatment with intravenous antibiotics in an inpatient setting. Antibiotics alone are not effective because they may not penetrate infected tissues sufficiently. Surgery Surgical removal of all dead tissue, however, is the mainstay of treatment for gangrene. Often, gangrene is associated with underlying infection, thus the gangrenous tissue must be debrided to hinder the spread of the associated infection. The extent of surgical debridement needed depends on the extent of the gangrene and may be limited to the removal of a finger, toe, or ear, but in severe cases may involve a limb amputation.Dead tissue alone does not require debridement, and in some cases, such as dry gangrene, the affected part falls off (autoamputates), making surgical removal unnecessary. Waiting for autoamputation, however, may cause health complications as well as decreased quality of life.After the gangrene is treated with debridement and antibiotics, the underlying cause can be treated. In the case of gangrene due to critical limb ischemia, revascularization can be performed to treat the underlying peripheral underlateral artery disease.Ischemic disease of the legs is the most common reason for amputations. In about a quarter of these cases, the other side requires amputation in the next three years.Angioplasty should be considered if severe blockage in lower leg vessels (tibial and peroneal artery) leads to gangrene. Other Hyperbaric oxygen therapy treatment is used to treat gas gangrene. It increases pressure and oxygen content to allow blood to carry more oxygen to inhibit anaerobic organism growth and reproduction.Regenerative medical treatments and stem-cell therapies have successfully altered gangrene and ulcer prognosis. History As early as 1028, flies and maggots were commonly used to treat chronic wounds or ulcers to prevent or arrest necrotic spread, as some species of maggots consume only dead flesh, leaving nearby living tissue unaffected. This practice largely died out after the introduction of antibiotics, acetonitrile, and enzyme to the range of treatments for wounds. In recent times, however, maggot therapy has regained some credibility and is sometimes employed with great efficacy in cases of chronic tissue necrosis.The French Baroque composer Jean-Baptiste Lully contracted gangrene in January 1687 when, while conducting a performance of his Te Deum, he stabbed his own toe with his pointed staff (which was used as a baton). The disease spread to his leg, but the composer refused to have his toe amputated, which eventually led to his death in March of that year.French King Louis XIV died of gangrene in his leg on 1 September 1715, four days prior to his 77th birthday.Sebald Justinus Brugmans, Professor at Leyden University, from 1795 on Director of the Medical Bureau of the Batavian Republic, and inspector-general of the French Imperial Military Health-Service in 1811, became a leading expert in the fight against hospital-gangrene and its prevention. He wrote a treatise on gangrene in 1814 in which he meticulously analyzed and explained the causes of this dreadful disease, which he was convinced was contagious. He completed his entry with a thorough evaluation of all possible and well experienced sanitary regulations. His work was very well received and was instrumental in convincing most later authors that gangrene was a contagious disease.John M. Trombold wrote: "Middleton Goldsmith, a surgeon in the Union Army during the American Civil War, meticulously studied hospital gangrene and developed a revolutionary treatment regimen. The cumulative Civil War hospital gangrene mortality was 45%. Goldsmiths method, which he applied to over 330 cases, yielded a mortality under 3%." Goldsmith advocated the use of debridement and topical and injected bromide solutions on infected wounds to reduce the incidence and virulence of "poisoned miasma". Copies of his book were issued to Union surgeons to encourage the use of his methods.Father Camille Bulcke also died of gangrene on 17 August 1982. Etymology The etymology of gangrene derives from the Latin word gangraena and from the Greek gangraina (γάγγραινα), which means "putrefaction of tissues". It has no etymological connection with the word green, despite the affected areas turning black, green, or yellowish brown. References External links Media related to Gangrene at Wikimedia Commons
Retroverted uterus	A retroverted uterus (tilted uterus, tipped uterus) is a uterus that is oriented posteriorly, towards the back of the body. This is in contrast to the typical uterus, which is oriented forward (slightly "anteverted") toward the bladder, with the anterior part slightly concave. Depending on the source, one in three to five uteruses are retroverted, or oriented backwards towards the spine. Related terms The following table distinguishes among some of the terms used for the position of the uterus: A retroverted uterus should be distinguished from the following: Additional terms include: retrocessed uterus: both the superior and inferior ends of the uterus are pushed posteriorly severely anteflexed uterus: a pronounced forward bend in an anteflexed uterus vertical uterus: the fundus (top of the uterus) is straight up Causes In most cases, a retroverted uterus is a normal variation present from birth. There are other factors, however, that can cause the uterus to become retroverted. Pelvic surgery, pelvic adhesions, endometriosis, fibroids, pelvic inflammatory disease, or the labor of childbirth can change the position of the uterus to retroverted. Diagnosis A retroverted uterus is usually noted during a routine pelvic examination or with an internal ultrasound.It usually does not pose any medical problems, though it can be associated with dyspareunia (pain during sexual intercourse) and dysmenorrhea (pain during menstruation). Fertility and pregnancy Rarely, a retroverted uterus is due to a disease such as endometriosis, an infection or prior surgery. Those conditions, but not the position of the uterus itself, can reduce fertility in some cases. A tipped uterus will usually move to the middle of the pelvis during the 10th to 12th week of pregnancy. Rarely (1 in 3,000 to 8,000 pregnancies), a retroverted uterus will cause painful and difficult urination and can cause severe urinary retention. Treatment for this condition (called "incarcerated uterus") includes manual anteversion of the uterus, and usually requires intermittent or continuous catheter drainage of the bladder until the problem is rectified or spontaneously resolves by the natural enlargement of the uterus, which brings it out of the tipped position. In addition to manual anteversion and bladder drainage, treatment of urinary retention due to a retroverted uterus can require the use of a pessary, or even surgery. If a uterus does not reposition, it may be labeled persistent. Treatment Treatment options are rarely needed, and include exercises, a pessary, manual repositioning, and surgery. References External links MedlinePlus Encyclopedia: 001506 Overview at mayoclinic.com Diagram at womens-health.co.uk
Esophoria	Esophoria is an eye condition involving inward deviation of the eye, usually due to extra-ocular muscle imbalance. It is a type of heterophoria. Cause Causes include: Refractive errors Divergence insufficiency Convergence excess; this can be due to nerve, muscle, congenital or mechanical anomalies.Unlike esotropia, fusion is possible and therefore diplopia is uncommon. References == External links ==
Muscle contracture	Muscle contractures can occur for many reasons, such as paralysis, muscular atrophy, and forms of muscular dystrophy. Fundamentally, the muscle and its tendons shorten, resulting in reduced flexibility. For example, in the case of partial paralysis (i.e. poliomyelitis) the loss of strength and muscle control tend to be greater in some muscles than in others, leading to an imbalance between the various muscle groups around specific joints. Case in point: when the muscles which dorsiflex (flex the foot upward) are less functional than the muscles which plantarflex (flex the foot downward) a contracture occurs, giving the foot a progressively downward angle and loss of flexibility. Various interventions can slow, stop, or even reverse muscle contractures, ranging from physical therapy to surgery. A common cause for having the ankle lose its flexibility in this manner is from having sheets tucked in at the foot of the bed when sleeping. The weight of the sheets keep the feet plantarflexed all night. Correcting this by not tucking the sheets in at the foot of the bed, or by sleeping with the feet hanging off the bed when in the prone position, is part of correcting this imbalance. It occurs also due to muscle tightening for example if after fracture when immobilization is done by putting plaster of paris the muscle length shortens because the muscle is not used for a large span of time. Cause Immobilization Joints are usually immobilized in a shortened position resulting in changes within the joint connective tissue, and the length of the muscle and associated tendon. Prolonged immobilization facilitates tissue proliferation which impinges on the joint space. Maintaining a shortened position for a prolonged period of time leads to: fibrous adhesion formation, loss of sarcomeres, and a loss of tissue extensibility. Spasticity If spasticity is left untreated, contractures can occur. A loss of muscle tone inhibition causes a muscle to become hyperactive resulting in constant contraction, which reduces an individual’s control of the affected area. The joint will remain in a flexed state producing similar effects as listed in immobilization. Muscle weakness A muscle imbalance between an agonist and antagonist muscle can occur due to a neurological disorder, spinal cord injury, and our lifestyle/postural habits. A decrease in muscle tone leads to continuous disuse and eventually muscular atrophy. The constant contraction of the agonist muscle with minimal resistance can result in a contracture. Treatment Passive stretching Typically performed by physical therapists, passive stretching is a more beneficial preventative measure and tool to maintain available range of motion (ROM) rather than used as a treatment. It is very important to continually move the limb throughout its full range at a specific velocity but a passive stretch can’t be maintained for the period of time required for optimal benefit. A 2017 Cochrane review found that stretching does not provide any short-term pain relief. Splinting A contracture corrective device (CCD) is a dynamic splint that provides a continuous stretch with a continuous force and operates based on the principles of creep. It is the most advantageous splint but more research is required. Splints are used in long term treatments and must be removed in order to stretch the antagonist muscle to maintain range of motion (passive stretching). Electrical stimulation Electrical stimulation improves passive range of motion but only temporarily. Once the treatment is withdrawn, all benefits are reduced. It can play a critical role in muscle atrophy prevention. Surgery Surgery is a solution to muscle shortening but other complications may arise. Following muscle lengthening surgery, force production and ROM is usually reduced due to the shift in sarcomere locations between a muscles maximal and minimal length. Shortening of the surgically lengthened muscle can re-occur. == References ==
Sickle cell nephropathy	Sickle cell nephropathy is a type of nephropathy associated with sickle cell disease which causes kidney complications as a result of sickling of red blood cells in the small blood vessels. The hypertonic and relatively hypoxic environment of the renal medulla, coupled with the slow blood flow in the vasa recta, favors sickling of red blood cells, with resultant local infarction (papillary necrosis). Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules. Also the sickle cell disease in young patients is characterized by renal hyperperfusion, glomerular hypertrophy, and glomerular hyperfiltration. Many of these individuals eventually develop a glomerulopathy leading to glomerular proteinuria (present in as many as 30%) and, in some, the nephrotic syndrome. Co-inheritance of microdeletions in the -globin gene (thalassemia) appear to protect against the development of nephropathy and are associated with lower mean arterial pressure and less protein in the urine. Mild increases in the blood levels of nitrogen and uric acid can also develop. Advanced kidney failure and high blood urea levels occur in 10% of cases. Pathologic examination reveals the typical lesion of "hyperfiltration nephropathy" namely, focal segmental glomerular sclerosis. This finding has led to the suggestion that anemia-induced hyperfiltration in childhood is the principal cause of the adult glomerulopathy. Nephron loss secondary to ischemic injury also contributes to the development of azotemia in these patients Pathophysiology The development of sickle cell nephropathy (SCN) typically occurs in childhood as seen in the appearance of hyperfiltration and proteinuria. Both are primarily caused by the polymerization of sickle cells in the kidney microvasculature due to the low O2 tension, high osmolarity, and low acidity. This polymerization fills and occludes blood vessels such as the vasa recta in the kidneys leading to microinfarctions, leakage into surrounding tissues and potentially papillary necrosis and renal infarcts. Renal papillae are especially susceptible to damage eventually causing papillary necrosis since these vessels are only supplied with blood by the vasa recta. The sickling of the cells also contribute to two other mechanisms which are chronic hypoxia and chronic hemolysis. Hypoxia is caused from both the insufficient ability for the red blood cells to transport oxygen alongside blood vessel occlusions promoting the activation of Hypoxia Inducible Factor-1𝛂. The hypoxia also causes the over expression of endothelin-1 and functional nitric oxide deficiency and due to the chronic hemolysis, reactive oxygen species are produced leading to vasoconstriction and further medullary hypoxia. This nitric oxide deficiency alongside endothelin-1 overproduction leads to the inability to properly respond to stress and hemodynamic changes which increases the likelihood of experiencing acute kidney injury.The hyperfiltration has multiple contributing factors such as the increased cardiac output caused by the normal physiological response to anemia leading to greater renal blood flow and an increase in glomerular filtration rate (GFR). This is not the only factor because having multiple blood transfusions does not reverse this effect. The other contributor is glomerular hypoxia in that it releases local prostaglandins: a potent vasodilator, and nitric oxide synthase which increases renal blood flow and therefore GFR. Hemolysis also plays a role in hyperfiltration through the release of heme oxygenase-1 (HO-1) in response to kidney injury and this enzyme converts heme to biliverdin with the by-product being carbon monoxide. Biliverdin and carbon monoxide both act as antioxidants and carbon monoxide also acts as a vasorelaxant, and this causes an increase in GFR. A consistent increase in GFR can lead to proteinuria, glomerulosclerosis, and can eventually worsen progressive chronic kidney disease (CKD).Albuminuria is caused by microvascular damage in the kidneys, hemolysis and endothelial dysfunction. From the increased GFR and the ischemic injury caused by the polymerization of sickle cells, scar tissue develops in the glomeruli which reduces the ability of the glomerulus to properly filter proteins leading to proteinuria. The chronic hemolysis causes the release of iron and free hemoglobin in the kidneys. The iron builds up and leaves deposits in the kidneys, and this causes the overproduction of mesangial cells eventually leading to interstitial and glomerular fibrosis. The free plasma hemoglobin contains cytotoxic heme groups which damage renal tubular epithelial cells and the hemoglobin ends up in the filtrate causing hemoglobinuria. Though the hemoglobin can be reabsorbed in the proximal tubules through binding cubilin and megalin, in doing so it competes with albumin, so the build up of hemoglobin in the filtrate reduces albumin resorption which can worsen albuminuria. When it comes to endothelial dysfunction, there is a correlation between soluble FMS-like tyrosine kinase-1 (sFLT-1) and worsening albuminuria. This is because sFLT-1 prevents the binding of vascular endothelial growth factor (VEGF) to a splice variant of its receptor (VEGFR-1) which induces endothelial dysfunction. This as well as other factors that reduce endothelial function such as stress, hypoxia, inflammation, leads to a production of endothelin-1 and this reduces the bioavailability of nitric oxide and releases reactive oxygen species. This induces widening of inter-podocyte radii and lowers the number of podocytes which increases the amount of albumin that is filtered in the glomerulus and worsens albuminuria. The use of endothelin receptor antagonism could have the potential effect to be renally protective. Presentation Signs and Symptoms Microalbuminuria is an early sign of SCN that has a 30-60% of developing in those with sickle cell disease (SCD).Hematuria can appear in a range of severities from painless and minute to excessive and painful. The presence of visible blood in the urine without pain occurs with a higher frequency in sickle trait than in sickle cell disease and likely results from infarctive episodes in the renal medulla. Despite this condition typically being self-limiting, investigation is recommended because of alternate causes such as renal stones, or medullary carcinoma, especially if bleeding is excessive and if also experiencing flank pain.Hyposthenuria is the inability for the kidneys to concentrate urine. Functional tubule abnormalities such as nephrogenic diabetes insipidus result from marked reduction in vasa recta blood flow, combined with ischemic tubule injury and sickled erythrocytes in the vasa recta of the inner medulla impairing free water absorption, all causing the production of dilute urine. The concentrating defect also occurs in individuals with sickle trait. This can lead to symptoms such as polyuria and dehydration due to the low water reabsorption.Increase risk of urinary tract infection from encapsulated bacteria due to hyposplenism from spontaneous infarctions in the spleen (autosplenectomy). Additionally, papillary necrosis can increase the risk of a UTI and all infections should be dealt with promptly to prevent sickle cell crisis.Initially, hyperfiltration occurs in pediatrics and then after 30 years old, the GFR slowly declines which is proportional to the development of proteinuria. Worsening proteinuria is gradual, but a sudden onset could have a secondary cause such as nephritic syndrome from FSGS or minimal change disease, membranoproliferative glomerulonephritis, or hepatitis C.Tubular dysfunction, specifically incomplete distal renal tubular acidosis, is caused by the impaired potassium and hydrogen excretion as well as the impaired bicarbonate reabsorption. These contribute to the development of metabolic acidosis, high blood potassium and defects in uric acid excretion which, combined with increased purine synthesis in the bone marrow, results in high blood uric acid levels.Renal infarcts from total occlusion which can present with pain, vomiting, fever, and high blood pressure. Complications Kidney complications of sickle cell disease include cortical infarcts leading to loss of function, persistent bloody urine, and perinephric hematomas. Papillary infarcts, demonstrable radiographically in 50% of patients with sickle trait, lead to an increased risk of bacterial infection in the scarred kidney tissues and functional tubule abnormalities. Other complications include end stage renal disease (ESRD), medullary carcinoma, nephritic syndrome due to concurrent HPV B19 infection (this infection can cause benign self-limiting red cell aplasia). Risk Factors Genetic When looking at SCN, the main contributors leading to either a decrease or increase in CKD progression are the type of hemoglobin inheritance, myosin heavy chain 9, and apolipoprotein L1 genes. In those with the HbSS or HbSβ0 (no normal hemoglobin), they exhibit more severe forms of renal dysfunction at a high occurrence rate compared to those with HbSS or HbSβ+ (reduced number of normal hemoglobin). This ties in with the fetal hemoglobin levels (HbF) in that HbF levels are directly proportional to renal protection, and it has been found that in those with HbSS, a greater than 20% elevation in HbF led to no significant loss in renal function. Alpha-thalassemia has also been found to decrease HbS levels where the co-inheritance of alpha gene deletions reduce red blood cells and hemolysis. This inheritance has been shown to protect against hyposthenuria but the effect on other symptoms are unknown. Specifically in the African American population, the inheritance of an S trait and/or a C trait increases the risk of developing ESRD. For myosin heavy chain 9, and apolipoprotein L1, polymorphisms in these genes can contribute to worsening proteinuria but are not specific towards SCD. Specifically variants in G1 and G2 of apolipoprotein L1 in the African American have shown increased risk of albuminuria, and hyperfiltration. Environmental Risk factors for papillary necrosis include analgesics, concomitant cirrhosis, diabetes, pyelonephritis, systemic vasculitis, renal vein thrombosis, and urinary tract obstruction. Diagnosis Diagnosis is done through the exclusion of other potential causes. These include acute tubular necrosis from chronic ischemia, membranoproliferative glomerulonephropathy from hepatitis C, nephrolithiasis causing obstructive nephropathy, and papillary necrosis which could be caused by pyelonephritis, diabetes mellitus, or from NSAIDs. The use of renal biopsy is not necessary unless there is a sudden onset of large protein excretions or signs of rapidly declining renal function. Urinalysis, microalbumin to creatinine ratio, quantification of urine protein and ultrasound (to exclude obstructive nephropathy and detect papillary necrosis) are methods used to determine renal function. Early signs include abnormally large and distended glomeruli causing hyperfiltration from as young as two years old. Albuminuria has been used for initial diagnosis in children from as young as four years old but significant damage may have already occurred by the time albuminuria has been detected. Creatinine measurements may not always be accurate because while the glomerulus completely filters creatinine, secondary secretion in the proximal tubules is maximally utilized in those with SCD so GFR may appear to be higher than what it actually is. If exhibiting hematuria, a CT scan should be done to exclude medullary carcinoma and due to multiple blood transfusions, serologies of the autoantibody and complement levels of HIV, hepatitis B and C should also be done. When predicting CKD progression, old age can be a contributor since there is an increase in renal injury and a decrease in GFR in those over 30 years old. Also albuminuria, GFR, and lactic hydrogenase are used in determining CKD progression. The use of cystatin C may not be clear since while it increases when GFR declines, it has been shown that some people with SCN have similar levels to a healthy individual. Treatment Lifestyle Management of sickle nephropathy is not separate from that of overall patient management. Three-year graft and patient survival in kidney transplant recipients with sickle nephropathy is lower when compared to those with other causes of end-stage kidney disease.Certain medications should be avoided because of potential damage to the kidneys or can precipitate secondary complications. Nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen) should be avoided because of the decrease in renal blood flow causing a decrease in GFR as well as causing hemodynamic injury from glomerular hypertension.For hematuria, if mild then bed rest and hydration is sufficient to prevent the breakage of clots and to maintain a healthy blood volume, and possibly antibiotics or analgesics if necessary. If severe, then it is recommended to do an ultrasound to see if there is a complication such as renal infarcts or papillary necrosis. At this point the use of epsilon-aminocaproic acid may be recommended to break down clots but its use can increase risk of obstructive nephropathy.In children, the administration of multiple blood transfusions has been shown to decrease overall kidney damage, but it is unclear how long this effect lasts. Maintaining good hydration is important in those with SCN because of the risk of dehydration from increased urination and there is a major concern of sickle cell crisis that can be prevented with adequate fluid intake.To manage proteinuria a low protein diet should be avoided because of the decrease in energy and growth in those with SCN but limiting protein to the maximum daily requirement without exceeding it is beneficial in retaining kidney function. A low protein diet may be considered in end stage renal disease (ESRD) alongside phosphate binders, and vitamin D, with the potential of using dialysis or kidney transplants. Medications Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are beneficial in reducing proteinuria by 50% over a period of at least six months alongside a slight reduction in GFR but there is an unclear effect in overall CKD progression. If the medication is stopped then the symptoms return to similar levels to what it was before starting the medications. The lowering of nocturia has also been shown most likely from the decrease in GFR. This addition can be done regardless of baseline blood pressure. Hydroxyurea is an antimetabolite which increases the production of HbF and decreases HbS synthesis leads to a decrease in HbS polymerization. One of the major concerns in using this medication is myelotoxicity and the development of tolerance over time. No significant effect on GFR but has potential benefit on proteinuria, specifically in the pediatric population. The use of hydroxyurea has been shown to decrease lactic hydrogenase and reticulocytes which is typically used as a predictor for CKD progression since it increases during hemolysis. Since a decrease in hemolysis is correlated with positive SCN outcomes, hydroxyurea may be beneficial in decreasing the risk of SCN complications.Erythropoietin stimulating agents (ESAs): During normal kidney function in those with SCD, in response to anemia and hypoxia, erythropoietin synthesis is induced, causing increased erythropoietin compared to baseline. Once GFR falls below 60 mL/min, erythropoietin production also declines and it is recommended to add on an ESA to the current therapy; usually at higher doses. The target hemoglobin level should be lower than a normal patient with CKD because of the risk of vaso-occlusive events. Even in ESRD when those with SCD become transfusion dependent, ESAs can still be used to increase the interval between infusions. If using ESAs, it is important to maintain iron levels to maintain the ability to produce red blood cells especially in those with CKD since sub-clinical bleeding is common, and there is decreased iron absorption. IV iron therapy is recommended if not receiving the necessary iron from blood transfusions but the dosing is unclear.Diuretics are generally not used because of the decrease in blood volume which can cause a person with SCD to have a sickle cell crisis but it can help treat circulatory overload; a condition caused from blood transfusions where there is too much fluid in the circulatory system. Loop diuretics (furosemide) have also been used in treating severe hematuria by increasing urine flow. == References ==
Bronchiectasis	Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung. Symptoms typically include a chronic cough with mucus production. Other symptoms include shortness of breath, coughing up blood, and chest pain. Wheezing and nail clubbing may also occur. Those with the disease often get frequent lung infections.Bronchiectasis may result from a number of infectious and acquired causes, including measles, pneumonia, tuberculosis, immune system problems, as well as the genetic disorder cystic fibrosis. Cystic fibrosis eventually results in severe bronchiectasis in nearly all cases. The cause in 10–50% of those without cystic fibrosis is unknown. The mechanism of disease is breakdown of the airways due to an excessive inflammatory response. Involved airways (bronchi) become enlarged and thus less able to clear secretions. These secretions increase the amount of bacteria in the lungs, resulting in airway blockage and further breakdown of the airways. It is classified as an obstructive lung disease, along with chronic obstructive pulmonary disease and asthma. The diagnosis is suspected based on symptoms and confirmed using computed tomography. Cultures of the mucus produced may be useful to determine treatment in those who have acute worsening and at least once a year.Periods of worsening may occur due to infection. In these cases, antibiotics are recommended. Common antibiotics used include amoxicillin, erythromycin, or doxycycline. Antibiotics, such as erythromycin, may also be used to prevent worsening of disease. Airway clearance techniques, a type of physical therapy, are also recommended. Medications to dilate the airways and inhaled steroids may be used during sudden worsening, but there are no studies to determine effectiveness. There are also no studies on the use of inhaled steroids in children. Surgery, while commonly done, has not been well studied. Lung transplantation may be an option in those with very severe disease.The disease affects between 1 per 1000 and 1 per 250,000 adults. The disease is more common in women and increases as people age. It became less common since the 1950s with the introduction of antibiotics. It is more common among certain ethnic groups (such as indigenous people in the US). It was first described by René Laennec in 1819. The economic costs in the United States are estimated at $630 million per year. Signs and symptoms Symptoms of bronchiectasis commonly include a cough productive of frequent green or yellow sputum lasting months to years. Other common symptoms include difficulty breathing, wheezing (a whistling sound when you breathe), and chest pain. Exacerbations of symptoms may occur, these exacerbations occur more frequently in advanced or severe disease. Systemic symptoms, including fevers, chills, night sweats, fatigue and weight loss may be seen with bronchiectasis. Bronchiectasis may also present with coughing up blood in the absence of sputum, which has been called "dry bronchiectasis." Exacerbations in bronchiectasis present as a worsening of cough, increasing sputum volume or thickened consistency lasting at least 48 hours, worsening shortness of breath (breathlessness), worsening exercise intolerance, increased fatigue or malaise and the development of hemoptysis.People often report frequent bouts of "bronchitis" requiring therapy with repeated courses of antibiotics. People with bronchiectasis may have bad breath from active infection. On examination, crepitations and expiratory rhonchi may be heard with auscultation. Nail clubbing is a rare symptom.The complications of bronchiectasis include serious health conditions, such as respiratory failure and atelectasis: collapse or closure of a lung. Respiratory failure occurs when not enough oxygen passes from the lungs into the blood. Atelectasis occur when one or more segments of the lungs collapse or do not inflate properly. Other pulmonary complications include lung abscess and empyema. Cardiovascular complications include cor pulmonale, in which there is enlargement and failure of the right side of the heart as a result of disease of the lungs. Causes There are many causes that can induce or contribute to the development of bronchiectasis. The frequency of these different causes varies with geographic location. Cystic fibrosis is identified as a cause in up to half of cases. Bronchiectasis without CF is known as non-CF bronchiectasis. Historically, about half of all case of non-CF bronchiectasis were found to be idiopathic, or without a known cause. However, more recent studies with a more thorough diagnostic work-up have found an etiology in 60 to 90% of patients. Cystic fibrosis Cystic fibrosis is the most common life-threatening autosomal recessive disease in the United States and Europe. It is a genetic disorder that affects the lungs, but also the pancreas, liver, kidneys, and intestine. It is caused by mutations in the CFTR protein, a chloride channel expressed in epithelial cells. Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. In later stages, changes to the structure of the lung, such as bronchiectasis, occur. Around 5 to 10% of all patients with cystic fibrosis develop bronchiectasis. Airway obstruction An airway obstruction can be caused by either an intraluminal mass such as a tumor or a foreign body. The presence of an airway obstruction leads to a cycle of inflammation. It is important to identify the presence of an obstruction because surgical resection is often curative if obstruction is the cause. In adults, foreign body aspiration is often associated with an altered state of consciousness. The foreign body is often unchewed food, or part of a tooth or crown. Bronchiectasis that results from foreign body aspiration generally occurs in the right lung in the lower lobe or posterior segments of the upper lobe. Lung infections A range of bacterial, mycobacterial, and viral lung infections are associated with the development of bronchiectasis. Bacterial infections commonly associated with bronchiectasis include P. aeruginosa, H. influenzae, and S. pneumoniae. Gram-negative bacteria are more commonly implicated than gram-positive bacteria. A history of mycobacterial infections such as tuberculosis can lead to damage of the airways that predisposes to bacterial colonization. Severe viral infections in childhood can also lead to bronchiectasis through a similar mechanism. Nontuberculous mycobacteria infections such as Mycobacterium avium complex are found to be a cause in some patients. Recent studies have also shown Nocardia infections to been implicated in bronchiectasis. Impaired host defenses Impairments in host defenses that lead to bronchiectasis may be congenital, such as with primary ciliary dyskinesia, or acquired, such as with the prolonged use of immunosuppressive drugs. Additionally, these impairments may be localized to the lungs, or systemic throughout the body. In these states of immunodeficiency, there is a weakened or absent immune system response to severe infections that repeatedly affect the lung and eventually result in bronchial wall injury. HIV/AIDS is an example of an acquired immunodeficiency that can lead to the development of bronchiectasis. Aspergillosis Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by hypersensitivity to the fungus Aspergillus fumigatus. It is suspected in patients with a long history of asthma and symptoms of bronchiectasis such as a productive, mucopurulent cough. Imaging often shows peripheral and central airway bronchiectasis, which is unusual in patients with bronchiectasis caused by other disorders. Autoimmune diseases Several autoimmune diseases have been associated with bronchiectasis. Specifically, individuals with rheumatoid arthritis and Sjögren syndrome have increased rates of bronchiectasis. In these diseases, the symptoms of bronchiectasis usually presents later in the disease course. Other autoimmune diseases such as ulcerative colitis and Crohns disease also have an association with bronchiectasis. Additionally, graft-versus-host disease in patients who have undergone stem cell transplantation can lead to bronchiectasis as well. Lung injury Bronchiectasis could be caused by: inhalation of ammonia and other toxic gases, chronic pulmonary aspiration of stomach acid from esophageal reflux, or a hiatal hernia. Congenital Bronchiectasis may result from congenital disorders that affect cilia motility or ion transport. A common genetic cause is cystic fibrosis, which affects chloride ion transport. Another genetic cause is primary ciliary dyskinesia, a rare disorder that leads to immotility of cilia and can lead to situs inversus. When situs inversus is accompanied by chronic sinusitis and bronchiectasis, this is known as Kartageners syndrome. Other rare genetic causes include Youngs syndrome and Williams-Campbell syndrome. Tracheobronchomegaly, or Mournier-Kuhn syndrome is a rare condition characterized by significant tracheobronchial dilation and recurrent lower respiratory tract infections. Individuals with alpha 1-antitrypsin deficiency have been found to be particularly susceptible to bronchiectasis, due to the loss of inhibition to enzyme elastase which cleaves elastin. This decreases the ability of the alveoli to return to normal shape during expiration. Cigarette smoking A causal role for tobacco smoke in bronchiectasis has not been demonstrated. Nonetheless, tobacco smoking can worsen pulmonary function and accelerate the progression of disease that is already present. Pathophysiology The development of bronchiectasis requires two factors: an initial injury to the lung (such as from infection, auto-immune destruction of lung tissue, or other destruction of lung tissue (as seen in gastroesophageal reflux disease or aspiration syndromes)) which leads to impaired mucociliary clearance, obstruction, or a defect in host defense. This triggers a host immune response from neutrophils (elastases), reactive oxygen species, and inflammatory cytokines that results in progressive destruction of normal lung architecture. In particular, the elastic fibers of bronchi are affected. The result is permanent abnormal dilation and destruction of the major bronchi and bronchiole walls.Disordered neutrophil function is believed to play a role in the pathogenesis of bronchiectasis. Neutrophil extracellular traps(NETs), which are extracellular fibers secreted by neutrophils that are used to trap and destroy pathogens, are hyperactive in bronchiectasis. Increased NET activity is associated with more severe bronchiectasis. Neutrophil elastase, which is an extracellular protein secreted by neutrophils to destroy pathogens as well as host tissue, is also hyperactive in many cases of bronchiectasis. An increased neutrophil elastase activity is also associated with worse outcomes and more severe disease in bronchiectasis. The initial lung injury in bronchiectasis leads to an impaired mucociliary clearance of the lung airways, which leads to mucous stasis. This mucous stasis leads to bacterial colonization in bronchiectasis which leads to neutrophil activation. This neutrophil activation leads to further further tissue destruction and airway distortion by neutrophils in addition to direct tissue destruction by the pathogenic bacteria. The distorted, damaged lung airways thus have impaired mucociliary clearance; leading to mucous stasis and bacterial colonization leading to further neutrophil activation and thus fueling a self-perpetuating "vicious cycle" of inflammation in bronchiectasis. This "vicious cycle" theory is the generally accepted explanation for the pathogenesis of bronchiectasis.Endobronchial tuberculosis commonly leads to bronchiectasis, either from bronchial stenosis or secondary traction from fibrosis. Traction bronchiectasis characteristically affects peripheral bronchi (which lack cartilage support) in areas of end-stage fibrosis. Diagnosis The goals of a diagnostic evaluation for bronchiectasis are radiographic confirmation of the diagnosis, identification of potential treatable causes, and functional assessment of the patient. A comprehensive evaluation consists of radiographic imaging, laboratory testing, and lung function testing.Laboratory tests that are commonly part of the initial evaluation include a complete blood count, sputum cultures for bacteria, mycobacteria, and fungi, testing for cystic fibrosis, and immunoglobulin levels. Additional tests that are sometimes indicated include testing for specific genetic disorders.Lung function testing is used for the assessment and monitoring of functional impairment due to bronchiectasis. These tests may include spirometry and walking tests. Obstructive lung impairment is the most common finding but restrictive lung impairment can be seen in advanced disease. Flexible bronchoscopy may be performed when sputum studies are negative and a focal obstructing lesion is suspected.A chest x-ray is abnormal in most patients with bronchiectasis. Computed tomography is recommended to confirm the diagnosis and is also used to describe the distribution and grade the severity of the disease. Radiographic findings include airway dilation, bronchial wall thickening, and atelectasis. There are three types bronchiectasis that can be seen on CT scan, namely cylindrical, varicose, and cystic bronchiectasis. Prevention In preventing bronchiectasis, it is necessary to prevent the lung infections and lung damage that can cause it. Children should be immunized against measles, pertussis, pneumonia, and other acute respiratory infections of childhood. Additionally, parents should stay alert to keep children from inhaling objects such as pieces of food or small toys that may get stuck in small airways. Smoking and other toxic fumes and gases should be avoided by all patients with bronchiectasis to decrease the development of infections (such as bronchitis) and further complications.Treatments to slow down the progression of this chronic disease include keeping bronchial airways clear and secretions weakened through various forms of airway clearance. Aggressively treating bronchial infections with antibiotics to prevent the destructive cycle of infection, damage to bronchi and bronchioles, and more infection is also standard treatment. Regular vaccination against pneumonia, influenza, and pertussis are generally advised. A healthy body mass index and regular doctor visits may have beneficial effects on the prevention of progressing bronchiectasis. The presence of hypoxemia, hypercapnia, dyspnea level and radiographic extent can greatly affect the mortality rate from this disease. Management A comprehensive approach to the management of bronchiectasis is recommended. It is important to establish whether an underlying modifiable cause, such as immunoglobulin deficiency or alpha-1 antitrypsin deficiency is present. The next steps include controlling infections and bronchial secretions, relieving airway obstructions, removing affected portions of lung by surgery, and preventing complications. Airway clearance The goal of airway clearance therapy is to loosen secretions and interrupt the cycle of inflammation and infection. Airway clearance techniques improve difficulty breathing, cough, and help patients cough up phlegm and mucus plugs. Airway clearance usually uses an inhaled agent (hypertonic saline) with chest physiotherapy, such as high-frequency chest wall oscillation. Many airway clearance techniques and devices exist. The choice of a technique or device is based on the frequency and tenacity of phlegm, patient comfort, cost, and the patients ability to use the technique or device with minimal interference to their lifestyle. The active cycle of breathing technique (ACBT), which can be employed with or without a flutter device, is beneficial in treating those with bronchiectasis. Mucolytic agents such as dornase alfa are not recommended for individuals with non-CF bronchiectasis. Mannitol is a hyperosmolar agent that is thought to hydrate airway secretions, however, clinical trials with it have not demonstrated efficacy. Anti-inflammatories The two most commonly used classes of anti-inflammatory therapies are macrolides and corticosteroids.Despite also being antibiotics, macrolides exert immunomodulatory effects on the host inflammatory response without systemic suppression of the immune system. These effects include modifying mucus production, inhibition of biofilm production, and suppression of inflammatory mediators. Three large multicenter, randomized trials have shown reduced rates of exacerbations and improved cough and dyspnea with use of macrolide therapy. The impact of adverse effects of macrolides such as gastrointestinal symptoms, hepatotoxicity, and increased antimicrobial resistance needs ongoing review and study.Inhaled corticosteroid therapy can reduce sputum production and decrease airway constriction over a period of time, helping prevent progression of bronchiectasis. Long term use of high-dose inhaled corticosteroids can lead to adverse consequences such as cataracts and osteoporosis. It is not recommended for routine use in children. One commonly used therapy is beclometasone dipropionate. Antibiotics Antibiotics are used in bronchiectasis to eradicate P. aeruginosa or MRSA, to suppress the burden of chronic bacterial colonization, and to treat exacerbations. The use of daily oral non-macrolide antibiotic treatment has been studied in small case series, but not in randomized trials. The role of inhaled antibiotics in non-CF bronchiectasis has recently evolved with two society guidelines and a systematic review suggesting a therapeutic trial of inhaled antibiotics in patients with three or more exacerbations per year and P. aeruginosa in their sputum. Options for inhaled antibiotics include aerosolized tobramycin, inhaled ciprofloxacin, aerosolized aztreonam, and aerosolized colistin. Bronchodilators Some clinical trials have shown a benefit with inhaled bronchodilators in certain people with bronchiectasis. In people with demonstrated bronchodilator reversibility on spirometry, the use of inhaled bronchodilators resulted in improved dyspnea, cough, and quality of life without any increase in adverse events. However, overall there is a lack of data to recommend use of bronchodilators in all patients with bronchiectasis. Surgery The primary role of surgery in the management of bronchiectasis is in localized disease to remove segments of the lung or to control massive hemoptysis. Additionally, surgery is used to remove an airway obstruction that is contributing to bronchiectasis. The goals are conservative, aiming to control specific disease manifestations rather than cure or eliminate all areas of bronchiectasis. Surgical case series have shown low operative mortality rate (less than 2%) and improvement of symptoms in the majority of patients selected to receive surgery. However, no randomized clinical trials have been performed evaluating the efficacy of surgery in bronchiectasis. Clinical trials Results from a phase 2 clinical trial were published in 2018. In a placebo-controlled, double-blind study conducted in 256 patients worldwide, patients who received Brensocatib reported prolonged time to the first exacerbation and also reduced rate of yearly exacerbation. Prognosis Two clinical scales have been used to predict disease severity and outcomes in bronchiectasis; the Bronchiectasis Severity Index and the FACED scale. The FACED scale uses the FEV-1 (forced expiratory volume in 1 second), age of the affected person, presence of chronic infection, extent of disease (number of lung lobes involved) and dyspnea scale rating (MRC dyspnea scale) to predict clinical outcomes in bronchiectasis. The Bronchiectasis Severity Index uses the same criteria as the FACED scale in addition to including criteria related to number of hospital admissions, annual exacerbations, colonization with other organisms and BMI (body mass index) less than 18.5. A decreased FEV-1, increasing age, presence of chronic infection (especially pseudomonas), a greater extent of lung involvement, high clinical dyspnea scale ratings, increased hospital admissions, a high number of annual exacerbations, and a BMI less than 18.5 lead to higher scores on both clinical scales and are associated with a poor prognosis in bronchiectasis; including increased mortality. Epidemiology The prevalence and incidence of bronchiectasis is unclear as the symptoms are variable. The disease affects between 1 per 1000 and 1 per 250,000 adults. The disease is more common in women and in the elderly. In a Medicare cohort study in the United States, consisting of adults 65 years and older, the prevalence of bronchiectasis was 701 per 100,000 persons. A similar prevalence rate of bronchiectasis has been reported in other countries including China, Germany, the United Kingdom, Spain and Singapore. Those with a dual COPD and bronchiectasis diagnosis are more likely to be cigarette smokers and more likely to be hospitalized as compared to those with bronchiectasis without COPD. It became less common since the 1950s, with the introduction of antibiotics. It is more common among certain ethnic groups such as indigenous people.An estimated 350,000 to 500,000 adults have bronchiectasis in the United States. Specifically, children of the indigenous populations of Australia, Alaska, Canada and New Zealand have significantly higher rates than other populations. Overall, a shortage of data exists concerning the epidemiology of bronchiectasis in Asia, Africa, and South America.The prevalence and incidence of bronchiectasis has increased greatly in the 21st century. In a Medicare cohort analysis, consisting of adults 65 years and older in the United States; the annual rates of diagnosis have increased by 8.7% every year between 2000 and 2007. This large increase in the diagnosis of bronchiectasis may be due to increased recognition of the disease (including more widespread use of CT scans) or it may be due to an increase in the underlying causes of bronchiectasis. History René Laennec, the man who invented the stethoscope, used his invention to first discover bronchiectasis in 1819.The disease was researched in greater detail by Sir William Osler, one of the four founding professors of Johns Hopkins Hospital, in the late 1800s. It is suspected that Osler himself died of complications from undiagnosed bronchiectasis. His biographies mention that he had frequent severe chest infections for many years.The term "bronchiectasis" comes from the Greek words bronkhia (meaning "airway") and ektasis (meaning "widening"). References == External links ==
Otofaciocervical syndrome	Otofaciocervical syndrome, also known as Fara Chlupackova syndrome, are a small group of rare developmental disorders of genetic origin which are characterized by facial dysmorphisms, long neck, preauricular and/or branchial pits, cervical muscle hypoplasia, hearing loss, and mild intellectual disabilities. Additional findings include vertebral anomalies and short stature. Types There are two types of OFC: Otofaciocervical syndrome type 1 It is characterized by facial dysmorphisms, low-set cup-shaped ears, preauricular sinus or cyst, hearing loss, branchial and skeletal anomalies, low-set clavicle bones, winged scapulae, sloping shoulders and mild intellectual disabilities. It is caused by autosomal dominant mutations in the EYA1 gene in chromosome 8. Only 11 cases have been reported in medical literature. Otofaciocervical syndrome type 2 It is characterized by the same symptoms in type 1, this disorder is different from type 1 because of its genetic cause and because of its additional features: thymus development alterations with T-cell immunodeficiency and recurrent infections which may turn fatal. It is caused by autosomal recessive mutations in the PAX1 gene in chromosome 20. Only 13 cases have been described in medical literature. == References ==
Haemophilus meningitis	Haemophilus meningitis is a form of bacterial meningitis caused by the Haemophilus influenzae bacteria. It is usually (but not always) associated with Haemophilus influenzae type b. Meningitis involves the inflammation of the protective membranes that cover the brain and spinal cord. Haemophilus meningitis is characterized by symptoms including fever, nausea, sensitivity to light, headaches, stiff neck, anorexia, and seizures. Haemophilus meningitis can be deadly, but antibiotics are effective in treating the infection, especially when cases are caught early enough that the inflammation has not done a great deal of damage. Before the introduction of the Hib vaccine in 1985, Haemophilus meningitis was the leading cause of bacterial meningitis in children under the age of five. However, since the creation of the Hib vaccine, only two in every 100,000 children contract this type of meningitis. Five to ten percent of cases can be fatal, although the average mortality rate in developing nations is seventeen percent, mostly due to lack of access to vaccination as well as lack of access to medical care needed to combat the meningitis. Symptoms and signs Possible symptoms of Haemophilus meningitis include: Nausea or vomiting Fever Headache Sensitivity to light Seizures Anorexia change in mental status, such as irritability stiff neck Risk factors While the Haemophilus influenzae bacteria are unable to survive in any environment outside of the human body, humans can carry the bacteria within their bodies without developing any symptoms of the disease. It spreads through the air when an individual carrying the bacteria coughs or sneezes. The risk of developing Haemophilus meningitis is most directly related to an individuals vaccination history, as well as the vaccination history of the general public. Herd immunity, or the protection that unvaccinated individuals experience when the majority of others in their proximity are vaccinated, does help in the reduction of meningitis cases, but it does not guarantee protection from the disease. Contact with other individuals with the disease also vastly increases the risk of infection. A child in the presence of family members sick with Haemophilus meningitis or carrying the bacteria is 585 times more likely to catch Haemophilus meningitis. Additionally, siblings of individuals with the Haemophilus influenzae meningitis receive reduced benefits from certain types of immunization. Similarly, children under two years of age have a greater risk of contracting the disease when attending day care, especially in their first month of attendance, due to the maintained contact with other children who might be asymptomatic carriers of the Hib bacteria. Diagnosis Prevention Before the widespread use of the Hib vaccine, Haemophilus meningitis accounted for 40%-60% of all meningitis cases in children under the age of fifteen, and 90% of all meningitis cases in children under the age of five. Vaccination can reduce incidence. Vaccination has reduced the occurrences of Haemophilus meningitis by 87-90% in countries with widespread access to the Hib vaccine. Rates are still high in areas with limited levels of vaccination. Less-developed countries as well as countries with medical infrastructure that has been damaged in any way, such as from warfare, do not have such widespread access to the vaccine and thus experience higher rates of meningitis cases. Multiple conjugate Hib vaccines are available for use, though, and are extremely effective when given to infants. Additionally, the vaccine has only the side effects of reddened skin and swelling at the location of the injection. Treatment Because it is a bacterial disease, the primary method of treatment for Haemophilus meningitis is anti-bacterial therapy. Common antibiotics include ceftriaxone or cefotaxime, both of which can combat the infection and thus reduce inflammation in the meninges, or the membranes that protect the brain and spinal cord. Anti-inflammatories such as corticosteroids, or steroids produced by the body to reduce inflammation, can also be used to fight the meningeal inflammation in an attempt to reduce risk of mortality and reduce the possibility of brain damage. Prognosis Survivors of Haemophilus meningitis may experience permanent damage caused by inflammation around the brain, mostly involving neurological disorders. Long-term complications include brain damage, hearing loss, and mental disability. Other possible long-term effects are reduced IQ, cerebral palsy, and the development of seizures. Children that survive the disease are more often held back in school, and are more likely to require special education services. Negative long-term effects are more likely in subjects whose treatments were delayed, as well as in subjects who were given antibiotics to which the bacteria was resistant. Ten percent of survivors develop epilepsy, while close to twenty percent of survivors develop hearing loss ranging from mild loss to deafness. About 45% of survivors experience no negative long-term effects. References == External links ==
Glutathione synthetase deficiency	Glutathione synthetase deficiency (GSD) is a rare autosomal recessive metabolic disorder that prevents the production of glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components. Genetics Mutations in the GSS gene cause glutathione synthetase deficiency. This gene provides instructions for making the enzyme glutathione synthetase. This enzyme is involved in a process called the gamma-glutamyl cycle, which takes place in most of the bodys cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules which are byproducts of energy production. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency. This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder each carry one copy of the defective gene, but usually are not affected by the disorder. Diagnosis Glutathione synthetase deficiency can be classified into three types: mild, moderate and severe. Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). Rarely, affected people also excrete large amounts of a compound called 5-oxoproline (also called pyroglutamic acid, or pyroglutamate) in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells. Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis). In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); intellectual disability; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections. Treatment As of 2018, there is no cure for GSD, and treatment is restricted to manage symptoms and associated problems. Thus, sodium bicarbonate is recommended to treat metabolic acidosis, and antioxidants, among them vitamins E and C, can reduce oxidative damage. References Further reading Glutathione synthetase deficiency at NLM Genetics Home Reference Beutler, E; Gelbart, T; Pegelow, C (1986). "Erythrocyte glutathione synthetase deficiency leads not only to glutathione but also to glutathione-S-transferase deficiency". Journal of Clinical Investigation. 77 (1): 38–41. doi:10.1172/JCI112298. PMC 423305. PMID 3944259. == External links ==
Choledochal cysts	Choledochal cysts (a.k.a. bile duct cyst) are congenital conditions involving cystic dilatation of bile ducts. They are uncommon in western countries but not as rare in East Asian nations like Japan and China. Signs and symptoms Most patients have symptoms in the first year of life. It is rare for symptoms to be undetected until adulthood, and usually adults have associated complications. The classic triad of intermittent abdominal pain, jaundice, and a right upper quadrant abdominal mass is found only in minority of patients.In infants, choledochal cysts usually lead to obstruction of the bile ducts and retention of bile. This leads to jaundice and an enlarged liver. If the obstruction is not relieved, permanent damage may occur to the liver - scarring and cirrhosis - with the signs of portal hypertension (obstruction to the flow of blood through the liver) and ascites (fluid accumulation in the abdomen). There is an increased risk of cancer in the wall of the cyst.In older individuals, choledochal cysts are more likely to cause abdominal pain and intermittent episodes of jaundice and occasionally cholangitis (inflammation within the bile ducts caused by the spread of bacteria from the intestine into the bile ducts). Inflammation of the pancreas also may occur. The cause of these complications may be related to either abnormal flow of bile within the ducts or the presence of gallstones. Diagnosis Direct hyperbilirubinemia Types They were classified into 5 types by Todani in 1977.Classification was based on site of the cyst or dilatation. Type I to IV has been subtyped. Type I: Most common variety (80-90%) involving saccular or fusiform dilatation of a portion or entire common bile duct (CBD) with normal intrahepatic duct. Type II: These cysts are present as an isolated diverticulum protruding from the CBD. Type III or Choledochocele: Arise from dilatation of duodenal portion of CBD or where pancreatic duct meets. Type IVa: Characterized by multiple dilatations of the intrahepatic and extrahepatic biliary tree. Type IVb: Multiple dilatations involving only the extrahepatic bile ducts. Type V: Cystic dilatation of intrahepatic biliary ducts without extrahepatic duct disease. The presence of multiple saccular or cystic dilations of the intrahepatic ducts is known as Carolis disease. Type VI: An isolated cyst of the cystic duct is an extremely rare lesion. Only single case reports are documented in the literature. The most accepted classification system of biliary cysts, the Todani classification, does not include this lesion. Cholecystectomy with cystic duct ligation near the common bile duct is curative. Treatment Choledochal cysts are treated by surgical excision of the cyst with the formation of a roux-en-Y anastomosis hepaticojejunostomy/ choledochojejunostomy to the biliary duct. Future complications include cholangitis and a 2% risk of malignancy, which may develop in any part of the biliary tree. A recent article published in the Journal of Surgery suggested that choledochal cysts could also be treated with single-incision laparoscopic hepaticojejunostomy with comparable results and less scarring. In cases of saccular type of cyst, excision and placement of T-shaped tube is done.Currently, there is no accepted indication for fetal intervention in the management of prenatally suspected choledochal cysts. References == External links ==
Glandular odontogenic cyst	A glandular odontogenic cyst (GOC) is a rare and usually benign odontogenic cyst developed at the odontogenic epithelium of the mandible or maxilla. Originally, the cyst was labeled as "sialo-odontogenic cyst" in 1987. However, the World Health Organization (WHO) decided to adopt the medical expression "glandular odontogenic cyst". Following the initial classification, only 60 medically documented cases were present in the population by 2003. GOC was established as its own biological growth after differentiation from other jaw cysts such as the "central mucoepidermoid carcinoma (MEC)", a popular type of neoplasm at the salivary glands. GOC is usually misdiagnosed with other lesions developed at the glandular and salivary gland due to the shared clinical signs. The presence of osteodentin supports the concept of an odontogenic pathway. This odontogenic cyst is commonly described to be a slow and aggressive development. The inclination of GOC to be large and multilocular is associated with a greater chance of remission. GOC is an infrequent manifestation with a 0.2% diagnosis in jaw lesion cases. Reported cases show that GOC mainly impacts the mandible and male individuals. The presentation of GOC at the maxilla has a very low rate of incidence. The GOC development is more common in adults in their fifth and sixth decades.GOC has signs and symptoms of varying sensitivities, and dysfunction. In some cases, the GOC will present no classic abnormalities and remains undiagnosed until secondary complications arise. The proliferation of GOC requires insight into the foundations of its unique histochemistry and biology. The comparable characteristics of GOC with other jaw lesions require the close examination of its histology, morphology, and immunocytochemistry for a differential diagnosis. Treatment modes of the GOC follow a case-by-case approach due to the variable nature of the cyst. The selected treatment must be accompanied with an appropriate pre and post-operative plan. Signs and Symptoms The appearance of a protrusive growth will be present at their mandible or maxilla. The expansive nature of this cyst may destruct the quality of symmetry at the facial region and would be a clear physical sign of abnormality. The area of impact may likely be at the anterior region of mandible as described in a significant number of reported cases. At this region, GOC would eventually mediate expansion at the molars. A painful and swollen sensation at the jaw region caused by GOC may be reported. Detailing of a painless feeling or facial paraesthesia can be experienced. Alongside GOC, "root resorption, cortical bone thinning and perforation, and tooth displacement may occur". Experience of swelling at the buccal and lingual zones can occur. Usually, the smaller sized GOCs present no classical signs or symptoms to the case (i.e. "asymptomatic"). GOC is filled with cystic a fluid that differs in viscosity and may appear as transparent, brownish-red, or creamy in colour. Causes The GOC can arise through a number of causes:The origin of the GOC can be understood through its biological and histochemistry foundations. It has been suggested that GOC can be a result of a traumatic event. The occurrence of GOC may be from a mutated cell from "the oral mucosa and the dental follicle" origin. Another probable cause is from pre-existing cysts or cancerous constituents. A potential biological origin of GOC is a cyst developed at a salivary gland or simple epithelium, which undergoes maturation at the glandular. Another origin is a primordial cyst that infiltrates the glandular epithelial tissue through a highly organised cellular differentiation. Pathologists discovered a BCL-2 protein, commonly present in neoplasms, to exist in the tissue layers of the GOC. The protein is capable of disrupting normal cell death function at the odontogenic region. The analysis of PTCH, a gene that specialises in neoplasm inhibition, was carried out to determine if any existing mutations played a role in the initiation of the GOC. It is confirmed that the gene had no assistance in triggering cystic advancement. Diagnosis Radiology The performance of radiographic imaging i.e. computed tomography, at the affected area is considered essential. Radiographic imaging of the GOC can display a defined unilocular or multilocular appearance that may be "rounded or oval" shaped upon clinical observation. Scans may present a distribution of the GOC at the upper jaw as it presents a 71.8% prevalence in cases. The margin surrounding the GOC is usually occupied with a scalloped definition. A bilateral presentation of the GOC is possible but is not common at either the maxilla or mandible sites. The GOC has an average size of 4.9 cm that can develop over the midline when positioned at the mandible or maxilla region. Analysis of scans allow for the differentiation of GOC from other parallel lesions, i.e. "ameloblastoma, odontogenic myxoma, or dentigerous cyst" in order to minimise the chance of a misdiagnosis. These scans can display the severity of cortical plate, root, and tooth complications, which is observed to determine the necessary action for reconstruction. Histology Histological features related to the GOC differ in each scenario; however, there is a general criterion to identify the cyst. The GOC usually features a "stratified squamous epithelium" attached to connective tissue that is filled with active immune cells. The lining of the epithelium features a very small diameter that is usually non-keratinised. In contrast, the lining of the GOC has rather an inconsistent diameter. The basal cells of the GOC usually has no association to a cancerous origin. Tissue cells can be faced with an abnormal increase in the concentration of calcium, which can cause the region to calcify. The transformation of the epithelium is associated with a focal luminal development. Eosinophilic organelles such as columnar and cuboidal cells can be observed during microscopy. Intra-epithelial crypts may be identified in the internal framework of the epithelium or at the external space where it presents itself as papillae protrusions. Mucin is observable after the application of "alcian blue dye" on the tissue specimen. The histological observation of goblet cells is a common feature with the "odontogenic dentigerous cyst". In some circumstances, the epithelium can have variable plaque structures that appear as swirls in the tissue layers. Interestingly, histologists were able to identify hyaline bodies within the tissue framework of the GOC. It is encouraged that the histological identification of at least seven of these biological characteristics is required to accurately distinguish the presence of the GOC. Intraepithelial Hemosiderin Pathologists have identified hemosiderin pigments that are considered unique to the GOC. The discovery of this pigment can be pivotal to the differentiation of the GOC from other lesions. The staining at the epithelium is due to the haemorrhaging of the lining. The cause of the haemorrhaging can be triggered by the type of treatment, cellular degradation, or structural deformation inflicted during GOC expansion. Examination of the GOC tissue section indicated that red blood cells from the intraluminal space had combined with the extracellular constituents. This process is carried out through transepithelial elimination. This clinical procedure is beneficial to confirm the benign or malignant nature of the GOC. Immunocytochemistry The examination of cytokeratin profiles is deemed useful when observing the differences between the GOC and the central MEC. These two lesions show individualised expression for cytokeratin 18 and 19. Past studies observed Ki-67, p53, and PCNA expression in common jaw cysts that shared similar characteristics. There was a lack of p53 expression found in radicular cysts. Similarly, Ki-67 was seen less in the central MEC compared to the other lesions, though this discovery is not essential to the process of differential diagnosis. Proliferating cell nuclear antigen readings were established to have no role in the differentiation process. The TGF-beta marker is present in the GOC and can explain the limited concentration of normal functioning cells. MAML2 rearrangement The observation of a MAML2 rearrangement is described as a procedure useful in the differential diagnosis of the GOC and its closely related lesion, the central MEC. A second cystic development displayed the presence of CRTC3-MAML2 fusion after an in-vitro application. The MAML2 rearrangement represents the developmental growth of the central MEC from the GOC. The use of fusion-gene transcript may be helpful towards the differentiation of the GOC from the central MEC of the jaw and salivary glands. Treatment Pre-treatment protocols A computed tomography and panoramic x-ray must be undertaken in order to observe the severity of internal complications. These scans allow for the observation of the GOC size, radiolucency, cortical bone, dentition, root, and vestibular zone. In some cases, the dentition may be embedded into the cavity walls of the lesion, depending on the position of expansion at the odontogenic tissue. The diagnosis of a smaller sized GOC is related to the attachment of only two teeth. While, a greater sized GOC develops over two teeth. Presentation of a greater sized lesion usually requires a biopsy for a differential diagnosis and a precise treatment plan. Treatment process The unilocular and multilocular nature is imperative to the determination of treatment style. Local anesthesia is regularly provided as the GOC is embedded within the tissue structure of the jaw and requires an invasive procedure for a safe and accurate extraction. For unilocular GOCs with minimal tissue deterioration, "enucleation, curettage, and marsupialization" is a suitable treatment plan. Notably, the performance of enucleation or curettage as the primary action is linked to an incomplete extraction of the GOC and is only recommended to the less invasive lesions. Multilocular GOCs require a more invasive procedure such as "peripheral ostectomy, marginal resection, or partial jaw resection". GOCs associated with a more severe structural damage are encouraged to undergo marsupialization as either an initial or supplementary surgery. The frequency of reappearance is likely due to the lingering cystic tissue structures that remain after the performance of curettage. The incorporation of a "dredging method i.e. repetition of enucleation and curettage" is also suggested until the remnants of the GOC diminishes for certain. The treatment ensures scar tissue is removed to promote the successful reconstruction of osseous material for jaw preservation. Alongside the main treatments, bone allograft application, cryosurgery, and apicoectomy are available but have not been consistently recommended. Though Carnoys solution, the chloroform-free version, is recommended with the treatment as it degenerates the majority of the damaged dental lamina. The most effective type of treatment remains unknown due to the lack of detailed data from reported cases. Post-treatment protocols Follow-up appointments are necessary after the removal of the GOC as there is a high chance of remission, which may be exacerbated in cases dealing with "cortical plate perforation". The GOC has a significant remission rate of 21 to 55% that can potentially develop during the period of 0.5 to 7 years post-surgery. Cases occupied with a lower risk lesion are expected to continue appointments with physicians for up to 3 years post-surgery. A higher risk lesion is encouraged to consistently consult with physicians during a 7-year period after treatment. Remission events require immediate attention and appropriate procedures such as enucleation or curettage. In more damaging cases of remission, tissue resection, and marsupialization may have to be performed. Epidemiology The clinical presentation of the GOC is very low in the population as noted by the 0.12 to 0.13% occurrence rate, extrapolated from a sample size of the 181 individuals. The GOC mainly affects older individuals in the population, especially those that are in their 40 to 60s. However, the GOC can affect younger individuals i.e. 11, and more older individuals i.e. 82 in the population. The age distribution starts at a much lower number for people living in Asia and Africa. Those in their first 10 years of life have not been diagnosed with the GOC. The GOC does present a tendency to proliferate in more males than females. There is no definitive conclusion towards the relevance of gender and its influence on the rate of incidence. References Bibliography AbdullGaffar, Badr; Koilelat, Mohamed (May 2017). "Glandular Odontogenic Cyst: The Value of Intraepithelial Hemosiderin". International Journal of Surgical Pathology. 25 (3): 250–252. doi:10.1177/1066896916672333. PMID 27829208. S2CID 46588216. Akkaş, İsmail; Toptaş, Orçun; Özan, Fatih; Yılmaz, Fahri (1 March 2015). "Bilateral Glandular Odontogenic Cyst of Mandible: A Rare Occurrence". Journal of Maxillofacial and Oral Surgery. 14 (1): 443–447. doi:10.1007/s12663-014-0668-y. PMC 4379287. PMID 25848155. Alaeddini, Mojgan; Eshghyar, Nosratollah; Etemad‐Moghadam, Shahroo (2017). "Expression of podoplanin and TGF-beta in glandular odontogenic cyst and its comparison with developmental and inflammatory odontogenic cystic lesions". Journal of Oral Pathology & Medicine. 46 (1): 76–80. doi:10.1111/jop.12475. PMID 27391558. S2CID 40879254. Borges, Leandro Bezerra; Fechine, Francisco Vagnaldo; Mota, Mário Rogério Lima; Sousa, Fabrício Bitu; Alves, Ana Paula Negreiros Nunes (March 2012). "Odontogenic lesions of the jaw: a clinical-pathological study of 461 cases". Revista Gaúcha de Odontologia. 60 (1): 71–78. S2CID 46982083. Cano, Jorge; Benito, Dulce María; Montáns, José; Rodríguez-Vázquez, José Francisco; Campo, Julián; Colmenero, César (1 July 2012). "Glandular odontogenic cyst: Two high-risk cases treated with conservative approaches". Journal of Cranio-Maxillofacial Surgery. 40 (5): e131–e136. doi:10.1016/j.jcms.2011.07.005. PMID 21865053. Faisal, Mohammad; Ahmad, Syed Ansar; Ansari, Uzma (September 2015). "Glandular odontogenic cyst – Literature review and report of a paediatric case". Journal of Oral Biology and Craniofacial Research. 5 (3): 219–225. doi:10.1016/j.jobcr.2015.06.011. PMC 4623883. PMID 26587384. Kaplan, Ilana; Gal, Gavriel; Anavi, Yakir; Manor, Ronen; Calderon, Shlomo (April 2005). "Glandular odontogenic cyst: Treatment and recurrence". Journal of Oral and Maxillofacial Surgery. 63 (4): 435–441. doi:10.1016/j.joms.2004.08.007. PMID 15789313. Motooka, Naomi; Ohba, Seigo; Uehara, Masataka; Fujita, Syuichi; Asahina, Izumi (1 January 2015). "A case of glandular odontogenic cyst in the mandible treated with the dredging method". Odontology. 103 (1): 112–115. doi:10.1007/s10266-013-0143-0. PMID 24374982. S2CID 21059170. Nagasaki, Atsuhiro; Ogawa, Ikuko; Sato, Yukiko; Takeuchi, Kengo; Kitagawa, Masae; Ando, Toshinori; Sakamoto, Shinnichi; Shrestha, Madhu; Uchisako, Kaori; Koizumi, Koichi; Toratani, Shigeaki; Konishi, Masaru; Takata, Takashi (January 2018). "Central mucoepidermoid carcinoma arising from glandular odontogenic cyst confirmed by analysis of MAML2 rearrangement: A case report: Central MEC arising from GOC". Pathology International. 68 (1): 31–35. doi:10.1111/pin.12609. PMID 29131467. S2CID 8932602. Neville, Brad W. (2016). "Cyst, Glandular Odontogenic". In Slootweg, Pieter (ed.). Dental and Oral Pathology. Encyclopedia of Pathology. Springer International Publishing. pp. 89–93. doi:10.1007/978-3-319-28085-1_677. ISBN 978-3-319-28084-4. Prabhu, Sudeendra; Rekha, K; Kumar, GS (2010). "Glandular odontogenic cyst mimicking central mucoepidermoid carcinoma". Journal of Oral and Maxillofacial Pathology. 14 (1): 12–5. doi:10.4103/0973-029X.64303. PMC 2996005. PMID 21180452. Momeni Roochi, Mehrnoush; Tavakoli, Iman; Ghazi, Fatemeh Mojgan; Tavakoli, Ali (1 July 2015). "Case series and review of glandular odontogenic cyst with emphasis on treatment modalities". Journal of Cranio-Maxillofacial Surgery. 43 (6): 746–750. doi:10.1016/j.jcms.2015.03.030. PMID 25971944. Patel, Govind; Shah, Monali; Kale, Hemant; Ranginwala, Amena (2014). "Glandular odontogenic cyst: A rare entity". Journal of Oral and Maxillofacial Pathology. 18 (1): 89–92. doi:10.4103/0973-029X.131922. PMC 4065455. PMID 24959044. Shah, AmishaA; Sangle, Amit; Bussari, Smita; Koshy, AjitV (2016). "Glandular odontogenic cyst: A diagnostic dilemma". Indian Journal of Dentistry. 7 (1): 38–43. doi:10.4103/0975-962X.179371. PMC 4836096. PMID 27134453. Shear, Mervyn; Speight, Paul, eds. (2007). "Glandular Odontogenic Cyst (Sialo-Odontogenic Cyst)". Cysts of the Oral and Maxillofacial Regions. pp. 94–99. doi:10.1002/9780470759769.ch7. ISBN 978-0-470-75976-9. == Further reading ==
Tropical acne	Tropical acne is unusually severe acne occurring in the tropics during seasons when the weather is hot and humid.: 500 Skin conditions including acne are seen with more frequency in dermatological consultations in hot and humid climates, where bacterial and fungal infections are more common than in drier climates. See also List of cutaneous conditions References External links Understanding Acne Blemishes with a Skin Specialist
Corticobasal degeneration	Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is characterized by marked disorders in movement and cognition, and is classified as one of the Parkinson plus syndromes. Diagnosis is difficult, as symptoms are often similar to those of other disorders, such as Parkinsons disease, progressive supranuclear palsy, and dementia with Lewy bodies, and a definitive diagnosis of CBD can only be made upon neuropathologic examination. Signs and symptoms Because CBD is progressive, a standard set of diagnostic criteria can be used, which is centered on the diseases evolution. Included in these fundamental features are problems with cortical processing, dysfunction of the basal ganglia, and a sudden and detrimental onset. Psychiatric and cognitive dysfunctions, although present in CBD, are much less prevalent and lack establishment as common indicators of the presence of the disease.Although corticobasal degeneration has a plethora of symptoms, some are more prevalent than others. In a study of 147 patients with CBD, it was found that all of them had at least one Parkinsonian sign, 95% having two and 93% had some higher order dysfunction (cognitive impairments like acalculia, sensory loss, dementia, neglect, etc.). In a separate study of 14 patients recorded 3 years after the onset of symptoms, many patients had high numbers of motor symptoms. 71% had bradykinesia (slow movements), 64% showed apraxia, 43% reported limb dystonia, and although more cognitive 36% had dementia. In another study of 36, over half had a useless/alien arm and 27% had a gait impediment[21]. From this, we can see why CBD is hard to diagnose. Even if it can be distinguished as different from one of the other similar diseases, the varying combinations of symptoms create a difficult path to diagnosis. Motor and associated cortical dysfunctions Some of the most prevalent symptom types in people exhibiting CBD pertain to identifiable movement disorders and problems with cortical processing. These symptoms are initial indicators of the presence of the disease. Each of the associated movement complications typically appears asymmetrically and the symptoms are not observed uniformly throughout the body. For example, a person exhibiting an alien hand syndrome (explained later) in one hand, will not correspondingly display the same symptom in the other hand. Predominant movement disorders and cortical dysfunctions associated with CBD include: Parkinsonism Alien hand syndrome Apraxia (ideomotor apraxia and limb-kinetic apraxia) Aphasia Parkinsonism The presence of parkinsonism as a clinical symptom of CBD is largely responsible for complications in developing unique diagnostic criteria for the disease. Other such diseases in which parkinsonism forms an integral diagnostic characteristic are Parkinsons disease (PD) and progressive supranuclear palsy (PSP). Parkinsonism in CBD is largely present in an extremity such as the arm, and is always asymmetric. It has been suggested that non-dominant arm is involved more often. Common associated movement dysfunctions that comprise parkinsonism are rigidity, bradykinesia, and gait disorder, with limb rigidity forming the most typical manifestation of parkinsonism in CBD. Despite being relatively indistinct, this rigidity can lead to disturbances in gait and correlated movements. Bradykinesia in CBD occurs when there is notable slowing in the completion of certain movements in the limbs. In an associated study, it was determined that, three years following first diagnosis, 71% of persons with CBD demonstrate the presence of bradykinesia. Alien hand syndrome Alien hand syndrome has been shown to be prevalent in roughly 60% of those people diagnosed with CBD. This disorder involves the failure of an individual to control the movements of their hand, which results from the sensation that the limb is "foreign". The movements of the alien limb are a reaction to external stimuli and do not occur sporadically or without stimulation. The presence of an alien limb has a distinct appearance in CBD, in which the diagnosed individual may have a "tactile mitgehen". This mitgehen (German, meaning "to go with") is relatively specific to CBD, and involves the active following of an experimenters hand by the subjects hand when both hands are in direct contact. Another, rarer form of alien hand syndrome has been noted in CBD, in which an individuals hand displays an avoidance response to external stimuli. Additionally, sensory impairment, revealed through limb numbness or the sensation of prickling, may also concurrently arise with alien hand syndrome, as both symptoms are indicative of cortical dysfunction. Like most of the movement disorders, alien hand syndrome also presents asymmetrically in those diagnosed with CBD. Apraxia Ideomotor apraxia (IMA), although clearly present in CBD, often manifests atypically due to the additional presence of bradykinesia and rigidity in those individuals exhibiting the disorders. The IMA symptom in CBD is characterized by the inability to repeat or mimic particular movements (whether significant or random) both with or without the implementation of objects. This form of IMA is present in the hands and arms, while IMA in the lower extremities may cause problems with walking. Those with CBD that exhibit IMA may appear to have trouble initiating walking, as the foot may appear to be fixed to floor. This can cause stumbling and difficulties in maintaining balance. IMA is associated with deterioration in the premotor cortex, parietal association areas, connecting white matter tracts, thalamus, and basal ganglia. Some individuals with CBD exhibit limb-kinetic apraxia, which involves dysfunction of more fine motor movements often performed by the hands and fingers. Aphasia Aphasia in CBD is revealed through the inability to speak or a difficulty in initiating spoken dialogue and falls under the non-fluent (as opposed to fluent or flowing) subtype of the disorder. This may be related to speech impairment such as dysarthria, and thus is not a true aphasia, as aphasia is related to a change in language function, such as difficulty retrieving words or putting words together to form meaningful sentences. The speech and/or language impairments in CBD result in disconnected speech patterns and the omission of words. Individuals with this symptom of CBD often lose the ability to speak as the disease progresses. Psychiatric and cognitive disorders Psychiatric problems associated with CBD often present as a result of the debilitating symptoms of the disease. Prominent psychiatric and cognitive conditions cited in individuals with CBD include dementia, depression, and irritability, with dementia forming a key feature that sometimes leads to the misdiagnosis of CBD as another cognitive disorder such as Alzheimers disease (AD). Frontotemporal dementia can be an early feature. Molecular features Neuropathological findings associated with CBD include the presence of astrocytic abnormalities within the brain and improper accumulation of the protein tau (referred to as tauopathy). Astroglial inclusions Postmortem histological examination of the brains of individuals diagnosed with CBD reveal unique characteristics involving the astrocytes in localized regions. The typical procedure used in the identification of these astroglial inclusions is the Gallyas-Braak staining method. This process involves exposing tissue samples to a silver staining material which marks for abnormalities in the tau protein and astroglial inclusions. Astroglial inclusions in CBD are identified as astrocytic plaques, which present as annularly displays of blurry outgrowths from the astrocyte. A recent study indicated that produces a high density of astrocytic plaques in the anterior portion of the frontal lobe and in the premotor area of the cerebral cortex. Tauopathy The protein tau is an important microtubule-associated protein (MAP), and is typically found in neuronal axons. However, malfunctioning of the development of the protein can result in unnatural, high-level expression in astrocytes and glial cells. As a consequence, this is often responsible for the astrocytic plaques prominently noted in histological CBD examinations. Although they are understood to play a significant role in neurodegenerative diseases such as CBD, their precise effect remains a mystery.In recent years Corticobasal Degeneration is seen to be a tauopathy[22]. This is believed due to the most common indicator of CBD being a faulty tau protein. Tau proteins are integral in keeping microtubules stable and these defective cells create 4 microtubule-binding repeats[23]. These 4 binding repeats have increased affinity in binding with microtubules[25]. Because of this increased affinity, they form insoluble fibers (also called "paired helical filaments). Microtubules themselves keep the cell and cytoskeletal structure stable[24]. Thus, when Tau proteins create unnatural configurations, microtubules become unstable, and eventually leads to cell death. Diagnosis New diagnostic criteria known as the Armstrong criteria were proposed in 2013, although the accuracy of these is limited and further research is needed. Criteria Insidious onset and gradual progression Lasts 1 year or more Meets one of the four subtypes: Possible CBS FBS or NAV PSPS plus at least one CBS feature other than limb rigidity or akinesia No exclusion criteria present More likely if onset is after age 50 More likely if no family history (2 or more relatives) More likely if no genetic mutation affecting T (e.g., MAPT) Possible corticobasal syndrome subtype Symptoms may be symmetric or asymmetric. One or more of: limb rigidity or akinesia limb dystonia limb myoclonus, plus one of: orobuccal or limb apraxia cortical sensory deficit alien limb phenomena (more than simple levitation)More likely (probable sporadic CBS) if: Asymmetric presentation Onset after age 50 No family history (2 or more relatives) No genetic mutation affecting T (e.g. MAPT) plus two of:limb rigidity or akinesia limb dystonia limb myoclonusplus two of:orobuccal or limb apraxia, cortical sensory deficit alien limb phenomena (more than simple levitation) Frontal behavioural-spatial syndrome subtype Two of: executive dysfunction behavioural or personality changes visuospatial deficits NAV of primary progressive aphasia subtype Effortful, agrammatic speech plus at least one of: impaired grammar/sentence comprehension with relatively preserved single word comprehension or groping, distorted speech production (apraxia of speech) Progressive supranuclear palsy syndrome subtype Three of: axial or symmetric limb rigidity or akinesia postural instability or falls urinary incontinence behavioural changes supranuclear vertical gaze palsy or decreased vertical saccade velocity Exclusion criteria These apply to all types of CBD. Evidence of Lewy body disease multiple system atrophy Alzheimers disease ALS semantic or logopenic variant primary progressive aphasia structural lesion suggestive of focal cause granulin mutation or reduced plasma progranulin levels TDP-43 or fused in sarcoma (FUS) mutationsThe diagnostic criteria for clinical use may result in a misdiagnosis of other tau-based diseases.The probable criteria are proposed for clinical research. Clinical vs. postmortem One of the most significant problems associated with CBD is the inability to perform a definitive diagnosis while an individual exhibiting the symptoms associated with CBD is still alive. A clinical diagnosis of CBD is performed based upon the specified diagnostic criteria, which focus mainly on the symptoms correlated with the disease. However, this often results in complications as these symptoms often overlap with numerous other neurodegenerative diseases. Frequently, a differential diagnosis for CBD is performed, in which other diseases are eliminated based on specific symptoms that do not overlap. However, some of the symptoms of CBD used in this process are rare to the disease, and thus the differential diagnosis cannot always be used.Postmortem diagnosis provides the only true indication of the presence of CBD. Most of these diagnoses utilize the Gallyas-Braak staining method, which is effective in identifying the presence of astroglial inclusions and coincidental tauopathy. Overlap with other diseases Progressive supranuclear palsy (PSP) is frequently the disease most often confused with CBD. Both PSP and CBD result in similar symptoms, and both display tauopathies upon histological inspection. However, it has been noted that tauopathy in PSP results in tuft-shaped astrocytes in contrast with the ring-shaped astrocytic plaques found as a result of CBD.Individuals diagnosed with PD often exhibit similar movement dysfunction as those diagnosed with CBD, which adds complexity to its diagnosis. Some other neurodegenerative diseases including Alzheimers disease (AD), dementia with Lewy bodies (DLB), chronic traumatic encephalopathy (CTE) and frontotemporal dementia (FTD) also show commonalities with CBD. Neuroimaging The types of imaging techniques that are most prominently utilized when studying and/or diagnosing CBD are: magnetic resonance imaging (MRI) single-photon emission computed tomography (SPECT) fluorodopa positron emission tomography (FDOPA PET)Developments or improvements in imaging techniques provide the future possibility for definitive clinical diagnosis prior to death. However, despite their benefits, information learned from MRI and SPECT during the beginning of CBD progression tend to show no irregularities that would indicate the presence of such a neurodegenerative disease. FDOPA PET is used to study the efficacy of the dopamine pathway.Despite the undoubted presence of cortical atrophy (as determined through MRI and SPECT) in individuals experiencing the symptoms of CBD, this is not an exclusive indicator for the disease. Thus, the utilization of this factor in the diagnosis of CBD should be used only in combination with other clinically present dysfunctions. MRI MRI images are useful in displaying atrophied portions of neuroanatomical positions within the brain. As a result, it is especially effective in identifying regions within different areas of the brain that have been negatively affected due to the complications associated with CBD. To be specific, MRI of CBD typically shows posterior parietal and frontal cortical atrophy with unequal representation in corresponding sides. In addition, atrophy has been noted in the corpus callosum.Functional MRI (fMRI) has been used to evaluate the activation patterns in various regions of the brain of individuals affected with CBD. Upon the performance of simple finger motor tasks, subjects with CBD experienced lower levels of activity in the parietal cortex, sensorimotor cortex, and supplementary motor cortex than those individuals tested in a control group. SPECT SPECT is currently being used to try to detect CBD. With many patients of CBD, there are areas in the basal ganglia which have difficulties receiving dopamine, typically asymmetrically. Specifically affected, are dopamine transporters which are presynaptic on the nigrostriatal cells. SPECT is used to detect these abnormalities in Dopamine transporters. Given that many patients have asymmetrical loss of function and metabolism this can help differentiate patients with CBD and those with Alzheimers.SPECT studies of individuals diagnosed with CBD involve perfusion analysis throughout the parts of the brain. SPECT evaluation through perfusion observation consists of monitoring blood release into different locations in tissue or organ regions, which, in the case of CBD, pertains to localized areas within the brain. Tissue can be characterized as experiencing overperfusion, underperfusion, hypoperfusion, or hyperperfusion. Overperfusion and underperfusion relate to a comparison with the overall perfusion levels within the entire body, whereas hypoperfusion and hyperperfusion are calculated in comparison to the blood flow requirements of the tissue in question. In general, the measurements taken for CBD using SPECT are referred to as regional cerebral blood flow (rCBF).In general, SPECT reveals hypoperfusion within both the posterior regions of the frontal and parietal lobes. As in images gathered through MRI, SPECT images indicated asymmetry in the presentation of abnormalities throughout the brain. Additional studies have revealed the presence of perfusion anomalies in the thalamus, temporal cortex, basal ganglia, and pontocerebellar (from the pons to the cerebellum) locations within subjects brains. FDOPA PET Research has suggested that the integrity of the dopamine system in the striatum has been damaged as an effect of CBD. Current studies employing the use of FDOPA PET scanning (FDOPA PET) as a possible method for identifying CBD have focused on analyzing the efficiency of neurons in the striatum that utilize the neurotransmitter dopamine. These studies have concluded that, in general, dopamine uptake was diminished in the caudate and the putamen. This characteristic also has the potential to be useful in distinguishing CBD from the similar PD, as individuals having been diagnosed with PD were more likely to have a lower uptake of dopamine than in individuals with CBD.Other clinical tests or procedures that monitor the presence of dopamine within the brain (β-CIT SPECT and IBZM SPECT) have shown similar findings. β-CIT serves as an indicator for presynaptic dopaminergic neurons, whereas IBZM is a tracer that shows an affinity for the postsynaptic neurons of the same type. Despite agreement with other imaging studies, these two SPECT methods suffer some scrutiny due to better accuracy in other imaging methods. However, β-CIT SPECT has proven to be helpful in distinguishing CBD from PSP and multiple system atrophy (MSA). Corticobasal syndrome All of the disorders and dysfunctions associated with CBD can often be categorized into a class of symptoms that present with the disease of CBD. These symptoms that aid in clinical diagnosis are collectively referred to as corticobasal syndrome (CBS) or corticobasal degeneration syndrome (CBDS). Alzheimers disease, Picks disease, FTDP-17 and progressive supranuclear palsy can display a corticobasal syndrome. It has been suggested that the nomenclature of corticobasal degeneration only be used for naming the disease after it has received verification through postmortem analysis of the neuropathology. CBS patients with greater temporoparietal degeneration are more likely to have AD pathology as opposed to frontotemporal lobar degeneration. Treatment Because the exact cause of CBD is unknown, there exists no formal treatment for the disease. Instead, treatments focus on minimizing the appearance or effect of the symptoms resulting from CBD. The most easily treatable symptom of CBD is parkinsonism, and the most common form of treatment for this symptom is the application of dopaminergic drugs. However, in general only moderate improvement is seen and the relief from the symptom is not long-lasting. In addition, palliative therapies, including the implementation of wheelchairs, speech therapy, and feeding techniques, are often used to alleviate many of the symptoms that show no improvement with drug administration.There is no consensus on what causes CBD and so most of the treatment goes in helping symptoms. Many treatments have low success rates or have not been tested thoroughly or produced frequently. For example, in relation to the motor aspect of disability, CBD has a high resistance against treatments to help the dopamine intake like levodopa. A number of studies have reported no real levels of improvement based with the use of similar drugs/dopaminergic agonists. Because of the brains levels of inhibition, some medications have focused on creating an inhibition that would negate the effect. Many of these relaxants and anticonvulsants have some success but also have unwanted side effects[21]. Cognitive and associative effects of CBD are also hard to treat as we are still unsure of many of the treatments for the symptomatic diseases that ensue like dementia, aphasia, neglect, apraxia and others. Epidemiology Clinical presentation of CBD usually does not occur until age 60, with the earliest recorded diagnosis and subsequent postmortem verification being age 28. Although men and women present with the disease, some analysis has shown a predominant appearance of CBD in women. Current calculations suggest that the prevalence of CBD is approximately 4.9 to 7.3 per 100,000 people. The prognosis for an individual diagnosed with CBD is death within approximately eight years, although some patients have been diagnosed over 17 years ago (2017) and are still in relatively good standing, but with serious debilitation such as dysphagia, and overall limb rigidity. The partial (or total) use of a feeding tube may be necessary and will help prevent aspiration pneumonia, primary cause of death in CBD. Incontinence is common, as patients often cant express their need to go, due to eventual loss of speech. Therefore, proper hygiene is mandatory to prevent urinary tract infections.CBD research has been limited by the rarity of the disease and the lack of research criteria. It is estimated to affect 0.6-0.9 per 100,000 per year.Progressive supranuclear palsy (PSP) without CBD is estimated to be ten times more common. CBD represents roughly 4–6% of patients with Parkinsonism. Average age at disease onset is about 64, with the youngest confirmed onset being at age 43. There may be a slight female predominance. History Corticobasal syndrome was first recognized in 1967 when Rebeiz, Kolodny, and Richardson Jr described three people with a progressive asymmetric akinetic-rigid syndrome combined with apraxia, which they named corticodentatonigral degeneration with neuronal achromasia. The condition was "mostly forgotten" until 1989, when Marsden et al. used the name corticobasal degeneration. In 1989 Gibb and colleagues provided detailed clinical and pathological descriptions in a further three cases adopting the name corticobasal degeneration, after which various other names included "corticonigral degeneration with nuclear achromasia" and "cortical basal ganglionic degeneration". Although the underlying cause of CBD is unknown, the disease occurs as a result of damage to the basal ganglia, specifically marked by neuronal degeneration or depigmentation (loss of melanin in a neuron) in the substantia nigra. Additional distinguishing neurological features of those diagnosed with CBD consist of asymmetric atrophy of the frontal and parietal cortical regions of the brain. Postmortem studies of patients diagnosed with CBD indicate that histological attributes often involve ballooning of neurons, gliosis, and tauopathy. Much of the pioneering advancements and research performed on CBD has been completed within the past decade or so, due to the relatively recent formal recognition of the disease.The Office of Rare Diseases in the United States created the first criteria in 2002, and the Armstrong clinical diagnostic criteria were created in 2013. Society and culture The Salt Path by Raynor Winn is an inspiring account of walking Englands 630 mile South West Coast Path with her husband who had corticobasal degeneration. See also Frontotemporal lobar degeneration References Boeve BF (2011). "The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: Implications for further study". Journal of Molecular Neuroscience. 45 (3): 350–3. doi:10.1007/s12031-011-9624-1. PMID 21853287. S2CID 30307394. Hassan A, Whitwell JL, Josephs KA (2011). "The corticobasal syndrome-alzheimers disease conundrum". Expert Review of Neurotherapeutics. 11 (11): 1569–78. doi:10.1586/ern.11.153. PMC 3232678. PMID 22014136.{{cite journal}}: CS1 maint: multiple names: authors list (link) Goode BL, Chau M, Denis PE, Feinstein SC (2000). "Structural and Functional Differences between 3-Repeat and 4-Repeat Tau Isoforms". Journal of Biological Chemistry. 275 (49): 38182–38189. doi:10.1074/jbc.m007489200. PMID 10984497. S2CID 30896096.{{cite journal}}: CS1 maint: multiple names: authors list (link) Mahapatra RK, Edwards MJ, Schott JM, Bhatia KP (2004). "Corticobasal degeneration". The Lancet Neurology. 3 (12): 736–43. doi:10.1016/s1474-4422(04)00936-6. PMID 15556806. S2CID 15324889. ProQuest 201513368.{{cite journal}}: CS1 maint: multiple names: authors list (link) Avila J (1992). "Microtubule functions". Life Sci. 50 (5): 327–334. doi:10.1016/0024-3205(92)90433-p. PMID 1732704. == External links ==
Balanitis circinata	Balanitis circinata (also known as circinate balanitis) is a skin condition of reactive arthritis comprising a serpiginous ring-shaped dermatitis of the glans penis. Circinate balanitis is one of the most common cutaneous manifestation of reactive arthritis. However, balanitis circinata can also occur independently. Topical corticosteroid therapy is the most commonly used treatment, and topical calcineurin inhibitors have also been used successfully. Signs and symptoms At the beginning, people show pin-sized dots with white plaque on them which constantly grow into flat, red areas hardly surrounded by white plaque. Despite the visible symptoms, patients in nearly all cases do not suffer from burning or itching, nor does it smell strange. Due to its analogy to a fungal skin infection, balanitis circinata is often misdiagnosed as mycosis – especially in cases where patients have no other symptoms of reactive arthritis. Cause Reactive arthritis is characterized by nongonococcal urethritis, conjunctivitis, and arthritis. Reactive arthritis belongs to the group of arthritides known as the spondyloarthritides. There are two main types of reactive arthritis: post-venereal and post-enteric. Chlamydia trachomatis is thought to be the most common cause of reactive arthritis, in general. Until recently, even the terminology for the condition itself was unclear as multiple eponyms and names have been associated with reactive arthritis. In recent years, a great deal has been learnt about the epidemiology, pathophysiology and treatment of reactive arthritis and chlamydia-induced reactive arthritis, specifically. Prospective epidemiologic data suggest that chlamydia-induced reactive arthritis is underdiagnosed. Other truths being actively revealed include data suggesting that the pathogen itself (i.e., chlamydia) might play an equally important role, or perhaps even more important, than the host with disease susceptibility; asymptomatic chlamydial infections might be a common cause of reactive arthritis and the two variants of reactive arthritis might respond differently to treatment in spite of the congruent clinical presentation. However, much about this syndrome remains shrouded in mystery. Recent data has been suggesting that Chlamydia-induced reactive arthritis might be a common condition that clinicians are simply failing to recognise. Therefore, an emphasis is placed on disease awareness since viable treatment options are emerging. Treatment Balanitis circinata is one out of multiple manifestations of the reactive arthritis.Right now, topical corticosteroid therapy is the most commonly used treatment, and topical calcineurin inhibitors have also been used successfully. Newer tests on patients showed that a less harmful off-label topical treatment with the immunomodulator pimecrolimus or the immunosuppressant tacrolimus can prevent all visible symptoms of this disease. Since reactive arthritis cannot be healed as such, affected people are forced to a continuous topical treatment – otherwise they will again note first symptoms after three to four days without it.However, strong debates and controversies continue regarding the exact indications of immunomodulators like pimecrolimus and their duration of use in the absence of active controlled trials. A study released in 2015 (tested were 7,457 children with a total of 26,792 person-years) did not find any evidence that pimecrolimus could cause cancer. == References ==
Acne mechanica	Acne mechanica is an acneiform eruption that has been observed after repetitive physical trauma to the skin such as rubbing, occurring from clothing (belts and straps) or sports equipment (football helmets and shoulder pads).: 499 In addition to those mechanisms, the skin not getting enough exposure to air also contributes to the formation of acne mechanica. It is often mistaken as a rash that forms on sweaty skin that is constantly being rubbed, but in reality, it is a breakout of acne mechanica. The term "acne" itself describes the occurrence in which hair follicles (also known as pores) in the skin get clogged by oil, dead skin cells, dirt and bacteria, or cosmetic products and create a pimple. Pimples can vary in type, size, and shape, but the sole basis of them occurring is the same - the oil gland in the pore becomes clogged and sometimes infected, which creates pus in order to fight the infection and subsequently causes the development of swollen, red lesions on the skin. Signs and symptoms The signs and symptoms at an early stage are harder to be seen. At first look, acne mechanica seems very similar to any other type of acne. However, it differs in how it is caused. A lot of acne has to do with hormones, the amount of oil production in the skin, and genetic predispositions. Acne mechanica specifically refers to the skin irritation that is formed by excess pressure, heat, and rubbing against the skin. When the skin is constantly rubbed, it initially becomes rough and then starts to develop acne-like bumps with continuing irritation like sweating or more friction. If the skin continues to be irritated for a longer period of time, a more serious acne lesion develops that grows in size and redness. They appear as small, red tender bumps called papules. There may be a combination of whiteheads and blackheads that also appear around the area affected, the difference being that whiteheads are closed and clogged pores whereas blackheads are also clogged but open pores. The symptoms may vary also depending on a persons skin type; overly oily or dry skin can cause a number of symptoms that heighten the possibility for acne mechanica to develop. Cause Repetitive rubbing of the skin, in instances such as backpack strings rubbing on your shoulders or helmet straps rubbing on your chin are actions that can irritate the skin and cause acne mechanica. Acne mechanica is a specific type of acne that is caused by friction, heat, and/or pressure on the skin. Especially occurs when the skin is not exposed to air. It is commonly found in athletes because sweaty, constantly rubbed skin by a tight uniform, for example, can result in a rash. What may look like a rash is actually acne mechanica. Another common area for acne mechanica to show up is on the sides of your face where you hold your cell phone, especially with the added bacteria it carries on it. There are some people who are more prone to develop acne mechanica. The biggest group of people affected by this type of acne are teenagers and young adults in their twenties who already experience issues with acne on their back, shoulders, and buttocks. Other people who have a type of acne commonly described as "sandpaper acne," which is characterized as small but rough acne lesions that are not very visible but feel like sandpaper to the touch, also are more prone to developing acne mechanica. Mechanism Acne mechanica specifically is triggered by both mechanical and heat stress on the skin working together to cause this irritation. The skin that is exposed to these stressors initially develops a harder surface to protect itself, but if the skin is continually dealing with this pressure, it gets irritated and forms a rash. At this point, it gets qualified as acne mechanica. When you are in a hot climate or are working out and your body temperature rises, the heat causes the pores in your skin to open up. The dilation of the pores makes it easier for bacteria, oil, and dead skin cells to collect in the pores and clog them. Every pore in your body has a tiny hair follicle, and the blockage causes the hair follicle to become irritated and inflamed, which ends up forming pimples; specifically acne mechanica. White blood cells flood the area of inflammation, and once they die, they accumulate on the surface of the pore, causing what is known as a "whitehead". When people pop pimples, pus comes out, which has the dead white blood cells in it that originally came to diffuse the inflammation. Depending on the continuation of the stressors, the inflammatory pimples (also known as papules and pustules) can develop into nodules and cysts, which are more severe forms of acne that are rooted deeper within the skin. Diagnosis Acne mechanica can be diagnosed by a dermatologist via a physical examination. In more extreme cases, a skin biopsy is performed to examine the pathology. Family and medical history are also looked at to see if the patient has a hereditary tendency to certain conditions that cause different types of acne, which may play a role in acne mechanica development. For example, if a patients parents had acne, there is a very strong probability they will also have similar issues. The issues can range from things like overproducing dead skin cells or the pores having a higher tendency to clog. Treatment Acne mechanica has no direct cure, however, there are preventive measures that can be taken to minimize its breakouts. The most obvious solution to prevent extra rubbing or heat entrapment on the surface of the skin is to wear either loose-fitting clothes or wearing clothes made out of more breathable fabrics, especially during exercising, playing sports, or when performing physical activities such as hiking. Loose clothes will not rub as much and create the mechanical stress on the skin. Instead of wearing clothes made out of polyester and rayon, choosing cotton materials will help relieve the heat stress on the skin and not trap sweat in the pores. Taking showers immediately after any form of physical exercise will also help keep the skin as clean as possible. Keeping up with a skin care regimen so the skin is moisturized helps as well. Using skin care products specifically with salicylic acid or benzoyl peroxide help exfoliate the skin in a gentle manner and get rid of bacteria. Both of these chemicals in a facial cleanser may create a tingling sensation on people with extremely sensitive skin. Other topical ointments can be used once consulted with a dermatologist. Prognosis Long term effects of acne mechanica include potential scarring and skin discoloration at the area of the acne lesion if rubbing of the skin continues. It is not a lethal condition and the acne will clear up on its own once the heat and pressure stressors are avoided and if the skin is kept clean so the pores do not continue to become clogged. Epidemiology Acne mechanica is most prevalent among athletes, soldiers in warm climates, teenagers and young adults. The athletes and soldiers can get rashes from their equipment and uniforms constantly rubbing their skin while sweating, which turn into acne mechanica lesions. Men tend to be more prone to develop acne mechanica because they produce more oil (also known as sebum) in their glands, even though their glands are actually smaller than womens. This is also a reason why mens acne tends to remain a problem for longer once its developed. Acne in general is hereditary from parents to child, so genetics play a factor as well. People who already have acne and have a problematic skin type that tends to create clogged pores are more likely to develop acne mechanica as well. Research Directions Although not exactly having to do with acne mechanica and the heat or pressure stressors that cause it, there is still not a lot of research relating to different organs health relating to acne appearing on different areas of the body and face. A correlation between the two could be explored in future studies. See also List of cutaneous conditions == References ==
Rheumatoid vasculitis	Rheumatoid vasculitis is skin condition that is a typical feature of rheumatoid arthritis, presenting as peripheral vascular lesions that are localized purpura, cutaneous ulceration, and gangrene of the distal parts of the extremities. See also Rheumatoid nodulosis List of cutaneous conditions References == External links ==
Rett syndrome	Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age in females. Symptoms include impairments in language, coordination, and repetitive movements. Those affected often have slower growth, difficulty walking, and a smaller head size. Complications of Rett syndrome can include seizures, scoliosis, and sleeping problems. The severity of the condition is variable.Rett syndrome is due to a genetic mutation in the MECP2 gene, on the X chromosome. It almost always occurs as a new mutation, with less than one percent of cases being inherited from a persons parents. It occurs almost exclusively in girls; boys who have a similar mutation typically die shortly after birth. Diagnosis is based on the symptoms and can be confirmed with genetic testing.There is no known cure for Rett syndrome. Treatment is directed at improving symptoms. Anticonvulsants may be used to help with seizures. Special education, physiotherapy, and braces may also be useful. Many of those with the condition live into middle age.The condition affects about 1 in 8,500 females. In 1999, Lebanese-American physician Huda Zoghbi discovered the mutation that causes the condition. Signs and symptoms Stage I Stage I, called early-onset, typically begins between 6 and 18 months of age. This stage is often overlooked because symptoms of the disorder may be somewhat vague, and parents and doctors may not notice the subtle slowing of development at first. The infant may begin to show less eye contact and have reduced interest in toys. There may be delays in gross motor skills such as sitting or crawling. Hand-wringing and decreasing head growth may occur, but not enough to draw attention. This stage usually lasts for a few months but can continue for more than a year. Stage II Stage II, or the rapid destructive stage, usually begins between ages 1 and 4 and may last for weeks or months. Its onset may be rapid or gradual as the child loses purposeful hand skills and spoken language. Characteristic hand movements such as wringing, washing, clapping, or tapping, as well as repeatedly moving the hands to the mouth often begin during this stage which is called mouthing. The child may hold the hands clasped behind the back or held at the sides, with random touching, grasping, and releasing. The movements continue while the child is awake but disappear during sleep. Breathing irregularities such as episodes of apnea and hyperventilation may occur, although breathing usually improves during sleep. Some girls also display autistic-like symptoms such as loss of social interaction and communication. Walking may be unsteady and initiating motor movements can be difficult. Slowed head growth is usually noticed during this stage. Stage III Stage III, or the plateau or pseudo-stationary stage, usually begins between ages 2 and 10 and can last for years. Apraxia, motor problems, and seizures are prominent during this stage. However, there may be improvement in behavior, with less irritability, crying, and autistic-like features. In stage III there may be more interest in the surroundings and alertness, attention span, and communication skills may improve. Many girls remain in this stage for most of their lives. Stage IV Stage IV, or the late motor deterioration stage, can last for years or decades. Prominent features include reduced mobility, curvature of the spine, and muscle weakness, rigidity, spasticity, and increased muscle tone with abnormal posturing of an arm or leg. Girls who were previously able to walk may stop walking. Cognition, communication, or hand skills generally do not decline in stage IV. Repetitive hand movements may decrease and eye gaze usually improves. Variants The signs and symptoms of the typical form of the Rett syndrome are well described. In addition to the classical form of Rett syndrome, several atypical forms have been described over the years; the main groups are: Congenital variant (Rolando variant): in this severe subtype of Rett syndrome, the development of the patients and their head circumference are abnormal from birth. The typical gaze of Rett syndrome patients is usually absent; Zappella variant of Rett Syndrome or preserved speech variant: in this subtype of Rett syndrome the patients acquire some manual skills and language is partially recovered around the age of 5 years (that is after the regression phase). Height, weight and head circumference are often in the normal range, and a good gross motor function can be observed. The Zappella variant is a milder form of Rett syndrome; Hanefeld variant or early epilepsy variant. In this form of Rett syndrome, the patients have epilepsy before 5 months of age.The definition itself of the Rett syndrome has been refined over the years: as the atypical forms subsist near to the classical form (Hagberg & Gillgerg, 1993), the "Rett Complex" terminology has been introduced. Cause Genetically, Rett syndrome (RTT) is caused by mutations in the gene MECP2 located on the X chromosome (which is involved in transcriptional silencing and epigenetic regulation of methylated DNA), and can arise sporadically or from germline mutations. In less than 10% of RTT cases, mutations in the genes CDKL5 or FOXG1 have also been found to resemble it. Rett syndrome is initially diagnosed by clinical observation, but the diagnosis is definitive when there is a genetic defect in the MECP2 gene. It has been argued that Rett syndrome is in fact a neurodevelopmental condition as opposed to a neurodegenerative condition. One piece of evidence for this is that mice with induced Rett Syndrome show no neuronal death, and some studies have suggested that their phenotypes can be partially rescued by adding functional MECP2 gene back when they are adults. This information has also helped lead to further studies aiming to treat the disorder. Sporadic mutations In at least 95% of Rett syndrome cases, the cause is a de novo mutation in the child. That is, it is not inherited from either parent. Parents are generally genotypically normal, without a MECP2 mutation.In cases of the sporadic form of RTT, the mutated MECP2 is thought to derive almost exclusively from a de novo mutation on the male copy of the X chromosome. It is not yet known what causes the sperm to mutate, and such mutations are rare. Germline mutations It can also be inherited from phenotypically normal mothers who have a germline mutation in the gene encoding methyl-CpG-binding protein-2, MeCP2. In these cases, inheritance follows an X-linked dominant pattern and is seen almost exclusively in females, as most males die in utero or shortly after birth. MECP2 is found near the end of the long arm of the X chromosome at Xq28. An atypical form of RTT, characterized by infantile spasms or early onset epilepsy, can also be caused by a mutation to the gene encoding cyclin-dependent kinase-like 5 (CDKL5). As stated by Aine Merwick, Margaret OBrien, and Norman Delanty in an article on gene disorders titled Complex single gene disorders and epilepsy, "Rett syndrome affects one in every 12,500 female live births by age 12 years." Mechanism Pontine noradrenergic deficits Brain levels of norepinephrine are lower in people with Rett syndrome (reviewed in). The genetic loss of MECP2 changes the properties of cells in the locus coeruleus, the exclusive source of noradrenergic innervation to the cerebral cortex and hippocampus. These changes include hyperexcitability and decreased functioning of its noradrenergic innervation. Moreover, a reduction of the tyrosine hydroxylase (Th) mRNA level, the rate-limiting enzyme in catecholamine synthesis, was detected in the whole pons of MECP2-null male as well as in adult heterozygous (MECP2+/-) female mice. Using immunoquantitative techniques, a decrease of Th protein staining level, number of locus coeruleus TH-expressing neurons and density of dendritic arborization surrounding the structure was shown in symptomatic MeCP2-deficient mice. However, locus coeruleus cells are not dying, but are more likely losing their fully mature phenotype, since no apoptotic neurons in the pons were detected.Researchers have concluded that "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett syndrome, such as respiration and cognition, we hypothesize that the locus coeruleus is a critical site at which loss of MECP2 results in CNS dysfunction." The restoration of normal locus coeruleus function may therefore be of potential therapeutic value in the treatment of Rett syndrome. Midbrain dopaminergic disturbances The majority of dopamine in the mammalian brain is synthesized by nuclei located in the mesencephalon. The substantia nigra pars compacta (SNpc), the ventral tegmental area (VTA) and the retrorubral field (RRF) contains dopaminergic neurons expressing tyrosine hydroxylase (Th, i.e. the rate-limiting enzyme in catecholamine synthesis).The nigro-striatal pathway originates from SNpc and irradiate its principal rostral target, the Caudate-Putamen (CPu) through the median forebrain bundle (MFB). This connection is involved in the tight modulation of motor strategies computed by a cortico-basal ganglia- thalamo-cortical loop.Indeed, based on the canonical anatomofunctional model of basal ganglia, nigrostriatal dopamine is able to modulate the motor loop by acting on dopaminergic receptors located on striatal GABAergic medium spiny neurons.Dysregulation of the nigrostriatal pathway is causative from Parkinson disease (PD) in humans. Toxic and/or genetic ablation of SNpc neurons produces experimental parkinsonism in mice and primates. The common features of PD and PD animal models are motor impairments (hypotonia, bradykinesia, hypokinesia). RTT pathology, in some aspects, overlaps the motor phenotype observed in PD patients. Several neuropathological studies on postmortem brain samples argued for an SNpc alteration evidenced by neuromelanin hypopigmentation, reduction in the structure area, and even controversial, signs of apoptosis. In parallel, an hypometabolism was underlined by a reduction of several catecholamines (dopamine, noradrenaline, adrenaline) and their principal metabolic by-products. Mouse models of RTT are available and the most studied are constitutively deleted Mecp2 mice developed by Adrian Bird or Katelyn McCormick laboratories.In accordance with the motor spectrum of the RTT phenotype, Mecp2-null mice show motor abnormalities from postnatal day 30 that worsen until death. These models offer a crucial substrate to elucidate the molecular and neuroanatomical correlates of an MeCP2-deficiency. Recently (2008), it was shown that the conditional deletion of Mecp2 in catecholaminergic neurons (by crossing of Th-Cre mice with loxP-flanked Mecp2 ones) recapitulates a motor symptomatology, it was further documented that brain levels of Th in mice lacking MeCP2 in catecholaminergic neurons only are reduced, participating to the motor phenotype.However, the most studied model for the evaluation of therapeutics is the Mecp2-null mouse (totally devoid of MeCP2). In this context, a reduction in the number and soma size of Th-expressing neurons is present from 5 weeks of age and is accompanied by a decrease of Th immunoreactivity in the caudate-putamen, the principal target of dopaminergic neurons arising from the SNpc. Moreover, a neurochemical analysis of dopaminergic contents in microdissected midbrain and striatal areas revealed a reduction of dopamine at five and nine weeks of age. It is noteworthy that later on (at nine weeks), the morphological parameters remain altered but not worsen, whereas the phenotype progresses and behavioral deficits are more severe. The amount of fully activated Th (Serine40-phosphorylated isoform) in neurons that remain in the SNpc is mildly affected at 5 weeks but severely impaired by 9 weeks. Finally, using a chronic and oral L-Dopa treatment on MeCP2-deficient mice authors reported an amelioration of some of the motor deficits previously identified. Altogether, these results argue for an alteration of the nigrostriatal dopaminergic pathway in MeCP2-deficient animals as a contributor of the neuromotor deficits.There is an association of the disease with brain-derived neurotrophic factor (BDNF). Molecular Functions of MECP2 in Rett Syndrome Pathology As reviewed by Sharifi and Yasui, MECP2 protein, encoded by the MECP2 gene binds to DNA with a high affinity for CpG methylated DNA sites and affects transcription. MECP2 can bind to 5mc (5-methylcytosine) and 5hmc (5-hydroxymethylcytosine) with similar affinity, and these dinucleotides account for the majority of MECP2 binding sites in the mammalian genome. MECP2 is involved in higher order chromatin organization and appears necessary for compacting chromosomes. MECP2 binding to DNA influences mRNA splicing events. MECP2 also appears to function in DNA repair processes. MECP2-/+ deficient female mice have elevated rates of cell death when exposed to DNA damaging agents and are prone to early senescence. Interactive pathway map An interactive pathway map of Rett syndrome has been published. Diagnosis Prior to the discovery of a genetic cause, Rett syndrome had been designated as a pervasive developmental disorder by the Diagnostic and Statistical Manual of Mental Disorders (DSM), together with the autism spectrum disorders. Some argued against this conclusive assignment because RTT resembles non-autistic disorders such as fragile X syndrome, tuberous sclerosis, or Down syndrome that also exhibit autistic features. After research proved the molecular mechanism, in 2013 the DSM-5 removed the syndrome altogether from classification as a mental disorder.Rett syndrome diagnosis involves close observation of the childs growth and development to observe any abnormalities in regards to developmental milestones. A diagnosis is considered when decreased head growth is observed. Conditions with similar symptoms must first be ruled out.There is a certain criteria that must be met for the diagnosis. A blood test can rule in or rule out the presence of the MECP2 mutation, however, this mutation is present in other conditions as well.For a classic diagnosis, all four criteria for ruling in a diagnosis must be met, as well as the two criteria for ruling out a diagnosis. Supportive criteria may also be present, but are not required for diagnosis. For an atypical or variant diagnosis, at least two of the four criteria for ruling in the diagnosis must be met, as well as five of the eleven supportive criteria. A period of symptom regression followed by recovery or symptom stabilization must also occur. Children are often misdiagnosed as having autism, cerebral palsy, or another form of developmental delay. A positive test for the MECP2 mutation is not enough to make a diagnosis.Ruling in Decreased or loss of use of fine motor skills Decreased or loss of verbal speech Abnormalities during gait Repetitive hand movements such as wringing/squeezing or clapping/tappingRuling out Traumatic or anoxic/hypoxic brain injury, neurometabolic disease, or severe infection that may better explain symptoms Abnormal psychomotor development during the first six months of lifeSupportive criteria Breathing disturbances when awake Bruxism while awake Impaired sleep pattern Abnormal muscle tone Peripheral vasomotor disturbances Scoliosis/kyphosis Growth retardation Small cold hands and feet Inappropriate laughing/screaming spells Diminished response to pain Intense eye communication (eye pointing) Differential diagnosis Signs of Rett syndrome that are similar to autism: Signs of Rett syndrome that are also present in cerebral palsy (regression of the type seen in Rett syndrome would be unusual in cerebral palsy; this confusion could rarely be made): Treatment Currently there is no cure for Rett syndrome. Treatment is directed towards improving function and addressing symptoms. A multi-disciplinary team approach is typically used to treat the person throughout life. This team may include primary care physician, physical therapist, occupational therapist, speech-language pathologist, nutritionist, and support services in academic and occupational settings. Some children may require special equipment and aids such as braces to arrest scoliosis, splints to modify hand movements, and nutritional programs to help them maintain adequate weight.Because of the increased risk of sudden cardiac death, when long QT syndrome is found on an annual screening EKG it is treated with an anti-arrhythmic such as a beta-blocker. There is some evidence that phenytoin may be more effective than a beta-blocker.While medicinal interventions to mitigate breathing challenges in children with Rett Syndrome (RTT) are still being developed, children with RTT may be prescribed rebreathing techniques (e.g., rebreathing masks), oxygen delivery, or non-invasive ventilation as preventative or rescue breathing treatments. High oxidative stress levels in individuals with RTT have exacerbated effects on their cardiorespiratory health and functionality, dramatically increasing the risk for sudden cardiac death—an anomaly that has an associated 300x increased occurrence risk in children with Rett Syndrome. Due to this, it is vital to closely monitor atypical breathing behaviors in children with RTT, making sure to effectively use lifesaving respiratory improvement devices and strategies as prescribed. Prescribed treatment methods may vary depending on the breathing characteristic phenotype expressed by the child. Physicians have identified three major RTT breathing phenotypes; forceful breathers, feeble breathers, and apneustic breathers. For forceful breathers, for example, rebreathing masks may be used while the child is awake. Prognosis Males with pathogenic MECP2 mutations usually die within the first 2 years from severe encephalopathy, unless they have one or more extra X chromosomes, or have somatic mosaicism. Male fetuses with the disorder rarely survive to term. Because the disease-causing gene is located on the X chromosome, a female born with an MECP2 mutation on her X chromosome has another X chromosome with an ostensibly normal copy of the same gene, while a male with the mutation on his X chromosome has no other X chromosome, only a Y chromosome; thus, he has no normal gene. Without a normal gene to provide normal proteins in addition to the abnormal proteins caused by a MECP2 mutation, the XY karyotype male fetus is unable to slow the development of the disease, hence the failure of many male fetuses with a MECP2 mutation to survive to term. Females with a MECP2 mutation, however, have a non-mutant chromosome that provides them enough normal protein to survive longer. Research shows that males with Rett syndrome may result from Klinefelters syndrome, in which the male has an XXY karyotype. Thus, a non-mutant MECP2 gene is necessary for a Retts-affected embryo to survive in most cases, and the embryo, male or female, must have another X chromosome. There have, however, been several cases of 46,XY karyotype males with a MECP2 mutation (associated with classical Rett syndrome in females) carried to term, who were affected by neonatal encephalopathy and died before 2 years of age. The incidence of Rett syndrome in males is unknown, partly owing to the low survival of male fetuses with the Rett syndrome-associated MECP2 mutations, and partly to differences between signs caused by MECP2 mutations and those caused by Retts.Females can live up to 40 years or more. Laboratory studies on Rett syndrome may show abnormalities such as: EEG abnormalities from 2 years of age atypical brain glycolipids elevated CSF levels of beta-endorphin and glutamate reduction of substance P decreased levels of CSF nerve growth factorsA high proportion of deaths are abrupt, but most have no identifiable cause; in some instances death is the result most likely of: spontaneous brainstem dysfunction cardiac arrest, likely due to long QT syndrome, ventricular tachycardia or other arrhythmias seizures gastric perforation History Andreas Rett, a pediatrician in Vienna, first described the condition in 1966. As his writings were in German, they did not become widely known in the English-speaking world. Bengt Hagberg, a Swedish pediatrician, published an English article in 1983 and named the condition after Rett. In 1999, Lebanese-American physician Huda Zoghbi discovered the mutation that causes the condition. Research Gene therapy is under study in animal models to achieve regulated expression of a normal MECP2 gene. In March 2022, Taysha Gene Therapies announced that they had received Clinical Trial Application (CTA) approval from Health Canada for a clinical trial of their investigational gene therapy for adult females with Rett Syndrome. In fiction In August 2021, a novel by British author Victoria Scott, Patience, was published by Head of Zeus. The novel featured a character with Rett syndrome and explored recent developments in gene therapy. References == External links ==
Degenerative disc disease	Degenerative disc disease (DDD) is a medical condition typically brought on by the normal aging process in which there are anatomic changes and possibly a loss of function of one or more intervertebral discs of the spine. DDD can take place with or without symptoms, but is typically identified once symptoms arise. The root cause is thought to be loss of soluble proteins within the fluid contained in the disc with resultant reduction of the oncotic pressure, which in turn causes loss of fluid volume. Normal downward forces cause the affected disc to lose height, and the distance between vertebrae is reduced. The anulus fibrosus, the tough outer layers of a disc, also weakens. This loss of height causes laxity of the longitudinal ligaments, which may allow anterior, posterior, or lateral shifting of the vertebral bodies, causing facet joint malalignment and arthritis; scoliosis; cervical hyperlordosis; thoracic hyperkyphosis; lumbar hyperlordosis; narrowing of the space available for the spinal tract within the vertebra (spinal stenosis); or narrowing of the space through which a spinal nerve exits (vertebral foramen stenosis) with resultant inflammation and impingement of a spinal nerve, causing a radiculopathy. DDD can cause mild to severe pain, either acute or chronic, near the involved disc, as well as neuropathic pain if an adjacent spinal nerve root is involved. Diagnosis is suspected when typical symptoms and physical findings are present; and confirmed by x-rays of the vertebral column. Occasionally the radiologic diagnosis of disc degeneration is made incidentally when a cervical x-ray, chest x-ray, or abdominal x-ray is taken for other reasons, and the abnormalities of the vertebral column are recognized. The diagnosis of DDD is not a radiologic diagnosis, since the interpreting radiologist is not aware whether there are symptoms present or not. Typical radiographic findings include disc space narrowing, displacement of vertebral bodies, fusion of adjacent vertebral bodies, and development of bone in adjacent soft tissue (osteophyte formation). An MRI is typically reserved for those with symptoms, signs, and x-ray findings suggesting the need for surgical intervention. Treatment may include chiropractic to reduce pain and increase any reduced range of motion (ROM) of the spine; Physical Therapy for pain relief, ROM, and appropriate muscle/strength training with emphasis on correcting abnormal posture, assisting the paravertebral (paraspinous) muscles in stabilizing the spine, and core muscle strengthening; stretching exercises; massage therapy; oral analgesia with non-steroidal anti-inflammatory agents (NSAIDS); and topical analgesia with lidocaine, ice and heat. Immediate surgery may be indicated if the symptoms are severe or sudden in onset, or there is a sudden worsening of symptoms. Elective surgery may be indicated after six months of conservative therapy with unsatisfactory relief of symptoms. Signs and symptoms Degenerative disc disease can result in lower back or upper neck pain. The amount of degeneration does not correlate well with the amount of pain patients experience. Many people experience no pain while others, with the same amount of damage have severe, chronic pain. Whether a patient experiences pain or not largely depends on the location of the affected disc and the amount of pressure that is being put on the spinal column and surrounding nerve roots. Nevertheless, degenerative disc disease is one of the most common sources of back pain and affects approximately 30 million people every year. With symptomatic degenerative disc disease, the pain can vary depending on the location of the affected disc. A degenerated disc in the lower back can result in lower back pain, sometimes radiating to the hips, as well as pain in the buttocks, thighs or legs. If pressure is being placed on the nerves by exposed nucleus pulposus, sporadic tingling or weakness through the knees and legs can also occur. A degenerated disc in the upper neck will often result in pain to the neck, arm, shoulders and hands; tingling in the fingers may also be evident if nerve impingement is occurring. Pain is most commonly felt or worsened by movements such as sitting, bending, lifting and twisting. After an injury, some discs become painful because of inflammation and the pain comes and goes. Some people have nerve endings that penetrate more deeply into the anulus fibrosus (outer layer of the disc) than others, making discs more likely to generate pain. In the alternative, the healing of trauma to the outer anulus fibrosus may result in the innervation of the scar tissue and pain impulses from the disc, as these nerves become inflamed by nucleus pulposus material. Degenerative disc disease can lead to a chronic debilitating condition and can have a serious negative impact on a persons quality of life. When pain from degenerative disc disease is severe, traditional nonoperative treatment may be ineffective. Cause There is a disc between each of the vertebrae in the spine. A healthy, well-hydrated disc will contain a great deal of water in its center, known as the nucleus pulposus, which provides cushioning and flexibility for the spine. Much of the mechanical stress that is caused by everyday movements is transferred to the discs within the spine and the water content within them allows them to effectively absorb the shock. At birth, a typical human nucleus pulposus will contain about 80% water. However natural daily stresses and minor injuries can cause these discs to gradually lose water as the annulus fibrosus, or the tough outer fibrous material of a disc, weakens. Because degenerative disc disease is largely due to natural daily stresses, the American Academy of Orthopaedic Manual Physical Therapists have suggested it is not truly a "disease" process.This water loss makes the discs more flexible and results in the gradual collapse and narrowing of the gap in the spinal column. As the space between vertebrae gets smaller, extra pressure can be placed on the discs causing tiny cracks or tears to appear in the annulus. If enough pressure is exerted, it is possible for the nucleus pulposus material to seep out through the tears in the annulus and can cause what is known as a herniated disc. As the two vertebrae above and below the affected disc begin to collapse upon each other, the facet joints at the back of the spine are forced to shift which can affect their function.Additionally, the body can react to the closing gap between vertebrae by creating bone spurs around the disc space in an attempt to stop excess motion. This can cause issues if the bone spurs start to grow into the spinal canal and put pressure on the spinal cord and surrounding nerve roots as it can cause pain and affect nerve function. This condition is called spinal stenosis. For women, there is evidence that menopause and related estrogen-loss are associated with lumbar disc degeneration, usually occurring during the first 15 years of the climacteric. The potential role of sex hormones in the etiology of degenerative skeletal disorders is being discussed for both genders.Mutations in several genes have been implicated in intervertebral disc degeneration. Probable candidate genes include type I collagen (sp1 site), type IX collagen, vitamin D receptor, aggrecan, asporin, MMP3, interleukin-1, and interleukin-6 polymorphisms. Mutation in genes – such as MMP2 and THBS2 – that encode for proteins and enzymes involved in the regulation of the extracellular matrix has been shown to contribute to lumbar disc herniation. Mechanisms Degenerative discs typically show degenerative fibrocartilage and clusters of chondrocytes, suggestive of repair. Inflammation may or may not be present. Histologic examination of disc fragments resected for presumed DDD is routine to exclude malignancy. Fibrocartilage replaces the gelatinous mucoid material of the nucleus pulposus as the disc changes with age. There may be splits in the anulus fibrosus, permitting herniation of elements of nucleus pulposus. There may also be shrinkage of the nucleus pulposus that produces prolapse or folding of the anulus fibrosus with secondary osteophyte formation at the margins of the adjacent vertebral body. The pathologic findings in DDD include protrusion, spondylolysis, and subluxation of vertebrae (spondylolisthesis) and spinal stenosis. It has been hypothesized that Cutibacterium acnes may play a role. Diagnosis Diagnosis of degenerative disc disease will usually consist of an analysis of a patients individual medical history, a physical exam designed to reveal muscle weakness, tenderness or poor range of motion, and an x-ray to confirm the diagnosis and rule out other causes. Treatment Often, the symptoms of degenerative disc disease can be successfully treated without surgery. One or a combination of treatments such as physical therapy, anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs, traction, or epidural steroid injection can provide adequate relief of troubling symptoms. Surgery may be recommended if the conservative treatment options do not provide relief within two to three months for cervical or 6 months for lumbar symptoms. If leg or back pain limits normal activity, if there is weakness or numbness in the legs, if it is difficult to walk or stand, or if medication or physical therapy are ineffective, surgery may be necessary, most often spinal fusion. There are many surgical options for the treatment of degenerative disc disease, including anterior and posterior approaches. The most common surgical treatments include: Traditional approaches in treating patients with DDD-resultant herniated discs oftentimes include discectomy—which, in essence, is a spine-related surgical procedure involving the removal of damaged intervertebral discs (either whole removal, or partially-based). The former of these two discectomy techniques involved in open discectomy is known as Subtotal Discectomy (SD; or, aggressive discectomy) and the latter, Limited Discectomy (LD; or, conservative discectomy). However, with either technique, the probability of post-operative reherniation exists and at a considerably high maximum of 21%, prompting patients to potentially undergo recurrent disk surgery.New treatments are emerging that are still in the beginning clinical trial phases. Glucosamine injections may offer pain relief for some without precluding the use of more aggressive treatment options. Adult stem cell or cell transplantation therapies for disc regeneration are in their infancy of development, but initial clinical trials have shown cell transplantation to be safe and initial observations suggest some beneficial effects for associated pain and disability. An optimal cell type, transplantation method, cell density, carrier, or patient indication remains to be determined. Investigation into mesenchymal stem cell therapy knife-less fusion of vertebrae in the United States began in 2006 and a DiscGenics nucleus pulposus progenitor cell transplantation clinical trial has started as of 2018 in the United States and Japan.Researchers and surgeons have conducted clinical and basic science studies to uncover the regenerative capacity possessed by the large animal species involved (humans and quadrupeds) for potential therapies to treat the disease. Some therapies, carried out by research laboratories in New York, include introduction of biologically engineered, injectable riboflavin cross-linked high density collagen (HDC-laden) gels into disease spinal segments to induce regeneration, ultimately restoring functionality and structure to the two main inner and outer components of vertebral discs—anulus fibrosus and the nucleus pulposus. Other animals Degenerative disc disease can occur in other mammals besides humans. It is a common problem in several dog breeds, and attempts to remove this disease from dog populations have led to several hybrid breeds, such as the Chiweenie. See also Failed back syndrome Herniated disk References == External links ==
Trigonitis	Trigonitis is a condition of inflammation of the trigone region of the bladder. It is more common in women.The cause of trigonitis is not known, and there is no solid treatment. Electrocautery is sometimes used, but is generally unreliable as a treatment, and typically does not have quick results. Several drugs, such as muscle relaxants, antibiotics, antiseptics such as Urised, have varied and unreliable results. Other forms of treatment include urethrotomy, cryosurgery, and neurostimulation. References == External links ==

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