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Familial Mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder.: 149  FMF is an autoinflammatory disease caused by mutations in Mediterranean fever gene, which encodes a 781–amino acid protein called pyrin. While all ethnic groups are susceptible to FMF, it usually occurs in people of Mediterranean origin—including Sephardic Jews, Mizrahi Jews, Ashkenazi Jews, Assyrians, Armenians, Azerbaijanis, Levantines, Kurds, Greeks, Turks and Italians.The disorder has been given various names, including familial paroxysmal polyserositis, periodic peritonitis, recurrent polyserositis, benign paroxysmal peritonitis, periodic disease or periodic fever, Reimann periodic disease or Reimann syndrome, Siegal-Cattan-Mamou disease, and Wolff periodic disease. Note that "periodic fever" can also refer to any of the periodic fever syndromes. Signs and symptoms Attacks There are seven types of attacks. Ninety percent of all patients have their first attack before they are 18 years old. All develop over 2–4 hours and last anywhere from 6 hours to 5 days. Most attacks involve fever. Abdominal attacks, featuring abdominal pain, affect the whole abdomen with all signs of peritonitis (inflammation of abdominal lining), and acute abdominal pain like appendicitis. They occur in 95% of all patients and may lead to unnecessary laparotomy. Incomplete attacks, with local tenderness and normal blood tests, have been reported. Joint attacks mainly occur in large joints, especially in the legs. Usually, only one joint is affected. 75% of all FMF patients experience joint attacks. Chest attacks include pleuritis (inflammation of the pleura) and pericarditis (inflammation of the pericardium). Pleuritis occurs in 40% of patients and makes it difficult to breathe or lie flat, but pericarditis is rare. Scrotal attacks due to inflammation of the tunica vaginalis are somewhat rare but may be mistaken for testicular torsion. Myalgia (rare in isolation) Erysipeloid rashes (a skin reaction on the legs that can mimic cellulitis, rare in isolation) Complications AA-amyloidosis with kidney failure is a complication and may develop without overt crises. AA amyloid protein is produced in very large quantities during attacks, and at a low rate between them, and accumulates mainly in the kidney, as well as the heart, spleen, gastrointestinal tract, and thyroid.There appears to be an increase in the risk for developing particular vasculitis-related diseases (e.g. Henoch–Schönlein purpura), spondylarthropathy, prolonged arthritis of certain joints and protracted myalgia. Genetics The MEFV gene is located on the short arm of chromosome 16 (16p13). Many different mutations of the MEFV gene can cause the disorder. Having one mutation is unlikely to cause the condition. Having two mutations either a copy from both parents, or two different mutations, one from each parent is the threshold for a genetic diagnosis of FMF. However, most individuals who comply with the genetic diagnosis of FMF remain asymptomatic or undiagnosed. Whether this is due to modifier genes or environmental factors remains to be established. Pathophysiology Virtually all cases are due to a mutation in the Mediterranean Fever (MEFV) gene on the chromosome 16, which codes for a protein called pyrin or marenostrin. Various mutations of this gene lead to FMF, although some mutations cause a more severe picture than others. Mutations occur mainly in exons 2, 3, 5 and 10.The function of pyrin has not been completely elucidated, but in short, it is a protein that binds to the adaptor ASC and the pro form of the enzyme caspase-1 to generate multiprotein complexes called inflammasomes in response to certain infections. In healthy individuals, pyrin-mediated inflammasome assembly (which leads to the caspase 1) dependent processing and secretion of the pro-inflammatory cytokines (such as interleukin-18 (IL-18) and IL-1β) is a response to enterotoxins from certain bacteria. The gain-of-function mutations in the MEFV gene render Pyrin hyperactive, and subsequently, the formation of the inflammasomes becomes more frequent.The pathophysiology of familial Mediterranean fever has recently undergone significant advances: at basal state, pyrin is kept inactive by a chaperone protein (belonging to the family of 14.3.3 proteins) linked to pyrin through phosphorylated serine residues. The dephosphoration of pyrin is an essential prerequisite for the activation of the pyrin inflammasome. Inactivation of RhoA GTPases (by bacterial toxins, for example) leads to the inactivation of PKN1 / PKN2 kinases and dephosphoration of pyrin. In healthy subjects, the dephosphorylation step alone does not cause activation of the pyrin inflammasome. In contrast, in FMF patients, the dephosphorylation of serines is sufficient to trigger the activation of the pyrin inflammasome. This suggests that there is a two-level regulation and that the second regulatory mechanism (independent of (de)phosphorylation) is deficient in FMF patients. This deficient mechanism is probably located at the level of the B30.2 domain (exon 10) where most of the pathogenic mutations associated with FMF are located. It is probably the interaction of this domain with the cytoskeleton (microtubules) that is failing, as suggested by the efficacy of colchicine.It is not conclusively known what exactly sets off the attacks, and why overproduction of IL-1 would lead to particular symptoms in particular organs (e.g. joints or the peritoneal cavity). Diagnosis The diagnosis is clinically made on the basis of the history of typical attacks, especially in patients from the ethnic groups in which FMF is more highly prevalent. An acute phase response is present during attacks, with high C-reactive protein levels, an elevated white blood cell count and other markers of inflammation. In patients with a long history of attacks, monitoring the kidney function is of importance in predicting chronic kidney failure.A genetic test is also available to detect mutations in the MEFV gene. Sequencing of exons 2, 3, 5, and 10 of this gene detects an estimated 97% of all known mutations.A specific and highly sensitive test for FMF is the "metaraminol provocative test (MPT)", whereby a single 10 mg infusion of metaraminol is administered to the patient. A positive diagnosis is made if the patient presents with a typical, albeit milder, FMF attack within 48 hours. As MPT is more specific than sensitive, it does not identify all cases of FMF, although a positive MPT can be very useful. Treatment Attacks are self-limiting, and require analgesia and NSAIDs (such as diclofenac). Colchicine, a drug otherwise mainly used in gout, decreases attack frequency in FMF patients. The exact way in which colchicine suppresses attacks is unclear. While this agent is not without side effects (such as abdominal pain and muscle pains), it may markedly improve quality of life in patients. The dosage is typically 1–2 mg a day. Development of amyloidosis is delayed with colchicine treatment. Interferon is being studied as a therapeutic modality. Some advise discontinuation of colchicine before and during pregnancy, but the data are inconsistent, and others feel it is safe to take colchicine during pregnancy.Approximately 5–10% of FMF cases are resistant to colchicine therapy alone. In these cases, adding anakinra to the daily colchicine regimen has been successful. Canakinumab, an anti-interleukin-1-beta monoclonal antibody, has likewise been shown to be effective in controlling and preventing flare-ups in patients with colchicine-resistant FMF and in two additional autoinflammatory recurrent fever syndromes: mevolonate kinase deficiency (hyper-immunoglobulin D syndrome, or HIDS) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Epidemiology FMF affects groups of people originating from around the Mediterranean Sea (hence its name). It is most prominently present in the Armenians, Sephardic Jews, Ashkenazi Jews, Mizrahi Jews, Cypriots, Kurds, Turks and Levantines. History A New York City allergist, Sheppard Siegal, first described the attacks of peritonitis in 1945; he termed this "benign paroxysmal peritonitis", as the disease course was essentially benign. Dr Hobart Reimann, working in the American University in Beirut, described a more complete picture which he termed "periodic disease". French physicians Henry Mamou and Roger Cattan described the complete disease with renal complications in 1952. See also List of cutaneous conditions Urticarial syndromes References External links Proteopedia 2wl1 information about the MEFV gene. GeneReview/NIH/UW entry on Familial Mediterranean Fever Familial Mediterranean Fever (FMF) - US National Institute of Arthritis and Musculoskeletal and Skin Diseases

Apprehension

Apprehension may refer to: Apprehension (understanding), awareness or understanding of something by the mind Arrest by law-enforcement officers Fear Anxiety Apprehension (film), a 1982 film by Lothar Warneke

Abdominal pain

Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a more serious underlying condition such as appendicitis, leaking or ruptured abdominal aortic aneurysm, diverticulitis, or ectopic pregnancy. In a third of cases the exact cause is unclear.Given that a variety of diseases can cause some form of abdominal pain, a systematic approach to the examination of a person and the formulation of a differential diagnosis remains important. Differential diagnosis The most frequent reasons for abdominal pain are gastroenteritis (13%), irritable bowel syndrome (8%), urinary tract problems (5%), inflammation of the stomach (5%) and constipation (5%). In about 30% of cases, the cause is not determined. About 10% of cases have a more serious cause including gallbladder (gallstones or biliary dyskinesia) or pancreas problems (4%), diverticulitis (3%), appendicitis (2%) and cancer (1%). More common in those who are older, ischemic colitis, mesenteric ischemia, and abdominal aortic aneurysms are other serious causes. Acute abdominal pain Acute abdomen can be defined as severe, persistent abdominal pain of sudden onset that is likely to require surgical intervention to treat its cause. The pain may frequently be associated with nausea and vomiting, abdominal distention, fever and signs of shock. One of the most common conditions associated with acute abdominal pain is acute appendicitis. Selected causes Traumatic: blunt or perforating trauma to the stomach, bowel, spleen, liver, or kidney Inflammatory: Infections such as appendicitis, cholecystitis, pancreatitis, pyelonephritis, Peritonitis, pelvic inflammatory disease, hepatitis, mesenteric adenitis, or a subdiaphragmatic abscess Perforation of a peptic ulcer, a diverticulum, or the caecum Complications of inflammatory bowel disease such as Crohns disease or ulcerative colitis Mechanical: Small bowel obstruction secondary to adhesions caused by previous surgeries, intussusception, hernias, benign or malignant neoplasms Large bowel obstruction caused by colorectal cancer, inflammatory bowel disease, volvulus, fecal impaction or hernia Vascular: occlusive intestinal ischemia, usually caused by thromboembolism of the superior mesenteric artery By system A more extensive list includes the following: Gastrointestinal GI tract Inflammatory: gastroenteritis, appendicitis, gastritis, esophagitis, diverticulitis, Crohns disease, ulcerative colitis, microscopic colitis Obstruction: hernia, intussusception, volvulus, post-surgical adhesions, tumors, severe constipation, hemorrhoids Vascular: embolism, thrombosis, hemorrhage, sickle cell disease, abdominal angina, blood vessel compression (such as celiac artery compression syndrome), superior mesenteric artery syndrome, postural orthostatic tachycardia syndrome Digestive: peptic ulcer, lactose intolerance, celiac disease, food allergies, indigestion Glands Bile system Inflammatory: cholecystitis, cholangitis Obstruction: cholelithiasis, tumours Liver Inflammatory: hepatitis, liver abscess Pancreatic Inflammatory: pancreatitis Renal and urological Inflammation: pyelonephritis, bladder infection Obstruction: kidney stones, urolithiasis, urinary retention, tumours Vascular: left renal vein entrapment Gynaecological or obstetric Inflammatory: pelvic inflammatory disease Mechanical: ovarian torsion Endocrinological: menstruation, Mittelschmerz Tumors: endometriosis, fibroids, ovarian cyst, ovarian cancer Pregnancy: ruptured ectopic pregnancy, threatened abortion Abdominal wall muscle strain or trauma muscular infection neurogenic pain: herpes zoster, radiculitis in Lyme disease, abdominal cutaneous nerve entrapment syndrome (ACNES), tabes dorsalis Referred pain from the thorax: pneumonia, pulmonary embolism, ischemic heart disease, pericarditis from the spine: radiculitis from the genitals: testicular torsion Metabolic disturbance uremia, diabetic ketoacidosis, porphyria, C1-esterase inhibitor deficiency, adrenal insufficiency, lead poisoning, black widow spider bite, narcotic withdrawal Blood vessels aortic dissection, abdominal aortic aneurysm Immune system sarcoidosis vasculitis familial Mediterranean fever Idiopathic irritable bowel syndrome (IBS)(affecting up to 20% of the population, IBS is the most common cause of recurrent and intermittent abdominal pain) By location The location of abdominal pain can provide information about what may be causing the pain. The abdomen can be divided into four regions called quadrants. Locations and associated conditions include: Diffuse Peritonitis Vascular: mesenteric ischemia, ischemic colitis, Henoch-Schonlein purpura, sickle cell disease, systemic lupus erythematosus, polyarteritis nodosa Small bowel obstruction Irritable bowel syndrome Metabolic disorders: ketoacidosis, porphyria, familial Mediterranean fever, adrenal crisis Epigastric Heart: myocardial infarction, pericarditis Stomach: gastritis, stomach ulcer, stomach cancer Pancreas: pancreatitis, pancreatic cancer Intestinal: duodenal ulcer, diverticulitis, appendicitis Right upper quadrant Liver: hepatomegaly, fatty liver, hepatitis, liver cancer, abscess Gallbladder and biliary tract: inflammation, gallstones, worm infection, cholangitis Colon: bowel obstruction, functional disorders, gas accumulation, spasm, inflammation, colon cancer Other: pneumonia, Fitz-Hugh-Curtis syndrome Left upper quadrant Splenomegaly Colon: bowel obstruction, functional disorders, gas accumulation, spasm, inflammation, colon cancer Peri-umbilical (the area around the umbilicus, aka the belly button) Appendicitis Pancreatitis Inferior myocardial infarction Peptic ulcer Diabetic ketoacidosis Vascular: aortic dissection, aortic rupture Bowel: mesenteric ischemia, Celiac disease, inflammation, intestinal spasm, functional disorders, small bowel obstruction Lower abdominal pain Diarrhea Colitis Crohns Dysentery Hernia Right lower quadrant Colon: intussusception, bowel obstruction, appendicitis (McBurneys point) Renal: kidney stone (nephrolithiasis), pyelonephritis Pelvic: cystitis, bladder stone, bladder cancer, pelvic inflammatory disease, pelvic pain syndrome Gynecologic: endometriosis, intrauterine pregnancy, ectopic pregnancy, ovarian cyst, ovarian torsion, fibroid (leiomyoma), abscess, ovarian cancer, endometrial cancer Left lower quadrant Bowel: diverticulitis, sigmoid colon volvulus, bowel obstruction, gas accumulation, Toxic megacolon Right low back pain Liver: hepatomegaly Kidney: kidney stone (nephrolithiasis), complicated urinary tract infection Left low back pain Spleen Kidney: kidney stone (nephrolithiasis), complicated urinary tract infection Low back pain kidney pain (kidney stone, kidney cancer, hydronephrosis) Ureteral stone pain Pathophysiology Abdominal pain can be referred to as visceral pain or peritoneal pain. The contents of the abdomen can be divided into the foregut, midgut, and hindgut. The foregut contains the pharynx, lower respiratory tract, portions of the esophagus, stomach, portions of the duodenum (proximal), liver, biliary tract (including the gallbladder and bile ducts), and the pancreas. The midgut contains portions of the duodenum (distal), cecum, appendix, ascending colon, and first half of the transverse colon. The hindgut contains the distal half of the transverse colon, descending colon, sigmoid colon, rectum, and superior anal canal.Each subsection of the gut has an associated visceral afferent nerve that transmits sensory information from the viscera to the spinal cord, traveling with the autonomic sympathetic nerves. The visceral sensory information from the gut traveling to the spinal cord, termed the visceral afferent, is non-specific and overlaps with the somatic afferent nerves, which are very specific. Therefore, visceral afferent information traveling to the spinal cord can present in the distribution of the somatic afferent nerve; this is why appendicitis initially presents with T10 periumbilical pain when it first begins and becomes T12 pain as the abdominal wall peritoneum (which is rich with somatic afferent nerves) is involved. Diagnosis A thorough patient history and physical examination is used to better understand the underlying cause of abdominal pain. The process of gathering a history may include: Identifying more information about the chief complaint by eliciting a history of present illness; i.e. a narrative of the current symptoms such as the onset, location, duration, character, aggravating or relieving factors, and temporal nature of the pain. Identifying other possible factors may aid in the diagnosis of the underlying cause of abdominal pain, such as recent travel, recent contact with other ill individuals, and for females, a thorough gynecologic history. Learning about the patients past medical history, focusing on any prior issues or surgical procedures. Clarifying the patients current medication regimen, including prescriptions, over-the-counter medications, and supplements. Confirming the patients drug and food allergies. Discussing with the patient any family history of disease processes, focusing on conditions that might resemble the patients current presentation. Discussing with the patient any health-related behaviors (e.g. tobacco use, alcohol consumption, drug use, and sexual activity) that might make certain diagnoses more likely. Reviewing the presence of non-abdominal symptoms (e.g., fever, chills, chest pain, shortness of breath, vaginal bleeding) that can further clarify the diagnostic picture. Using Carnetts sign to differentiate between visceral pain and pain originating in the muscles of the abdominal wall.After gathering a thorough history, one should perform a physical exam in order to identify important physical signs that might clarify the diagnosis, including a cardiovascular exam, lung exam, thorough abdominal exam, and for females, a genitourinary exam.Additional investigations that can aid diagnosis include: Blood tests including complete blood count, basic metabolic panel, electrolytes, liver function tests, amylase, lipase, troponin I, and for females, a serum pregnancy test. Urinalysis Imaging including chest and abdominal X-rays ElectrocardiogramIf diagnosis remains unclear after history, examination, and basic investigations as above, then more advanced investigations may reveal a diagnosis. Such tests include: Computed tomography of the abdomen/pelvis Abdominal or pelvic ultrasound Endoscopy and/or colonoscopy Management The management of abdominal pain depends on many factors, including the etiology of the pain. In the emergency department, a person presenting with abdominal pain may initially require IV fluids due to decreased intake secondary to abdominal pain and possible emesis or vomiting. Treatment for abdominal pain includes analgesia, such as non-opioid (ketorolac) and opioid medications (morphine, fentanyl). Choice of analgesia is dependent on the cause of the pain, as ketorolac can worsen some intra-abdominal processes. Patients presenting to the emergency department with abdominal pain may receive a "GI cocktail" that includes an antacid (examples include omeprazole, ranitidine, magnesium hydroxide, and calcium chloride) and lidocaine. After addressing pain, there may be a role for antimicrobial treatment in some cases of abdominal pain. Butylscopolamine (Buscopan) is used to treat cramping abdominal pain with some success. Surgical management for causes of abdominal pain includes but is not limited to cholecystectomy, appendectomy, and exploratory laparotomy. Emergencies Below is a brief overview of abdominal pain emergencies. Epidemiology Abdominal pain is the reason about 3% of adults see their family physician. Rates of emergency department (ED) visits in the United States for abdominal pain increased 18% from 2006 through to 2011. This was the largest increase out of 20 common conditions seen in the ED. The rate of ED use for nausea and vomiting also increased 18%. References == External links ==

Cirrhosis

Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repair and subsequent formation of scar tissue, which over time can replace normal functioning tissue, leading to the impaired liver function of cirrhosis. The disease typically develops slowly over months or years. Early symptoms may include tiredness, weakness, loss of appetite, unexplained weight loss, nausea and vomiting, and discomfort in the right upper quadrant of the abdomen. As the disease worsens, symptoms may include itchiness, swelling in the lower legs, fluid build-up in the abdomen, jaundice, bruising easily, and the development of spider-like blood vessels in the skin. The fluid build-up in the abdomen may become spontaneously infected. More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer.Cirrhosis is most commonly caused by alcoholic liver disease, non-alcoholic steatohepatitis (NASH – the progressive form of non-alcoholic fatty liver disease), heroin abuse, chronic hepatitis B, and chronic hepatitis C. Heavy drinking over a number of years can cause alcoholic liver disease. Liver damage has also been attributed to heroin usage over an extended period of time as well. NASH has a number of causes, including obesity, high blood pressure, abnormal levels of cholesterol, type 2 diabetes, and metabolic syndrome. Less common causes of cirrhosis include autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis that disrupts bile duct function, genetic disorders such as Wilsons disease and hereditary hemochromatosis, and chronic heart failure with liver congestion.Diagnosis is based on blood tests, medical imaging, and liver biopsy.Hepatitis B vaccine can prevent hepatitis B and the development of cirrhosis, but no vaccination against hepatitis C is available. No specific treatment for cirrhosis is known, but many of the underlying causes may be treated by a number of medications that may slow or prevent worsening of the condition. Avoiding alcohol is recommended in all cases. Hepatitis B and C may be treatable with antiviral medications. Autoimmune hepatitis may be treated with steroid medications. Ursodiol may be useful if the disease is due to blockage of the bile duct. Other medications may be useful for complications such as abdominal or leg swelling, hepatic encephalopathy, and dilated esophageal veins. If cirrhosis leads to liver failure, a liver transplant may be an option.Cirrhosis affected about 2.8 million people and resulted in 1.3 million deaths in 2015. Of these deaths, alcohol caused 348,000, hepatitis C caused 326,000, and hepatitis B caused 371,000. In the United States, more men die of cirrhosis than women. The first known description of the condition is by Hippocrates in the fifth century BCE. The term "cirrhosis" was derived in 1819 from the Greek word "kirrhos," which describes the yellowish color of a diseased liver. Signs and symptoms Cirrhosis can take quite a long time to develop, and symptoms may be slow to emerge. Some early symptoms include tiredness, weakness, loss of appetite, weight loss, and nausea. People may also feel discomfort in the right upper abdomen around the liver.As cirrhosis progresses, symptoms can include neurological changes. This can consist of cognitive impairments, confusion, memory loss, sleep disorders, and personality changes.Worsening cirrhosis can cause a build-up of fluid in different parts of the body such as the legs (edema) and abdomen (ascites). Other signs of advancing disease include itchy skin, bruising easily, dark urine, and yellowing of the skin. Liver dysfunction These features are a direct consequence of liver cells not functioning: Spider angiomata or spider nevi happen when there is dilatation of vasculature beneath the skin surface. There is a central, red spot with reddish extensions that radiate outward. This creates a visual effect that resembles a spider. It occurs in about one-third of cases. The likely cause is an increase in estrogen. Cirrhosis causes a rise of estrogen due to increased conversion of androgens into estrogen. Palmar erythema presents as reddish palms below the thumb and little finger. This is seen in about 23% of cirrhosis cases. This is a result of increased estrogen. Gynecomastia, or the increase of breast size in men, is caused by increased estradiol (a potent type of estrogen). This can occur in up to two-thirds of cases. Hypogonadism signifies a decreased functionality of the gonads. This can result in impotence, infertility, loss of sexual drive, and testicular atrophy. A swollen scrotum may also be evident. Liver size can be enlarged, normal, or shrunken in people with cirrhosis. As the disease progresses, the liver will typically shrink due to the result of scarring. Jaundice is the yellowing of the skin. It can additionally cause yellowing of mucous membranes notably of the white of the eyes. This phenomenon is due to increased levels of bilirubin, which may also cause the urine to be dark-colored. Portal hypertension Liver cirrhosis makes it hard for blood to flow in the portal venous system. This resistance creates a backup of blood and increases pressure. This results in portal hypertension. Effects of portal hypertension include: Ascites is a build-up of fluid in the peritoneal cavity in the abdomen An enlarged spleen in 35 to 50% of cases Esophageal varices and gastric varices result from collateral circulation in the esophagus and stomach (a process called portacaval anastomosis). When the blood vessels in this circulation become enlarged, they are called varices. Varices are more likely to rupture at this point. Variceal rupture often leads to severe bleeding, which can be fatal. Caput medusae are dilated paraumbilical collateral veins due to portal hypertension. Blood from the portal venous system may be forced through the paraumbilical veins and ultimately to the abdominal wall veins. The created pattern resembles the head of Medusa, hence the name. Cruveilhier-Baumgarten bruit is bruit in the epigastric region (on examination by stethoscope). It is due to extra connections forming between the portal system and the paraumbilical veins. Other nonspecific signs Some signs that may be present include changes in the nails (such as Muehrckes lines, Terrys nails, and nail clubbing). Additional changes may be seen in the hands (Dupuytrens contracture) as well as the skin/bones (hypertrophic osteoarthropathy). Advanced disease As the disease progresses, complications may develop. In some people, these may be the first signs of the disease. Bruising and bleeding can result from decreased production of clotting factors Hepatic encephalopathy (HE) occurs when ammonia and related substances build up in the blood. This build-up affects brain function when they are not cleared from the blood by the liver. Symptoms can include unresponsiveness, forgetfulness, trouble concentrating, changes in sleep habits, or psychosis. One classic physical examination finding is asterixis. This is the asynchronous flapping of outstretched, dorsiflexed hands. Fetor hepaticus is a musty breath odor resulting from increased dimethyl sulfide and is a feature of HE. Sensitivity to medication can be caused by decreased metabolism of the active compounds Acute kidney injury (particularly hepatorenal syndrome) Cachexia associated with muscle wasting and weakness Causes Cirrhosis has many possible causes, and more than one cause may be present. History taking is of importance in trying to determine the most likely cause. Globally, 57% of cirrhosis is attributable to either hepatitis B (30%) or hepatitis C (27%). Alcohol use disorder is another major cause, accounting for about 20-40% of the cases. Common causes Alcoholic liver disease (ALD, or alcoholic cirrhosis) develops for 10–20% of individuals who drink heavily for a decade or more. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates. This injury happens through the formation of acetaldehyde from alcohol. Acetaldehyde is reactive and leads to the accumulation of other reactive products in the liver. People with ALD may also have concurrent alcoholic hepatitis. Associated symptoms are fever, hepatomegaly, jaundice, and anorexia. AST and ALT blood levels are both elevated, but at less than 300 IU/liter, with an AST:ALT ratio > 2.0, a value rarely seen in other liver diseases. In the United States, 40% of cirrhosis-related deaths are due to alcohol. In non-alcoholic fatty liver disease (NAFLD), fat builds up in the liver and eventually causes scar tissue. This type of disorder can be caused by obesity, diabetes, malnutrition, coronary artery disease, and steroids. Though similar in signs to alcoholic liver disease, no history of notable alcohol use is found. Blood tests and medical imaging are used to diagnose NAFLD and NASH, and sometimes a liver biopsy is needed. Chronic hepatitis C, an infection with the hepatitis C virus, causes inflammation of the liver and a variable grade of damage to the organ. Over several decades, this inflammation and damage can lead to cirrhosis. Among patients with chronic hepatitis C, 20–30% develop cirrhosis. Cirrhosis caused by hepatitis C and alcoholic liver disease are the most common reasons for liver transplant. Both hepatitis C and hepatitis B-related cirrhosis can also be attributed with heroin addiction. Chronic hepatitis B causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is dependent on the presence of hepatitis B and accelerates cirrhosis in co-infection. Less common causes In primary biliary cholangitis (previously known as primary biliary cirrhosis), the bile ducts become damaged by an autoimmune process. This leads to liver damage. Patients may have no symptoms. While other people could present with fatigue, pruritus, or skin hyperpigmentation. The liver is typically enlarged which is referred to as hepatomegaly. Rises in alkaline phosphatase, cholesterol, and bilirubin levels occur. Patients are usually positive for anti-mitochondrial antibodies. Primary sclerosing cholangitis is a disorder of the bile ducts that presents with pruritus, steatorrhea, fat-soluble vitamin deficiencies, and metabolic bone disease. A strong association with inflammatory bowel disease is seen, especially ulcerative colitis. Autoimmune hepatitis is caused by an attack of the liver by lymphocytes. This causes inflammation and eventually scarring as well as cirrhosis. Findings include elevations in serum globulins, especially gamma globulins. Hereditary hemochromatosis usually presents with skin hyperpigmentation, diabetes mellitus, pseudogout, or cardiomyopathy, All of these are due to signs of iron overload. Family history of cirrhosis is common as well. Wilsons disease is an autosomal recessive disorder characterized by low ceruloplasmin in the blood and increased copper of the liver. Copper in the urine is also elevated. Patients may also have Kayser-Fleischer rings in the cornea and altered mental status. Indian childhood cirrhosis is a form of neonatal cholestasis characterized by deposition of copper in the liver Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder of low levels of the enzyme alpha-1 antitrypsin Cardiac cirrhosis is due to chronic right-sided heart failure, which leads to liver congestion Galactosemia Glycogen storage disease type IV Cystic fibrosis Hepatotoxic drugs or toxins, such as acetaminophen (paracetamol), methotrexate, or amiodarone Pathophysiology The liver plays a vital role in the synthesis of proteins (for example, albumin, clotting factors and complement), detoxification, and storage (for example, of vitamin A and glycogen). In addition, it participates in the metabolism of lipids and carbohydrates.Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are fully reversible.The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal tissue. This scar tissue blocks the portal flow of blood through the organ, raising the blood pressure and disturbing normal function. Research has shown the pivotal role of the stellate cell, that normally stores vitamin A, in the development of cirrhosis. Damage to the liver tissue from inflammation leads to the activation of stellate cells, which increases fibrosis through the production of myofibroblasts, and obstructs hepatic blood flow. In addition, stellate cells secrete TGF beta 1, which leads to a fibrotic response and proliferation of connective tissue. TGF-β1 have been implicated in the process of activating hepatic stellate cells (HSCs) with the magnitude of fibrosis being in proportion to increase in TGF β levels. ACTA2 is associated with TGF β pathway that enhances contractile properties of HSCs leading to fibrosis. Furthermore, it secretes TIMP1 and TIMP2, naturally occurring inhibitors of matrix metalloproteinases, which prevents them from breaking down the fibrotic material in the extracellular matrix.As this cascade of processes continues, fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, and enlarged, resulting in its retention of platelets, which are needed for normal blood clotting. Portal hypertension is responsible for the most severe complications of cirrhosis. Diagnosis The diagnosis of cirrhosis in an individual is based on multiple factors. Cirrhosis may be suspected from laboratory findings, physical exam, and patient history. Imaging is generally obtained to evaluate the liver. A liver biopsy will confirm the diagnosis; however, is generally not required. Imaging Ultrasound is routinely used in the evaluation of cirrhosis. It may show a small and shrunken liver in advanced disease. On ultrasound, there is increased echogenicity with irregular appearing areas. Other suggestive findings are an enlarged caudate lobe, widening of the fissures and enlargement of the spleen. An enlarged spleen, which normally measures less than 11–12 cm in adults, may suggest underlying portal hypertension. Ultrasound may also screen for hepatocellular carcinoma and portal hypertension. This is done by assessing flow in the hepatic vein. An increased portal vein pulsatility may be seen. However, this may be a sign of elevated right atrial pressure. Portal vein pulsatility are usually measured by an pulsatility indices (PI). A number above a certain values indicates cirrhosis (see table below). Other scans include CT of the abdomen and MRI. A CT scan is non-invasive and may be helpful in the diagnosis. Compared to the ultrasound, CT scans tend to be more expensive. MRI provides excellent evaluation; however, is a high expense. Cirrhosis is also diagnosable through a variety of new elastography techniques. When a liver becomes cirrhotic it will generally become stiffer. Determining the stiffness through imaging can determine the location and severity of disease. Techniques include transient elastography, acoustic radiation force impulse imaging, supersonic shear imaging and magnetic resonance elastography. Transient elastography and magnetic resonance elastography can help identify the stage of fibrosis. Compared to a biopsy, elastography can sample a much larger area and is painless. It shows a reasonable correlation with the severity of cirrhosis. Other modalities have been introduced which are incorporated into ultrasonagraphy systems. These include 2-dimensional shear wave elastography and point shear wave elastography which uses acoustic radiation force impulse imaging.Rarely are diseases of the bile ducts, such as primary sclerosing cholangitis, causes of cirrhosis. Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas) may aid in the diagnosis. Lab findings The best predictors of cirrhosis are ascites, platelet count < 160,000/mm3, spider angiomata, and a Bonacini cirrhosis discriminant score greater than 7 (as the sum of scores for platelet count, ALT/AST ratio and INR as per table). These findings are typical in cirrhosis: Thrombocytopenia, typically multifactorial, is due to alcoholic marrow suppression, sepsis, lack of folate, platelet sequestering in the spleen, and decreased thrombopoietin. However, this rarely results in a platelet count < 50 000/mL. Aminotransferases AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferase levels do not preclude cirrhosis. Alkaline phosphatase – slightly elevated but less than 2–3 times the upper limit of normal. Gamma-glutamyl transferase – correlates with AP levels. Typically much higher in chronic liver disease from alcohol. Bilirubin levels are normal when compensated, but may elevate as cirrhosis progresses. Albumin levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver. Prothrombin time increases, since the liver synthesizes clotting factors. Globulins increase due to shunting of bacterial antigens away from the liver to lymphoid tissue. Serum sodium levels fall(hyponatremia) due to inability to excrete free water resulting from high levels of ADH and aldosterone. Leukopenia and neutropenia are due to splenomegaly with splenic margination. Coagulation defects occur, as the liver produces most of the coagulation factors, thus coagulopathy correlates with worsening liver disease. Glucagon is increased in cirrhosis. Vasoactive intestinal peptide is increased as blood is shunted into the intestinal system because of portal hypertension. Vasodilators are increased (such as nitric oxide and carbon monoxide) reducing afterload with compensatory increase in cardiac output, mixed venous oxygen saturation. Renin is increased (as well as sodium retention in kidneys) secondary to a fall in systemic vascular resistance.FibroTest is a biomarker for fibrosis that may be used instead of a biopsy.Other laboratory studies performed in newly diagnosed cirrhosis may include: Serology for hepatitis viruses, autoantibodies (ANA, antismooth muscle, antimitochondria, anti-LKM) Ferritin and transferrin saturation: markers of iron overload as in hemochromatosis, copper and ceruloplasmin: markers of copper overload as in Wilsons disease Immunoglobulin levels (IgG, IgM, IgA) – these immunoglobins are nonspecific, but may help in distinguishing various causes. Cholesterol and glucose Alpha 1-antitrypsinMarkers of inflammation and immune cell activation are typically elevated in cirrhotic patients, especially in the decompensated disease stage: C-reactive protein (CRP) Procalcitonin (PCT) Presepsin soluble CD14 soluble CD163 soluble CD206 (mannose receptor) soluble TREM-1A recent study identified15 microbial biomarkers from the gut microbiota. These could potentially be used to discriminate patients with liver cirrhosis from healthy individuals. Pathology The gold standard for diagnosis of cirrhosis is a liver biopsy. This is usually carried out as a fine-needle approach, through the skin (percutaneous), or internal jugular vein (transjugular). Endoscopic ultrasound-guided liver biopsy (EUS), using the percutaneous or transjugular route, has become a good alternative to use. EUS can target liver areas that are widely separated, and can deliver bi-lobar biopsies. A biopsy is not necessary if the clinical, laboratory, and radiologic data suggest cirrhosis. Furthermore, a small but significant risk of complications is associated with liver biopsy, and cirrhosis itself predisposes for complications caused by liver biopsy.Once the biopsy is obtained, a pathologist will study the sample. Cirrhosis is defined by its features on microscopy: (1) the presence of regenerating nodules of hepatocytes and (2) the presence of fibrosis, or the deposition of connective tissue between these nodules. The pattern of fibrosis seen can depend on the underlying insult that led to cirrhosis. Fibrosis can also proliferate even if the underlying process that caused it has resolved or ceased. The fibrosis in cirrhosis can lead to destruction of other normal tissues in the liver: including the sinusoids, the space of Disse, and other vascular structures, which leads to altered resistance to blood flow in the liver, and portal hypertension. As cirrhosis can be caused by many different entities which injure the liver in different ways, cause-specific abnormalities may be seen. For example, in chronic hepatitis B, there is infiltration of the liver parenchyma with lymphocytes. In congestive hepatopathy there are erythrocytes and a greater amount of fibrosis in the tissue surrounding the hepatic veins. In primary biliary cholangitis, there is fibrosis around the bile duct, the presence of granulomas and pooling of bile. Lastly in alcoholic cirrhosis, there is infiltration of the liver with neutrophils.Macroscopically, the liver is initially enlarged, but with the progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm, and if associated with steatosis the color is yellow. Depending on the size of the nodules, there are three macroscopic types: micronodular, macronodular, and mixed cirrhosis. In the micronodular form (Laennecs cirrhosis or portal cirrhosis), regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. Mixed cirrhosis consists of nodules of different sizes. Grading The severity of cirrhosis is commonly classified with the Child–Pugh score (also known as the Child–Pugh–Turcotte score). This system was devised in 1964 by Child and Turcotte, and modified in 1973 by Pugh and others. It was first established to determine who would benefit from elective surgery for portal decompression. This scoring system uses multiple lab values including bilirubin, albumin, and INR. The presence of ascites and severity of encephalopathy is also included in the scoring. Patients are classified into class A, B, or C. Class A has a favorable prognosis while class C is at high risk of death. The Child-Pugh score is a validated predictor of mortality after a major surgery. For example, Child class A patients have a 10% mortality rate and Child class B patients have a 30% mortality rate while Child class C patients have a 70 to 80% mortality rate after abdominal surgery. Elective surgery is usually reserved for those in Child class A patients. There is an increased risk for child class B individuals and they may require medical optimization. Overall, it is not recommended for Child class C patients to undergo elective surgery.In the past, the Child-Pugh classification was used to determine patients who were candidates for a liver transplant. Child-Pugh class B is usually an indication for evaluation for transplant. However, there were many issues when applying this score to liver transplant eligibility. Thus, the MELD score was created. The Model for End-Stage Liver Disease (MELD) score was later developed and approved in 2002. It was approved by the United Network for Organ Sharing (UNOS) as a way to determine the allocation of liver transplants to awaiting people in the United States. It is also used as a validated survival predictor of cirrhosis, alcoholic hepatitis, acute liver failure, and acute hepatitis. The variables included bilirubin, INR, creatinine, and dialysis frequency. In 2016, sodium was added to the variables and the score is often referred to as MELD-Na.MELD-Plus is a further risk score to assess severity of chronic liver disease. It was developed in 2017 as a result of a collaboration between Massachusetts General Hospital and IBM. Nine variables were identified as effective predictors for 90-day mortality after a discharge from a cirrhosis-related hospital admission. The variables include all Model for End-Stage Liver Disease (MELD)s components, as well as sodium, albumin, total cholesterol, white blood cell count, age, and length of stay.The hepatic venous pressure gradient (difference in venous pressure between incoming and outgoing blood to the liver) also determines the severity of cirrhosis, although it is hard to measure. A value of 16 mm or more means a greatly increased risk of death. Prevention Key prevention strategies for cirrhosis are population-wide interventions to reduce alcohol intake (through pricing strategies, public health campaigns, and personal counseling), programs to reduce the transmission of viral hepatitis, and screening of relatives of people with hereditary liver diseases.Little is known about factors affecting cirrhosis risk and progression. However, many studies have provided increasing evidence for the protective effects of coffee consumption against the progression of liver disease. These effects are more noticeable in liver disease that is associated with alcohol use disorder. Coffee has antioxidant and antifibrotic effects. Caffeine may not be the important component; polyphenols may be more important. Drinking two or more cups of coffee a day is associated with improvements in the liver enzymes ALT, AST, and GGT. Even in those with liver disease, coffee consumption can lower fibrosis and cirrhosis. Treatment Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. A recommended diet consists of high-protein, high-fiber diet plus supplementation with branched-chain amino acids. Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease the risk of constipation. Carvedilol increases survival benefit for patients with cirrhosis and portal hypertension.Alcoholic cirrhosis caused by alcohol use disorder is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis.Cirrhosis caused by Wilsons disease is treated by removing the copper which builds up in organs. This is carried out using chelation therapy such as penicillamine. When the cause is an iron overload, iron is removed using a chelation agent such as deferoxamine or by bloodletting.As of 2021, there are recent studies studying drugs to prevent cirrhosis caused by non-alcoholic fatty liver disease (NAFLD or NASH). A drug called semaglutide was shown to provide greater NASH resolution versus placebo. No improvement in fibrosis was observed. A combination of cilofexor/firsocostat was studied in patients with bridging fibrosis and cirrhosis. It was observed to have led to improvements in NASH activity with a potential antifibrotic effect. Lanifibranor is also shown to prevent worsening fibrosis. Preventing further liver damage Regardless of the underlying cause of cirrhosis, consumption of alcohol and other potentially damaging substances are discouraged. There is no evidence that supports the avoidance or dose reduction of paracetamol in people with compensated cirrhosis; it is thus considered a safe analgesic for said individuals.Vaccination of susceptible patients should be considered for hepatitis A and hepatitis B. Treating the cause of cirrhosis prevents further damage; for example, giving oral antivirals such as entecavir and tenofovir where cirrhosis is due to hepatitis B prevents progression of cirrhosis. Similarly, control of weight and diabetes prevents deterioration in cirrhosis due to non-alcoholic fatty liver disease.Avoid drugs that could further harm the liver. These include several drugs such as anti-depressants, certain antibiotics, and NSAIDs (like ibuprofen). These agents are hepatotoxic as they are metabolized by the liver. If medication that harms the liver is still recommended by your doctor, the dosage can be adjusted. Lifestyle According to a 2018 systematic review based on studies that implemented 8 to 14 week-long exercise programs, there is currently insufficient scientific evidence regarding either the beneficial or harmful effects of physical exercise in people with cirrhosis on all-cause mortality, morbidity (including both serious and non-serious adverse events), health-related quality of life, exercise capacity and anthropomorphic measures. These conclusions were based on low to very low quality research, which imposes the need to develop further research with higher quality, especially to evaluate its effects on clinical outcomes. Transplantation If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary. Survival from liver transplantation has been improving over the 1990s, and the five-year survival rate is now around 80%. The survival rate depends largely on the severity of disease and other medical risk factors in the recipient. In the United States, the MELD score is used to prioritize patients for transplantation. Transplantation necessitates the use of immune suppressants (ciclosporin or tacrolimus). Decompensated cirrhosis Manifestations of decompensation in cirrhosis include gastrointestinal bleeding, hepatic encephalopathy, jaundice or ascites. In patients with previously stable cirrhosis, decompensation may occur due to various causes, such as constipation, infection (of any source), increased alcohol intake, medication, bleeding from esophageal varices or dehydration. It may take the form of any of the complications of cirrhosis listed below. People with decompensated cirrhosis generally require admission to a hospital, with close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical treatment – often with diuretics, antibiotics, laxatives or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline. Administration of saline is avoided, as it would add to the already high total body sodium content that typically occurs in cirrhosis. Life expectancy without liver transplant is low, at most 3 years. Palliative care Palliative care is specialized medical care that focuses on providing patients with relief from the symptoms, pain, and stress of a serious illness, such as cirrhosis. The goal of palliative care is to improve quality of life for both the patient and the patients family and it is appropriate at any stage and for any type of cirrhosis.Especially in the later stages, people with cirrhosis experience significant symptoms such as abdominal swelling, itching, leg edema, and chronic abdominal pain which would be amenable for treatment through palliative care. Because the disease is not curable without a transplant, palliative care can also help with discussions regarding the persons wishes concerning health care power of attorney, do not resuscitate decisions and life support, and potentially hospice. Despite proven benefit, people with cirrhosis are rarely referred to palliative care. Immunity Cirrhosis is known to cause immune dysfunction in numerous ways. It impedes the immune system from working normally. Bleeding and blood clot risk Cirrhosis can increase the risk of bleeding. The liver produces various proteins in the coagulation cascade (coagulation factors II, VII, IX, X, V, and VI). When damaged, the liver is impaired in its production of these proteins. This will ultimately increase bleeding as clotting factors are diminished. Clotting function is estimated by lab values, mainly platelet count, prothrombin time (PT), and international normalized ratio (INR). The American Gastroenterological Association (AGA) provided recommendations in 2021 in regards to coagulopathy management of cirrhotic patients in certain scenarios. The AGA does not recommend for extensive pre-procedural testing, including repeated measurements of PT/INR or platelet count before patients with stable cirrhosis undergo common gastrointestinal procedures. Nor do they suggest the routine use of blood products, such as platelets, for bleeding prevention. Cirrhosis is stable when there are no changes in baseline abnormalities of coagulation lab values. For patients with stable cirrhosis and low platelet count undergoing common low-risk procedures, the AGA does not recommend the routine use of thrombopoietin receptor agonists for bleeding prevention. In hospitalized patients who meet standard guidelines for clot prevention, the AGA suggests standard prevention. The AGA does not recommend in routine screening for portal vein thrombosis. If there is a portal vein thrombosis, the AGA suggests treatment by anticoagulation. In the case of cirrhosis with atrial fibrillation, the AGA recommends using anticoagulation over no anticoagulation. Complications Ascites Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). Diuretics may be necessary to suppress ascites. Diuretic options for inpatient treatment include aldosterone antagonists (spironolactone) and loop diuretics. Aldosterone antagonists are preferred for people who can take oral medications and are not in need of an urgent volume reduction. Loop diuretics can be added as additional therapy.Where salt restriction and the use of diuretics are ineffective then paracentesis may be the preferred option. This procedure requires the insertion of a plastic tube into the peritoneal cavity. Human serum albumin solution is usually given to prevent complications from the rapid volume reduction. In addition to being more rapid than diuretics, 4–5 liters of paracentesis is more successful in comparison to diuretic therapy. Esophageal and gastric variceal bleeding For portal hypertension, nonselective beta blockers such as propranolol or nadolol are commonly used to lower blood pressure over the portal system. In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting (TIPS) is occasionally indicated to relieve pressure on the portal vein. As this shunting can worsen hepatic encephalopathy, it is reserved for those patients at low risk of encephalopathy. TIPS is generally regarded only as a bridge to liver transplantation or as a palliative measure. Balloon-occluded retrograde transvenous obliteration can be used to treat gastric variceal bleeding.Gastroscopy (endoscopic examination of the esophagus, stomach, and duodenum) is performed in cases of established cirrhosis. If esophageal varices are found, prophylactic local therapy may be applied such as sclerotherapy or banding, and beta blockers may be used. Hepatic encephalopathy Hepatic encephalopathy is a potential complication of cirrhosis. It may lead to functional neurological impairment ranging from mild confusion to coma. Goal of treatment is reducing ammonia. This can can achieved by administering lactulose or lactitol to increase potassium. Hydration and nutritional support is also provided. Protein uptake is encouraged. The underlying cause may also need to be identified and treated. Causes include alcohol use, excess protein, gastrointestinal bleeding, infection, constipation, and vomiting/diarrhea. Drugs like benzodiazepines, diuretics, or narcotics can also precipitate hepatic encephalopathy. A low protein diet is recommended with gastrointestinal bleeding. Rifaximin is administered if mental state does not improve in 48 hours. Antibiotic treatment may need to be continued for at least 3 months. The grading or severity of hepatic encephalopathy is determined by mental status. Hepatorenal syndrome Hepatorenal syndrome is a serious complication of end-stage cirrhosis when kidney damage is also involved. Spontaneous bacterial peritonitis People with ascites due to cirrhosis are at risk of spontaneous bacterial peritonitis. Portal hypertensive gastropathy Portal hypertensive gastropathy refers to changes in the mucosa of the stomach in people with portal hypertension, and is associated with cirrhosis severity. Infection Cirrhosis can cause immune system dysfunction, leading to infection. Signs and symptoms of infection may be nonspecific and are more difficult to recognize (for example, worsening encephalopathy but no fever). Moreover, infections in cirrhosis are major triggers for other complications (ascites, variceal bleading, hepatic enecphalopathy, organ failures, death). Hepatocellular carcinoma Hepatocellular carcinoma is the most common primary liver cancer, and the most common cause of death in people with cirrhosis. Screening using an MRI scan can detect this cancer and is often carried out for early signs which has been shown to improve outcomes. Epidemiology Each year, approximately one million deaths are due to complications of cirrhosis, making cirrhosis the 11th most common cause of death globally. Cirrhosis and chronic liver disease were the tenth leading cause of death for men and the twelfth for women in the United States in 2001, killing about 27,000 people each year.The cause of cirrhosis can vary; alcohol and non-alcoholic fatty liver disease are main causes in western and industrialized countries, whereas viral hepatitis is the predominant cause in low and middle-income countries. Cirrhosis is more common in men than in women. The cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high. Globally, age-standardized disability-adjusted life year (DALY) rates have decreased from 1990 to 2017, with the values going from 656.4 years per 100,000 people to 510.7 years per 100,000 people. In males DALY rates have decreased from 903.1 years per 100,000 population in 1990, to 719.3 years per 100,000 population in 2017; in females the DALY rates have decreased from 415.5 years per 100,000 population in 1990, to 307.6 years per 100,000 population in 2017. However, globally the total number of DALYs have increased by 10.9 million from 1990 to 2017, reaching the value of 41.4 million DALYs. Etymology The word "cirrhosis" is a neologism derived from Greek: κίρρωσις; kirrhos κιρρός, meaning "yellowish, tawny" (the orange-yellow colour of the diseased liver) and the suffix -osis, i.e. "condition" in medical terminology. While the clinical entity was known before, René Laennec gave it this name in an 1819 paper. See also References External links Cirrhosis of the Liver at the National Digestive Diseases Information Clearinghouse (NDDIC). NIH Publication No. 04-1134, December 2003. "Cirrhosis". MedlinePlus. U.S. National Library of Medicine.

Ventricular tachycardia

Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period of time are referred to as an electrical storm. Short periods may occur without symptoms, or present with lightheadedness, palpitations, or chest pain. Ventricular tachycardia may result in ventricular fibrillation (VF) and turn into cardiac arrest. This conversion of the VT into VF is called the degeneration of the VT. It is found initially in about 7% of people in cardiac arrest.Ventricular tachycardia can occur due to coronary heart disease, aortic stenosis, cardiomyopathy, electrolyte problems, or a heart attack. Diagnosis is by an electrocardiogram (ECG) showing a rate of greater than 120 beats per minute and at least three wide QRS complexes in a row. It is classified as non-sustained versus sustained based on whether it lasts less than or more than 30 seconds. The term ventricular arrhythmia refers to the group of abnormal cardiac rhythms originating from the ventricle, which includes ventricular tachycardia, ventricular fibrillation, and torsades de pointes.In those who have normal blood pressure and strong pulse, the antiarrhythmic medication procainamide may be used. Otherwise, immediate cardioversion is recommended, preferably with a biphasic DC shock of 200 joules. In those in cardiac arrest due to ventricular tachycardia, cardiopulmonary resuscitation (CPR) and defibrillation is recommended. Biphasic defibrillation may be better than monophasic. While waiting for a defibrillator, a precordial thump may be attempted (However reserved to those who have the prior experience of doing so) in those on a heart monitor who are seen going into an unstable ventricular tachycardia. In those with cardiac arrest due to ventricular tachycardia, survival is about 45%. An implantable cardiac defibrillator or medications such as calcium channel blockers or amiodarone may be used to prevent recurrence. Signs and symptoms While a few seconds may not result in problems, longer periods are dangerous. Short periods may occur without symptoms or present with lightheadedness, palpitations, or chest pain. Ventricular tachycardia may turn into ventricular fibrillation and can result in cardiac arrest. Cause Ventricular tachycardia can occur due to coronary heart disease, aortic stenosis, cardiomyopathy, electrolyte problems (e.g., low blood levels of magnesium or potassium), inherited channelopathies (e.g., long-QT syndrome), catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, alcohol withdrawal syndrome (typically following atrial fibrillation), or a myocardial infarction. Pathophysiology The morphology of the tachycardia depends on its cause and the origin of the re-entry electrical circuit in the heart.In monomorphic ventricular tachycardia, the shape of each heart beat on the ECG looks the same because the impulse is either being generated from increased automaticity of a single point in either the left or the right ventricle, or due to a reentry circuit within the ventricle. The most common cause of monomorphic ventricular tachycardia is scarring of the heart muscle from a previous myocardial infarction (heart attack). This scar cannot conduct electrical activity, so there is a potential circuit around the scar that results in the tachycardia. This is similar to the re-entrant circuits that are the cause of atrial flutter and the re-entrant forms of supraventricular tachycardia. Other rarer congenital causes of monomorphic VT include right ventricular dysplasia, and right and left ventricular outflow tract VT.Polymorphic ventricular tachycardia, on the other hand, is most commonly caused by abnormalities of ventricular muscle repolarization. The predisposition to this problem usually manifests on the ECG as a prolongation of the QT interval. QT prolongation may be congenital or acquired. Congenital problems include long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Acquired problems are usually related to drug toxicity or electrolyte abnormalities, but can occur as a result of myocardial ischemia. Class III anti-arrhythmic drugs such as sotalol and amiodarone prolong the QT interval and may in some circumstances be pro-arrhythmic. Other relatively common drugs including some antibiotics and antihistamines may also be a danger, in particular in combination with one another. Problems with blood levels of potassium, magnesium and calcium may also contribute. High-dose magnesium is often used as an antidote in cardiac arrest protocols. Diagnosis The diagnosis of ventricular tachycardia is made based on the rhythm seen on either a 12-lead ECG or a telemetry rhythm strip. It may be very difficult to differentiate between ventricular tachycardia and a wide-complex supraventricular tachycardia in some cases. In particular, supraventricular tachycardias with aberrant conduction from a pre-existing bundle branch block are commonly misdiagnosed as ventricular tachycardia. Other rarer phenomena include Ashman beats and antidromic atrioventricular re-entry tachycardias.Various diagnostic criteria have been developed to determine whether a wide complex tachycardia is ventricular tachycardia or a more benign rhythm. In addition to these diagnostic criteria, if the individual has a history of a myocardial infarction, congestive heart failure, or recent angina, the wide complex tachycardia is much more likely to be ventricular tachycardia.The proper diagnosis is important, as the misdiagnosis of supraventricular tachycardia when ventricular tachycardia is present is associated with worse prognosis. This is particularly true if calcium channel blockers, such as verapamil, are used to attempt to terminate a presumed supraventricular tachycardia. Therefore, it is wisest to assume that all wide complex tachycardia is VT until proven otherwise.ECG features of Ventricular Tachycardia in addition to the increased Heart rate are: i) A wide QRS Complex ( Because the ectopics for the generation of the cardiac impulse originates in the Ventricular Myocyte and propagated via the intermyocyte conduction, which is a delayed conduction) ii) A Josephsons sign where there is the notch in the downsloping of the S wave near its nadir.(Considered very specific for the VT). iii) Capture beats (Normal QRS complex in between when the Heart pick up the sinus rhythm from the impulses generated by the SA node), fusion beats ( due to the fusion of the Abnormal and the Normal QRS complexes) which has a unique morphology . iv) Positive or negative concordance. v) Extreme Axis deviation or NORTH WEST axis . ( Axis between -90 to +180 degrees) Classification Ventricular tachycardia can be classified based on its morphology: Monomorphic ventricular tachycardia means that the appearance of all the beats match each other in each lead of a surface electrocardiogram (ECG). Scar-related monomorphic ventricular tachycardia is the most common type and a frequent cause of death in patients having survived a heart attack, especially if they have weak heart muscle. Right ventricular outflow tract (RVOT) tachycardia is a type of monomorphic ventricular tachycardia originating in the right ventricular outflow tract. RVOT morphology refers to the characteristic pattern of this type of tachycardia on an ECG. The source of the re-entry circuit can be identified by evaluating the morphology of the QRS complex in the V1 lead of a surface ECG. If the R wave is dominant (consistent with a right bundle branch block morphology), this indicates the origin of the VT is the left ventricle. Conversely, if the S wave is dominant (consistent with a left bundle branch block morphology, this is consistent with VT originating from the right ventricle or interventricular septum. Polymorphic ventricular tachycardia, on the other hand, has beat-to-beat variations in morphology. This may appear as a cyclical progressive change in cardiac axis, previously referred to by its French name torsades de pointes ("twisting of the spikes"). However, at the current time, the term torsades de pointes is reserved for polymorphic VT occurring in the context of a prolonged resting QT interval.Another way to classify ventricular tachycardias is the duration of the episodes: Three or more beats in a row on an ECG that originate from the ventricle at a rate of more than 120 beats per minute constitute a ventricular tachycardia. If the fast rhythm self-terminates within 30 seconds, it is considered a non-sustained ventricular tachycardia. If the rhythm lasts more than 30 seconds, it is known as a sustained ventricular tachycardia (even if it terminates on its own after 30 seconds).A third way to classify ventricular tachycardia is on the basis of its symptoms: Pulseless VT is associated with no effective cardiac output, hence, no effective pulse, and is a cause of cardiac arrest (see also: pulseless electrical activity [PEA]). In this circumstance, it is best treated the same way as ventricular fibrillation (VF), and is recognized as one of the shockable rhythms on the cardiac arrest protocol. Some VT is associated with reasonable cardiac output and may even be asymptomatic. The heart usually tolerates this rhythm poorly in the medium to long term, and patients may certainly deteriorate to pulseless VT or to VF.Occasionally in ventricular tachycardia, supraventricular impulses are conducted to the ventricles, generating QRS complexes with normal or aberrant supraventricular morphology (ventricular capture). Or, those impulses can be merged with complexes that are originated in the ventricle and produce a summation pattern (fusion complexes).Less common is ventricular tachycardia that occurs in individuals with structurally normal hearts. This is known as idiopathic ventricular tachycardia and in the monomorphic form coincides with little or no increased risk of sudden cardiac death. In general, idiopathic ventricular tachycardia occurs in younger individuals diagnosed with VT. While the causes of idiopathic VT are not known, in general it is presumed to be congenital, and can be brought on by any number of diverse factors. Treatment Therapy may be directed either at terminating an episode of the abnormal heart rhythm or at reducing the risk of another VT episode. The treatment for stable VT is tailored to the specific person, with regard to how well the individual tolerates episodes of ventricular tachycardia, how frequently episodes occur, their comorbidities, and their wishes. Individuals with pulseless VT or unstable VT are hemodynamically compromised and require immediate electric cardioversion to shock them out of the VT rhythm. Cardioversion If a person still has a pulse, it is usually possible to terminate the episode using electric cardioversion. This should be synchronized to the heartbeat if the waveform is monomorphic if possible, in order to avoid degeneration of the rhythm to ventricular fibrillation. An initial energy of 100J is recommended. If the waveform is polymorphic, then higher energies and an unsynchronized shock should be provided (also known as defibrillation). Defibrillation A person with pulseless VT is treated the same as ventricular fibrillation with high-energy (360J with a monophasic defibrillator, or 200J with a biphasic defibrillator) unsynchronised cardioversion (defibrillation). They will be unconscious. The shock may be delivered to the outside of the chest using the two pads of an external defibrillator, or internally to the heart by an implantable cardioverter-defibrillator (ICD) if one has previously been inserted.An ICD may also be set to attempt to overdrive pace the ventricle. Pacing the ventricle at a rate faster than the underlying tachycardia can sometimes be effective in terminating the rhythm. If this fails after a short trial, the ICD will usually stop pacing, charge up and deliver a defibrillation grade shock. Medication For those who are stable with a monomorphic waveform the medications procainamide or sotalol may be used and are better than lidocaine. Evidence does not show that amiodarone is better than procainamide.As a low magnesium level in the blood is a common cause of VT, magnesium sulfate can be given for torsades de pointes or if a low blood magnesium level is found/suspected.Long-term anti-arrhythmic therapy may be indicated to prevent recurrence of VT. Beta-blockers and a number of class III anti-arrhythmics are commonly used, such as the beta-blockers carvedilol, metoprolol, and bisoprolol, and the Potassium-Channel-Blockers amiodarone, dronedarone, bretylium, sotalol, ibutilide, and dofetilide. Angiotensin-converting-enzyme (ACE) inhibitors and aldosterone antagonists are also sometimes used in this setting. Invasive treatment An ICD (implantable cardioverter defibrillator ) is more effective than drug therapy for prevention of sudden cardiac death due to VT and VF, but does not prevent these rhythm from happening. Catheter ablation is a potentially definitive treatment option for those with recurrent VT. Remote magnetic navigation is one effective method to do the procedure.In the past, ablation was often not considered until pharmacological options had been exhausted, often after the patient had developed substantial morbidity from recurrent episodes of VT and ICD shocks. Antiarrhythmic medications can reduce the frequency of ICD therapies, but have efficacy varies and side effects can be significant. Advances in technology and understanding of VT substrates now allow ablation of multiple and unstable VTs with acceptable safety and efficacy, even in patients with advanced heart disease. References == External links ==

Uterine tachysystole

Uterine tachysystole is a condition of excessively frequent uterine contractions during pregnancy. It is most often seen in induced or augmented labor, though it can also occur during spontaneous labor.Because contraction counts are often measured over periods of ten minutes but averaged over periods of thirty minutes, there can be slight differences in how the cutoff is calculated. Generally it is defined as more frequently than once every two minutes. Although definitions may vary among studies, most use the terms defined by the American Congress of Obstetricians and Gynecologists (1999a) to describe increased uterine activity as follows: Uterine tachysystole is defined as more than 5 contractions in 10 minutes, averaged over a 30-minute window. Uterine hypertonus is described as a single contraction lasting longer than 2 minutes. Uterine hyperstimulation is when either condition leads to a nonreassuring fetal heart rate pattern.The American Congress of Obstetricians and Gynecologists amended these definitions in 2008. Uterine tachysystole is defined as more than 5 contractions in 10 minutes, averaged over a 30-minute period. The terms "hypertonus" and "hyperstimulation" are not recommended to be used. Uterine tachysystole has been reported to follow vaginally administered Prostaglandin E2 in 1 to 5 percent of women (Brindley and Sokol, 1988; Rayburn, 1989). It can be associated with placental abruption and perhaps with uterine leiomyomas. It can also refer to hyperstimulation with oxytocin. == References ==

Arterial occlusion

Arterial occlusion is a condition involving partial or complete blockage of blood flow through an artery. Arteries are blood vessels that carry oxygenated blood to body tissues. An occlusion of arteries disrupts oxygen and blood supply to tissues, leading to ischemia. Depending on the extent of ischemia, symptoms of arterial occlusion range from simple soreness and pain that can be relieved with rest, to a lack of sensation or paralysis that could require amputation.Arterial occlusion can be classified into three types based on etiology: embolism, thrombosis, and atherosclerosis. These three types of occlusion underlie various common conditions, including coronary artery disease, peripheral artery disease, and pulmonary embolism, which may be prevented by lowering risk factors. With improper prevention or management, these diseases can progress into life-threatening complications of myocardial infarction, gangrene, ischemic stroke, and in severe cases, terminate in brain death or cardiac arrest.Arterial occlusion is diagnosed by exercise testing, ultrasonic duplex testing, and multi-detector coronary tomography angiography. Meanwhile, treatment can vary from surgical interventions such as bypass, endarterectomy, and embolectomy, to blood-thinning medication. Signs and symptoms Signs and symptoms of arterial occlusion depend on several factors, including the location, extent, and onset of blockage. Normally, the blockage should affect approximately 70% of the artery for symptoms to become noticeable. Symptoms can be less severe during gradual narrowing, as this allows time for the widening of existing vessels and the formation of new ones (collateral vessels), allowing blood to still reach the area. Symptoms in this case will simply be intermittent claudication. Sudden narrowing leads to more severe consequences, given the lack of time for collateral vessels to grow. As such, coldness, numbness or even paralysis of the affected body parts may result.The commonest symptom of arterial occlusion is intermittent claudication, which consists of a painful, aching sensation in the affected muscle. This is often provoked with physical activity and relieved with rest. Pain and muscle aching may build up with walking, and accelerate with light jogging or walking uphill. Often, pain is relieved after several minutes of rest. However, affected individuals are limited to short spurts of activity, impairing their quality of life. For severe symptoms, the signs are usually visible and lead to ischemia. The clinical presentation of ischemia consists of the 6 Ps, including pallor, pain, paresthesia, paralysis, pulselessness, and poikilothermia. Affected individuals initially notice a paleness of the affected region and feel severe pain. As the condition worsens, the region appears bluish and numb. In extreme cases, this will give way to paralysis and poikilothermia, possibly requiring amputation of the affected limb. Types of arterial occlusion Commonly observed types of arterial occlusion include thrombosis, atherosclerosis, and embolism. Embolism An embolism involves the occlusion of blood vessels by an embolus. Arterial occlusion by an embolus is termed arterial embolism. An embolus is an agent that blocks blood flow by physically obstructing blood vessels. This includes gas bubbles, fatty deposits, amniotic fluid, blood clots, and foreign material. Arterial emboli occasionally detach from primary sites and travel via circulation to occlude secondary arteries, causing multiple ischemic sites. Thrombosis Thrombosis occurs when thrombi occlude vessels in the body. A thrombus, or a blood clot, is a mobilized mass of blood cells that circulates within the body. Thrombi can occlude veins (venous thrombosis) or arteries (arterial thrombosis). The etiology of thrombosis is described by Virchows Triad, which includes hemostasis, vascular wall damage, and hypercoagulability. Arterial thromboses significantly narrow or completely block arterial blood flow and oxygen delivery to tissues. Atherosclerosis In atherosclerosis, the inner endothelial layer of arteries is stiffened by the deposition of an atheromatous plaque. Atheromatous plaques, also called atherosclerotic plaques, are made of fats and lipid-laden macrophages. Plaque deposition both physically narrows an artery and impairs the function of endothelial cells, potentiating their production of vasoconstrictive chemicals to constrict the arterial lumen. This leads to turbulent blood flow in the arteries, affecting oxygen supply to tissues downstream. Diseases of arterial occlusion The pathophysiology of diseases of arterial occlusion depends on the type of occlusion, the severity of blockage, and the location of the occluded artery. Common diseases of arterial occlusion include Coronary Artery Disease, Peripheral Artery Disease, and Pulmonary Embolism. Coronary Artery Disease Coronary Artery Disease (CAD) results from the stenosis of coronary arteries by an atherosclerotic plaque. The coronary arteries perfuse the cardiomyocytes located within the myocardium. Cardiomyocytes require constant perfusion to aid the pumping of the heart. In CAD, atheromatous plaque formation in a coronary artery limits oxygen supply to cardiomyocytes, impairing heart contractility. CAD severity varies based on the extent of coronary artery occlusion. At 75% luminal narrowing, patients experience symptoms associated with limited perfusion of cardiomyocytes, especially under strenuous conditions. Under physical exertion, CAD induces chest pain, termed stable angina. Stable angina may deteriorate into unstable angina, marking the initiation of Acute Coronary Syndrome, which may further deteriorate into a myocardial infarction. Risk factors for CAD include smoking, high cholesterol, obesity, and family history of CAD. Primarily, the accumulation of cholesterol in the bloodstream from high-fat diets lead to atherosclerotic occlusion and its clinical consequences. Therefore, preventative measures for CAD mainly involve diet changes. A diet low in saturated and trans fats with an abundance of vegetables, fruits, and grains may lower the incidence of CAD. Peripheral Artery Disease Peripheral artery disease (PAD), or limb ischemia, affects the femoral, popliteal, or iliac arteries. PAD is caused by atherosclerotic plaques that occlude blood flow to extremities. Once blood flow is impeded, ischemic muscle cells switch from aerobic to anaerobic metabolism to cope with oxygen scarcity. Anaerobic metabolism, however, is energy-inefficient, lowering the concentration of the intracellular energy molecule, ATP, within muscles. ATP depletion leads to a leakage of calcium into muscle cells, disrupting various muscular components and eventually causing muscle fiber necrosis.Risk factors for PAD include old age, smoking, hypertension, and high cholesterol, with smoking being the greatest contributing factor. This is because tobacco smoke contains potent chemicals that severely increase the occurrence of PAD. Thus, primary prevention of PAD is achieved with smoking cessation. Pulmonary Embolism Pulmonary embolism (PE) involves occlusion of a pulmonary artery by an embolus, most often a thrombus, obstructing blood flow to the lungs. Impairment of pulmonary circulation leads to severe ventilation-perfusion mismatching of the lungs, terminating in hypoxemia and respiratory failure. Most PEs are sequelae of Deep Vein Thrombosis (DVT), resulting from the breakage and propagation of a venous thrombus formed within the extremities to a pulmonary artery.As DVT commonly precedes PE, risk factors for PE overlap with risk factors for DVT. These include a sedentary lifestyle, prior surgery, trauma, history of DVT, and hypertension. A sedentary lifestyle and lack of movement are critical modifiable risk factors for PE. Immobility reduces the rate of leg muscle contraction, enhancing thrombus formation in vessels of the calves that may propagate to the lungs. Thus, physical activity is essential in preventing PE. Complications Diseases of arterial occlusion may progress into life-threatening conditions with improper prevention or management. Myocardial infarction, gangrene, and ischemic stroke are among the complications of severe arterial occlusion. Myocardial Infarction A myocardial infarction (MI), or heart attack, arises from complete occlusion of a coronary artery. The most frequent cause of MI is the rupturing of an atherosclerotic plaque formed in CAD. Plaque rupture exposes the subendothelial matrix beneath the plaque, initiating thrombus formation within the vasculature. The thrombus deposits on the ruptured plaque to completely block the coronary artery, halting oxygen supply to cardiomyocytes. Under hypoxia, cardiomyocytes perform anaerobic respiration, producing more lactate. With blocked coronary circulation, lactate clearance from cardiomyocytes is also hindered. Lactate accumulation reduces contractility and eventually necroses cardiomyocytes, releasing their troponin storage into the bloodstream. Serum troponin elevation is a characteristic biomarker of MI.Depending on the severity of ischemia, MIs are categorized as NSTEMI or STEMI. NSTEMI stands for Non-ST Elevation Myocardial Infarction, referencing the lack of ST-segment elevation in ECG traces. This is because in NSTEMI, only part of the myocardial wall is infarcted, which does not diagnostically present with ST-elevation. NSTEMI becomes STEMI when the entire myocardial wall is infarcted. Diagnostically, STEMI displays prolonged ST-segment elevation in ECG traces, and is thus named ST-Elevation Myocardial Infarction. Minutes after STEMI, fatal cardiac arrest could occur. STEMI is life-threatening if immediate reperfusion therapy is not initiated. Gangrene Gangrene, specifically dry gangrene, is caused by an atherosclerotic or thromboembolic arterial occlusion. Gangrene is a complication of prolonged PAD, leading to shriveling, blackening, and infarction of peripheral tissue, commonly in the extremities. In severe cases, amputation of the affected limb is required. Ischemic Stroke Ischemic stroke is a thrombotic, or rarely, thromboembolic or atherosclerotic complication of arteries supplying the brain. Occlusion of brain arteries leads to rapid ischemic death of neurons, both at the infarct core and ischemic penumbra. Similar to cardiomyocytes, neurons require constant perfusion for proper function. Any interruption of blood supply causes neurons to switch to anaerobic metabolism, exhausting intracellular ATP levels. ATP depletion causes an influx of calcium cations into neurons and efflux of excess glutamate, triggering the apoptosis and necroptosis of neurons.Neuronal necrosis precipitates irreversible brain damage. Cerebral areas most susceptible to ischemic damage include the speech and motor cortices, leading to contralateral paralysis, speech, and comprehension loss. Severe or prolonged strokes may terminate in coma or brain death. Therefore, the diagnosis and treatment of ischemic stroke are time-dependent. Diagnosis There are several methods of diagnosing arterial occlusion, ranging from straightforward setups like exercise testing, to advanced scanning equipment such as ultrasonic duplex scanning or Multi-Detector Coronary Tomography (MDCT) angiography. Exercise Testing Exercise testing is a simplistic, non-invasive method of diagnosing intermittent claudication. Blood pressure measurements at the suspected area can be taken before and after exercise, as some symptoms only appear during strenuous activity. Commonly, a treadmill setting at 2 mph with a 12-degree slope is utilized. Subjects are asked to walk on the treadmill for a maximum of 5 minutes or until moderate pain is felt. The time to pain or maximal walking duration is recorded and compared with baselines. Healthy individuals maintain systolic blood pressures at a normal range. Once exercise becomes more intense, there may be a temporary fall in systolic pressure, which quickly returns to normal with rest. However, those with intermittent claudication struggle to maintain standard values of systolic pressure, while recovery back to baseline is prolonged. Ultrasonic Duplex Testing Ultrasonic duplex scanning was developed to primarily determine the extent of atherosclerosis in carotid arteries. Since then, its application has widened to include arteries in the limbs. The technique utilizes high-frequency sound waves for visualization of flow direction and velocity within the arteries in an area of interest. The term duplex refers to 2 modes of ultrasound scanning being conducted. The B-mode transducer allows for an image of the vessel to be obtained, providing visual cues on the extent of occlusion. Meanwhile, the doppler probe is used to acquire data on velocity and direction of blood flow. Multi-Detector Coronary Tomography (MDCT) Angiography Traditionally, angiography is an invasive technique which involves inserting a flexible plastic catheter into the artery of interest. A radioactive contrast dye is then injected through the catheter and viewed on an X-ray. This contrast material does not permanently discolor any organs, but simply interacts with X-rays to produce a more precise diagnosis.Due to technological advances, clinicians have begun to use a less invasive approach called Multi-Detector Coronary Tomography (MDCT) angiography. Rather than inserting a large catheter into the artery, this technique requires a small injection of contrast dye using a standard intravenous catheter inserted into the arm, much like a regular injection. MDCT scanners then locate the contrast dye to show blockages within the arteries. MDCT angiography is more sensitive in detecting blockage and subsequent diseases such as CAD compared to invasive X-ray angiography. Treatment Treatment for arterial occlusion varies depending on the extent of blockage. In severe cases, surgical intervention is needed to remove the blockage from the affected artery. Currently, there are 3 types of surgical approaches, including surgical bypass, endarterectomy, and embolectomy. If surgery is not required, blood-thinning medication may be prescribed. Surgical Bypass A surgical bypass is a procedure performed to treat CAD. This procedure involves bypassing the blocked portion of the artery by replacing it with a healthy vessel from elsewhere in the body. The surgeon attaches one end of the new vessel right before the blockage, and the other end in the area after the affected portion. This reestablishes proper blood flow toward the desired area. Endarterectomy An endarterectomy is an intervention aiming to remove accumulated plaques directly from the affected artery. This involves an incision on the side of the neck of the affected artery. The plaque is then exposed and removed accordingly, with the artery then stitched back together. With the plaque removed, blood can travel through the artery unimpeded. Embolectomy An embolectomy is a procedure conducted when a blockage moves from its original site to another place in the body, thus forming an embolus. There are two methods of performing embolectomy. The first method is catheter embolectomy, which involves the insertion of a catheter into the affected artery and the subsequent removal of the embolus. This option is minimally invasive, and thus lowers risk and recovery time. The other option is a traditional surgical option, where the surgeon will expose the affected region, open the blood vessel and remove the embolus. Blood-thinning Medication Blood-thinning medications are beneficial short-term options in managing arterial occlusion. Anticoagulants such as warfarin and antiplatelets such as aspirin and clopidogrel reduce the risk of thrombosis by making blood flow easily through arteries. Side effects include increased bleeding and heavier bruising. == References ==

Vaginitis

Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy.The three main causes are infections, specifically bacterial vaginosis, vaginal yeast infection, and trichomoniasis. Other causes include allergies to substances such as spermicides or soaps or as a result of low estrogen levels during breast-feeding or after menopause. More than one cause may exist at a time. The common causes vary by age. Prepubescent girls are often at risk for development of vulvovaginitis because of low amounts of estrogen and an underdeveloped labia minora.Diagnosis generally include examination, measuring the pH, and culturing the discharge. Other causes of symptoms such as inflammation of the cervix, pelvic inflammatory disease, cancer, foreign bodies, and skin conditions should be ruled out.Treatment depends on the underlying cause. Infections should be treated. Sitz baths may help with symptoms. Soaps and feminine hygiene products such as sprays should not be used. About a third of women have vaginitis at some point in time. Women of reproductive age are most often affected. Signs and symptoms A woman may have vaginal irritation, itching, or burning or may notice a foul-smelling or abnormal discharge that could appear green or yellow.The following signs or symptoms may indicate the presence of infection: Irritation or itching of the genital area inflammation (irritation, redness, and swelling caused by the presence of extra immune cells) of the labia majora, labia minora, or perineal area vaginal discharge foul vaginal odor pain/irritation with sexual intercourse Complications Vaginal infections left untreated can lead to further complications, especially for the pregnant woman. For bacterial vaginosis, these include "premature delivery, postpartum infections, clinically apparent and subclinical pelvic inflammatory disease, [as well as] postsurgical complications (after abortion, hysterectomy, caesarian section), increased vulnerability to HIV infection and, possibly, infertility". Studies have also linked trichomoniasis with increased likelihood of acquiring HIV; theories include that "vaginitis increases the number of immune cells at the site of infection, and HIV then infects those immune cells." Other theories suggest that trichomoniasis increases the amount of HIV genital shedding, thereby increasing the risk of transmission to sexual partners. While the exact association between trichomoniasis infection and HIV genital shedding has not been consistently demonstrated, "there is good evidence that TV treatment reduces HIV genital shedding. Five studies were reported in the literature and, of these, four found a decrease in HIV genital shedding after TV treatment."Further, there are complications which lead to daily discomfort such as: persistent discomfort superficial skin infection (from scratching) complications of the causative condition (such as gonorrhea and candida infection) Causes Infection Vaginitis is often caused by an infection or the disruption of the healthy vaginal flora. The vaginal flora consists of those organisms which generally do not cause symptoms and is dominated mainly by Lactobacillus species. Disruption of the normal flora can cause a vaginal yeast infection. Vaginal yeast infection can affect women of all ages and is very common. The yeast Candida albicans is the most common cause of vaginitis. Specific forms of vaginal inflammation include the following types: Infectious vaginitis accounts for 90% of all cases in reproductive age women: Candidiasis: vaginitis caused by proliferation of Candida albicans, Candida tropicalis, Candida krusei Bacterial vaginosis: vaginitis caused by increased growth of Gardnerella (a bacterium). Aerobic vaginitisOther less common infections are caused by gonorrhea, chlamydia, Mycoplasma, herpes, Campylobacter, improper hygiene, and some parasites, notably Trichomonas vaginalis. Rare cases of amebic vaginitis have been reported, primarily in tropical, developing countries. Women who have diabetes develop infectious vaginitis more often than women who do not.Further, either a change in pH balance or introduction of foreign bacteria in the vagina can lead to infectious vaginitis. Physical factors that have been claimed to contribute to the development of infections include the following: constantly wet vulva due to tight clothing, chemicals coming in contact with the vagina via scented tampons, antibiotics, birth control pills, or a diet favoring refined sugar and yeast. Hormonal Hormonal vaginitis includes atrophic vaginitis usually found in postmenopausal women. Irritation/allergy Irritant vaginitis can be caused by allergies or reactions to vaginal sprays, douches, spermicides, soaps, detergents, or fabric softeners. It can also be caused by hot tubs, abrasion, tissue, tampons, or topical medications. Foreign body vaginitis (most common foreign bodies are retained tampons or condoms) may cause extremely malodorous vaginal discharges. Treatment consists of removal, for which ring forceps may be useful. Further treatment is generally not necessary. Diagnosis Diagnosis is typically suspected based on a womens symptoms. Diagnosis is made with microscopy (mostly by vaginal wet mount) and culture of the discharge after a careful history and physical examination have been completed. The color, consistency, acidity, and other characteristics of the discharge may be predictive of the causative agent. Determining the agent is especially important because women may have more than one infection, or have symptoms that overlap those of another infection, which dictates different treatment processes to cure the infection. For example, women often self-diagnose for yeast infections but due to the 89% misdiagnosis rate, self-diagnoses of vaginal infections are highly discouraged.Another type of vaginitis, called desquamative inflammatory vaginitis (DIV) also exists. The cause behind this type is still poorly understood. DIV corresponds to the severe forms of aerobic vaginitis. About 5 to 10% of women are affected by aerobic vaginitis.The International Statistical Classification of Diseases and Related Health Problems codes for the several causes of vaginitis are: Prevention Prevention of candidiasis, the most common type of vaginitis, includes using loose cotton underwear. The vaginal area should be washed with water. Perfumed soaps, shower gels, and vaginal deodorants should be avoided. Douching is not recommended. The practice upsets the normal balance of yeast in the vagina and does more harm than good.Prevention of bacterial vaginosis includes healthy diets and behaviors as well as minimizing stress as all these factors can affect the pH balance of the vagina.Prevention of trichomoniasis revolves around avoiding other peoples wet towels and hot tubs, and safe-sex procedures, such as condom use.Some women consume good bacteria in food with live culture, such as yogurt, sauerkraut and kimchi, or in probiotic supplements either to try to prevent candidiasis, or to reduce the likelihood of developing bacterial vaginitis following antibiotic treatment. There is no firm evidence to suggest that eating live yogurt or taking probiotic supplements will prevent candidiasis.Studies have suggested a possible clinical role for the use of standardized oral or vaginal probiotics in the treatment of bacterial vaginosis, either in addition to or in place of the typical antibiotic regimens. However, recent articles question their efficacy in preventing recurrence compared with other means, or conclude that there is insufficient evidence for or against recommending probiotics for the treatment of bacterial vaginosis. Treatment The cause of the infection determines the appropriate treatment. It may include oral or topical antibiotics and/or antifungal creams, antibacterial creams, or similar medications. A cream containing cortisone may also be used to relieve some of the irritation. If an allergic reaction is involved, an antihistamine may also be prescribed. For women who have irritation and inflammation caused by low levels of estrogen (postmenopausal), a topical estrogen cream might be prescribed. The following are typical treatments for trichomoniasis, bacterial vaginosis, and yeast infections: Trichomoniasis: Oral treatment with either metronidazole or tinidazole. "Sexual partner(s) should be treated simultaneously. Patients should be advised to avoid sexual intercourse for at least 1 week and until they and their partner(s) have completed treatment and follow-up." Bacterial vaginosis: The most commonly used antibiotics are metronidazole, available in both pill and gel form, and clindamycin available in both pill and cream form. Yeast infections: Local azole, in the form of ovula and cream. All agents appear to be equally effective. These anti-fungal medications, which are available in over the counter form, are generally used to treat yeast infections. Treatment may last anywhere between one, three, or seven days. Aerobic vaginitis Treatment can include topical steroids to diminish the inflammation. Antibiotics to diminish the proportion of aerobic bacteria is still a matter of debate. The use of local antibiotics, preferably local non-absorbed and broad spectrum, covering enteric gram-positive and gram-negative aerobes, can be an option. In some cases, systemic antibiotics can be helpful, such as amoxicillin/clavulanate or moxifloxacin. Vaginal rinsing with povidone iodine can provide relief of symptoms but does not provide long-term reduction of bacterial loads. Dequalinium chloride can also be an option for treatment. In children Vulvovaginitis in children may be "nonspecific", or caused by irritation with no known infectious cause, or infectious, caused by a pathogenic organism. Nonspecific vulvovaginitis may be triggered by fecal contamination, sexual abuse, chronic diseases, foreign bodies, nonestrogenized epithelium, chemical irritants, eczema, seborrhea, or immunodeficiency. It is treated with topical steroids; antibiotics may be given in cases where itching has resulted in a secondary infection.Infectious vulvovaginitis can be caused by group A beta-hemolytic Streptococcus (7-20% of cases), Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Shigella, Yersinia, or common STI organisms (Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, herpes simplex virus, and human papillomavirus). Symptoms and treatment of infectious vulvovaginitis vary depending on the organism causing it. Shigella infections of the reproductive tract usually coexist with infectious of the gastrointestinal tract and cause mucous, purulent discharge. They are treated with trimethoprim-sulfamethoxazole. Streptococcus infections cause similar symptoms to nonspecific vulvovaginitis and are treated with amoxicillin. STI-associated vulvovaginitis may be caused by sexual abuse or vertical transmission, and are treated and diagnosed like adult infections. See also List of bacterial vaginosis microbiota References == External links ==

Benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss of bladder control. Complications can include urinary tract infections, bladder stones, and chronic kidney problems.The cause is unclear. Risk factors include a family history, obesity, type 2 diabetes, not enough exercise, and erectile dysfunction. Medications like pseudoephedrine, anticholinergics, and calcium channel blockers may worsen symptoms. The underlying mechanism involves the prostate pressing on the urethra and thereby making it difficult to pass urine out of the bladder. Diagnosis is typically based on symptoms and examination after ruling out other possible causes.Treatment options include lifestyle changes, medications, a number of procedures, and surgery. In those with mild symptoms, weight loss, exercise, and decreasing caffeine intake are recommended, although the quality of the evidence for exercise is low. In those with more significant symptoms, medications may include alpha blockers such as terazosin or 5α-reductase inhibitors such as finasteride. Surgical removal of part of the prostate may be carried out in those who do not improve with other measures. Some herbal medicines that have been studied, such as saw palmetto, have not been shown to help. Other herbal medicines somewhat effective at improving urine flow include beta-sitosterol from Hypoxis rooperi (African star grass), pygeum (extracted from the bark of Prunus africana), pumpkin seeds (Cucurbita pepo), and stinging nettle (Urtica dioica) root.About 105 million men are affected globally. BPH typically begins after the age of 40. Half of males age 50 and over are affected. After the age of 80, that figure climbs to as high as about 90% of males affected. Although prostate specific antigen levels may be elevated in males with BPH, the condition does not increase the risk of prostate cancer. Signs and symptoms BPH is the most common cause of lower urinary tract symptoms (LUTS), which are divided into storage, voiding, and symptoms which occur after urination. Storage symptoms include the need to urinate frequently, waking at night to urinate, urgency (compelling need to void that cannot be deferred), involuntary urination, including involuntary urination at night, or urge incontinence (urine leak following a strong sudden need to urinate). Voiding symptoms include urinary hesitancy (a delay between trying to urinate and the flow actually beginning), intermittency (not continuous), involuntary interruption of voiding, weak urinary stream, straining to void, a sensation of incomplete emptying, and uncontrollable leaking after the end of urination. These symptoms may be accompanied by bladder pain or pain while urinating, called dysuria.Bladder outlet obstruction (BOO) can be caused by BPH. Symptoms are abdominal pain, a continuous feeling of a full bladder, frequent urination, acute urinary retention (inability to urinate), pain during urination (dysuria), problems starting urination (urinary hesitancy), slow urine flow, starting and stopping (urinary intermittency), and nocturia.BPH can be a progressive disease, especially if left untreated. Incomplete voiding results in residual urine or urinary stasis, which can lead to an increased risk of urinary tract infection. Causes Hormones Most experts consider androgens (testosterone and related hormones) to play a permissive role in the development of BPH. This means that androgens must be present for BPH to occur, but do not necessarily directly cause the condition. This is supported by evidence suggesting that castrated boys do not develop BPH when they age. In an unusual study of 26 eunuchs from the palace of the Qing dynasty still living in Beijing in 1960, the prostate could not be felt in 81% of the studied eunuchs. The average time since castration was 54 years (range, 41–65 years). On the other hand, some studies suggest that administering exogenous testosterone is not associated with a significant increase in the risk of BPH symptoms, so the role of testosterone in prostate cancer and BPH is still unclear. Further randomized controlled trials with more participants are needed to quantify any risk of giving exogenous testosterone.Dihydrotestosterone (DHT), a metabolite of testosterone, is a critical mediator of prostatic growth. DHT is synthesized in the prostate from circulating testosterone by the action of the enzyme 5α-reductase, type 2. DHT can act in an autocrine fashion on the stromal cells or in paracrine fashion by diffusing into nearby epithelial cells. In both of these cell types, DHT binds to nuclear androgen receptors and signals the transcription of growth factors that are mitogenic to the epithelial and stromal cells. DHT is ten times more potent than testosterone because it dissociates from the androgen receptor more slowly. The importance of DHT in causing nodular hyperplasia is supported by clinical observations in which an inhibitor of 5α-reductase such as finasteride is given to men with this condition. Therapy with a 5α-reductase inhibitor markedly reduces the DHT content of the prostate and, in turn, reduces prostate volume and BPH symptoms.Testosterone promotes prostate cell proliferation, but relatively low levels of serum testosterone are found in patients with BPH. One small study has shown that medical castration lowers the serum and prostate hormone levels unevenly, having less effect on testosterone and dihydrotestosterone levels in the prostate.While there is some evidence that estrogen may play a role in the cause of BPH, this effect appears to be mediated mainly through local conversion of androgens to estrogen in the prostate tissue rather than a direct effect of estrogen itself. In canine in vivo studies castration, which significantly reduced androgen levels but left estrogen levels unchanged, caused significant atrophy of the prostate. Studies looking for a correlation between prostatic hyperplasia and serum estrogen levels in humans have generally shown none.In 2008, Gat et al. published evidence that BPH is caused by failure in the spermatic venous drainage system resulting in increased hydrostatic pressure and local testosterone levels elevated more than 100 fold above serum levels. If confirmed, this mechanism explains why serum androgen levels do not seem to correlate with BPH and why giving exogenous testosterone would not make much difference. Diet Studies indicate that dietary patterns may affect development of BPH, but further research is needed to clarify any important relationship. Studies from China suggest that greater protein intake may be a factor in development of BPH. Men older than 60 in rural areas had very low rates of clinical BPH, while men living in cities and consuming more animal protein had a higher incidence. On the other hand, a study in Japanese-American men in Hawaii found a strong negative association with alcohol intake, but a weak positive association with beef intake. In a large prospective cohort study in the US (the Health Professionals Follow-up Study), investigators reported modest associations between BPH (men with strong symptoms of BPH or surgically confirmed BPH) and total energy and protein, but not fat intake. There is also epidemiological evidence linking BPH with metabolic syndrome (concurrent obesity, impaired glucose metabolism and diabetes, high triglyceride levels, high levels of low-density cholesterol, and hypertension). Degeneration Benign prostatic hyperplasia is an age-related disease. Misrepair-accumulation aging theory suggests that development of benign prostatic hyperplasia is a consequence of fibrosis and weakening of the muscular tissue in the prostate. The muscular tissue is important in the functionality of the prostate, and provides the force for excreting the fluid produced by prostatic glands. However, repeated contractions and dilations of myofibers will unavoidably cause injuries and broken myofibers. Myofibers have a low potential for regeneration; therefore, collagen fibers need to be used to replace the broken myofibers. Such misrepairs make the muscular tissue weak in functioning, and the fluid secreted by glands cannot be excreted completely. Then, the accumulation of fluid in glands increases the resistance of muscular tissue during the movements of contractions and dilations, and more and more myofibers will be broken and replaced by collagen fibers. Pathophysiology As men age, the enzymes aromatase and 5-alpha reductase increase in activity. These enzymes are responsible for converting androgen hormones into estrogen and dihydrotestosterone, respectively. This metabolism of androgen hormones leads to a decrease in testosterone but increased levels of DHT and estrogen. Both the glandular epithelial cells and the stromal cells (including muscular fibers) undergo hyperplasia in BPH. Most sources agree that of the two tissues, stromal hyperplasia predominates, but the exact ratio of the two is unclear.:694Anatomically the median and lateral lobes are usually enlarged, due to their highly glandular composition. The anterior lobe has little in the way of glandular tissue and is seldom enlarged. (Carcinoma of the prostate typically occurs in the posterior lobe – hence the ability to discern an irregular outline per rectal examination). The earliest microscopic signs of BPH usually begin between the age of 30 and 50 years old in the PUG, which is posterior to the proximal urethra.:694 In BPH, the majority of growth occurs in the transition zone (TZ) of the prostate.:694 In addition to these two classic areas, the peripheral zone (PZ) is also involved to a lesser extent.:695 Prostatic cancer typically occurs in the PZ. However, BPH nodules, usually from the TZ are often biopsied anyway to rule out cancer in the TZ.:695 BPH can be a progressive growth that in rare instances leads to exceptional enlargement. In some males, the prostate enlargement exceeds 200 to 500 grams. This condition has been defined as giant prostatic hyperplasia (GPH). Diagnosis The clinical diagnosis of BPH is based on a history of LUTS (lower urinary tract symptoms), a digital rectal exam, and exclusion of other causes of similar signs and symptoms. The degree of LUTS does not necessarily correspond to the size of the prostate. An enlarged prostate gland on rectal examination that is symmetric and smooth supports a diagnosis of BPH. However, if the prostate gland feels asymmetrical, firm, or nodular, this raises concern for prostate cancer.Validated questionnaires such as the American Urological Association Symptom Index (AUA-SI), the International Prostate Symptom Score (I-PSS), and more recently the UWIN score (urgency, weak stream, incomplete emptying, and nocturia) are useful aids to making the diagnosis of BPH and quantifying the severity of symptoms. Laboratory investigations Urinalysis is typically performed when LUTS are present and BPH is suspected to evaluate for signs of a urinary tract infection, glucose in the urine (suggestive of diabetes), or protein in the urine (suggestive of kidney disease). Bloodwork including kidney function tests and prostate specific antigen (PSA) are often ordered to evaluate for kidney damage and prostate cancer, respectively. However, checking blood PSA levels for prostate cancer screening is controversial and not necessarily indicated in every evaluation for BPH. Benign prostatic hyperplasia and prostate cancer are both capable of increasing blood PSA levels and PSA elevation is unable to differentiate these two conditions well. If PSA levels are checked and are high, then further investigation is warranted. Measures including PSA density, free PSA, rectal examination, and transrectal ultrasonography may be helpful in determining whether a PSA increase is due to BPH or prostate cancer. Imaging and other investigations Uroflowmetry is done to measure the rate of urine flow and total volume of urine voided when the subject is peeing.Abdominal ultrasound examination of the prostate and kidneys is often performed to rule out hydronephrosis and hydroureter. Incidentally, cysts, tumours, and stones may be found on ultrasound. Post-void residual volume of more than 100 ml may indicate significant obstruction. Prostate size of 30 cc or more indicates enlargement of the prostate.Prostatic calcification can be detected through transrectal ultrasound (TRUS). Calcification is due to solidification of prostatic secretions or calcified corpora amylacea (hyaline masses on the prostate gland). Calcification is also found in a variety of other conditions such as prostatitis, chronic pelvic pain syndrome, and prostate cancer. For those with elevated levels of PSA, TRUS guided biopsy is performed to take a sample of the prostate for investigation. Although MRI is more accurate than TRUS in determining prostate volume, TRUS is less expensive and almost as accurate as MRI. Therefore, TRUS is still preferred to measure prostate volume. Differential diagnosis Medical conditions The differential diagnosis for LUTS is broad and includes various medical conditions, neurologic disorders, and other diseases of the bladder, urethra, and prostate such as bladder cancer, urinary tract infection, urethral stricture, urethral calculi (stones), chronic prostatitis, and prostate cancer. Neurogenic bladder can cause urinary retention and cause symptoms similar to those of BPH. This may occur as a result of uncoordinated contraction of the bladder muscle or impairment in the timing of bladder muscle contraction and urethral sphincter relaxation. Notable causes of neurogenic bladder include disorders of the central nervous system such as Parkinsons disease, multiple sclerosis, and spinal cord injuries as well as disorders of the peripheral nervous system such as diabetes mellitus, vitamin B12 deficiency, and alcohol-induced nerve damage. Individuals affected by heart failure often experience nighttime awakenings to urinate due to redistribution of fluid accumulated in swollen legs. Medications Certain medications can increase urination difficulties by increasing bladder outlet resistance due to increased smooth muscle tone at the prostate or bladder neck and contribute to LUTS. Alpha-adrenergic agonist medications, such as decongestants with pseudoephedrine can increase bladder outlet resistance. In contrast, calcium channel blockers and anticholinergic medications can worsen urinary retention by promoting bladder muscle relaxation. Diuretic medications such as loop diuretics (e.g., furosemide) or thiazides (e.g., chlorthalidone) can cause or worsen urinary frequency and nighttime awakenings to urinate. Management When treating and managing benign prostatic hyperplasia, the aim is to prevent complications related to the disease and improve or relieve symptoms. Approaches used include lifestyle modifications, medications, and surgery. Lifestyle Lifestyle alterations to address the symptoms of BPH include physical activity, decreasing fluid intake before bedtime, moderating the consumption of alcohol and caffeine-containing products and following a timed voiding schedule. Patients can also attempt to avoid products and medications with anticholinergic properties that may exacerbate urinary retention symptoms of BPH, including antihistamines, decongestants, opioids, and tricyclic antidepressants; however, changes in medications should be done with input from a medical professional. Physical activity Physical activity has been recommended as a treatment for urinary tract symptoms. A 2019 Cochrane review of six studies involving 652 men assessing the effects of physical activity alone, physical activity as a part of a self-management program, among others. However, the quality of evidence was very low and therefore it remains uncertain whether physical activity is helpful in men experiencing urinary symptoms caused by benign prostatic hyperplasia. Voiding position Voiding position when urinating may influence urodynamic parameters (urinary flow rate, voiding time, and post-void residual volume). A meta-analysis found no differences between the standing and sitting positions for healthy males, but that, for elderly males with lower urinary tract symptoms, voiding in the sitting position-- decreased the post void residual volume; increased the maximum urinary flow, comparable with pharmacological intervention; and decreased the voiding time.This urodynamic profile is associated with a lower risk of urologic complications, such as cystitis and bladder stones. Medications The two main medication classes for BPH management are alpha blockers and 5α-reductase inhibitors. Alpha blockers Selective α1-blockers are the most common choice for initial therapy. They include alfuzosin, doxazosin, silodosin, tamsulosin, terazosin, and naftopidil. They have a small to moderate benefit at improving symptoms. Selective alpha-1 blockers are similar in effectiveness but have slightly different side effect profiles. Alpha blockers relax smooth muscle in the prostate and the bladder neck, thus decreasing the blockage of urine flow. Common side effects of alpha blockers include orthostatic hypotension (a head rush or dizzy spell when standing up or stretching), ejaculation changes, erectile dysfunction, headaches, nasal congestion, and weakness. For men with LUTS due to an enlarged prostate, the effects of naftopidil, tamsulosin and silodosin on urinary symptoms and quality of life may be similar. Naftopidil and tamsulosin may have similar levels of unwanted sexual side effects but fewer unwanted side effects than silodosin.Tamsulosin and silodosin are selective α1 receptor blockers that preferentially bind to the α1A receptor in the prostate instead of the α1B receptor in the blood vessels. Less-selective α1 receptor blockers such as terazosin and doxazosin may lower blood pressure. The older, less selective α1-adrenergic blocker prazosin is not a first line choice for either high blood pressure or prostatic hyperplasia; it is a choice for patients who present with both problems at the same time. The older, broadly non-selective alpha blocker medications such as phenoxybenzamine are not recommended for control of BPH. Non-selective alpha blockers such as terazosin and doxazosin may also require slow dose adjustments as they can lower blood pressure and cause syncope (fainting) if the response to the medication is too strong. 5α-reductase inhibitors The 5α-reductase inhibitors finasteride and dutasteride may also be used in men with BPH. These medications inhibit the 5α-reductase enzyme, which, in turn, inhibits production of DHT, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, no benefit was reported in short-term trials, but in a longer-term study (3–4 years) there was a greater reduction in BPH progression to acute urinary retention and surgery than with either agent alone, especially in people with more severe symptoms and larger prostates. Other trials have confirmed reductions in symptoms, within 6 months in one trial, an effect that was maintained after withdrawal of the alpha blocker. Side effects include decreased libido and ejaculatory or erectile dysfunction. The 5α-reductase inhibitors are contraindicated in pregnant women because of their teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets. Phosphodiesterase inhibitors (PDE) A 2018 Cochrane review of studies on men over 60 with moderate to severe lower urinary tract symptoms analyzed the impacts of phosphodiesterase inhibitors (PDE) in comparison to other drugs. These drugs may improve urinary symptoms slightly and reduce urinary bother but may also cause more side effects compared to placebo. The evidence in this review found that there is probably no difference between PDE and alpha blockers, however when used in combination they may provide a greater improvement in symptoms (with more side effects). PDE also likely improves symptoms when used in combination with 5-alpha reductase inhibitors. Several phosphodiesterase-5 inhibitors are also effective, but may require multiple doses daily to maintain adequate urine flow. Tadalafil, a phosphodiesterase-5 inhibitor, was considered then rejected by NICE in the UK for the treatment of symptoms associated with BPH. In 2011, the U.S. Food and Drug Administration approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia, and for the treatment of BPH and erectile dysfunction (ED), when the conditions occur simultaneously. Others Antimuscarinics such as tolterodine may also be used, especially in combination with alpha blockers. They act by decreasing acetylcholine effects on the smooth muscle of the bladder, thus helping control symptoms of an overactive bladder. Self-catheterization Intermittent urinary catheterization is used to relieve the bladder in people with urinary retention. Self-catheterization is an option in BPH when it is difficult or impossible to completely empty the bladder. Urinary tract infection is the most common complication of intermittent catheterization. Several techniques and types of catheter are available, including sterile (single-use) and clean (multiple use) catheters, but, based on current information, none is superior to others in reducing the incidence of urinary tract infection. Surgery If medical treatment is not effective, surgery may be performed. Surgical techniques used include the following: Transurethral resection of the prostate (TURP): the gold standard. TURP is thought to be the most effective approach for improving urinary symptoms and urinary flow, however, this surgical procedure may be associated with complications in up to 20% of men. Surgery carries some risk of complications, such as retrograde ejaculation (most commonly), erectile dysfunction, urinary incontinence, urethral strictures. Transurethral incision of the prostate (TUIP): rarely performed; the technique is similar to TURP but less definitive. Open prostatectomy: not usually performed nowadays due to its high morbidity, even if results are very good.Other less invasive surgical approaches (requiring spinal anesthesia) include: Holmium laser ablation of the prostate (HoLAP) Holmium laser enucleation of the prostate (HoLeP) Photoselective vaporization of the prostate (PVP). Aquablation therapy: a type of surgery using a water jet to remove prostatic tissue. Minimally invasive procedures Some less invasive procedures are available according to patients preferences and co-morbidities. These are performed as outpatient procedures with local anesthesia. Prostatic artery embolization: an endovascular procedure performed in interventional radiology. Through catheters, embolic agents are released in the main branches of the prostatic artery, in order to induce a decrease in the size of the prostate gland, thus reducing the urinary symptoms. Water vapor thermal therapy (marketed as Rezum): This is a newer office procedure for removing prostate tissue using steam aimed at preserving sexual function. Prostatic urethral lift (marketed as UroLift): This intervention consists of a system of a device and an implant designed to pull the prostatic lobe away from the urethra. Transurethral microwave thermotherapy (TUMT) is an outpatient procedure that is less invasive compared to surgery and involves using microwaves (heat) to shrink prostate tissue that is enlarged. Temporary implantable nitinol device (TIND and iTIND): is a device that is placed in the urethra that, when released, is expanded, reshaping the urethra and the bladder neck. Alternative medicine While herbal remedies are commonly used, a 2016 review found the herbs studied to be no better than placebos. Particularly, several systematic reviews found that saw palmetto extract, while one of the most commonly used, is no better than a placebo both in symptom relief and in decreasing prostate size. Other herbal medicines somewhat effective at improving urine flow include beta-sitosterol from Hypoxis rooperi (African star grass), pygeum (extracted from the bark of Prunus africana), pumpkin seeds (Cucurbita pepo), and stinging nettle (Urtica dioica) root. A systematic review of Chinese herbal medicines found that Chinese herbal medicine, both alone and together with Western medicine, was similar to either placebos or Western medicine in the treatment of BPH. Chinese herbal medicine was found to be superior to Western medicine in improving the quality of life and in reducing prostate volume. Epidemiology Globally, benign prostatic hyperplasia affects about 210 million males as of 2010 (6% of the population).The prostate gets larger in most men as they get older. For a symptom-free man of 46 years, the risk of developing BPH over the next 30 years is 45%. Incidence rates increase from 3 cases per 1000 man-years at age 45–49 years, to 38 cases per 1000 man-years by the age of 75–79 years. While the prevalence rate is 2.7% for men aged 45–49, it increases to 24% by the age of 80 years. References External links Extrinsic Compression by Prostate

Steatorrhea

Steatorrhea (or steatorrhoea) is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the fecal fat level. The definition of how much fecal fat constitutes steatorrhea has not been standardized. Causes Impaired digestion or absorption can result in fatty stools. Possible causes include exocrine pancreatic insufficiency, with poor digestion from lack of lipases, loss of bile salts, which reduces micelle formation, and small intestinal disease-producing malabsorption. Various other causes include certain medicines that block fat absorption or indigestible or excess oil/fat in diet.The absence of bile secretion can cause the feces to turn gray or pale. Bile is responsible for the brownish color of feces. Other features of fat malabsorption may also occur such as reduced bone density, difficulty with vision under low light levels, bleeding, bruising, and slow blood clotting times. Associated diseases Conditions affecting the pancreas. Exocrine pancreatic insufficiency can be caused by chronic pancreatitis, cystic fibrosis and pancreatic cancer (if it obstructs biliary outflow). Conditions affecting bile salts. Obstruction of the bile ducts by gallstones (choledocholithiasis), primary sclerosing cholangitis, liver damage (intrahepatic cholestasis), hypolipidemic drugs, or changes following gallbladder removal (cholecystectomy). Conditions producing intestinal malabsorption. These include celiac disease, bacterial overgrowth, tropical sprue, Giardiasis (a protozoan parasite infection), Zollinger-Ellison syndrome, short bowel syndrome, inflammatory bowel disease and abetalipoproteinemia. Other causes: Drugs that can produce steatorrhea include orlistat, a slimming pill, or as adverse effect of octreotide or lanreotide, used to treat acromegaly or other neuroendocrine tumors. It can be found in Graves disease / hyperthyroidism. Medications Orlistat (also known by trade names Xenical and Alli) is a diet pill that works by blocking the enzymes that digest fat. As a result, some fat cannot be absorbed from the gut and is excreted in the feces instead of being metabolically digested and absorbed, sometimes causing oily anal leakage. Vytorin (ezetimibe/simvastatin) tablets can cause steatorrhea in some people. Excess whole nuts in diet Some studies have shown that stool lipids are increased when whole nuts are eaten, compared to nut butters, oils or flour and that lipids from whole nuts are significantly less well absorbed. Natural fats Consuming jojoba oil has been documented to cause steatorrhea and anal leakage because it is indigestible.Consuming escolar and oilfish (sometimes mislabelled as butterfish) will often cause steatorrhea, also referred to as Gempylotoxism or Gempylid Fish Poisoning or keriorrhea. Artificial fats The fat substitute Olestra, used to reduce digestible fat in some foods, was reported to cause leakage in some consumers during the test-marketing phase. As a result, the product was reformulated before general release to a hydrogenated form that is not liquid at physiologic temperature. The U.S. Food and Drug Administration warning indicated excessive consumption of Olestra could result in "loose stools"; however, this warning has not been required since 2003. Diagnosis Steatorrhea should be suspected when the stools are bulky, floating and foul-smelling. Specific tests are needed to confirm that these properties are in fact due to excessive levels of fat. Fats in feces can be measured over a defined time (often five days). Other tests include the (13)C-mixed triglycerides test and fecal elastase, to detect possible fat maldigestion due to exocrine pancreatic insufficiency, or various specific tests to detect other causes of malabsorption such as celiac disease. Treatment Treatments are mainly correction of the underlying cause, as well as digestive enzyme supplements. See also Rectal discharge Keriorrhea Fecal leakage Steatocrit References == External links ==

Ovarian cyst

An ovarian cyst is a fluid-filled sac within the ovary. Often they cause no symptoms. Occasionally they may produce bloating, lower abdominal pain, or lower back pain. The majority of cysts are harmless. If the cyst either breaks open or causes twisting of the ovary, it may cause severe pain. This may result in vomiting or feeling faint, and even cause head aches. Most ovarian cysts are related to ovulation, being either follicular cysts or corpus luteum cysts. Other types include cysts due to endometriosis, dermoid cysts, and cystadenomas. Many small cysts occur in both ovaries in polycystic ovary syndrome (PCOS). Pelvic inflammatory disease may also result in cysts. Rarely, cysts may be a form of ovarian cancer. Diagnosis is undertaken by pelvic examination with an ultrasound or other testing used to gather further details.Often, cysts are simply observed over time. If they cause pain, medications such as paracetamol (acetaminophen) or ibuprofen may be used. Hormonal birth control may be used to prevent further cysts in those who are frequently affected. However, evidence does not support birth control as a treatment of current cysts. If they do not go away after several months, get larger, look unusual, or cause pain, they may be removed by surgery.Most women of reproductive age develop small cysts each month. Large cysts that cause problems occur in about 8% of women before menopause. Ovarian cysts are present in about 16% of women after menopause and if present are more likely to be cancer. Signs and symptoms Some or all of the following symptoms may be present, though it is possible not to experience any symptoms: Abdominal pain. Dull aching pain within the abdomen or pelvis, especially during intercourse. Uterine bleeding. Pain during or shortly after beginning or end of menstrual period; irregular periods, or abnormal uterine bleeding or spotting. Fullness, heaviness, pressure, swelling, or bloating in the abdomen. When a cyst ruptures from the ovary, there may be sudden and sharp pain in the lower abdomen on one side. Change in frequency or ease of urination (such as inability to fully empty the bladder), or difficulty with bowel movements due to pressure on adjacent pelvic anatomy. Constitutional symptoms such as fatigue, headaches. Nausea or vomiting Weight gainOther symptoms may depend on the cause of the cysts: Symptoms that may occur if the cause of the cysts is polycystic ovarian syndrome (PCOS) may include increased facial hair or body hair, acne, obesity and infertility. If the cause is endometriosis, then periods may be heavy, and intercourse painful.The effect of cysts not related to PCOS on fertility is unclear. Cyst rupture A ruptured ovarian cyst is usually self-limiting, and only requires keeping an eye on the situation and pain medications. The main symptom is abdominal pain, which may last a few days to several weeks, but they can also be asymptomatic. Rupture of large ovarian cysts can cause bleeding inside the abdominal cavity and in some cases shock. Ovarian torsion Ovarian cysts increase the risk for ovarian torsion; cysts which are larger than 4 cm are associated with approximately 17% risk. The torsion can cause obstruction of blood flow and lead to infarction. Types Functional Functional cysts form as a normal part of the menstrual cycle. There are several types of functional cysts: Follicular cyst, the most common type of ovarian cyst. In menstruating women, a follicle containing the ovum, an unfertilized egg, will rupture during ovulation. If this does not occur, a follicular cyst of more than 2.5 cm diameter may result. Corpus luteum cysts appear after ovulation. The corpus luteum is the remnant of the follicle after the ovum has moved to the fallopian tubes. This normally degrades within 5 to 9 days. A corpus luteum that is more than 3 cm is defined as cystic. Theca lutein cysts occur within the thecal layer of cells surrounding developing oocytes. Under the influence of excessive hCG, thecal cells may proliferate and become cystic. This is usually on both ovaries. Non-functional Non-functional cysts may include the following: An ovary with many cysts, which may be found in normal women, or within the setting of polycystic ovary syndrome Cysts caused by endometriosis, known as chocolate cysts Hemorrhagic ovarian cyst Dermoid cyst Ovarian serous cystadenoma Ovarian mucinous cystadenoma Paraovarian cyst Cystic adenofibroma Borderline tumoral cysts Diagnosis Ovarian cysts are usually diagnosed by ultrasound, CT scan, or MRI, and correlated with clinical presentation and endocrinologic tests as appropriate. Ultrasound Follow-up imaging in women of reproductive age for incidentally discovered simple cysts on ultrasound is not needed until 5 cm, as these are usually normal ovarian follicles. Simple cysts 5 to 7 cm in premenopausal females should be followed yearly. Simple cysts larger than 7 cm require further imaging with MRI or surgical assessment. Because they are large, they cannot be reliably assessed by ultrasound alone; it can be difficult to see posterior wall soft tissue nodularity or thickened septation due to limited ultrasound beam penetrance at this size and depth. For the corpus luteum, a dominant ovulating follicle that typically appears as a cyst with circumferentially thickened walls and crenulated inner margins, follow up is not needed if the cyst is less than 3 cm in diameter. In postmenopausal patients, any simple cyst greater than 1 cm but less than 7 cm needs yearly follow-up, while those greater than 7 cm need MRI or surgical evaluation, similar to reproductive age females. For incidentally discovered dermoids, diagnosed on ultrasound by their pathognomonic echogenic fat, either surgical removal or yearly follow up is indicated, regardless of patient age. For peritoneal inclusion cysts, which have a crumpled tissue-paper appearance and tend to follow the contour of adjacent organs, follow up is based on clinical history. Hydrosalpinx, or fallopian tube dilation, can be mistaken for an ovarian cyst due to its anechoic appearance. Follow-up for this is also based on clinical presentation.For multiloculate cysts with thin septation less than 3 mm, surgical evaluation is recommended. The presence of multiloculation suggests a neoplasm, although the thin septation implies that the neoplasm is benign. For any thickened septation, nodularity, vascular flow on color doppler, or growth over several ultrasounds, surgical removal may be considered due to concern of cancer. Scoring systems There are several systems to assess risk of an ovarian cyst of being an ovarian cancer, including the RMI (risk of malignancy index), LR2 and SR (simple rules). Sensitivities and specificities of these systems are given in tables below: Ovarian cysts may be classified according to whether they are a variant of the normal menstrual cycle, referred to as a functional or follicular cyst.Ovarian cysts are considered large when they are over 5 cm and giant when they are over 15 cm. In children, ovarian cysts reaching above the level of the umbilicus are considered giant. Associated conditions In juvenile hypothyroidism multicystic ovaries are present in about 75% of cases, while large ovarian cysts and elevated ovarian tumor marks are one of the symptoms of the Van Wyk and Grumbach syndrome.The CA-125 marker in children and adolescents can be frequently elevated even in absence of malignancy and conservative management should be considered. Polycystic ovarian syndrome involves the development of multiple small cysts in both ovaries due to an elevated ratio of leutenizing hormone to follicle stimulating hormone, typically more than 25 cysts in each ovary, or an ovarian volume of greater than 10 mL.Larger bilateral cysts can develop as a result of fertility treatment due to elevated levels of HCG, as can be seen with the use of clomifene for follicular induction, in extreme cases resulting in a condition known as ovarian hyperstimulation syndrome. Certain malignancies can mimic the effects of clomifene on the ovaries, also due to increased HCG, in particular gestational trophoblastic disease. Ovarian hyperstimulation occurs more often with invasive moles and choriocarcinoma than complete molar pregnancies. Risk of cancer A widely recognised method of estimating the risk of malignant ovarian cancer based on initial workup is the risk of malignancy index (RMI). It is recommended that women with an RMI score over 200 should be referred to a centre with experience in ovarian cancer surgery.The RMI is calculated as follows: RMI = ultrasound score × menopausal score × CA-125 level in U/ml.There are two methods to determine the ultrasound score and menopausal score, with the resultant RMI being called RMI 1 and RMI 2, respectively, depending on what method is used: An RMI 2 of over 200 has been estimated to have a sensitivity of 74 to 80%, a specificity of 89 to 92% and a positive predictive value of around 80% of ovarian cancer. RMI 2 is regarded as more sensitive than RMI 1. Histopathology In case an ovarian cyst is surgically removed, a more definite diagnosis can be made by histopathology: Treatment Cysts associated with hypothyroidism or other endocrine problems are managed by treating the underlying condition. About 95% of ovarian cysts are benign, not cancerous. Functional cysts and hemorrhagic ovarian cysts usually resolve spontaneously. However, the bigger an ovarian cyst is, the less likely it is to disappear on its own. Treatment may be required if cysts persist over several months, grow, or cause increasing pain. Cysts that persist beyond two or three menstrual cycles, or occur in post-menopausal women, may indicate more serious disease and should be investigated through ultrasonography and laparoscopy, especially in cases where family members have had ovarian cancer. Such cysts may require surgical biopsy. Additionally, a blood test may be taken before surgery to check for elevated CA-125, a tumour marker, which is often found in increased levels in ovarian cancer, although it can also be elevated by other conditions resulting in a large number of false positives. Pain Pain associated with ovarian cysts may be treated in several ways: Pain relievers such as acetaminophen, nonsteroidal anti-inflammatory drugs, or opioids. While hormonal birth control prevents the development of new cysts in those who frequently get them, it is not useful for the treatment of current cysts. Surgery Although most cases of ovarian cysts involve monitoring, some cases require surgery. This may involve removing the cyst, or one or both ovaries. Technique is typically laparoscopic, unless the cyst is particularly large, or if pre-operative imaging suggests malignancy or complex anatomy. In certain situations, the cyst is entirely removed, while with cysts with low recurrence risk, younger patients, or which are in anatomically eloquent areas of the pelvis, they can be drained. Features that may indicate the need for surgery include: Persistent complex ovarian cysts Persistent cysts that are causing symptoms Complex ovarian cysts larger than 5 cm Simple ovarian cysts larger 10 cm or larger than 5 cm in postmenopausal patients Women who are menopausal or perimenopausal Frequency Most women of reproductive age develop small cysts each month, and large cysts that cause problems occur in about 8% of women before menopause. Ovarian cysts are present in about 16% of women after menopause and if present are more likely to be cancer.Benign ovarian cysts are common in asymptomatic premenarchal girls and found in approximately 68% of ovaries of girls 2–12 years old and in 84% of ovaries of girls 0–2 years old. Most of them are smaller than 9 mm while about 10–20% are larger macrocysts. While the smaller cysts mostly disappear within 6 months the larger ones appear to be more persistent. References Further reading McBee, W. C; Escobar, P. F; Falcone, T. (1 February 2007). "Which ovarian masses need intervention?". Cleveland Clinic Journal of Medicine. 74 (2): 149–157. doi:10.3949/ccjm.74.2.149. PMID 17333642. S2CID 45443236. Simcock, B; Anderson, N (February 2005). "Diagnosis and management of simple ovarian cysts: An audit". Australasian Radiology. 49 (1): 27–31. doi:10.1111/j.1440-1673.2005.01389.x. PMID 15727606. Ross, Elisa K.; Kebria, Medhi (August 2013). "Incidental ovarian cysts: When to reassure, when to reassess, when to refer". Cleveland Clinic Journal of Medicine. 80 (8): 503–514. doi:10.3949/ccjm.80a.12155. PMID 23908107. S2CID 28081941. "Ovarian cyst - Treatment". National Health Service. 3 October 2018. Gerber, B.; Müller, H.; Külz, T.; Krause, A.; Reimer, T. (1 April 1997). "Simple ovarian cysts in premenopausal patients". International Journal of Gynecology & Obstetrics. 57 (1): 49–55. doi:10.1016/S0020-7292(97)02832-4. PMID 9175670. S2CID 34289061. Potter, Andrew W.; Chandrasekhar, Chitra A. (October 2008). "US and CT Evaluation of Acute Pelvic Pain of Gynecologic Origin in Nonpregnant Premenopausal Patients". RadioGraphics. 28 (6): 1645–1659. doi:10.1148/rg.286085504. PMID 18936027. Crespigny, Lachlan Ch.; Robinson, Hugh P.; Davoren, Ruth A. M.; Fortune, Denys (September 1989). "The simple ovarian cyst: aspirate or operate?". BJOG. 96 (9): 1035–1039. doi:10.1111/j.1471-0528.1989.tb03377.x. PMID 2679871. S2CID 22501317.

Constrictive pericarditis

Constrictive pericarditis is a medical condition characterized by a thickened, fibrotic pericardium, limiting the hearts ability to function normally. In many cases, the condition continues to be difficult to diagnose and therefore benefits from a good understanding of the underlying cause. Signs and symptoms Signs and symptoms of constrictive pericarditis are consistent with the following: fatigue, swollen abdomen, difficulty breathing (dyspnea), swelling of legs and general weakness. Related conditions are bacterial pericarditis, pericarditis and pericarditis after a heart attack. Causes The cause of constrictive pericarditis in the developing world are idiopathic in origin, though likely infectious in nature. In regions where tuberculosis is common, it is the cause in a large portion of cases. Causes of constrictive pericarditis include: Tuberculosis Incomplete drainage of purulent pericarditis Fungal and parasitic infections Chronic pericarditis Postviral pericarditis Postsurgical Following MI, post-myocardial infarction In association with pulmonary asbestos Pathophysiology The pathophysiological characteristics of constrictive pericarditis are due to a thickened, fibrotic pericardium that forms a non-compliant shell around the heart. This shell prevents the heart from expanding when blood enters it. This results in significant respiratory variation in blood flow in the chambers of the heart.During inspiration, pressure in the thoracic cavity decreases but is not relayed to the left atrium, subsequently a reduction in flow to the left atrium and ventricle happens. During diastole, less blood flow in left ventricle allows for more room for filling in right ventricle and therefore a septal shift occurs.During expiration, the amount of blood entering the left ventricle will increase, allowing the interventricular septum to bulge towards the right ventricle, decreasing the right heart ventricular filing. Diagnosis The diagnosis of constrictive pericarditis is often difficult to make. In particular, restrictive cardiomyopathy has many similar clinical features to constrictive pericarditis, and differentiating them in a particular individual is often a diagnostic dilemma. Chest X-Ray - pericardial calcification (common but not specific), pleural effusions are common findings. Echocardiography - the principal echographic finding is changes in cardiac chamber volume. CT and MRI - CT scan is useful in assessing the thickness of pericardium, calcification, and ventricular contour. Cardiac MRI may find pericardial thickening and pericardial-myocardial adherence. Ventricular septum shift during breathing can also be found using cardiac MRI. Late gadolinium enhancement can show enhancement of the pericardium due to fibroblast proliferation and neovascularization. BNP blood test - tests for the existence of the cardiac hormone brain natriuretic peptide, which is only present in restrictive cardiomyopathy but not in constrictive pericarditis Conventional cardiac catheterization Physical examination - can reveal clinical features including Kussmauls sign and a pericardial knock. Treatment The definitive treatment for constrictive pericarditis is pericardial stripping, which is a surgical procedure where the entire pericardium is peeled away from the heart. This procedure has significant risk involved, with mortality rates of 6% or higher in major referral centers.A poor outcome is almost always the result after a pericardiectomy is performed for constrictive pericarditis whose origin was radiation-induced, further some patients may develop heart failure post-operatively. References Further reading Hoit, B. D. (25 June 2002). "Management of Effusive and Constrictive Pericardial Heart Disease". Circulation. 105 (25): 2939–2942. doi:10.1161/01.CIR.0000019421.07529.C5. PMID 12081983. Retrieved 21 September 2015. == External links ==

Cervical intraepithelial neoplasia

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix. CIN most commonly occurs at the squamocolumnar junction of the cervix, a transitional area between the squamous epithelium of the vagina and the columnar epithelium of the endocervix. It can also occur in vaginal walls and vulvar epithelium. CIN is graded on a 1–3 scale, with 3 being the most abnormal (see classification section below). Human papillomavirus (HPV) infection is necessary for the development of CIN, but not all with this infection develop cervical cancer. Many women with HPV infection never develop CIN or cervical cancer. Typically, HPV resolves on its own. However, those with an HPV infection that lasts more than one or two years have a higher risk of developing a higher grade of CIN.Like other intraepithelial neoplasias, CIN is not cancer and is usually curable. Most cases of CIN either remain stable or are eliminated by the persons immune system without need for intervention. However, a small percentage of cases progress to cervical cancer, typically cervical squamous cell carcinoma (SCC), if left untreated. Signs and symptoms There are no specific symptoms of CIN alone. Generally, signs and symptoms of cervical cancer include: abnormal or post-menopausal bleeding abnormal discharge changes in bladder or bowel function pelvic pain on examination abnormal appearance or palpation of cervix.HPV infection of the vulva and vagina can cause genital warts or be asymptomatic. Causes The cause of CIN is chronic infection of the cervix with HPV, especially infection with high-risk HPV types 16 or 18. It is thought that the high-risk HPV infections have the ability to inactivate tumor suppressor genes such as the p53 gene and the RB gene, thus allowing the infected cells to grow unchecked and accumulate successive mutations, eventually leading to cancer.Some groups of women have been found to be at a higher risk of developing CIN: Infection with a high-risk type of HPV, such as 16, 18, 31, or 33 Immunodeficiency (e.g. HIV infection) Poor diet Multiple sex partners Lack of condom use Cigarette smokingAdditionally, a number of risk factors have been shown to increase an individuals likelihood of developing CIN 3/carcinoma in situ (see below): Women who give birth before age 17 Women who have > 1 full term pregnancies Pathophysiology The earliest microscopic change corresponding to CIN is epithelial dysplasia, or surface lining, of the cervix, which is essentially undetectable by the woman. The majority of these changes occur at the squamocolumnar junction, or transformation zone, an area of unstable cervical epithelium that is prone to abnormal changes. Cellular changes associated with HPV infection, such as koilocytes, are also commonly seen in CIN. While infection with HPV is needed for development of CIN, most women with HPV infection do not develop high-grade intraepithelial lesions or cancer. HPV is not alone enough causative.Of the over 100 different types of HPV, approximately 40 are known to affect the epithelial tissue of the anogenital area and have different probabilities of causing malignant changes. Diagnosis A test for HPV called the Digene HPV test is highly accurate and serves as both a direct diagnosis and adjuvant to the Pap smear, which is a screening device that allows for an examination of cells but not tissue structure, needed for diagnosis. A colposcopy with directed biopsy is the standard for disease detection. Endocervical brush sampling at the time of Pap smear to detect adenocarcinoma and its precursors is necessary along with doctor/patient vigilance on abdominal symptoms associated with uterine and ovarian carcinoma. The diagnosis of CIN or cervical carcinoma requires a biopsy for histological analysis. Classification Historically, abnormal changes of cervical epithelial cells were described as mild, moderate, or severe epithelial dysplasia. In 1988 the National Cancer Institute developed "The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses". This system provides a uniform way to describe abnormal epithelial cells and determine specimen quality, thus providing clear guidance for clinical management. These abnormalities were classified as squamous or glandular and then further classified by the stage of dysplasia: atypical cells, mild, moderate, severe, and carcinoma.Depending on several factors and the location of the lesion, CIN can start in any of the three stages and can either progress or regress. The grade of squamous intraepithelial lesion can vary. CIN is classified in grades: Changes in Terminology The College of American Pathology and the American Society of Colposcopy and Cervical Pathology came together in 2012 to publish changes in terminology to describe HPV-associated squamous lesions of the anogenital tract as LSIL or HSIL as follows below:CIN 1 is referred to as LSIL. CIN 2 that is negative for p16, a marker for high-risk HPV, is referred to as LSIL. Those that are p16-positive are referred to as HSIL. CIN 3 is referred to as HSIL. Screening The two screening methods available are the Pap smear and testing for HPV.CIN is usually discovered by a screening test, the Pap smear. The purpose of this test is to detect potentially precancerous changes through random sampling of the transformation zone. Pap smear results may be reported using the Bethesda system (see above). The sensitivity and specificity of this test were variable in a systematic review looking at accuracy of the test. An abnormal Pap smear result may lead to a recommendation for colposcopy of the cervix, an in office procedure during which the cervix is examined under magnification. A biopsy is taken of any abnormal appearing areas.Colposcopy can be painful and so researchers have tried to find which pain relief is best for women with CIN to use. Research suggests that compared to a placebo, the injection of a local anaesthetic and vasoconstrictor (medicine that causes blood vessels to narrow) into the cervix may lower blood loss and pain during colposcopy.HPV testing can identify most of the high-risk HPV types responsible for CIN. HPV screening happens either as a co-test with the Pap smear or can be done after a Pap smear showing abnormal cells, called reflex testing. Frequency of screening changes based on guidelines from the Society of Lower Genital Tract Disorders (ASCCP). The World Health Organization also has screening and treatment guidelines for precancerous cervical lesions and prevention of cervical cancer. Primary prevention HPV vaccination is the approach to primary prevention of both CIN and cervical cancer. It is important to note that these vaccines do not protect against 100% of types of HPV known to cause cancer. Therefore, screening is still recommended in vaccinated individuals. Secondary prevention Appropriate management with monitoring and treatment is the approach to secondary prevention of cervical cancer in cases of persons with CIN. Treatment Treatment for CIN 1, mild dysplasia, is not recommended if it lasts fewer than two years. Usually, when a biopsy detects CIN 1, the woman has an HPV infection, which may clear on its own within 12 months. Therefore, it is instead followed for later testing rather than treated. In young women closely monitoring CIN 2 lesions also appears reasonable.Treatment for higher-grade CIN involves removal or destruction of the abnormal cervical cells by cryocautery, electrocautery, laser cautery, loop electrical excision procedure (LEEP), or cervical conization. The typical threshold for treatment is CIN 2+, although a more restrained approach may be taken for young persons and pregnant persons. A Cochrane review found no clear evidence to show which surgical technique may be superior for treating CIN. Evidence suggests that while retinoids are not effective in preventing the progression of CIN, they may be effective in causing regression of disease in people with CIN2. Therapeutic vaccines are currently undergoing clinical trials. The lifetime recurrence rate of CIN is about 20%, but it isnt clear what proportion of these cases are new infections rather than recurrences of the original infection. Research to investigate if prophylactic antibiotics can help prevent infection in women undergoing excision of the cervical transformation zone found a lack of quality evidence.Surgical treatment of CIN lesions is associated with an increased risk of infertility or subfertility. A case-control study found that there is an approximately two-fold increase in risk i.The findings of low quality observational studies suggest that women receiving treatment for CIN during pregnancy may be at an increased risk of premature birth. People with HIV and CIN 2+ should be initially managed according to the recommendations for the general population according to the 2012 updated ASCCP consensus guidelines. Outcomes It used to be thought that cases of CIN progressed through grades 1–3 toward cancer in a linear fashion.However most CIN spontaneously regress. Left untreated, about 70% of CIN 1 will regress within one year; 90% will regress within two years. About 50% of CIN 2 cases will regress within two years without treatment.Progression to cervical carcinoma in situ (CIS) occurs in approximately 11% of CIN 1 and 22% of CIN 2 cases. Progression to invasive cancer occurs in approximately 1% of CIN 1, 5% of CIN 2, and at least 12% of CIN 3 cases.Progression to cancer typically takes 15 years with a range of 3 to 40 years. Also, evidence suggests that cancer can occur without first detectably progressing through CIN grades and that a high-grade intraepithelial neoplasia can occur without first existing as a lower grade.Research suggests that treatment does not affect the chances of getting pregnant but it is associated with an increased risk of miscarriage in the second trimester. Epidemiology Between 250,000 and 1 million American women are diagnosed with CIN annually. Women can develop CIN at any age, however women generally develop it between the ages of 25 to 35. The estimated annual incidence of CIN in the United States among persons who undergo screening is 4% for CIN 1 and 5% for CIN 2 and CIN 3. References == External links ==

Megaloblastic anemia

Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency. Loss of micronutrients may also be a cause. Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim). The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (defined as the presence of neutrophils with six or more lobes or the presence of more than 3% of neutrophils with at least five lobes). These hypersegmented neutrophils can be detected in the peripheral blood (using a diagnostic smear of a blood sample). Causes Vitamin B12 deficiency: Achlorhydria-induced malabsorption Deficient intake Deficient intrinsic factor, a molecule produced by cells in the stomach that is required for B12 absorption (pernicious anemia or gastrectomy) Coeliac disease Biological competition for vitamin B12 by diverticulosis, fistula, intestinal anastomosis, or infection by the marine parasite Diphyllobothrium latum (fish tapeworm) Selective vitamin B12 malabsorption (congenital—juvenile megaloblastic anemia 1—and drug-induced) Chronic pancreatitis Ileal resection and bypass Nitrous oxide anesthesia (usually requires repeated instances). Folate deficiency: Alcoholism Deficient intake Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis Malabsorption (congenital and drug-induced) Intestinal and jejunal resection (indirect) Deficient thiamine and factors (e.g., enzymes) responsible for abnormal folate metabolism. Combined Deficiency: vitamin B12 & folate. Inherited Pyrimidine Synthesis Disorders: Orotic aciduria Inherited DNA Synthesis Disorders Toxins and Drugs: Folic acid antagonists (methotrexate) Purine synthesis antagonists (6-mercaptopurine, azathioprine) Pyrimidine antagonists (cytarabine) Phenytoin Nitrous Oxide Erythroleukemia Inborn genetic mutations of the Methionine synthase gene Di Guglielmos syndrome Congenital dyserythropoietic anemia Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause. Pathophysiology There is a defect in DNA synthesis in the rapidly dividing cells and to a lesser extent, RNA and protein synthesis are also impaired. Therefore, unbalanced cell proliferation and impaired cell division occur as a result of arrested nuclear maturation so the cells show nuclear-cytoplasmic asynchrony. In the bone marrow, most megaloblasts are destroyed prior to entering the peripheral blood (intramedullary hemolysis). Some can escape the bone marrow (macrocytes) to peripheral blood but they are destroyed by the reticulo-endothelial system (extramedullary hemolysis). Diagnosis The gold standard for the diagnosis of Vitamin B12 deficiency is a low blood level of Vitamin B12. A low level of blood Vitamin B12 is a finding that normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis. Hypovitaminosis B12 can result from a number of mechanisms, including those listed above. For determination of cause, further patient history, testing, and empirical therapy may be clinically indicated. A measurement of methylmalonic acid (methylmalonate) can provide an indirect method for partially differentiating Vitamin B12 and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. Direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B12 is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. Vitamin B12 deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood. Due to the lack of available radioactive Vitamin B12, the Schilling test is now largely a historical artifact. The Schilling test was performed in the past to help determine the nature of the vitamin B12 deficiency. An advantage of the Schilling test was that it often included Vitamin B12 with intrinsic factor. Blood findings The blood film can point towards vitamin deficiency: Decreased red blood cell (RBC) count and hemoglobin levels Increased mean corpuscular volume (MCV, >100 fL) and mean corpuscular hemoglobin (MCH) Normal mean corpuscular hemoglobin concentration (MCHC, 32–36 g/dL) Decreased reticulocyte count due to destruction of fragile and abnormal megaloblastic erythroid precursor. The platelet count may be reduced. Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age. Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs). Macrocytes (larger than normal RBCs) are present. Ovalocytes (oval-shaped RBCs) are present. Howell-Jolly bodies (chromosomal remnant) also present.Blood chemistries will also show: An increased lactic acid dehydrogenase (LDH) level. The isozyme is LDH-2 which is typical of the serum and hematopoietic cells. Increased homocysteine and methylmalonic acid in Vitamin B12 deficiency Increased homocysteine in folate deficiencyNormal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia. See also List of circulatory system conditions List of hematologic conditions References External links GeneReview/NCBI/NIH/UW entry on Thiamine-Responsive Megaloblastic Anemia Syndrome Rare Anemias Foundation

Hypochloremia

Hypochloremia (or Hypochloraemia) is an electrolyte disturbance in which there is an abnormally low level of the chloride ion in the blood. The normal serum range for chloride is 97 to 107 mEq/L. It rarely occurs in the absence of other abnormalities. It is sometimes associated with hypoventilation. It can be associated with chronic respiratory acidosis. If it occurs together with metabolic alkalosis (decreased blood acidity) it is often due to vomiting. It is usually the result of hyponatremia or elevated bicarbonate concentration. It occurs in cystic fibrosis. References == External links ==

Urinary bladder disease

Urinary bladder disease includes urinary bladder inflammation such as cystitis, bladder rupture and bladder obstruction (tamponade). Cystitis is common, sometimes referred to as urinary tract infection (UTI) caused by bacteria, bladder rupture occurs when the bladder is overfilled and not emptied while bladder tamponade is a result of blood clot formation near the bladder outlet. Cystitis Cystitis is a urinary bladder inflammation that results from any one of a number of distinct syndromes. It is most commonly caused by a bacterial infection in which case it is referred to as a urinary tract infection. Bladder trauma Bladder rupture (rupture of bladder, N32.4) may occur if the bladder is overfilled and not emptied. This can occur in the case of binge drinkers who have consumed large quantities of fluids, but are not conscious of the need to urinate due to stupor. This condition is very rare in women, but does occur. Signs and symptoms include localized pain and uraemia (poisoning due to reabsorbed waste). Intra- and extraperitoneal rupture Bladder rupture is divided into intraperitoneal and extraperitoneal rupture, with the latter encompassing 85% of post-traumatic bladder rupture. Intraperitoneal rupture is both more rare and associated with greater morbidity, requiring surgical repair due to the risk of non-healing and gram negative sepsis. Bladder tamponade Bladder tamponade is obstruction of the bladder outlet due to heavy blood clot formation within it. It generally requires surgery. Such heavy bleeding is usually due to bladder cancer. See also Underactive bladder Overactive bladder References External links http://kidney.niddk.nih.gov/kudiseases/topics/bladder.asp

Ascending cholangitis

Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum (first part of the small intestine). It tends to occur if the bile duct is already partially obstructed by gallstones.Cholangitis can be life-threatening, and is regarded as a medical emergency. Characteristic symptoms include yellow discoloration of the skin or whites of the eyes, fever, abdominal pain, and in severe cases, low blood pressure and confusion. Initial treatment is with intravenous fluids and antibiotics, but there is often an underlying problem (such as gallstones or narrowing in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy to relieve obstruction of the bile duct. The word is from Greek chol-, bile + ang-, vessel + -itis, inflammation. Signs and symptoms A person with cholangitis may complain of abdominal pain (particularly in the right upper quadrant of the abdomen), fever, rigors (uncontrollable shaking) and a feeling of uneasiness (malaise). Some may report jaundice (yellow discoloration of the skin and the whites of the eyes).Physical examination findings typically include jaundice and right upper quadrant tenderness. Charcots triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever. This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%. Reynolds pentad includes the findings of Charcots triad with the presence of septic shock and mental confusion. This combination of symptoms indicates worsening of the condition and the development of sepsis, and is seen less commonly still.In the elderly, the presentation may be atypical; they may directly collapse due to sepsis without first showing typical features. Those with an indwelling stent in the bile duct (see below) may not develop jaundice. Causes Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system).Parasites which may infect the liver and bile ducts may cause cholangitis; these include the roundworm Ascaris lumbricoides and the liver flukes Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. In people with AIDS, a large number of opportunistic organisms has been known to cause AIDS cholangiopathy, but the risk has rapidly diminished since the introduction of effective AIDS treatment. Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure. Pathogenesis Bile is produced by the liver, and serves to eliminate cholesterol and bilirubin from the body, as well as emulsifying of fats to make them more soluble in water and aid in their digestion. Bile is formed in the liver by hepatocytes (liver cells) and excreted into the common hepatic duct. Part of the bile is stored in the gall bladder because of back pressure (exerted by the sphincter of Oddi), and may be released at the time of digestion. The gallbladder also concentrates the bile by absorbing water and dissolved salts from it. All bile reaches the duodenum (first part of the small intestine) through the common bile duct and the ampulla of Vater. The sphincter of Oddi, located at the junction of the ampulla of Vater and the duodenum, is a circular muscle that controls the release of both bile and pancreatic secretions into the digestive tract.The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 cmH2O) and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow the establishment of an infection. The constitution of bile—bile salts and immunoglobulin secreted by the epithelium of the bile duct also has a protective role. Bacterial contamination alone in absence of obstruction does not usually result in cholangitis. However increased pressure within the biliary system (above 20 cmH2O) resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of Kupffer cells, which are specialized macrophage cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of IgA immunoglobulins in the bile. This results in bacteremia (bacteria in the blood stream) and gives rise to the systemic inflammatory response syndrome (SIRS) comprising fever (often with rigors), tachycardia, increased respiratory rate and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called sepsis. Biliary obstruction itself disadvantages the immune system and impairs its capability to fight infection, by impairing the function of certain immune system cells (neutrophil granulocytes) and modifying the levels of immune hormones (cytokines).In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi. Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon, are considered less likely. Diagnosis Blood tests Routine blood tests show features of acute inflammation (raised white blood cell count and elevated C-reactive protein level), and usually abnormal liver function tests (LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis, with elevations in alanine transaminase and aspartate transaminase.Blood cultures are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases, usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli: Escherichia coli (25–50%), Klebsiella (15–20%) and Enterobacter (5–10%). Of the gram-positive cocci, Enterococcus causes 10–20%. Medical imaging Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound, as this is the most easily available. Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones farther down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis (inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound. A better test is magnetic resonance cholangiopancreatography (MRCP), which uses magnetic resonance imaging (MRI); this has a comparable sensitivity to ERCP. Smaller stones, however, can still be missed on MRCP depending on the quality of the hospitals facilities.The gold standard test for biliary obstruction is still endoscopic retrograde cholangiopancreatography (ERCP). This involves the use of endoscopy (passing a tube through the mouth into the esophagus, stomach and thence to the duodenum) to pass a small cannula into the bile duct. At that point, radiocontrast is injected to opacify the duct, and X-rays are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.If other causes rather than gallstones are suspected (such as a tumor), computed tomography and endoscopic ultrasound (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy (tissue sample) of suspicious masses. EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability. Treatment Fluids and antibiotics Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure. Endoscopy The definitive treatment for cholangitis is relief of the underlying biliary obstruction. This is usually deferred until 24–48 hours after admission, when the patient is stable and has shown some improvement with antibiotics, but may need to happen as an emergency in case of ongoing deterioration despite adequate treatment, or if antibiotics are not effective in reducing the signs of infection (which happens in 15% of cases).Endoscopic retrograde cholangiopancreatography (ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the common bile duct; alternatively or additionally, the common bile duct orifice can be dilated with a balloon. Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical lithotriptor in order to crush the stone prior to removal. Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by extracorporeal shock wave lithotripsy. This technique uses acoustic shock waves administered outside the body to break down the stones. An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone. Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with laparoscopy, is required to remove the stone.Narrowed areas may be bridged by a stent, a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent self-expanding metal stents with a longer lifespan are used if the obstruction is due to pressure from a tumor such as pancreatic cancer. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a nasogastric tube, but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment. Certain treatments may be unsafe if blood clotting is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as clopidogrel (which inhibits platelet aggregation) or if the prothrombin time is significantly prolonged. For a prolonged prothrombin time, vitamin K or fresh frozen plasma may be administered to reduce bleeding risk. Percutaneous biliary drainage In cases where a person is too ill to tolerate endoscopy or when a retrograde endoscopic approach fails to access the obstruction, a percutaneous transhepatic cholangiogram (PTC) may be performed to evaluate the biliary system for placement of a percutaneous biliary drain (PBD). This is often necessary in the case of a proximal stricture or a bilioenteric anastomosis (a surgical connection between the bile duct and small bowel, such as the duodenum or jejunum). Once access across the stricture is obtained, balloon dilation can be performed and stones can be swept forward into the duodenum. Due to potential complications of percutaneous biliary drain placement and the necessity of regular drain maintenance, a retrograde approach via ERCP remains first-line therapy. Cholecystectomy Not all gallstones implicated in ascending cholangitis actually originate from the gallbladder, but cholecystectomy (surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones. Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or cholecystostomy; the risk of death is also significantly increased. Prognosis Acute cholangitis carries a significant risk of death, the leading cause being irreversible shock with multiple organ failure (a possible complication of severe infections). Improvements in diagnosis and treatment have led to a reduction in mortality: before 1980, the mortality rate was greater than 50%, but after 1980 it was 10–30%. Patients with signs of multiple organ failure are likely to die unless they undergo early biliary drainage and treatment with systemic antibiotics. Other causes of death following severe cholangitis include heart failure and pneumonia.Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis, biliary narrowing due to cancer, acute kidney injury and the presence of liver abscesses. Complications following severe cholangitis include kidney failure, respiratory failure (inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), abnormal heart rhythms, wound infection, pneumonia, gastrointestinal bleeding and myocardial ischemia (lack of blood flow to the heart, leading to heart attacks). Epidemiology In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten years, 15–26% will have one or more episodes of biliary colic (abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: acute pancreatitis, cholecystitis or acute cholangitis. Prevalence of gallstone disease increases with age and body mass index (a marker of obesity). However, the risk is also increased in those who lose weight rapidly (e.g. after weight loss surgery) due to alterations in the composition of the bile that makes it prone to form stones. Gallstones are slightly more common in women than in men, and pregnancy increases the risk further. History Dr Jean-Martin Charcot, working at the Salpêtrière Hospital in Paris, France, is credited with early reports of cholangitis, as well as his eponymous triad, in 1877. He referred to the condition as "hepatic fever" (fièvre hépatique). Dr Benedict M. Reynolds, an American surgeon, reignited interest in the condition in his 1959 report with colleague Dr Everett L. Dargan, and formulated the pentad that carries his name. It remained a condition generally treated by surgeons, with exploration of the bile duct and excision of gallstones, until the ascendancy of ERCP in 1968. ERCP is generally performed by internal medicine or gastroenterology specialists. In 1992 it was shown that ERCP was generally safer than surgical intervention in ascending cholangitis. See also Primary sclerosing cholangitis (an autoimmune disease leading to narrowing of the bile ducts) Gallstone-related pancreatitis References == External links ==

Cardiomegaly

Cardiomegaly (sometimes megacardia or megalocardia) is a medical condition in which the heart is enlarged. As such, it is more commonly referred to simply as "having an enlarged heart". It is usually the result of underlying conditions that make the heart work harder, such as obesity, heart valve disease, high blood pressure (hypertension), and coronary artery disease. Cardiomyopathy is also associated with cardiomegaly.Cardiomegaly can be serious depending on what part of the heart is enlarged, and can result in congestive heart failure. Recent studies suggest that cardiomegaly is associated with a higher risk of sudden cardiac death.Cardiomegaly may improve over time, but many people with an enlarged heart (dilated cardiomyopathy) need lifelong treatment with medication. Having an immediate family member who has or had cardiomegaly may indicate that a person is more susceptible to getting this condition. Signs and symptoms For many people, cardiomegaly is asymptomatic. For others, if the enlarged heart begins to affect the bodys ability to pump blood effectively, then symptoms associated with congestive heart failure may arise, including: Heart palpitations – the irregular beating of the heart, usually associated with a valve issue inside the heart. Severe shortness of breath (especially when physically active) – irregularly unable to catch ones breath. Chest pain Coughing, when lying down Fatigue Swelling in legs Increased abdominal girth Weight gain Edema – swelling FaintingThere is not much variation in these symptoms because they are mostly specific to the chest area. However, some are more common than others depending on each patient. Causes The causes of cardiomegaly are not well understood and many cases of cardiomegaly have no known cause. Prevention of cardiomegaly starts with detection. If a person has a family history of cardiomegaly, one should let ones doctor know so that treatments can be implemented to help prevent the worsening of the condition. In addition, prevention includes avoiding certain lifestyle risk factors such as tobacco use and controlling ones high cholesterol, high blood pressure, and diabetes. Non-lifestyle risk factors include a family history of cardiomegaly, coronary artery disease (CAD), congenital heart failure, atherosclerotic disease, valvular heart disease, exposure to cardiac toxins, sleep-disordered breathing (such as sleep apnea), sustained cardiac arrhythmias, abnormal electrocardiograms, and cardiomegaly on chest X-ray. Lifestyle factors that can help prevent cardiomegaly include eating a healthy diet, controlling blood pressure, exercise, medications, and not abusing alcohol and cocaine. Current research and the evidence of previous cases link the following (below) as possible causes of cardiomegaly.The most common known causes of cardiomegaly are congenital (patients are born with the condition based on a genetic inheritance), high blood pressure (which can enlarge the left ventricle causing the heart muscle to weaken over time), and coronary artery disease. In the latter case, the disease creates blockages in the hearts blood supply, leading to tissue death which causes other areas of the heart to work harder, causing the heart to expand in size.Other possible causes include: Heart valve disease Cardiomyopathy (disease of the heart muscle) Pulmonary hypertension Pericardial effusion (fluid around the heart) Thyroid Disorders Hemochromatosis (excessive iron in the blood) Amyloidosis Chagas disease, an important cause of cardiomegaly in Latin America Viral infection of the heart Pregnancy, with enlarged heart developing around the time of delivery (peripartum cardiomyopathy) Kidney disease requiring dialysis Alcohol or cocaine abuse HIV infection Diabetes Mechanism Cardiomegaly is a condition affecting the cardiovascular system, specifically the heart. This condition is strongly associated with congestive heart failure. Within the heart, the working fibers of the myocardial tissue increase in size. As the heart works harder the actin and myosin filaments experience less overlap which increases the size of the myocardial fibers. If there is less overlap of the protein filaments within the sarcomeres of the muscle fibers, they will not be able to effectively pull on one another. If the heart tissue gets too big and stretches too far, then those filaments cannot effectively pull on one another to shorten the muscle fibers, impacting the hearts sliding filament mechanism. If fibers cannot shorten properly and the heart cannot contract properly, then blood cannot be effectively pumped to the lungs to be re-oxygenated or to the body to deliver oxygen to the working tissues of the body.A person with an enlarged heart is more susceptible to forming blood clots in the lining of their heart. These clots can also be formed in other parts of the body. Once they enter the bloodstream, it makes it difficult for the organs in the body to receive blood, due to the blockage caused by the clots. This can impact other body systems as well and lead to other problems. Diagnosis There are many techniques and tests used to diagnose an enlarged heart. The results of these tests can often be used to see how efficiently the heart is pumping, determine which chambers of the heart are enlarged, look for evidence of previous heart attacks and determine if a person has congenital heart disease. Chest X-Ray: X-ray images help see the condition of the lungs and heart. If the heart is enlarged on an X-ray, other tests will usually be needed to find the cause. A useful measurement on X-ray is the cardio-thoracic ratio, which is the transverse diameter of the heart, compared with that of the thoracic cage." These diameters are taken from PA chest x-rays using the widest point of the chest and measuring as far as the lung pleura, not the lateral skin margins. If the cardiac thoracic ratio is greater than 50%, pathology is suspected, assuming the x-ray has been taken correctly. The measurement was first proposed in 1919 to screen military recruits. A newer approach to using these x-rays for evaluating heart health takes the ratio of heart area to chest area and has been called the two-dimensional cardiothoracic ratio. Electrocardiogram: This test records the electrical activity of the heart through electrodes attached to the persons skin. Impulses are recorded as waves and displayed on a monitor or printed on paper. This test helps diagnose heart rhythm problems and assess the damage to a persons heart from a heart attack. Echocardiogram: This test for diagnosing and monitoring an enlarged heart uses sound waves to produce a video image of the heart. With this test, the four chambers of the heart can be evaluated. Stress test: A stress test, also called an exercise stress test, provides information about how well the heart works during physical activity. It usually involves walking on a treadmill or riding a stationary bike while the heart rhythm, blood pressure, and breathing are monitored. Cardiac computerized tomography (CT) or magnetic resonance imaging (MRI). In a cardiac CT scan, one lies on a table inside a machine called a gantry. An X-ray tube inside the machine rotates around the body and collects images of the heart and chest. In a cardiac MRI, one lies on a table inside a long tube-like machine that uses a magnetic field and radio waves to produce signals that create images of the heart. Blood tests: Blood tests may be ordered to check the levels of substances in the blood that may show a heart problem. Blood tests can also help rule out other conditions that may cause ones symptoms. Cardiac catheterization and biopsy: In this procedure, a thin tube (catheter) is inserted into the groin and threaded through the blood vessels to the heart, where a small sample (biopsy) of the heart, if indicated, can be extracted for laboratory analysis. For deceased people, cardiomegaly at autopsy has been suggested when the heart weighs more than >399 grams in women and >449 grams in men. Classification Cardiomegaly can be classified by the main enlarged location of the heart, and/or by the structure of the enlargement. There are also specific additional subtypes. For example, the athletic heart syndrome is a non-pathological condition commonly seen in sports medicine in which the human heart is enlarged, and the resting heart rate is lower than normal. By enlarged location Ventricular hypertrophy Left Right / Cor pulmonale Atrial enlargement Left Right Structure of enlargement Dilated cardiomyopathy is the most common type of cardiomegaly. In this condition, the walls of the left and/or right ventricles of the heart become thin and stretched. The result is an enlarged heart.In the other types of cardiomegaly, the hearts large muscular left ventricle becomes abnormally thick. Hypertrophy is usually what causes left ventricular enlargement. Hypertrophic cardiomyopathy is typically an inherited condition. Treatment Treatments for cardiomegaly include a combination of medication treatment and medical/surgical procedures. Below are some of the treatment options for individuals with cardiomegaly: Medications Diuretics: to lower the amount of sodium and water in the body, which can help lower the pressure in the arteries and heart. Angiotensin-converting enzyme (ACE) inhibitors: to lower the blood pressure and improve the hearts pumping ability. Angiotensin receptor blockers (ARBs): to provide the benefits of ACE inhibitors for those who cant take ACE inhibitors. Beta blockers: to lower blood pressure and improve heart function. Digoxin: to help improve the pumping function of the heart and lessen the need for hospitalization for heart failure. Anticoagulants: to reduce the risk of blood clots that could cause a heart attack or stroke. Anti-arrhythmics: to keep the heart beating with a normal rhythm.Medical devices to regulate the heartbeat Pacemaker: Coordinates the contractions between the left and right ventricle. In people who may be at risk of serious arrhythmias, drug therapy or an implantable cardioverter-defibrillator (ICD) may be used. ICDs: Small devices implanted in the chest to constantly monitor the heart rhythm and deliver electrical shocks when needed to control abnormal, rapid heartbeats. The devices can also work as pacemakers.Surgical procedures Heart valve surgery: If an enlarged heart is caused by a problem with one of the heart valves, one may have surgery to remove the valve and replace it with either an artificial valve or a tissue valve from a pig, cow or deceased human donor. If blood leaks backward through a valve (valve regurgitation), the leaky valve may be surgically repaired or replaced. Coronary bypass surgery: If an enlarged heart is related to coronary artery disease, one may opt to have coronary artery bypass surgery. Left ventricular assist device: (LVAD): This implantable mechanical pump helps a weak heart pump. LVADs are often implanted while a patient waits for a heart transplant or, if the patient is not a heart transplant candidate, as a long-term treatment for heart failure. Heart transplant: If medications cant control the symptoms, a heart transplant is often a final option.Cardiomegaly can progress and certain complications are common: Heart failure: One of the most serious types of enlarged heart, an enlarged left ventricle, increases the risk of heart failure. In heart failure, the heart muscle weakens, and the ventricles stretch (dilate) to the point that the heart cant pump blood efficiently throughout the body. Blood clots: Having an enlarged heart may make one more susceptible to forming blood clots in the lining of the heart. If clots enter the bloodstream, they can block blood flow to vital organs, even causing a heart attack or stroke. Clots that develop on the right side of the heart may travel to the lungs, a dangerous condition called a pulmonary embolism. Heart murmur: For people who have an enlarged heart, two of the hearts four valves — the mitral and tricuspid valves — may not close properly because they become dilated, leading to a backflow of blood. This flow creates sounds called heart murmurs. The exact mortality rate for people with cardiomegaly is unknown. However, many people live for a very long time with an enlarged heart and, if detected early, treatment can help improve the condition and prolong their lives. For some people cardiomegaly is a temporary condition, which can resolve on its own, making ones lifestyle normal like before. Others may have a permanent enlargement, which would then need to be taken care of by the above treatment options.Lifestyle changes Smoking cessation Limiting alcohol and caffeine intake Maintaining a healthy weight Increasing fruits and vegetables in a daily diet Limiting consumption of high-fat and/or high-sugar foods Getting adequate restful sleep References Further reading Amin, Hina; Siddiqui, Waqas J. (2019). "Cardiomegaly". StatPearls. StatPearls Publishing. PMID 31194436. Ampanozi, Garyfalia; Krinke, Eileen; Laberke, Patrick; Schweitzer, Wolf; Thali, Michael J.; Ebert, Lars C. (1 September 2018). "Comparing fist size to heart size is not a viable technique to assess cardiomegaly". Cardiovascular Pathology. 36: 1–5. doi:10.1016/j.carpath.2018.04.009. PMID 29859507. S2CID 44086023. Agostoni, PierGiuseppe; Cattadori, Gaia; Guazzi, Marco; Palermo, Pietro; Bussotti, Maurizio; Marenzi, Giancarlo (1 November 2000). "Cardiomegaly as a possible cause of lung dysfunction in patients with heart failure". American Heart Journal. 140 (5): A17–A21. doi:10.1067/mhj.2000.110282. PMID 11054632. Luedde, Mark; Katus, Hugo; Frey, Norbert (1 January 2006). "Novel Molecular Targets in the Treatment of Cardiac Hypertrophy". Recent Patents on Cardiovascular Drug Discovery. 1 (1): 1–20. doi:10.2174/157489006775244290. PMID 18221071. External links American Heart Association

Pyuria

Pyuria is the condition of urine containing white blood cells or pus. Defined as the presence of 6-10 or more neutrophils per high power field of unspun, voided mid-stream urine, it can be a sign of a bacterial urinary tract infection. Pyuria may be present in people with sepsis, or in older people with pneumonia. Others additionally require discoloration, clouding or change in the smell of urine for a pyuria to be present. Without these additional features, there is said to be leukocyturia. Sterile pyuria is urine which contains white blood cells while appearing sterile by standard culturing techniques. It is often caused by sexually transmitted infections, such as gonorrhea, or viruses which will not grow in bacterial cultures. Sterile pyuria is listed as a side effect from some medications such as paracetamol (acetaminophen). Its occurrence is also associated with certain disease processes, such as Kawasaki disease and genitourinary tuberculosis. However, there are many known causes, including systemic or infectious disease, structural and physiological reasons, intrinsic kidney pathology, or drugs. Leukocyturia Under normal conditions, fewer than two million leukocytes are expelled in urine per day. A number greater than two million is called leucocyturia and can be determined when determining the Addis count.However, this method requires a 24-hour urine collection, so it is not practical. Currently, the number of leukocytes is estimated under the microscope for which morning urine is taken. It has been arbitrarily assumed that a number of over 4-5 leukocytes in the field of vision of the microscope indicates leukocyturia.At the moment, there are also quick test strips available, allowing after wetting a special diagnostic bar, the detection of granulocytes in the urine, as evidenced by the color change of the test strip. The principle of their operation is based on the detection of granulocytes esterases, including leukocytes. This method, however, is burdened with a large number of false positive results (use of antibiotics, such as imipenem, meropenem, clavulanic acid, which is sometimes combined with penicillin derivatives) or false negative (gentamicin, cefalexin, glycosuria, proteinuria).Leukocyturia is a laboratory symptom of many diseases like glomerulonephritis or pyelonephritis. It may occur in the case of diseases of the urinary tract, reproductive system and diseases of the abdominal organs. Leukocyturia is mostly a sign of urinary tract infection, especially if significant bacteriuria is found (for most people, the number of bacteria in a culture is > 10^5) and other symptoms associated with passing urine. The presence of leukocyturia does not indicate the need for antimicrobial therapy yet. Additional images See also Urinalysis Bacteriuria References == External links ==

Hemolysis

Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo or in vitro. One cause of hemolysis is the action of hemolysins, toxins that are produced by certain pathogenic bacteria or fungi. Another cause is intense physical exercise. Hemolysins damage the red blood cells cytoplasmic membrane, causing lysis and eventually cell death. Etymology From hemo- + -lysis, from Ancient Greek: [n] αἷμα (haîma, "blood") + λύσις (lúsis, "loosening"). Inside the body Hemolysis inside the body can be caused by a large number of medical conditions, including some parasites (e.g., Plasmodium), some autoimmune disorders (e.g., autoimmune haemolytic anaemia, drug-induced hemolytic anemia, atypical hemolytic uremic syndrome (aHUS)), some genetic disorders (e.g., Sickle-cell disease or G6PD deficiency), or blood with too low a solute concentration (hypotonic to cells).Hemolysis can lead to hemoglobinemia due to hemoglobin released into the blood plasma, which plays a significant role in the pathogenesis of sepsis and can lead to increased risk of infection due to its inhibitory effects on the innate immune system. Parasitic hemolysis Because the feeding process of the Plasmodium parasites damages red blood cells, malaria is sometimes called "parasitic hemolysis" in medical literature. HELLP, pre-eclampsia, or eclampsia See HELLP syndrome, Pre-eclampsia, and Eclampsia Hemolytic disease of the newborn Hemolytic disease of the newborn is an autoimmune disease resulting from the mothers antibodies crossing the placenta to the fetus. This most often occurs when the mother has previously been exposed to blood antigens present on the fetus but foreign to her, through either a blood transfusion or a previous pregnancy. Hemolytic anemia Because in vivo hemolysis destroys red blood cells, in uncontrolled, chronic or severe cases it can lead to hemolytic anemia. Hemolytic crisis A hemolytic crisis, or hyperhemolytic crisis, is characterized by an accelerated rate of red blood cell destruction leading to anemia, jaundice, and reticulocytosis. Hemolytic crises are a major concern with sickle-cell disease and G6PD deficiency. Toxic agent ingestion or poisoning Paxillus involutus ingestion can cause hemolysis. Space hemolysis Spaceflight can cause hemolysis. Intrinsic causes Hemolysis may result from intrinsic defects in the red blood cell itself: Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis) Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia) Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency) Paroxysmal nocturnal hemoglobinuria (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia. Extrinsic causes Extrinsic hemolysis is caused by the red blood cells environment: Immune-mediated causes could include transient factors as in Mycoplasma pneumoniae infection (cold agglutinin disease) or permanent factors as in autoimmune diseases like autoimmune hemolytic anemia (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkins lymphoma, and chronic lymphocytic leukemia). Spur cell hemolytic anemia Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension. Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria). Lead poisoning or poisoning by arsine or stibine causes non-immune hemolytic anemia. Runners can develop hemolytic anemia due to "footstrike hemolysis", the destruction of red blood cells in feet at foot impact. Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%. Intravascular hemolysis Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbilirubinemia.Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as Babesia. Additionally, thrombotic microangiopathy (TMA) can result in hemolysis of red blood cells. TMA is frequently observed in aHUS patients where clots form in the small vessels of the kidney resulting in damaged red blood cells as they attempt to pass through the restricted vessels. Extravascular hemolysis Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. In this case little hemoglobin escapes into blood plasma. The macrophages of the reticuloendothelial system in these organs engulf and destroy structurally-defective red blood cells, or those with antibodies attached, and release unconjugated bilirubin into the blood plasma circulation. Typically, the spleen destroys mildly abnormal red blood cells or those coated with IgG-type antibodies, while severely abnormal red blood cells or those coated with IgM-type antibodies are destroyed in the circulation or in the liver.If extravascular hemolysis is extensive, hemosiderin can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in hemosiderosis. Outside the body In vitro hemolysis can be caused by improper technique during collection of blood specimens, by the effects of mechanical processing of blood, or by bacterial action in cultured blood specimens. From specimen collection Most causes of in vitro hemolysis are related to specimen collection. Difficult collections, unsecure line connections, contamination, and incorrect needle size, as well as improper tube mixing and incorrectly filled tubes are all frequent causes of hemolysis. Excessive suction can cause the red blood cells to be smashed on their way through the hypodermic needle owing to turbulence and physical forces. Such hemolysis is more likely to occur when a patients veins are difficult to find or when they collapse when blood is removed by a syringe or a modern vacuum tube. Experience and proper technique are key for any phlebotomist, nurse or doctor to prevent hemolysis. In vitro hemolysis during specimen collection can cause inaccurate laboratory test results by contaminating the surrounding plasma with the contents of hemolyzed red blood cells. For example, the concentration of potassium inside red blood cells is much higher than in the plasma and so an elevated potassium level is usually found in biochemistry tests of hemolyzed blood. After the blood collection process, in vitro hemolysis can still occur in a sample due to external factors, such as prolonged storage, incorrect storage conditions and excessive physical forces by dropping or vigorously mixing the tube. From mechanical blood processing during surgery In some surgical procedures (especially some heart operations) where substantial blood loss is expected, machinery is used for intraoperative blood salvage. A centrifuge process takes blood from the patient, washes the red blood cells with normal saline, and returns them to the patients blood circulation. Hemolysis may occur if the centrifuge rotates too quickly (generally greater than 500 rpm)—essentially this is hemolysis occurring outside of the body. Increased hemolysis occurs with massive amounts of sudden blood loss, because the process of returning a patients cells must be done at a correspondingly higher speed to prevent hypotension, pH imbalance, and a number of other hemodynamic and blood level factors. Modeling of fluid flows to predict the likelihood of red cell membrane rupture in response to stress is an active area of research. From bacteria culture Visualizing the physical appearance of hemolysis in cultured blood samples may be used as a tool to determine the species of various Gram-positive bacteria infections (e.g., Streptococcus). Nomenclature Hemolysis is sometimes called hematolysis, erythrolysis, or erythrocytolysis. The words hemolysis () and hematolysis () both use combining forms conveying the idea of "lysis of blood" (hemo- or hemato- + -lysis). The words erythrolysis () and erythrocytolysis () both use combining forms conveying the idea of "lysis of erythrocytes" (erythro- ± cyto- + -lysis). Red blood cells (erythrocytes) have a short lifespan (approximately 120 days), and old (senescent) cells are constantly removed and replaced with new ones via erythropoiesis. This breakdown/replacement process is called erythrocyte turnover. In this sense, erythrolysis or hemolysis is a normal process that happens continually. However, these terms are usually used to indicate that the lysis is pathological. Complications Pulmonary hypertension has been gaining recognition as a complication of chronic hereditary and acquired hemolysis. Free hemoglobin released during hemolysis inactivates the vasodilator nitric oxide (NO). Hemolysis also releases arginase that depletes L-arginine, the substrate needed for NO synthesis. This reduces NO-dependent vasodilation and induces platelet activation, thrombin generation, procoagulant factors and tissue factor activation, contributing to the formation of thrombosis. This can lead to esophageal spasm and dysphagia, abdominal pain, erectile dysfunction, systemic hypertension, decreased organ perfusion, promotion of inflammation and coagulation, and thrombosis.Chronic hemolysis may also lead to endothelial dysfunction, heightened endothelin-1-mediated responses and vasculopathy. The release of heme leads to the production of bilirubin and depletion of plasma proteins, such as albumin, haptoglobin, and hemopexin, which may lead to jaundice. It may also lead to increased levels of the heme breakdown product stercobilin in the stool.Splenectomy of those with hemolytic disorders appears to increase risk of developing pulmonary thrombosis.Complications may also arise from the increased workload for the kidney as it secretes erythropoietin to stimulate the bone marrow to produce more reticulocytes (red blood cell precursors) to compensate for the loss of red blood cells due to hemolysis. See also Hemolysin Glucose-6-phosphate dehydrogenase deficiency References External links Effects of Hemolysis on Clinical Specimens

Hypopnea

Hypopnea is overly shallow breathing or an abnormally low respiratory rate. Hypopnea is defined by some to be less severe than apnea (the complete cessation of breathing), while other researchers have discovered hypopnea to have a "similar if not indistinguishable impact" on the negative outcomes of sleep breathing disorders. In sleep clinics, obstructive sleep apnea syndrome or obstructive sleep apnea–hypopnea syndrome is normally diagnosed based on the frequent presence of apneas and/or hypopneas rather than differentiating between the two phenomena. Hypopnea is typically defined by a decreased amount of air movement into the lungs and can cause oxygen levels in the blood to drop. It commonly is due to partial obstruction of the upper airway. Hypopnea during sleep is classed as a sleep disorder. With moderate to severe hypopnea, sleep is disturbed such that patients may get a full nights sleep but still not feel rested because they did not get the right kind of sleep. The disruption in breathing causes a drop in blood oxygen level, which may in turn disrupt the stages of sleep. Daytime hypopnea events, however, are mostly limited to those with severely compromised respiratory muscles, as occurs in certain neuromuscular diseases or compromised central respiratory drive, as occurs in conditions such as acquired or congenital central hypoventilation syndrome (ACHS or CCHS). Daytime hypopnea can also cause a drop in blood oxygen level. Symptoms The most common hypopnea symptom is excessive sleepiness, which results from constant sleep interruption. People with hypopnea due to airflow obstruction often have loud, heavy snoring that is interrupted with choking sounds or loud snorts followed by periods of silence, because not enough air can flow into the lungs through the mouth and nose. The periods of silence can last 20 seconds or longer and can happen many times each hour, resulting in poor sleep and reduced levels of oxygen in the blood. Other symptoms of hypopnea may include depression, forgetfulness, mood or behaviour changes, trouble concentrating, loss of energy, nervousness, and morning headaches. Not all people with hypopnea experience all of these symptoms and not everyone who has these symptoms has hypopnea. Consequences Hypopnea is a disorder that may result in excessive daytime sleepiness and compromised quality of life, including traffic accidents, diminished productivity in the workplace, and emotional problems. Cardiovascular consequences of hypopnea may include myocardial infarction, hypertension, coronary heart disease as well other problems such as stroke, psychiatric problems, impotence, cognitive dysfunction and memory loss. Causes Among the causes of hypopnea are: anatomical defects such as nasal septum deformation or congenital narrowness of nasal meatus and the gullet acute tonsillitis and/or adenoiditis obesity or being overweight neuromuscular disease or any condition that entails weakened respiratory muscles hypoventilation syndromes involving compromised or failed respiratory drive use of sedatives, for example sleeping pills hazardous alcohol use smoking aging others, most of which are also typical causes of airway obstruction, snoring and sleep apnea Diagnosis In the context of diagnosis and treatment of sleep disorders, a hypopnea is not considered to be clinically significant unless there is a 30% or greater reduction in flow lasting for 10 seconds or longer and an associated 4% or greater desaturation in the persons O2 levels, or if it results in arousal or fragmentation of sleep. The direct consequence of hypopnea (as well as apnea) is that the CO2 in the blood increases and the oxygen level in the patients blood decrease is proportionate to the severity of the airway obstruction. This disruptive pattern of breathing generates disruptive sleep patterns, the consequences of which being that those individuals may exhibit increased fatigability, lethargy, decreased ability to concentrate, increased irritability, and morning headaches. Basically, those individuals are extremely tired due to their inability to get a good nights sleep. Hypopneas can be either central i.e., as part of a waxing and waning in breathing effort, or obstructive in origin. During an obstructive hypopnea, in comparison to an obstructive apnea, the airway is only partially closed. However, this closure is still enough to cause a physiological effect i.e., an oxygen desaturation and/or an increase in breathing effort terminating in arousal. A Hypopnea Index (HI) can be calculated by dividing the number of hypopnea events during the sleep period by the number of hours of sleep. The Apnea-Hypopnea Index (AHI) is an index of severity that combines apneas and hypopneas. Combining them both gives an overall severity of sleep apnea including sleep disruptions and desaturations (a low level of oxygen in the blood). The apnea-hypopnea index, like the apnea index and hypopnea index, is calculated by dividing the number of apneas and hypopneas by the number of hours of sleep. Another index that is used to measure sleep apnea is the Respiratory Disturbance Index (RDI). The RDI is similar to the AHI, however, RDI also includes respiratory events that do not technically meet the definitions of apneas or hypopneas, such as a Respiratory Effort Related Arousal (RERA), but do disrupt sleep. Treatment Obstructive hypopnea One treatment for obstructive hypopnea is continuous positive airway pressure (CPAP). CPAP is a treatment in which the patient wears a mask over the nose and/or mouth. An air blower forces air through the upper airway. The air pressure is adjusted so that it is just enough to maintain the oxygen saturation levels in the blood. Another treatment is sometimes a custom fitted oral appliance. The American Academy of Sleep Medicines protocol for obstructive sleep apnea (OSA) recommends oral appliances for those who prefer them to CPAP and have mild to moderate sleep apnea or those that do not respond to/cannot wear a CPAP. Severe cases of OSA may be treated with an oral appliance if the patient has had a trial run with a CPAP. Oral appliances should be custom made by a dentist with training in dental sleep medicine.Mild obstructive hypopnea can often be treated by losing weight or by avoiding sleeping on ones back. Also quitting smoking, and avoiding alcohol, sedatives and hypnotics (soporifics) before sleep can be quite effective. Surgery is generally a last resort in hypopnea treatment, but is a site-specific option for the upper airway. Depending on the cause of obstruction, surgery may focus on the soft palate, the uvula, tonsils, adenoids or the tongue. There are also more complex surgeries that are performed with the adjustment of other bone structures - the mouth, nose and facial bones. Central hypopnea People with neuromuscular disorders or hypoventilation syndromes involving failed respiratory drive experience central hypoventilation. The most common treatment for this form is the use of non-invasive ventilation such as a bilevel positive airway pressure (BPAP) machine. Etymology The word hypopnea uses combining forms of hypo- + -pnea, from the Greek roots hypo- (meaning low, under, beneath, down, below normal) and pnoia (meaning breathing). See pronunciation information at dyspnea. See also List of terms of lung size and activity Bradypnea References http://www2.merriam-webster.com/cgi-bin/mwmednlm?book=Medical&va=hypopnea http://www.emedicine.com/neuro/TOPIC419.HTM http://www.sleepdex.org/dyssomnias.htm https://www.sciencedaily.com/releases/2007/10/071015081737.htm http://www.aasmnet.org/Resources/PracticeParameters/PP_MedicalTherapyOSA.pdf Alcohol and health

Pseudofolliculitis barbae

Pseudofolliculitis barbae (PFB) is a persistent irritation caused by shaving. It was first described in 1956. Signs and symptoms Related conditions Razor burn is a less serious condition caused by shaving, characterized by mild to moderate redness and irritation on the surface of the skin. Unlike PFB, it is usually transient and there is no infection involved. There is also a condition called folliculitis barbae. The difference between the two is the cause of the inflammation in the hair follicles. Where folliculitis barbae is caused by viral or bacterial infections, pseudofolliculitis is created by irritation from shaving and ingrown hairs. Pseudofolliculitis nuchae, a related condition, occurs on the back of the neck, often along the posterior hairline, when curved hairs are cut short and allowed to grow back into the skin. Left untreated, this can develop into acne keloidalis nuchae, a condition in which hard, dark keloid-like bumps form on the neck. Both occur frequently in black men in the military. Here it is so common that services often have known protocols for management. Cause Pseudofolliculitis barbae (PFB) is most common on the face, but it can also happen on other parts of the body where hair is shaved or plucked, especially areas where hair is curly and the skin is sensitive, such as genital shaving (more properly termed pseudofolliculitis pubis or PFP).After a hair has been shaved, it begins to grow back. Curly hair tends to curl into the skin instead of straight out of the follicle, leading to an inflammation reaction. PFB can make the skin look itchy and red, and in some cases, it can even look like pimples. These inflamed papules or pustules can form especially if the area becomes infected.This is especially a problem for some men who have naturally coarse or tightly curling thick hair. Curly hair increases the likelihood of PFB by a factor of 50. If left untreated over time, this can cause keloid scarring in the beard area.Pseudofolliculitis barbae can further be divided into two types of ingrown hairs: transfollicular and extrafollicular. The extrafollicular hair is a hair that has exited the follicle and reentered the skin. The transfollicular hair never exits the follicle, but because of its naturally curly nature curls back into the follicle causing fluid build-up and irritation.A common polymorphism in a keratin gene (K6hf) has been linked to PFB, suggesting that it may be a genetic risk factor. This sequence change leads to an amino acid substitution in the highly conserved helix initiation motif of the K6hf rod domain. Carriers of the A12T polymorphism are six times more likely to develop PFB compared with people homozygous for the wild-type K6hf sequence. This suggests K6hf mutation structurally weakens the companion layer separating the inner and outer root sheath and increases the chances that a beard hair will in-grow. Prevention The most efficient prevention is to grow a beard. For men who are required to, or simply prefer to shave, studies show the optimal length to be about 0.5 mm to 1 mm to prevent the hair growing back into the skin. Using a beard trimmer at the lowest setting (0.5mm or 1mm) instead of shaving is an efficient alternative. The resulting faint stubble can be shaped using a standard electric razor on non-problematic areas (cheeks, lower neck).For most cases, completely avoiding shaving for three to four weeks allows all lesions to subside, and most extrafollicular hairs will resolve themselves within at least ten days. Permanent removal of the hair follicle is the only definitive treatment for PFB. Electrolysis is effective but limited by its slow pace, pain and expense. Laser-assisted hair removal is effective. There is a risk of skin discoloration and a very small risk of scarring.Some men use electric razors to control PFB. Those who use a razor should use a single blade or special wire-wrapped blade to avoid shaving too closely, with a new blade each shave. Shaving in the direction of hair growth every other day, rather than daily, may improve pseudofolliculitis barbae. If one must use a blade, softening the beard first with a hot, wet washcloth for five minutes or shave while showering in hot water can be helpful. Some use shaving powders (a kind of chemical depilatory) to avoid the irritation of using a blade. Barium sulfide-based depilatories are most efficient, but produce an unpleasant smell. Treatment The simplest treatment for PFB is to let the beard grow. Complete removal of the hair from its follicle is not recommended. Severe or transfollicular hairs may require removal by a dermatologist.Medications are also prescribed to speed healing of the skin. Clinical trials have shown glycolic acid-based peels to be an effective and well-tolerated therapy which resulted in significantly fewer PFB lesions on the face and neck. The mechanism of action of glycolic acid is unknown, but it is hypothesized that straighter hair growth is caused by the reduction of sulfhydrylbonds in the hair shaft by glycolic acid, which results in reduced re-entry of the hair shaft into the follicular wall or epidermis. Salicylic acid peels are also effective. Prescription antibiotic gels (Benzamycin, Cleocin-T) or oral antibiotics are also used. Benzoyl peroxide may be used topically, combined or not with prescription antibiotics. Retin-A is a potent treatment that helps even out any scarring after a few months. It is added as a nightly application of Retin-A cream 0.05–0.1% to the beard skin while beard is growing out. Tea tree oil, witch hazel, and hydrocortisone are also noted as possible treatments and remedies for razor bumps.>×<[-([[ vinegar }clap~lymebean》baking powder < thyme parsley > alcohol sugar laundrysoap dishsoap Legal In 1991, the Eighth Circuit Court of Appeals found that Dominos Pizzas policy of not allowing beards for employees created a disparate impact by excluding a quarter of black men from employment, but not an equivalent number of white men, thus violating Title VII of the Civil Rights Act of 1964. In contrast, in 1993, the Eleventh Circuit Court of Appeals upheld the Atlanta fire departments "no-beard" policy because it was justified by a "business necessity", in that case the fact that even short beards interfered with firefighters use of self-contained breathing apparatus. See also Laser hair removal List of cutaneous conditions References == External links ==

Colitis

Colitis is an inflammation of the colon. Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label colitis (without qualification) is used if: The cause of the inflammation in the colon is undetermined; for example, colitis may be applied to Crohns disease at a time when the diagnosis is unknown, or The context is clear; for example, an individual with ulcerative colitis is talking about their disease with a physician who knows the diagnosis. Signs and symptoms The signs and symptoms of colitis are quite variable and dependent on the cause of the given colitis and factors that modify its course and severity.Common symptoms of colitis may include: mild to severe abdominal pains and tenderness (depending on the stage of the disease), persistent hemorrhagic diarrhea with pus either present or absent in the stools, fecal incontinence, flatulence, fatigue, loss of appetite and unexplained weight loss.More severe symptoms may include: shortness of breath, a fast or irregular heartbeat and fever.Other less common or rare non-specific symptoms that may accompany colitis include: arthritis, mouth ulcers, painful, red and swollen skin and irritated, bloodshot eyes.Signs seen on colonoscopy include: colonic mucosal erythema (redness of the colons inner surface), ulcerations and hemorrhage. Diagnosis Symptoms suggestive of colitis are worked-up by obtaining the medical history, a physical examination and laboratory tests (CBC, electrolytes, stool culture and sensitivity, stool ova and parasites et cetera). Additional tests may include medical imaging (e.g. abdominal computed tomography, abdominal X-rays) and an examination with a camera inserted into the rectum (sigmoidoscopy, colonoscopy).An important investigation in the assessment of colitis is biopsy. A very small piece of tissue (usually about 2mm) is removed from the bowel mucosa during endoscopy and examined under the microscope by a histopathologist. It can provide important information regarding the cause of the disease and the extent of bowel damage. Types There are many types of colitis. They are usually classified by the cause. Types of colitis include: Autoimmune Inflammatory bowel disease (IBD) – a group of chronic colitides. Ulcerative colitis (UC) – a chronic colitis that affects the large intestine. Crohns disease (CD) – another type of IBD that often leads to colitis. Unknown Microscopic colitis – a colitis diagnosed by microscopic examination of colonic tissue; macroscopically ("to the eye") it appears normal. Lymphocytic colitis Collagenous colitis Treatment-caused Diversion colitis Chemical colitis Chemotherapy-induced colitis Radiation colitis Checkpoint inhibitor induced colitis Vascular disease Ischemic colitis Infectious Infectious colitisA subtype of infectious colitis is Clostridioides difficile colitis, which is informally abbreviated as "C-diff colitis". It classically forms pseudomembranes and is often referred to as pseudomembranous colitis, which is its (nonspecific) histomorphologic description. Enterohemorrhagic colitis may be caused by Shiga toxin in Shigella dysenteriae or Shigatoxigenic group of Escherichia coli (STEC), which includes serotype O157:H7 and other enterohemorrhagic E. coli.Parasitic infections, like those caused by Entamoeba histolytica, can also cause colitis. Unclassifiable colitides Indeterminate colitis is the classification for colitis that has features of both Crohns disease and ulcerative colitis. Indeterminate colitis behaviour is usually closer to ulcerative colitis than Crohns disease.Atypical colitis is a phrase that is occasionally used by physicians for a colitis that does not conform to criteria for accepted types of colitis. It is not an accepted diagnosis per se and, as such, a colitis that cannot be definitively classified. Treatment Some people may be admitted into the hospital following the colonoscopy depending on results. It is sometimes necessary to get the patient started on a steroid to speed up the healing of the colon. It may also be necessary to get the patient hydrated from the fluid loss and iron replaced from the loss of blood. After a hospital stay, the patient may be put on a daily medication to manage their chronic colitis. The medication can be an anti-inflammatory or an immunosuppressant. There are many different types of medication used and the doctor will prescribe the one they see fit. If the patient doesnt respond, new medications will be tried until there is a good fit.Moreover, several studies recently have found significant relationship between colitis and dairy allergy (including: cow milk, cow milk UHT and casein), suggesting some patients may benefit from an elimination diet. Research In the lab, the CRISPR-Cas systems effectively killed C. difficile bacteria. Researchers tested this approach in mice infected with C. difficile. Two days after the CRISPR treatment, the mice showed reduced C. difficile levels. Next steps include retooling the phage to prevent C. difficile from returning after the initial effective killing. References == External links ==

Cardiac arrest

Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that without immediate medical intervention will result within minutes in sudden cardiac death. Cardiopulmonary resuscitation (CPR), and possibly defibrillation are needed until further treatment can be provided. Cardiac arrest results in a rapid loss of consciousness, and breathing may be abnormal or absent.While cardiac arrest may be caused by heart attack or heart failure, these are not the same, and in 15 to 25% of cases there is a non-cardiac cause. Some individuals may experience chest pain, shortness of breath, nausea, an elevated heart rate and feeling light-headed immediately before entering cardiac arrest.The most common cause of cardiac arrest is an underlying heart problem like coronary artery disease which decreases the amount of oxygenated blood supplying the heart muscle. This, in turn, damages the structure of the muscle, which can alter its function. These changes can over time cause ventricular fibrillation (V-fib) which most commonly precedes cardiac arrest. Less common causes include major blood loss, lack of oxygen, very low potassium, electrical injury, heart failure, inherited heart arrhythmias and intense physical exercise. Cardiac arrest is diagnosed by the inability to find a pulse.CPR and defibrillation can reverse a cardiac arrest, leading to return of spontaneous circulation, but without such intervention it will prove fatal. In some cases, cardiac arrest is an anticipated outcome of serious illnesses where death is expected. Treatment for cardiac arrest includes immediate CPR and, if a shockable rhythm is present, defibrillation. Two protocols have been established for CPR: basic life support (BLS) and advanced cardiac life support (ACLS). Among those whose pulses are reestablished, targeted temperature management may improve outcomes. In addition, the care team may initiate measures to protect the patient from brain injury and preserve brain function. In post-resuscitation care, an implantable cardiac defibrillator may be considered to reduce the chance of death from recurrence.In the United States, approximately 535,000 cases occur a year (about 13 per 10,000 people). Of these, 326,000 (61%) experience cardiac arrest outside of a hospital setting, while 209,000 (39%) occur within a hospital. Cardiac arrest becomes more common with age and affects males more often than females.The percentage of people who survive out-of-hospital cardiac arrest with treatment by emergency medical services is about 8%. However, fictional media in the U.S. has often portrayed the immediate survival rate of cardiac arrest to be unreasonably high. This may contribute to misinformed expectations of the resuscitative efforts from the general public with many studies showing the expected survival rate of resuscitative efforts after cardiac arrest exceeding 40–50%. These portrayals may also contribute to a patients or medical decision makers desire to pursue aggressive measures. However, it has been shown that many of the critically ill are less likely to choose resuscitation when given accurate information about its limitations.In the event that cardiopulmonary resuscitation is successful, complete recovery is not guaranteed as many survivors experience an array of disability including partial paralysis, seizures, difficulty with walking, speaking, or memory, limited consciousness, or persistent vegetative state and brain death. Signs and symptoms Cardiac arrest is not preceded by any warning symptoms in approximately 50 percent of people. For individuals who do experience symptoms, the symptoms are usually nonspecific to the cardiac arrest. This can present in the form of new or worsening: chest pain fatigue blackouts dizziness shortness of breath weakness vomitingWhen cardiac arrest is suspected due to signs of unconsciousness or abnormal breathing, a bystander should attempt to feel a pulse for 10 seconds; if no pulse is felt, it should be assumed the victim is in cardiac arrest. As a result of loss of cerebral perfusion (blood flow to the brain), the person will rapidly lose consciousness and can stop breathing. Near-death experiences are reported by 10 to 20 percent of people who survived cardiac arrest, which demonstrates a certain level of cognitive processes that are still active during resuscitation. Risk factors The risk factors for sudden cardiac arrest (SCA) are similar to those of coronary artery disease and include age, cigarette smoking, high blood pressure, high cholesterol, lack of physical exercise, obesity, diabetes, and family history of cardiac disease. A prior episode of sudden cardiac arrest also increases the likelihood of future episodes. A statistical analysis of many of these risk factors determined that approximately 50% of all cardiac arrests occur in 10% of the population perceived to be at greatest risk due to aggregate harm of multiple risk factors demonstrating that cumulative risk of multiple comorbidities exceeds the sum of each risk individually.Previous adverse cardiac events, non-sustained ventricular tachycardia (NSVT), syncope, and left ventricular hypertrophy (LVT) have been shown to predict sudden cardiac death in children. Current cigarette smokers with coronary artery disease were found to have a two to threefold increase in the risk of sudden death between ages 30 and 59. Furthermore, it was found that former smokers risk was closer to that of those who had never smoked.Functional changes in the heart such as reduced ejection fraction or cardiac arrhythmia have been shown to increase the risk of cardiac arrest and act independently from the risk factors previously mentioned. Conditions that produce these functional changes can be acquired following previous cardiac injury, or inherited through familial history of arrhythmogenic disorders.: 828 Causes and mechanisms Sudden cardiac arrest (SCA), or sudden cardiac death (SCD), occur when the heart abruptly begins to beat in an abnormal or irregular rhythm (arrhythmia). Without organized electrical activity in the heart muscle, there is no consistent contraction of the ventricles, which results in the hearts inability to generate an adequate cardiac output (forward pumping of blood from heart to rest of the body). There are many different types of arrhythmias, but the ones most frequently recorded in sudden cardiac arrest are ventricular tachycardia and ventricular fibrillation. Less common causes of dysrhythmias in cardiac arrest include pulseless electrical activity (PEA), bradyarrhythmias or asystole. Such rhythms are seen when there is prolonged cardiac arrest, progression of ventricular fibrillation, or efforts such as defibrillation executed to resuscitate the person. The rhythm changes also appear to have a correlation to the underlying cause of cardiac injury when present (ischemic vs. nonischemic causes).: 831 Sudden cardiac arrest can result from cardiac and non-cardiac causes including the following: Cardiac causes Coronary artery disease Coronary artery disease (CAD), also known as ischemic heart disease, is responsible for 62 to 70 percent of all sudden cardiac deaths. CAD is a much less frequent cause of sudden cardiac death in people under the age of 40. Cases have shown that the most common finding at postmortem examination of sudden cardiac death is chronic high-grade stenosis of at least one segment of a major coronary artery, the arteries that supply the heart muscle with its blood supply. This stenosis is often the result of narrowing and hardening of the arteries following deposition of cholesterol plaques and inflammation over several years. This accumulation and remodeling of the coronary vessels along with other systemic blood vessels characterizes the progression of Atherosclerotic Cardiovascular Disease. When a stable plaque ruptures, it can block the flow of blood and oxygen through small arteries resulting in ischemic injury as a result. The injury to tissue following ischemia can lead to structural and functional changes preventing the heart from continuing normal conduction cycles and altering heart rate.: 829 : 829 Non-atherosclerotic coronary artery abnormalities Abnormalities of the coronary arteries not related to atherosclerosis include congenital coronary artery anomalies (most commonly anomalous origin of left coronary artery from the pulmonary artery), inflammation known as coronary arteritis, embolism, vasospasm, and mechanical abnormalities related to connective tissue diseases or trauma. These conditions account for 10-15% of cardiac arrest and sudden cardiac death.: 829  Coronary arteritis commonly results from a pediatric febrile inflammatory condition known as Kawasaki disease. Other vasculitides can also contribute to increased risk of sudden cardiac death. Embolism, or clotting, of the coronary arteries most commonly occurs from septic emboli secondary to endocarditis with involvement of the aortic valve, tricuspid valve, or prosthetic valves. Coronary vasospasm may result in cardiac arrhythmias, altering the electrical conduction of the heart with a risk of complete cardiac arrest from severe or prolonged rhythm changes. Mechanical abnormalities with associated risk of cardiac arrest may arise from coronary artery dissection which can be attributed to Marfan Syndrome or trauma.: 829 Structural heart disease Structural heart diseases not related to coronary artery disease account for 10% of all sudden cardiac deaths. Examples of these include: cardiomyopathies (hypertrophic, dilated, or arrythmogenic), cardiac rhythm disturbances, myocarditis, hypertensive heart disease, and congestive heart failure. Left ventricular hypertrophy is thought to be a leading cause of sudden cardiac deaths in the adult population. This is most commonly the result of longstanding high blood pressure, or hypertension, which has caused a maladaptive change to the wall of the main pumping chamber of the heart, the left ventricle. Increased blood pressure means that the heart must pump even harder to adequately circulate blood throughout the body. If the heart does this for a prolonged period of time due to uncontrolled hypertension, the left ventricle can hypertrophy (grow larger) in a way that decreases the effectiveness of the heart. Left ventricular hypertrophy can be demonstrated on echocardiogram and electrocardiogram (EKG).A 1999 review of sudden cardiac deaths in the United States found that structural heart diseases accounted for over 30% of sudden cardiac arrests for those under 30 years. A study of military recruits age 18-35 found that this accounted for over 40% of sudden cardiac deaths.Congestive heart failure increases the risk of sudden cardiac death fivefold.Structural abnormalities of the cardiac conduction system (notably the Atrioventricular Node and His-Purkinje system) may predispose an individual to arrhythmias with risk of progressing to sudden cardiac arrest, albeit this risk remains low. Many of these conduction blocks can be treated with internal cardiac defibrillators for those determined to be at high risk due to severity of fibrosis or severe electrophysiologic disturbances.: 833 Inherited arrhythmia syndromes Arrhythmias that are not due to structural heart disease account for 5 to 10% of sudden cardiac arrests. These are frequently caused by genetic disorders that lead to abnormal heart rhythms. The genetic mutations often affect specialized proteins known as ion channels that conduct electrically charged particles across the cell membrane, and this group of conditions are therefore often referred to as channelopathies. Examples of these inherited arrhythmia syndromes include Long QT syndrome (LQTS), Brugada Syndrome, Catecholaminergic polymorphic ventricular tachycardia, and Short QT syndrome. Many are also associated with environmental or neurogenic triggers such as response to loud sounds that can initiate lethal arrhythmias.: 833  Other conditions that promote arrhythmias but are not caused by genetic mutations include Wolff-Parkinson-White syndrome.Long QT syndrome, a condition often mentioned in young peoples deaths, occurs in one of every 5000 to 7000 newborns and is estimated to be responsible for 3000 deaths each year compared to the approximately 300,000 cardiac arrests seen by emergency services. These conditions are a fraction of the overall deaths related to cardiac arrest but represent conditions which may be detected prior to arrest and may be treatable. The symptomatic expression of Long-QT syndrome is quite broad and more often presents with syncope rather than cardiac arrest. However, the risk of cardiac arrest is still present and individuals with family history of sudden cardiac arrests should be screened for LQTS and other treatable causes of lethal arrhythmia. Higher levels of risk for cardiac arrest are associated with female sex, more significant QT prolongation, history of unexplained syncope (fainting spells) or premature sudden cardiac death.: 833  Additionally, individuals with LQTS should avoid certain medications that carry the risk of increasing the severity of this conduction abnormality such as certain anti-arrhythmic, anti-depressant, and quinolone or macrolide antibiotics. Non-cardiac causes Non-cardiac causes accounts for 15 to 25% of cardiac arrests. The most common non-cardiac causes are trauma, major bleeding (gastrointestinal bleeding, aortic rupture, or intracranial hemorrhage), hypovolemic shock, overdose, drowning, and pulmonary embolism. Cardiac arrest can also be caused by poisoning like the stings of certain jellyfish, or through electrocution, like lightning. Reversible causes Other non-cardiac causes of cardiac arrest may result from temporary disturbances in the bodies homeostasis. This may be the result from changes in electrolyte ratios, oxygen saturation, or alterations of other ions influencing the bodys pH. Mnemonic for reversible causes "Hs and Ts" is the name for a mnemonic used to remember the treatable or reversible causes of cardiac arrest. Note: This mnemonic includes causes of cardiac and non-cardiac origin, but all are reversible with appropriate and time-sensitive treatment. HsHypovolemia – A lack of blood volume Hypoxia – A lack of oxygen Hydrogen ions (acidosis) – An abnormal pH in the body Hyperkalemia or hypokalemia – Both increased and decreased potassium can be life-threatening Hypothermia – A low core body temperature Hypoglycemia or hyperglycemia – A low or high blood glucoseTsTablets or toxins such as drug overdose Cardiac tamponade – Fluid building up around the heart Tension pneumothorax – A collapsed lung Thrombosis (myocardial infarction) – A heart attack Thromboembolism (pulmonary embolism) – A blood clot in the lung Traumatic cardiac arrest Children In children, the most common cause of cardiopulmonary arrest is shock or respiratory failure that has not been treated. Heart arrhythmia is not the most common cause in children. When there is a cardiac arrhythmia, it is most often asystole or bradycardia, in contrast to ventricular fibrillation or tachycardia as seen in adults. Other causes can include drugs such as cocaine, methamphetamine, or overdose of medications such as antidepressants in a child who was previously healthy but is now presenting with a dysrhythmia that has progressed to cardiac arrest. Common causes of sudden unexplained cardiac arrest in children include hypertrophic cardiomyopathy, coronary artery abnormalities, and arrhythmias. Mechanism The definitive electrical mechanisms of cardiac arrest, which may arise from any of the functional, structural or physiologic abnormalities mentioned above are characterized by tachyarrhythmic or bradyarrhythmic events that do not result in systole.: 837–838  The tachyarrhythmias can be further classified as Ventricular fibrillation (V-fib) and pulseless or sustained Ventricular tachycardia (V-tach), both of which are rapid and erratic arrhythmias that alter the circulatory pathway such that adequate blood flow cannot be sustained and is inadequate to meet the bodys needs.: 837–838 The mechanism responsible for the majority of sudden cardiac deaths is ventricular fibrillation. Ventricular fibrillation is a tachyarrhythmia characterized by turbulent electrical activity in the ventricular myocardium leading to a heart rate too disorganized and rapid to produce any meaningful cardiac output, thus resulting in insufficient perfusion of the brain and essential organs. In ventricular tacycardia, the heart also beats faster than normal, which may prevent the heart chambers from properly filling with blood. Some of the electrophysiologic mechanisms underpinning ventricular fibrillations include ectopic automaticity, re- entry, and triggered activity. Structural changes in the diseased heart as a result of inherited factors (mutations in ion-channel coding genes for example) cannot explain the suddenness of sudden cardiac death.Both ventricular fibrillation and ventricular tachycardia can result in the heart ineffectively pumping blood to the body. Ventricular tachycardia is characterized by an altered QRS complex and a heart rate greater than 100 beats per minute. When V-tach is sustained (lasts for at least 30 seconds), inadequate blood flow to heart tissue can lead to cardiac arrest.Bradyarrhthmias occur following dissociation of spontaneous electrical conduction and the mechanical function of the heart resulting in pulseless electrical activity (PEA) or through complete absence of electrical activity of the heart resulting in asystole. Similar to the result of tachyarrhthmias, these conditions lead to an inability to sustain adequate blood flow as well, though in the case of bradyarrhthmias, the underlying cause is absence mechanical activity and not rapid beats leading to disorganization.: 837–838 Diagnosis Cardiac arrest is synonymous with clinical death. Historical information and a physical exam can diagnose cardiac arrest and provide information regarding the potential cause and the prognosis. The provider taking the persons clinical history should aim to determine if the episode was observed by anyone else, what time the episode took place, what the person was doing (in particular if there was any trauma), and if there were involvement of drugs. The physical examination portion of diagnosing cardiac arrest focuses on the absence of a pulse. In many cases, lack of a carotid pulse is the gold standard for diagnosing cardiac arrest. Lack of a pulse in the periphery (radial/pedal) may also result from other conditions (e.g. shock), or simply an error on the part of the rescuer. Studies have shown that rescuers may often make a mistake when checking the carotid pulse in an emergency, whether they are healthcare professionals or lay persons.Point-of-care ultrasound (POCUS) is a tool that can be used to examine the movement of the heart and its force of contraction at the person experiencing cardiac arrests bedside. POCUS can accurately diagnose cardiac arrest in hospital settings, overcoming some of the shortcomings of diagnosis through checking the central pulse (carotid arteries or subclavian arteries), as well as detecting movement and contractions of the heart.Using POCUS, clinicians can have limited, two-dimensional views of different parts of the heart during arrest. These images can help clinicians determine whether electrical activity within the heart is pulseless or pseudo-pulseless, as well as help them diagnose the potentially reversible causes of an arrest. Published guidelines from the American Society of Echocardiography, American College of Emergency Physicians, European Resuscitation Council, and the American Heart Association, as well as the 2018 preoperative Advanced Cardiac Life Support guidelines, have recognized the potential benefits of using POCUS in diagnosing and managing cardiac arrest.Owing to the inaccuracy in this method of diagnosis, some bodies such as the European Resuscitation Council (ERC) have de-emphasised its importance. Instead, the current guidelines prompt individuals to begin CPR on any unconscious person who has absent or abnormal breathing. The Resuscitation Council in the United Kingdom stand in line with the ERCs recommendations and those of the American Heart Association. They have suggested that the technique to check carotid pulses should be used only by healthcare professionals with specific training and expertise, and even then that it should be viewed in conjunction with other indicators such as agonal respiration.Various other methods for detecting circulation, and therefore diagnosing cardiac arrest have been proposed. Guidelines following the 2000 International Liaison Committee on Resuscitation (ILCOR) recommendations were for rescuers to look for "signs of circulation", but not specifically the pulse. These signs included coughing, gasping, colour, twitching, and movement. However, in face of evidence that these guidelines were ineffective, the current recommendation of ILCOR is that cardiac arrest should be diagnosed in all casualties who are unconscious and not breathing normally, a similar protocol that of which the European Resuscitation Council has adopted. In a non-acute setting where the patient is expired, diagnosis of cardiac arrest can be done via molecular autopsy or postmortem molecular testing which uses a set of molecular techniques to find the ion channels that are cardiac defective. This could help elucidate the cause of death in the patient. Other physical signs or symptoms can help determine the potential cause of the cardiac arrest. Below is a chart of the clinical findings and signs/symptoms a person may have and a potential cause associated with it. Classifications Clinicians classify cardiac arrest into "shockable" versus "non-shockable", as determined by the EKG rhythm. This refers to whether a particular class of cardiac dysrhythmia is treatable using defibrillation. The two "shockable" rhythms are ventricular fibrillation and pulseless ventricular tachycardia, while the two "non-shockable" rhythms are asystole and pulseless electrical activity. Prevention With the lack of positive outcomes following cardiac arrest, efforts have been spent finding effective strategies to prevent cardiac arrest. With the prime causes of cardiac arrest being ischemic heart disease, efforts to promote a healthy diet, exercise, and smoking cessation are important. For people at risk of heart disease, measures such as blood pressure control, cholesterol lowering, and other medico-therapeutic interventions are used.[1] Of note, however, a Cochrane review published in 2016 found moderate-quality evidence to show that blood pressure-lowering drugs do not actually reduce the risk of sudden cardiac death. Exercise is an effective preventative measure for cardiac arrest in the general population but may be risky for those with pre-existing conditions. The risk of a transient catastrophic cardiac event increases in individuals with heart disease during and immediately after exercise. However, both the lifetime and acute risk of cardiac arrest are decreased in individuals with heart disease that perform regular exercise, suggesting the risks of exercise are outweighed by the benefits. Diet According to a study published in the Journal of the American Heart Association in 2021, diet may be a modifiable risk factor that leads to a lower incidence of sudden cardiac death. The study found that those who fell under the category of having "Southern diets" representing those of "added fats, fried food, eggs, organ and processed meats, and sugar‐sweetened beverages" had a positive association with an increased risk of cardiac arrest, while those deemed following the "Mediterranean diets" of had an inverse relationship regarding the risk of cardiac arrest. The American Heart Association also has diet recommendations here that is aimed to prevent cardiovascular disease. Here, the readers may find broad information regarding healthy eating and some tips on what to look for and what to avoid from grocery stores to restaurant dining.Additionally, marine-derived omega-3 polyunsaturated fatty acids (PUFAs) have been promoted for the prevention of sudden cardiac death due to their postulated ability to lower triglyceride levels, prevent arrhythmias, decrease platelet aggregation, and lower blood pressure. However, according to a systematic review published in 2012, omega-3 PUFA supplementation are not being associated with a lower risk of sudden cardiac death. Code teams In medical parlance, cardiac arrest is referred to as a "code" or a "crash". This typically refers to "code blue" on the hospital emergency codes. A dramatic drop in vital sign measurements is referred to as "coding" or "crashing", though coding is usually used when it results in cardiac arrest, while crashing might not. Treatment for cardiac arrest is sometimes referred to as "calling a code". People in general wards often deteriorate for several hours or even days before a cardiac arrest occurs. This has been attributed to a lack of knowledge and skill amongst ward-based staff, in particular, a failure to carry out measurement of the respiratory rate, which is often the major predictor of a deterioration and can often change up to 48 hours prior to a cardiac arrest. In response to this, many hospitals now have increased training for ward-based staff. A number of "early warning" systems also exist which aim to quantify the persons risk of deterioration based on their vital signs and thus provide a guide to staff. In addition, specialist staff are being used more effectively in order to augment the work already being done at ward level. These include: Crash teams (or code teams) – These are designated staff members with particular expertise in resuscitation who are called to the scene of all arrests within the hospital. This usually involves a specialized cart of equipment (including defibrillator) and drugs called a "crash cart" or "crash trolley". Medical emergency teams – These teams respond to all emergencies, with the aim of treating the people in the acute phase of their illness in order to prevent a cardiac arrest. These teams have been found to decrease the rates of in-hospital cardiac arrest and improve survival. Critical care outreach – As well as providing the services of the other two types of team, these teams are also responsible for educating non-specialist staff. In addition, they help to facilitate transfers between intensive care/high dependency units and the general hospital wards. This is particularly important, as many studies have shown that a significant percentage of patients discharged from critical care environments quickly deteriorate and are re-admitted; the outreach team offers support to ward staff to prevent this from happening. Implantable cardioverter defibrillator An implantable cardioverter defibrillator (ICD) is a battery-powered device that monitors electrical activity in the heart and when an arrhythmia is detected is able to deliver an electrical shock to terminate the abnormal rhythm. ICDs are used to prevent sudden cardiac death (SCD) in those that have survived a prior episode of sudden cardiac arrest (SCA) due to ventricular fibrillation or ventricular tachycardia (secondary prevention). ICDs are also used prophylactically to prevent sudden cardiac death in certain high risk patient populations (primary prevention).Numerous studies have been conducted on the use of ICDs for the secondary prevention of SCD. These studies have shown improved survival with ICDs compared to the use of anti-arrhythmic drugs. ICD therapy is associated with a 50% relative risk reduction in death caused by an arrhythmia and a 25% relative risk reduction in all cause mortality.Primary prevention of SCD with ICD therapy for high-risk patient populations has similarly shown improved survival rates in a number of large studies. The high-risk patient populations in these studies were defined as those with severe ischemic cardiomyopathy (determined by a reduced left ventricular ejection fraction (LVEF)). The LVEF criteria used in these trials ranged from less than or equal to 30% in MADIT-II to less than or equal to 40% in MUSTT. Management Sudden cardiac arrest may be treated via attempts at resuscitation. This is usually carried out based upon basic life support, advanced cardiac life support (ACLS), pediatric advanced life support (PALS), or neonatal resuscitation program (NRP) guidelines. Cardiopulmonary resuscitation Early cardiopulmonary resuscitation (CPR) is essential to surviving cardiac arrest with good neurological function. It is recommended that it be started as soon as possible with minimal interruptions once begun. The components of CPR that make the greatest difference in survival are chest compressions and defibrillating shockable rhythms. After defibrillation, chest compressions should be continued for two minutes before a rhythm check is again done. This is based on a compression rate of 100-120 compressions per minute, a compression depth of 5–6 centimeters into the chest, full chest recoil, and a ventilation rate of 10 breath ventilations per minute. Correctly performed bystander CPR has been shown to increase survival; however, it is performed in less than 30% of out of hospital arrests as of 2007. If high-quality CPR has not resulted in return of spontaneous circulation and the persons heart rhythm is in asystole, discontinuing CPR and pronouncing the persons death is reasonable after 20 minutes. Exceptions to this include certain cases with hypothermia or who have drowned. Some of these cases should have longer and more sustained CPR until they are nearly normothermic. Longer durations of CPR may be reasonable in those who have cardiac arrest while in hospital. Bystander CPR, by the lay public, before the arrival of EMS also improves outcomes.Either a bag valve mask or an advanced airway may be used to help with breathing particularly since vomiting and regurgitation are common, particularly in out-of-hospital cardiac arrest (OHCA). If this occurs, then modification to existing oropharyngeal suction may be required, such as the use of Suction Assisted Laryngoscopy Airway Decontamination. High levels of oxygen are generally given during CPR. Tracheal intubation has not been found to improve survival rates or neurological outcome in cardiac arrest and in the prehospital environment may worsen it. Endotracheal tube and supraglottic airways appear equally useful. When done by EMS 30 compressions followed by two breaths appear better than continuous chest compressions and breaths being given while compressions are ongoing.For bystanders, CPR which involves only chest compressions results in better outcomes as compared to standard CPR for those who have gone into cardiac arrest due to heart issues. Mouth-to-mouth as a means of providing respirations to the patient has been phased out due to the risk of contracting infectious diseases from the patient. Mechanical chest compressions (as performed by a machine) are no better than chest compressions performed by hand. It is unclear if a few minutes of CPR before defibrillation results in different outcomes than immediate defibrillation. If cardiac arrest occurs after 20 weeks of pregnancy someone should pull or push the uterus to the left during CPR. If a pulse has not returned by four minutes emergency Cesarean section is recommended. Defibrillation Defibrillation is indicated if an electric-shockable heart rhythm is present. The two shockable rhythms are ventricular fibrillation and pulseless ventricular tachycardia. In children 2 to 4 J/Kg is recommended.The defibrillation is made by an automated external defibrillator (AED), a portable machine that can be used even by any user because it produces voice instructions that guide the process, automatically checks the victims condition, and applies the correct electric shocks. Some defibrillators even provide feedback on the quality of CPR compressions, encouraging the lay rescuer to press the persons chest hard enough to circulate blood.In addition, there is increasing use of public access defibrillation. This involves placing an automated external defibrillator in public places, and training staff in these areas how to use them. This allows defibrillation to take place prior to the arrival of emergency services and has been shown to lead to increased chances of survival. It has been shown that those who have arrests in remote locations have worse outcomes following cardiac arrest. Medications As of 2016, medications other than epinephrine (adrenaline), while included in guidelines, have not been shown to improve survival to hospital discharge following out-of-hospital cardiac arrest. This includes the use of atropine, lidocaine, and amiodarone. Epinephrine in adults, as of 2019, appears to improve survival but does not appear to improve neurologically normal survival. It is generally recommended every five minutes. Epinephrine acts on the alpha-1 receptor, which in turn increases the blood flow that supplies the heart. This would assist with providing more oxygen to the heart. Based on 2019 guidelines, 1 mg of epinephrine may be administered to patients every 3–5 minutes, but doses higher than 1 mg epinephrine are not recommended for routine use in cardiac arrest. If the patient has a non-shockable rhythm, the epinephrine should be administered as soon as possible. For a shockable rhythm, epinephrine should only be administered after initial defibrillation attempts have failed. Vasopressin overall does not improve or worsen outcomes compared to epinephrine. The combination of epinephrine, vasopressin, and methylprednisolone appears to improve outcomes. Some of the lack of long-term benefit may be related to delays in epinephrine use. While evidence does not support its use in children, guidelines state its use is reasonable. Lidocaine and amiodarone are also deemed reasonable in children with cardiac arrest who have a shockable rhythm. The general use of sodium bicarbonate or calcium is not recommended. The use of calcium in children has been associated with poor neurological function as well as decreased survival. Correct dosing of medications in children is dependent on weight. To minimize time spent calculating medication doses, the use of a Broselow tape is recommended.The 2010 guidelines from the American Heart Association no longer contain the recommendation for using atropine in pulseless electrical activity and asystole for want of evidence for its use. Neither lidocaine nor amiodarone, in those who continue in ventricular tachycardia or ventricular fibrillation despite defibrillation, improves survival to hospital discharge but both equally improve survival to hospital admission.Thrombolytics when used generally may cause harm but may be of benefit in those with a confirmed pulmonary embolism as the cause of arrest. Evidence for use of naloxone in those with cardiac arrest due to opioids is unclear but it may still be used. In those with cardiac arrest due to local anesthetic, lipid emulsion may be used. Targeted temperature management Current international guidelines suggest cooling adults after cardiac arrest using targeted temperature management (TTM), which was previously known as therapeutic hypothermia. People are typically cooled for a 24-hour period, with a target temperature of 32–36 °C (90–97 °F). There are a number of methods used to lower the body temperature, such as applying ice packs or cold-water circulating pads directly to the body, or infusing cold saline. This is followed by gradual rewarming over the next 12 to 24 hrs.Effectiveness of TTM after out-of-hospital cardiac arrest is an area of ongoing study. Pre-hospital TTM after out-of-hospital cardiac arrest has been shown to increase the risk of adverse outcomes. The rates of re-arrest may be higher in people who were treated with pre-hospital TTM, however, more research is needed on the effectiveness and risks of TTM. TTM in post-arrest care has not been found to improve mortality or neurological outcomes. Moreover, TTM may have adverse neurological effects in people who survive post cardiac arrest. Do not resuscitate Some people choose to avoid aggressive measures at the end of life. A do not resuscitate order (DNR) in the form of an advance health care directive makes it clear that in the event of cardiac arrest, the person does not wish to receive cardiopulmonary resuscitation. Other directives may be made to stipulate the desire for intubation in the event of respiratory failure or, if comfort measures are all that are desired, by stipulating that healthcare providers should "allow natural death". Chain of survival Several organizations promote the idea of a chain of survival. The chain consists of the following "links": Early recognition If possible, recognition of illness before the person develops a cardiac arrest will allow the rescuer to prevent its occurrence. Early recognition that a cardiac arrest has occurred is key to survival for every minute a patient stays in cardiac arrest, their chances of survival drop by roughly 10%. Early CPR improves the flow of blood and of oxygen to vital organs, an essential component of treating a cardiac arrest. In particular, by keeping the brain supplied with oxygenated blood, chances of neurological damage are decreased. Early defibrillation is effective for the management of ventricular fibrillation and pulseless ventricular tachycardia Early advanced care Early post-resuscitation care which may include percutaneous coronary interventionIf one or more links in the chain are missing or delayed, then the chances of survival drop significantly. These protocols are often initiated by a code blue, which usually denotes impending or acute onset of cardiac arrest or respiratory failure, although in practice, code blue is often called in less life-threatening situations that require immediate attention from a physician. Other Resuscitation with extracorporeal membrane oxygenation devices has been attempted with better results for in-hospital cardiac arrest (29% survival) than out-of-hospital cardiac arrest (4% survival) in populations selected to benefit most. Cardiac catheterization in those who have survived an out-of-hospital cardiac arrest appears to improve outcomes although high quality evidence is lacking. It is recommended that it is done as soon as possible in those who have had a cardiac arrest with ST elevation due to underlying heart problems.The precordial thump may be considered in those with witnessed, monitored, unstable ventricular tachycardia (including pulseless VT) if a defibrillator is not immediately ready for use, but it should not delay CPR and shock delivery or be used in those with unwitnessed out of hospital arrest. Prognosis The overall chance of survival among those who have cardiac arrest outside hospital is poor, at 10%. Among those who have an out-of-hospital cardiac arrest, 70% occur at home and their survival rate is 6%. For those who have an in-hospital cardiac arrest, the survival rate one year from at least the occurrence of cardiac arrest is estimated to be 13%. One year survival is estimated to be higher in people with cardiac admission diagnoses (39%), when compared to those with non-cardiac admission diagnoses (11%). Among children rates of survival are 3 to 16% in North America. For in hospital cardiac arrest survival to discharge is around 22%. Those who survive to Return-of-Spontaneous-Circulation (ROSC) and hospital admission frequently present with Post-Cardiac Arrest Syndrome which usually presents with neurological injury that can range from mild memory problems to coma.Hypoxic ischemic brain injury is the most detrimental outcome for people suffering a cardiac arrest. Poor neurological outcomes following cardiac arrest are much more prevalent in countries that do not use withdrawal of life support (~50%) as compared to those that do (less than 10%). Most improvements in cognition occur during the first three months following cardiac arrest, with some individuals reporting improvement up to one-year post cardiac arrest. 50 – 70% of cardiac arrest survivors report fatigue as a symptom, making fatigue the most prevalent patient-reported symptom.Prognosis is typically assessed 72 hours or more after cardiac arrest. Rates of survival are better in those who someone saw collapse, got bystander CPR, or had either ventricular tachycardia or ventricular fibrillation when assessed. Survival among those with Vfib or Vtach is 15 to 23%. Women are more likely to survive cardiac arrest and leave hospital than men.A 1997 review found rates of survival to discharge of 14% although different studies varied from 0 to 28%. In those over the age of 70 who have a cardiac arrest while in hospital, survival to hospital discharge is less than 20%. How well these individuals are able to manage after leaving hospital is not clear.The global rate of people who were able to recover from out-of-hospital cardiac arrest after receiving CPR has been found to be approximately 30%, and the rate of survival to discharge from the hospital has been estimated at 9%. Survival to discharge from the hospital is more likely among people whose cardiac arrest was witnessed by a bystander or emergency medical services, who received bystander CPR and among those living in Europe and North America. Relatively lower survival to hospital discharge rates have been observed in Asian countries. Epidemiology The risk of cardiac arrest varies with geographical region, age, and gender. The lifetime risk is three times greater in men (12.3%) than women (4.2%) based on analysis of the Framingham Heart Study. However this gender difference disappeared beyond 85 years of age. Around half of these individuals are younger than 65 years of age. North America Based on death certificates, sudden cardiac death accounts for about 20% of all deaths in the United States. In the United States, approximately 326,000 cases of out-of-hospital and 209,000 cases of in-hospital cardiac arrest occur among adults a year, which works out to be an incidence of approximately 110.8 per 100,000 adults a year. In the United States, during-pregnancy cardiac arrest occurs in about one in twelve-thousand deliveries or 1.8 per 10,000 live births. Rates are lower in Canada. Other regions Non-Western regions of the world have differing incidences. The incidence of sudden cardiac death in China is 41.8 per 100,000 and South India is 39.7 per 100,000. Society and culture Names In many publications the stated or implicit meaning of "sudden cardiac death" is sudden death from cardiac causes. However, sometimes physicians call cardiac arrest "sudden cardiac death" even if the person survives. Thus one can hear mentions of "prior episodes of sudden cardiac death" in a living person.In 2021, the American Heart Association clarified that "heart attack" is often mistakenly used to describe cardiac arrest. While a heart attack refers to death of heart muscle tissue as a result of blood supply loss, cardiac arrest is caused when the hearts electrical system malfunctions. Furthermore, the American Heart Association explains that "if corrective measures are not taken rapidly, this condition progresses to sudden death. Cardiac arrest should be used to signify an event as described above, that is reversed, usually by CPR and/or defibrillation or cardioversion, or cardiac pacing. Sudden cardiac death should not be used to describe events that are not fatal". Slow code A "slow code" is a slang term for the practice of deceptively delivering sub-optimal CPR to a person in cardiac arrest, when CPR is considered to have no medical benefit. A "show code" is the practice of faking the response altogether for the sake of the persons family.Such practices are ethically controversial, and are banned in some jurisdictions. The European Resuscitation Council Guidelines released a statement in 2021 that clinicians are not suggested to participate/take part in "slow codes". According to the American College of Physicians, half-hearted resuscitation efforts are deceptive and should not be performed by physicians or nurses. See also Chain of survival Sudden cardiac death of athletes Post-cardiac arrest syndrome References External links The Center for Resuscitation Science at the Hospital of the University of Pennsylvania

Intravascular hemolysis

Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbilirubinemia. Mechanism Intravascular hemolysis is the state when the red blood cell ruptures as a result of the complex of complement autoantibodies attached (fixed) on the surfaces of RBCs attack and rupture RBCs membranes, or a parasite such as Babesia exits the cell that ruptures the RBCs membrane as it goes.Upon RBCs rupture, components of which are released and circulating in the blood plasma.These components comprise hemoglobin and others. At this stage, the hemoglobin is called free hemoglobin. Free hemoglobin (also called naked hemoglobin) is the un-bound hemoglobin that is not enclosed in the red blood cell. The naked hemoglobin is devoid of its anti-oxidant sentries that are normally available within the RBC. Free hemoglobin is thus vulnerable to be oxidized.When the serum concentration of free hemoglobin is within the physiologic range of haptoglobin, the potential deleterious effects of free hemoglobin are prevented because haptoglobin will bind to "free hemoglobin" forming a complex of "free hemoglobin-haptoglobin" evidenced by reduced amount of haptoglobin. However, during hyper-hemolytic conditions or with chronic hemolysis, haptoglobin is depleted so the remaining free hemoglobin readily distribute to tissues where it might be exposed to oxidative conditions, thus some of the ferrous heme (FeII), the oxygen-binding component of hemoglobin, of the free hemoglobin are oxidized and becoming met-hemoglobin (ferric hemoglobin). In such conditions, heme along with globin chains can be released from further oxidization of met-hemoglobin (ferric Hb). In which, the free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. At this time, hemopexin, another plasma glycoprotein come to bind with heme with its privilege of high heme affinity, forming a complex of heme-hemopexin, which is non-toxic, and travel together to a receptor on hepatocytes and macrophages within the spleen, liver and bone marrow. (Note that the "free hemoglobin-haptoglobin" complex is taken up by hepatocytes and, to the lesser extent, macrophages.) Thereafter, these complexes will undergo the metabolic mechanisms like extravascular hemolysis.Nevertheless, if the binding capacities of haptoglobin and hemopexin are saturated, the remaining "free hemoglobin" in the plasma will be oxidized to met-hemoglobin eventually, and then further disassociates into free heme and others. At this stage, the "free heme" will bind to albumin, forming met-hemalbumin. As to the remaining unbound (met)hemoglobin is filtered into the primary urine and re-absorbed via proximal tubules of the kidney. In proximal tubules, the iron is extracted and stored as hemosiderin. (Long-term hemoglobinuria is associated with substantial deposition of hemosiderin in proximal tubule (excessive accumulation of hemosiderin in proximal tubule), Fanconi syndrome (damaged renal re-absorption capability of small molecules which give rises to hyper-aminoaciduria, glycosuria, hyperphosphaturia, and bicarbonate and dehydration), and chronic kidney failure.) In the end, if the plasma concentration of the "free met-hemoglobin" and/or "free hemoglobin" is still too high for proximal tubule to absorb back into the body, then hemoglobinuria occurs, indicating an extensive intravascular hemolysis. These remaining free hemoglobin entities also begin to consume nitric oxide, which is critical regulators of vascular homeostasis and basal and stress-mediated smooth muscle relaxation and vasomotor tone, endothelial adhesion molecule expression, and platelet activation and aggregation. The reduction of nitric oxide deeply disturbs the bodys mechanism to maintain the stability of the hemodynamics. Additionally, free hemoglobin manifests direct cytotoxic, inflammatory, and pro-oxidant effects that in turn negatively impact endothelial function. At the meantime, free heme exerts its multiple pro-inflammatory and pro-oxidant effects to the tissues it goes through.It is important to note that although hemosiderins are also included in the urine in the setting of intravascular hemolytic hemoglobinuria, it will be detected only several days after the onset of the extensive intravascular hemolysis and will remain detectable several days after termination of intravascular hemolysis. The phenomenon tells that the detection of hemosiderin in urine is indicative of either ongoing or recent intravascular hemolysis characterized by excessive hemoglobin and/or met-hemoglobin filtered through the renal glomerulus as well as the loss of hemosiderin-laden necrotic tubular cells. See also Extravascular hemolysis Note == References ==

Fibrosing colonopathy

Fibrosing colonopathy is a disease that arises in people with cystic fibrosis treated with high doses of pancreatic enzyme supplements. Symptoms are non-specific with abdominal pain, abdominal swelling, vomiting, and constipation.Risk factors include being young, prior surgery of the intestines, and the use of certain medications including corticosteroids and H2 blockers. It may appear similar to distal intestinal obstruction syndrome or inflammatory colitis such as Crohns disease.A maximum dose of 10,000 IU of lipase per kilogram per day is recommended for pancreatic enzyme supplementation to prevent this condition. More than 60 cases have been described as of 1999. The disease was suggested to be caused by methacrylic acid copolymer which is used as coating for delayed release of enzymes but there is no reliable evidence for that. == References ==

Peliosis hepatis

Peliosis hepatis is an uncommon vascular condition characterised by multiple, randomly distributed, blood-filled cavities throughout the liver. The size of the cavities usually ranges between a few millimetres and 3 cm in diameter. In the past, it was a mere histological curiosity occasionally found at autopsies, but has been increasingly recognised with wide-ranging conditions from AIDS to the use of anabolic steroids. It also occasionally affects spleen, lymph nodes, lungs, kidneys, adrenal glands, bone marrow, and other parts of gastrointestinal tract.Peliosis hepatis is often erroneously written "peliosis hepatitis", despite its not being one of the hepatitides. The correct term arises from the Greek pelios, i.e. discoloured by extravasated blood, livid, and the Latinized genitive case (hepatis) of the Greek hepar, liver. Presentation Disease associations Infections: HIV, bacillary peliosis (caused by genus Bartonella, bacteria responsible for cat-scratch disease which are identified histologically adjacent to the peliotic lesions), Staphylococcus aureus Chronic conditions: End stage kidney failure, kwashiorkor, tuberculosis, and other chronic infections Malignancy: Monoclonal gammopathies (multiple myeloma and Waldenströms macroglobulinemia), Hodgkin disease, malignant histiocytosis, seminoma, hepatocellular adenoma, and hepatocarcinoma Kidney transplants: It can be found in up to 20% patients, can be related to azathioprine or cyclosporine use, and may be associated with increased risk of transplant rejection. Drugs and toxins: Corticosteroids, androgens, azathioprine, tamoxifen Pathophysiology The pathogenesis of peliosis hepatis is unknown. Several hypotheses are given, such as it arises from sinusoidal epithelial damage, increased sinusoidal pressure due to obstruction in blood outflow from the liver, or hepatocellular necrosis.Two morphologic patterns of hepatic peliosis were described by Yanoff and Rawson. In the phlebectatic type, the blood-filled spaces are lined with endothelium and are associated with aneurysmal dilatation of the central vein; in the parenchymal type, the spaces have no endothelial lining and they usually are associated with haemorrhagic parenchymal necrosis. Some consider both patterns to be one process, initiated by focal necrosis of liver parenchyma, observed in parenchymal type, progressing into formation of fibrous wall and endothelial lining around haemorrhage of phlebectatic type. Fibrosis, cirrhosis, regenerative nodules, and tumours may also be seen. Diagnosis The condition is typically asymptomatic and is discovered following evaluation of abnormal liver function test. However, when severe, it can manifest as jaundice, hepatomegaly, liver failure, and haemoperitoneum. Other cystic conditions of liver Polycystic liver disease Solitary congenital cysts Congenital hepatic fibrosis Hydatid cyst Von Meyenburg complexes Caroli disease (type V choledochal cyst) Type IV choledochal cysts Treatment Treatment is usually directed towards management of the underlying cause. Withdrawal of azathioprine leads to remission in kidney transplant; bacillary peliosis responds to antibiotics. In rare circumstances partial resection of liver or transplant may be required. References == External links ==

Dysuria

Dysuria refers to painful or uncomfortable urination.It is one of a constellation of irritative bladder symptoms (also sometimes referred to as lower urinary tract symptoms), which includes nocturia and urinary frequency. Diagnosis The clinician should also look for physical findings of fever, rash, direct tenderness over the bladder area, and joint pain. Physical findings of increased temperature, increased pulse, low blood pressure in the presence of dysuria can indicate systemic infection. Urological obstruction due to stone or tumor can result in findings of hematuria, decreased urination, and bladder spasms. All these physical findings should be looked for carefully while obtaining history. History regarding recent sexual activity is crucial.Urinalysis is the most useful test to start the work up in a patient of dysuria. Urinalysis positive for nitrite carries a high predictive value of a positive urine culture. Also, urine dipstick showing leukocytes as equal predictive value as the presence of nitrites. When both are present, the predictive value goes even higher. If the patient only has leukocyte esterase or bacteria in the urine, then dysuria may suggest that the patient probably has urethritis. Differential diagnosis This is typically described to be a burning or stinging sensation. It is most often a result of a urinary tract infection. It may also be due to an STD, bladder stones, bladder tumors, and virtually any condition of the prostate. It can also occur as a side effect of anticholinergic medication used for Parkinsons disease. Drugs and irritants Chemical irritants, e.g., soaps, tampons, toilet papers Drugs, e.g., Cyclophosphamide, Ketamine Capsaicin consumption, e.g., habanero peppers Genital Benign prostatic hyperplasia (male) Endometriosis (female) Prostatic cancer (male) Prostatitis (male) Vaginitis (female) Urinary tract One of the most common causes of dysuria is urinary tract infection. Urinary tract infections are more common in females than males due to female anatomy, having a shorter and straight urethra compared to males who have a longer and curved urethra due to male anatomy. In females, bacteria can reach the bladder more easily due to shorter and straight urethra as they have less distance to travel. Because of these reasons, females tend to experience dysuria more frequently compared to males. Also, most urinary tract infections are uncomplicated. Chlamydia Cystitis Hemorrhagic cystitis Kidney stones Malignancy, i.e., bladder cancer, prostatic cancer, or urethral cancer Prostatic enlargement, i.e., benign prostatic hyperplasia (male), prostatic cancer Prostatitis (male) Pyelonephritis Sexually transmitted disease Trichomoniasis Urethral stricture Urethritis Urinary schistosomiasis Urinary tract infection (UTI) caused by bacterial infection Other Diverticulitis Hypotension Mass in the abdomen Reactive arthritis Acute intermittent porphyria Hereditary coproporphyria Variegate porphyria References == External links ==

Apnea

Apnea (BrE: apnoea) is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are (patency), there may or may not be a flow of gas between the lungs and the environment, but if theres sufficient flow, gas exchange within the lungs and cellular respiration wouldnt be severely affected. Voluntarily doing this is called holding ones breath. Apnea may first be diagnosed in childhood, and it is recommended to consult an ENT specialist, allergist or sleep physician to discuss symptoms when noticed; malformation and/or malfunctioning of the upper airways may be observed by an orthodontist. Cause Apnea can be involuntary—for example, drug-induced (such as by opiate toxicity), mechanically / physiologically induced (for example, by strangulation or choking), or a consequence of neurological disease or trauma. During sleep, people with severe sleep apnea can have over thirty episodes of intermittent apnea per hour every night.Apnea can also be observed during periods of heightened emotion, such as during crying or accompanied by the Valsalva maneuver when a person laughs. Apnea is a common feature of sobbing while crying, characterised by slow but deep and erratic breathing followed by brief periods of breath holding when crying. Another example of apnea are breath-holding spells; these are sometimes emotional in cause and are usually observed in children as a result of frustration, emotional stress and other psychological extremes. Voluntary apnea can be achieved by closing the vocal cords, simultaneously keeping the mouth closed and blocking the nasal vestibule, or constantly activating expiratory muscles, not allowing any inspiration. Complications Under normal conditions, humans cannot store much oxygen in the body. Prolonged apnea leads to severe lack of oxygen in the blood circulation, leading to dysfunction of organ systems. Permanent brain damage can occur after as little as three minutes and death will inevitably ensue after a few more minutes unless ventilation is restored. However, under special circumstances such as hypothermia, hyperbaric oxygenation, apneic oxygenation (see below), or extracorporeal membrane oxygenation, much longer periods of apnea may be tolerated without severe detrimental consequences. Untrained humans usually cannot sustain voluntary apnea for more than one or two minutes, since the urge to breathe becomes unbearable. The reason for the time limit of voluntary apnea is that the rate of breathing and the volume of each breath are tightly regulated to maintain constant values of CO2 tension and pH of the blood more than oxygen levels. In apnea, CO2 is not removed through the lungs and accumulates in the blood. The consequent rise in CO2 tension and drop in pH result in stimulation of the respiratory centre in the brain which eventually cannot be overcome voluntarily. The accumulation of carbon dioxide in the lungs will eventually irritate and trigger impulses from the respiratory center part of the brain and the phrenic nerve. Rising levels of carbon dioxide signal the body to breathe and resume unconscious respiration forcibly. The lungs start to feel as if they are burning, and the signals the body receives from the brain when CO2 levels are too high include strong, painful, and involuntary contractions or spasms of the diaphragm and the muscles in between the ribs. At some point, the spasms become so frequent, intense and unbearable that continued holding of the breath is nearly impossible.When a person is immersed in water, physiological changes due to the mammalian diving reflex enable somewhat longer tolerance of apnea even in untrained persons as breathing isnt possible underwater. Tolerance can in addition be trained. The ancient technique of free-diving requires breath-holding, and world-class free-divers can hold their breath underwater up to depths of 214 metres (702 ft) and for more than four minutes. Apneists, in this context, are people who can hold their breath for a long time. Hyperventilation Voluntary hyperventilation before beginning voluntary apnea is commonly believed to allow the person involved to safely hold their breath for a longer period. In reality, it will give the impression that one does not need to breathe, while the body is actually experiencing a blood-oxygen level that would normally, and indirectly, invoke a strong dyspnea and eventually involuntary breathing. Some have incorrectly attributed the effect of hyperventilation to increased oxygen in the blood, not realizing that it is actually due to a decrease in CO2 in the blood and lungs. Blood leaving the lungs is normally fully saturated with oxygen, so hyperventilation of normal air cannot increase the amount of oxygen available, as oxygen in blood is the direct factor. Lowering the CO2 concentration increases the pH of the blood, thus increasing the time before blood becomes acidic enough so the respiratory center becomes stimulated, as described above. While hyperventilation will yield slightly longer breath-holding times, any small time increase is at the expense of possible hypoxia, though it might not be felt as easily. One using this method can suddenly lose consciousness unnoticed—a shallow water blackout—as a result. If a person loses consciousness underwater, there is considerable danger that they will drown. An alert diving partner or nearby lifeguard would be in the best position to rescue such a person. Static apnea blackout occurs at the surface when a motionless diver holds their breath long enough for the circulating oxygen in blood to fall below that required for the brain to maintain consciousness. It involves no pressure changes in the body and is usually performed to enhance breath-hold time. It should never be practiced alone, but under strict safety protocols with a safety guard or equipment beside the diver. Apneic oxygenation Because the exchange of gases between the blood and airspace of the lungs is independent of the movement of gas to and from the lungs, enough oxygen can be delivered to the circulation even if a person is apneic, even if the diaphragm doesnt move. With the onset of apnea, low pressure develops in the airspace of the lungs because more oxygen is absorbed than CO2 is released. With the airways closed or obstructed, this will lead to a gradual collapse of the lungs and suffocation. However, if the airways are open, any gas supplied to the upper airways will follow the pressure gradient and flow into the lungs to replace the oxygen consumed. If pure oxygen is supplied, this process will serve to replenish the oxygen stored in the lungs and resume sufficient ventilation. The uptake of oxygen into the blood will then remain at the usual level, and the normal functioning of the organs will not be affected. A detriment to this hyperoxygenation is the occurrence of nitrogen washout, which can lead to absorption atelectasis.However, no CO2 is removed during apnea. The partial pressure of CO2 in the airspace of the lungs will quickly equilibrate with that of the blood. As the blood is loaded with CO2 from the metabolism without a way to remove it, more and more CO2 will accumulate and eventually displace oxygen and other gases from the airspace. CO2 will also accumulate in the tissues of the body, resulting in respiratory acidosis. Under ideal conditions (i.e., if pure oxygen is breathed before onset of apnea to remove all nitrogen from the lungs, and pure supplemental oxygen is insufflated), apneic oxygenation could theoretically be sufficient to provide enough oxygen for survival of more than one hours duration in a healthy adult. However, accumulation of carbon dioxide (described above) would remain the limiting factor. Apneic oxygenation is more than a physiologic curiosity. It can be employed to provide a sufficient amount of oxygen in thoracic surgery when apnea cannot be avoided, and during manipulations of the airways such as bronchoscopy, intubation, and surgery of the upper airways. However, because of the limitations described above, apneic oxygenation is inferior to extracorporal circulation using a heart-lung machine and is therefore used only in emergencies, short procedures, or where extracorporal circulation cant be accessed. Use of PEEP valves is also an accepted alternative (5 cm H2O in average weight patients and 10 cm H2O significantly improved lung and chest wall compliance in morbidly obese patients).In 1959, Frumin described the use of apneic oxygenation during anesthesia and surgery. Of the eight test subjects in this landmark study, the highest recorded PaCO2 was 250 millimeters of mercury, and the lowest arterial pH was 6.72 after 53 minutes of apnea. Apnea scientific studies Studies found spleen volume is slightly reduced during short breath-hold apnea in healthy adults. Apnea test in determining brain death A recommended practice for the clinical diagnosis of brain death formulated by the American Academy of Neurology hinges on the conjunction of three diagnostic criteria: a coma, absence of brainstem reflexes, and apnea (defined as the inability of the patient to breathe unaided: that is, with no life support systems like ventilators). The apnea test follows a delineated protocol. Apnea testing is not suitable in patients who are hemodynamically unstable with increasing vasopressor needs, metabolic acidosis, or require high levels of ventilatory support. Apnea testing carries the risk of arrhythmias, worsening hemodynamic instability, or metabolic acidosis beyond the level of recovery and can potentially make the patient unsuitable for organ donation (see above). In this situation a confirmatory test is warranted as it is unsafe to perform the apnea test to the patient. Etymology and pronunciation The word apnea (or apnoea) uses combining forms of a- + -pnea, from Greek Greek: ἄπνοια, from ἀ-, privative, πνέειν, to breathe. See pronunciation information at dyspnea. See also Apnea and Work Apnea-hypopnea index References ‌ Nunn, J. F. (1993). Applied Respiratory Physiology (4th ed.). Butterworth-Heinemann. ISBN 0-7506-1336-X. External links Sleep Apnea, a resource from the Harvard Division of Sleep Medicine on Obstructive Sleep Apnea apneacalculator.com, information about Apnea and the apnea-calculator for clinical treatment of Obstructive Sleep Apnea Freediving Courses & Training in the UK, information about learning the sport of Freediving, the club is called Apneists UK DiveWise.Org Non-profit scientific and educational resource for apnea divers DAN Breath-Hold Workshop Divers Alert Network 2006 Breath-Hold Diving Workshop PDF

Coarse facial features

Coarse facial features or coarse facies describes a constellation of facial features that are present in many inborn errors of metabolism. Features include: large, bulging head prominent scalp veins "saddle-like, flat bridged nose with broad, fleshy tip" large lips and tongue small, widely spaced and/or malformed teeth hypertrophic alveolar ridges and/or gumsHeads tend to be longer than normal from front to back, with a bulging forehead. This is because of the earlier than normal or premature fusion of skull bones in an affected individual. Causes Several conditions are associated with coarse facial features. Acromegaly Alpha-mannosidosis type II Aspartylglycosaminuria Battaglia Neri syndrome Borjeson Syndrome Chromosome 6q deletion syndrome Coarse face - hypotonia - constipation Congenital hypothyroidism Dandy-Walker malformation (with mental retardation basal ganglia disease and seizures) Dyggve-Melchior-Clausen Syndrome Fucosidosis type 1 Fucosidosis type II Gangliosidosis generalized GM1 (type 1) Gangliosidosis GM1 (type 3) GM1 gangliosidosis Goldberg syndrome Hyde-Forster-Mccarthy-Berry syndrome Hyper IgE Hypomelanosis of Ito I cell disease Immunodeficiency due to defect in MAPBP-interacting protein Infantile sialic acid storage disorder Job syndrome Mannosidosis (alpha B lysosomal) McCune-Albright Syndrome Mental retardation (X-linked - epilepsy - progressive joint contractures - typical face) Mental retardation (X-linked Raynaud type) Mieschers syndrome Morquio syndrome Morquio syndrome type A Morquio syndrome type B MPS 3 C MPS 3 D Mucolipidosis III Mucopolysaccharidosis type 2 Hunter syndrome- mild form Mucopolysaccharidosis type 2 Hunter syndrome- severe form Mucopolysaccharidosis type 3 Mucopolysaccharidosis type 6 Mucopolysaccharidosis type 7 Sly syndrome Mucopolysaccharidosis type I Hurler syndrome Mucopolysaccharidosis type I Hurler/Scheie syndrome Mucopolysaccharidosis type I Scheie syndrome Multiple endocrine abnormalities - adenylyl cyclase dysfunction Multiple endocrine neoplasia type 2b Neuraminidase deficiency (type II juvenile form) Nodulosis-arthropathy-osteolysis syndrome Nonkeratan-sulfate-excreting Morquio syndrome Pituitary tumors (adult) Sialidosis type II (congenital) Sialidosis type II (infantile) Sialuria syndrome Simpson-Golabi-Behmel syndrome Simpson-Golabi-Behmel syndrome - type 1 (SGBS1) Skeletal dysplasia - coarse facies - mental retardation Spondyloepimetaphyseal dysplasia (genevieve type) Sulfatidosis juvenile (Austin type) Winchester syndrome See also Facies (medical) References External links https://web.archive.org/web/20090106211640/http://www.mps1disease.com/patient/about/mps_pt_symptom_coarse_facial_features.asp

Reflex bradycardia

Reflex bradycardia is a bradycardia (decrease in heart rate) in response to the baroreceptor reflex, one of the bodys homeostatic mechanisms for preventing abnormal increases in blood pressure. In the presence of high mean arterial pressure, the baroreceptor reflex produces a reflex bradycardia as a method of decreasing blood pressure by decreasing cardiac output.Blood pressure (BP) is determined by cardiac output (CO) and total peripheral resistance (TPR), as represented by the formula BP = CO x TPR. Cardiac output (CO) is affected by two factors, the heart rate (HR) and the stroke volume (SV), the volume of blood pumped from one ventricle of the heart with each beat (CO = HR x SV, therefore BP = HR x SV x TPR). In reflex bradycardia, blood pressure is reduced by decreasing cardiac output (CO) via a decrease in heart rate (HR).An increase in blood pressure can be caused by increased cardiac output, increased total peripheral resistance, or both. The baroreceptors in the carotid sinus sense this increase in blood pressure and relay the information to the cardiovascular centres in the medulla oblongata. In order to maintain homeostasis, the cardiovascular centres activate the parasympathetic nervous system. Via the vagus nerve, the parasympathetic nervous system stimulates neurons that release the neurotransmitter acetylcholine (ACh) at synapses with cardiac muscle cells. Acetylcholine then binds to M2 muscarinic receptors, causing the decrease in heart rate that is referred to as reflex bradycardia.The M2 muscarinic receptors decrease the heart rate by inhibiting depolarization of the sinoatrial node via Gi protein-coupled receptors and through modulation of muscarinic potassium channels. Additionally, M2 receptors reduce the contractile forces of the atrial cardiac muscle and reduce the conduction velocity of the atrioventricular node (AV node). However, M2 receptors have no effect on the contractile forces of the ventricular muscle.Stimuli causing reflex bradycardia include: Oculocardiac reflex Sympathetic response to intracranial hypertension Systemically administered norepinephrine (α-adrenergic effects on systemic vasculature exceed the effects of β1-adrenergic effects on the heart) == References ==

Cyanosis

Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that reflect cyanosis are usually in locations where the skin is thinner, including the mucous membranes, lips, nail beds, and ear lobes. Some medications containing amiodarone or silver, Mongolian spots, large birth marks, and the consumption of food products with blue or purple dyes can also result in the bluish skin tissue discoloration and may be mistaken for cyanosis.Cyanosis is further classified into central cyanosis vs. peripheral cyanosis. Pathophysiology The mechanism behind cyanosis is different depending on whether it is central or peripheral. Central cyanosis Central cyanosis is caused by a decrease in arterial oxygen saturation (SaO2) and begins to show once the concentration of deoxyhemoglobin in the blood reaches a concentration of ≥ 5.0 g/dL (≥ 3.1 mmol/L or oxygen saturation of ≤ 85 %). Causes of central cyanosis are discussed below. Peripheral cyanosis Peripheral cyanosis happens when there is increased concentration of deoxyhemoglobin on the venous side of the peripheral circulation. In other words, cyanosis is dependent on the concentration of deoxyhemoglobin. Patients with severe anemia may appear normal despite higher than normal concentrations of deoxyhemoglobin. On the other hand, patients with increased amounts of red blood cells (e.g. polycythemia vera) can appear cyanotic even with lower concentrations of deoxyhemoglobin. Causes Central cyanosis Central cyanosis is often due to a circulatory or ventilatory problem that leads to poor blood oxygenation in the lungs. It develops when arterial oxygen saturation drops below 85% or 75%.Acute cyanosis can be a result of asphyxiation or choking and is one of the definite signs that ventilation is being blocked. Central cyanosis may be due to the following causes: Central nervous system (impairing normal ventilation):Intracranial hemorrhage Drug overdose (e.g. heroin) Generalized tonic–clonic seizure (GTCS) Respiratory system:Pneumonia Bronchiolitis Bronchospasm (e.g. asthma) Pulmonary hypertension Pulmonary embolism Hypoventilation Chronic obstructive pulmonary disease, or COPD (emphysema) Cardiovascular system:Congenital heart disease (e.g. Tetralogy of Fallot, right to left shunts in heart or great vessels) Heart failure Valvular heart disease Myocardial infarction Hemoglobinopathies:Methemoglobinemia Sulfhemoglobinemia Polycythemia Congenital cyanosis (HbM Boston) arises from a mutation in the α-codon which results in a change of primary sequence, H → Y. Tyrosine stabilises the Fe(III) form (oxyhaemoglobin) creating a permanent T-state of Hb. Others: High altitude, cyanosis may develop in ascents to altitudes >2400 m. Hypothermia Frostbite Obstructive sleep apnea Peripheral cyanosis Peripheral cyanosis is the blue tint in fingers or extremities, due to an inadequate or obstructed circulation. The blood reaching the extremities is not oxygen-rich and when viewed through the skin a combination of factors can lead to the appearance of a blue color. All factors contributing to central cyanosis can also cause peripheral symptoms to appear but peripheral cyanosis can be observed in the absence of heart or lung failures. Small blood vessels may be restricted and can be treated by increasing the normal oxygenation level of the blood. Peripheral cyanosis may be due to the following causes: All common causes of central cyanosis Reduced cardiac output (e.g. heart failure or hypovolemia) Cold exposure Chronic obstructive pulmonary disease (COPD) Arterial obstruction (e.g. peripheral vascular disease, Raynaud phenomenon) Venous obstruction (e.g. deep vein thrombosis) Differential cyanosis Differential cyanosis is the bluish coloration of the lower but not the upper extremity and the head. This is seen in patients with a patent ductus arteriosus. Patients with a large ductus develop progressive pulmonary vascular disease, and pressure overload of the right ventricle occurs. As soon as pulmonary pressure exceeds aortic pressure, shunt reversal (right-to-left shunt) occurs. The upper extremity remains pink because deoxygenated blood flows through the patent duct and directly into the descending aorta while sparing the brachiocephalic trunk, left common carotid, and left subclavian arteries. Evaluation A detailed history and physical examination (particularly focusing on the cardiopulmonary system) can guide further management and help determine the choice of testing to be performed. Tests that can be performed include pulse oximetry, arterial blood gas, complete blood count, methemoglobin level, electrocardiogram, echocardiogram, X-Ray, CT scan, cardiac catheterization, and hemoglobin electrophoresis. In newborns, peripheral cyanosis typically presents in the distal extremities, circumoral, and periorbital areas. Of note, mucous membranes remain pink in peripheral cyanosis as compared to central cyanosis where the mucous membranes are cyanotic. It is important to note that skin pigmentation and hemoglobin concentration can affect the evaluation of cyanosis. Cyanosis may be more difficult to detect on people with darker skin pigmentation. However, cyanosis can still be diagnosed with careful examination of the typical body areas such as nail beds, tongue, and mucous membranes where the skin is thinner and more vascular. As mentioned above, patients with severe anemia may appear normal despite higher than normal concentrations of deoxyhemoglobin. Signs of severe anemia may include pale mucosa (lips, eyelids, and gums), fatigue, lightheadedness, and irregular heartbeats. Management Cyanosis is a symptom rather than a disease itself, so management should be focused on treating the underlying cause. If it is an emergency, management should always begin with securing the airway, breathing, and circulation. In patients with significant respiratory distress, supplemental oxygen (in the form of nasal canula or continuous positive airway pressure depending on severity) should be given immediately.If the methemoglobin levels are positive for methemoglobinemia, first-line treatment is to administer methylene blue. History The name cyanosis literally means the blue disease or the blue condition. It is derived from the color cyan, which comes from cyanós (κυανός), the Greek word for blue.It is postulated by Dr. Christen Lundsgaard that cyanosis was first described in 1749 by Jean-Baptiste de Sénac, a French physician who served King Louis XV. De Sénac concluded from an autopsy that cyanosis was caused by a heart defect that led to the mixture of arterial and venous blood circulation. But it was not until 1919, when Dr. Lundsgaard was able to derive the concentration of deoxyhemoglobin (8 volumes per cent) that could cause cyanosis. See also Acrocyanosis Blue baby syndrome Raynauds phenomenon Blue Fugates References == External links ==

Eczema vaccinatum

Eczema vaccinatum is a rare severe adverse reaction to smallpox vaccination. It is characterized by serious local or disseminated, umbilicated, vesicular, crusting skin rashes in the face, neck, chest, abdomen, upper limbs and hands, caused by widespread infection of the skin in people with previous diagnosed skin conditions such as eczema or atopic dermatitis, even if the conditions are not active at the time. Other signs and symptoms include fever and facial and supraglottic edema. The condition may be fatal if severe and left untreated. Survivors are likely to have some scarring (pockmarks). Smallpox vaccine should not be given to patients with a history of eczema. Because of the danger of transmission of vaccinia, it also should not be given to people in close contact with anyone who has active eczema and who has not been vaccinated. People with other skin diseases (such as atopic dermatitis, burns, impetigo, or herpes zoster) also have an increased risk of contracting eczema vaccinatum and should not be vaccinated against smallpox. Presentation Associations Eczema is also associated with increased complications related to other vesiculating viruses such as chickenpox; this is called eczema herpeticum. Diagnosis A culture of vesicular fluid will grow vaccinia virus. Skin biopsy shows necrotic epidermal cells with intranuclear inclusions. Treatment Eczema vaccinatum is a serious medical condition that requires immediate and intensive medical care. Therapy has been supportive, such as antibiotics, fluid replacement, antipyretics and analgesics, skin healing, etc.; vaccinia immune globulin (VIG) could be very useful but supplies may be deficient as of 2006. Antiviral drugs have been examined for activity in pox viruses and cidofovir is believed to display potential in this area. Recent cases In March 2007, a two-year-old Indiana boy and his mother contracted the life-threatening vaccinia infection from his father who was vaccinated against smallpox as part of the standard vaccination protocol for individuals serving in the US armed forces beginning in 2002. The child developed the pathognomonic rash which typifies eczema vaccinatum over 80 percent of his body surface area. The boy has a history of eczema, which is a known risk factor for vaccinia infection. See also List of cutaneous conditions References External links Side Effects of Smallpox Vaccination. Centers for Disease Control and Prevention Fact Sheet. Vaccine Reaction Images. CDC.

Hyperalgesia

Hyperalgesia ( or ; hyper from Greek ὑπέρ (huper, “over”), -algesia from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can cause hypersensitivity to stimulus. Prostaglandins E and F are largely responsible for sensitizing the nociceptors. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection. Types Hyperalgesia can be experienced in focal, discrete areas, or as a more diffuse, body-wide form. Conditioning studies have established that it is possible to experience a learned hyperalgesia of the latter, diffuse form. The focal form is typically associated with injury, and is divided into two subtypes: Primary hyperalgesia describes pain sensitivity that occurs directly in the damaged tissues. Secondary hyperalgesia describes pain sensitivity that occurs in surrounding undamaged tissues.Opioid-induced hyperalgesia may develop as a result of long-term opioid use in the treatment of chronic pain. Various studies of humans and animals have demonstrated that primary or secondary hyperalgesia can develop in response to both chronic and acute exposure to opioids. This side effect can be severe enough to warrant discontinuation of opioid treatment. Causes Hyperalgesia is induced by platelet-activating factor (PAF) which comes about in an inflammatory or an allergic response. This seems to occur via immune cells interacting with the peripheral nervous system and releasing pain-producing chemicals (cytokines and chemokines).One unusual cause of focal hyperalgesia is platypus venom.Long-term opioid (e.g. heroin, morphine) users and those on high-dose opioid medications for the treatment of chronic pain, may experience hyperalgesia and experience pain out of proportion to physical findings, which is a common cause for loss of efficacy of these medications over time. As it can be difficult to distinguish from tolerance, opioid-induced hyperalgesia is often compensated for by escalating the dose of opioid, potentially worsening the problem by further increasing sensitivity to pain. Chronic hyperstimulation of opioid receptors results in altered homeostasis of pain signalling pathways in the body with several mechanisms of action involved. One major pathway being through stimulation of the nociceptin receptor, and blocking this receptor may therefore be a means of preventing the development of hyperalgesia.Stimulation of nociceptive fibers in a pattern consistent with that from inflammation switches on a form of amplification in the spinal cord, long term potentiation. This occurs where the pain fibres synapse to pain pathway, the periaqueductal grey. Amplification in the spinal cord may be another way of producing hyperalgesia. The release of proinflammatory cytokines such as interleukin-1 by activated leukocytes triggered by lipopolysaccharides, endotoxins and other signals of infection also increases pain sensitivity as part of sickness behavior, the evolved response to illness. Diagnosis Simple bedside tests include response (pain intensity and character) to cotton swab, finger pressure, pinprick, cold and warm stimuli, e.g., metal thermo rollers at 20°C and 40°C, as well as mapping of the area of abnormality.Quantitative sensory testing can be used to determine pain thresholds (decreased pain threshold indicates allodynia) and stimulus/response functions (increased pain response indicate hyperalgesia). Dynamic mechanical allodynia can be assessed using a cotton swab or a brush. A pressure algometer and standardized monofilaments or weighted pinprick stimuli are used for assessing pressure and punctate allodynia and hyperalgesia and a thermal tester is used for thermal testing. Treatment Hyperalgesia is similar to other sorts of pain associated with nerve irritation or damage such as allodynia and neuropathic pain, and consequently may respond to standard treatment for these conditions, using various drugs such as SSRI or tricyclic antidepressants, Nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, gabapentin or pregabalin, NMDA antagonists, or atypical opioids such as tramadol. Where hyperalgesia has been produced by chronic high doses of opioids, reducing the dose may result in improved pain management. However, as with other forms of nerve dysfunction associated pain, treatment of hyperalgesia can be clinically challenging, and finding a suitable drug or drug combination that is effective for a particular patient may require trial and error. The use of a transcutaneous electrical nerve stimulation device has been shown to alleviate hyperalgesia. See also Allodynia References == External links ==

Thoracic outlet syndrome

Thoracic outlet syndrome (TOS) is a condition in which there is compression of the nerves, arteries, or veins in the passageway from the lower neck to the armpit. There are three main types: neurogenic, venous, and arterial. The neurogenic type is the most common and presents with pain, weakness, paraesthesia, and occasionally loss of muscle at the base of the thumb. The venous type results in swelling, pain, and possibly a bluish coloration of the arm. The arterial type results in pain, coldness, and pallor of the arm.TOS may result from trauma, repetitive arm movements, tumors, pregnancy, or anatomical variations such as a cervical rib. The diagnosis may be supported by nerve conduction studies and medical imaging. TOS is difficult to diagnose and there are many potential differential diagnoses as well as other diseases that are often co-occurrent with TOS.Initial treatment for the neurogenic type is with exercises to strengthen the chest muscles and improve posture. NSAIDs such as naproxen may be used for pain. Surgery is typically done for the arterial and venous types and for the neurogenic type if it does not improve with other treatments. Blood thinners may be used to treat or prevent blood clots. The condition affects about 1% of the population. It is more common in women than men and it occurs most commonly between 20 and 50 years of age. The condition was first described in 1818 and the current term "thoracic outlet syndrome" first used in 1956. Signs and symptoms TOS affects mainly the upper limbs, with signs and symptoms manifesting in the shoulders, neck, arms and hands. Pain can be present on an intermittent or permanent basis. It can be sharp/stabbing, burning, or aching. TOS can involve only part of the hand (as in the pinky and adjacent half of the ring finger), all of the hand, or the inner aspect of the forearm and upper arm. Pain can also be in the side of the neck, the pectoral area below the clavicle, the armpit/axillary area, and the upper back (i.e., the trapezius and rhomboid area). Discoloration of the hands, one hand colder than the other hand, weakness of the hand and arm muscles, and tingling are commonly present.Only 1% of people with carpal tunnel syndrome have concomitant TOS.Repetitive motions can cause enlargement of muscles which causes compression of veins. Besides, overuse injury of the upper limbs causes swellings, small bleeding, and subsequent fibrosis which would cause the thrombosis of the subclavian vein, leading to Paget–Schroetter disease or effort-induced thrombosis.TOS can be related to cerebrovascular arterial insufficiency when affecting the subclavian artery. It also can affect the vertebral artery, in which case it could produce vision disturbances, including transient blindness, and embolic cerebral infarction.TOS can also lead to eye problems and vision loss as a circumstance of vertebral artery compression. Although very rare, if compression of the brain stem is also involved in an individual presentation of TOS, transient blindness may occur while the head is held in certain positions. If left untreated, TOS can lead to neurological deficits as a result of the hypoperfusion and hypometabolism of certain areas of the brain and cerebellum.TOS has similar symptoms to pectoralis minor syndrome (PMS), which usually results from compression of the braxial plexus beneath the pectoralis minor muscle (while neurogenic TOS is caused by compression of the same nerves above the clavicle). Unlike TOS there is typically few headaches or neck pain in patients with PMS only, instead with pain in the chest area. Initially, it was believed that 95 percent of patients with TOS had nerve compression in the scalene area, but in the twenty-first century it is now recognized that the majority have nerve compression under the pectoralis minor, either by itself or in addition to the scalene area. One study of 100 patients diagnosed with neurogenic TOS found that 75 percent had neurogenic PMS and 30 percent in fact had PMS without TOS. Causes TOS can be attributed to one or more of the following factors: Congenital abnormalities are frequently found in persons with TOS. These include cervical rib, prolonged transverse process, and muscular abnormalities (e.g., in the scalenus anterior muscle, a sickle-shaped scalenus medius) or fibrous connective tissue anomalies. Trauma (e.g., whiplash injuries) or repetitive strain is frequently implicated. Rarer acquired causes include tumors (especially pancoast tumor), hyperostosis, and osteomyelitis Diagnosis Adsons sign and the costoclavicular maneuver lack specificity and sensitivity and should make up only a small part of the mandatory comprehensive history and physical examination undertaken with a patient suspected of having TOS. There is currently no single clinical sign that makes the diagnosis of TOS with any degree of certainty.Additional maneuvers that may be abnormal in TOS include Wrights Test, which involves hyperabducting the arms over the head with some extension and evaluating for loss of radial pulses or signs of blanching of the skin in the hands indicating a decrease in blood flow with the maneuver. The "compression test" is also used, exerting pressure between the clavicle and medial humeral head causes radiation of pain and/or numbness into the affected arm.Doppler arteriography, with probes at the fingertips and arms, tests the force and "smoothness" of the blood flow through the radial arteries, with and without having the patient perform various arm maneuvers (which causes compression of the subclavian artery at the thoracic outlet). The movements can elicit symptoms of pain and numbness and produce graphs with diminished arterial blood flow to the fingertips, providing strong evidence of impingement of the subclavian artery at the thoracic outlet. Doppler arteriography does not utilize probes at the fingertips and arms, and in this case is likely being confused with plethysmography, which is a different method that utilizes ultrasound without direct visualization of the affected vessels. Doppler ultrasound (not really arteriography) would not be used at the radial artery in order to make the diagnosis of TOS. Finally, even if a Doppler study of the appropriate artery were to be positive, it would not diagnose neurogenic TOS, by far the most common subtype of TOS. There is plenty of evidence in the medical literature to show that arterial compression does not equate to brachial plexus compression, although they may occur together, in varying degrees. Additionally, arterial compression by itself does not make the diagnosis of arterial TOS (the rarest form of TOS). Lesser degrees of arterial compression have been shown in normal individuals in various arm positions and are thought to be of little significance without the other criteria for arterial TOS.MRI scan can show the anatomy of the thoracic outlet, the soft tissues causing compression, and can show directly the brachial plexus compression. Classification By structures affected and symptomatology There are three main types of TOS, named according to the cause of the symptoms; however, these three classifications have been coming into disfavor because TOS can involve all three types of compression to various degrees. The compression can occur in three anatomical structures (arteries, veins and nerves), it can be isolated, or, more commonly, two or three of the structures are compressed to greater or lesser degrees. In addition, the compressive forces can be of different magnitude in each affected structure. Therefore, symptoms can be variable. Neurogenic TOS includes disorders produced by compression of components of the brachial plexus nerves. The neurogenic form of TOS accounts for 95% of all cases of TOS. Arterial TOS is due to compression of the subclavian artery. This is less than one percent of cases. Venous TOS is due to compression of the subclavian vein. This makes up about 4% of cases. By event There are many causes of TOS. The most frequent cause is trauma, either sudden (as in a clavicle fracture caused by a car accident), or repetitive (as in a legal secretary who works with his/her hands, wrists, and arms at a fast-paced desk station with non-ergonomic posture for many years). TOS is also found in certain occupations involving much lifting of the arms and repetitive use of the wrists and arms. One cause of arterial compression is trauma, and a recent case involving fracture of the clavicle has been reported.The two groups of people most likely to develop TOS are those with neck injuries due to traffic accidents and those who use computers in non-ergonomic postures for extended periods of time. TOS is frequently a repetitive stress injury (RSI) caused by certain types of work environments. By structure causing constriction It is also possible to classify TOS by the location of the obstruction: Anterior scalene syndrome (compression on brachial plexus and/or subclavian artery caused by muscle growth). Cervical rib syndrome (compression on brachial plexus and/or subclavian artery caused by bone growth). Costoclavicular syndrome (narrowing between the clavicle and the first rib) – diagnosed with the costoclavicular maneuver.Some people are born with an extra incomplete and very small rib above their first rib, which protrudes out into the superior thoracic outlet space. This rudimentary rib causes fibrous changes around the brachial plexus nerves, inducing compression and causing the symptoms and signs of TOS. This is called a "cervical rib" because of its attachment to C-7 (the seventh cervical vertebra), and its surgical removal is almost always recommended. The symptoms of TOS can first appear in the early teen years as a child is becoming more athletic. Treatment Evidence for the treatment of thoracic outlet syndrome as of 2014 is poor. Physical measures Stretching, occupational and physical therapy are common non-invasive approaches used in the treatment of TOS. The goal of stretching is to relieve compression in the thoracic cavity, reduce blood vessel and nerve impingement, and realign the bones, muscles, ligaments, or tendons that are causing the problem. One commonly prescribed set of stretches includes moving the shoulders anteriorly (forward – called "hunching"), then back to a neutral position, then extending them posteriorly (backward, called "arching"), then back to neutral, followed by lifting the shoulders up as high as possible, and then back down to neutral, repeated in cycles as tolerated. Another set of stretches involves tilting and extending the neck opposite to the side of the injury while keeping the injured arm down or wrapped around the back. Occupational or Physical therapy can include passive or active range of motion exercises, working up to weighted or restricted sets (as tolerated).TOS is rapidly aggravated by poor posture. Active breathing exercises and ergonomic desk setup and motion practices can help maintain active posture. Often the muscles in the back become weak due to prolonged (years of) "hunching" and other poor postures.Ice can be used to decrease inflammation of sore or injured muscles. Heat can also aid in relieving sore muscles by improving blood circulation to them. While the whole arm generally feels painful in TOS, some relief can be seen when ice or heat is intermittently applied to the thoracic region (collar bone, armpit, or shoulder blades). Medications In a review, botox was compared to a placebo injected into the scalene muscles. No effect in terms of pain relief or improved movement was noted. However, in a six-months follow-up, paresthesia (abnormal sensations such as in pins and needles) was seen to be significantly improved. Surgery Surgical approaches have also been used successfully in TOS. Microsurgery can be used approaching the area from above the collar bone (supraclavicular) followed by neurolysis of the brachial plexus, removal of the scalene muscle (scalenectomy), and the release of the underlying (subclavicular) blood vessels. This approach avoids the use of resection, and has been found to be an effective treatment. In cases where the first rib (or a fibrous band extending from the first rib) is compressing a vein, artery, or the nerve bundle, part of the first rib and any compressive fibrous tissue, can be removed in a first rib resection and thoracic outlet decompression surgical procedure; scalene muscles may also need to be removed (scalenectomy). This allows increased blood flow and the reduction of nerve compression. In some cases there may be a rudimentary rib or a cervical rib that can be causing the compression, which can be removed using the same technique.Physical therapy is often used before and after the operation to improve recovery time and outcomes. Potential complications include pneumothorax, infection, loss of sensation, motor problems, subclavian vessel damage, and, as in all surgeries, a very small risk of permanent serious injury or death. Notable cases SportsSeveral Major League Baseball players, especially pitchers, have been diagnosed with thoracic outlet syndrome, including Stephen Strasburg, Chris Archer, Matt Harvey, Chris Carpenter, Jaime Garcia, Shaun Marcum, Matt Harrison, Clayton Richard, Nate Karns, and Noah Lowry. Starting pitcher Chris Young, who previously struggled with shoulder problems, underwent surgery for TOS in 2013 and felt "completely different" post-recovery. Young exceeded expectations on his return to the major leagues at age 35, becoming a valuable member of the 2014 Seattle Mariners starting rotation. In July 1980, Houston Astros starting pitcher J.R. Richard collapsed while playing a game of catch, and was found to have experienced a stroke due to severe blockage of his right carotid artery. Given the fact that shortly beforehand, he had been found to have near-total obstruction of the arteries supplying his right arm, he was eventually diagnosed with extensive arterial thoracic outlet syndrome. Although he attempted a comeback, his professional baseball career was effectively ended.NHL defenseman Adam McQuaid was diagnosed with TOS in September 2012, and as a result was nominated for the Bill Masterton Memorial Trophy. Forward Chris Kreider was diagnosed with a malformed rib in 2017. Kreider dealt with multiple symptoms prior to the diagnosis, such as shortness of breath on the ice, swelling/numbness in his right arm, coughing up blood and a blood clot in his right arm. Kreider underwent successful surgery to resect a rib in January 2018 (the same surgery as TOS) and has performed well since returning to the Rangers.NBA guard Markelle Fultz was diagnosed with TOS in December 2018.UFC fighter Matt Serra had a rib removed to alleviate TOS. MusicMusician Isaac Hanson had a pulmonary embolism as a consequence of thoracic outlet syndrome.The Japanese band Maria disbanded in 2010 due to drummer Tattsus TOS which made it impossible for her to continue playing.In 2015, singer Tamar Braxton had to leave Dancing With The Stars due to TOS. See also Pectoralis minor syndrome May–Thurner syndrome – a similar compressive pathology involving the left common iliac vein Backpack palsy – a similar compressive pathology involving the long thoracic nerve, or adjacent brachial plexus nerves References External links thoracic at NINDS

Prion

Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It is not known what causes a normal protein to misfold, but the resulting abnormal three-dimensional structure confers infectious properties by collapsing nearby protein molecules into the same shape. The word prion is derived from the term, "proteinaceous infectious particle". In comparison to all other known infectious agents such as viroids, viruses, bacteria, fungi, and parasites, all of which contain nucleic acids (DNA, RNA, or both), the hypothesized role of a protein as an infectious agent stands in contrast. Prion isoforms of the prion protein (PrP), whose specific function is uncertain, are hypothesized as the cause of transmissible spongiform encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle (commonly known as "mad cow disease") and Creutzfeldt–Jakob disease (CJD) in humans. All known prion diseases in mammals affect the structure of the brain or other neural tissue; all are progressive, have no known effective treatment, and are always fatal. Until 2015, all known mammalian prion diseases were caused by the prion protein (PrP); however, in 2015 it was hypothesized that multiple system atrophy (MSA) was caused by a prion form of alpha-synuclein.Prions are a type of intrinsically disordered protein, which change their conformation unless they are bound to a specific partner such as another protein. With a prion, two protein chains are stabilized if one binds to another in the same conformation. The probability of this happening is low, but once it does the combination of the two is very stable. Then more units can get added, making a sort of "fibril". Prions form abnormal aggregates of proteins called amyloids, which accumulate in infected tissue and are associated with tissue damage and cell death. Amyloids are also responsible for several other neurodegenerative diseases such as Alzheimers disease and Parkinsons disease.A prion disease is a type of proteopathy, or disease of structurally abnormal proteins. In humans, prions are believed to be the cause of Creutzfeldt–Jakob disease (CJD), its variant (vCJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), fatal familial insomnia (FFI), and kuru. There is also evidence suggesting prions may play a part in the process of Alzheimers disease, Parkinsons disease, and amyotrophic lateral sclerosis (ALS); these have been termed prion-like diseases. Several yeast proteins have also been identified as having prionogenic properties, as well as a protein involved in modification of synapses during the formation of memories (see Eric Kandel § Molecular changes during learning). Prion replication is subject to epimutation and natural selection just as for other forms of replication, and their structure varies slightly between species.Prion aggregates are stable, and this structural stability means that prions are resistant to denaturation by chemical and physical agents: they cannot be destroyed by ordinary disinfection or cooking. This makes disposal and containment of these particles difficult. Etymology and pronunciation The word prion, coined in 1982 by Stanley B. Prusiner, is derived from protein and infection, hence prion, and is short for "proteinaceous infectious particle", in reference to its ability to self-propagate and transmit its conformation to other proteins. Its main pronunciation is (listen), although , as the homographic name of the bird (prions or whalebirds) is pronounced, is also heard. In his 1982 paper introducing the term, Prusiner specified that it is "pronounced pree-on". Prion protein Structure The protein that prions are made of (PrP) is found throughout the body, even in healthy people and animals. However, PrP found in infectious material has a different structure and is resistant to proteases, the enzymes in the body that can normally break down proteins. The normal form of the protein is called PrPC, while the infectious form is called PrPSc – the C refers to cellular PrP, while the Sc refers to scrapie, the prototypic prion disease, occurring in sheep. While PrPC is structurally well-defined, PrPSc is certainly polydisperse and defined at a relatively poor level. PrP can be induced to fold into other more-or-less well-defined isoforms in vitro, and their relationship to the form(s) that are pathogenic in vivo is not yet clear. PrPC PrPC is a normal protein found on the membranes of cells, "including several blood components of which platelets constitute the largest reservoir in humans." It has 209 amino acids (in humans), one disulfide bond, a molecular mass of 35–36 kDa and a mainly alpha-helical structure. Several topological forms exist; one cell surface form anchored via glycolipid and two transmembrane forms. The normal protein is not sedimentable; meaning that it cannot be separated by centrifuging techniques. Its function is a complex issue that continues to be investigated. PrPC binds copper (II) ions with high affinity. The significance of this finding is not clear, but it is presumed to relate to PrP structure or function. PrPC is readily digested by proteinase K and can be liberated from the cell surface in vitro by the enzyme phosphoinositide phospholipase C (PI-PLC), which cleaves the glycophosphatidylinositol (GPI) glycolipid anchor. PrP has been reported to play important roles in cell-cell adhesion and intracellular signaling in vivo, and may therefore be involved in cell-cell communication in the brain. PrPres Protease-resistant PrPSc-like protein (PrPres) is the name given to any isoform of PrPc which is structurally altered and converted into a misfolded proteinase K-resistant form in vitro. To model conversion of PrPC to PrPSc in vitro, Saborio et al. rapidly converted PrPC into a PrPres by a procedure involving cyclic amplification of protein misfolding. The term "PrPres" has been used to distinguish between PrPSc, which is isolated from infectious tissue and associated with the transmissible spongiform encephalopathy agent. For example, unlike PrPSc, PrPres may not necessarily be infectious. PrPSc The infectious isoform of PrP, known as PrPSc, or simply the prion, is able to convert normal PrPC proteins into the infectious isoform by changing their conformation, or shape; this, in turn, alters the way the proteins interconnect. PrPSc always causes prion disease. Although the exact 3D structure of PrPSc is not known, it has a higher proportion of β-sheet structure in place of the normal α-helix structure. Aggregations of these abnormal isoforms form highly structured amyloid fibers, which accumulate to form plaques. The end of each fiber acts as a template onto which free protein molecules may attach, allowing the fiber to grow. Under most circumstances, only PrP molecules with an identical amino acid sequence to the infectious PrPSc are incorporated into the growing fiber. However, rare cross-species transmission is also possible. Normal function of PrP The physiological function of the prion protein remains poorly understood. While data from in vitro experiments suggest many dissimilar roles, studies on PrP knockout mice have provided only limited information because these animals exhibit only minor abnormalities. In research done in mice, it was found that the cleavage of PrP in peripheral nerves causes the activation of myelin repair in Schwann cells and that the lack of PrP proteins caused demyelination in those cells. PrP and regulated cell death MAVS, RIP1, and RIP3 are prion-like proteins found in other parts of the body. They also polymerise into filamentous amyloid fibers which initiate regulated cell death in the case of a viral infection to prevent the spread of virions to other, surrounding cells. PrP and long-term memory A review of evidence in 2005 suggested that PrP may have a normal function in maintenance of long-term memory. As well, a 2004 study found that mice lacking genes for normal cellular PrP protein show altered hippocampal long-term potentiation. A recent study that might explain why this is found that neuronal protein CPEB has a similar genetic sequence to yeast prion proteins. The prion-like formation of CPEB is essential for maintaining long-term synaptic changes associated with long-term memory formation. PrP and stem cell renewal A 2006 article from the Whitehead Institute for Biomedical Research indicates that PrP expression on stem cells is necessary for an organisms self-renewal of bone marrow. The study showed that all long-term hematopoietic stem cells express PrP on their cell membrane and that hematopoietic tissues with PrP-null stem cells exhibit increased sensitivity to cell depletion. PrP and innate immunity There is some evidence that PrP may play a role in innate immunity, as the expression of PRNP, the PrP gene, is upregulated in many viral infections and PrP has antiviral properties against many viruses, including HIV. Prion replication The first hypothesis that tried to explain how prions replicate in a protein-only manner was the heterodimer model. This model assumed that a single PrPSc molecule binds to a single PrPC molecule and catalyzes its conversion into PrPSc. The two PrPSc molecules then come apart and can go on to convert more PrPC. However, a model of prion replication must explain both how prions propagate, and why their spontaneous appearance is so rare. Manfred Eigen showed that the heterodimer model requires PrPSc to be an extraordinarily effective catalyst, increasing the rate of the conversion reaction by a factor of around 1015. This problem does not arise if PrPSc exists only in aggregated forms such as amyloid, where cooperativity may act as a barrier to spontaneous conversion. What is more, despite considerable effort, infectious monomeric PrPSc has never been isolated. An alternative model assumes that PrPSc exists only as fibrils, and that fibril ends bind PrPC and convert it into PrPSc. If this were all, then the quantity of prions would increase linearly, forming ever longer fibrils. But exponential growth of both PrPSc and of the quantity of infectious particles is observed during prion disease. This can be explained by taking into account fibril breakage. A mathematical solution for the exponential growth rate resulting from the combination of fibril growth and fibril breakage has been found. The exponential growth rate depends largely on the square root of the PrPC concentration. The incubation period is determined by the exponential growth rate, and in vivo data on prion diseases in transgenic mice match this prediction. The same square root dependence is also seen in vitro in experiments with a variety of different amyloid proteins.The mechanism of prion replication has implications for designing drugs. Since the incubation period of prion diseases is so long, an effective drug does not need to eliminate all prions, but simply needs to slow down the rate of exponential growth. Models predict that the most effective way to achieve this, using a drug with the lowest possible dose, is to find a drug that binds to fibril ends and blocks them from growing any further.Researchers at Dartmouth College discovered that endogenous host cofactor molecules such as the phospholipid molecule (e.g. phosphatidylethanolamine) and polyanions (e.g. single stranded RNA molecules) are necessary to form PrPSc molecules with high levels of specific infectivity in vitro, whereas protein-only PrPSc molecules appear to lack significant levels of biological infectivity. Transmissible spongiform encephalopathies Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloids, which disrupt the normal tissue structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the vacuole formation in the neurons. Other histological changes include astrogliosis and the absence of an inflammatory reaction. While the incubation period for prion diseases is relatively long (5 to 20 years), once symptoms appear the disease progresses rapidly, leading to brain damage and death. Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes. Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals. Due to small differences in PrP between different species it is unusual for a prion disease to transmit from one species to another. The human prion disease variant Creutzfeldt–Jakob disease, however, is thought to be caused by a prion that typically infects cattle, causing bovine spongiform encephalopathy and is transmitted through infected meat.All known prion diseases are untreatable and fatal. However, a vaccine developed in mice may provide insight into providing a vaccine to resist prion infections in humans. Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production – thus theoretically making them immune to BSE, building on research indicating that mice lacking normally occurring prion protein are resistant to infection by scrapie prion protein. In 2013, a study revealed that 1 in 2,000 people in the United Kingdom might harbour the infectious prion protein that causes vCJD.Until 2015 all known mammalian prion diseases were considered to be caused by the prion protein, PrP; in 2015 multiple system atrophy was found to be transmissible and was hypothesized to be caused by a new prion, the misfolded form of a protein called alpha-synuclein. The endogenous, properly folded form of the prion protein is denoted PrPC (for Common or Cellular), whereas the disease-linked, misfolded form is denoted PrPSc (for Scrapie), after one of the diseases first linked to prions and neurodegeneration. The precise structure of the prion is not known, though they can be formed spontaneously by combining PrPC, homopolymeric polyadenylic acid, and lipids in a protein misfolding cyclic amplification (PMCA) reaction even in the absence of pre-existing infectious prions. This result is further evidence that prion replication does not require genetic information. Transmission It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic. It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSc by bringing a molecule of each of the two together into a complex.The primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then linger in the soil by binding to clay and other minerals.A University of California research team has provided evidence for the theory that infection can occur from prions in manure. And, since manure is present in many areas surrounding water reservoirs, as well as used on many crop fields, it raises the possibility of widespread transmission. It was reported in January 2011 that researchers had discovered prions spreading through airborne transmission on aerosol particles, in an animal testing experiment focusing on scrapie infection in laboratory mice. Preliminary evidence supporting the notion that prions can be transmitted through use of urine-derived human menopausal gonadotropin, administered for the treatment of infertility, was published in 2011. Prions in plants In 2015, researchers at The University of Texas Health Science Center at Houston found that plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with chronic wasting disease (CWD) was buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment. Sterilization Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions, therefore, requires the denaturation of the protein to a state in which the molecule is no longer able to induce the abnormal folding of normal proteins. In general, prions are quite resistant to proteases, heat, ionizing radiation, and formaldehyde treatments, although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein hydrolysis or reduction or destruction of protein tertiary structure. Examples include sodium hypochlorite, sodium hydroxide, and strongly acidic detergents such as LpH.The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions: Immerse in 1N sodium hydroxide and place in a gravity-displacement autoclave at 121 °C for 30 minutes; clean; rinse in water; and then perform routine sterilization processes. Immerse in 1N sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121 °C for 1 hour; clean; and then perform routine sterilization processes. Immerse in 1N sodium hydroxide or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121 °C) or in a porous-load (134 °C) autoclave for 1 hour; clean; and then perform routine sterilization processes.134 °C (273 °F) for 18 minutes in a pressurized steam autoclave has been found to be somewhat effective in deactivating the agent of disease. Ozone sterilization is currently being studied as a potential method for prion denaturation and deactivation. Other approaches being developed include thiourea-urea treatment, guanidinium chloride treatment, and special heat-resistant subtilisin combined with heat and detergent. A method sufficient for sterilizing prions on one material may fail on another.Renaturation of a completely denatured prion to infectious status has not yet been achieved; however, partially denatured prions can be renatured to an infective status under certain artificial conditions. Degradation resistance in nature Overwhelming evidence shows that prions resist degradation and persist in the environment for years, and proteases do not degrade them. Experimental evidence shows that unbound prions degrade over time, while soil-bound prions remain at stable or increasing levels, suggesting that prions likely accumulate in the environment. One 2015 study by US scientists found that repeated drying and wetting may render soil bound prions less infectious, although this was dependent on the soil type they were bound to. Fungi Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions do not appear to cause disease in their hosts. In yeast, protein refolding to the prion configuration is assisted by chaperone proteins such as Hsp104. All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloid aggregates are fibrils, growing at their ends, and replicate when breakage causes two growing ends to become four growing ends. The incubation period of prion diseases is determined by the exponential growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates.Fungal proteins exhibiting templated conformational change were discovered in the yeast Saccharomyces cerevisiae by Reed Wickner in the early 1990s. For their mechanistic similarity to mammalian prions, they were termed yeast prions. Subsequent to this, a prion has also been found in the fungus Podospora anserina. These prions behave similarly to PrP, but, in general, are nontoxic to their hosts. Susan Lindquists group at the Whitehead Institute has argued some of the fungal prions are not associated with any disease state, but may have a useful role; however, researchers at the NIH have also provided arguments suggesting that fungal prions could be considered a diseased state. There is evidence that fungal proteins have evolved specific functions that are beneficial to the microorganism that enhance their ability to adapt to their diverse environments.Research into fungal prions has given strong support to the protein-only concept, since purified protein extracted from cells with a prion state has been demonstrated to convert the normal form of the protein into a misfolded form in vitro, and in the process, preserve the information corresponding to different strains of the prion state. It has also shed some light on prion domains, which are regions in a protein that promote the conversion into a prion. Fungal prions have helped to suggest mechanisms of conversion that may apply to all prions, though fungal prions appear distinct from infectious mammalian prions in the lack of cofactor required for propagation. The characteristic prion domains may vary between species – e.g., characteristic fungal prion domains are not found in mammalian prions. Treatments There are no effective treatments for prion diseases. Clinical trials in humans have not met with success and have been hampered by the rarity of prion diseases. Although some potential treatments have shown promise in the laboratory, none have been effective once the disease has commenced. In other diseases Prion-like domains have been found in a variety of other mammalian proteins. Some of these proteins have been implicated in the ontogeny of age-related neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimers disease, Parkinsons disease, and Huntingtons disease. They are also implicated in some forms of systemic amyloidosis including AA amyloidosis that develops in humans and animals with inflammatory and infectious diseases such as tuberculosis, Crohns disease, rheumatoid arthritis, and HIV/AIDS. AA amyloidosis, like prion disease, may be transmissible. This has given rise to the prion paradigm, where otherwise harmless proteins can be converted to a pathogenic form by a small number of misfolded, nucleating proteins.The definition of a prion-like domain arises from the study of fungal prions. In yeast, prionogenic proteins have a portable prion domain that is both necessary and sufficient for self-templating and protein aggregation. This has been shown by attaching the prion domain to a reporter protein, which then aggregates like a known prion. Similarly, removing the prion domain from a fungal prion protein inhibits prionogenesis. This modular view of prion behaviour has led to the hypothesis that similar prion domains are present in animal proteins, in addition to PrP. These fungal prion domains have several characteristic sequence features. They are typically enriched in asparagine, glutamine, tyrosine and glycine residues, with an asparagine bias being particularly conducive to the aggregative property of prions. Historically, prionogenesis has been seen as independent of sequence and only dependent on relative residue content. However, this has been shown to be false, with the spacing of prolines and charged residues having been shown to be critical in amyloid formation.Bioinformatic screens have predicted that over 250 human proteins contain prion-like domains (PrLD). These domains are hypothesized to have the same transmissible, amyloidogenic properties of PrP and known fungal proteins. As in yeast, proteins involved in gene expression and RNA binding seem to be particularly enriched in PrLDs, compared to other classes of protein. In particular, 29 of the known 210 proteins with an RNA recognition motif also have a putative prion domain. Meanwhile, several of these RNA-binding proteins have been independently identified as pathogenic in cases of ALS, FTLD-U, Alzheimers disease, and Huntingtons disease. Role in neurodegenerative disease The pathogenicity of prions and proteins with prion-like domains is hypothesized to arise from their self-templating ability and the resulting exponential growth of amyloid fibrils. The presence of amyloid fibrils in patients with degenerative diseases has been well documented. These amyloid fibrils are seen as the result of pathogenic proteins that self-propagate and form highly stable, non-functional aggregates. While this does not necessarily imply a causal relationship between amyloid and degenerative diseases, the toxicity of certain amyloid forms and the overproduction of amyloid in familial cases of degenerative disorders supports the idea that amyloid formation is generally toxic.Specifically, aggregation of TDP-43, an RNA-binding protein, has been found in ALS/MND patients, and mutations in the genes coding for these proteins have been identified in familial cases of ALS/MND. These mutations promote the misfolding of the proteins into a prion-like conformation. The misfolded form of TDP-43 forms cytoplasmic inclusions in affected neurons, and is found depleted in the nucleus. In addition to ALS/MND and FTLD-U, TDP-43 pathology is a feature of many cases of Alzheimers disease, Parkinsons disease and Huntingtons disease. The misfolding of TDP-43 is largely directed by its prion-like domain. This domain is inherently prone to misfolding, while pathological mutations in TDP-43 have been found to increase this propensity to misfold, explaining the presence of these mutations in familial cases of ALS/MND. As in yeast, the prion-like domain of TDP-43 has been shown to be both necessary and sufficient for protein misfolding and aggregation.Similarly, pathogenic mutations have been identified in the prion-like domains of heterogeneous nuclear riboproteins hnRNPA2B1 and hnRNPA1 in familial cases of muscle, brain, bone and motor neuron degeneration. The wild-type form of all of these proteins show a tendency to self-assemble into amyloid fibrils, while the pathogenic mutations exacerbate this behaviour and lead to excess accumulation. Weaponization Prions could theoretically be employed as a weaponized agent. With potential fatality rates of 100%, prions could be an effective bio-weapon. An unfavorable aspect is prions very long incubation periods. Persistent heavy exposure of prions to the intestine might shorten the overall onset. Another aspect of using prions in warfare is the difficulty of detection and decontamination. History In the 18th and 19th centuries, exportation of sheep from Spain was observed to coincide with a disease called scrapie. This disease caused the affected animals to "lie down, bite at their feet and legs, rub their backs against posts, fail to thrive, stop feeding and finally become lame". The disease was also observed to have the long incubation period that is a key characteristic of transmissible spongiform encephalopathies (TSEs). Although the cause of scrapie was not known back then, it is probably the first transmissible spongiform encephalopathy to be recorded. In the 1950s, Carleton Gajdusek began research which eventually showed that kuru could be transmitted to chimpanzees by what was possibly a new infectious agent, work for which he eventually won the 1976 Nobel prize. During the 1960s, two London-based researchers, radiation biologist Tikvah Alper and biophysicist John Stanley Griffith, developed the hypothesis that the transmissible spongiform encephalopathies are caused by an infectious agent consisting solely of proteins. Earlier investigations by E.J. Field into scrapie and kuru had found evidence for the transfer of pathologically inert polysaccharides that only become infectious post-transfer, in the new host. Alper and Griffith wanted to account for the discovery that the mysterious infectious agent causing the diseases scrapie and Creutzfeldt–Jakob disease resisted ionizing radiation. Griffith proposed three ways in which a protein could be a pathogen.In the first hypothesis, he suggested that if the protein is the product of a normally suppressed gene, and introducing the protein could induce the genes expression, that is, wake the dormant gene up, then the result would be a process indistinguishable from replication, as the genes expression would produce the protein, which would then go wake the gene up in other cells. His second hypothesis forms the basis of the modern prion theory, and proposed that an abnormal form of a cellular protein can convert normal proteins of the same type into its abnormal form, thus leading to replication. His third hypothesis proposed that the agent could be an antibody if the antibody was its own target antigen, as such an antibody would result in more and more antibody being produced against itself. However, Griffith acknowledged that this third hypothesis was unlikely to be true due to the lack of a detectable immune response.Francis Crick recognized the potential significance of the Griffith protein-only hypothesis for scrapie propagation in the second edition of his "Central dogma of molecular biology" (1970): While asserting that the flow of sequence information from protein to protein, or from protein to RNA and DNA was "precluded", he noted that Griffiths hypothesis was a potential contradiction (although it was not so promoted by Griffith). The revised hypothesis was later formulated, in part, to accommodate reverse transcription (which both Howard Temin and David Baltimore discovered in 1970).In 1982, Stanley B. Prusiner of the University of California, San Francisco, announced that his team had purified the hypothetical infectious protein, which did not appear to be present in healthy hosts, though they did not manage to isolate the protein until two years after Prusiners announcement. The protein was named a prion, for "proteinacious infectious particle", derived from the words protein and infection. When the prion was discovered, Griffiths first hypothesis, that the protein was the product of a normally silent gene was favored by many. It was subsequently discovered, however, that the same protein exists in normal hosts but in different form.Following the discovery of the same protein in different form in uninfected individuals, the specific protein that the prion was composed of was named the prion protein (PrP), and Griffiths second hypothesis that an abnormal form of a host protein can convert other proteins of the same type into its abnormal form, became the dominant theory. Prusiner won the Nobel Prize in Physiology or Medicine in 1997 for his research into prions. See also Diseases of abnormal polymerization Prion pseudoknot Subviral agents Tau protein References External links CDC – US Center for Disease Control and Prevention – information on prion diseases World Health Organisation – WHO information on prion diseases The UK BSE Inquiry – Report of the UK public inquiry into BSE and variant CJD UK Spongiform Encephalopathy Advisory Committee (SEAC)

Frontotemporal dementia

Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as behavioral or language disorders with gradual onsets. The three main subtypes or variant syndromes are a behavioral variant (bvFTD) previously known as Picks disease, and two variants of primary progressive aphasia – semantic variant (svPPA), and nonfluent variant (nfvPPA). Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID), and basophilic inclusion body disease. Other related disorders include corticobasal syndrome and FTD with amyotrophic lateral sclerosis (ALS) FTD-ALS also called FTD-MND.Frontotemporal dementias are mostly early-onset syndromes that are linked to frontotemporal lobar degeneration (FTLD), which is characterized by progressive neuronal loss predominantly involving the frontal or temporal lobes, and a typical loss of more than 70% of spindle neurons, while other neuron types remain intact.FTD was first described by Arnold Pick in 1892 and was originally called Picks disease, a term now reserved only for behavioral variant FTD which shows the presence of Pick bodies and Pick cells. Second only to Alzheimers disease (AD) in prevalence, FTD accounts for less than, or actually, 20% (number is perhaps rounded) of degenerative dementia cases found at autopsy.Signs and symptoms typically manifest in late adulthood, more commonly between the ages of 45 and 65, approximately equally affecting men and women.Common signs and symptoms include significant changes in social and personal behavior, apathy, blunting of emotions, and deficits in both expressive and receptive language. Currently, there is no cure for FTD, but there are treatments that help alleviate symptoms. Signs and symptoms Frontotemporal dementia (FTD) is an early-onset disorder that mostly occurs before the age of 65, but can begin earlier, and in 20–25% of cases onset is later. It is the most common early presenting dementia.The International Classification of Diseases recognizes the disease as causative to disorder affecting mental and behavioural aspects of the human organism. Dissociation from family, extreme oniomania, vulgar speech characteristics, screaming, inability to control emotions, behavior, personality, and temperament are characteristic social display patterns. A gradual onset and progression of changes in behavior or language deficits are reported to have begun several years prior to presentation to a neurologist. Subtypes and related disorders The main subtypes of frontotemporal dementia are behavioral variant FTD, semantic dementia, progressive nonfluent aphasia, and FTD associated with amyotrophic lateral sclerosis (FTD–ALS). Two distinct rare subtypes are neuronal intermediate filament inclusion disease, and basophilic inclusion body disease. Related disorders are corticobasal syndrome, and progressive supranuclear palsy. Behavioral variant frontotemporal dementia Behavioral variant frontotemporal dementia (BvFTD) was previously known as Picks disease, and is the most common of the FTD types. BvFTD is diagnosed four times as often as the PPA variants. Behavior can change in BvFTD in either of two ways—it can change to being impulsive and disinhibited, acting in socially unacceptable ways; or it can change to being listless and apathetic. About 12–13% of people with bvFTD develop motor neuron disease.The Pick bodies in behavioral variant FTD are spherical inclusion bodies found in the cytoplasm of affected cells. They consist of tau fibrils as a major component together with a number of other protein products including ubiquitin and tubulin. Semantic dementia Semantic dementia (SD) is characterized by the loss of semantic understanding, resulting in impaired word comprehension. However, speech remains fluent and grammatical. Progressive nonfluent aphasia Progressive nonfluent aphasia (PNFA) is characterized by progressive difficulties in speech production. Neuronal intermediate filament inclusion disease Neuronal intermediate filament inclusion disease (NIFID) is a rare distinct variant. The inclusion bodies that are present in NIFID are cytoplasmic and made up of type IV intermediate filaments. NIFID has an early age of onset between 23 and 56. Symptoms can include behavioural, and personality changes, memory and cognitive impairments, language difficulties, motor weakness, and extrapyramidal symptoms. NIFID is one of the FTLD-FUS proteopathies. Imaging commonly shows atrophy in the frontotemporal region, and in part of the striatum in the basal ganglia. Post-mortem studies show a marked reduction in the caudate nucleus of the striatum; frontal temporal gyri are narrowed with widened intervening sulci, and the lateral ventricles are enlarged. Basophilic inclusion body disease Another rare FTD variant, also a FTLD-FUS proteopathy, is basophilic inclusion body disease (BIBD). Other characteristics In later stages of FTD, the clinical phenotypes may overlap. People with FTD tend to struggle with binge eating and compulsive behaviors. Binge eating habits are often associated with changes in food preferences (cravings for more sweets, carbohydrates), eating inedible objects and snatching food from others. Recent findings from structural MRI research have indicated that eating changes in FTD are associated with atrophy (wasting) in the right ventral insula, striatum, and orbitofrontal cortex.People with FTD show marked deficiencies in executive functioning and working memory. Most become unable to perform skills that require complex planning or sequencing. In addition to the characteristic cognitive dysfunction, a number of primitive reflexes known as frontal release signs are often able to be elicited. Usually the first of these frontal release signs to appear is the palmomental reflex which appears relatively early in the disease course whereas the palmar grasp reflex and rooting reflex appear late in the disease course.In rare cases, FTD can occur in people with amyotrophic lateral sclerosis (ALS) a motor neuron disease. The prognosis for people with ALS is worse when combined with FTD, shortening survival by about a year. Genetics A higher proportion of frontotemporal dementias seem to have a familial component than other neurodegenerative diseases such as Alzheimers disease. More and more mutations and genetic variants are being identified all the time, needing constant updating of genetic influences. Tau-positive frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is caused by mutations in the MAPT gene on chromosome 17 that encodes the tau protein. It has been determined that there is a direct relationship between the type of tau mutation and the neuropathology of gene mutations. The mutations at the splice junction of exon 10 of tau lead to the selective deposition of the repetitive tau in neurons and glia. The pathological phenotype associated with mutations elsewhere in tau is less predictable with both typical neurofibrillary tangles (consisting of both 3 repeat and 4 repeat tau) and Pick bodies (consisting of 3 repeat tau) having been described. The presence of tau deposits within glia is also variable in families with mutations outside of exon 10. This disease is now informally designated FTDP-17T. FTD shows a linkage to the region of the tau locus on chromosome 17, but it is believed that there are two loci leading to FTD within megabases of each other on chromosome 17. The only other known autosomal dominant genetic cause of FTLD-tau is a hypomorphic mutation in VCP which is associated with a unique neuropathology called vacuolar tauopathy. FTD caused by FTLD-TDP43 has numerous genetic causes. Some cases are due to mutations in the GRN gene, also located on chromosome 17. Others are caused by hypomorphic VCP mutations, although these patients present with a complex picture of multisystem proteinopathy that can include amyotrophic lateral sclerosis, inclusion body myopathy, Pagets disease of bone, and FTD. The most recent addition to the list is a hexanucleotide repeat expansion in intron 1 of C9ORF72. Only one or two cases have been reported describing TARDBP (the TDP-43 gene) mutations in a clinically pure FTD (FTD without MND). Several other genes have been linked to this condition. These include CYLD, OPTN, SQSTM1 and TBK1. These genes have been implicated in the autophagy pathway. No genetic causes of FUS pathology in FTD have yet been reported. Pathology There are three main histological subtypes found at post-mortem: FTLD-tau, FTLD-TDP, and FTLD-FUS. In rare cases, patients with clinical FTD were found to have changes consistent with Alzheimers disease on autopsy. The most severe brain atrophy appears to be associated with behavioral variant FTD, and corticobasal degeneration.With regard to the genetic defects that have been found, repeat expansion in the C9orf72 gene is considered a major contribution to frontotemporal lobar degeneration, although defects in the GRN and MAPT genes are also associated with it. Diagnosis FTD is traditionally difficult to diagnose owing to the diverse nature of the associated symptoms. Signs and symptoms are classified into three groups based on the affected functions of the frontal and temporal lobes: These are behavioural variant frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. An overlap between symptoms can occur as the disease progresses and spreads through the brain regions. Structural MRI scans often reveal frontal lobe and/or anterior temporal lobe atrophy but in early cases the scan may seem normal. Atrophy can be either bilateral or asymmetric. Registration of images at different points of time (e.g., one year apart) can show evidence of atrophy that otherwise (at individual time points) may be reported as normal. Many research groups have begun using techniques such as magnetic resonance spectroscopy, functional imaging and cortical thickness measurements in an attempt to offer an earlier diagnosis to the FTD patient. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) scans classically show frontal and/or anterior temporal hypometabolism, which helps differentiate the disease from Alzheimers disease. The PET scan in Alzheimers disease classically shows biparietal hypometabolism. Meta-analyses based on imaging methods have shown that frontotemporal dementia mainly affects a frontomedial network discussed in the context of social cognition or theory of mind. This is entirely in keeping with the notion that on the basis of cognitive neuropsychological evidence, the ventromedial prefrontal cortex is a major locus of dysfunction early on in the course of the behavioural variant of frontotemporal degeneration. The language subtypes of frontotemporal lobar degeneration (semantic dementia and progressive nonfluent aphasia) can be regionally dissociated by imaging approaches in vivo.The confusion between Alzheimers and FTD is justifiable due to the similarities between their initial symptoms. Patients do not have difficulty with movement and other motor tasks. As FTD symptoms appear, it is difficult to differentiate between a diagnosis of Alzheimers disease and FTD. There are distinct differences in the behavioral and emotional symptoms of the two dementias, notably, the blunting of emotions seen in FTD patients. In the early stages of FTD, anxiety and depression are common, which may result in an ambiguous diagnosis. However, over time, these ambiguities fade away as this dementia progresses and defining symptoms of apathy, unique to FTD, start to appear.Recent studies over several years have developed new criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD).The confirmatory diagnosis is made by brain biopsy, but other tests can be used to help, such as MRI, EEG, CT, and physical examination and history. Six distinct clinical features have been identified as symptoms of bvFTD. Disinhibition Apathy/Inertia Loss of Sympathy/Empathy Perseverative/compulsive behaviors Hyperorality Dysexecutive neuropsychological profileOf the six features, three must be present in a patient to diagnose one with possible bvFTD. Similar to standard FTD, the primary diagnosis stems from clinical trials that identify the associated symptoms, instead of imaging studies. The above criteria are used to distinguish bvFTD from disorders such as Alzheimers and other causes of dementia. In addition, the new criteria allow for a diagnostic hierarchy distinguished possible, probable, and definite bvFTD based on the number of symptoms present.A 2021 study, led by researchers at the University of Pennsylvania, determined that using cerebrospinal fluid (CSF) biomarkers of pathologic amyloid plaques, tangles, and neurodegeneration, collectively called ATN, can be useful in diagnosing FTD. Neuropsychological tests The progression of the degeneration caused by bvFTD may follow a predictable course. The degeneration begins in the orbitofrontal cortex and medial aspects such as ventromedial cortex. In later stages, it gradually expands its area to the dorsolateral cortex and the temporal lobe. Thus, the detection of dysfunction of the orbitofrontal cortex and ventromedial cortex is important in the detection of early stage bvFTD. As stated above, a behavioural change may occur before the appearance of any atrophy in the brain in the course of the disease. Because of that, image scanning such as MRI can be insensitive to the early degeneration and it is difficult to detect early-stage bvFTD.In neuropsychology, there is an increasing interest in using neuropsychological tests such as the Iowa gambling task or Faux Pas Recognition test as an alternative to imaging for the diagnosis of bvFTD. Both the Iowa gambling task and the Faux Pas test are known to be sensitive to dysfunction of the orbitofrontal cortex.Faux Pas Recognition test is intended to measure ones ability to detect faux pas types of social blunders (accidentally make a statement or an action that offends others). It is suggested that people with orbitofrontal cortex dysfunction show a tendency to make social blunders due to a deficit in self-monitoring. Self-monitoring is the ability of individuals to evaluate their behaviour to make sure that their behaviour is appropriate in particular situations. The impairment in self-monitoring leads to a lack of social emotion signals. The social emotions such as embarrassment are important in the way that they signal the individual to adapt social behaviour in an appropriate manner to maintain relationships with others. Though patients with damage to the OFC retain intact knowledge of social norms, they fail to apply it to actual behaviour because they fail to generate social emotions that promote adaptive social behaviour.The other test, the Iowa gambling task, is a psychological test intended to simulate real-life decision making. The underlying concept of this test is the somatic marker hypothesis. This hypothesis argues that when people have to make complex uncertain decisions, they employ both cognitive and emotional processes to assess the values of the choices available to them. Each time a person makes a decision, both physiological signals and evoked emotion (somatic marker) are associated with their outcomes and it accumulates as experience. People tend to choose the choice which might produce the outcome reinforced with positive stimuli, thus it biases decision-making towards certain behaviours while avoiding others. It is thought that somatic marker is processed in orbitofrontal cortex.The symptoms observed in bvFTD are caused by dysfunction of the orbitofrontal cortex, thus these two neuropsychological tests might be useful in detecting the early stage bvFTD. However, as self-monitoring and somatic marker processes are so complex, it likely involves other brain regions. Therefore, neuropsychological tests are sensitive to the dysfunction of orbitofrontal cortex, yet not specific to it. The weakness of these tests is that they do not necessarily show dysfunction of the orbitofrontal cortex.In order to solve this problem, some researchers combined neuropsychological tests which detect the dysfunction of orbitofrontal cortex into one so that it increases its specificity to the degeneration of the frontal lobe in order to detect the early-stage bvFTD. They invented the Executive and Social Cognition Battery which comprises five neuropsychological tests. Iowa gambling task Faux Pas test Hotel task Mind in the Eyes Multiple Errands TaskThe result has shown that this combined test is more sensitive in detecting the deficits in early bvFTD. Management Currently, there is no cure for FTD. Treatments are available to manage the behavioral symptoms. Disinhibition and compulsive behaviors can be controlled by selective serotonin reuptake inhibitors (SSRIs). Although Alzheimers and FTD share certain symptoms, they cannot be treated with the same pharmacological agents because the cholinergic systems are not affected in FTD.Because FTD often occurs in younger people (i.e. in their 40s or 50s), it can severely affect families. Patients often still have children living in the home. Prognosis Symptoms of frontotemporal dementia progress at a rapid, steady rate. Patients with the disease can survive for 2–20 years. Eventually patients will need 24-hour care for daily function.CSF leaks are a known cause of reversible frontotemporal dementia. History Frontotemporal dementia was first described by Pick in 1892. In 1989, Snowden suggested the term “semantic dementia” to describe the patient with predominant left temporal atrophy and aphasia that Pick described. The first research criteria for FTD “Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups,” was developed in 1994. The clinical diagnostic criteria were revised in the late 1990s, when the FTD spectrum was divided into a behavioral variant, a nonfluent aphasia variant and a semantic dementia variant. The most recent revision of the clinical research criteria was by International Behavioural Variant FTD Criteria Consortium (FTDC) in 2011. Notable cases Notable cases of bvFTD when mostly were referred to as Picks disease. John Berry (1963-2016), American hardcore punk musician and founding member of the Beastie Boys. Don Cardwell (1935–2008), Major League Baseball pitcher Charmian Carr (1942–2016), who played Liesl, from the Sound of Music, born Charmian Anne Farnon. Jerry Corbetta (1947–2016), frontman, organist and keyboardist of American psychedelic rock band Sugarloaf Ted Darling (1935–1996), Buffalo Sabres television announcer Robert W. Floyd (1936–2001), computer scientist Lee Holloway (born 1981), co-founder of Cloudflare Colleen Howe (1933–2009), sports agent and hockey team manager, known as "Mrs. Hockey" Kazi Nazrul Islam (1899–1976), notable Bengali poet and National Poet of Bangladesh Ralph Klein (1942–2013), former premier of Alberta, Canada Terry Jones (1942-2020), Welsh comedian (Monty Python) and director. Kevin Moore (1958–2013), English footballer Pat Moran (1947–2011), British record producer, singer and Mellotron player with progressive rock band Spring Ernie Moss (1949–2021), English footballer Nic Potter (1951–2013), British bassist for Van der Graaf Generator Christina Ramberg (1946–1995), American painter associated with the Chicago Imagists David Rumelhart (1942–2011), American cognitive psychologist Colin Savage, father of footballer Robbie Savage Sir Nicholas Wall (1945–2017), English judge Mark Wirtz (1943–2020), pop musician, composer and producer See also References Further reading External links OMIM on Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis and Chromosome 9 Open Reading Frame 72; C9ORF72

Wiskott–Aldrich syndrome

Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrichs original description in 1954. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present with similar but less severe symptoms and are caused by mutations of the same gene. Signs and symptoms WAS occurs most often in males due to its X-linked recessive pattern of inheritance, affecting between 1 and 10 males per million. The first signs are usually petechiae and bruising, resulting from a low platelet count (i.e. thrombocytopenia). Spontaneous nose bleeds and bloody diarrhea are also common and eczema typically develops within the first month of life. Recurrent bacterial infections typically develop by three months of age. The majority of children with WAS develop at least one autoimmune disorder, and cancers (mainly lymphoma and leukemia) develop in up to a third of patients. Immunoglobulin M (IgM) levels are reduced, IgA and IgE are elevated, and IgG levels can be normal, reduced, or elevated. In addition to thrombocytopenia, WAS patients have abnormally small platelets (i.e. microthrombocytes) and ~30% also have elevated eosinophil counts (i.e. eosinophilia). Pathophysiology The microthrombocytes seen in WAS patients have only been observed in one other condition, ARPC1B deficiency. In both conditions the defective platelets are thought to be removed from circulation by the spleen and/or liver, leading to low platelet counts. WAS patients have increased susceptibility to infections, particularly of the ears and sinuses, and this immune deficiency has been linked to decreased antibody production and the inability of immune T cells to effectively combat infection. Genetics WAS is associated with mutations in a gene on the short arm of the X chromosome (Xp11.23) that was originally termed the Wiskott-Aldrich syndrome protein gene and is officially known as WAS (Gene ID: 7454). X-linked thrombocytopenia (XLT) is also linked to pathogenic variants in the WAS gene, although some variants tend to be more strongly associated with XLT versus others that are more associated with WAS. The rare disorder X-linked neutropenia has also been linked to a specific subset of WAS mutations.The protein product of WAS is known as WASp. It contains 502 amino acids and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by serving as a nucleation-promoting factor (NPF) for the Arp2/3 complex, which generates branched actin filaments. Several proteins can serve as NPFs, and it has been observed that in WAS platelets the Arp2/3 complex functions normally, indicating that WASp is not required for its activation in platelets. In T-cells, WASp is important because it is known to be activated via T-cell receptor signaling pathways to induce cortical actin cytoskeleton rearrangements that are responsible for forming the immunological synapse.The severity of the symptoms produced by pathogenic variants in the WAS gene generally correlates with their effects on WASp. Missense variants generally are associated with less severe disease than truncating variants that produce no protein due to nonsense-mediated decay. However, this correlation is not perfect, and sometimes the same variant can be seen both in XLT and in WAS (sometimes within two different members of the same family), a concept in genetics referred to as variable expressivity. Although autoimmune disease and malignancy may occur in both conditions, patients with loss of WASp are at higher risk. A defect in the CD43 molecule has also been found in WAS patients. CD43, a transmembrane sialoglycoprotein also known as a leukosialin, is part of a greater complex involved in T-cell activation and acts as a sensitive indicator of abnormal, malignant B cell populations. Defects in this molecule may be detrimental to WAS patients, who are at a much higher risk of autoimmune diseases that may be exasperated in later-detected B-cell lymphomas. Diagnosis The diagnosis can be made on the basis of clinical findings, the peripheral blood smear, and low immunoglobulin levels. Typically, IgM levels are low, IgA levels are elevated, and IgE levels may be elevated; paraproteins are occasionally observed. Skin immunologic testing (allergy testing) may reveal hyposensitivity. Individuals with Wiskott–Aldrich syndrome however are at higher risk for severe food allergies. Not all patients have a positive family history of the disorder; new mutations do occur. Often, leukemia may be suspected on the basis of low platelets and infections, and bone marrow biopsy may be performed. Decreased levels of WASp are typically observed. The current gold standard for diagnosis is DNA sequence analysis, which can detect WAS and the related disorders XLT and XLN in 95% of patients and carriers. Classification Jin et al. (2004) employ a numerical grading of severity: This score, which ranges from 0 to 5, may have clinical utility for predicting disease severity. Those with higher WAS scores (e.g., 5) at younger ages (e.g., age less than 5 years old), are thought to be at highest risk for increased morbidity and mortality related to their condition. As individuals can develop more WAS-related symptoms (e.g. autoimmune disease, malignancy) with age, ones WAS score can increase over time. A lower WAS score may be more compatible with conservative management versus higher WAS scores that may favor intervention with treatments such as hematopoietic stem cell transplant. Treatment Hematopoietic stem cell transplant Treatment of Wiskott–Aldrich syndrome depends on the severity of the disease. WAS is primarily a disorder of the blood-forming tissues, so in cases of severe disease (WAS score 3–5) the only widely available curative treatment currently available is a hematopoietic stem cell transplant (HCT). In this procedure stem cells are harvested from umbilical cord blood, bone marrow, or peripheral blood following treatment with medications that cause stem cells to leave the bone marrow and circulate systemically. The best outcomes are with HLA-identical or similar donors (often siblings). In cases of milder disease the potential benefits of HCT (>90% probability of cure if transplant occurs before age two) must be considered in the context of non-trivial risks presented by the procedure itself and the potential need for lifelong immunosuppression to prevent graft-versus-host disease. Generally outcomes are better if HCT occurs prior to the development of autoimmune disease or malignancy, however there are risks associated with chemotherapy (needed to make room for the new stem cells) especially in young infants (risk of a second cancer, or infertility).Bleeding complications Otherwise WAS treatment is focused on managing symptoms and preventing complications. The greatest mortality risk in WAS before age 30 is from bleeding so aspirin and other nonsteroidal anti-inflammatory drugs that may interfere with already compromised platelet function should generally be avoided. Circumcision, as well as elective surgeries, should generally be deferred in males with thrombocytopenia until after HCT if possible. Protective helmets can help protect children from life-threatening intracranial hemorrhage (brain bleed) which could result from head injuries. Patients may require platelet transfusions when there is extreme bloodloss (such as during surgery) or for very low platelets splenectomy (removal of the spleen) may also be lifesaving. However, splenectomy is generally considered palliative and is not universally recommended in WAS because it can increase the risk of life-threatening infections. Post-splenectomy patients will require lifelong antibiotic prophyllaxis to prevent infections. Study of eltrombopag, a thrombopoietic agent used to increase platelets in immune thrombocytopenic purpura (ITP), in WAS concluded that although it increased platelet numbers it failed to increase platelet activation in most patients. It has since been proposed the eltrombopag may be used to bridge to HCT in patients with severe thrombocytopenia to normalize platelet numbers without transfusions and decrease bleeding events. Anemia from bleeding may require iron supplementation or blood transfusion. Regular surveillance of blood counts is recommended. Infections and autoimmune disease For patients with frequent infections, intravenous immunoglobulins (IVIG) or subcutaneous immunoglobulins can be regularly scheduled to boost the immune system. Adequacy of IVIG replacement can be assessed via periodic lab draws. WAS patients with immune system compromise may benefit from antibiotic prophylaxis, for example by taking trimethoprim-sulfamethoxazole to prevent Pneumocystis jirovecii-related pneumonia. Similarly, prophylactic antibiotic use may also be considered in patients with recurrent bacterial sinus or lung infections. When there are signs or symptoms of an infection, prompt and thorough evaluation is important including blood cultures to guide therapy (often IV antibiotics). Live vaccines (such as MMR or rotavirus) should be avoided during routine childhood vaccination. Inactivated vaccines may be given safely but may not provide protective levels of immunity. Eczema is generally treated with topical steroids, and if chronic skin infections exacerbate eczema an antibiotic may also be given. Autoimmune disease is managed with judicious use of appropriate immunosuppressants.Gene therapy For severely affected males without an HLA-matched donor, studies of correcting Wiskott–Aldrich syndrome with gene therapy using a lentivirus are underway. Proof-of-principle for successful hematopoietic stem cell gene therapy has been provided for patients with Wiskott–Aldrich syndrome. In July 2013 the Italian San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) reported that three children with Wiskott–Aldrich syndrome showed significant improvement (improved platelet counts, immune functiona, and clinical symptoms) 20–30 months after being treated with a genetically modified lentivirus. In April 2015 results from a follow-up British and French trial six out of seven individuals showed improvement of immune function and clinical symptoms an average of 27 months after treatment with gene therapy. Importantly, neither study showed evidence of leukemic proliferation following treatment, a complication of early attempts at gene therapy using a retroviral vector. It is unknown why these gene therapies did not restore normal platelet numbers, but gene therapy treatment was still associated with transfusion-independence and a significant reduction in bleeding events. A version of this treatment, OTL-103, is being developed by Orchard Therapeutics and (as of 28 June 2021) is undergoing Phase I/II clinical trials. Prognosis Outcomes from Wiskott–Aldrich syndrome are variable and depend on how severely an individual is affected (the WAS score may be used to assess disease severity). The milder end of the disease spectrum associated with the WAS gene is referred to as X-linked neutropenia or X-linked thrombocytopenia, and the latter is thought to have a normal life expectancy with reports of minimally affected males surviving into their seventh decade without treatment. Traditionally however Wiskott–Aldrich syndrome has been associated with premature death from causes including bleeding, infections, or malignancy. Wiskott–Aldrich syndrome is a condition with variable expressivity, meaning that even within the same family some may exhibit only chronic thrombocytopenia while others experience severe, life-threatening complications of Wiskott–Aldrich syndrome in infancy or childhood. Given symptoms often progress with age, it is challenging to predict how affected a newly diagnosed infant will eventually be. There is some genotype-phenotype correlation, with most individuals with X-linked thrombocytopenia having missense variants in the WAS gene versus 86.5% of those that make no WAS protein having the classic Wiskott–Aldrich syndrome phenotype. Overall the prognosis for individuals with Wiskott–Aldrich syndrome has improved considerably over the past decades due to earlier diagnoses and more access to treatments. Epidemiology The estimated incidence of Wiskott–Aldrich syndrome in the United States is one in 250,000 live male births. While still a rare disease, this makes it more common than many genetic immunodeficiency syndromes such as hyper-IgM syndrome or SCID, which have an estimated incidence of about one in 1,000,000 live births, and Wiskott–Aldrich syndrome is thought to account for 1.2% of all inherited immunodeficiencies in the United States. WAS occurs worldwide and is not known to be more common in any particular ethnic group. History The syndrome is named after Dr. Alfred Wiskott (1898–1978), a German pediatrician who first noticed the syndrome in 1937, and Dr. Robert Anderson Aldrich (1917–1998), an American pediatrician who described the disease in a family of Dutch-Americans in 1954. Wiskott described three brothers with a similar disease, whose sisters were unaffected. In 2006, a German research group analyzed family members of Wiskotts three cases, and surmised they probably shared a novel frameshift mutation of the first exon of the WASp gene. References Further reading GeneReviews/NIH/NCBI/UW entry on WAS-Related Disorders including Wiskott-Aldrich syndrome WAS X-linked thrombocytopenia XLT and X-linked congenital neutropenia XLN Immune Deficiency Foundation - "Wiskott-Aldrich Syndrome" Wiskott-Aldrich Foundation == External links ==

Hypothyroidism

Hypothyroidism (also called underactive thyroid, low thyroid or hypothyreosis) is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goiter. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.Worldwide, too little iodine in the diet is the most common cause of hypothyroidism. Hashimotos thyroiditis is the most common cause of hypothyroidism in countries with sufficient dietary iodine. Less common causes include previous treatment with radioactive iodine, injury to the hypothalamus or the anterior pituitary gland, certain medications, a lack of a functioning thyroid at birth, or previous thyroid surgery. The diagnosis of hypothyroidism, when suspected, can be confirmed with blood tests measuring thyroid-stimulating hormone (TSH) and thyroxine levels.Salt iodization has prevented hypothyroidism in many populations. Thyroid hormone replacement with levothyroxine treats hypothyroidism. Medical professionals adjust the dose according to symptoms and normalization of the thyroxine and TSH levels. Thyroid medication is safe in pregnancy. Although an adequate amount of dietary iodine is important, too much may worsen specific forms of hypothyroidism.Worldwide about one billion people are estimated to be iodine-deficient; however, it is unknown how often this results in hypothyroidism. In the United States, hypothyroidism occurs in 0.3–0.4% of people. Subclinical hypothyroidism, a milder form of hypothyroidism characterized by normal thyroxine levels and an elevated TSH level, is thought to occur in 4.3–8.5% of people in the United States. Hypothyroidism is more common in women than in men. People over the age of 60 are more commonly affected. Dogs are also known to develop hypothyroidism, as are cats and horses, albeit more rarely. The word hypothyroidism is from Greek hypo- reduced, thyreos shield, and eidos form. Signs and symptoms People with hypothyroidism often have no or only mild symptoms. Numerous symptoms and signs are associated with hypothyroidism and can be related to the underlying cause, or a direct effect of having not enough thyroid hormones. Hashimotos thyroiditis may present with the mass effect of a goiter (enlarged thyroid gland). In middle-aged women, the symptoms may be mistaken for those of menopause. Delayed relaxation after testing the ankle jerk reflex is a characteristic sign of hypothyroidism and is associated with the severity of the hormone deficit. Myxedema coma Myxedema coma is a rare but life-threatening state of extreme hypothyroidism. It may occur in those with established hypothyroidism when they develop an acute illness. Myxedema coma can be the first presentation of hypothyroidism. People with myxedema coma typically have a low body temperature without shivering, confusion, a slow heart rate and reduced breathing effort. There may be physical signs suggestive of hypothyroidism, such as skin changes or enlargement of the tongue. Pregnancy Even mild or subclinical hypothyroidism leads to possible infertility and an increased risk of miscarriage. Hypothyroidism in early pregnancy, even with limited or no symptoms, may increase the risk of pre-eclampsia, offspring with lower intelligence, and the risk of infant death around the time of birth. Women are affected by hypothyroidism in 0.3–0.5% of pregnancies. Subclinical hypothyroidism during pregnancy is associated with gestational diabetes, low birth-weight, placental abruption, and the birth of the baby before 37 weeks of pregnancy. Children Newborn children with hypothyroidism may have normal birth weight and height (although the head may be larger than expected and the posterior fontanelle may be open). Some may have drowsiness, decreased muscle tone, a hoarse-sounding cry, feeding difficulties, constipation, an enlarged tongue, umbilical hernia, dry skin, a decreased body temperature, and jaundice. A goiter is rare, although it may develop later in children who have a thyroid gland that does not produce functioning thyroid hormone. A goiter may also develop in children growing up in areas with iodine deficiency. Normal growth and development may be delayed, and not treating infants may lead to an intellectual impairment (IQ 6–15 points lower in severe cases). Other problems include the following: difficulty with large scale and fine motor skills and coordination, reduced muscle tone, squinting, decreased attention span, and delayed speaking. Tooth eruption may be delayed.In older children and adolescents, the symptoms of hypothyroidism may include fatigue, cold intolerance, sleepiness, muscle weakness, constipation, a delay in growth, overweight for height, pallor, coarse and thick skin, increased body hair, irregular menstrual cycles in girls, and delayed puberty. Signs may include delayed relaxation of the ankle reflex and a slow heartbeat. A goiter may be present with a completely enlarged thyroid gland; sometimes only part of the thyroid is enlarged and it can be knobby. Related disorders Thyroid hormone abnormalities are common in major psychiatric disorders including bipolar disorder; clinical research has shown there is a high rate of thyroid dysfunction in mood disorders and schizophrenia-spectrum disorders, concluding that there is a case for screening for the latter among people with thyroid illness. Causes Hypothyroidism is caused by inadequate function of the gland itself (primary hypothyroidism), inadequate stimulation by thyroid-stimulating hormone from the pituitary gland (secondary hypothyroidism), or inadequate release of thyrotropin-releasing hormone from the brains hypothalamus (tertiary hypothyroidism). Primary hypothyroidism is about a thousandfold more common than central hypothyroidism.Iodine deficiency is the most common cause of primary hypothyroidism and endemic goiter worldwide. In areas of the world with sufficient dietary iodine, hypothyroidism is most commonly caused by the autoimmune disease Hashimotos thyroiditis (chronic autoimmune thyroiditis). Hashimotos may be associated with a goiter. It is characterized by infiltration of the thyroid gland with T lymphocytes and autoantibodies against specific thyroid antigens such as thyroid peroxidase, thyroglobulin and the TSH receptor.After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.Autoimmune thyroiditis (Hashimotos) is associated with other immune-mediated diseases such as diabetes mellitus type 1, pernicious anemia, myasthenia gravis, celiac disease, rheumatoid arthritis and systemic lupus erythematosus. It may occur as part of autoimmune polyendocrine syndrome (type 1 and type 2).Iatrogenic hypothyroidism can be surgical (a result of thyroidectomy, usually for thyroid nodules or cancer) or following radioiodine ablation (usually for Graves disease). Pathophysiology Thyroid hormone is required for the normal functioning of numerous tissues in the body. In healthy individuals, the thyroid gland predominantly secretes thyroxine (T4), which is converted into triiodothyronine (T3) in other organs by the selenium-dependent enzyme iodothyronine deiodinase. Triiodothyronine binds to the thyroid hormone receptor in the nucleus of cells, where it stimulates the turning on of particular genes and the production of specific proteins. Additionally, the hormone binds to integrin αvβ3 on the cell membrane, thereby stimulating the sodium–hydrogen antiporter and processes such as formation of blood vessels and cell growth. In blood, almost all thyroid hormone (99.97%) are bound to plasma proteins such as thyroxine-binding globulin; only the free unbound thyroid hormone is biologically active.The thyroid gland is the only source of thyroid hormone in the body; the process requires iodine and the amino acid tyrosine. Iodine in the bloodstream is taken up by the gland and incorporated into thyroglobulin molecules. The process is controlled by the thyroid-stimulating hormone (TSH, thyrotropin), which is secreted by the pituitary. Not enough iodine, or not enough TSH, can result in decreased production of thyroid hormones.The hypothalamic–pituitary–thyroid axis plays a key role in maintaining thyroid hormone levels within normal limits. Production of TSH by the anterior pituitary gland is stimulated in turn by thyrotropin-releasing hormone (TRH), released from the hypothalamus. Production of TSH and TRH is decreased by thyroxine by a negative feedback process. Not enough TRH, which is uncommon, can lead to not enough TSH and thereby to not enough thyroid hormone production.Pregnancy leads to marked changes in thyroid hormone physiology. The gland is increased in size by 10%, thyroxine production is increased by 50%, and iodine requirements are increased. Many women have normal thyroid function but have immunological evidence of thyroid autoimmunity (as evidenced by autoantibodies) or are iodine deficient, and develop evidence of hypothyroidism before or after giving birth. Diagnosis Laboratory testing of thyroid stimulating hormone levels in the blood is considered the best initial test for hypothyroidism; a second TSH level is often obtained several weeks later for confirmation. Levels may be abnormal in the context of other illnesses, and TSH testing in hospitalized people is discouraged unless thyroid dysfunction is strongly suspected, as the cause of the acute illness. An elevated TSH level indicates that the thyroid gland is not producing enough thyroid hormone, and free T4 levels are then often obtained. Measuring T3 is discouraged by the AACE in the assessment for hypothyroidism. In England and Wales, the National Institute for Health and Care Excellence (NICE) recommends routine T4 testing in children, and T3 testing in both adults and children if central hypothyroidism is suspected and the TSH is low. There are a number of symptom rating scales for hypothyroidism; they provide a degree of objectivity but have limited use for diagnosis. Many cases of hypothyroidism are associated with mild elevations in creatine kinase and liver enzymes in the blood. They typically return to normal when hypothyroidism has been fully treated. Levels of cholesterol, low-density lipoprotein and lipoprotein (a) can be elevated; the impact of subclinical hypothyroidism on lipid parameters is less well-defined.Very severe hypothyroidism and myxedema coma are characteristically associated with low sodium levels in the blood together with elevations in antidiuretic hormone, as well as acute worsening of kidney function due to a number of causes. In most causes, however, it is unclear if the relationship is causal.A diagnosis of hypothyroidism without any lumps or masses felt within the thyroid gland does not require thyroid imaging; however, if the thyroid feels abnormal, diagnostic imaging is then recommended. The presence of antibodies against thyroid peroxidase (TPO) makes it more likely that thyroid nodules are caused by autoimmune thyroiditis, but if there is any doubt, a needle biopsy may be required. Central If the TSH level is normal or low and serum free T4 levels are low, this is suggestive of central hypothyroidism (not enough TSH or TRH secretion by the pituitary gland or hypothalamus). There may be other features of hypopituitarism, such as menstrual cycle abnormalities and adrenal insufficiency. There might also be symptoms of a pituitary mass such as headaches and vision changes. Central hypothyroidism should be investigated further to determine the underlying cause. Overt In overt primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. Overt hypothyroidism may also be diagnosed in those who have a TSH on multiple occasions of greater than 5mIU/L, appropriate symptoms, and only a borderline low T4. It may also be diagnosed in those with a TSH of greater than 10mIU/L. Subclinical Subclinical hypothyroidism is a milder form of hypothyroidism characterized by an elevated serum TSH level, but with a normal serum free thyroxine level. This milder form of hypothyroidism is most commonly caused by Hashimotos thyroiditis. In adults it is diagnosed when TSH levels are greater than 5 mIU/L and less than 10mIU/L. The presentation of subclinical hypothyroidism is variable and classic signs and symptoms of hypothyroidism may not be observed. Of people with subclinical hypothyroidism, a proportion will develop overt hypothyroidism each year. In those with detectable antibodies against thyroid peroxidase (TPO), this occurs in 4.3%, while in those with no detectable antibodies, this occurs in 2.6%. Those with subclinical hypothyroidism and detectable anti-TPO antibodies who do not require treatment should have repeat thyroid function tests more frequently (e.g. yearly) compared with those who do not have antibodies. Pregnancy During pregnancy, the thyroid gland must produce 50% more thyroid hormone to provide enough thyroid hormone for the developing fetus and the expectant mother. In pregnancy, free thyroxine levels may be lower than anticipated due to increased binding to thyroid binding globulin and decreased binding to albumin. They should either be corrected for the stage of pregnancy, or total thyroxine levels should be used instead for diagnosis. TSH values may also be lower than normal (particularly in the first trimester) and the normal range should be adjusted for the stage of pregnancy.In pregnancy, subclinical hypothyroidism is defined as a TSH between 2.5 and 10 mIU/L with a normal thyroxine level, while those with TSH above 10 mIU/L are considered to be overtly hypothyroid even if the thyroxine level is normal. Antibodies against TPO may be important in making decisions about treatment, and should, therefore, be determined in women with abnormal thyroid function tests.Determination of TPO antibodies may be considered as part of the assessment of recurrent miscarriage, as subtle thyroid dysfunction can be associated with pregnancy loss, but this recommendation is not universal, and presence of thyroid antibodies may not predict future outcome. Prevention Hypothyroidism may be prevented in a population by adding iodine to commonly used foods. This public health measure has eliminated endemic childhood hypothyroidism in countries where it was once common. In addition to promoting the consumption of iodine-rich foods such as dairy and fish, many countries with moderate iodine deficiency have implemented universal salt iodization. Encouraged by the World Health Organization, 70% of the worlds population across 130 countries are receiving iodized salt. In some countries, iodized salt is added to bread. Despite this, iodine deficiency has reappeared in some Western countries as a result of attempts to reduce salt intake.Pregnant and breastfeeding women, who require 66% more daily iodine than non-pregnant women, may still not be getting enough iodine. The World Health Organization recommends a daily intake of 250 µg for pregnant and breastfeeding women. As many women will not achieve this from dietary sources alone, the American Thyroid Association recommends a 150 µg daily supplement by mouth. Screening Screening for hypothyroidism is performed in the newborn period in many countries, generally using TSH. This has led to the early identification of many cases and thus the prevention of developmental delay. It is the most widely used newborn screening test worldwide. While TSH-based screening will identify the most common causes, the addition of T4 testing is required to pick up the rarer central causes of neonatal hypothyroidism. If T4 determination is included in the screening done at birth, this will identify cases of congenital hypothyroidism of central origin in 1:16,000 to 1:160,000 children. Considering that these children usually have other pituitary hormone deficiencies, early identification of these cases may prevent complications.In adults, widespread screening of the general population is a matter of debate. Some organizations (such as the United States Preventive Services Task Force) state that evidence is insufficient to support routine screening, while others (such as the American Thyroid Association) recommend either intermittent testing above a certain age in all sexes or only in women. Targeted screening may be appropriate in a number of situations where hypothyroidism is common: other autoimmune diseases, a strong family history of thyroid disease, those who have received radioiodine or other radiation therapy to the neck, those who have previously undergone thyroid surgery, those with an abnormal thyroid examination, those with psychiatric disorders, people taking amiodarone or lithium, and those with a number of health conditions (such as certain heart and skin conditions). Yearly thyroid function tests are recommended in people with Down syndrome, as they are at higher risk of thyroid disease. Guidelines for England and Wales from the National Institute for Health and Care Excellence (NICE) recommend testing for thyroid disease in people with type 1 diabetes and new-onset atrial fibrillation, and suggests testing in those with depression or unexplained anxiety (all ages), in children with abnormal growth, or unexplained change in behaviour or school performance. On diagnosis of autoimmune thyroid disease, NICE also recommends screening for celiac disease. Management Hormone replacement Most people with hypothyroidism symptoms and confirmed thyroxine deficiency are treated with a synthetic long-acting form of thyroxine, known as levothyroxine (L-thyroxine). In young and otherwise healthy people with overt hypothyroidism, a full replacement dose (adjusted by weight) can be started immediately; in the elderly and people with heart disease a lower starting dose is recommended to prevent over supplementation and risk of complications. Lower doses may be sufficient in those with subclinical hypothyroidism, while people with central hypothyroidism may require a higher than average dose.Blood free thyroxine and TSH levels are monitored to help determine whether the dose is adequate. This is done 4–8 weeks after the start of treatment or a change in levothyroxine dose. Once the adequate replacement dose has been established, the tests can be repeated after 6 and then 12 months, unless there is a change in symptoms. Normalization of TSH does not mean that other abnormalities associated with hypothyroidism improve entirely, such as elevated cholesterol levels.In people with central/secondary hypothyroidism, TSH is not a reliable marker of hormone replacement and decisions are based mainly on the free T4 level. Levothyroxine is best taken 30–60 minutes before breakfast, or four hours after food, as certain substances such as food and calcium can inhibit the absorption of levothyroxine. There is no direct way of increasing thyroid hormone secretion by the thyroid gland. Liothyronine Treatment with liothyronine alone has not received enough study to make a recommendation as to its use; due to its shorter half-life it would need to be taken more often than levothyroxine.Adding liothyronine (synthetic T3) to levothyroxine has been suggested as a measure to provide better symptom control, but this has not been confirmed by studies. In 2007, the British Thyroid Association stated that combined T4 and T3 therapy carried a higher rate of side effects and no benefit over T4 alone. Similarly, American guidelines discourage combination therapy due to a lack of evidence, although they acknowledge that some people feel better when receiving combination treatment. Guidelines by NICE for England and Wales discourage liothyronine.People with hypothyroidism who do not feel well despite optimal levothyroxine dosing may request adjunctive treatment with liothyronine. A 2012 guideline from the European Thyroid Association recommends that support should be offered with regards to the chronic nature of the disease and that other causes of the symptoms should be excluded. Addition of liothyronine should be regarded as experimental, initially only for a trial period of 3 months, and in a set ratio to the current dose of levothyroxine. The guideline explicitly aims to enhance the safety of this approach and to counter its indiscriminate use. Desiccated animal thyroid Desiccated thyroid extract is an animal-based thyroid gland extract, most commonly from pigs. It is a combination therapy, containing forms of T4 and T3. It also contains calcitonin (a hormone produced in the thyroid gland involved in the regulation of calcium levels), T1 and T2; these are not present in synthetic hormone medication. This extract was once a mainstream hypothyroidism treatment, but its use today is unsupported by evidence; British Thyroid Association and American professional guidelines discourage its use, as does NICE. Subclinical hypothyroidism There is no evidence of a benefit from treating subclinical hypothyroidism in those who are not pregnant, and there are potential risks of overtreatment. Untreated subclinical hypothyroidism may be associated with a modest increase in the risk of coronary artery disease when the TSH is over 10 mIU/L. A 2007 review found no benefit of thyroid hormone replacement except for "some parameters of lipid profiles and left ventricular function". There is no association between subclinical hypothyroidism and an increased risk of bone fractures, nor is there a link with cognitive decline.Since 2008, consensus American opinion has been that in general people with TSH under 10 to 20 mIU/L do not require treatment.American guidelines recommend that treatment should be considered in people with symptoms of hypothyroidism, detectable antibodies against thyroid peroxidase, a history of heart disease or are at an increased risk for heart disease, if the TSH is elevated but below 10 mIU/L. NICE recommends that those with a TSH above 10 mIU/L should be treated in the same way as overt hypothyroidism. Those with an elevated TSH but below 10 mIU/L who have symptoms suggestive of hypothyroidism should have a trial of treatment but with the aim to stopping this if the symptoms persist despite normalisation of the TSH.A recent meta-analysis, however, found an increased risk for cardiovascular death in subclinical hypothyreoidism. Myxedema coma Myxedema coma or severe decompensated hypothyroidism usually requires admission to the intensive care, close observation and treatment of abnormalities in breathing, temperature control, blood pressure, and sodium levels. Mechanical ventilation may be required, as well as fluid replacement, vasopressor agents, careful rewarming, and corticosteroids (for possible adrenal insufficiency which can occur together with hypothyroidism). Careful correction of low sodium levels may be achieved with hypertonic saline solutions or vasopressin receptor antagonists. For rapid treatment of the hypothyroidism, levothyroxine or liothyronine may be administered intravenously, particularly if the level of consciousness is too low to be able to safely swallow medication. While administration through a nasogastric tube is possible, this may be unsafe and is discouraged. Pregnancy In women with known hypothyroidism who become pregnant, it is recommended that serum TSH levels are closely monitored. Levothyroxine should be used to keep TSH levels within the normal range for that trimester. The first trimester normal range is below 2.5 mIU/L and the second and third trimesters normal range is below 3.0 mIU/L. Treatment should be guided by total (rather than free) thyroxine or by the free T4 index. Similarly to TSH, the thyroxine results should be interpreted according to the appropriate reference range for that stage of pregnancy. The levothyroxine dose often needs to be increased after pregnancy is confirmed, although this is based on limited evidence and some recommend that it is not always required; decisions may need to based on TSH levels.Women with anti-TPO antibodies who are trying to become pregnant (naturally or by assisted means) may require thyroid hormone supplementation even if the TSH level is normal. This is particularly true if they have had previous miscarriages or have been hypothyroid in the past. Supplementary levothyroxine may reduce the risk of preterm birth and possibly miscarriage. The recommendation is stronger in pregnant women with subclinical hypothyroidism (defined as TSH 2.5–10 mIU/L) who are anti-TPO positive, in view of the risk of overt hypothyroidism. If a decision is made not to treat, close monitoring of the thyroid function (every 4 weeks in the first 20 weeks of pregnancy) is recommended. If anti-TPO is not positive, treatment for subclinical hypothyroidism is not currently recommended. It has been suggested that many of the aforementioned recommendations could lead to unnecessary treatment, in the sense that the TSH cutoff levels may be too restrictive in some ethnic groups; there may be little benefit from treatment of subclinical hypothyroidism in certain cases. Alternative medicine The effectiveness and safety of using Chinese herbal medicines to treat hypothyroidism is not known. Epidemiology Worldwide about one billion people are estimated to be iodine deficient; however, it is unknown how often this results in hypothyroidism. In large population-based studies in Western countries with sufficient dietary iodine, 0.3–0.4% of the population have overt hypothyroidism. A larger proportion, 4.3–8.5%, have subclinical hypothyroidism. Undiagnosed hypothyroidism is estimated to affect about 4–7% of community-derived populations in the US and Europe. Of people with subclinical hypothyroidism, 80% have a TSH level below the 10 mIU/L mark regarded as the threshold for treatment. Children with subclinical hypothyroidism often return to normal thyroid function, and a small proportion develops overt hypothyroidism (as predicted by evolving antibody and TSH levels, the presence of celiac disease, and the presence of a goiter).Women are more likely to develop hypothyroidism than men. In population-based studies, women were seven times more likely than men to have TSH levels above 10 mU/L. 2–4% of people with subclinical hypothyroidism will progress to overt hypothyroidism each year. The risk is higher in those with antibodies against thyroid peroxidase. Subclinical hypothyroidism is estimated to affect approximately 2% of children; in adults, subclinical hypothyroidism is more common in the elderly, and in Caucasians. There is a much higher rate of thyroid disorders, the most common of which is hypothyroidism, in individuals with Down syndrome and Turner syndrome.Very severe hypothyroidism and myxedema coma are rare, with it estimated to occur in 0.22 per million people a year. The majority of cases occur in women over 60 years of age, although it may happen in all age groups.Most hypothyroidism is primary in nature. Central/secondary hypothyroidism affects 1:20,000 to 1:80,000 of the population, or about one out of every thousand people with hypothyroidism. History In 1811, Bernard Courtois discovered iodine was present in seaweed, and iodine intake was linked with goiter size in 1820 by Jean-Francois Coindet. Gaspard Adolphe Chatin proposed in 1852 that endemic goiter was the result of not enough iodine intake, and Eugen Baumann demonstrated iodine in thyroid tissue in 1896.The first cases of myxedema were recognized in the mid-19th century (the 1870s), but its connection to the thyroid was not discovered until the 1880s when myxedema was observed in people following the removal of the thyroid gland (thyroidectomy). The link was further confirmed in the late 19th century when people and animals who had had their thyroid removed showed improvement in symptoms with transplantation of animal thyroid tissue. The severity of myxedema, and its associated risk of mortality and complications, created interest in discovering effective treatments for hypothyroidism. Transplantation of thyroid tissue demonstrated some efficacy, but recurrences of hypothyroidism was relatively common, and sometimes required multiple repeat transplantations of thyroid tissue.In 1891, the English physician George Redmayne Murray introduced subcutaneously injected sheep thyroid extract, followed shortly after by an oral formulation. Purified thyroxine was introduced in 1914 and in the 1930s synthetic thyroxine became available, although desiccated animal thyroid extract remained widely used. Liothyronine was identified in 1952.Early attempts at titrating therapy for hypothyroidism proved difficult. After hypothyroidism was found to cause a lower basal metabolic rate, this was used as a marker to guide adjustments in therapy in the early 20th century (around 1915). However, a low basal metabolic rate was known to be non-specific, also present in malnutrition. The first laboratory test to be helpful in assessing thyroid status was the serum protein-bound iodine, which came into use around the 1950s. In 1971, the thyroid stimulating hormone (TSH) radioimmunoassay was developed, which was the most specific marker for assessing thyroid status in patients. Many people who were being treated based on basal metabolic rate, minimizing hypothyroid symptoms, or based on serum protein-bound iodine, were found to have excessive thyroid hormone. The following year, in 1972, a T3 radioimmunoassay was developed, and in 1974, a T4 radioimmunoassay was developed. Other animals In veterinary practice, dogs are the species most commonly affected by hypothyroidism. The majority of cases occur as a result of primary hypothyroidism, of which two types are recognized: lymphocytic thyroiditis, which is probably immune-driven and leads to destruction and fibrosis of the thyroid gland, and idiopathic atrophy, which leads to the gradual replacement of the gland by fatty tissue. There is often lethargy, cold intolerance, exercise intolerance, and weight gain. Furthermore, skin changes and fertility problems are seen in dogs with hypothyroidism, as well as a number of other symptoms. The signs of myxedema can be seen in dogs, with prominence of skin folds on the forehead, and cases of myxedema coma are encountered. The diagnosis can be confirmed by blood test, as the clinical impression alone may lead to overdiagnosis. Lymphocytic thyroiditis is associated with detectable antibodies against thyroglobulin, although they typically become undetectable in advanced disease. Treatment is with thyroid hormone replacement.Other species that are less commonly affected include cats and horses, as well as other large domestic animals. In cats, hypothyroidism is usually the result of other medical treatment such as surgery or radiation. In young horses, congenital hypothyroidism has been reported predominantly in Western Canada and has been linked with the mothers diet. References External links Hypothyroidism at Curlie "Hypothyroidism information for patients". American Thyroid Association. Retrieved 2017-03-25. "UK Guidelines for the use of thyroid function tests" (PDF). The Association for Clinical Biochemistry, British Thyroid Association and British Thyroid Foundation. 2006. Retrieved 2013-12-25. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S (March 2017). "2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum". Thyroid. 27 (3): 315–389. doi:10.1089/thy.2016.0457. PMC 3472679. PMID 28056690.

Frostbite

Frostbite is a skin injury that occurs when exposed to extreme low temperatures, causing the freezing of the skin or other tissues, commonly affecting the fingers, toes, nose, ears, cheeks and chin areas. Most often, frostbite occurs in the hands and feet. The initial symptom is typically numbness. This may be followed by clumsiness with a white or bluish color to the skin. Swelling or blistering may occur following treatment. Complications may include hypothermia or compartment syndrome.People who are exposed to low temperatures for prolonged periods, such as winter sports enthusiasts, military personnel, and homeless individuals, are at greatest risk. Other risk factors include drinking alcohol, smoking, mental health problems, certain medications, and prior injuries due to cold. The underlying mechanism involves injury from ice crystals and blood clots in small blood vessels following thawing. Diagnosis is based on symptoms. Severity may be divided into superficial (1st and 2nd degree) or deep (3rd and 4th degree). A bone scan or MRI may help in determining the extent of injury.Prevention is by wearing proper, fully-covering clothing, maintaining hydration and nutrition, avoiding low temperatures, and minimizing strenuous physical activity while maintaining a sufficient core temperature. Treatment is by gradual rewarming, generally from cold to warm water, and should only be done when consistent temperature can be maintained and refreezing is not a concern. Rapid heating or cooling should be avoided since it could potentially cause heart stress or cause burning. Rubbing or applying force to the affected areas should be avoided as it may cause further damage such as abrasions. The use of ibuprofen and tetanus toxoid is recommended for pain relief or to reduce swelling or inflammation. For severe injuries, iloprost or thrombolytics may be used. Surgery is sometimes necessary. Amputation should be considered a few months after exposure in order to consider whether the extent of injury is permanent damage and thus necessitates drastic treatment.Evidence of frostbite occurring in people dates back 5,000 years. Evidence was documented in a pre-Columbian mummy discovered in the Andes. The number of cases of frostbite is unknown. Rates may be as high as 40% a year among those who mountaineer. The most common age group affected is those 30 to 50 years old. Frostbite has also played an important role in a number of military conflicts. The first formal description of the condition was in 1813 by Dominique Jean Larrey, a physician in Napoleons army, during its invasion of Russia. Signs and symptoms Areas that are usually affected include cheeks, ears, nose and fingers and toes. Frostbite is often preceded by frostnip. The symptoms of frostbite progress with prolonged exposure to cold. Historically, frostbite has been classified by degrees according to skin and sensation changes, similar to burn classifications. However, the degrees do not correspond to the amount of long term damage. A simplification of this system of classification is superficial (first or second degree) or deep injury (third or fourth degree). First degree First degree frostbite is superficial, surface skin damage that is usually not permanent. Early on, the primary symptom is loss of feeling in the skin. In the affected areas, the skin is numb, and possibly swollen, with a reddened border. In the weeks after injury, the skins surface may slough off. Second degree In second degree frostbite, the skin develops clear blisters early on, and the skins surface hardens. In the weeks after injury, this hardened, blistered skin dries, blackens, and peels. At this stage, lasting cold sensitivity and numbness can develop. Third degree In third degree frostbite, the layers of tissue below the skin freeze. Symptoms include blood blisters and "blue-grey discoloration of the skin". In the weeks after injury, pain persists and a blackened crust (eschar) develops. There can be longterm ulceration and damage to growth plates. Fourth degree In fourth degree frostbite, structures below the skin are involved like muscles, tendon, and bone. Early symptoms include a colorless appearance of the skin, a hard texture, and painless rewarming. Later, the skin becomes black and mummified. The amount of permanent damage can take one month or more to determine. Autoamputation can occur after two months. Causes Risk factors The major risk factor for frostbite is exposure to cold through geography, occupation and/or recreation. Inadequate clothing and shelter are major risk factors. Frostbite is more likely when the bodys ability to produce or retain heat is impaired. Physical, behavioral, and environmental factors can all contribute to the development of frostbite. Immobility and physical stress (such as malnutrition or dehydration) are also risk factors. Disorders and substances that impair circulation contribute, including diabetes, Raynauds phenomenon, tobacco and alcohol use. Homeless individuals and individuals with some mental illnesses may be at higher risk. Mechanism Freezing In frostbite, cooling of the body causes narrowing of the blood vessels (vasoconstriction). Temperatures below −23 °C (−9 °F) are required to form ice crystals in the tissues. The process of freezing causes ice crystals to form in the tissue, which in turn causes damage at the cellular level. Ice crystals can damage cell membranes directly. In addition, ice crystals can damage small blood vessels at the site of injury. Scar tissue forms when fibroblasts replace the dead cells. Rewarming Rewarming causes tissue damage through reperfusion injury, which involves vasodilation, swelling (edema), and poor blood flow (stasis). Platelet aggregation is another possible mechanism of injury. Blisters and spasm of blood vessels (vasospasm) can develop after rewarming. Non-freezing cold injury The process of frostbite differs from the process of non-freezing cold injury (NFCI). In NFCI, temperature in the tissue decreases gradually. This slower temperature decrease allows the body to try to compensate through alternating cycles of closing and opening blood vessels (vasoconstriction and vasodilation). If this process continues, inflammatory mast cells act in the area. Small clots (microthrombi) form and can cut off blood to the affected area (known as ischemia) and damage nerve fibers. Rewarming causes a series of inflammatory chemicals such as prostaglandins to increase localized clotting. Pathophysiology The pathological mechanism by which frostbite causes body tissue injury can be characterized by four stages: Prefreeze, freeze-thaw, vascular stasis, and the late ischemic stage. Prefreeze phase: involves the cooling of tissues without ice crystal formation. Freeze-thaw phase: ice-crystals form, resulting in cellular damage and death. Vascular stasis phase: marked by blood coagulation or the leaking of blood out of the vessels. Late ischemic phase: characterized by inflammatory events, ischemia and tissue death. Diagnosis Frostbite is diagnosed based on signs and symptoms as described above, and by patient history. Other conditions that can have a similar appearance or occur at the same time include: Frostnip is similar to frostbite, but without ice crystal formation in the skin. Whitening of the skin and numbness reverse quickly after rewarming. Trench foot is damage to nerves and blood vessels that results exposure to wet, cold (non-freezing) conditions. This is reversible if treated early. Pernio or chilblains are inflammation of the skin from exposure to wet, cold (non-freezing) conditions. They can appear as various types of ulcers and blisters. Bullous pemphigoid is a condition that causes itchy blisters over the body that can mimic frostbite. It does not require exposure to cold to develop. Levamisole toxicity is a vasculitis that can appear similar to frostbite. It is caused by contamination of cocaine by levamisole. Skin lesions can look similar those of frostbite, but do not require cold exposure to occur.People who have hypothermia often have frostbite as well. Since hypothermia is life-threatening this should be treated first. Technetium-99 or MR scans are not required for diagnosis, but might be useful for prognostic purposes. Prevention The Wilderness Medical Society recommends covering the skin and scalp, taking in adequate nutrition, avoiding constrictive footwear and clothing, and remaining active without causing exhaustion. Supplemental oxygen might also be of use at high elevations. Repeated exposure to cold water makes people more susceptible to frostbite. Additional measures to prevent frostbite include: Avoiding temperatures below −23 °C (-9 °F) Avoiding moisture, including in the form of sweat and/or skin emollients Avoiding alcohol and drugs that impair circulation or natural protective responses Layering clothing Using chemical or electric warming devices Recognizing early signs of frostnip and frostbite Treatment Individuals with frostbite or potential frostbite should go to a protected environment and get warm fluids. If there is no risk of re-freezing, the extremity can be exposed and warmed in the groin or underarm of a companion. If the area is allowed to refreeze, there can be worse tissue damage. If the area cannot be reliably kept warm, the person should be brought to a medical facility without rewarming the area. Rubbing the affected area can also increase tissue damage. Aspirin and ibuprofen can be given in the field to prevent clotting and inflammation. Ibuprofen is often preferred to aspirin because aspirin may block a subset of prostaglandins that are important in injury repair.The first priority in people with frostbite should be to assess for hypothermia and other life-threatening complications of cold exposure. Before treating frostbite, the core temperature should be raised above 35 °C. Oral or intravenous (IV) fluids should be given.Other considerations for standard hospital management include: wound care: blisters can be drained by needle aspiration, unless they are bloody (hemorrhagic). Aloe vera gel can be applied before breathable, protective dressings or bandages are put on. antibiotics: if there is trauma, skin infection (cellulitis) or severe injury tetanus toxoid: should be administered according to local guidelines. Uncomplicated frostbite wounds are not known to encourage tetanus. pain control: NSAIDs or opioids are recommended during the painful rewarming process. Rewarming If the area is still partially or fully frozen, it should be rewarmed in the hospital with a warm bath with povidone iodine or chlorhexidine antiseptic. Active rewarming seeks to warm the injured tissue as quickly as possible without burning. The faster tissue is thawed, the less tissue damage occurs. According to Handford and colleagues, "The Wilderness Medical Society and State of Alaska Cold Injury Guidelines recommend a temperature of 37–39 °C, which decreases the pain experienced by the patient whilst only slightly slowing rewarming time." Warming takes 15 minutes to 1 hour. The faucet should be left running so the water can circulate. Rewarming can be very painful, so pain management is important. Medications People with potential for large amputations and who present within 24 hours of injury can be given TPA with heparin. These medications should be withheld if there are any contraindications. Bone scans or CT angiography can be done to assess damage.Blood vessel dilating medications such as iloprost may prevent blood vessel blockage. This treatment might be appropriate in grades 2–4 frostbite, when people get treatment within 48 hours. In addition to vasodilators, sympatholytic drugs can be used to counteract the detrimental peripheral vasoconstriction that occurs during frostbite.A systematic review and metaanalysis revealed that iloprost alone or iloprost plus recombinant tissue plasminogen activator (rtPA) may decrease amputation rate in case of severe frostbite in comparison to buflomedil alone with no major adverse events reported from iloprost or iloprost plus rtPA in the included studies. Surgery Various types of surgery might be indicated in frostbite injury, depending on the type and extent of damage. Debridement or amputation of necrotic tissue is usually delayed unless there is gangrene or systemic infection (sepsis). This has led to the adage "Frozen in January, amputate in July". If symptoms of compartment syndrome develop, fasciotomy can be done to attempt to preserve blood flow. Prognosis Tissue loss and autoamputation are potential consequences of frostbite. Permanent nerve damage including loss of feeling can occur. It can take several weeks to know what parts of the tissue will survive. Time of exposure to cold is more predictive of lasting injury than temperature the individual was exposed to. The classification system of grades, based on the tissue response to initial rewarming and other factors is designed to predict degree of longterm recovery. Grades Grade 1: if there is no initial lesion on the area, no amputation or lasting effects are expected Grade 2: if there is a lesion on the distal body part, tissue and fingernails can be destroyed Grade 3: if there is a lesion on the intermediate or near body part, auto-amputation and loss of function can occur Grade 4: if there is a lesion very near the body (such as the carpals of the hand), the limb can be lost. Sepsis and/or other systemic problems are expected.A number of long term sequelae can occur after frostbite. These include transient or permanent changes in sensation, paresthesia, increased sweating, cancers, and bone destruction/arthritis in the area affected. Epidemiology There is a lack of comprehensive statistics about the epidemiology of frostbite. In the United States, frostbite is more common in northern states. In Finland, annual incidence was 2.5 per 100,000 among civilians, compared with 3.2 per 100,000 in Montreal. Research suggests that men aged 30–49 are at highest risk, possibly due to occupational or recreational exposures to cold. History Frostbite has been described in military history for millennia. The Greeks encountered and discussed the problem of frostbite as early as 400 BCE. Researchers have found evidence of frostbite in humans dating back 5,000 years, in an Andean mummy. Napoleons Army was the first documented instance of mass cold injury in the early 1800s. According to Zafren, nearly 1 million combatants fell victim to frostbite in the First and Second World Wars, and the Korean War. Society and culture Several notable cases of frostbite include: Captain Lawrence Oates, an English army captain and Antarctic explorer who in 1912 died of complications of frostbite; Harold Bride, the junior wireless operator of RMS Titanic, who suffered severe frostbite on his feet as he and other survivors stood for over an hour on the back of a capsized lifeboat knee-deep in freezing water--Bride had to be carried off from the rescue vessel RMS Carpathia after it arrived in New York; noted American rock climber Hugh Herr, who in 1982 lost both legs below the knee to frostbite after being stranded on Mount Washington (New Hampshire) in a blizzard; Beck Weathers, a survivor of the 1996 Mount Everest disaster who lost his nose and hands to frostbite; Scottish mountaineer Jamie Andrew, who in 1999 had all four limbs amputated due to sepsis from frostbite sustained after becoming trapped for four nights whilst climbing Les Droites in the Mont Blanc massif. Research directions Evidence is insufficient to determine whether or not hyperbaric oxygen therapy as an adjunctive treatment can assist in tissue salvage. Cases have been reported, but no randomized control trial has been performed on humans.Medical sympathectomy using intravenous reserpine has also been attempted with limited success. Studies have suggested that administration of tissue plasminogen activator (tPa) either intravenously or intra-arterially may decrease the likelihood of eventual need for amputation. References External links Mayo Clinic Definition

Meningitis

Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or altered consciousness, nausea, vomiting, and an inability to tolerate light or loud noises. Young children often exhibit only nonspecific symptoms, such as irritability, drowsiness, or poor feeding. A non-blanching rash (a rash that does not fade when a glass is rolled over it) may also be present.The inflammation may be caused by infection with viruses, bacteria or other microorganisms. Non-infectious causes include malignancy (cancer), subarachnoid haemorrhage, chronic inflammatory disease (sarcoidosis) and certain drugs. Meningitis can be life-threatening because of the inflammations proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency. A lumbar puncture, in which a needle is inserted into the spinal canal to collect a sample of cerebrospinal fluid (CSF), can diagnose or exclude meningitis.Some forms of meningitis are preventable by immunization with the meningococcal, mumps, pneumococcal, and Hib vaccines. Giving antibiotics to people with significant exposure to certain types of meningitis may also be useful. The first treatment in acute meningitis consists of promptly giving antibiotics and sometimes antiviral drugs. Corticosteroids can also be used to prevent complications from excessive inflammation. Meningitis can lead to serious long-term consequences such as deafness, epilepsy, hydrocephalus, or cognitive deficits, especially if not treated quickly.In 2019, meningitis was prevalent in about 7.7 million people worldwide. This resulted in 236,000 deaths, down from 433,000 deaths in 1990. With appropriate treatment, the risk of death in bacterial meningitis is less than 15%. Outbreaks of bacterial meningitis occur between December and June each year in an area of sub-Saharan Africa known as the meningitis belt. Smaller outbreaks may also occur in other areas of the world. The word meningitis comes from the Greek μῆνιγξ meninx, "membrane", and the medical suffix -itis, "inflammation". Signs and symptoms Clinical features In adults, the most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of bacterial meningitis, followed by neck stiffness (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness). The classic triad of diagnostic signs consists of neck stiffness, sudden high fever, and altered mental status; however, all three features are present in only 44–46% of bacterial meningitis cases. If none of the three signs are present, acute meningitis is extremely unlikely. Other signs commonly associated with meningitis include photophobia (intolerance to bright light) and phonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only be irritable and look unwell. The fontanelle (the soft spot on the top of a babys head) can bulge in infants aged up to 6 months. Other features that distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities, and an abnormal skin color.Nuchal rigidity occurs in 70% of bacterial meningitis in adults. Other signs include the presence of positive Kernigs sign or Brudziński sign. Kernigs sign is assessed with the person lying supine, with the hip and knee flexed to 90 degrees. In a person with a positive Kernigs sign, pain limits passive extension of the knee. A positive Brudzinskis sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernigs sign and Brudzinskis sign are both commonly used to screen for meningitis, the sensitivity of these tests is limited. They do, however, have very good specificity for meningitis: the signs rarely occur in other diseases. Another test, known as the "jolt accentuation maneuver" helps determine whether meningitis is present in those reporting fever and headache. A person is asked to rapidly rotate the head horizontally; if this does not make the headache worse, meningitis is unlikely.Other problems can produce symptoms similar to those above, but from non-meningitic causes. This is called meningism or pseudomeningitis.Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal meningitis") can be differentiated from meningitis with other causes by a rapidly spreading petechial rash, which may precede other symptoms. The rash consists of numerous small, irregular purple or red spots ("petechiae") on the trunk, lower extremities, mucous membranes, conjunctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically non-blanching; the redness does not disappear when pressed with a finger or a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific for the disease; it does, however, occasionally occur in meningitis due to other bacteria. Other clues on the cause of meningitis may be the skin signs of hand, foot and mouth disease and genital herpes, both of which are associated with various forms of viral meningitis. Early complications Additional problems may occur in the early stage of the illness. These may require specific treatment, and sometimes indicate severe illness or worse prognosis. The infection may trigger sepsis, a systemic inflammatory response syndrome of falling blood pressure, fast heart rate, high or abnormally low temperature, and rapid breathing. Very low blood pressure may occur at an early stage, especially but not exclusively in meningococcal meningitis; this may lead to insufficient blood supply to other organs. Disseminated intravascular coagulation, the excessive activation of blood clotting, may obstruct blood flow to organs and paradoxically increase the bleeding risk. Gangrene of limbs can occur in meningococcal disease. Severe meningococcal and pneumococcal infections may result in hemorrhaging of the adrenal glands, leading to Waterhouse-Friderichsen syndrome, which is often fatal.The brain tissue may swell, pressure inside the skull may increase and the swollen brain may herniate through the skull base. This may be noticed by a decreasing level of consciousness, loss of the pupillary light reflex, and abnormal posturing. The inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus). Seizures may occur for various reasons; in children, seizures are common in the early stages of meningitis (in 30% of cases) and do not necessarily indicate an underlying cause. Seizures may result from increased pressure and from areas of inflammation in the brain tissue. Focal seizures (seizures that involve one limb or part of the body), persistent seizures, late-onset seizures and those that are difficult to control with medication indicate a poorer long-term outcome.Inflammation of the meninges may lead to abnormalities of the cranial nerves, a group of nerves arising from the brain stem that supply the head and neck area and which control, among other functions, eye movement, facial muscles, and hearing. Visual symptoms and hearing loss may persist after an episode of meningitis. Inflammation of the brain (encephalitis) or its blood vessels (cerebral vasculitis), as well as the formation of blood clots in the veins (cerebral venous thrombosis), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area of the brain. Causes Meningitis is typically caused by an infection with microorganisms. Most infections are due to viruses, with bacteria, fungi, and protozoa being the next most common causes. It may also result from various non-infectious causes. The term aseptic meningitis refers to cases of meningitis in which no bacterial infection can be demonstrated. This type of meningitis is usually caused by viruses but it may be due to bacterial infection that has already been partially treated, when bacteria disappear from the meninges, or pathogens infect a space adjacent to the meninges (e.g. sinusitis). Endocarditis (an infection of the heart valves which spreads small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection with spirochetes, a group of bacteria that includes Treponema pallidum (the cause of syphilis) and Borrelia burgdorferi (known for causing Lyme disease). Meningitis may be encountered in cerebral malaria (malaria infecting the brain) or amoebic meningitis, meningitis due to infection with amoebae such as Naegleria fowleri, contracted from freshwater sources. Bacterial The types of bacteria that cause bacterial meningitis vary according to the infected individuals age group. In premature babies and newborns up to three months old, common causes are group B streptococci (subtypes III which normally inhabit the vagina and are mainly a cause during the first week of life) and bacteria that normally inhabit the digestive tract such as Escherichia coli (carrying the K1 antigen). Listeria monocytogenes (serotype IVb) can be contracted when consuming improperly prepared food such as dairy products, produce and deli meats, and may cause meningitis in the newborn. Older children are more commonly affected by Neisseria meningitidis (meningococcus) and Streptococcus pneumoniae (serotypes 6, 9, 14, 18 and 23) and those under five by Haemophilus influenzae type B (in countries that do not offer vaccination). In adults, Neisseria meningitidis and Streptococcus pneumoniae together cause 80% of bacterial meningitis cases. Risk of infection with Listeria monocytogenes is increased in persons over 50 years old. The introduction of pneumococcal vaccine has lowered rates of pneumococcal meningitis in both children and adults.Recent skull trauma potentially allows nasal cavity bacteria to enter the meningeal space. Similarly, devices in the brain and meninges, such as cerebral shunts, extraventricular drains or Ommaya reservoirs, carry an increased risk of meningitis. In these cases, the persons are more likely to be infected with Staphylococci, Pseudomonas, and other Gram-negative bacteria. These pathogens are also associated with meningitis in people with an impaired immune system. An infection in the head and neck area, such as otitis media or mastoiditis, can lead to meningitis in a small proportion of people. Recipients of cochlear implants for hearing loss are more at risk for pneumococcal meningitis.Tuberculous meningitis, which is meningitis caused by Mycobacterium tuberculosis, is more common in people from countries in which tuberculosis is endemic, but is also encountered in persons with immune problems, such as AIDS.Recurrent bacterial meningitis may be caused by persisting anatomical defects, either congenital or acquired, or by disorders of the immune system. Anatomical defects allow continuity between the external environment and the nervous system. The most common cause of recurrent meningitis is a skull fracture, particularly fractures that affect the base of the skull or extend towards the sinuses and petrous pyramids. Approximately 59% of recurrent meningitis cases are due to such anatomical abnormalities, 36% are due to immune deficiencies (such as complement deficiency, which predisposes especially to recurrent meningococcal meningitis), and 5% are due to ongoing infections in areas adjacent to the meninges. Viral Viruses that cause meningitis include enteroviruses, herpes simplex virus (generally type 2, which produces most genital sores; less commonly type 1), varicella zoster virus (known for causing chickenpox and shingles), mumps virus, HIV, LCMV, Arboviruses (acquired from a mosquito or other insect), and the Influenza virus. Mollarets meningitis is a chronic recurrent form of herpes meningitis; it is thought to be caused by herpes simplex virus type 2. Fungal There are a number of risk factors for fungal meningitis, including the use of immunosuppressants (such as after organ transplantation), HIV/AIDS, and the loss of immunity associated with aging. It is uncommon in those with a normal immune system but has occurred with medication contamination. Symptom onset is typically more gradual, with headaches and fever being present for at least a couple of weeks before diagnosis. The most common fungal meningitis is cryptococcal meningitis due to Cryptococcus neoformans. In Africa, cryptococcal meningitis is now the most common cause of meningitis in multiple studies, and it accounts for 20–25% of AIDS-related deaths in Africa. Other less common fungal pathogens which can cause meningitis include: Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, and Candida species. Parasitic A parasitic cause is often assumed when there is a predominance of eosinophils (a type of white blood cell) in the CSF. The most common parasites implicated are Angiostrongylus cantonensis, Gnathostoma spinigerum, Schistosoma, as well as the conditions cysticercosis, toxocariasis, baylisascariasis, paragonimiasis, and a number of rarer infections and noninfective conditions. Non-infectious Meningitis may occur as the result of several non-infectious causes: spread of cancer to the meninges (malignant or neoplastic meningitis) and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins). It may also be caused by several inflammatory conditions, such as sarcoidosis (which is then called neurosarcoidosis), connective tissue disorders such as systemic lupus erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such as Behçets disease. Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space. Rarely, migraine may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated. Mechanism The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and protect the brain and spinal cord (the central nervous system). The pia mater is a delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull. In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream (hematogenous spread) or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live on mucosal surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucosal surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood–brain barrier is vulnerable – such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is much less common in adults. Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of the dura mater can be identified.The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The blood–brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered blood pressure often encountered in sepsis, this means that it is harder for blood to enter the brain; consequently brain cells are deprived of oxygen and undergo apoptosis (programmed cell death).It is recognized that administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune systems response to this phenomenon. Diagnosis Diagnosing meningitis as promptly as possible can improve outcomes. There is no specific sign or symptom that can diagnose meningitis and a lumbar puncture (spinal tap) to examine the cerebrospinal fluid is recommended for diagnosis. Lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or the intracranial pressure (ICP) is elevated, as it may lead to brain herniation. If someone is at risk for either a mass or raised ICP (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a CT or MRI scan is recommended prior to the lumbar puncture. This applies in 45% of all adult cases.There are no physical tests that can rule out or determine if a person has meningitis. The jolt accentuation test is not specific or sensitive enough to completely rule out meningitis.If someone is suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. C-reactive protein, complete blood count), as well as blood cultures. If a CT or MRI is required before LP, or if LP proves difficult, professional guidelines suggest that antibiotics should be administered first to prevent delay in treatment, especially if this may be longer than 30 minutes. Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis.In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia is common in bacterial meningitis. The cause of hyponatremia, however, is controversial and may include dehydration, the inappropriate secretion of the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration. Lumbar puncture A lumbar puncture is done by positioning the person, usually lying on the side, applying local anesthetic, and inserting a needle into the dural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening pressure" of the CSF is measured using a manometer. The pressure is normally between 6 and 18 cm water (cmH2O); in bacterial meningitis the pressure is usually elevated. In cryptococcal meningitis, intracranial pressure is markedly elevated. The initial appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis.The CSF sample is examined for presence and types of white blood cells, red blood cells, protein content and glucose level. Gram staining of the sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the sample was taken. Gram staining is also less reliable in particular infections such as listeriosis. Microbiological culture of the sample is more sensitive (it identifies the organism in 70–85% of cases) but results can take up to 48 hours to become available. The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant), although at the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others.The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis; in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal. High levels of lactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count. If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics then this may rule out bacterial meningitis.Various other specialized tests may be used to distinguish between different types of meningitis. A latex agglutination test may be positive in meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli and group B streptococci; its routine use is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, the limulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful. Polymerase chain reaction (PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agents DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus, herpes simplex virus 2 and mumps in those not vaccinated for this). Serology (identification of antibodies to viruses) may be useful in viral meningitis. If tuberculous meningitis is suspected, the sample is processed for Ziehl–Neelsen stain, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly. Diagnosis of cryptococcal meningitis can be made at low cost using an India ink stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive.A diagnostic and therapeutic difficulty is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g. a positive enterovirus PCR). Postmortem Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a widespread inflammation of the pia mater and arachnoid layers of the meninges. Neutrophil granulocytes tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord, may be surrounded with pus – as may the meningeal vessels. Prevention For some causes of meningitis, protection can be provided in the long term through vaccination, or in the short term with antibiotics. Some behavioral measures may also be effective. Behavioral Bacterial and viral meningitis are contagious, but neither is as contagious as the common cold or flu. Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but bacterial meningitis cannot be spread by only breathing the air where a person with meningitis has been. Viral meningitis is typically caused by enteroviruses, and is most commonly spread through fecal contamination. The risk of infection can be decreased by changing the behavior that led to transmission. Vaccination Since the 1980s, many countries have included immunization against Haemophilus influenzae type B in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young children in those countries. In the countries in which the disease burden is highest, however, the vaccine is still too expensive. Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps.Meningococcus vaccines exist against groups A, B, C, W135 and Y. In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially. A quadrivalent vaccine now exists, which combines four vaccines with the exception of B; immunization with this ACW135Y vaccine is now a visa requirement for taking part in Hajj. Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make a vaccine) only elicit a weak response from the immune system, or cross-react with normal human proteins. Still, some countries (New Zealand, Cuba, Norway and Chile) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules. Two new vaccines, both approved in 2014, are effective against a wider range of group B meningococci strains. In Africa, until recently, the approach for prevention and control of meningococcal epidemics was based on early detection of the disease and emergency reactive mass vaccination of the at-risk population with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines, though the introduction of MenAfriVac (meningococcus group A vaccine) has demonstrated effectiveness in young people and has been described as a model for product development partnerships in resource-limited settings.Routine vaccination against Streptococcus pneumoniae with the pneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of pneumococcal meningitis. The pneumococcal polysaccharide vaccine, which covers 23 strains, is only administered to certain groups (e.g. those who have had a splenectomy, the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children. Childhood vaccination with Bacillus Calmette-Guérin has been reported to significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine. Antibiotics Short-term antibiotic prophylaxis is another method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, preventative treatment in close contacts with antibiotics (e.g. rifampicin, ciprofloxacin or ceftriaxone) can reduce their risk of contracting the condition, but does not protect against future infections. Resistance to rifampicin has been noted to increase after use, which has caused some to recommend considering other agents. While antibiotics are frequently used in an attempt to prevent meningitis in those with a basilar skull fracture there is not enough evidence to determine whether this is beneficial or harmful. This applies to those with or without a CSF leak. Management Meningitis is potentially life-threatening and has a high mortality rate if untreated; delay in treatment has been associated with a poorer outcome. Thus, treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted. If meningococcal disease is suspected in primary care, guidelines recommend that benzylpenicillin be administered before transfer to hospital. Intravenous fluids should be administered if hypotension (low blood pressure) or shock are present. It is not clear whether intravenous fluid should be given routinely or whether this should be restricted. Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early and to admit the person to an intensive care unit if deemed necessary.Mechanical ventilation may be needed if the level of consciousness is very low, or if there is evidence of respiratory failure. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure and various treatments to decrease the intracranial pressure with medication (e.g. mannitol). Seizures are treated with anticonvulsants. Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or long-term drainage device, such as a cerebral shunt. The osmotic therapy, glycerol, has an unclear effect on mortality but may decrease hearing problems. Bacterial meningitis Antibiotics Empiric antibiotics (treatment without exact diagnosis) should be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place and population. For instance, in the United Kingdom, empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone. In the US, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended. Chloramphenicol, either alone or in combination with ampicillin, however, appears to work equally well.Empirical therapy may be chosen on the basis of the persons age, whether the infection was preceded by a head injury, whether the person has undergone recent neurosurgery and whether or not a cerebral shunt is present. In young children and those over 50 years of age, as well as those who are immunocompromised, the addition of ampicillin is recommended to cover Listeria monocytogenes. Once the Gram stain results become available, and the broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens. The results of the CSF culture generally take longer to become available (24–48 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics. For an antibiotic to be effective in meningitis it must not only be active against the pathogenic bacterium but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on people with meningitis in clinical trials. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbits. Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of the lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer. Fluid Therapy Fluid given intravenously are an essential part of treatment of bacterial meningitis. There is no difference in terms of mortality or acute severe neurological complications in children given a maintenance regimen over restricted-fluid regimen, but evidence is in favor of the maintenance regimen in terms of emergence of chronic severe neurological complications. Steroids Additional treatment with corticosteroids (usually dexamethasone) has shown some benefits, such as a reduction of hearing loss, and better short term neurological outcomes in adolescents and adults from high-income countries with low rates of HIV. Some research has found reduced rates of death while other research has not. They also appear to be beneficial in those with tuberculosis meningitis, at least in those who are HIV negative.Professional guidelines therefore recommend the commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics is given, and continued for four days. Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified. The likely mechanism is suppression of overactive inflammation.Additional treatment with corticosteroids have a different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income countries is not supported by the evidence; the reason for this discrepancy is not clear. Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to the first dose of antibiotics, and is greatest in cases of H. influenzae meningitis, the incidence of which has decreased dramatically since the introduction of the Hib vaccine. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause is H. influenzae, and only if given prior to the first dose of antibiotics; other uses are controversial. Viral meningitis Viral meningitis typically only requires supportive therapy; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus and varicella zoster virus may respond to treatment with antiviral drugs such as aciclovir, but there are no clinical trials that have specifically addressed whether this treatment is effective. Mild cases of viral meningitis can be treated at home with conservative measures such as fluid, bedrest, and analgesics. Fungal meningitis Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of high dose antifungals, such as amphotericin B and flucytosine. Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended, or alternatively a lumbar drain. Prognosis Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment, mortality (risk of death) from bacterial meningitis depends on the age of the person and the underlying cause. Of newborns, 20–30% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19–37% in adults.Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid, the severity of the generalized illness, a decreased level of consciousness or an abnormally low count of white blood cells in the CSF. Meningitis caused by H. influenzae and meningococci has a better prognosis than cases caused by group B streptococci, coliforms and S. pneumoniae. In adults, too, meningococcal meningitis has a lower mortality (3–7%) than pneumococcal disease.In children there are several potential disabilities which may result from damage to the nervous system, including sensorineural hearing loss, epilepsy, learning and behavioral difficulties, as well as decreased intelligence. These occur in about 15% of survivors. Some of the hearing loss may be reversible. In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment (in 10%).Tuberculous meningitis in children continues to be associated with a significant risk of death even with treatment (19%), and a significant proportion of the surviving children have ongoing neurological problems. Just over a third of all cases survives with no problems. Epidemiology Although meningitis is a notifiable disease in many countries, the exact incidence rate is unknown. In 2013 meningitis resulted in 303,000 deaths – down from 464,000 deaths in 1990. In 2010 it was estimated that meningitis resulted in 420,000 deaths, excluding cryptococcal meningitis.Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries. Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000, and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8 per 100,000 annually. Sub-Saharan Africa has been plagued by large epidemics of meningococcal meningitis for over a century, leading to it being labeled the "meningitis belt". Epidemics typically occur in the dry season (December to June), and an epidemic wave can last two to three years, dying out during the intervening rainy seasons. Attack rates of 100–800 cases per 100,000 are encountered in this area, which is poorly served by medical care. These cases are predominantly caused by meningococci. The largest epidemic ever recorded in history swept across the entire region in 1996–1997, causing over 250,000 cases and 25,000 deaths.Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, university and college campuses and the annual Hajj pilgrimage. Although the pattern of epidemic cycles in Africa is not well understood, several factors have been associated with the development of epidemics in the meningitis belt. They include: medical conditions (immunological susceptibility of the population), demographic conditions (travel and large population displacements), socioeconomic conditions (overcrowding and poor living conditions), climatic conditions (drought and dust storms), and concurrent infections (acute respiratory infections).There are significant differences in the local distribution of causes for bacterial meningitis. For instance, while N. meningitides groups B and C cause most disease episodes in Europe, group A is found in Asia and continues to predominate in Africa, where it causes most of the major epidemics in the meningitis belt, accounting for about 80% to 85% of documented meningococcal meningitis cases. History Some suggest that Hippocrates may have realized the existence of meningitis, and it seems that meningism was known to pre-Renaissance physicians such as Avicenna. The description of tuberculous meningitis, then called "dropsy in the brain", is often attributed to Edinburgh physician Sir Robert Whytt in a posthumous report that appeared in 1768, although the link with tuberculosis and its pathogen was not made until the next century.It appears that epidemic meningitis is a relatively recent phenomenon. The first recorded major outbreak occurred in Geneva in 1805. Several other epidemics in Europe and the United States were described shortly afterward, and the first report of an epidemic in Africa appeared in 1840. African epidemics became much more common in the 20th century, starting with a major epidemic sweeping Nigeria and Ghana in 1905–1908.The first report of bacterial infection underlying meningitis was by the Austrian bacteriologist Anton Weichselbaum, who in 1887 described the meningococcus. Mortality from meningitis was very high (over 90%) in early reports. In 1906, antiserum was produced in horses; this was developed further by the American scientist Simon Flexner and markedly decreased mortality from meningococcal disease. In 1944, penicillin was first reported to be effective in meningitis. The introduction in the late 20th century of Haemophilus vaccines led to a marked fall in cases of meningitis associated with this pathogen, and in 2002, evidence emerged that treatment with steroids could improve the prognosis of bacterial meningitis. World Meningitis Day is observed on 24 April each year. References External links Meningitis at Curlie Meningitis Centers for Disease Control and Prevention (CDC)

Epiglottitis

Epiglottitis is the inflammation of the epiglottis—the flap at the base of the tongue that prevents food entering the trachea (windpipe). Symptoms are usually rapid in onset and include trouble swallowing which can result in drooling, changes to the voice, fever, and an increased breathing rate. As the epiglottis is in the upper airway, swelling can interfere with breathing. People may lean forward in an effort to open the airway. As the condition worsens stridor and bluish skin may occur.Epiglottitis was historically mostly caused by infection by H. influenzae type b. With vaccination it is now more often caused by other bacteria. Other possible causes include burns and trauma to the area. The most accurate way to make the diagnosis is to look directly at the epiglottis. X-rays of the neck from the side may show a "thumbprint sign" but the lack of this sign does not mean the condition is absent.An effective vaccine, the Hib vaccine, has been available since the 1980s. The antibiotic rifampicin may also be used to prevent the disease among those who have been exposed to the disease and are at high risk. The most important part of treatment involves securing the airway, which is often done by endotracheal intubation. Intravenous antibiotics such as ceftriaxone and possibly vancomycin or clindamycin is then given. Corticosteroids are also typically used. With appropriate treatment, the risk of death among children with the condition is about one percent and among adults is seven percent.With the use of the Hib vaccine, the number of cases of epiglottitis has decreased by more than 95%. While, historically, young children were mostly affected, it is now more common among older children and adults. In the United States it affects about 1.3 per 100,000 children a year. In adults between 1 and 4 per 100,000 are affected a year. It occurs more commonly in the developing world. In children the risk of death is about 6%; however, if they are intubated early it is less than 1%. Signs and symptoms Epiglottitis is associated with fever, throat pain, difficulty in swallowing, drooling, hoarseness of voice, and stridor. Onset is typically over a day. The throat itself may appear normal.Stridor is a sign of upper airways obstruction and is a surgical emergency. The child often appears acutely ill, anxious, and will have very quiet shallow breathing often keeping the head held forward and insisting on sitting up in bed. The early symptoms are usually insidious but rapidly progressive, and swelling of the throat may lead to cyanosis and asphyxiation. Causes Epiglottitis is primarily caused by an acquired bacterial infection of the epiglottis. Historically it was most often caused by Haemophilus influenzae type B, but with the availability of immunization this is no longer the case. Presently the bacteria most often causing infection are Streptococcus pneumoniae, Streptococcus pyogenes, or Staphylococcus aureus.Alternate risk factors and causes associated with infection include burns and other trauma to the area. Medical research has also identified a link between epiglottitis and crack cocaine usage. Underlying health conditions, such as Graft-versus-host disease and Lymphoproliferative disorders, have also been identified as contributors of increased risk for developing the infection . This is in part caused by the hosts decreased immune response coupled with the common sites targeting the soft tissue of the lymphatic system, both of which are already negatively impacted by the pre-existing illnesses. Diagnosis Diagnosis may be confirmed by direct inspection using a laryngoscope, although this may provoke airway spasm. If epiglottitis is suspected, attempts to visualise the epiglottis using a tongue depressor are discouraged for this reason; therefore, diagnosis is made on basis of indirect fiberoptic laryngoscopy carried out in a controlled environment like an operating room. Imaging is rarely useful, and treatment should not be delayed for this test to be carried out. Imaging On lateral C-spine X-ray, the thumbprint sign describes a swollen, enlarged epiglottis. A normal X-ray, however, does not exclude the diagnosis. An ultrasound may be helpful if specific changes are present, but its use (as of 2018) is in the early stages of study.On CT imaging, the "Halloween sign" describes an epiglottis of normal thickness. It can safely exclude the acute epiglottitis. Furthermore, CT imaging can help to diagnose other conditions such as peritonsillar abscess or retropharyngeal abscess which have similar clinical features. Prevention An effective vaccine, the Hib vaccine, has been available since the 1980s. The antibiotic rifampicin may also be used to prevent the disease among those who have been exposed to the disease and are at high risk. Management Airway management The most important part of treatment involves securing the airway. Epiglottitis may require urgent tracheal intubation to protect the airway. Tracheal intubation can be difficult due to distorted anatomy and profuse secretions. Spontaneous respiration is ideally maintained until tracheal intubation is successful. A surgical airway opening (cricothyrotomy) may be required if intubation is not possible. Medication Intravenous antibiotics such as ceftriaxone and possibly vancomycin or clindamycin is then given. If allergy to penicillins is present, trimethoprim/sulfamethoxazole or clindamycin may be an alternative. Nebulized epinephrine may be useful to improve the situation temporarily. Corticosteroids are also typically used. Evidence for benefit, however, is poor. Prognosis With appropriate treatment, the risk of death among children with the condition is about one percent and among adults is seven percent.Some people may develop pneumonia, lymphadenopathy, or septic arthritis. Epidemiology While, historically, young children were mostly affected, it is now more common among older children and adults. Before Hemophilus influenzae (Hib) immunization children of two to four were most commonly affected. With immunization about 1.3 per 100,000 children are affected a year. Notable cases Bill Bixbys 6-year-old son Christopher died of the condition in 1981.Jeannie Mai spent some time in an ICU with epiglottitis.Sarah Silverman spent a week in the ICU at Cedars Sinai Hospital with epiglottitis.George Washington is thought to have died of epiglottitis. The treatments given to George Washington, such as severe bloodletting, an enema, vinegar, sage, molasses, butter, blistering his throat with Spanish fly, requiring him to swallow mercurous chloride and antimony potassium tartrate, and applying wheat poultices to various parts of the body, are no longer used. References External links Medscape

Leptospirosis

Leptospirosis is a blood infection caused by the bacteria Leptospira. Signs and symptoms can range from none to mild (headaches, muscle pains, and fevers) to severe (bleeding in the lungs or meningitis). Weils disease, the acute, severe form of leptospirosis, causes the infected individual to become jaundiced (skin and eyes become yellow), develop kidney failure, and bleed. Bleeding from the lungs associated with leptospirosis is known as severe pulmonary haemorrhage syndrome.More than ten genetic types of Leptospira cause disease in humans. Both wild and domestic animals can spread the disease, most commonly rodents. The bacteria are spread to humans through animal urine, or water and soil contaminated with animal urine, coming into contact with the eyes, mouth, nose or breaks in the skin. In developing countries, the disease occurs most commonly in farmers and low-income people who live in areas with poor sanitation. In developed countries, it occurs during heavy downpours and is a risk to sewage workers and those involved in outdoor activities in warm and wet areas. Diagnosis is typically by testing for antibodies against the bacteria or finding bacterial DNA in the blood.Efforts to prevent the disease include protective equipment to block contact when working with potentially infected animals, washing after contact, and reducing rodents in areas where people live and work. The antibiotic doxycycline is effective in preventing leptospirosis infection. Human vaccines are of limited usefulness; vaccines for other animals are more widely available. Treatment when infected is with antibiotics such as doxycycline, penicillin, or ceftriaxone. The overall risk of death is 5–10%. However, when the lungs are involved, the risk of death increases to the range of 50–70%.It is estimated that one million severe cases of leptospirosis occur every year, causing about 58,900 deaths. The disease is most common in tropical areas of the world but may occur anywhere. Outbreaks may arise after heavy rainfall. The disease was first described by physician Adolf Weil in 1886 in Germany. Infected animals may have no, mild or severe symptoms. These may vary by the type of animal. In some animals Leptospira live in the reproductive tract, leading to transmission during mating. Signs and symptoms The symptoms of leptospirosis usually appear one to two weeks after infection, but the incubation period can be as long as a month. The illness is biphasic in a majority of symptomatic cases. Symptoms of the first phase (acute or leptospiremic phase) last five to seven days. In the second phase (immune phase), the symptoms resolve as antibodies against the bacteria are produced. Additional symptoms develop in the second phase. The phases of illness may not be distinct, especially in patients with severe illness. 90% of those infected experience mild symptoms while 10% experience severe leptospirosis.Leptospiral infection in humans causes a range of symptoms, though some infected persons may have none. The disease begins suddenly with fever accompanied by chills, intense headache, severe muscle aches and abdominal pain. A headache brought on by leptospirosis causes throbbing pain and is characteristically located at the heads bilateral temporal or frontal regions. The person could also have pain behind the eyes and a sensitivity to light. Muscle pain usually involves the calf muscle and the lower back. The most characteristic feature of leptospirosis is the conjunctival suffusion (conjunctivitis without exudate) which is rarely found in other febrile illnesses. Other characteristic findings on the eye include subconjunctival bleeding and jaundice. A rash is rarely found in leptospirosis. When one is found alternative diagnoses such as dengue fever and chikungunya fever should be considered. Dry cough is observed in 20–57% of people with leptospirosis. Thus, this clinical feature can mislead a doctor to diagnose the disease as a respiratory illness. Additionally, gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhoea frequently occur. Vomiting and diarrhea may contribute to dehydration. The abdominal pain can be due to acalculous cholecystitis or inflammation of the pancreas. Rarely, the lymph nodes, liver, and spleen may be enlarged and palpable.There will be a resolution of symptoms for one to three days. The immune phase starts after this and can last from four to 30 days and can be anything from brain to kidney complications. The hallmark of the second phase is inflammation of the membranes covering the brain. Signs and symptoms of meningitis include severe headache and neck stiffness. Kidney involvement is associated with reduced or absent urine output.The classic form of severe leptospirosis, known as Weils disease, is characterised by liver damage (causing jaundice), kidney failure, and bleeding, which happens in 5–10% of those infected. Lung and brain damage can also occur. For those with signs of inflammation of membranes covering the brain and the brain itself, altered level of consciousness can happen. A variety of neurological problems such as paralysis of half of the body, complete inflammation of a whole horizontal section of spinal cord, and muscle weakness due to immune damage of the nerves supplying the muscles are the complications. Signs of bleeding such as non-traumatic bruises at 1 mm (0.039 in), non-traumatic bruises more than 1 cm (0.39 in), nose bleeding, blackish stools due to bleeding in the stomach, vomiting blood and bleeding from the lungs can also be found. Prolongation of prothrombin time in coagulation testing is associated with severe bleeding manifestation. However, low platelet count is not associated with severe bleeding. Pulmonary haemorrhage is alveolar haemorrhage (bleeding into the alveoli of the lungs) leading to massive coughing up of blood, and causing acute respiratory distress syndrome, where the risk of death is more than 50%. Rarely, inflammation of the heart muscles, inflammation of membranes covering the heart, abnormalities in the hearts natural pacemaker and abnormal heart rhythms may occur. Cause Bacteria Leptospirosis is caused by spirochaete bacteria that belong to the genus Leptospira, which are aerobic, right-handed helical, and 6–20 micrometers long. Like Gram-negative bacteria, Leptospira have an outer membrane studded with lipopolysaccharide (LPS) on the surface, an inner membrane and a layer of peptidoglycan cell wall. However, unlike Gram-negative bacteria, the peptidoglycan layer in Leptospira lies closer to the inner than the outer membrane. This results in a fluid outer membrane loosely associated with the cell wall. In addition, Leptospira have a flagellum located in the periplasm, associated with corkscrew style movement. Chemoreceptors at the poles of the bacteria sense various substrates and change the direction of its movement. The bacteria are traditionally visualised using dark-field microscopy without staining.A total of 66 species of Leptospira has been identified. Based on their genomic sequence, they are divided into two clades and four subclades: P1, P2, S1, and S2. The 19 members of the P1 subclade include the 8 species that can cause severe disease in humans: L. alexanderi, L. borgpetersenii, L. interrogans, L. kirschneri, L. mayottensis, L. noguchii, L. santarosai, and L. weilii. The P2 clade comprises 21 species that may cause mild disease in humans. The remaining 26 species comprise the S1 and S2 subclades, which include "saprophytes" known to consume decaying matter (saprotrophic nutrition). Pathogenic Leptospira do not multiply in the environment. Leptospira require high humidity for survival but can remain alive in environments such as stagnant water or contaminated soil. The bacterium can be killed by temperatures of 50 °C (122 °F) and can be inactivated by 70% ethanol, 1% sodium hypochlorite, formaldehyde, detergents and acids.Leptospira are also classified based on their serovar. The diverse sugar composition of the lipopolysaccharide on the surface of the bacteria is responsible for the antigenic difference between serovars. About 300 pathogenic serovars of Leptospira are recognised. Antigenically related serovars (belonging to the same serogroup) may belong to different species because of horizontal gene transfer of LPS biosynthetic genes between different species. Currently, the cross agglutination absorption test and DNA-DNA hybridisation are used to classify Leptospira species, but are time consuming. Therefore, total genomic sequencing could potentially replace these two methods as the new gold standard of classifying Leptospira species. Transmission The bacteria can be found in ponds, rivers, puddles, sewers, agricultural fields and moist soil. Pathogenic Leptospira have been found in the form of aquatic biofilms, which may aid survival in the environment.The number of cases of leptospirosis is directly related to the amount of rainfall, making the disease seasonal in temperate climates and year-round in tropical climates. The risk of contracting leptospirosis depends upon the risk of disease carriage in the community and the frequency of exposure. In rural areas, farming and animal husbandry are the major risk factors for contracting leptospirosis. Poor housing and inadequate sanitation also increase the risk of infection. In tropical and semi-tropical areas, the disease often becomes widespread after heavy rains or after flooding.Leptospira are found mostly in mammals. However, reptiles and cold-blooded animals such as frogs, snakes, turtles, and toads have been shown to have the infection. Whether there are reservoirs of human infection is unknown. Rats, mice, and moles are important primary hosts, but other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, swine, raccoons, opossums, and skunks can also carry the disease. In Africa, a number of wildlife hosts have been identified as carriers, including the banded mongoose, Egyptian fox, Rusa deer, and shrews. There are various mechanisms whereby animals can infect each other. Dogs may lick the urine of an infected animal off the grass or soil, or drink from an infected puddle. House-bound domestic dogs have contracted leptospirosis, apparently from licking the urine of infected mice in the house. Leptospirosis can also be transmitted via the semen of infected animals. The duration of bacteria being consistently present in animal urine may persist for years.Humans are the accidental host of Leptospira. Humans become infected through contact with water or moist soil that contains urine from infected animals. The bacteria enter through cuts, abrasions, ingestion of contaminated food, or contact with mucous membrane of the body (e.g. mouth, nose, and eyes). Occupations at risk of contracting leptospirosis include farmers, fishermen, garbage collectors and sewage workers. The disease is also related to adventure tourism and recreational activities. It is common among water-sports enthusiasts in specific areas, including triathlons, water rafting, canoeing and swimming, as prolonged immersion in water promotes the entry of the bacteria. However, Leptospira are unlikely to penetrate intact skin. The disease is not known to spread between humans, and bacterial dissemination in recovery period is extremely rare in humans. Once humans are infected, bacterial shedding from the kidneys usually persists for up to 60 days.Rarely, leptospirosis can be transmitted through an organ transplant. Infection through the placenta during pregnancy is also possible. It can cause miscarriage and infection in infants. Leptospirosis transmission through eating raw meat of wildlife animals have also been reported (e.g. psychiatric patients with allotriophagy). Pathogenesis When animals ingest the bacteria, they circulate in the bloodstream, then lodge themselves into the kidneys through the glomerulular or peritubular capillaries. The bacteria then pass into the lumens of the renal tubules and colonise the brush border and proximal convoluted tubule. This causes the continuous shedding of bacteria in the urine without the animal experiencing significant ill effects. This relationship between the animal and the bacteria is known as a commensal relationship, and the animal is known as a reservoir host.Humans are the accidental host of Leptospira. The pathogenesis of leptospirosis remains poorly understood despite research efforts. The bacteria enter the human body through either breaches in the skin or the mucous membrane, then into the bloodstream. The bacteria later attach to the endothelial cells of the blood vessels and extracellular matrix (complex network of proteins and carbohydrates present between cells). The bacteria use their flagella for moving between cell layers. They bind to cells such as fibroblasts, macrophages, endothelial cells, and kidney epithelial cells. They also bind to several human proteins such as complement proteins, thrombin, fibrinogen, and plasminogen using surface leptospiral immunoglobulin-like (Lig) proteins such as LigB and LipL32, whose genes are found in all pathogenic species.Through innate immune system, endothelial cells of the capillaries in the human body are activated by the presence of these bacteria. The endothelial cells produce cytokines and antimicrobial peptides against the bacteria. These products regulate the coagulation cascade and movements of white blood cells. Macrophages presented in humans are able to engulf Leptospira. However, Leptospira are able to reside and proliferate in the cytoplasmic matrix after being ingested by macrophages. Those with severe leptospirosis can experience a high level of cytokines such as interleukin 6, tumor necrosis factor alpha (TNF-α), and interleukin 10. The high level of cytokines causes sepsis-like symptoms which is life-threatening instead of helping to fight against the infection. Those who have a high risk of sepsis during a leptospirosis infection are found to have the HLA-DQ6 genotype, possibly due to superantigen activation, which damages bodily organs.Leptospira LPS only activates toll-like receptor 2 (TLR2) in monocytes in humans. The lipid A molecule of the bacteria is not recognised by human TLR4 receptors. Therefore, the lack of Leptospira recognition by TLR4 receptors probably contributes to the leptospirosis disease process in humans.Although there are various mechanisms in the human body to fight against the bacteria, Leptospira is well adapted to such an inflammatory condition created by it. In the bloodstream, it can activate host plasminogen to become plasmin that breaks down extracellular matrix, degrades fibrin clots and complemental proteins (C3b and C5) to avoid opsonisation. It can also recruit complement regulators such as Factor H, C4b-binding protein, factor H-like binding protein, and vitronectin to prevent the activation of membrane attack complex on its surface. It also secretes proteases to degrade complement proteins such as C3. It can bind to thrombin that decreases the fibrin formation. Reduced fibrin formation increases the risk of bleeding. Leptospira also secretes sphingomyelinase and haemolysin that target red blood cells.Leptospira spreads rapidly to all organs through the bloodstream. They mainly affect the liver. They invade spaces between hepatocytes, causing apoptosis. The damaged hepatocytes and hepatocyte intercellular junctions cause leakage of bile into the bloodstream, causing elevated levels of bilirubin, resulting in jaundice. Congested liver sinusoids and perisinusoidal spaces have been reported. Meanwhile, in the lungs, petechiae or frank bleeding can be found at the alveolar septum and spaces between alveoli. Leptospira secretes toxins that cause mild to severe kidney failure or interstitial nephritis. The kidney failure can recover completely or lead to atrophy and fibrosis. Rarely, inflammation of the heart muscles, coronary arteries, and aorta are found. Diagnosis Laboratory tests For those who are infected, a complete blood count may show a high white cell count and a low platelet count. When a low haemoglobin count is present together with a low white cell count and thrombocytopenia, bone marrow suppression should be considered. Erythrocyte sedimentation rate and C-reactive protein may also be elevated.The kidneys are commonly involved in leptospirosis. Blood urea and creatinine levels will be elevated. Leptospirosis increases potassium excretion in urine, which leads to a low potassium level and a low sodium level in the blood. Urinalysis may reveal the presence of protein, white blood cells, and microscopic haematuria. Because the bacteria settle in the kidneys, urine cultures will be positive for leptospirosis starting after the second week of illness until 30 days of infection.For those with liver involvement, transaminases and direct bilirubin are elevated in liver function tests. The Icterohaemorrhagiae serogroup is associated with jaundice and elevated bilirubin levels. Hemolytic anemia contributes to jaundice. A feature of leptospirosis is acute haemolytic anaemia and conjugated hyperbilirubinemia, especially in patients with glucose-6-phosphate dehydrogenase deficiency. Abnormal serum amylase and lipase levels (associated with pancreatitis) are found in those who are admitted to hospital due to leptospirosis. Impaired kidney function with creatinine clearance less than 50 ml/min is associated with elevated pancreatic enzymes.For those with severe headache who show signs of meningitis, a lumbar puncture can be attempted. If infected, cerebrospinal fluid (CSF) examination shows lymphocytic predominance with a cell count of about 500/mm3, protein between 50 and 100 mg/ml and normal glucose levels. These findings are consistent with aseptic meningitis. Serological tests Rapid detection of Leptospira can be done by quantifying the IgM antibodies using ELISA. Typically, L. biflexa antigen is used to detect the IgM antibodies. This test can quickly determine the diagnosis and help in early treatment. However, the test specificity depends upon the type of antigen used and the presence of antibodies from previous infections. The presence of other diseases such as Epstein–Barr virus infection, viral hepatitis, and cytomegalovirus infection can cause false-positive results. Other rapid screening tests have been developed such as dipsticks, latex and slide agglutination tests.The microscopic agglutination test (MAT) is the reference test for the diagnosis of leptospirosis. MAT is a test where serial dilutions of patient sera are mixed with different serovars of Leptospira. The mixture is then examined under a dark field microscope to look for agglutination. The highest dilution where 50% agglutination occurs is the result. MAT titres of 1:100 to 1:800 are diagnostic of leptospirosis. A fourfold or greater rise in titre of two sera taken at symptoms onset and three to 10 days of disease onset confirms the diagnosis. During the acute phase of the disease, MAT is not specific in detecting a serotype of Leptospira because of cross-reactivity between the serovars. In the convalescent phase, MAT is more specific in detecting the serovar types. MAT requires a panel of live antigens and requires laborious work. Molecular tests Leptospiral DNA can be amplified by using polymerase chain reaction (PCR) from serum, urine, aqueous humour, CSF, and autopsy specimens. It detects the presence of bacteria faster than MAT during the first few days of infection without waiting for the appearance of antibodies. As PCR detects the presence of leptospiral DNA in the blood it is useful even when the bacteria is killed by antibiotics. Imaging In those who have lung involvement, a chest X-ray may demonstrate diffuse alveolar opacities. Diagnostic criteria In 1982, the World Health Organization (WHO) proposed the Faines criteria for the diagnosis of leptospirosis. It consists of three parts: A (clinical findings), B (epidemiological factors), and C (lab findings and bacteriological data). Since the original Faines criteria only included culture and MAT in part C, which is difficult and complex to perform, the modified Faines criteria was proposed in 2004 to include ELISA and slide agglutination tests which are easier to perform. In 2012, modified Faines criteria (with amendment) was proposed to include shortness of breath and coughing up blood in the diagnosis. In 2013, India recommended modified Faines criteria in the diagnosis of leptospirosis. Prevention Rates of leptospirosis can be reduced by improving housing, infrastructure, and sanitation standards. Rodent abatement efforts and flood mitigation projects can also help to prevent it. Proper use of personal protective equipment (PPE) by people who have a high risk of occupational exposure can prevent leptospirosis infections in most cases.There is no human vaccine suitable for worldwide use. Only a few countries such as Cuba, Japan, France, and China have approved the use of inactivated vaccines with limited protective effects. Side effects such as nausea, injection site redness and swelling have been reported after the vaccine was injected. Since the immunity induced by one Leptospiraserovar is only protective against that specific one, trivalent vaccines have been developed. However, they do not confer long-lasting immunity to humans or animals. Vaccines for other animals are more widely available.Doxycycline is given once a week as a prophylaxis and is effective in reducing the rate of leptospirosis infections amongst high-risk individuals in flood-prone areas. In one study, it reduced the number of leptospirosis cases in military personnel undergoing exercises in the jungles. In another study, it reduced the number of symptomatic cases after exposure to leptospirosis under heavy rainfall in endemic areas. Treatment Most leptospiral cases resolve spontaneously. Early initiation of antibiotics may prevent the progression to severe disease. Therefore, in resource-limited settings, antibiotics can be started once leptospirosis is suspected after history taking and examination.For mild leptospirosis, antibiotic recommendations such as doxycycline, azithromycin, ampicillin and amoxicillin were based solely on in vitro testing. In 2001, the WHO recommended oral doxycycline (2 mg/kg up to 100 mg every 12 hours) for five to seven days for those with mild leptospirosis. Tetracycline, ampicillin, and amoxicillin can also be used in such cases. However, in areas where rickettsia and leptospirosis are both endemic, azithromycin and doxycycline are the drugs of choice.Based on a 1988 study, intravenous (IV) benzylpenicillin (also known as penicillin G) is recommended for the treatment of severe leptospirosis. Intravenous benzylpenicillin (30 mg/kg up to 1.2 g every six hours) is used for five to seven days. Amoxicillin, ampicillin, and erythromycin may also be used for severe cases. Ceftriaxone (1 g IV every 24 hours for seven days) is also effective for severe leptospirosis. Cefotaxime (1 g IV every six hours for seven days) and doxycycline (200 mg initially followed by 100 mg IV every 12 hours for seven days) are equally effective as benzylpenicillin (1.5 million units IV every six hours for seven days). Therefore, there is no evidence on differences in death reduction when benzylpenicillin is compared with ceftriaxone or cefotaxime. Another study conducted in 2007 also showed no difference in efficacy between doxycycline (200 mg initially followed by 100 mg orally every 12 hours for seven days) or azithromycin (2 g on day one followed by 1 g daily for two more days) for suspected leptospirosis. There was no difference in the resolution of fever and azithromycin is better tolerated than doxycycline.Outpatients are given doxycycline or azithromycin. Doxycycline can shorten the duration of leptospirosis by two days, improve symptoms, and prevent the shedding of organisms in their urine. Azithromycin and amoxicillin are given to pregnant women and children. Rarely, a Jarisch–Herxheimer reaction can develop in the first few hours after antibiotic administration. However, according to a meta-analysis done in 2012, the benefit of antibiotics in the treatment of leptospirosis was unclear although the use of antibiotics may reduce the duration of illness by two to four days. Another meta-analysis done in 2013 reached a similar conclusion.For those with severe leptospirosis, including potassium wasting with high kidney output dysfunction, intravenous hydration and potassium supplements can prevent dehydration and hypokalemia. When acute kidney failure occurs, early initiation of haemodialysis or peritoneal dialysis can help to improve survival. For those with respiratory failure, tracheal intubation with low tidal volume improves survival rates.Corticosteroids have been proposed to suppress inflammation in leptospirosis because Leptospira infection can induce the release of chemical signals which promote inflammation of blood vessels in the lungs. However, there is insufficient evidence to determine whether the use of corticosteroids is beneficial. Prognosis The overall risk of death for leptospirosis is 5–10%. For those with jaundice, the case fatality can increase up to 15%. For those infected who present with confusion and neurological signs, there is a high risk of death. Other factors that increase the risk of death include reduced urine output, age more than 36 years, and respiratory failure. With proper care, most of those infected will recover completely. Those with acute kidney failure may develop persistent mild kidney impairment after they recover. In those with severe lung involvement, the risk of death is 50–70%. Thirty percent of people with acute leptospirosis complained of long-lasting symptoms characterised by weakness, muscle pain, and headaches. Eye complications Eye problems can occur in 10% of those who recovered from leptospirosis in the range from two weeks to a few years post-infection. Most commonly, eye complications can occur at six months after the infection. This is due to the immune privilege of the eye which protects it from immunological damage during the initial phase of leptospiral infection. These complications can range from mild anterior uveitis to severe panuveitis (which involves all three vascular layers of the eye). The uveitis is more commonly happen in young to a middle-aged man and those working in agricultural farming. In up to 80% of those infected, Leptospira DNA can be found in the aqueous humour of the eye. Eye problems usually have a good prognosis following treatment or they are self-limiting. In anterior uveitis, only topical steroids and mydriatics (an agent that causes dilation of the pupil) are needed while in panuveitis, it requires periocular corticosteroids. Leptospiral uveitis is characterised by hypopyon, rapidly maturing cataract, free floating vitreous membranes, disc hyperemia and retinal vasculitis. Epidemiology It is estimated that one million severe cases of leptospirosis occur annually, with 58,900 deaths. Severe cases account for 5–15% of all leptospirosis cases. Leptospirosis is found in both urban and rural areas in tropical, subtropical, and temperate regions. The global health burden for leptospirosis can be measured by disability-adjusted life year (DALY). The score is 42 per 100,000 people per year, which is more than other diseases such as rabies and filariasis.The disease is observed persistently in parts of Asia, Oceania, the Caribbean, Latin America and Africa. Antarctica is the only place not affected by leptospirosis. In the United States, there were 100 to 150 leptospirosis cases annually. In 1994, leptospirosis ceased to be a notifiable disease in the United States except in 36 states/territories where it is prevalent such as Hawaii, Texas, California, and Puerto Rico. About 50% of the reported cases occurred in Puerto Rico. In January 2013, leptospirosis was reinstated as a nationally notifiable disease in the United States. Research on epidemiology of leptospirosis in high-risk groups and risk factors is limited in India.The global rates of leptospirosis have been underestimated because most affected countries lack notification or notification is not mandatory. Distinguishing clinical signs of leptospirosis from other diseases and lack of laboratory diagnostic services are other problems. The socioeconomic status of many of the worlds population is closely tied to malnutrition; subsequent lack of micronutrients may lead to increased risk of infection and death due to leptospirosis infection. Micronutrients such as iron, calcium, and magnesium represent important areas for future research. History The disease was first described by Adolf Weil in 1886 when he reported an "acute infectious disease with enlargement of spleen, jaundice, and nephritis." Before Weils description, the disease was known as "rice field jaundice" in ancient Chinese text, "autumn fever", "seven-day fever", and "nanukayami fever" in Japan; in Europe and Australia, the disease was associated with certain occupations and given names such as "cane-cutters disease", "swine-herds disease", and "Schlammfieber" (mud fever). It has been known historically as "black jaundice", or "dairy farm fever" in New Zealand. Leptospirosis was postulated as the cause of an epidemic among Native Americans along the coast of what is now New England during 1616–19. The disease was most likely brought to the New World by Europeans.Leptospira was first observed in 1907 in a post mortem kidney tissue slice by Arthur Stimson using silver deposition staining technique. He called the organism Spirocheta interrogans because the bacteria resembled a question mark. In 1908, a Japanese research group led by Ryukichi Inada and Yutaka Ito first identified this bacterium as the causative agent of leptospirosis and noted its presence in rats in 1916. Japanese coal mine workers frequently contracted leptospirosis. In Japan, the organism was named Spirocheta icterohaemorrhagiae. The Japanese group also experimented with the first leptospiral immunisation studies in guinea pigs. They demonstrated that by injecting the infected guinea pigs with sera from convalescent humans or goats, passive immunity could be provided to the guinea pigs. In 1917, the Japanese group discovered rats as the carriers of leptospirosis. Unaware of the Japanese groups work, two German groups independently and almost simultaneously published their first demonstration of transmitting leptospiral infection in guinea pigs in October 1915. They named the organism Spirochaeta nodosa and Spirochaeta Icterogenes respectively.Leptospirosis was subsequently recognised as a disease of all mammalian species. In 1933, Dutch workers reported the isolation of Leptospira canicola which specifically infects dogs. In 1940, the strain that specifically infects cattle was first reported in Russia. In 1942, soldiers at Fort Bragg, North Carolina, were recorded to have an infectious disease which caused a rash over their shinbones. This disease was later known to be caused by leptospirosis. By the 1950s, the number of serovars that infected various mammals had expanded significantly. In the 1980s, leptospirosis was recognised as a veterinary disease of major economic importance.In 1982, there were about 200 serovars of Leptospira available for classification. The International Committee on Systematic Bacteriologys subcommittee on taxonomy of Leptospira proposed classifying these serovars into two big groups: L. interrogans containing pathogenic serovars and L. biflexa containing saprophytic serovars. In 1979, the leptospiral family of Leptospiraceae was proposed. In the same year, Leptospira illini was reclassified as the new genus Leptonema. In 2002, "Lepthangamushi syndrome" was coined to describe a series of overlapping symptoms of leptospirosis with Hantavirus hemorrhagic fever with renal syndrome, and scrub typhus caused by Orientia tsutsugamushi. In 2005, Leptospira parva was classified as Turneriella. With DNA-DNA hybridisation technology, L. interrogans was divided into seven species. More Leptospira species have been discovered since then. The WHO established the Leptospirosis Burden Epidemiology Reference Group (LERG) to review the latest disease epidemiological data of leptospirosis, formulate a disease transmission model, and identify gaps in knowledge and research. The first meeting was convened in 2009. In 2011, LERG estimated that the global yearly rate of leptospirosis is five to 14 cases per 100,000 population. Other animals Infected animals can have no, mild, or severe symptoms; the presenting symptoms may vary by the type of animal. In some animals the bacteria live in the reproductive tract, leading to transmission during mating.Animals also present with similar clinical features when compared to humans. Clinical signs can appear in 5–15 days in dogs. The incubation period can be prolonged in cats. Leptospirosis can cause abortions after 2–12 weeks in cattle, and 1–4 weeks of infection in pigs. The illness tends to be milder in reservoir hosts. The most commonly affected organs are the kidneys, liver, and reproductive system, but other organs can be affected. In dogs, the acute clinical signs include fever, loss of appetite, shivering, muscle pain, weakness, and urinary symptoms. Vomiting, diarrhea, and abdominal pain may also present. Petechiae and ecchymoses may be seen on mucous membranes. Bleeding from the lungs may also be seen in dogs. In chronic presentations, the affected dog may have no symptoms. In animals that have died of leptospirosis, their kidneys may be swollen with grey and white spots, mottling, or scarring. Their liver may be enlarged with areas of cell death. Petechiae and ecchymoses may be found in various organs. Inflammation of the blood vessels, inflammation of the heart, meningeal layers covering the brain and spinal cord, and uveitis are also possible. Equine recurrent uveitis (ERU) is the most common disease associated with Leptospira infection in horses in North America and may lead to blindness. ERU is an autoimmune disease involving antibodies against Leptospira proteins LruA and LruB cross-reacting with eye proteins. Live Leptospira can be recovered from the aqueous or vitreous fluid of many horses with Leptospira-associated ERU. Risk of death or disability in infected animals varies depending upon the species and age of the animals. In adult pigs and cattle, reproductive signs are the most common signs of leptospirosis. Up to 40% of cows may have a spontaneous abortion. Younger animals usually develop more severe disease. About 80% of dogs can survive with treatment, but the survival rate is reduced if the lungs are involved.ELISA and microscopic agglutination tests are most commonly used to diagnose leptospirosis in animals. The bacteria can be detected in blood, urine, and milk or liver, kidney, or other tissue samples by using immunofluorescence or immunohistochemical or polymerase chain reaction techniques. Silver staining or immunogold silver staining is used to detect Leptospira in tissue sections. The organisms stain poorly with Gram stain. Dark-field microscopy can be used to detect Leptospira in body fluids, but it is neither sensitive nor specific in detecting the organism. A positive culture for leptospirosis is definitive, but the availability is limited, and culture results can take 13–26 weeks for a result, limiting its utility. Paired acute and convalescent samples are preferred for serological diagnosis of leptospirosis in animals. A positive serological sample from an aborted fetus is also diagnostic of leptospirosis.Various antibiotics such as doxycycline, penicillins, dihydrostreptomycin, and streptomycin have been used to treat leptospirosis in animals. Fluid therapy, blood transfusion, and respiratory support may be required in severe disease. For horses with ERU, the primary treatment is with anti-inflammatory drugs.Leptospirosis vaccines are available for animals such as pigs, dogs, cattle, sheep, and goats. Vaccines for cattle usually contain Leptospira serovar Hardjo and Pomona, for dogs, the vaccines usually contain serovar Icterohaemorrhagiae and Canicola. Vaccines containing multiple serovars do not work for cattle as well as vaccines containing a single serovar, yet the multivalent vaccines continue to be sold. Isolation of infected animals and prophylactic antibiotics are also effective in preventing leptospirosis transmission between animals. Environmental control and sanitation also reduce transmission rates. References This article was submitted to WikiJournal of Medicine for external academic peer review in 2019 (reviewer reports). The updated content was reintegrated into the Wikipedia page under a CC-BY-SA-3.0 license (2022). The version of record as reviewed is: Siang Ching Raymond Chieng; et al. (21 June 2022). "Leptospirosis". WikiJournal of Medicine. 9 (1): 2. doi:10.15347/WJM/2022.002. ISSN 2002-4436. Wikidata Q100400590. External links "Leptospirosis". U.S. Disease Control and Prevention Center. 21 November 2018. "Leptospira". NCBI Taxonomy Browser. 171.

Hereditary spherocytosis

Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (spherocytosis), rather than the normal biconcave disk-shaped, their morphology interferes with these cells abilities to be flexible during circulation throughout the entirety of the body - arteries, arterioles, capillaries, venules, veins, and organs. This difference in shape also makes the red blood cells more prone to rupture under osmotic and/or mechanical stress. Cells with these dysfunctional proteins are degraded in the spleen, which leads to a shortage of erythrocytes resulting in hemolytic anemia. HS was first described in 1871, and is the most common cause of inherited hemolysis in populations of northern European descent, with an incidence of 1 in 5000 births. The clinical severity of HS varies from mild (symptom-free carrier), to moderate (anemic, jaundiced, and with splenomegaly), to severe (hemolytic crisis, in-utero hydrops fetalis), because HS is caused by genetic mutations in a multitude of structural membrane proteins and exhibits incomplete penetrance in its expression.Early symptoms include anemia, jaundice, splenomegaly, and fatigue. Acute cases can threaten to cause hypoxia secondary to anemia and acute kernicterus through high blood levels of bilirubin, particularly in newborns. Most cases can be detected soon after birth. Testing for HS is available for the children of affected adults. Occasionally, the disease will go unnoticed until the child is about 4 or 5 years of age. A person may also be a carrier of the disease and show no signs or symptoms of the disease. Late complications may result in the development of pigmented gallstones, which is secondary to the detritus of the broken-down blood cells (unconjugated or indirect bilirubin) accumulating within the gallbladder. Also, patients who are heterozygous for a hemochromatosis gene may exhibit iron overload, despite the hemochromatosis genes being recessive. In chronic patients, an infection or other illness can cause an increase in the destruction of red blood cells, resulting in the appearance of acute symptoms, a hemolytic crisis. On a blood smear, Howell-Jolly bodies may be seen within red blood cells. Primary treatment for patients with symptomatic HS has been total splenectomy, which eliminates the hemolytic process, allowing normal hemoglobin, reticulocyte and bilirubin levels. The resultant asplenic patient is susceptible to encapsulated bacterial infection, and prevented with vaccination. If other symptoms, such as abdominal pain persist, the removal of the gallbladder may be warranted for symptomatic cholelithiasis. Epidemiology Hereditary spherocytosis is the heritable hemolytic disorder, affecting 1 in 2,000 people of Northern European ancestry. According to Harrisons Principles of Internal Medicine, the frequency is at least 1 in 5,000 within the United States of America. While HS is most commonly (though not exclusively) found in Northern European and Japanese families, an estimated 25% of cases are due to spontaneous mutations. Etiology Hereditary spherocytosis is an erythrocytic disorder of that affects the following red cell membrane proteins in a congenital fashion: Spectrin (alpha and beta) Ankyrin Band-3 Protein Protein-4.2 Lesser proteins of significanceHereditary spherocytosis can be an autosomal recessive or autosomal dominant trait. The autosomal recessive inheritance pattern accounts for close to 25% of the clinical cases. The autosomal dominant inheritance patter accounts for over 75% of the clinical cases. Many positive individuals will not present clinically, thus the etiologic data may be artificially skewed towards the more prominent dominant forms. These dominant forms tend to leave a family history that yields generational splenectomies and black gallstones cholelithiasis. Lastly, an estimated 25% of cases are due to spontaneous mutations. Pathophysiology Causative Genetic Mutations and Phenotypic Expressions Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for the red blood cell proteins spectrin (alpha and beta), ankyrin, band 3 protein, protein 4.2, and other red blood cell membrane proteins: *Online Mendelian Inheritance in Man (OMIM). The Alpha-1 refers the Alpha-1 Subunit of the Spectrin protein. The Beta refers the Beta Subunit of the Spectrin protein. These genetic mutations are acted upon and executed by erythrocyte progenitor cells within the bone marrow, where red blood cells are normally produced in the non-pathological state (see Extramedullary Hematopoiesis for pathological production outside of the bone marrow). Pathophysiology of Mutated Erythrocytic Membrane Proteins These proteins are necessary to maintain the normal shape of a red blood cell, which is a biconcave disk. The integrating protein that is most commonly defective is spectrin which is responsible for incorporation and binding of spectrin to the greater actin cytoskeleton. This dysfunction of cytoskeletal instabilities ensue, and leave the plasma membrane of the cell less supported and/or weakened. Cellular Implications A secondary defect in hereditary spherocytosis is a deficiency of membrane surface area. The decrease in surface area leads to less efficient gas exchange of the erythrocyte at the alveoli of the lungs and throughout circulation. Decreased surface area may be produced by two different mechanisms: Defects of Spectrin, Ankyrin (most commonly), or Protein 4.2 lead to reduced structural integrity of the plasma membrane, destabilizing the overlying lipid bilayer, and releasing band 3-containing microvesicles. Band-3 is important for gas exchange (as seen above). Defects of band 3 lead to band 3 deficiency and loss of its lipid-stabilizing effect within the plasma membrane lipid bilayer. This results in the release of band 3-free microvesicles.Both pathways result in compromised plasma membrane integrity, decreased surface area, and formation of spherocytes with decreased mechanical compliance during circulation. Cardiovascular and Organ Sequelae Spherocytes have less plasma membrane compliance and fluidity, and this has implications throughout the entirety of circulation within the body, i.e. arteries, arterioles, capillaries, venules, veins, and organs. The lack of compliance and fluidity lead to a higher viscosity value for blood (thickened blood), which can have implications for both larger and smaller diameter vasculature. However, the most pronounced issues with the lack of compliance and fluidity declare themselves in the failure of the erythrocyte to deform itself when transiting arterioles, capillary beds, and venules. These vessels are smaller, and can become congested or blocked altogether. Studies have demonstrated that HS is related to deep vein thrombosis (DVT) and arterial cardiovascular disease for this reason. The spleen typically acts as a filter for blood, and targets pathogens and other damaged cells within circulation. Removing blood contaminants promotes entire-body homeostasis. The following facts about the spleens role in normal body functioning are crucial to understanding the implications of HS on the overall health of the individual: Removal of pathogens includes encapsulated bacteria, which reduces sepsis risk (see Complications below). Removal of damaged erythrocytes reduces iron burden from heme via hepatosplenic recycling, which reduces sepsis risk (see Complications below). Removal of damaged erythrocytes continues healthy signaling to bone marrow, where erythropoiesis replaces red blood cells lost to wear and tear.In relation to the three facts above, the spleen misguidedly filters spherocytes - regardless of the age or functional status of the cell. The spleen is not dysfunctional itself when selecting spherocytes for destruction, as this is the regular function of the spleen both at an anatomic structure level, and at the molecular cellular level. At the anatomic level, the passage from the Cords of Billroth into the Sinusoids may be seen as a "bottleneck", where red blood cells need to be flexible in order to pass through. In HS, the erythrocytes fail to pass through fenestrations, and this is where resident splenic macrophages sample, or "bite," part of the stuck spherocytes plasma membranes. The macrophages recognize that the spherocyte is not normal, and the macrophage is "programmed" to destroy irregularities filtered at the spleen from the blood. The resident splenic macrophages therefore phagocytose the spherocytes, causing extravascular hemolysis. This leads to both splenomegaly and anemia. Should this process continue unchecked chronically, inappropriate regulation of erythropoeisis leads to extramedullary hematopoiesis. Clinical Presentation HS patients present in a vast array of presentations from being asymptomatic, to the extreme situations of splenic rupture and/or hemolytic crisis, or in-utero demise. Asymptomatic HS (mild): 20-30% of patients. Infantile-Onset HS (moderate): 60-75% of patients. Neonatal or In-Utero Onset HS (severe): <5% of patients.The most common presentation will demonstrate jaundice (due to increased unconjugated bilirubin), anemia (with secondary pallor), and a palpable spleen sometimes with concomitant tenderness (due to splenic congestion and splenomegaly). Its worth noting that a subsection of HS patients will also have incidental black pigmented gallstones (made of calcium bilirubinate consequence of the extravascular hemolysis), and some of these patients will develop cholelithiasis and/or the potential complex sequelae of this condition, i.e. cholecystisis, choledocholithiasis, etc. Diagnostics Laboratory Testing Available lab testing that may aid in the diagnosis of HS is as follows: Coombs Test Osmotic Fragility Test Acidified Glycerol Lysis Test Supportive blood work: mean cell volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), red blood cell count (RBC), reticulocytes, unconjugated bilirubin, haptoglobin, lactate dehydrogenase (LDH). Peripheral Blood Smear Eosin-5-maleimide Binding Test Common Laboratory Findings The common findings of lab testing in setting of a patient with hereditary spherocytosis: Coombs Test: Negative (rules-out autoimmune hemolytic anemia) Osmotic Fragility Test: Positive (Spherocytes will rupture in liquid solutions less concentrated than the inside of the red blood cell. This is due to increased permeability of the spherocyte membrane to salt and water, which enters the concentrated inner environment of the RBC and leads to its rupture. Although the osmotic fragility test is no longer considered the gold standard for diagnosing hereditary spherocytosis, as it misses ~25% of cases). Acidified Glycerol Lysis Test: Positive (A newer version of the osmotic fragility test that adds glycerol to a hypotonic solution. This produces lysis, a positive test, quicker that the traditional saline version). Supportive blood work: Mean Cell Volume (MCV): Normocytic (normal range: 80-100fL), or slightly lower. Spherocytes are slightly smaller than normal biconcave red blood cells. Mean Corpuscular Hemoglobin Concentration (MCHC): Increased (normal range: 31-36% Hb/cell). This is secondary to less water being in the cell. Red Blood Cell Distribution Width (RDW): Increased (normal range: 11-15%). The spherocytes create variation in the size of the red blood cells on average, thus expanding the distribution. Red Blood Cell Count (RBC): Sometimes Increased Early (normal range males: 4.3-5.9 million/mm3; normal range females: 3.5-5.5million/mm3). The loss of surface area per cells cause the body to mass produce red blood cells. The spleen will filter spherocytes out and change this value. Reticulocytes: Increased (normal range: 0.5%-1.5% of the RBC listed above). The body to mass produces red blood cells (reticulocytes being young erythrocytes) even as the spleen filters spherocytes out. This is known as reticulocytosis. Unconjugated Bilirubin: Increased (normal range: 0.2-1.2 mg/dL). This is caused by heme released into the hepatosplenic circulation by macrophages that have phagocytosed erythrocytes. The unconjugated bilirubin is not soluble in water (blood), so it binds to albumin, and is processed in the liver. Haptoglobin (Free): Decreased (normal range: 41–165 mg/dL). This is caused by hemoglobin binding to haptoglobin, thus making it no longer "free." lactate dehydrogenase (LDH): Increased (Normal range: 110-295U/L in children). This is due to extravascular hemolysis. Peripheral Blood Smear: Directly shows spherocytes on microscope. Eosin-5-maleimide Binding Test: Positive (reduced mean fluorescence), as the test will demonstrate a reduced ability of the Eosin-5-maleimide dye to bind to erythrocyte plasma membrane proteins. The process relies upon flow cytometry. Gold standard test that produces results at low cost within ~2 hours.In chronic cases, patients who have taken iron supplementation, have heterozygous hemochromatosis, or received numerous blood transfusions, iron overload may cause additional health issues. Measuring iron stores is sometimes considered part of the diagnostic approach to hereditary spherocytosis in older patients presenting with heart muscle damage of unknown etiology or liver disease without apparent cause. Imaging Ultrasound is often used to evaluate the dimensions of the spleen, and also the gallbladder in preparation for functionally curative splenectomy with or without cholecystectomy. Treatment Although research is ongoing, currently there is no genetic-level cure for the myriad of mutations that cause the various presentations of hereditary spherocytosis. Common current management focuses on interventions prevent the body from inappropriately destroying the functional spherocytes produced by erythrocyte progenitor cells within the bone marrow. Typical treatment options include: Splenectomy (operative): This is the operative removal of the entire spleen by a surgeon, thus stopping the extravascular hemolysis, but also removing the immune functions the spleen naturally provide to the body. Partial splenectomy (operative): This is when only a section of the spleen is removed, instead of the entire organ. The goal is to lower the extravascular hemolysis to a level compatible with homeostasis of the patient, while preserving the immune function of the spleens presence. Research on outcomes is currently ongoing, and is routine at childrens hospitals within the United States of America. Splenic ablation (interventional radiology): This option is non-operative, and is when an interventional radiologist (instead of a surgeon) uses radiologic techniques to coil or cauterize vasculature within the splenic circulation. There are various points in the circulatory pathway where the treatment can be applied to produces varying amounts of retained viability of the spleen, thus giving the option to attempt to preserve splenic immune function.All operative and interventional treaments require the immunization of HS patients against the influenza virus, SARS-CoV-2, and encapsulated bacteria such as Streptococcus pneumoniae and meningococcus. Antibiotics are no longer recommended for maintenance use, even in post-splenectomy HS patients. Since the spleen is important for protecting against encapsulated organisms, sepsis caused by encapsulated organisms is a possible complication of splenectomy.Additional elective treatments offered: Surgical removal of the gallbladder.Experimental treatment: Bone marrow transplant (heme-oncology intervention): The replacement of the bone marrow with bone marrow from an individual without spherocytosis. The transplanted progenitor cells do not have the genetic mutations found in individuals with hereditary spherocytosis, and therefore do not produce spherocytes. This results in an individual with biconcave-disc-shaped erythrocytes. This treatment is not standard of care, and is not offered as it has only been documented incidentally during treatment for other diseases, such as myelodysplastic sydnrome.Symptomatic treatments: Folic acid supplementation. Complications Common Complications Hemolytic crisis, with more pronounced jaundice due to accelerated hemolysis (may be precipitated by infection). Aplastic crisis with dramatic fall in hemoglobin level and (reticulocyte count)-decompensation, usually due to maturation arrest and often associated with megaloblastic changes; may be precipitated by infection, such as influenza, notably with parvovirus B19. Folate deficiency caused by increased bone marrow requirement. Pigmented gallstones occur in approximately half of untreated patients. Increased hemolysis of red blood cells leads to increased bilirubin levels, because bilirubin is a breakdown product of heme. The high levels of bilirubin must be excreted into the bile by the liver, which may cause the formation of a pigmented gallstone, which is composed of calcium bilirubinate. Since these stones contain high levels of calcium carbonates and phosphate, they are radiopaque and are visible on x-ray. Hyperglycemia with concomitant low hemoglobin A1C levels. Hemoglobin A1C (glycated hemoglobin) is a test for determining the average blood glucose levels over an extended period of time, and is often used to evaluate glucose control in diabetics. The hemoglobin A1C levels are abnormally low because the life span of the red blood cells is decreased - providing less time for the non-enzymatic glycosylation of hemoglobin. Thus, even with high overall blood sugar, the A1C will be lower than expected. Iron overload. Leg ulcer. Deep vein thrombosis (DVT). Cardiovascular disease. Research Modern ongoing research interests: Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy. Bone marrow transplant. Paradoxical endurance-based athleticism associated with hereditary spherocytosis. Evolution of spherocytic erythrocyte adaptation in those of Northern European and Japanese descent. Increased ability to defend against viral infections in hereditary spherocytosis patients. See also Spherocytosis Anemia Hematology References External links A short article from WebMD A picture of spherocytes from Medline

Kwashiorkor

Kwashiorkor ( KWOSH-ee-OR-kor, -⁠kər, UK also KWASH-) is a form of severe protein malnutrition characterized by edema and an enlarged liver with fatty infiltrates. It is thought to be caused by sufficient calorie intake, but with insufficient protein consumption (or lack of good quality protein), which distinguishes it from marasmus. Recent studies have found that a lack of antioxidant micronutrients such as β-carotene, lycopene, other carotenoids, and vitamin C as well as the presence of aflatoxins may play a role in the development of the disease. However, the exact cause of kwashiorkor is still unknown. Inadequate food supply is correlated with occurrences of kwashiorkor; occurrences in high income countries are rare. It occurs amongst weaning children to ages of about five years old.Conditions analogous to kwashiorkor were well documented around the world throughout history. However, Jamaican pediatrician Cicely Williams introduced the term in 1935, two years after she published the diseases first formal description. Williams was the first to conduct research on kwashiorkor and differentiate it from other dietary deficiencies. She was the first to suggest that this might be a deficiency of protein. The name is derived from the Ga language of coastal Ghana, translated as "the sickness the baby gets when the new baby comes" or "the disease of the deposed child", and reflecting the development of the condition in an older child who has been weaned from the breast when a younger sibling comes. Breast milk contains amino acids vital to a childs growth. In at-risk populations, kwashiorkor may develop after children are weaned from breast milk and begin consuming a diet high in carbohydrates, including maize, cassava or rice. Classification Children with severe malnutrition have an increased risk of serious illness and death. Kwashiorkor is one of the main forms of childhood malnutrition living in low-income and middle-income countries. Kwashiorkor is oftentimes referred to as severe acute malnutrition (SAM). Severe forms of malnutritions are recognized, including stunting, marasmus, and kwashiorkor. Both kwashiorkor and marasmus fall under the umbrella of deficiencies called protein–energy malnutrition (PEM). These diseases are oftentimes discussed together, but can be distinguished. Kwashiorkor is classified by its insufficient protein consumption whereas marasmus is related to general energy deficiency and severe muscle wasting. Kwashiorkor is also distinguished from marasmus by the presence of edema. There is also marasmic kwashiorkor that is the deficiency in calories and in protein. Although they are both different types of severe acute malnutrition, there was greater consumption of antioxidants, vitamins, and minerals seen in those with kwashiorkor compared to those with marasmus. Wellcomes classification Wellcome classification is a system for classifying protein-energy malnutrition in children based on weight for their age and based on presence of edema. Other classifications include Gomez classification and Waterlow classification. Signs and symptoms The defining sign of kwashiorkor in a malnourished child is pitting edema (particularly swelling of the hands and feet). Unlike marasmus, where the liver and other essential organs are reduced in size, kwashiorkor is characterized by "an enlarged fatty liver, fibrosis, and dysfunction of several organs (such as the liver, kidneys, and nervous system)". Other signs include a distended abdomen, thinning of hair, loss of teeth, skin or hair depigmentation, and dermatitis. Children with kwashiorkor often develop irritability and anorexia. Generally, the disease can be treated by adding protein to the diet; however, it can have a long-term impact on a childs physical and mental development, and in severe cases may lead to death.In dry climates, marasmus is the more frequent disease associated with malnutrition. Another malnutrition syndrome includes cachexia, although it is often caused by underlying illnesses. These are important considerations in the treatment of individuals with kwashiorkor. Causes The precise etiology of kwashiorkor remains unclear. Several hypotheses have been proposed that are associated with and explain some, but not all aspects of the pathophysiology of kwashiorkor. They include, but are not limited to protein deficiency causing hypoalbuminemia, amino acid deficiency, oxidative stress, and gut microbiome changes. Low protein intake Kwashiorkor is a severe form of malnutrition associated with a deficiency in dietary protein. The extreme lack of protein causes an osmotic imbalance in the gastrointestinal system causing swelling of the gut diagnosed as an edema or retention of water.Extreme fluid retention observed in individuals suffering from kwashiorkor is a direct result of irregularities in the lymphatic system and an indication of capillary exchange. The lymphatic system serves three major purposes: fluid recovery, immunity, and lipid absorption. Victims of kwashiorkor commonly exhibit reduced ability to recover fluids, immune system failure, and low lipid absorption, all of which result from a state of severe undernourishment. Fluid recovery in the lymphatic system is accomplished by re-absorption of water and proteins which are then returned to the blood. Compromised fluid recovery results in the characteristic belly distension observed in highly malnourished children.Capillary exchange between the lymphatic system and the bloodstream is stunted due to the inability of the body to effectively overcome the hydrostatic pressure gradient. Proteins, mainly albumin, are responsible for creating the colloid osmotic pressure (COP) observed in the blood and tissue fluids. The difference in the COP of the blood and tissue is called the oncotic pressure. The oncotic pressure is in direct opposition with the hydrostatic pressure and tends to draw water back into the capillary by osmosis. However, due to the lack of proteins, no substantial pressure gradient can be established to draw fluids from the tissue back into the blood stream. This results in the pooling of fluids, causing the swelling and distention of the abdomen.The low protein intake leads to some specific signs: edema of the hands and feet, irritability, anorexia, a desquamative rash, hair discolouration, and a large fatty liver. The typical swollen abdomen is due to two causes: ascites because of hypoalbuminemia (low oncotic pressure), and enlarged fatty liver.Ignorance of nutrition can be a cause. A case was described where parents who fed their child cassava failed to recognize malnutrition because of the edema caused by the syndrome and believed the child was well-nourished despite the lack of dietary protein.Protein should be supplied only for anabolic purposes. The catabolic needs should be satisfied with carbohydrate and fat. Protein catabolism involves the urea cycle, which is located in the liver and can easily overwhelm the capacity of an already damaged organ. The resulting liver failure can be fatal. This means in individuals suffering from kwashiorkor, protein must be introduced back into the diet gradually. Clinical solutions include weaning the affected with milk products and increasing the intake of proteinaceous material progressively to daily recommended amounts. Aflatoxins Recent studies have attempted to pinpoint a relationship between kwashiorkor and high levels of aflatoxins. Aflatoxins are naturally occurring toxins produced by the mold Aspergillus flavus, a fungus found in areas with hot and humid climates. These toxins tend to grow and can be found in agricultural crops such as millet, maize, and rice. An analysis found that the presence of aflatoxins was found more frequently and in higher concentrations in individuals with kwashiorkor when compared to individuals with marasmus (another form of severe acute malnutrition). In particular, biological samples showed greater levels of aflatoxins in the brain, heart, kidney, liver, lungs, serum, stool, and urine. Aflatoxins were not found in liver samples of individuals with marasmus. It has been known that the liver organ is the main target of aflatoxins and chronic toxicity can result in immunosuppressive and carcinogenic effects. However, there is currently conflicting evidence to pinpoint a connection between kwashiorkor and aflatoxins. Studies have shown that not all children with kwashiorkor present with detectable aflatoxin levels. It has also been proposed that damage done by aflatoxins may be due to glutathione depletion (another proposed mechanism of the disease) in children with kwashiorkor. Mechanisms Peripheral edema and hypoalbuminemia Kwashiorkor is a form of protein deficiency, which can result in both osmotic imbalances and irregularities in the lymphatic system.Kwashiorkor is most notable for peripheral edema. The presence of edema in kwashiorkor is correlated with very low albumin concentration (hypoalbuminemia). Edema results from a loss of fluid balance between the hydrostatic and oncotic pressures across the capillary blood vessel walls due to the lack of protein which affects the bodys ability to draw fluid from the tissues into the bloodstream. Low albumin concentration influences negatively the strength of oncotic pressure. Failure leads to the fluid buildup in the abdomen, resulting in edema and belly distension.Furthermore, the release of antidiuretic hormone is stimulated by hypovolemia, also leading to the development of peripheral edema. Plasma renin is also stimulated, promoting sodium retention.It is important to distinguish the pathophysiology of marasmus and kwashiorkor when it comes to treating malnourished children who may have hypovolemic shock that is cause by an acute loss of salt and water. Children with severe albumin deficiency struggle physiologically to maintain their blood volume. Low glutathione levels Kwashiorkor is also marked by low glutathione levels. Glutathione is used in many of the body processes on a molecule level.It is believed to be related to high oxidant levels commonly seen in people who suffer from starvation and rarely in chronic inflammation. Glutathione serves vital functions including management of oxidative stress which is an imbalance that plays a key role in the pathogenesis of many diseases. Cysteine is an essential amino acid that acts as the limiting amino acid for glutathione synthesis in humans. Factors that stimulate cysteine uptake by cells will increase glutathione levels and prevent glutathione deficiency in humans under various conditions including protein malnutrition.Evidence indicates that dietary amino acids balance has an important effect on protein nutrition and therefore on glutathione homeostasis. Others A proposed experimental theory suggests that alterations in the microbiome/virone contributes to edematous malnutrition, but further studies are required to understand the mechanism. Diagnosis Kwashiorkor, or edematous malnutrition, like many other malnutrition diseases, is indirectly assessed using anthropometry. Kwashiorkor is a subtype of severe acute malnutrition (SAM) characterized by bilateral peripheral pitting edema. According to the World Health Organization, the SAM diagnosis parameters are a "mid-upper arm circumference (MUAC) of < 115 mm, weight-for-height/length Z-score (WHZ) of < -3Z and nutritional edema or any combination of these parameters." Additional clinical findings on physical exam include marked muscle atrophy, abdominal distension, dermatitis, and hepatomegaly.WHO criteria for clinical assessment of malnutrition are based on the degree of wasting (MUAC), stunting (weight-for-height Z-score), and the presence of edema (mild to severe). Screening Because it can be difficult to measure weight-for-height Z scores (WHZ) frequently, screening is performed using mid-upper arm circumference (MUAC) < 115 mm. To properly screen for severe malnutrition in children, MUAC measurements should be done every month to reduce the risk of complications. Additionally, getting a better sense of what they eat, how often they eat, and any issues they may have with eating, may give more insight on their nutrition and what changes may need to be made to improve it. Prevention As for the prevention of childhood malnutrition, there needs to be public health changes such as improving agriculture and improving access to healthcare to effectively reduce the rates of malnutrition in children. By educating individuals of childbearing age on proper nutrition and health during and after pregnancy, they can provide their children with the appropriate nutrients from a young age. By ensuring they are equipped with the proper education and resources, caretakers and infants are in better health, ultimately preventing childhood malnutrition.Because edema can hide decreased muscle mass, it can be hard to diagnose kwashiorkor in young children; however, if cases are overlooked, children become more susceptible to infections and can ultimately lead to morbidity and mortality. To prevent this from happening, parents can be educated on proper nutrition and the importance of breastfeeding infants to ensure they receive all the nutrients they need.A diet rich in carbohydrates, fats that make up 10% of the total caloric needs, and proteins that make up 15% of the caloric needs can prevent kwashiorkor. Proteins can be found in the following foods Seafood Peas Nuts Seeds Eggs Lean meat Beans Treatment WHO guidelines outline 10 general principles for the inpatient management of severely malnourished children. Treat/prevent hypoglycemia Treat/prevent hypothermia Treat/prevent dehydration Correct electrolyte imbalance Treat/prevent infection Correct micronutrient deficiencies Start cautious feeding Achieve catch-up growth Provide sensory stimulation and emotional support Prepare for follow-up after recoveryBoth clinical subtypes of severe acute malnutrition (kwashiorkor and marasmus) are treated similarly. Upon initial treatment, children with kwashiorkor may experience weight loss as their edema resolves. Therefore, after concerns of refeeding syndrome have passed, children may require 120-140% of their estimated caloric needs in order to achieve catch-up growth.The cause, type, and severity of malnutrition determines what type of treatment would be most appropriate. For primary acute malnutrition, children with no complications are treated at home and are encouraged to either continue breastfeeding (for infants) or start using ready-to-use therapeutic foods (for children). For secondary acute malnutrition, the underlying cause needs to be identified to appropriately treat children. Only after the primary disease is determined can an appropriate dietary plan be made, as fluid, vitamins, and macronutrients may need to be considered to not exacerbate the cause of the malnutrition.Ready-to-use therapeutic foods (RUTFs) and F-75 and F-100 milks were created to provide appropriate nutrition and caloric intake to those experiencing malnutrition. F-75 milk would be ideal when trying to reintroduce food into a malnourished person, and F-100 milk would be used to aid in weight gain. While RUTFs and F-100 milk were made to have the same nutritional value, RUTFs are beneficial as they are dehydrated and do not require much preparation. Prognosis Kwashiorkor is associated with a high risk of mortality and long-term complications. Treatment under the guidelines of the World Health Organization has proven to reduce this mortality risk and affected children tend to recover faster than children with other severe malnutrition diseases. However, physical and intellectual capabilities are not fully restored. Growth stunting and chronic disruption of microbiota are commonly observed after recovery.A high risk of death is identified by a brachial perimeter < 11 cm or by a weight-for-age threshold < −3 z-scores below the median of the WHO child growth standards. In practice, malnourished children with edema are suffering from potentially life-threatening severe malnutrition. Epidemiology Kwashiorkor is rare in high income countries. It is mostly observed in low-income and middle income nations and regions such as Southeast Asia, Central America, Congo, Ethiopia, Puerto Rico, Jamaica, South Africa, and Uganda, where poverty is prominent. Occurrences of severe malnutrition also tend to trend higher under conditions of food insecurity, higher prevalence of infectious diseases, lack of access to appropriate care, and poor living situations with inadequate sanitation. Communities experiencing famine are affected the most especially during the rainy season. Prevalence varies, but it affects children of either sex commonly under five years old. "Globally, kwashiorkor indirected accounted for 53% of deaths among children under five between 2000 and 2003 when associated with other common childhood diseases like acute respiratory infections, malaria, measles, HIV/AIDS and other causes of perinatal deaths."When compared to marasmus in developing countries, kwashiorkor has a lower prevalence, "0.2%-1.6% for kwashiorkor and 1.2%-6.8% for marasmus." Factors such as "diet, geographical locations, climate and aflatoxin exposure" are associated with the difference in prevalence for kwashiorkor and marasmus. History It is likely that kwashiorkor was commonly seen around the world long before 1933, when Cicely Williams published research which took the Ga name for the disease. There were already many names for the illness which referenced the cessation of breastfeeding, or the consumption of diets which were too high in starch. However, Williams was the first to suggest that this might be a deficiency of protein. Despite publishing in 1933, it was only in 1949 that the World Health Organization officially recognized kwashiorkor as a public health concern. This period also correlated with the promotion of infant formula, often by European colonial powers. The substitution of breastmilk for formula contributed significantly to the increasing visibility of kwashiorkor throughout the twentieth century. Cicely Williams later described the promotion of formula as "the most criminal form of sedition, and that those deaths should be regarded as murder." These arguments underpinned the 1970s Nestlé boycott. Effects on pharmacokinetics Those experiencing poverty-related infectious diseases (PRDs) such as malaria and tuberculosis are also likely to be malnourished. Malnutrition can affect the pharmacokinetics of various drugs used to treat PRDs by changing a drugs bioavailability, distribution, and elimination. To optimize treatment of those diseases, there needs to be more research into how severe malnutrition, specifically kwashiorkor, can affect treatment response. Research directions Current research and recommendations to manage severe acute malnutrition (SAM), such as kwashiorkor, in children are largely based on expert opinions. Only one-third of the WHO guidelines for management of SAM are based on epidemiological and clinical research. Further studies are needed in order to "improve treatment outcomes in the large number of children with SAM." See also Anemia Emaciation Starvation Marasmus Protein poisoning References External links Picot, J; Hartwell, D; Harris, P; Mendes, D; Clegg, A J; Takeda, A (2012). "The effectiveness of interventions to treat severe acute malnutrition in young children: a systematic review". Health Technology Assessment. 16 (19). doi:10.3310/hta16190. PMC 4781582. PMID 22480797. NBK98566. Media related to Kwashiorkor at Wikimedia Commons

Vascular dementia

Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting of a complex interaction of cerebrovascular disease and risk factors that lead to changes in brain structures due to strokes and lesions, resulting in changes in cognition. The temporal relationship between a stroke and cognitive deficits is needed to make the diagnosis. Signs and symptoms Differentiating dementia syndromes can be challenging, due to the frequently overlapping clinical features and related underlying pathology. In particular, Alzheimers disease often co-occurs with vascular dementia.People with vascular dementia present with progressive cognitive impairment, acutely or sub-acutely as in mild cognitive impairment, frequently step-wise, after multiple cerebrovascular events (strokes). Some people may appear to improve between events and decline after further silent strokes. A rapidly deteriorating condition may lead to death from a stroke, heart disease, or infection.The disease is described as both a mental disorder and behavioural disorder within the International Classification of Diseases. Signs and symptoms are cognitive, motor, behavioral, and for a significant proportion of patients, also affective. These changes typically occur over a period of 5–10 years. Signs are typically the same as in other dementias, but mainly include cognitive decline and memory impairment of sufficient severity as to interfere with activities of daily living, sometimes with presence of focal neurologic signs, and evidence of features consistent with cerebrovascular disease on brain imaging (CT or MRI). The neurologic signs localizing to certain areas of the brain that can be observed are hemiparesis, bradykinesia, hyperreflexia, extensor plantar reflexes, ataxia, pseudobulbar palsy, as well as gait problems and swallowing difficulties. People have patchy deficits in terms of cognitive testing. They tend to have better free recall and fewer recall intrusions when compared with patients with Alzheimers disease. In the more severely affected patients, or patients affected by infarcts in Wernickes or Brocas areas, specific problems with speaking called dysarthria and aphasias may be present.In small vessel disease, the frontal lobes are often affected. Consequently, patients with vascular dementia tend to perform worse than their Alzheimers disease counterparts in frontal lobe tasks, such as verbal fluency, and may present with frontal lobe problems: apathy, abulia (lack of will or initiative), problems with attention, orientation, and urinary incontinence. They tend to exhibit more perseverative behavior. VaD patients may also present with general slowing of processing ability, difficulty shifting sets, and impairment in abstract thinking. Apathy early in the disease is more suggestive of vascular dementia.Rare genetic disorders that cause vascular lesions in the brain have other presentation patterns. As a rule, they tend to occur earlier in life and have a more aggressive course. In addition, infectious disorders, such as syphilis, can cause arterial damage, strokes, and bacterial inflammation of the brain. Causes Vascular dementia can be caused by ischemic or hemorrhagic infarcts affecting multiple brain areas, including the anterior cerebral artery territory, the parietal lobes, or the cingulate gyrus. On rare occasion, infarcts in the hippocampus or thalamus are the cause of dementia. A history of stroke increases the risk of developing dementia by around 70%, and recent stroke increases the risk by around 120%. Brain vascular lesions can also be the result of diffuse cerebrovascular disease, such as small vessel disease.Risk factors for vascular dementia include age, hypertension, smoking, hypercholesterolemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease. Other risk factors include geographic origin, genetic predisposition, and prior strokes.Vascular dementia can sometimes be triggered by cerebral amyloid angiopathy, which involves accumulation of beta amyloid plaques in the walls of the cerebral arteries, leading to breakdown and rupture of the vessels. Since amyloid plaques are a characteristic feature of Alzheimers disease, vascular dementia may occur as a consequence. Cerebral amyloid angiopathy can, however, appear in people with no prior dementia condition. Amyloid beta accumulation is often present in cognitively normal elderly people.Two reviews of 2018 and 2019 found potentially an association between celiac disease and vascular dementia. Diagnosis Several specific diagnostic criteria can be used to diagnose vascular dementia, including the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, the International Classification of Diseases, Tenth Edition (ICD-10) criteria, the National Institute of Neurological Disorders and Stroke criteria, Association Internationale pour la Recherche et lEnseignement en Neurosciences (NINDS-AIREN) criteria, the Alzheimers Disease Diagnostic and Treatment Center criteria, and the Hachinski Ischemic Score (after Vladimir Hachinski).The recommended investigations for cognitive impairment include: blood tests (for anemia, vitamin deficiency, thyrotoxicosis, infection, etc.), chest X-Ray, ECG, and neuroimaging, preferably a scan with a functional or metabolic sensitivity beyond a simple CT or MRI. When available as a diagnostic tool, single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroimaging may be used to confirm a diagnosis of multi-infarct dementia in conjunction with evaluations involving mental status examination. In a person already having dementia, SPECT appears to be superior in differentiating multi-infarct dementia from Alzheimers disease, compared to the usual mental testing and medical history analysis. Advances have led to the proposal of new diagnostic criteria.The screening blood tests typically include full blood count, liver function tests, thyroid function tests, lipid profile, erythrocyte sedimentation rate, C reactive protein, syphilis serology, calcium serum level, fasting glucose, urea, electrolytes, vitamin B-12, and folate. In selected patients, HIV serology and certain autoantibody testing may be done.Mixed dementia is diagnosed when people have evidence of Alzheimers disease and cerebrovascular disease, either clinically or based on neuro-imaging evidence of ischemic lesions. Pathology Gross examination of the brain may reveal noticeable lesions and damage to blood vessels. Accumulation of various substances such as lipid deposits and clotted blood appear on microscopic views. The white matter is most affected, with noticeable atrophy (tissue loss), in addition to calcification of the arteries. Microinfarcts may also be present in the gray matter (cerebral cortex), sometimes in large numbers. Although atheroma of the major cerebral arteries is typical in vascular dementia, smaller vessels and arterioles are mainly affected. Prevention Early detection and accurate diagnosis are important, as vascular dementia is at least partially preventable. Ischemic changes in the brain are irreversible, but the patient with vascular dementia can demonstrate periods of stability or even mild improvement. Since stroke is an essential part of vascular dementia, the goal is to prevent new strokes. This is attempted through reduction of stroke risk factors, such as high blood pressure, high blood lipid levels, atrial fibrillation, or diabetes mellitus. Meta-analyses have found that medications for high blood pressure are effective at prevention of pre-stroke dementia, which means that high blood pressure treatment should be started early. These medications include angiotensin converting enzyme inhibitors, diuretics, calcium channel blockers, sympathetic nerve inhibitors, angiotensin II receptor antagonists or adrenergic antagonists. Elevated lipid levels, including HDL, were found to increase risk of vascular dementia. However, six large recent reviews showed that therapy with statin drugs was ineffective in treatment or prevention of this dementia. Aspirin is a medication that is commonly prescribed for prevention of strokes and heart attacks; it is also frequently given to patients with dementia. However, its efficacy in slowing progression of dementia or improving cognition has not been supported by studies. Smoking cessation and Mediterranean diet have not been found to help patients with cognitive impairment; physical activity was consistently the most effective method of preventing cognitive decline. Treatment Currently, there are no medications that have been approved specifically for prevention or treatment of vascular dementia. The use of medications for treatment of Alzheimers dementia, such as cholinesterase inhibitors and memantine, has shown small improvement of cognition in vascular dementia. This is most likely due to the drugs actions on co-existing AD-related pathology. Multiple studies found a small benefit in VaD treatment with: memantine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; cholinesterase inhibitors galantamine, donepezil, rivastigmine; Studies have been proposed to evaluate whether an extract of Ginkgo biloba EGb761 improves cognition, daily activities, and quality of life in treating vascular dementia.In those with celiac disease or non-celiac gluten sensitivity, a strict gluten-free diet may relieve symptoms of mild cognitive impairment. It should be started as soon as possible. There is no evidence that a gluten free diet is useful against advanced dementia. People with no digestive symptoms are less likely to receive early diagnosis and treatment.General management of dementia includes referral to community services, aid with judgment and decision-making regarding legal and ethical issues (e.g., driving, capacity, advance directives), and consideration of caregiver stress. Behavioral and affective symptoms deserve special consideration in this patient group. These problems tend to resist conventional psychopharmacological treatment, and often lead to hospital admission and placement in permanent care. Prognosis Many studies have been conducted to determine average survival of patients with dementia. The studies were frequently small and limited, which caused contradictory results in the connection of mortality to the type of dementia and the patients gender. A very large study conducted in Netherlands in 2015 found that the one-year mortality was three to four times higher in patients after their first referral to a day clinic for dementia, when compared to the general population. If the patient was hospitalized for dementia, the mortality was even higher than in patients hospitalized for cardiovascular disease. Vascular dementia was found to have either comparable or worse survival rates when compared to Alzheimers Disease; another very large 2014 Swedish study found that the prognosis for VaD patients was worse for male and older patients.Unlike Alzheimers disease, which weakens the patient, causing them to succumb to bacterial infections like pneumonia, vascular dementia can be a direct cause of death due to the possibility of a fatal interruption in the brains blood supply. Epidemiology Vascular dementia is the second-most-common form of dementia after Alzheimers disease (AD) in older adults. The prevalence of the illness is 1.5% in Western countries and approximately 2.2% in Japan. It accounts for 50% of all dementias in Japan, 20% to 40% in Europe and 15% in Latin America. 25% of stroke patients develop new-onset dementia within one year of their stroke. One study found that in the United States, the prevalence of vascular dementia in all people over the age of 71 is 2.43%, and another found that the prevalence of the dementias doubles with every 5.1 years of age. The incidence peaks between the fourth and the seventh decades of life and 80% of patients have a history of hypertension.A recent meta-analysis identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% confidence interval: 1.49–1.92; P < .00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% confidence interval: 1.90–2.50; P < .00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex, which explained 50.2% of between-study heterogeneity for prevalent stroke. These results confirm that stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia. See also Binswangers disease Cerebrovascular accident References External links Multi-Infarct Dementia Fact Sheet at ninds.nih.gov American Academy of Neurology (December 21, 2007). "Walking and Moderate Exercise Help Prevent Dementia". ScienceDaily. Retrieved December 21, 2007, from https://www.sciencedaily.com/releases/2007/12/071219202948.htm

Labyrinthitis

Labyrinthitis is inflammation of the labyrinth – a maze of fluid-filled channels in the inner ear. Vestibular neuritis is inflammation of the vestibular nerve – the nerve in the inner ear that sends messages related to motion and position to the brain. Both conditions involve inflammation of the inner ear. Labyrinths that house the vestibular system sense changes in the heads position or the heads motion. Inflammation of these inner ear parts results in a sensation of the world spinning and also possible hearing loss or ringing in the ears. It can occur as a single attack, a series of attacks, or a persistent condition that diminishes over three to six weeks. It may be associated with nausea, vomiting, and eye nystagmus. The cause is often not clear. It may be due to a virus, but it can also arise from bacterial infection, head injury, extreme stress, an allergy, or as a reaction to medication. 30% of affected people had a common cold prior to developing the disease. Either bacterial or viral labyrinthitis can cause a permanent hearing loss in rare cases. This appears to result from an imbalance of neuronal input between the left and right inner ears. Signs and symptoms The main symptoms are severe vertigo and nystagmus. The most common symptom for vestibular neuritis is the onset of vertigo that has formed from an ongoing infection or trauma. The dizziness sensation that is associated with vertigo is thought to be from the inner ear labyrinth. Rapid and undesired eye motion (nystagmus) often results from the improper indication of rotational motion. Nausea, anxiety, and a general ill feeling are common due to the distorted balance signals that the brain receives from the inner ear system. Other common symptoms include tinnitus, ear ache, and a feeling of fullness in the ear. Causes Some people will report having an upper respiratory infection (common cold) or flu prior to the onset of the symptoms of vestibular neuritis; others will have no viral symptoms prior to the vertigo attack. Some cases of vestibular neuritis are thought to be caused by an infection of the vestibular ganglion by the herpes simplex type 1 virus. However, the cause of this condition is not fully understood, and in fact, many different viruses may be capable of infecting the vestibular nerve. Acute localized ischemia of these structures also may be an important cause. Especially in children, vestibular neuritis may be preceded by symptoms of a common cold. However, the causative mechanism remains uncertain.This can also be brought on by pressure changes such as those experienced while flying or scuba diving. Mechanism In the vestibular system, there are three canals that are semicircular in shape that input sensory clues. These canals allow the brain to sense rotational motion and linear motion changes. The brain then uses the sensory input clues and the visual input clues from the vestibular system to retain balance. The vestibulo–ocular reflex retains continuous visual focus during motion which is also the vestibular systems job during activity. Treatment The treatment for vestibular neuritis depends on the cause. However, symptoms of vertigo can be treated in the same way as other vestibular dysfunctions with vestibular rehabilitation. Physical therapy Typical treatments include combinations of head and eye movements, postural changes, and walking exercises. Specifically, exercises that may be prescribed include keeping eyes fixated on a specific target while moving the head, moving the head right to left at two targets at a significant distance apart, walking while keeping eyes fixated on a specific target, and walking while keeping eyes fixated on a specific target while also turning the head in different directions. The main function behind repeating a combination of head and eye movements, postural changes and walking is that through this repetition, compensatory changes for the dysfunctions arising from peripheral vestibular structures may be promoted in the central vestibular system (brainstem and cerebellum).Vestibular rehabilitation therapy is a highly effective way to substantially reduce or eliminate residual dizziness from labyrinthitis. VRT works by causing the brain to use already existing neural mechanisms for adaptation, neuroplasticity, and compensation. Vestibular neuritis rehabilitation is an effective and safe management to improve symptoms. The vestibular neuritis rehabilitation can improve symptoms or resolve the symptoms which is dependent on each individual. Rehabilitation strategies most commonly used are: Gaze stability exercises – moving the head from side to side while fixated on a stationary object (aimed at assisting the eye to fixate during head rotation without the input from the lost canal vestibulo–ocular reflex). An advanced progression of this exercise would be walking in a straight line while looking side to side by turning the head. Habituation exercises – movements designed to provoke symptoms and subsequently reduce the negative vestibular response upon repetition. Examples of these include Brandt–Daroff exercises. Functional retraining – including postural control, relaxation, and balance training.These exercises function by challenging the vestibular system. Progression occurs by increasing the amplitude of the head or focal point movements, increasing the speed of movement, and combining movements such as walking and head turning.One study found that patients who believed their illness was out of their control showed the slowest progression to full recovery, long after the initial vestibular injury had healed. The study revealed that the patient who compensated well was one who, at the psychological level, was not afraid of the symptoms and had some positive control over them. Notably, a reduction in negative beliefs over time was greater in those patients treated with rehabilitation than in those untreated. "Of utmost importance, baseline beliefs were the only significant predictor of change in a handicap at 6 months follow-up." Medication Vestibular neuritis is generally a self-limiting disease. Treatment with drugs is neither necessary nor possible. The effect of glucocorticoids has been studied, but they have not been found to significantly affect long-term outcome.Symptomatic treatment with antihistaminics such as cinnarizine, however, can be used to suppress the symptoms of vestibular neuritis while it spontaneously regresses. Prochlorperazine is another commonly prescribed medication to help alleviate the symptoms of vertigo and nausea. Mental disorders Because mood disorders can hamper recovery from labyrinthitis, treatment may also include any co-occurring anxiety disorder or depression. Severe anxiety episodes are usually addressed by short-term benzodiazepine therapy. Prognosis Recovery from acute labyrinthine inflammation generally takes from one to six weeks, but it is not uncommon for residual symptoms such as dysequilibrium and dizziness to last for a couple of months.Recovery from a temporary damaged inner ear typically follows two phases: An acute period, which may include severe vertigo and vomiting approximately two weeks of sub-acute symptoms and rapid recovery Epidemiology Labyrinthitis affects approximately 35 million people per year (approximately 3.5 cases per 100,000 people). It typically occurs in those between 30 and 60 years of age, and there are no significant differences between male and female incidence rates. In 95% of cases, sufferers experience a single attack and fully recover. Vestibular rehabilitation showed a statistically significant increase in controlling symptoms over no intervention in people who have vestibular neuritis. References External links Labyrinthitis at Curlie

Cryptosporidiosis

Cryptosporidiosis, sometimes informally called crypto, is a parasitic disease caused by Cryptosporidium, a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tract in both immunocompetent (i.e., individuals with a normal functioning immune system) and immunocompromised (e.g., persons with HIV/AIDS or autoimmune disorders) individuals, resulting in watery diarrhea with or without an unexplained cough. In immunosuppressed individuals, the symptoms are particularly severe and can be fatal. It is primarily spread through the fecal-oral route, often through contaminated water; recent evidence suggests that it can also be transmitted via fomites contaminated with respiratory secretions.Cryptosporidium is commonly isolated in HIV-positive patients presenting with diarrhea. Despite not being identified until 1976, it is one of the most common waterborne diseases and is found worldwide. The infection begins when a human consumes food or water containing cysts of the Cryptosporidium organism. Signs and symptoms Cryptosporidiosis may occur as an asymptomatic infection, an acute infection (i.e., duration shorter than 2 weeks), as recurrent acute infections in which symptoms reappear following a brief period of recovery for up to 30 days, and as a chronic infection (i.e., duration longer than 2 weeks) in which symptoms are severe and persistent. It may be fatal in individuals with a severely compromised immune system. Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks in immunocompetent individuals; symptoms are usually more severe and persist longer in immunocompromised individuals. Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection. The likelihood of re-infection is high in immunocompromised adults, and low in those with normal immune systems.In immunocompetent individuals, cryptosporidiosis is primarily localized to the distal small intestine and sometimes the respiratory tract as well. In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including the hepatobiliary system, pancreas, upper gastrointestinal tract, and urinary bladder; pancreatic and biliary infection can involve acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis. Intestinal cryptosporidiosis Common signs and symptoms of intestinal cryptosporidiosis include: Moderate to severe watery diarrhea, sometimes contains mucus and rarely contains blood or leukocytesIn very severe cases, diarrhea may be profuse and cholera-like with malabsorption and hypovolemia Low-grade fever Crampy abdominal pain Dehydration Weight loss Fatigue Nausea and vomiting – suggests upper GI tract involvement and may lead to respiratory cryptosporidiosis Epigastric or right upper quadrant tendernessLess common or rare signs and symptoms include: Reactive arthritis (may affect the hands, knees, ankles, and feet) Jaundice – suggests hepatobiliary involvement Ascites – suggests pancreatic involvement Respiratory cryptosporidiosis Symptoms of upper respiratory cryptosporidiosis include: Inflammation of the nasal mucosa, sinuses, larynx, or trachea Nasal discharge Voice change (e.g., hoarseness)Symptoms of lower respiratory cryptosporidiosis include: Cough Shortness of breath Fever Hypoxemia Reason Cryptosporidium is a genus of protozoan pathogens which is categorized under the phylum Apicomplexa. Other apicomplexan pathogens include the malaria parasite Plasmodium, and Toxoplasma, the causative agent of toxoplasmosis. A number of Cryptosporidium infect mammals. In humans, the main causes of disease are C. parvum and C. hominis (previously C. parvum genotype 1). C. canis, C. felis, C. meleagridis, and C. muris can also cause disease in humans. Cryptosporidium is capable of completing its life cycle within a single host, resulting in microbial cyst stages that are excreted in feces and are capable of transmission to a new host via the fecal-oral route. Other vectors of disease transmission also exist.The pattern of Cryptosporidium life cycle fits well with that of other intestinal homogeneous coccidian genera of the suborder Eimeriina: macro- and microgamonts develop independently; a microgamont gives rise to numerous male gametes; and oocysts serving for parasites spreading in the environment. Electron microscopic studies made from the 1970s have shown the intracellular, although extracytoplasmic localization of Cryptosporidium species.These species possess a number of unusual features: an endogenous phase of development in microvilli of epithelial surfaces two morphofunctional types of oocysts the smallest number of sporozoites per oocyst a multi-membraneous "feeder" organelleDNA studies suggest a relationship with the gregarines rather than the coccidia. The taxonomic position of this group has not yet been finally agreed upon. The genome of Cryptosporidium parvum was sequenced in 2004 and was found to be unusual amongst Eukaryotes in that the mitochondria seem not to contain DNA. A closely related species, C. hominis, also has its genome sequence available. CryptoDB.org is a NIH-funded database that provides access to the Cryptosporidium genomics data sets. Transfer Infection is through contaminated material such as earth, water, uncooked or cross-contaminated food that has been in contact with the feces of an infected individual or animal. Contact must then be transferred to the mouth and swallowed. It is especially prevalent amongst those in regular contact with bodies of fresh water including recreational water such as swimming pools. Other potential sources include insufficiently treated water supplies, contaminated food, or exposure to feces. The high resistance of Cryptosporidium oocysts to disinfectants such as chlorine bleach enables them to survive for long periods and still remain infective. Some outbreaks have happened in day care related to diaper changes.The following groups have an elevated risk of being exposed to Cryptosporidium: Child care workers Parents of infected children People who take care of other people with cryptosporidiosis International travelers Backpackers, hikers, and campers who drink unfiltered, untreated water People, including swimmers, who swallow water from contaminated sources People who handle infected cattle People exposed to human feces through sexual contactCases of cryptosporidiosis can occur even in cities that have a properly de-contaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have other origins. Testing of water, as well as epidemiological study, are necessary to determine the sources of specific infections. Cryptosporidium is causing serious illness more frequently in immunocompromised than in apparently healthy individuals. It may chronically sicken some children, as well as adults who are exposed and immunocompromised. A subset of the immunocompromised population is people with AIDS. Some sexual behaviors can transmit the parasite directly. Life cycle Cryptosporidium spp. exist as multiple cell types which correspond to different stages in an infection (e.g., a sexual and asexual stage). As an oocyst – a type of hardy, thick-walled spore – it can survive in the environment for months and is resistant to many common disinfectants, particularly chlorine-based disinfectants. After being ingested, the sporozoites within oocysts excyst (i.e., are released) in the small intestine. The released sporozoites subsequently attach to the microvilli of the epithelial cells of the small intestine. From there they become trophozoites that reproduce asexually by multiple fission, a process known as schizogony. The trophozoites develop into Type 1 meronts [1] that contain 8 daughter cells.These daughter cells are Type 1 merozoites, which get released by the meronts. Some of these merozoites can cause autoinfection by attaching to epithelial cells. Others of these merozoites become Type II meronts, which contain 4 Type II merozoites. These merozoites get released and they attach to the epithelial cells. From there they become either macrogamonts or microgamonts. These are the female and male sexual forms, respectively. This stage, when sexual forms arise, is called gametogony.Zygotes are formed by microgametes from the microgamont penetrating the macrogamonts. The zygotes develop into oocysts of two types. 20% of oocysts have thin walls and so can reinfect the host by rupturing and releasing sporozoites that start the process over again. The thick-walled oocysts are excreted into the environment. The oocysts are mature and infective upon being excreted. Pathogenesis The oocysts are ovoid or spherical and measure 5 to 6 micrometers across. When in flotation preparations they appear highly refractile. The oocysts contains up to 4 sporozoites that are bow-shaped.As few as 2 to 10 oocysts can initiate an infection. The parasite is located in the brush border of the epithelial cells of the small intestine. They are mainly located in the jejunum. When the sporozoites attach the epithelial cells membrane envelops them. Thus, they are "intracellular but extracytoplasmic". The parasite can cause damage to the microvilli where it attaches. The infected human excretes the most oocysts during the first week. Oocysts can be excreted for weeks after the diarrhea subsides from infections by C. parvum or C. hominis; however, immunocompetent individuals with C. muris infections have been observed excreting oocysts for seven months.The immune system reduces the formation of Type 1 merozoites as well as the number of thin-walled oocysts. This helps prevent autoinfection. B cells do not help with the initial response or the fight to eliminate the parasite. Previous infection in immunocompetent individuals produces little resistance to future infection, however it may decrease the severity of disease and the number of oocysts excreted. Diagnosis There are many diagnostic tests for Cryptosporidium. They include microscopy, staining, and detection of antibodies. Microscopy can help identify oocysts in fecal matter. To increase the chance of finding the oocysts, the diagnostician should inspect at least 3 stool samples. There are several techniques to concentrate either the stool sample or the oocysts. The modified formalin-ethyl acetate (FEA) concentration method concentrates the stool. Both the modified zinc sulfate centrifugal flotation technique and the Sheathers sugar flotation procedure can concentrate the oocysts by causing them to float. Another form of microscopy is fluorescent microscopy done by staining with auramine.Other staining techniques include acid-fast staining, which will stain the oocysts red. One type of acid-fast stain is the Kinyoun stain. Giemsa staining can also be performed. Part of the small intestine can be stained with hematoxylin and eosin (H & E), which will show oocysts attached to the epithelial cells.Detecting antigens is yet another way to diagnose the disease. This can be done with direct fluorescent antibody (DFA) techniques. It can also be achieved through indirect immunofluorescence assay. Enzyme-linked immunosorbent assay (ELISA) also detects antigens.Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis. It can even identify the specific species of Cryptosporidium. If the patient is thought to have biliary cryptosporidiosis, then an appropriate diagnostic technique is ultrasonography. If that returns normal results, the next step would be to perform endoscopic retrograde cholangiopancreatography. Prevention Many treatment plants that take raw water from rivers, lakes, and reservoirs for public drinking water production use conventional filtration technologies. This involves a series of processes, including coagulation, flocculation, sedimentation, and filtration. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration, but not sedimentation. Other common filtration processes, including slow sand filters, diatomaceous earth filters and membranes will remove 99% of Cryptosporidium. Membranes and bag and cartridge filters remove Cryptosporidium product-specifically.While Cryptosporidium is highly resistant to chlorine disinfection, with high enough concentrations and contact time, Cryptosporidium will be inactivated by chlorine dioxide and ozone treatment. The required levels of chlorine generally preclude the use of chlorine disinfection as a reliable method to control Cryptosporidium in drinking water. Ultraviolet light treatment at relatively low doses will inactivate Cryptosporidium. Water Research Foundation-funded research originally discovered UVs efficacy in inactivating Cryptosporidium.One of the largest challenges in identifying outbreaks is the ability to identify Cryptosporidium in the laboratory. Real-time monitoring technology is now able to detect Cryptosporidium with online systems, unlike the spot and batch testing methods used in the past.The most reliable way to decontaminate drinking water that may be contaminated by Cryptosporidium is to boil it.In the US the law requires doctors and labs to report cases of cryptosporidiosis to local or state health departments. These departments then report to the Center for Disease Control and Prevention. The best way to prevent getting and spreading cryptosporidiosis is to have good hygiene and sanitation. An example would be hand-washing. Prevention is through washing hands carefully after going to the bathroom or contacting stool, and before eating. People should avoid contact with animal feces. They should also avoid possibly contaminated food and water. In addition, people should refrain from engaging in sexual activities that can expose them to feces.Standard water filtration may not be enough to eliminate Cryptosporidium; boiling for at least 1 minute (3 minutes above 6,500 feet (2,000 m) of altitude) will decontaminate it. Heating milk at 71.7 °C (161 °F) for 15 seconds pasteurizes it and can destroy the oocysts ability to infect. Water can also be made safe by filtering with a filter with pore size not greater than 1 micrometre, or by filters that have been approved for "cyst removal" by NSF International National Sanitation Foundation. Bottled drinking water is less likely to contain Cryptosporidium, especially if the water is from an underground source.People with cryptosporidiosis should not swim in communal areas because the pathogen can reside in the anal and genital areas and be washed off. They should wait until at least two weeks after diarrhea stops before entering public water sources, since oocysts can still be shed for a while. Also, they should stay away from immunosuppressed people. Immunocompromised people should take care to protect themselves from water in lakes and streams. They should also stay away from animal stools and wash their hands after touching animals. To be safe, they should boil or filter their water. They should also wash and cook their vegetables.The US CDC notes the recommendation of many public health departments to soak contaminated surfaces for 20 minutes with a 3% hydrogen peroxide (99% kill rate) and then rinse them thoroughly, with the caveat that no disinfectant is guaranteed to be completely effective against Cryptosporidium. However, hydrogen peroxide is more effective than standard bleach solutions. Treatment Symptomatic treatment primarily involves fluid rehydration, electrolyte replacement (sodium, potassium, bicarbonate, and glucose), and antimotility agents (e.g., loperamide). Supplemental zinc may improve symptoms, particularly in recurrent or persistent infections or in others at risk for zinc deficiency. Immunocompetent Immunocompetent individuals with cryptosporidiosis typically experience a short (i.e., duration of less than 2 weeks) self-limiting course of diarrhea that may require symptomatic treatment and ends with spontaneous recovery; in some circumstances, antiparasitic medication may be required (e.g., recurrent, severe, or persistent symptoms); however reinfection frequently occurs.As of 2015, nitazoxanide is the only antiparasitic drug treatment with proven efficacy for cryptosporidiosis in immunocompetent individuals; however, it lacks efficacy in severely immunocompromised patients. Certain agents such as paromomycin and azithromycin are sometimes used as well, but they only have partial efficacy. Immunocompromised In immunocompromised individuals, such as AIDS patients, cryptosporidiosis resolves slowly or not at all, and frequently causes a particularly severe and persistent form of watery diarrhea coupled with a greatly decreased ability to absorb key nutrients through the intestinal tract. As a result, infected individuals may experience severe dehydration, electrolyte imbalances, malnutrition, wasting, and potentially death. In general, the mortality rate for infected AIDS patients is based on CD4+ marker counts. Patients with CD4+ counts over 180 cells/mm³ recover with supportive hospital care and medication; but, in patients with CD4+ counts below 50 cells/mm³, the effects are usually fatal within 3 to 6 months. During the Milwaukee cryptosporidiosis epidemic (the largest of its kind), 73% of AIDS patients with CD4+ counts lower than 50 cells/mm³ and 36% of those with counts between 50 and 200 cells/mm³ died within the first year of contracting the infection.The best treatment approach is to improve the immune status in immunodeficient individuals using highly active antiretroviral therapy that includes an HIV protease inhibitor along with continued use of antiparasitic medication. Antiparasitic drug treatment for immunocompromised individuals usually involves the combination of nitazoxanide, paromomycin, and azithromycin together; these drugs are only partially active in HIV/AIDS patients compared to their effect in immunocompetent persons. A Cochrane Collaboration review recommended that nitazoxanide be considered for use in treatment despite its reduced effectiveness in immunocompromised individuals.Currently, research is being done in molecular-based immunotherapy. For example, synthetic isoflavone derivates have been shown to fight off Cryptosporidium parvum both in vitro and in animal studies. Derivates of nitazoxanide, known as thiazolides, have also shown promising results in vitro. rifaximin is also sometimes used for immunocompromised patients/patients with severe disease. Epidemiology Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites. In developing countries, 8–19% of diarrheal diseases can be attributed to Cryptosporidium. Ten percent of the population in developing countries excretes oocysts. In developed countries, the number is lower at 1–3%. The age group most affected are children from 1 to 9 years old.In Eastern Europe cryptosporidiosis in humans and animals is common, but there are considerable gaps in surveillance and a lack of comparable methods which is limit the understanding of the disease and detection of outbreaks. Research show a rich diversity of zoonotic subtypes of the parasite in animals indicating a rich potential of animal to human transmission. Roughly 30% of adults in the United States are seropositive for cryptosporidiosis, meaning that they contracted the infection at some point in their lives. History The organism was first described in 1907 by Tyzzer, who recognised it was a coccidian. Research A recombinant Cryptosporidium parvum oocyst surface protein (rCP15/60) vaccine has produced an antibody response in a large group of cows and also antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. This is very promising. Human Cryptosporidium parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDS patients. There is no commercially available effective vaccine against Cryptosporidium parvum, although passive immunization utilizing different zoite surface (glyco)proteins has shown promise. Developmental stages of the life cycle of the parasite might act as possible targets for vaccine development. The organism is detected in 65–97% of the surface-water supply in the United States and is resistant to most disinfectants used for the treatment of drinking water. Antibodies in the serum of humans and animals infected with Cryptosporidium parvum react with several antigens, one of which is a 15 kDa protein (CP15) located on the surface of the organism. This protein is a good candidate for use as a molecular vaccine because previous studies have shown that a monoclonal antibody to CP15 confers passive immunity to mice. Currently, there is no vaccine or completely effective drug therapy against Cryptosporidium parvum in HIV/AIDS individuals.A summary of discoveries presented at the most recent (June 2019) international symposium on Cryptosporidium has been published in 2020. Other animals The most important zoonotic reservoirs are cattle, sheep and goats. In addition, in recent years, cryptosporidiosis has plagued many commercial leopard gecko breeders. Several species of the Cryptosporidium family (C. serpentes and others) are involved, and outside of geckos it has been found in monitor lizards, iguanas and tortoises, as well as several snake species. Notable cases Before 2000 In 1987, 13,000 people in Carrollton, Georgia, United States, became ill with cryptosporidiosis. This was the first report of its spread through a municipal water system that met all state and federal drinking water standards. In 1993, a waterborne cryptosporidiosis outbreak occurred in Milwaukee, Wisconsin, US. An estimated 403,000 people became ill, including 4,400 people hospitalized. The source of the Cryptosporidium is believed to be overflow from the Milwaukee area combined sanitary and storm sewer system into Lake Michigan, which was then taken into the Howard Avenue Water Purification Plant and distributed to an estimated 880,000 residents (of the 1.61 million residents in the Milwaukee area who receive their drinking water from Lake Michigan). These residents, who receive their drinking water from Lake Michigan, were told to boil their water before drinking it. More people were affected in this one outbreak than the combined number of people affected in every cryptosporidiosis outbreak in the 24 years since then. An estimated 69 people died during the outbreak, according to the CDC. The UKs biggest outbreak occurred in Torbay in Devon in 1995. In the summer of 1996, Cryptosporidium affected approximately 2,000 people in Cranbrook, British Columbia, Canada. Weeks later, a separate incident occurred in Kelowna, British Columbia, where 10,000 to 15,000 people got sick. 2001–2009 In April 2001, an outbreak occurred in the city of North Battleford, Saskatchewan, Canada. Between 5800 and 7100 people had diarrheal illness, and 1907 cases of cryptosporidiosis were confirmed. Equipment failures at the citys antiquated water filtration plant following maintenance were found to have caused the outbreak. In the summer of 2005, after numerous reports by patrons of gastrointestinal upset, a water park at Seneca Lake State Park, in the Finger Lakes region of upstate New York was found to have two water storage tanks infected with Cryptosporidium. By early September 2005, over 3,800 people reported symptoms of a Cryptosporidium infection. The "Sprayground" was ordered closed for the season on 15 August. In October 2005, the Gwynedd and Anglesey areas of North Wales, the United Kingdom, suffered an outbreak of cryptosporidiosis. The outbreak may have been linked to the drinking water supply from Llyn Cwellyn, but this is not yet confirmed. As a result, 231 people fell ill and the company Welsh Water (Dwr Cymru) advised 61,000 people to boil their water before use. In March 2007, a suspected outbreak occurred in Galway, Ireland, after the source of water for much of the county, Lough Corrib, was suspected to be contaminated with the parasite. A large population (90,000 people), including areas of both Galway City and County, were advised to boil water for drinking, food preparation and for brushing teeth. On 21 March 2007, it was confirmed that the city and countys water supply was contaminated with the parasite. The areas water supply was finally given approval on 20 August 2007, five months after Cryptosporidium was first detected. Around 240 people are known to have contracted the disease; experts say the true figure could be up to 5,000. Hundreds of public pools in 20 Utah counties were closed to young children in 2007, as children under 5 are most likely to spread the disease, especially children wearing diapers. As of 10 September 2007 the Utah Department of Health had reported 1302 cases Archived 25 September 2007 at the Wayback Machine of cryptosporidiosis in the year; a more usual number would be 30. On 25 September the pools were reopened to those not requiring diapers, but hyperchlorination requirements were not lifted. On 21 September 2007, a Cryptosporidium outbreak attacked the Western United States: 230 Idaho residents, with hundreds across the Rocky Mountain area; in the Boise and Meridian areas; Utah, 1,600 illnesses; Colorado and other Western states — Montana, decrease. On 25 June 2008, Cryptosporidium was found in England in water supplies in Northampton, Daventry, and some surrounding areas supplied from the Pitsford Reservoir, as reported on the BBC. People in the affected areas were warned not to drink tap water unless it had been boiled. Anglian Water confirmed that 108,000 households were affected, about 250,000 people. They advised that water might not be fit for human consumption for many weeks. The boil notice was lifted for all the affected customers on 4 July 2008. Throughout the summer of 2008; many public swimming areas, water parks, and public pools in the Dallas/Fort Worth Metroplex of Texas suffered an outbreak of cryptosporidiosis. Burgers Lake in Fort Worth was the first to report such an outbreak. This prompted some, if not all, city-owned and private pools to close and hyperchlorinate. To the 13 August 2008 there were 400 reported cases of Cryptosporidium. In September 2008, a gym in Cambridge, the United Kingdom, was forced to close its swimming pool until further notice after health inspectors found an outbreak of cryptosporidiosis. Environmental Health authorities requested that the water be tested after it was confirmed that a young man had been infected. 2010 and later In May 2010, the Behana creek water supply south of Cairns, Australia, was found to be contaminated by cryptosporidium. In July 2010, a local sports center in Cumbernauld (Glasgow, UK) detected traces of cryptosporidium in its swimming pools, causing a temporary closure of the swimming pools. In November 2010, over 4000 cases of cryptosporidiosis were reported in Östersund, Sweden. The source of contamination was the tap water. In mid December 2010 the number of reported cases was 12,400 according to local media. As of April 2011, there has been an ongoing outbreak in Skellefteå, Sweden. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Several tests have been taken around the water treatment unit "Abborren", but so far no results have turned up positive. Residents are being advised to boil the tap water as they continue to search for the contaminating source. Since May 2011, there has been an ongoing outbreak in South Roscommon in Ireland. Although many people have been diagnosed with cryptosporidiosis, the source of the parasite has not yet been found. Testing continues and Roscommon County Council are now considering introducing Ultra Violet Filtration to their water treatment process in the next 12 months. Residents are being advised to boil the tap water and there is no sign of this boil notice being lifted in the near future. In May 2013, in Roscommon, Ireland, another outbreak of the cryptosporidiosis was reported and a boil water notice was issued. This was the second time the parasite was detected in a month in the Roscommon water supply. The source of one of the outbreaks had been linked to the agricultural community. At least 13 people were treated for Cryptosporidiosis. See also Cryptosporidium was the basis of the 1998 television film, Thirst, in which it mutates and passes through a towns water filters. Cryptosporidium was shown on three episodes in three seasons of the television show, Monsters Inside Me References White, A. Clinton Jr. (2005). "Cryptosporidiosis". In Mandell, G; et al. (eds.). Principles and Practice of Infectious Diseases (6th ed.). Elsevier. pp. 3215–28. Upton, Steve J. (12 September 2003). "Basic Biology of Cryptosporidium" (Website). Kansas State University: Parasitology Laboratory. S.J. Brands (Compiler) (2000). "The Taxonomicon & Systema Naturae" (Website database). Taxon: Genus Cryptosporidium. Universal Taxonomic Services, Amsterdam, The Netherlands. Heymann, David (2015). Control of communicable diseases manual : an official report of the American Public Health Association. APHA Press, the American Public Health Association. ISBN 9780875530185. External links Cryptosporidiosis — Centers for Disease Control and Prevention Aquatics International Article Regarding Infection via Spray Parks CryptoDB: The Cryptosporidium Genome Resource

Epidural abscess

An epidural abscess refers to a collection of pus and infectious material located in the epidural space superficial to the dura mater which surrounds the central nervous system. Due to its location adjacent to brain or spinal cord, epidural abscesses have the potential to cause weakness, pain, and paralysis. Types Spinal epidural abscess A spinal epidural abscess (SEA) is a collection of pus or inflammatory granulation between the dura mater and the vertebral column. Currently the annual incidence rate of SEAs is estimated to be 2.5-3 per 10,000 hospital admissions. Incidence of SEA is on the rise, due to factors such as an aging population, increase in use of invasive spinal instrumentation, growing number of patients with risk factors such as diabetes and intravenous drug use. SEAs are more common in posterior than anterior areas, and the most common location is the thoracolumbar area, where epidural space is larger and contains more fat tissue. SEAs are more common in males, and can occur in all ages, although highest prevalence is during the fifth and seventh decades of life.Combined treatment - emergency surgery and antibiotics is the preferred treatment for the spinal epidural abscess, removing existing pus (which is tested for microorganisms to select the most appropriate antibiotic) and removing pressure from the spinal cord and nerve roots. Antibiotic therapy should start after obtaining pus for microbiological investigation. Cranial epidural abscess A cranial epidural abscess involves pus and granulation tissue accumulation in between the dura mater and cranial bone. These typically arise (along with osteomyelitis of a cranial bone) from infections of the ear or paranasal sinuses. They rarely can be caused by distant infection or an infected cerebral venous sinus thrombosis. Staphylococcus aureus is the most common pathogen. Symptoms include pain at the forehead or ear, pus draining from the ear or sinuses, tenderness overlying the infectious site, fever, neck stiffness, and in rare cases focal seizures. Treatment requires a combination of antibiotics and surgical removal of infected bone. References article/232570 at eMedicine

Primary aldosteronism

Primary aldosteronism (PA), also known as primary hyperaldosteronism or Conns syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high blood pressure. This abnormality is caused by hyperplasia or tumors. Many experience fatigue, potassium deficiency and high blood pressure which may cause poor vision, confusion or headaches. Symptoms may also include: muscular aches and weakness, muscle spasms, low back and flank pain from the kidneys, trembling, tingling sensations, dizziness/vertigo, nocturia and excessive urination. Complications include cardiovascular disease such as stroke, myocardial infarction, kidney failure and abnormal heart rhythms.Primary hyperaldosteronism has a number of causes. About 33% of cases are due to an adrenal adenoma that produces aldosterone, and 66% of cases are due to an enlargement of both adrenal glands. Other uncommon causes include adrenal cancer and an inherited disorder called familial hyperaldosteronism. Some recommend screening people with high blood pressure who are at increased risk, while others recommend screening all people with high blood pressure for the disease. Screening is usually done by measuring the aldosterone-to-renin ratio in the blood (ARR) whilst off interfering medications and a serum potassium over 4, with further testing used to confirm positive results. While low blood potassium is classically described in primary hyperaldosteronism, this is only present in about a quarter of people. To determine the underlying cause, medical imaging is carried out.Some cases may be cured by removing the adenoma by surgery after localization with adrenal venous sampling (AVS). A single adrenal gland may also be removed in cases where only one is enlarged. In cases due to enlargement of both glands, treatment is typically with medications known as aldosterone antagonists such as spironolactone or eplerenone. Other medications for high blood pressure and a low salt diet, e.g. DASH diet, may also be needed. Some people with familial hyperaldosteronism may be treated with the steroid dexamethasone.Primary aldosteronism is present in about 10% of people with high blood pressure. It occurs more often in women than men. Often, it begins in those between 30 and 50 years of age. Conns syndrome is named after Jerome W. Conn (1907–1994), an American endocrinologist who first described adenomas as a cause of the condition in 1955. Signs and symptoms People often have few or no symptoms. They may get occasional muscular weakness, muscle spasms, tingling sensations, or excessive urination.High blood pressure, manifestations of muscle cramps (due to hyperexcitability of neurons secondary to low blood calcium), muscle weakness (due to hypoexcitability of skeletal muscles secondary to hypokalemia), and headaches (due to low blood potassium or high blood pressure) may be seen.Secondary hyperaldosteronism is often related to decreased cardiac output, which is associated with elevated renin levels. Causes The condition is due to: Bilateral idiopathic (micronodular) adrenal hyperplasia: 66% of cases Adrenal adenoma (Conns disease): 33% of cases Primary (unilateral) adrenal hyperplasia: 2% of cases Aldosterone-producing adrenocortical carcinoma: <1% of cases Familial Hyperaldosteronism (FH) Glucocorticoid-remediable aldosteronism (FH type I): <1% of cases FH type II (APA or IHA): <2% of cases Ectopic aldosterone-producing adenoma or carcinoma: < 0.1% of cases Genetics 40% of people with an adrenal aldosterone producing adenoma have somatic gain-of-function mutations in a single gene (KCNJ5). This gene is mutated in inherited cases of early onset primary aldosteronism and bilateral adrenal hyperplasia, albeit less frequently. These mutations tend to occur in young women with the adenoma in the cortisol secreting zona fasciculata. Adenomas without this mutation tend to occur in older men with resistant hypertension.Other genes commonly mutated in aldosterone producing adenomas are ATP1A1 ATP2B3, CACNA1D, and CTNNB1. Epidemiology In the past, the prevalence of primary aldosteronism was considered to be less than 1% of patients with hypertension. More recent studies have reported much higher prevalence of primary aldosteronism, up-to 12.7% in primary care and to 29.8% in referral centers. Very low rates of compliance with screening guidelines lead to the underdiagnoses of primary aldosteronism. Pathophysiology Aldosterone has effects on most or all cells of the body but, clinically, the most important actions are in the kidney, on cells of the late distal convoluted tubule and medullary collecting duct. In the principal cells aldosterone increases activity of basolateral membrane sodium-potassium ATPase and apical epithelial sodium channels, ENaC, as well as potassium channels, ROMK. These actions increase sodium reabsorption and potassium secretion. Since more sodium is reabsorbed than potassium secreted, it also makes the lumen more electrically negative, causing chloride to follow sodium. Water then follows sodium and chloride by osmosis. In Conn syndrome, these actions cause increased extracellular sodium and fluid volume and reduced extracellular potassium. Aldosterone also acts on intercalated cells to stimulate an apical proton ATPase, causing proton secretion that acidifies urine and alkalizes extracellular fluid.In summary, hyperaldosteronism causes hypernatremia, hypokalemia, and metabolic alkalosis.Finer notes on aldosterone include the fact that it stimulates sodium-potassium ATPase in muscle cells, increasing intracellular potassium and also increases sodium reabsorption all along the intestine and nephron, possibly due to widespread stimulation of sodium-potassium ATPase. Finally, epithelial cells of sweat gland ducts and distal colon surface respond exactly the same as the principal cells of the nephron. These responses are important in climate adaptation and as a cause of constipation with elevated aldosterone. The sodium retention leads to plasma volume expansion and elevated blood pressure. The increased blood pressure will lead to increased glomerular filtration rate and cause a decrease in renin released from the granular cells of the juxtaglomerular apparatus in the kidney decreasing sodium reabsorption and returning sodium renal excretion to near normal levels allowing sodium to escape the effect of mineralocorticoids (also known as Aldosterone escape mechanism in primary hyperaldosteronism also contributed to by increased ANP level). If there is primary hyperaldosteronism, the decreased renin (and subsequent decreased angiotensin II) will not lead to a decrease in aldosterone levels (a very helpful clinical tool in diagnosis of primary hyperaldosteronism). Diagnosis Screening may be considered in people with high blood pressure presenting with low blood potassium, high blood pressure that is difficult to treat, other family members with the same condition, or a mass on the adrenal gland.Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. Rather, both renin and aldosterone are measured, and a resultant aldosterone-to-renin ratio (ARR) is used for case detection. A high aldosterone-to-renin ratio suggests the presence of primary hyperaldosteronism. The diagnosis is made by performing a saline suppression test, ambulatory salt loading test, or fludrocortisone suppression test.Measuring sodium and potassium concentrations simultaneously in serum and urine specimens has been suggested for screening purposes. Calculating the serum sodium over urinary sodium to serum potassium over urinary potassium (SUSPUP) and the (serum sodium to urinary sodium to (serum potassium)2 (SUSPPUP) ratios delivers calculated structure parameters of the RAAS, which may be used as a static function test. Its results have to be confirmed by calculating the ARR.If primary hyperaldosteronism is confirmed biochemically, CT scanning or other cross-sectional imaging can confirm the presence of an adrenal abnormality, possibly an adrenal cortical adenoma (aldosteronoma), adrenal carcinoma, bilateral adrenal hyperplasia, or other less common changes. Imaging findings may ultimately lead to other necessary diagnostic studies, such as adrenal venous sampling, to clarify the cause. It is not uncommon for adults to have bilateral sources of aldosterone hypersecretion in the presence of a nonfunctioning adrenal cortical adenoma, making adrenal venous sampling (AVS) mandatory in cases where surgery is being considered. For cases where AVS is unable to provide lateralisation of the source/sources of aldosterone hypersecretion, radionuclide imaging such as NP-59 scintigraphy or PET/CT with 11C-Metomidate is an option. Since 11C-Metomidate is unspecific for CYP11B1/CYP11B2 the patient needs pre-treatment with dexamethasone to downregulate the expression of CYP11B1.The diagnosis is best accomplished by an appropriately-trained subspecialist, though primary care providers are critical in recognizing clinical features of primary aldosteronism and obtaining the first blood tests for case detection. Classification Some people only use Conns syndrome for when it occurs due to an adrenal adenoma (a type of benign tumor). In practice, however, the terms are often used interchangeably, regardless of the underlying physiology. Differential diagnosis Primary hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizin. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis (an anise-flavored aperitif containing glycyrrhizinic acid). Treatment The treatment for hyperaldosteronism depends on the underlying cause. In people with a single benign tumor (adenoma), surgical removal (adrenalectomy) may be curative. This is usually performed laparoscopically, through several very small incisions. For people with hyperplasia of both glands, successful treatment is often achieved with spironolactone or eplerenone, drugs that block the aldosterone receptor. With its antiandrogen effect, spironolactone drug therapy may have a range of side effects in males and females, including gynecomastia and irregular menses. These symptoms occur less frequently with eplerenone drug therapy.In the absence of treatment, individuals with hyperaldosteronism often have poorly controlled high blood pressure, which may be associated with increased rates of stroke, heart disease, and kidney failure. With appropriate treatment, the prognosis is considered good.Esaxerenone, the first non-steroidal mineralocorticoid blocker, was approved in 2019 in Japan to treat essential hypertension. Finerenone, a drug belonging to the same class, reached phase 3 clinical trial in 2020, but is not yet considered for hypertension. More importantly, next-generation Aldosterone Synthase Inhibitors have entered the research pipeline with CIN-107 undergoing Phase 2 clinical trial as of 2021 Society and culture The Primary Aldosteronism Foundation is a patient-driven initiative committed to creating the paradigm shift that will lead to optimum diagnosis and treatment of primary aldosteronism by raising awareness, fostering research, and providing support to patients and healthcare professionals worldwide. Eponym Conns syndrome is named after Jerome W. Conn (1907–1994), the American endocrinologist who first described the condition at the University of Michigan in 1955. References External links Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. (May 2016). "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 101 (5): 1889–1916. doi:10.1210/jc.2015-4061. PMID 26934393.

Gestational diabetes

Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it does increase the risk of pre-eclampsia, depression, and requiring a Caesarean section. Babies born to mothers with poorly treated gestational diabetes are at increased risk of being too large, having low blood sugar after birth, and jaundice. If untreated, it can also result in a stillbirth. Long term, children are at higher risk of being overweight and developing type 2 diabetes.Gestational diabetes can occur during pregnancy because of insulin resistance or reduced production of insulin. Risk factors include being overweight, previously having gestational diabetes, a family history of type 2 diabetes, and having polycystic ovarian syndrome. Diagnosis is by blood tests. For those at normal risk, screening is recommended between 24 and 28 weeks gestation. For those at high risk, testing may occur at the first prenatal visit.Prevention is by maintaining a healthy weight and exercising before pregnancy. Gestational diabetes is treated with a diabetic diet, exercise, medication (such as metformin), and possibly insulin injections. Most women are able to manage their blood sugar with diet and exercise. Blood sugar testing among those who are affected is often recommended four times a day. Breastfeeding is recommended as soon as possible after birth.Gestational diabetes affects 3–9% of pregnancies, depending on the population studied. It is especially common during the last three months of pregnancy. It affects 1% of those under the age of 20 and 13% of those over the age of 44. A number of ethnic groups including Asians, American Indians, Indigenous Australians, and Pacific Islanders are at higher risk. In 90% of cases, gestational diabetes will resolve after the baby is born. Women, however, are at an increased risk of developing type 2 diabetes. Classification Gestational diabetes is formally defined as "any degree of glucose intolerance with onset or first recognition during pregnancy". This definition acknowledges the possibility that a woman may have previously undiagnosed diabetes mellitus, or may have developed diabetes coincidentally with pregnancy. Whether symptoms subside after pregnancy is also irrelevant to the diagnosis. A woman is diagnosed with gestational diabetes when glucose intolerance continues beyond 24 to 28 weeks of gestation. The White classification, named after Priscilla White, who pioneered research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. It distinguishes between gestational diabetes (type A) and pregestational diabetes (diabetes that existed prior to pregnancy). These two groups are further subdivided according to their associated risks and management.The two subtypes of gestational diabetes under this classification system are: Type A1: abnormal oral glucose tolerance test (OGTT), but normal blood glucose levels during fasting and two hours after meals; diet modification is sufficient to control glucose levels Type A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is requiredDiabetes which existed prior to pregnancy is also split up into several subtypes under this system: Type B: onset at age 20 or older and duration of less than 10 years. Type C: onset at age 10–19 or duration of 10–19 years. Type D: onset before age 10 or duration greater than 20 years. Type E: overt diabetes mellitus with calcified pelvic vessels. Type F: diabetic nephropathy. Type R: proliferative retinopathy. Type RF: retinopathy and nephropathy. Type H: ischemic heart disease. Type T: prior kidney transplant.An early age of onset or long-standing disease comes with greater risks, hence the first three subtypes.Two other sets of criteria are available for diagnosis of gestational diabetes, both based on blood-sugar levels.Criteria for diagnosis of gestational diabetes, using the 100 gram Glucose Tolerance Test, according to Carpenter and Coustan: Fasting 95 mg/dl 1 hour 180 mg/dl 2 hours 155 mg/dl 3 hours 140 mg/dlCriteria for diagnosis of gestational diabetes according to National Diabetes Data Group: Fasting 105 mg/dl 1 hour 190 mg/dl 2 hours 165 mg/dl 3 hours 145 mg/dl Risk factors Classical risk factors for developing gestational diabetes are: Polycystic ovary syndrome A previous diagnosis of gestational diabetes or prediabetes, impaired glucose tolerance, or impaired fasting glycaemia A family history revealing a first-degree relative with type 2 diabetes Maternal age – a womans risk factor increases as she gets older (especially for women over 35 years of age). Paternal age – one study found that a fathers age over 55 years was associated with GD Ethnicity (those with higher risk factors include African-Americans, Afro-Caribbeans, Native Americans, Hispanics, Pacific Islanders, and people originating from South Asia) Being overweight, obese or severely obese increases the risk by a factor 2.1, 3.6 and 8.6, respectively. A previous pregnancy which resulted in a child with a macrosomia (high birth weight: >90th centile or >4000 g (8 lbs 12.8 oz)) Previous poor obstetric history Other genetic risk factors: There are at least 10 genes where certain polymorphism are associated with an increased risk of gestational diabetes, most notably TCF7L2.In addition to this, statistics show a double risk of GDM in smokers. Some studies have looked at more controversial potential risk factors, such as short stature.About 40–60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women. Typically, women with GDM exhibit no symptoms (another reason for universal screening), but some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, yeast infections and blurred vision. Pathophysiology The precise mechanisms underlying gestational diabetes remain unknown. The hallmark of GDM is increased insulin resistance. Pregnancy hormones and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor. The interference probably occurs at the level of the cell signaling pathway beyond the insulin receptor. Since insulin promotes the entry of glucose into most cells, insulin resistance prevents glucose from entering the cells properly. As a result, glucose remains in the bloodstream, where glucose levels rise. More insulin is needed to overcome this resistance; about 1.5–2.5 times more insulin is produced than in a normal pregnancy.Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which in cases of GDM progresses thereafter to levels seen in a non-pregnant woman with type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women with GDM have an insulin resistance that they cannot compensate for with increased production in the β-cells of the pancreas. Placental hormones, and, to a lesser extent, increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol and progesterone are the main culprits, but human placental lactogen, prolactin and estradiol contribute, too. Multivariate stepwise regression analysis reveals that, in combination with other placental hormones, leptin, tumor necrosis factor alpha, and resistin are involved in the decrease in insulin sensitivity occurring during pregnancy, with tumor necrosis factor alpha named as the strongest independent predictor of insulin sensitivity in pregnancy. An inverse correlation with the changes in insulin sensitivity from the time before conception through late gestation accounts for about half of the variance in the decrease in insulin sensitivity during gestation: in other words, low levels or alteration of TNF alpha factors corresponds with a greater chance of, or predisposition to, insulin resistance or sensitivity.It is unclear why some women are unable to balance insulin needs and develop GDM; however, a number of explanations have been given, similar to those in type 2 diabetes: autoimmunity, single gene mutations, obesity, along with other mechanisms.Though the clinical presentation of gestational diabetes is well characterized, the biochemical mechanism behind the disease is not well known. One proposed biochemical mechanism involves insulin-producing β-cell adaptation controlled by the HGF/c-MET signaling pathway. β-cell adaption refers to the change that pancreatic islet cells undergo during pregnancy in response to maternal hormones in order to compensate for the increased physiological needs of mother and baby. These changes in the β-cells cause increased insulin secretion as a result of increased β-cell proliferation. HGF/c-MET has also been implicated in β-cell regeneration, which suggests that HGF/c-MET may help increase β-cell mass in order to compensate for insulin needs during pregnancy. Recent studies support that loss of HGF/c-MET signaling results in aberrant β-cell adaptation.c-MET is a receptor tyrosine kinase (RTK) that is activated by its ligand, hepatocyte growth factor (HGF), and is involved in the activation of several cellular processes. When HGF binds c-MET, the receptor homodimerizes and self-phosphorylates to form an SH2 recognition domain. The downstream pathways activated include common signaling molecules such as RAS and MAPK, which affect cell motility, and cell cycle progression.Studies have shown that HGF is an important signaling molecule in stress related situations where more insulin is needed. Pregnancy causes increased insulin resistance and so a higher insulin demand. The β-cells must compensate for this by either increasing insulin production or proliferating. If neither of the processes occur, then markers for gestational diabetes are observed. It has been observed that pregnancy increases HGF levels, showing a correlation that suggests a connection between the signaling pathway and increased insulin needs. In fact, when no signaling is present, gestational diabetes is more likely to occur.The exact mechanism of HGF/c-MET regulated β-cell adaptation is not yet known but there are several hypotheses about how the signaling molecules contribute to insulin levels during pregnancy. c-MET may interact with FoxM1, a molecule important in the cell cycle, as FOXM1 levels decrease when c-MET is not present. Additionally, c-MET may interact with p27 as the protein levels increase with c-MET is not present. Another hypothesis says that c-MET may control β-cell apoptosis because a lack of c-MET causes increases cell death but the signaling mechanisms have not been elucidated.Although the mechanism of HGF/c-MET control of gestational diabetes is not yet well understood, there is a strong correlation between the signaling pathway and the inability to produce an adequate amount of insulin during pregnancy and thus it may be the target for future diabetic therapies.Because glucose travels across the placenta (through diffusion facilitated by GLUT1 carrier), which is located in the syncytiotrophoblast on both the microvillus and basal membranes, these membranes may be the rate-limiting step in placental glucose transport. There is a two- to three-fold increase in the expression of syncytiotrophoblast glucose transporters with advancing gestation. Finally, the role of GLUT3/GLUT4 transport remains speculative. If the untreated gestational diabetes fetus is exposed to consistently higher glucose levels, this leads to increased fetal levels of insulin (insulin itself cannot cross the placenta). The growth-stimulating effects of insulin can lead to excessive growth and a large body (macrosomia). After birth, the high glucose environment disappears, leaving these newborns with ongoing high insulin production and susceptibility to low blood glucose levels (hypoglycemia). Screening A number of screening and diagnostic tests have been used to look for high levels of glucose in plasma or serum in defined circumstances. One method is a stepwise approach where a suspicious result on a screening test is followed by diagnostic test. Alternatively, a more involved diagnostic test can be used directly at the first prenatal visit for a woman with a high-risk pregnancy. (for example in those with polycystic ovarian syndrome or acanthosis nigricans).Non-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with glucose solutions. A blood glucose level is determined when fasting, two hours after a meal, or simply at any random time. In contrast, challenge tests involve drinking a glucose solution and measuring glucose concentration thereafter in the blood; in diabetes, they tend to remain high. The glucose solution has a very sweet taste which some women find unpleasant; sometimes, therefore, artificial flavours are added. Some women may experience nausea during the test, and more so with higher glucose levels.There is currently not enough research to show which way is best at diagnosing gestational diabetes. Routine screening of women with a glucose challenge test may find more women with gestational diabetes than only screening women with risk factors. It is not clear how these screening tests affect the rest of the pregnancy. Future research should include how the method of screening impacts the mother and baby. Pathways Opinions differ about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. The most elaborate regimen entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, a woman may be tested earlier.In the United States, most obstetricians prefer universal screening with a screening glucose challenge test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the woman is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. The U.S. Preventive Services Task Force found there is insufficient evidence to recommend for or against routine screening, and a 2017 a Cochrane review found that there is not evidence to determine which screening method is best for women and their babies.Some pregnant women and careproviders choose to forgo routine screening due to the absence of risk factors, however this is not advised due to the large proportion of women who develop gestational diabetes despite having no risk factors present and the dangers to the mother and baby if gestational diabetes remains untreated. Non-challenge blood glucose tests When a plasma glucose level is found to be higher than 126 mg/dL (7.0 mmol/L) after fasting, or over 200 mg/dL (11.1 mmol/L) on any occasion, and if this is confirmed on a subsequent day, the diagnosis of GDM is made, and no further testing is required. These tests are typically performed at the first antenatal visit. They are simple to administer and inexpensive, but have a lower test performance compared to the other tests, with moderate sensitivity, low specificity and high false positive rates. Screening glucose challenge test The screening glucose challenge test (sometimes called the OSullivan test) is performed between 24 and 28 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). No previous fasting is required for this screening test, in contrast to the OGTT. The OSullivan test involves drinking a solution containing 50 grams of glucose, and measuring blood levels one hour later.If the cut-off point is set at 140 mg/dL (7.8 mmol/L), 80% of women with GDM will be detected. If this threshold for further testing is lowered to 130 mg/dL, 90% of GDM cases will be detected, but there will also be more women who will be subjected to a consequent OGTT unnecessarily. Oral glucose tolerance test A standardized oral glucose tolerance test (OGTT) should be done in the morning after an overnight fast of between 8 and 14 hours. During the three previous days the subject must have an unrestricted diet (containing at least 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated during the test and should not smoke throughout the test. The test involves drinking a solution containing a certain amount of glucose, usually 75 g or 100 g, and drawing blood to measure glucose levels at the start and on set time intervals thereafter. The diagnostic criteria from the National Diabetes Data Group (NDDG) have been used most often, but some centers rely on the Carpenter and Coustan criteria, which set the cutoff for normal at lower values. Compared with the NDDG criteria, the Carpenter and Coustan criteria lead to a diagnosis of gestational diabetes in 54 percent more pregnant women, with an increased cost and no compelling evidence of improved perinatal outcomes.The following are the values which the American Diabetes Association considers to be abnormal during the 100 g of glucose OGTT: Fasting blood glucose level ≥95 mg/dL (5.33 mmol/L) 1 hour blood glucose level ≥180 mg/dL (10 mmol/L) 2 hour blood glucose level ≥155 mg/dL (8.6 mmol/L) 3 hour blood glucose level ≥140 mg/dL (7.8 mmol/L)An alternative test uses a 75 g glucose load and measures the blood glucose levels before and after one and two hours, using the same reference values. This test will identify fewer women who are at risk, and there is only a weak concordance (agreement rate) between this test and a three-hour 100 g test.The glucose values used to detect gestational diabetes were first determined by OSullivan and Mahan (1964) in a retrospective cohort study (using a 100 grams of glucose OGTT) designed to detect risk of developing type 2 diabetes in the future. The values were set using whole blood and required two values reaching or exceeding the value to be positive. Subsequent information led to alterations in OSullivans criteria. When methods for blood glucose determination changed from the use of whole blood to venous plasma samples, the criteria for GDM were also changed. Urinary glucose testing Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed. Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first two trimesters is only around 10% and the positive predictive value is around 20%. Prevention Vitamin D supplementation during pregnancy may help to prevent gestational diabetes. A 2015 review found that when done during pregnancy moderate physical exercise is effective for the prevention of gestational diabetes. A 2014 review however did not find a significant effect. It is uncertain if additional dietary advice interventions help to reduce the risk of gestational diabetes. However, data from the Nurses Health Study shows that adherence to a healthy plant-based diet is associated with lower risk for GDM.Diet and physical activity interventions designed to prevent excessive gestational weight gain reduce the rates of gestational diabetes. However, the impact of these interventions varies with the body-mass index of the person as well as with the region in which the studies were performed.Moderate-quality evidence suggest that there is a reduced risk of gestational diabetes mellitus and caesarean section with combined diet and exercise interventions during pregnancy as well as reductions in gestational weight gain, compared with standard care.It has been suggested that for women who have had gestational diabetes, support between pregnancies may lower their chances of having gestational diabetes again in future pregnancies. This support might include diet and exercise, education, and lifestyle advice. However, there is no research to show whether interventions between pregnancies lower the number of women who develop gestational diabetes again.Theoretically, smoking cessation may decrease the risk of gestational diabetes among smokers. Management Treatment of GDM with diet and insulin reduces health problems mother and child. Treatment of GDM is also accompanied by more inductions of labour.A repeat OGTT should be carried out 6 weeks after delivery, to confirm the diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is advised.Lifestyle interventions include exercise, diet advice, behavioural interventions, relaxation, self-monitoring glucose, and combined interventions. Women with gestational diabetes who receive lifestyle interventions seem to have less postpartum depression, and were more likely to reach their weight loss targets after giving birth, than women who had no intervention. Their babies are also less likely to be large for their gestational age, and have less percentage of fat when they are born. More research is needed to find out which lifestyle interventions are best. Some women with GDM use probiotics but it is very uncertain if there are any benefits in terms of blood glucose levels, high blood pressure disorders or induction of labour.If a diabetic diet or G.I. Diet, exercise, and oral medication are inadequate to control glucose levels, insulin therapy may become necessary. The development of macrosomia can be evaluated during pregnancy by using sonography. Women who use insulin, with a history of stillbirth, or with hypertension are managed like women with overt diabetes. Lifestyle Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes. Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy. Some women will need antidiabetic drugs, most commonly insulin therapy. Any diet needs to provide sufficient calories for pregnancy, typically 2,000–2,500 kcal with the exclusion of simple carbohydrates. The main goal of dietary modifications is to avoid peaks in blood sugar levels. This can be done by spreading carbohydrate intake over meals and snacks throughout the day, and using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin resistance is highest in mornings, breakfast carbohydrates need to be restricted more. Ingesting more fiber in foods with whole grains, or fruit and vegetables can also reduce the risk of gestational diabetes. There is not enough evidence to indicate if one type of dietary advice is better than another.Regular moderately intense physical exercise is advised, although there is no consensus on the specific structure of exercise programs for GDM. Pregnant women who exercise have lower blood sugar levels when fasting and after meals compared to those who do not exercise. It is not clear which form of exercise is best when pregnant.Self monitoring can be accomplished using a handheld capillary glucose dosage system. Compliance with these glucometer systems can be low. There is not a lot of research into what target blood sugar levels should be for women with gestational diabetes and targets recommended to women vary around the world. Target ranges advised by the Australasian Diabetes in Pregnancy Society are as follows: fasting capillary blood glucose levels <5.5 mmol/L 1 hour postprandial capillary blood glucose levels <8.0 mmol/L 2 hour postprandial blood glucose levels <6.7 mmol/LRegular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes and related risks for both mother and child. Medication If monitoring reveals failing control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, treatment with insulin might be necessary. This is most commonly fast-acting insulin given just before eating to blunt glucose rises after meals. Care needs to be taken to avoid low blood sugar levels due to excessive insulin. Insulin therapy can be normal or very tight; more injections can result in better control but requires more effort, and there is no consensus that it has large benefits. A 2016 Cochrane review concluded that quality evidence is not yet available to determine the best blood sugar range for improving health for pregnant women with GDM and their babies.There is some evidence that certain medications by mouth might be safe in pregnancy, or at least, are less dangerous to the developing fetus than poorly controlled diabetes. When comparing which diabetes tablets (medication by mouth) work best and are safest, there is not enough quality research to support one medication over another. The medication metformin is better than glyburide. If blood glucose cannot be adequately controlled with a single agent, the combination of metformin and insulin may be better than insulin alone. Another review found good short term safety for both the mother and baby with metformin but unclear long term safety.People may prefer metformin by mouth to insulin injections. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels.Almost half of the women did not reach sufficient control with metformin alone and needed supplemental therapy with insulin; compared to those treated with insulin alone, they required less insulin, and they gained less weight. With no long-term studies into children of women treated with the drug, there remains a possibility of long-term complications from metformin therapy. Babies born to women treated with metformin have been found to develop less visceral fat, making them less prone to insulin resistance in later life. Prognosis Gestational diabetes generally resolves once the baby is born. Based on different studies, the chances of developing GDM in a second pregnancy, if a woman had GDM in her first pregnancy, are between 30 and 84%, depending on ethnic background. A second pregnancy within one year of the previous pregnancy has a large likelihood of GDM recurrence.Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. The risk is highest in women who needed insulin treatment, had antibodies associated with diabetes (such as antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2), women with more than two previous pregnancies, and women who were obese (in order of importance). Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years. Depending on the population studied, the diagnostic criteria and the length of follow-up, the risk can vary enormously. The risk appears to be highest in the first 5 years, reaching a plateau thereafter. One of the longest studies followed a group of women from Boston, Massachusetts; half of them developed diabetes after 6 years, and more than 70% had diabetes after 28 years. In a retrospective study in Navajo women, the risk of diabetes after GDM was estimated to be 50 to 70% after 11 years. Another study found a risk of diabetes after GDM of more than 25% after 15 years. In populations with a low risk for type 2 diabetes, in lean subjects and in women with auto-antibodies, there is a higher rate of women developing type 1 diabetes (LADA).Children of women with GDM have an increased risk for childhood and adult obesity and an increased risk of glucose intolerance and type 2 diabetes later in life. This risk relates to increased maternal glucose values. It is currently unclear how much genetic susceptibility and environmental factors contribute to this risk, and whether treatment of GDM can influence this outcome.Relative benefits and harms of different oral anti-diabetic medications are not yet well understood as of 2017.There are scarce statistical data on the risk of other conditions in women with GDM; in the Jerusalem Perinatal study, 410 out of 37,962 women were reported to have GDM, and there was a tendency towards more breast and pancreatic cancer, but more research is needed to confirm this finding.Research is being conducted to develop a web-based clinical decision support system for GDM prediction using machine learning techniques. Results so far demonstrated great potential in clinical practicality for automatic GDM prognosis. Complications GDM poses a risk to mother and child. This risk is largely related to uncontrolled blood glucose levels and its consequences. The risk increases with higher blood glucose levels. Treatment resulting in better control of these levels can reduce some of the risks of GDM considerably.The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit. Infants born to mothers with GDM are at risk of being both large for gestational age (macrosomic) in unmanaged GDM, and small for gestational age and Intrauterine growth retardation in managed GDM. Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps, ventouse and caesarean section) or problems during vaginal delivery (such as shoulder dystocia). Macrosomia may affect 12% of normal women compared to 20% of women with GDM. However, the evidence for each of these complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study for example, there was an increased risk for babies to be large but not small for gestational age in women with uncontrolled GDM. In a recent birth cohot study of 5150 deliveries, a research group active at the University of Helsinki and Helsinki University Hospital, Finland demonstrated that the mothers GDM is an independent factor that increases the risk of fetal hypoxia, during labour. The study was published in the Acta Diabetologica in June 2021. Another finding was that GDM increased the susceptibility of the fetus to intrapartum hypoxia, regardless of the size of the fetus. The risk of hypoxia and the resulting risk of poor condition in newborn infants was nearly 7-fold in the fetuses of mothers with GDM compared to the fetuses of non-diabetic mothers. Furthermore, according to the findings, the risk of needing to perform resuscitation on the newborn after birth was 10-fold.Another finding was that gestational diabetes increased the susceptibility of the fetus to intrapartal hypoxia, regardless of the size of the fetus. "The risk of hypoxia and the resulting risk of poor condition in newborn infants was nearly seven-fold in the fetuses of mothers with gestational diabetes compared to the fetuses of non-diabetic mothers," says researcher Mikko Tarvonen. According to the findings, the risk of needing to perform resuscitation on the newborn was ten-fold.Research into complications for GDM is difficult because of the many confounding factors (such as obesity). Labelling a woman as having GDM may in itself increase the risk of having an unnecessary caesarean section.Neonates born from women with consistently high blood sugar levels are also at an increased risk of low blood glucose (hypoglycemia), jaundice, high red blood cell mass (polycythemia) and low blood calcium (hypocalcemia) and magnesium (hypomagnesemia). Untreated GDM also interferes with maturation, causing dysmature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis.Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to be an independent risk factor for birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy, whereas GDM gradually develops and is least pronounced during the first and early second trimester. Studies have shown that the offspring of women with GDM are at a higher risk for congenital malformations. A large case-control study found that gestational diabetes was linked with a limited group of birth defects, and that this association was generally limited to women with a higher body mass index (≥ 25 kg/m2). It is difficult to make sure that this is not partially due to the inclusion of women with pre-existent type 2 diabetes who were not diagnosed before pregnancy. Because of conflicting studies, it is unclear at the moment whether women with GDM have a higher risk of preeclampsia. In the HAPO study, the risk of preeclampsia was between 13% and 37% higher, although not all possible confounding factors were corrected. Epidemiology Gestational diabetes affects 3–10% of pregnancies, depending on the population studied. References External links IDF Diabetes Atlas International Diabetes Federation National Institute of Child Health and Human Development – Am I at Risk for Gestational Diabetes? National Institute of Child Health and Human Development – Managing Gestational Diabetes: A Patients Guide to a Healthy Pregnancy Gestational Diabetes Resource Guide – American Diabetes Association Diabetes.co.uk: Gestational Diabetes

Beta thalassemia

Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.HBB blockage over time leads to decreased beta-chain synthesis. The bodys inability to construct new beta-chains leads to the underproduction of HbA (adult hemoglobin). Reductions in HbA available overall to fill the red blood cells in turn leads to microcytic anemia. Microcytic anemia ultimately develops in respect to inadequate HBB protein for sufficient red blood cell functioning. Due to this factor, the patient may require blood transfusions to make up for the blockage in the beta-chains. Repeated blood transfusions cause severe problems associated with iron overload. Signs and symptoms Three main forms have been described: thalassemia minor, thalassemia intermedia, and thalassemia major which vary from asymptomatic or mild symptoms to severe anemia requiring lifelong transfusions. Individuals with beta thalassemia major (those who are homozygous for thalassemia mutations, or inheriting 2 mutations) usually present within the first two years of life with symptomatic severe anemia, poor growth, and skeletal abnormalities. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, prenatal screening is very important. Those with beta thalassemia intermedia (those who are compound heterozygoutes for the beta thalassemia mutation) usually present later in life with mild to moderate symptoms of anemia. Beta thalassemia trait (also known as beta thalassemia minor) involves heterozygous inheritance of a beta-thalassemia mutation and patients usually have borderline microcytic, hypochromic anemia and they are usually asymptomatic or have mild symptoms. Beta thalassemia minor can also present as beta thalassemia silent carriers; those who inherit a beta thalassemic mutation but have no hematologic abnormalities nor symptoms. Some people with thalassemia are susceptible to health complications that involve the spleen (hypersplenism) and gallstones (due to hyperbilirubinemia from peripheral hemolysis). These complications are mostly found in thalassemia major and intermedia patients.Excess iron (from hemolysis or transfusions) causes serious complications within the liver, heart, and endocrine glands. Severe symptoms include liver cirrhosis, liver fibrosis, and in extreme cases, liver cancer. Heart failure, growth impairment, diabetes and osteoporosis are life-threatening conditions which can be caused by beta thalassemia major. The main cardiac abnormalities seen as a result of beta thalassemia and iron overload include left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valvulopathy, arrhythmias, and pericarditis. Increased gastrointestinal iron absorption is seen in all grades of beta thalassemia, and increased red blood cell destruction by the spleen due to ineffective erythropoiesis further releases additional iron into the bloodstream.Additional symptoms of beta thalassemia major or intermedia include the classic symptoms of moderate to severe anemia including fatigue, growth and developmental delay in childhood, leg ulcers and organ failure. Ineffective erythropoiesis (red blood cell production) can also lead to compensatory bone marrow expansion which can then lead to bony changes/deformities, bone pain and craniofacial abnormalities. Extramedullary organs such as the liver and spleen that can also undergo erythropoiesis become activated leading to hepatosplenomegaly (enlargement of the liver and spleen). Other tissues in the body can also become sites of erythropoiesis, leading to extramedullary hematopoietic pseudotumors which may cause compressive symptoms if they occur in the thoracic cavity or spinal canal. Cause Mutations Two major groups of mutations can be distinguished: Nondeletion forms: These defects, in general, involve a single base substitution or small insertions near or upstream of the β globin gene. Most often, mutations occur in the promoter regions preceding the beta-globin genes. Less often, abnormal splice variants are believed to contribute to the disease. Deletion forms: Deletions of different sizes involving the β globin gene produce different syndromes such as (βo) or hereditary persistence of fetal hemoglobin syndromes.Mutations are characterized as (βo) if they prevent any formation of β globin chains, mutations are characterized as (β+) if they allow some β globin chain formation to occur. mRNA assembly Beta thalassemia is a hereditary disease affecting hemoglobin. As with about half of all hereditary diseases, an inherited mutation damages the assembly of the messenger-type RNA (mRNA) that is transcribed from a chromosome. DNA contains both the instructions (genes) for stringing amino acids together into proteins, as well as stretches of DNA that play important roles in regulating produced protein levels.In thalassemia, an additional, contiguous length or a discontinuous fragment of non-coding instructions is included in the mRNA. This happens because the mutation obliterates the boundary between the intronic and exonic portions of the DNA template. Because all the coding sections may still be present, normal hemoglobin may be produced and the added genetic material, if it produces pathology, instead disrupts regulatory functions enough to produce anemia. Hemoblogins normal alpha and beta subunits each have an iron-containing central portion (heme) that allows the protein chain of a subunit to fold around it. Normal adult hemoglobin contains 2 alpha and 2 beta subunits. Thalassemias typically affect only the mRNAs for production of the beta chains (hence the name). Since the mutation may be a change in only a single base (single-nucleotide polymorphism), on-going efforts seek gene therapies to make that single correction. Risk factors Family history and ancestry are factors that increase the risk of beta thalassemia. Depending on family history, if a persons parents or grandparents had beta thalassemia major or intermedia, there is a 75% (3 out of 4) probability (see inheritance chart at top of page) of the mutated gene being inherited by an offspring. Even if a child does not have beta thalassemia major or intermedia, they can still be a carrier, possibly resulting in future generations of their offspring having beta thalassemia.Another risk factor is ancestry. Beta thalassemia occurs most often in people of Italian, Greek, Middle Eastern, Southern Asian, and African ancestry. Diagnosis Abdominal pain due to hypersplenism, splenic infarction and right-upper quadrant pain caused by gallstones are major clinical manifestations. However, diagnosing thalassemia from symptoms alone is inadequate. Physicians note these signs as associative due to this diseases complexity. The following associative signs can attest to the severity of the phenotype: pallor, poor growth, inadequate food intake, splenomegaly, jaundice, maxillary hyperplasia, dental malocclusion, cholelithiasis, systolic ejection murmur in the presence of severe anemia and pathologic fractures. Based on symptoms, tests are ordered for a differential diagnosis. These tests include complete blood count; hemoglobin electrophoresis; serum transferrin, ferritin, total iron-binding capacity; urine urobilin and urobilogen; peripheral blood smear, which may show codocytes, or target cells; hematocrit; and serum bilirubin. The expected pattern on hemoglobin electrophoresis in people with beta-thalassemia is an increased level of hemoglobin A2 and slightly increased hemoglobin F. The diagnosis is confirmed with hemoglobin electrophoresis or high performance liquid chromatography.Skeletal changes associated with expansion of the bone marrow: Chipmunk facies: bossing of the skull, prominent malar eminence, depression of the bridge of the nose, tendency to a mongoloid slant of the eye, and exposure of the upper teeth due to hypertrophy of the maxillae. Hair-on-end (or "crew cut") on skull X-ray: new bone formation due to the inner table. DNA analysis All beta thalassemias may exhibit abnormal red blood cells; a family history is followed by DNA analysis. This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: fatigue, breathlessness and poor exercise tolerance. Further genetic analysis may include HPLC should routine electrophoresis prove difficult. Prevention Beta thalassemia is a hereditary disease allowing for a preventative treatment by carrier screening and prenatal diagnosis. It can be prevented if one parent has normal genes, giving rise to screenings that empower carriers to select partners with normal hemoglobin. A study aimed at detecting the genes that could give rise to offspring with sickle cell disease. Patients diagnosed with beta thalassemia have MCH ≤ 26 pg and an RDW < 19. Of 10,148 patients, 1,739 patients had a hemoglobin phenotype and RDW consistent with beta thalassemia. After the narrowing of patients, the HbA2 levels were tested presenting 77 patients with beta thalassemia. This screening procedure proved insensitive in populations of West African ancestry because of the indicators has high prevalence of alpha thalassemia. Countries have programs distributing information about the reproductive risks associated with carriers of haemoglobinopathies. Thalassemia carrier screening programs have educational programs in schools, armed forces, and through mass media as well as providing counseling to carriers and carrier couples. Screening has shown reduced incidence; by 1995 the prevalence in Italy reduced from 1:250 to 1:4000, and a 95% decrease in that region. The decrease in incidence has benefitted those affected with thalassemia, as the demand for blood has decreased, therefore improving the supply of treatment. Treatment Beta thalassemia major Affected children require regular lifelong blood transfusions. Bone marrow transplants can be curative for some children. Patients receive frequent blood transfusions that lead to or potentiate iron overload. Iron chelation treatment is necessary to prevent damage to internal organs in cases of iron overload. Advances in iron chelation treatments allow patients with thalassemia major to live long lives with access to proper treatment. Popular chelators include deferoxamine and deferiprone.The oral chelator deferasirox was approved for use in 2005 in some countries. Bone marrow transplantation is the only cure and is indicated for patients with severe thalassemia major. Transplantation can eliminate a patients dependence on transfusions. Absent a matching donor, a savior sibling can be conceived by preimplantation genetic diagnosis (PGD) to be free of the disease as well as to match the recipients human leukocyte antigen (HLA) type.Serum ferritin (the storage form of iron) is routinely measured in those with beta thalassemia to determine the degree of iron overload; with increased ferritin levels directing the use of iron chelation therapy. The three iron chelators; subcutaneous deferoxamine, oral deferiprone and oral deferasirox can be used as monotherapy or in combination, they have all been shown to decrease serum/systemic iron levels, hepatic and cardiac iron levels as well as decreasing the risk of cardiac arrhythmia, heart failure and death. Hepatic and myocardial MRI is also used to quantify the iron deposition in target organs, especially the heart and liver, to guide therapy.Scientists at Weill Cornell Medical College have developed a gene therapy strategy that could feasibly treat both beta-thalassemia and sickle cell disease. The technology is based on delivery of a lentiviral vector carrying both the human β-globin gene and an ankyrin insulator to improve gene transcription and translation, and boost levels of β-globin production.On June 10, 2022, a U.S. federal advisory panel recommended that the FDA approve a gene therapy treatment for use with beta thalassemia. Surgical Patients with thalassemia major are more inclined to have a splenectomy. The use of splenectomies have been declining in recent years due to decreased prevalence of hypersplenism in adequately transfused patients. Splenectomy is also associated with increased risk of infections and increased morbidity due to vascular disease, as the spleen is involved in scavenging to rid the body of pathologic or abnormal red blood cells. Patients with hypersplenism are more likely to have a lower amount of healthy blood cells in their body than normal and reveal symptoms of anemia. The different surgical techniques are the open and laparoscopic method. The laparoscopic method requires longer operating time but a shorter recovery period with a smaller and less prominent surgical scar. If it is unnecessary to remove the entire spleen a partial splenectomy may occur; this method preserves some of the immune function while reducing the probability of hypersplenism. Those undergoing splenectomy should receive an appropriate pneumococcal vaccine at least one week (preferably three weeks) before the surgery. Therapeutic Long-term transfusion therapy (in those with transfusion dependent beta thalassemia) is a treatment used to maintain hemoglobin levels at a target pre-transfusion hemoglobin level of 9–10.5 g/dL (11-12 g/dL in those with concomitant heart disease). To ensure quality blood transfusions, the packed red blood cells should be leucoreduced. By having leucoreduced blood packets, the patient is at a lower risk to develop adverse reactions by contaminated white cells and preventing platelet alloimmunisation. Patients with allergic transfusion reactions or unusual red cell antibodies must receive washed red cells or cryopreserved red cells. Washed red cells have been removed of plasma proteins that would have become a target of the patients antibodies allowing the transfusion to be carried out safely. Cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens. These regular transfusions promote normal growth, physical activities and suppress bone marrow hyperactivity. Pharmaceutical During normal iron homeostasis the circulating iron is bound to transferrin. But with iron overload (such as with frequent blood transfusions), the ability for transferrin to bind iron is exceeded and non-transferrin bound iron accumulated. This unbound iron is toxic due to its high propensity to induce oxygen species and is responsible for cellular damage. The prevention of iron overload protects patients from morbidity and mortality. The primary aim is to bind to and remove iron from the body and a rate equal to the rate of transfusional iron input or greater than iron input. Iron chelation is a medical therapy that may prevent the complications of iron overload. Every unit of transfused blood contains 200–250 mg of iron and the body has no natural mechanism to remove excess iron. The excess iron can be removed by iron chelators (deferoxamine, deferiprone and deferasirox).Luspatercept (ACE-536) is a recombinant fusion protein that is used as a treatment in adults with transfusion dependent beta thalassemia. It consists of a modified extra-cellular domain of human activin receptor type IIB bound to the Fc portion of the human IgG1 antibody. The molecule binds to select transforming growth factor beta superfamily ligands to block SMAD2 and 3 signaling, thus enhancing erythroid maturation. The medication has been shown to reduce the transfusion burden by 33% in adults with transfusion dependent beta thalassemia as compared to placebo and was also associated with decreased ferritin levels (with no significant decreases in liver or cardiac iron levels). Beta thalassemia intermedia Patients with beta thalassemia intermedia require no transfusions or may require episodic blood transfusions during certain circumstances (infection, pregnancy, surgery). Patients with frequent transfusions may develop iron overload and require chelation therapy. Transmission is autosomal recessive; however, dominant mutations and compound heterozygotes have been reported. Genetic counseling is recommended and prenatal diagnosis may be offered. Beta thalassemia minor Patients with beta thalassemia minor are usually asymptomatic and are often monitored without treatment. Beta thalassemia minor may coexist with other conditions such as chronic hepatitis B, chronic hepatitis C, non-alcoholic fatty liver disease and alcoholic liver disease that, when combined or co-existing, may cause a person to have iron overload of the liver and more severe liver disease. Epidemiology The beta form of thalassemia is particularly prevalent among the Mediterranean peoples and this geographical association is responsible for its naming: thalassa (θάλασσα) is the Greek word for sea and haima (αἷμα) is the Greek word for blood. In Europe, the highest concentrations of the disease are found in Greece and the Turkish coastal regions. The major Mediterranean islands (except the Balearics) such as Sicily, Sardinia, Corsica, Cyprus, Malta and Crete are heavily affected in particular. Other Mediterranean peoples, as well as those in the vicinity of the Mediterranean, also have high incidence rates, including people from West Asia and North Africa. The data indicate that 15% of the Greek and Turkish Cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes. Evolutionary adaptation The thalassemia trait may confer a degree of protection against malaria, which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers (known as heterozygous advantage), thus perpetuating the mutation. In that respect, the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease. Incidence The disorder is more prevalent in certain ethnicities and age groups. Beta thalassemia is most prevalent in the "thalassemia belt" which includes areas in Sub-Saharan Africa, the Mediterranean extending into the Middle East and Southeast Asia. This geographical distribution is thought to be due to beta-thalassemia carrier state (beta thalassemia minor) conferring a resistance to malaria. In the United States, thalassemias prevalence is approximately 1 in 272,000 or 1,000 people. There have been 4,000 hospitalized cases in England in 2002 and 9,233 consultant episodes for thalassemia. Men accounted for 53% of hospital consultant episodes and women accounted for 47%. The mean patient age is 23, with only 1% of consultants being older than 75, and 69% being 15–59. It is estimated that 1.5% of the worlds population are carriers and 40,000 affected infants are born with the disease annually. Beta thalassemia major is usually fatal in infancy if blood transfusions are not initiated immediately. See also Alpha-thalassemia Anisopoikilocytosis (variance in red blood cell size, usually as a result of beta thalassemia) Delta-thalassemia Hemoglobinopathy References Further reading Cao, Antonio; Galanello, Renzo (2010). "Beta-Thalassemia". In Pagon, Roberta A; Bird, Thomas D; Dolan, Cynthia R; Stephens, Karen; Adam, Margaret P (eds.). GeneReviews. University of Washington, Seattle. PMID 20301599. Bahal, Raman; McNeer, Nicole Ali; Quijano, Elias; Liu, Yanfeng; Sulkowski, Parker; Turchick, Audrey; Lu, Yi-Chien; Bhunia, Dinesh C.; Manna, Arunava; Greiner, Dale L.; Brehm, Michael A.; Cheng, Christopher J.; López-Giráldez, Francesc; Ricciardi, Adele; Beloor, Jagadish; Krause, Diane S.; Kumar, Priti; Gallagher, Patrick G.; Braddock, Demetrios T.; Saltzman, W. Mark; Ly, Danith H.; Glazer, Peter M. (26 October 2016). "In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery". Nature Communications. 7: 13304. Bibcode:2016NatCo...713304B. doi:10.1038/ncomms13304. ISSN 2041-1723. PMC 5095181. PMID 27782131. == External links ==

Pyloric stenosis

Pyloric stenosis is a narrowing of the opening from the stomach to the first part of the small intestine (the pylorus). Symptoms include projectile vomiting without the presence of bile. This most often occurs after the baby is fed. The typical age that symptoms become obvious is two to twelve weeks old.The cause of pyloric stenosis is unclear. Risk factors in babies include birth by cesarean section, preterm birth, bottle feeding, and being first born. The diagnosis may be made by feeling an olive-shaped mass in the babys abdomen. This is often confirmed with ultrasound.Treatment initially begins by correcting dehydration and electrolyte problems. This is then typically followed by surgery, although some treat the condition without surgery by using atropine. Results are generally good both in the short term and in the long term.About one to two per 1,000 babies are affected, and males are affected about four times more often than females. The condition is very rare in adults. The first description of pyloric stenosis was in 1888 with surgery management first carried out in 1912 by Conrad Ramstedt. Before surgical treatment most babies died. Signs and symptoms Babies with this condition usually present any time in the first weeks to 6 months of life with progressively worsening vomiting. It is more likely to affect the first-born with males more commonly than females at a ratio of 4 to 1. The vomiting is often described as non-bile stained ("non bilious") and "projectile vomiting", because it is more forceful than the usual spitting up (gastroesophageal reflux) seen at this age. Some infants present with poor feeding and weight loss but others demonstrate normal weight gain. Dehydration may occur which causes a baby to cry without having tears and to produce less wet or dirty diapers due to not urinating for hours or for a few days. Symptoms usually begin between 3 and 12 weeks of age. Findings include epigastric fullness with visible peristalsis in the upper abdomen from the infants left to right. Constant hunger, belching, and colic are other possible signs that the baby is unable to eat properly. Cause Rarely, infantile pyloric stenosis can occur as an autosomal dominant condition. It is uncertain whether it is a congenital anatomic narrowing or a functional hypertrophy of the pyloric sphincter muscle. Pathophysiology The gastric outlet obstruction due to the hypertrophic pylorus impairs emptying of gastric contents into the duodenum. As a consequence, all ingested food and gastric secretions can only exit via vomiting, which can be of a projectile nature. While the exact cause of the hypertrophy remains unknown, one study suggested that neonatal hyperacidity may be involved in the pathogenesis. This physiological explanation for the development of clinical pyloric stenosis at around 4 weeks and its spontaneous long term cure without surgery if treated conservatively, has recently been further reviewed.Persistent vomiting results in loss of stomach acid (hydrochloric acid). The vomited material does not contain bile because the pyloric obstruction prevents entry of duodenal contents (containing bile) into the stomach. The chloride loss results in a low blood chloride level which impairs the kidneys ability to excrete bicarbonate. This is the factor that prevents correction of the alkalosis leading to metabolic alkalosis.A secondary hyperaldosteronism develops due to the decreased blood volume. The high aldosterone levels causes the kidneys to avidly retain Na+ (to correct the intravascular volume depletion), and excrete increased amounts of K+ into the urine (resulting in a low blood level of potassium).The bodys compensatory response to the metabolic alkalosis is hypoventilation resulting in an elevated arterial pCO2. Diagnosis Diagnosis is via a careful history and physical examination, often supplemented by radiographic imaging studies. Pyloric stenosis should be suspected in any young infant with severe vomiting. On physical exam, palpation of the abdomen may reveal a mass in the epigastrium. This mass, which consists of the enlarged pylorus, is referred to as the olive, and is sometimes evident after the infant is given formula to drink. Rarely, there are peristaltic waves that may be felt or seen (video on NEJM) due to the stomach trying to force its contents past the narrowed pyloric outlet.Most cases of pyloric stenosis are diagnosed/confirmed with ultrasound, if available, showing the thickened pylorus and non-passage of gastric contents into the proximal duodenum. Muscle wall thickness 3 millimeters (mm) or greater and pyloric channel length of 15 mm or greater are considered abnormal in infants younger than 30 days. Gastric contents should not be seen passing through the pylorus because if it does, pyloric stenosis should be excluded and other differential diagnoses such as pylorospasm should be considered. The positions of superior mesenteric artery and superior mesenteric vein should be noted because altered positions of these two vessels would be suggestive of intestinal malrotation instead of pyloric stenosis.Although the baby is exposed to radiation, an upper GI series (X-rays taken after the baby drinks a special contrast agent) can be diagnostic by showing the pylorus with elongated, narrow lumen and a dent in the duodenal bulb. This phenomenon caused "string sign" or the "railroad track/double track sign" on X-rays after contrast is given. Plain x-rays of the abdomen sometimes shows a dilated stomach.Although upper gastrointestinal endoscopy would demonstrate pyloric obstruction, physicians would find it difficult to differentiate accurately between hypertrophic pyloric stenosis and pylorospasm.Blood tests will reveal low blood levels of potassium and chloride in association with an increased blood pH and high blood bicarbonate level due to loss of stomach acid (which contains hydrochloric acid) from persistent vomiting. There will be exchange of extracellular potassium with intracellular hydrogen ions in an attempt to correct the pH imbalance. These findings can be seen with severe vomiting from any cause. Treatment Infantile pyloric stenosis is typically managed with surgery; very few cases are mild enough to be treated medically. The danger of pyloric stenosis comes from the dehydration and electrolyte disturbance rather than the underlying problem itself. Therefore, the baby must be initially stabilized by correcting the dehydration and the abnormally high blood pH seen in combination with low chloride levels with IV fluids. This can usually be accomplished in about 24–48 hours.Intravenous and oral atropine may be used to treat pyloric stenosis. It has a success rate of 85-89% compared to nearly 100% for pyloromyotomy, however it requires prolonged hospitalization, skilled nursing and careful follow up during treatment. It might be an alternative to surgery in children who have contraindications for anesthesia or surgery, or in children whose parents do not want surgery. Surgery The definitive treatment of pyloric stenosis is with surgical pyloromyotomy known as Ramstedts procedure (dividing the muscle of the pylorus to open up the gastric outlet). This surgery can be done through a single incision (usually 3–4 cm long) or laparoscopically (through several tiny incisions), depending on the surgeons experience and preference.Today, the laparoscopic technique has largely supplanted the traditional open repairs which involved either a tiny circular incision around the navel or the Ramstedt procedure. Compared to the older open techniques, the complication rate is equivalent, except for a markedly lower risk of wound infection. This is now considered the standard of care at the majority of childrens hospitals across the US, although some surgeons still perform the open technique. Following repair, the small 3mm incisions are hard to see. The vertical incision, pictured and listed above, is no longer usually required, though many incisions have been horizontal in the past years. Once the stomach can empty into the duodenum, feeding can begin again. Some vomiting may be expected during the first days after surgery as the gastrointestinal tract settles. Rarely, the myotomy procedure performed is incomplete and projectile vomiting continues, requiring repeat surgery. Pyloric stenosis generally has no long term side-effects or impact on the childs future. Epidemiology Males are more commonly affected than females, with firstborn males affected about four times as often, and there is a genetic predisposition for the disease. It is commonly associated with people of Scandinavian ancestry, and has multifactorial inheritance patterns. Pyloric stenosis is more common in Caucasians than Hispanics, Blacks, or Asians. The incidence is 2.4 per 1000 live births in Caucasians, 1.8 in Hispanics, 0.7 in Blacks, and 0.6 in Asians. It is also less common amongst children of mixed race parents. Caucasian male babies with blood type B or O are more likely than other types to be affected.Infants exposed to erythromycin are at increased risk for developing hypertrophic pyloric stenosis, especially when the drug is taken around two weeks of life and possibly in late pregnancy and through breastmilk in the first two weeks of life. References External links 00675 at CHORUSPeristaltic waves video on NEJM

Essential tremor

Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations (oscillations or twitching movements) of certain muscle groups in one or more body parts of unknown cause. It is typically symmetrical, and affects the arms, hands, or fingers; but sometimes involves the head, vocal cords, or other body parts. Essential tremor is either an action (intention) tremor—it intensifies when one tries to use the affected muscles during voluntary movements such as eating and writing—or it is a postural tremor, present with sustained muscle tone. This means that it is distinct from a resting tremor, such as that caused by Parkinsons disease, which is not correlated with movement.Essential tremor is a progressive neurological disorder, and the most common movement disorder. Its onset is usually after age 40, but it can occur at any age. The cause is unknown. Diagnosis is by observing the typical pattern of the tremor coupled with the exclusion of known causes of such a tremor. While essential tremor is distinct from Parkinsons disease, which causes a resting tremor, essential tremor is nevertheless sometimes misdiagnosed as Parkinsons disease. Some patients have been found to have both essential tremors and resting tremors.Treatments for essential tremor include medications, typically given sequentially to determine which provides the best compromise between effectiveness and troublesome side effects. Clostridium botulinum toxin (Botox) injections and ultrasound are also sometimes used for cases refractory to medications. Signs and symptoms In mild cases, ET can manifest as the inability to stop the tongue or hands from shaking, the ability to sing only in vibrato, and difficulty doing small, precise tasks such as threading a needle. Even simple tasks such as cutting in a straight line or using a ruler can range from difficult to impossible, depending on the severity of the condition. In disabling cases, ET can interfere with a persons activities of daily living, including feeding, dressing, and taking care of personal hygiene. Essential tremor generally presents as a rhythmic tremor (4–12 Hz) that occurs only when the affected muscle is exerting effort. Any sort of physical or mental stress tends to make the tremor worse.The tremor may also occur in the head (neck), jaw, and voice, as well as other body regions, with the general pattern being that the tremor begins in the arms and then spreads to these other regions in some people. Women are more likely to develop the head tremor than are men. Other types of tremor may also occur, including postural tremor of the outstretched arms, intention tremor of the arms, and rest tremor in the arms. Some people may have unsteadiness and problems with gait and balance.ET-related tremors do not occur during sleep, but people with ET sometimes complain of an especially coarse tremor upon awakening that becomes noticeably less coarse within the first few minutes of wakefulness. Tremor and disease activity/intensity can worsen in response to fatigue, strong emotions, low blood sugar, cold and heat, caffeine, lithium salts, some antidepressants, and other factors. Typically, the tremor worsens in "performance" situations, such as when writing a cheque for payment at a store or giving a presentation.Parkinsons disease and parkinsonism can also occur simultaneously with ET. The degree of tremor, rigidity, and functional disability did not differ from patients with idiopathic Parkinsons disease. Hand tremor predominated (as it did in Parkinsons disease), and occurred in nearly all cases, followed by head tremor, voice tremor, neck, face, leg, tongue, and trunk tremor. Most other tremors occurred in association with hand tremor. More severe tremors, a lower sleep disorder frequency, and a similar prevalence of other non-motor symptoms also can occur.Walking difficulties in essential tremor are common. About half of patients have associated dystonia, including cervical dystonia, writers cramp, spasmodic dysphonia, and cranial dystonia, and 20% of the patients had associated parkinsonism. Olfactory dysfunction (loss of sense of smell) is common in Parkinsons disease, and has also been reported to occur in patients with essential tremor. A number of patients with essential tremor also exhibit many of the same neuropsychiatric disturbances seen in idiopathic Parkinsons disease.Essential tremor with tremor onset after the age of 65 has been associated with mild cognitive impairment, as well as dementia; although the link between these conditions, if any, is still not understood.Essential tremor has two tremor components, central and peripheral. These two tremor components were identified by measuring the tremor of ET patients once with no weights on their hands and then with 1-lb weights on their hands. The addition of the weights resulted in a tremor spectrum with two peaks, one that maintained the same frequency (the central tremor) and one that decreased in frequency (the peripheral tremor). Only with the addition of the weights was the peripheral tremor distinguishable from the central tremor.The frequency of essential tremor is 4 to 11 Hz, depending on which body segment is affected. Proximal segments are affected at lower frequencies, and distal segments are affected at higher frequencies Cause Genetic The underlying cause of essential tremor is not clear, but many cases seem to be familial. About half of the cases are due to a genetic mutation and the pattern of inheritance is most consistent with autosomal dominant transmission. No genes have been identified yet, but genetic linkage has been established with several chromosomal regions. Toxins Some environmental factors, including toxins, are also under active investigation, as they may play a role in the diseases cause. Pathophysiology In terms of pathophysiology, clinical, physiological and imaging studies point to an involvement of the cerebellum and/or cerebellothalamocortical circuits. Changes in the cerebellum could also be mediated by alcoholic beverage consumption. Purkinje cells are especially susceptible to ethanol excitotoxicity. Impairment of Purkinje synapses is a component of cerebellar degradation that could underlie essential tremor. Some cases have Lewy bodies in the locus ceruleus. ET cases that progress to Parkinsons disease are less likely to have had cerebellar problems. Recent neuroimaging studies have suggested that the efficiency of the overall brain functional network in ET is disrupted. Recent post mortem studies have evidenced alterations in (leucine-rich repeat and Ig domain containing 1 (LINGO1) gene and GABA receptors in the cerebellum of people with essential tremor. HAPT1 mutations have also been linked to ET, as well as to Parkinsons disease, multiple system atrophy, and progressive supranuclear palsy.In 2012, the National Toxicology Program concluded that sufficient evidence exists of an association between blood lead exposure at levels >10 μg/dl and essential tremor in adults, and limited evidence at blood lead levels >5 μg/dl. Diagnosis Usually, the diagnosis is established on clinical grounds. Tremors can start at any age, from birth through advanced ages (senile tremor). Any voluntary muscle in the body may be affected, although the tremor is most commonly seen in the hands and arms and slightly less commonly in the neck (causing the persons head to shake), tongue, and legs. A resting tremor of the hands is sometimes present. Tremor occurring in the legs might be diagnosable as orthostatic tremor. ET occurs within multiple neurological disorders besides Parkinsons disease. This includes migraine disorders, where co-occurrences between ET and migraines have been examined. Treatment General measures Not all individuals with ET require treatment, but many treatment options are available depending on symptom severity. Caffeine and stress should be avoided, and adequate good-quality sleep is recommended. Oral medications First-line When symptoms are sufficiently troublesome to warrant treatment, the first medication choices are beta blockers such as propranolol or alternately, nadolol and timolol. Atenolol and pindolol are not effective for tremor. The anticonvulsant primidone may also be effective. ET is generally responsive to alcohol, but the risks of regular drinking are greater than the potential benefit. Nonetheless, ET patients sometimes self-medicate with alcohol.Propranolol and primidone only have tremor-reducing effects on about half of ET patients, and the effects are moderate. Second-line Second-line medications are the anticonvulsants topiramate, gabapentin (as monotherapy) or levetiracetam, or benzodiazepines such as alprazolam. Third-line Third-line medications are clonazepam and mirtazapine. Fourth-line Theophylline has been used by some practitioners to treat ET, though it may also induce tremor. However, its use is debated due to conflicting data on its efficacy. Some evidence shows that low doses may lead to improvement.Ethanol has shown superior efficacy to those of benzodiazepines in small trials. It improves tremor in small doses and its effects are usually noticeable within 20 minutes for 3–5 hours, but occasionally appears in a rebound tremor augmentation later.Some systematic reviews of medications for the treatment of ET have been conducted. A 2017 review of topiramate found limited data and low quality evidence to support its efficacy and the occurrence of treatment-limiting adverse effects, a 2017 review of zonisamide found insufficient information to assess efficacy and safety, and a 2016 review of pregabalin determined the effects to be uncertain due to the low quality of evidence. Botulinum injection When medications do not control the tremor or the person does not tolerate medication, C. botulinum toxin, deep brain stimulation, or occupational therapy can be helpful. The electrodes for deep brain stimulation are usually placed in the "tremor center" of the brain, the ventral intermediate nucleus of the thalamus. Ultrasound Additionally, MRI-guided high-intensity focused ultrasound is a nonsurgical treatment option for people with essential tremor who are medication refractory. MRI-guided high-intensity focused ultrasound does not achieve healing, but can improve the quality of life. While its long-term effects are not yet established, the improvement in tremor score from baseline was durable at 1 year and 2 years following the treatment. To date, reported adverse events and side effects have been mild to moderate. Possible adverse events include gait difficulties, balance disturbances, paresthesias, headache, skin burns with ulcerations, skin retraction, scars, and blood clots. This procedure is contraindicated in pregnant women, persons who have non-MRI compatible implanted metallic devices, allergy to MR contrast agents, cerebrovascular disease, abnormal bleeding, hemorrhage and/or blood clotting disorders, advanced kidney disease or on dialysis, heart conditions, severe hypertension, and ethanol or substance abuse, among others. The US Food and Drug Administration (FDA) approved Insightecs Exablate Neuro system to treat essential tremor in 2016.Another treatment for essential tremor is a surgical option; deep brain stimulation is used. Prognosis Although essential tremor is often mild, people with severe tremor have difficulty performing many of their routine activities of daily living. ET is generally progressive in most cases (sometimes rapidly, sometimes very slowly), and can be disabling in severe cases. Epidemiology ET is one of the most common neurological diseases, with a prevalence around 4% in persons age 40 and older and considerably higher among persons in their 60s, 70s, and 80s, with an estimated 20% of individuals in their 90s and over. Aside from enhanced physiological tremor, it is the most common type of tremor and one of the most commonly observed movement disorders. Society and culture Actress Katharine Hepburn (1907–2003) had an essential tremor, possibly inherited from her grandfather, that caused her head—and sometimes her hands—to shake. The tremor was noticeable by the time of her performance in the 1979 film The Corn Is Green, when critics mentioned the "palsy that kept her head trembling". Hepburns tremor worsened in her later life.Charles M. Schulz, American cartoonist and creator of the Peanuts comic strip, was affected during the last two decades of his life. West Virginia Senator Robert Byrd also had essential tremor. In 2010, musician Daryl Dragon of The Captain and Tennille was diagnosed with essential tremor, with the condition becoming so severe that Dragon was no longer able to play the keyboards.Director-writer-producer-comedian Adam McKay was diagnosed with essential tremor.Downton Abbey creator Julian Fellowes has the condition, as does the shows character Charlie Carson.In 2022, Matthew Caws of Nada Surf and his son made a PSA called "Living with a Mild Essential Tremor". Research Harmaline is a widely used model of essential tremor (ET) in rodents. Harmaline is thought to act primarily on neurons in the inferior olive. Olivocerebellar neurons exhibit rhythmic excitatory action when harmaline is applied locally.Harmane or harmaline has been implicated not only in essential tremors, but is also found in greater quantities in the brain fluid of people with Parkinsons disease as well as cancer. Higher levels of the neurotoxin are associated with greater severity of the tremors. Harmane is particularly abundant in meats, and certain cooking practices (e.g., long cooking times) increase its concentration, however, at least one study has shown that harmane blood concentrations do not go up after meat consumption in ET patients with already elevated harmane levels, where as the control groups harmane levels increase accordingly, suggesting that another factor, like a metabolic defect, may be responsible for the higher harmane levels in E.T. patients.Caprylic acid is being researched as a possible treatment for essential tremor. It has currently been approved by the FDA and designated as GRAS, and is used as a food additive and has been studied as part of a ketogenic diet for treatment of epilepsy in children. Research on caprylic acid as a possible treatment for ET begun because researchers recognized that ethanol was effective in reducing tremor, and because of this, they looked into longer-chain alcohols reducing tremor. They discovered that 1-octanol reduced tremor and did not have the negative side effects of ethanol. Pharmacokinetic research on 1-octanol lead to the discovery that 1-octanol metabolized into caprylic acid in the body and that caprylic acid actually was the tremor-reducing agent. Many studies of the effects of caprylic acid on essential tremor have been done, including a dose-escalation study on ET patients and a study testing the effects of caprylic acid on central and peripheral tremor. The dose-escalation study examined doses of 8 mg/kg to 128 mg/kg and determined that these concentrations were safe with mild side effects. The maximum tolerated dose was not reached in this study. The study testing the effects of caprylic acid on central and peripheral tremors determined that caprylic acid reduced both. Terminology This type of tremor is often referred to as "kinetic tremor". Essential tremor has been known as "benign essential tremor", but the adjective "benign" has been removed in recognition of the sometimes disabling nature of the disorder. See also Intention tremor References External links Essential tremor at Curlie

Pressure ulcer

Pressure ulcers, also known as pressure sores, bed sores or pressure injuries, are localised damage to the skin and/or underlying tissue that usually occur over a bony prominence as a result of usually long-term pressure, or pressure in combination with shear or friction. The most common sites are the skin overlying the sacrum, coccyx, heels, and hips, though other sites can be affected, such as the elbows, knees, ankles, back of shoulders, or the back of the cranium. Pressure ulcers occur due to pressure applied to soft tissue resulting in completely or partially obstructed blood flow to the soft tissue. Shear is also a cause, as it can pull on blood vessels that feed the skin. Pressure ulcers most commonly develop in individuals who are not moving about, such as those who are on chronic bedrest or consistently use a wheelchair. It is widely believed that other factors can influence the tolerance of skin for pressure and shear, thereby increasing the risk of pressure ulcer development. These factors are protein-calorie malnutrition, microclimate (skin wetness caused by sweating or incontinence), diseases that reduce blood flow to the skin, such as arteriosclerosis, or diseases that reduce the sensation in the skin, such as paralysis or neuropathy. The healing of pressure ulcers may be slowed by the age of the person, medical conditions (such as arteriosclerosis, diabetes or infection), smoking or medications such as anti-inflammatory drugs. Although often prevented and treatable if detected early, pressure ulcers can be very difficult to prevent in critically ill people, frail elders and individuals with impaired mobility such as wheelchair users (especially where spinal injury is involved). Primary prevention is to redistribute pressure by regularly turning the person. The benefit of turning to avoid further sores is well documented since at least the 19th century. In addition to turning and re-positioning the person in the bed or wheelchair, eating a balanced diet with adequate protein and keeping the skin free from exposure to urine and stool is important.The rate of pressure ulcers in hospital settings is high; the prevalence in European hospitals ranges from 8.3% to 23%, and the prevalence was 26% in Canadian healthcare settings from 1990 to 2003. In 2013, there were 29,000 documented deaths from pressure ulcers globally, up from 14,000 deaths in 1990. Presentation Complications Pressure ulcers can trigger other ailments, cause considerable suffering, and can be expensive to treat. Some complications include autonomic dysreflexia, bladder distension, bone infection, pyarthrosis, sepsis, amyloidosis, anemia, urethral fistula, gangrene and very rarely malignant transformation (Marjolins ulcer - secondary carcinomas in chronic wounds). Sores may recur if those with pressure ulcers do not follow recommended treatment or may instead develop seromas, hematomas, infections, or wound dehiscence. Paralyzed individuals are the most likely to have pressure sores recur. In some cases, complications from pressure sores can be life-threatening. The most common causes of fatality stem from kidney failure and amyloidosis. Pressure ulcers are also painful, with individuals of all ages and all stages of pressure ulcers reporting pain. Cause There are four mechanisms that contribute to pressure ulcer development: External (interface) pressure applied over an area of the body, especially over the bony prominences can result in obstruction of the blood capillaries, which deprives tissues of oxygen and nutrients, causing ischemia (deficiency of blood in a particular area), hypoxia (inadequate amount of oxygen available to the cells), edema, inflammation, and, finally, necrosis and ulcer formation. Ulcers due to external pressure occur over the sacrum and coccyx, followed by the trochanter and the calcaneus (heel). Friction is damaging to the superficial blood vessels directly under the skin. It occurs when two surfaces rub against each other. The skin over the elbows can be injured due to friction. The back can also be injured when patients are pulled or slid over bed sheets while being moved up in bed or transferred onto a stretcher. Shearing is a separation of the skin from underlying tissues. When a patient is partially sitting up in bed, their skin may stick to the sheet, making them susceptible to shearing in case underlying tissues move downward with the body toward the foot of the bed. This may also be possible on a patient who slides down while sitting in a chair. Moisture is also a common pressure ulcer culprit. Sweat, urine, feces, or excessive wound drainage can further exacerbate the damage done by pressure, friction, and shear. It can contribute to maceration of surrounding skin thus potentially expanding the deleterious effects of pressure ulcers. Risk factors There are over 100 risk factors for pressure ulcers. Factors that may place a patient at risk include immobility, diabetes mellitus, peripheral vascular disease, malnutrition, cerebral vascular accident and hypotension. Other factors are age of 70 years and older, current smoking history, dry skin, low body mass index, urinary and fecal incontinence, physical restraints, malignancy, and history of pressure ulcers. Pathophysiology Pressure ulcers may be caused by inadequate blood supply and resulting reperfusion injury when blood re-enters tissue. A simple example of a mild pressure sore may be experienced by healthy individuals while sitting in the same position for extended periods of time: the dull ache experienced is indicative of impeded blood flow to affected areas. Within 2 hours, this shortage of blood supply, called ischemia, may lead to tissue damage and cell death. The sore will initially start as a red, painful area. The other process of pressure ulcer development is seen when pressure is high enough to damage the cell membrane of muscle cells. The muscle cells die as a result and skin fed through blood vessels coming through the muscle die. This is the deep tissue injury form of pressure ulcers and begins as purple intact skin.According to Centers for Medicare and Medicaid Services, pressure ulcers are one of the eight preventable iatrogenic illnesses. If a pressure ulcer is acquired in the hospital, the hospital will no longer receive reimbursement for the persons care. Hospitals spend about $5 billion annually for treatment of pressure ulcers. Sites Common pressure sore sites include the skin over the ischial tuberosity, the sacrum, the heels of the feet, over the heads of the long bones of the foot, buttocks, over the shoulder, and over the back of the head. Biofilm Biofilm is one of the most common reasons for delayed healing in pressure ulcers. Biofilm occurs rapidly in wounds and stalls healing by keeping the wound inflamed. Frequent debridement and antimicrobial dressings are needed to control the biofilm. Infection prevents healing of pressure ulcers. Signs of pressure ulcer infection include slow or delayed healing and pale granulation tissue. Signs and symptoms of systemic infection include fever, pain, redness, swelling, warmth of the area, and purulent discharge. Additionally, infected wounds may have a gangrenous smell, be discolored, and may eventually produce more pus.In order to eliminate this problem, it is imperative to apply antiseptics at once. Hydrogen peroxide (a near-universal toxin) is not recommended for this task as it increases inflammation and impedes healing. Dressings with cadexomer iodine, silver, or honey have been shown to penetrate bacterial biofilms. Systemic antibiotics are not recommended in treating local infection in a pressure ulcer, as it can lead to bacterial resistance. They are only recommended if there is evidence of advancing cellulitis, bony infection, or bacteria in the blood. Diagnosis Classification The definitions of the pressure ulcer stages are revised periodically by the National Pressure Injury Advisory Panel (NPUAP) in the United States and the European Pressure Ulcer Advisory Panel (EPUAP) in Europe. Different classification systems are used around the world, depending upon the health system, the health discipline and the purpose for the classifying (e.g. health care versus, prevalence studies versus funding. Briefly, they are as follows: Stage I: Intact skin with non-blanchable redness of a localized area usually over a bony prominence. Darkly pigmented skin may not have visible blanching; its color may differ from the surrounding area. The area differs in characteristics such as thickness and temperature as compared to adjacent tissue. Stage 1 may be difficult to detect in individuals with dark skin tones. May indicate "at risk" persons (a heralding sign of risk). Stage II: Partial thickness loss of dermis presenting as a shallow open ulcer with a red pink wound bed, without slough. May also present as an intact or open/ruptured serum-filled blister. Presents as a shiny or dry shallow ulcer without slough or bruising. This stage should not be used to describe skin tears, tape burns, perineal dermatitis, maceration or excoriation. Stage III: Full thickness tissue loss. Subcutaneous fat may be visible but bone, tendon or muscle are not exposed. Slough may be present but does not obscure the depth of tissue loss. May include undermining and tunneling. The depth of a stage 3 pressure ulcer varies by anatomical location. The bridge of the nose, ear, occiput and malleolus do not have (adipose) subcutaneous tissue and stage 3 ulcers can be shallow. In contrast, areas of significant adiposity can develop extremely deep stage 3 pressure ulcers. Bone/tendon is not visible or directly palpable. Stage IV: Full thickness tissue loss with exposed bone, tendon or muscle. Slough or eschar may be present on some parts of the wound bed. Often include undermining and tunneling. The depth of a stage 4 pressure ulcer varies by anatomical location. The bridge of the nose, ear, occiput and malleolus do not have (adipose) subcutaneous tissue and these ulcers can be shallow. Stage 4 ulcers can extend into muscle and/or supporting structures (e.g., fascia, tendon or joint capsule) making osteomyelitis likely to occur. Exposed bone/tendon is visible or directly palpable. In 2012, the National Pressure Injury Advisory Panel stated that pressure ulcers with exposed cartilage are also classified as a stage 4. Unstageable: Full thickness tissue loss in which actual depth of the ulcer is completely obscured by slough (yellow, tan, gray, green or brown) and/or eschar (tan, brown or black) in the wound bed. Until enough slough and/or eschar is removed to expose the base of the wound, the true depth, and therefore stage, cannot be determined. Stable (dry, adherent, intact without erythema or fluctuance) eschar on the heels is normally protective and should not be removed. Suspected deep tissue injury: A purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue from pressure and/or shear. The area may be preceded by tissue that is painful, firm, mushy, boggy, warmer or cooler as compared to adjacent tissue. A deep tissue injury may be difficult to detect in individuals with dark skin tones. Evolution may include a thin blister over a dark wound bed. The wound may further evolve and become covered by thin eschar. Evolution may be rapid exposing additional layers of tissue even with optimal treatment.The term medical device related pressure ulcer refers to a cause rather than a classification. Pressure ulcers from a medical device are classified according to the same classification system being used for pressure ulcers arising from other causes, but the cause is usually noted. Ischemic fasciitis Ischemic fasciitis (IF) is a benign tumor in the class of fibroblastic and myofibroblastic tumors that, like pressure ulcers, may develop in elderly, bed-ridden individuals. These tumors commonly form in the subcutaneous tissues (i.e. lower most tissue layer of the skin) that overlie bony protuberances such as those in or around the hip, shoulder, greater trochanter of the femur, iliac crest, lumbar region, or scapular region. IF tumors differ from pressure ulcers in that they typically do not have extensive ulcerations of the skin and on histopathological microscopic analysis lack evidence of acute inflammation as determined by the presence of various types of white blood cells. These tumors are commonly treated by surgical removal. Prevention In the United Kingdom, the Royal College of Nursing has published guidelines in Pressure Ulcer Risk Assessment and Prevention that call for identifying people at risk and taking preventive action; the UK National Standards for Care Homes to do so as well. Recent efforts in the United States and South Korea have sought to automate risk assessment and classification by training machine learning models on electronic health records.Internationally, the NPIAP, EPUAP and Pan Pacific Pressure Injury Alliance, together with wound organizations from 15 countries around the world, published updated the international evidence-based clinical practice guideline in 2019. The 2019 guideline was developed by an international team of over 180 clinical specialists and updates the 2009 EPUAP/NPUAP clinical guideline and the 2014 NPUAP/EPUAP/PPPIA clinical guideline. The guideline includes recommendations on strategies to treat pressure ulcers, including the use of bed rest, pressure redistributing support surfaces, nutritional support, repositioning, wound care (e.g. debridement, wound dressings) and biophysical agents (e.g. electrical stimulation). Reliable scientific evidence to support the use of many of these interventions, though, is lacking. More research is needed to assess how to best support the treatment of pressure ulcers, for example by repositioning. Also, the benefit of using systemic or topical antibiotics in the management of pressure ulcer is still unclear. Redistributing pressure The most important care for a person at risk for pressure ulcers and those with bedsores is the redistribution of pressure so that no pressure is applied to the pressure ulcer. In the 1940s Ludwig Guttmann introduced a program of turning paraplegics every two hours thus allowing bedsores to heal. Previously such individuals had a two-year life-expectancy, normally succumbing to blood and skin infections. Guttmann had learned the technique from the work of Boston physician Donald Munro.There is lack of evidence on prevention of pressure ulcer whether the patient is put in 30 degrees position or at the standard 90 degrees position.Nursing homes and hospitals usually set programs in place to avoid the development of pressure ulcers in those who are bedridden, such as using a routine time frame for turning and repositioning to reduce pressure. The frequency of turning and repositioning depends on the persons level of risk. Support surfaces A 2015 Cochrane systematic review found that people who lay on high specification or high density foam mattresses were 60% less likely to develop new pressure ulcers compared to regular foam mattresses. Sheepskin overlays on top of mattresses were also found to prevent new pressure ulcer formation. There is unclear research on the effectiveness of alternating pressure mattresses. Pressure-redistributive mattresses are used to reduce high values of pressure on prominent or bony areas of the body. There are several important terms used to describe how these support surfaces work. These terms were standardized through the Support Surface Standards Initiative of the NPUAP. Many support surfaces redistribute pressure by immersing and/or enveloping the body into the surface. Some support surfaces, including antidecubitus mattresses and cushions, contain multiple air chambers that are alternately pumped. Methods to standardize the products and evaluate the efficacy of these products have only been developed in recent years through the work of the S3I within NPUAP. For individuals with paralysis, pressure shifting on a regular basis and using a wheelchair cushion featuring pressure relief components can help prevent pressure wounds. A 2022 Cochrane systematic review aimed to find out how effective pressure redistributing static chairs (as opposed to wheelchairs) are for preventing pressure ulcers. Static chairs can include: standard hospital chairs; chairs with no cushions or manual/dynamic function; and chairs with integrated pressure redistributing surfaces and recline, rise or tilt functions. The authors did not find any randomised controlled trials that were eligible for inclusion. More research is needed to establish how effective pressure redistributing static chairs are for preventing pressure ulcers. Controlling the heat and moisture levels of the skin surface, known as skin microclimate management, also plays a significant role in the prevention and control of pressure ulcers. Nutrition In addition, adequate intake of protein and calories is important. Vitamin C has been shown to reduce the risk of pressure ulcers. People with higher intakes of vitamin C have a lower frequency of bed sores in those who are bedridden than those with lower intakes. Maintaining proper nutrition in newborns is also important in preventing pressure ulcers. If unable to maintain proper nutrition through protein and calorie intake, it is advised to use supplements to support the proper nutrition levels. Skin care is also important because damaged skin does not tolerate pressure. However, skin that is damaged by exposure to urine or stool is not considered a pressure ulcer. These skin wounds should be classified as Incontinence Associated Dermatitis. Organisational changes There is some suggestion that organisational changes may reduce incidence of pressure ulcers. Cochrane systematic reviews on organisation of health services, risk assessment tools, wound care teams, and education have concluded that evidence is uncertain as to the benefit of these organisational changes. This is largely due to the lack of high-quality research in these areas. Other prevention therapies A Cochrane systematic review found use of creams containing fatty acids may be more effective in reducing incidence of pressure ulcers compared to creams without fatty acids. Silicone dressings may also reduce pressure ulcer incidence. There is no evidence that massage reduces pressure ulcer incidence. Treatment Internationally, the NPIAP, EPUAP and Pan Pacific Pressure Injury Alliance, together with wound organizations from 15 countries around the world published updated their international evidence-based clinical practice guideline in 2019. The 2019 guideline was developed by an international team of over 180 clinical specialists and updates the 2009 EPUAP/NPUAP clinical guideline and the 2014 NPUAP/EPUAP/PPPIA clinical guideline. The guideline includes recommendations on strategies to treat pressure ulcers, including the use of bed rest, pressure redistributing support surfaces, nutritional support, repositioning, wound care (e.g. debridement, wound dressings) and biophysical agents (e.g. electrical stimulation). Reliable scientific evidence to support the use of many of these interventions, though, is lacking. More research is needed to assess how to best support the treatment of pressure ulcers, for example by repositioning. A 2020 Cochrane systematic review of randomized controlled trials concluded that more research is needed to determine whether or not electrical stimulation is an effective treatment for pressure ulcers. In addition, the benefit of using systemic or topical antibiotics in the management of pressure ulcer is still unclear. Debridement Necrotic tissue should be removed in most pressure ulcers. The heel is an exception in many cases when the limb has an inadequate blood supply. Necrotic tissue is an ideal area for bacterial growth, which has the ability to greatly compromise wound healing. There are five ways to remove necrotic tissue. Autolytic debridement is the use of moist dressings to promote autolysis with the bodys own enzymes and white blood cells. It is a slow process, but mostly painless, and is most effective in individuals with a properly functioning immune system. Biological debridement, or maggot debridement therapy, is the use of medical maggots to feed on necrotic tissue and therefore clean the wound of excess bacteria. Although this fell out of favor for many years, in January 2004, the FDA approved maggots as a live medical device. Chemical debridement, or enzymatic debridement, is the use of prescribed enzymes that promote the removal of necrotic tissue. Mechanical debridement, is the use of debriding dressings, whirlpool or ultrasound for slough in a stable wound. Surgical debridement, or sharp debridement, is the fastest method, as it allows a surgeon to quickly remove dead tissue. Dressings A 2017 Cochrane review found that it was unclear whether one topical agent or dressing was better than another for treating pressure ulcers. Protease-modulating dressings, foam dressings or collagenase ointment may be better at healing than gauze. The wound dressing should be selected based on the wound and condition of the surrounding skin. There are some studies that indicate that antimicrobial products that stimulate the epithelization may improve the wound healing. However, there is no international consensus on the selection of the dressings for pressure ulcers. Cochrane reviews summarise evidence on alginate dressings, foam dressings, and hydrogel dressings. Due to a lack of robust evidence, the benefits of these dressings over other treatments is unclear. Some guidelines for dressing are: Other treatments Other treatments include anabolic steroids, negative pressure wound therapy, phototherapy, support surfaces, reconstructive surgery, ultrasound, topical phenytoin and pressure relieving devices. There is little or no evidence to support or refute the benefits of most of these treatments compared to each other and placebo. When selecting treatments, consideration should be given to patients quality of life as well as the interventions ease of use, reliability, and cost. Epidemiology Pressure ulcers resulted in 29,000 deaths worldwide in 2013 up from 14,000 deaths in 1990.Each year, more than 2.5 million people in the United States develop pressure ulcers. In acute care settings in the United States, the incidence of bedsores is 0.4% to 38%; within long-term care it is 2.2% to 23.9%, and in home care, it is 0% to 17%. Similarly, there is wide variation in prevalence: 10% to 18% in acute care, 2.3% to 28% in long-term care, and 0% to 29% in home care. There is a much higher rate of bedsores in intensive care units because of immunocompromised individuals, with 8% to 40% of those in the ICU developing bedsores. However, pressure ulcer prevalence is highly dependent on the methodology used to collect the data. Using the European Pressure Ulcer Advisory Panel (EPUAP) methodology there are similar figures for pressure ulcers in acutely sick people in the hospital. There are differences across countries, but using this methodology, pressure ulcer prevalence in Europe was consistently high, from 8.3% (Italy) to 22.9% (Sweden). A recent study in Jordan also showed a figure in this range. Some research shows differences in pressure-ulcer detection among white and black residents in nursing homes. See also Perfusion—systemic biomechanics of blood delivery References Nathaniel Avilla, John Soto, Toni Tweedy, The Cochrane Database of Systematic Reviews diariodelyaqui Further reading External links Media related to Pressure ulcers at Wikimedia Commons

Otitis media

Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, increased crying, and poor sleep. Decreased eating and a fever may also be present. The other main type is otitis media with effusion (OME), typically not associated with symptoms, although occasionally a feeling of fullness is described; it is defined as the presence of non-infectious fluid in the middle ear which may persist for weeks or months often after an episode of acute otitis media. Chronic suppurative otitis media (CSOM) is middle ear inflammation that results in a perforated tympanic membrane with discharge from the ear for more than six weeks. It may be a complication of acute otitis media. Pain is rarely present. All three types of otitis media may be associated with hearing loss. If children with hearing loss due to OME do not learn sign language, it may affect their ability to learn.The cause of AOM is related to childhood anatomy and immune function. Either bacteria or viruses may be involved. Risk factors include exposure to smoke, use of pacifiers, and attending daycare. It occurs more commonly among indigenous peoples and those who have cleft lip and palate or Down syndrome. OME frequently occurs following AOM and may be related to viral upper respiratory infections, irritants such as smoke, or allergies. Looking at the eardrum is important for making the correct diagnosis. Signs of AOM include bulging or a lack of movement of the tympanic membrane from a puff of air. New discharge not related to otitis externa also indicates the diagnosis.A number of measures decrease the risk of otitis media including pneumococcal and influenza vaccination, breastfeeding, and avoiding tobacco smoke. The use of pain medications for AOM is important. This may include paracetamol (acetaminophen), ibuprofen, benzocaine ear drops, or opioids. In AOM, antibiotics may speed recovery but may result in side effects. Antibiotics are often recommended in those with severe disease or under two years old. In those with less severe disease they may only be recommended in those who do not improve after two or three days. The initial antibiotic of choice is typically amoxicillin. In those with frequent infections tympanostomy tubes may decrease recurrence. In children with otitis media with effusion antibiotics may increase resolution of symptoms, but may cause diarrhoea, vomiting and skin rash.Worldwide AOM affects about 11% of people a year (about 325 to 710 million cases). Half the cases involve children less than five years of age and it is more common among males. Of those affected about 4.8% or 31 million develop chronic suppurative otitis media. The total number of people with CSOM is estimated at 65–330 million people. Before the age of ten OME affects about 80% of children at some point. Otitis media resulted in 3,200 deaths in 2015 – down from 4,900 deaths in 1990. Signs and symptoms The primary symptom of acute otitis media is ear pain; other possible symptoms include fever, reduced hearing during periods of illness, tenderness on touch of the skin above the ear, purulent discharge from the ears, irritability, ear blocking sensation and diarrhea (in infants). Since an episode of otitis media is usually precipitated by an upper respiratory tract infection (URTI), there are often accompanying symptoms like a cough and nasal discharge. One might also experience a feeling of fullness in the ear. Discharge from the ear can be caused by acute otitis media with perforation of the eardrum, chronic suppurative otitis media, tympanostomy tube otorrhea, or acute otitis externa. Trauma, such as a basilar skull fracture, can also lead to cerebrospinal fluid otorrhea (discharge of CSF from the ear) due to cerebral spinal drainage from the brain and its covering (meninges). Causes The common cause of all forms of otitis media is dysfunction of the Eustachian tube. This is usually due to inflammation of the mucous membranes in the nasopharynx, which can be caused by a viral upper respiratory tract infection (URTI), strep throat, or possibly by allergies.By reflux or aspiration of unwanted secretions from the nasopharynx into the normally sterile middle-ear space, the fluid may then become infected — usually with bacteria. The virus that caused the initial upper respiratory infection can itself be identified as the pathogen causing the infection. Diagnosis As its typical symptoms overlap with other conditions, such as acute external otitis, symptoms alone are not sufficient to predict whether acute otitis media is present; it has to be complemented by visualization of the tympanic membrane. Examiners may use a pneumatic otoscope with a rubber bulb attached to assess the mobility of the tympanic membrane. Other methods to diagnose otitis media is with a tympanometry, reflectometry or hearing test. In more severe cases, such as those with associated hearing loss or high fever, audiometry, tympanogram, temporal bone CT and MRI can be used to assess for associated complications, such as mastoid effusion, subperiosteal abscess formation, bony destruction, venous thrombosis or meningitis.Acute otitis media in children with moderate to severe bulging of the tympanic membrane or new onset of otorrhea (drainage) is not due to external otitis. Also, the diagnosis may be made in children who have mild bulging of the ear drum and recent onset of ear pain (less than 48 hours) or intense erythema (redness) of the ear drum. To confirm the diagnosis, middle-ear effusion and inflammation of the eardrum have to be identified; signs of these are fullness, bulging, cloudiness and redness of the eardrum. It is important to attempt to differentiate between acute otitis media and otitis media with effusion (OME), as antibiotics are not recommended for OME. It has been suggested that bulging of the tympanic membrane is the best sign to differentiate AOM from OME, with a bulging of the membrane suggesting AOM rather than OME.Viral otitis may result in blisters on the external side of the tympanic membrane, which is called bullous myringitis (myringa being Latin for "eardrum").However, sometimes even examination of the eardrum may not be able to confirm the diagnosis, especially if the canal is small. If wax in the ear canal obscures a clear view of the eardrum it should be removed using a blunt cerumen curette or a wire loop. Also, an upset young childs crying can cause the eardrum to look inflamed due to distension of the small blood vessels on it, mimicking the redness associated with otitis media. Acute otitis media The most common bacteria isolated from the middle ear in AOM are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Otitis media with effusion Otitis media with effusion (OME), also known as serous otitis media (SOM) or secretory otitis media (SOM), and colloquially referred to as glue ear, is fluid accumulation that can occur in the middle ear and mastoid air cells due to negative pressure produced by dysfunction of the Eustachian tube. This can be associated with a viral upper respiratory infection (URI) or bacterial infection such as otitis media. An effusion can cause conductive hearing loss if it interferes with the transmission of vibrations of middle ear bones to the vestibulocochlear nerve complex that are created by sound waves.Early-onset OME is associated with feeding of infants while lying down, early entry into group child care, parental smoking, lack, or too short a period of breastfeeding and greater amounts of time spent in group child care, particularly those with a large number of children. These risk factors increase the incidence and duration of OME during the first two years of life. Chronic suppurative otitis media Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear and mastoid cavity that is characterised by discharge from the middle ear through a perforated tympanic membrane for at least 6 weeks. CSOM occurs following an upper respiratory tract infection that has led to acute otitis media. This progresses to a prolonged inflammatory response causing mucosal (middle ear) oedema, ulceration and perforation. The middle ear attempts to resolve this ulceration by production of granulation tissue and polyp formation. This can lead to increased discharge and failure to arrest the inflammation, and to development of CSOM, which is also often associated with cholesteatoma. There may be enough pus that it drains to the outside of the ear (otorrhea), or the pus may be minimal enough to be seen only on examination with an otoscope or binocular microscope. Hearing impairment often accompanies this disease. People are at increased risk of developing CSOM when they have poor eustachian tube function, a history of multiple episodes of acute otitis media, live in crowded conditions, and attend paediatric day care facilities. Those with craniofacial malformations such as cleft lip and palate, Down syndrome, and microcephaly are at higher risk.Worldwide approximately 11% of the human population is affected by AOM every year, or 709 million cases. About 4.4% of the population develop CSOM.According to the World Health Organization, CSOM is a primary cause of hearing loss in children. Adults with recurrent episodes of CSOM have a higher risk of developing permanent conductive and sensorineural hearing loss. In Britain, 0.9% of children and 0.5% of adults have CSOM, with no difference between the sexes. The incidence of CSOM across the world varies dramatically where high income countries have a relatively low prevalence while in low income countries the prevalence may be up to three times as great. Each year 21,000 people worldwide die due to complications of CSOM. Adhesive otitis media Adhesive otitis media occurs when a thin retracted ear drum becomes sucked into the middle-ear space and stuck (i.e., adherent) to the ossicles and other bones of the middle ear. Prevention AOM is far less common in breastfed infants than in formula-fed infants, and the greatest protection is associated with exclusive breastfeeding (no formula use) for the first six months of life. A longer duration of breastfeeding is correlated with a longer protective effect.Pneumococcal conjugate vaccines (PCV) in early infancy decrease the risk of acute otitis media in healthy infants. PCV is recommended for all children, and, if implemented broadly, PCV would have a significant public health benefit. Influenza vaccination in children appears to reduce rates of AOM by 4% and the use of antibiotics by 11% over 6 months. However, the vaccine resulted in increased adverse-effects such as fever and runny nose. The small reduction in AOM may not justify the side effects and inconvenience of influenza vaccination every year for this purpose alone. PCV does not appear to decrease the risk of otitis media when given to high-risk infants or for older children who have previously experienced otitis media.Risk factors such as season, allergy predisposition and presence of older siblings are known to be determinants of recurrent otitis media and persistent middle-ear effusions (MEE). History of recurrence, environmental exposure to tobacco smoke, use of daycare, and lack of breastfeeding have all been associated with increased risk of development, recurrence, and persistent MEE. Pacifier use has been associated with more frequent episodes of AOM.Long-term antibiotics, while they decrease rates of infection during treatment, have an unknown effect on long-term outcomes such as hearing loss. This method of prevention has been associated with emergence of antibiotic-resistant otitic bacteria. They are thus not recommended.There is moderate evidence that the sugar substitute xylitol may reduce infection rates in those who go to daycare.Evidence does not support zinc supplementation as an effort to reduce otitis rates except maybe in those with severe malnutrition such as marasmus.Probiotics do not show evidence of preventing acute otitis media in children. Management Oral and topical pain killers are effective to treat the pain caused by otitis media. Oral agents include ibuprofen, paracetamol (acetaminophen), and opiates. Evidence for the combination over single agents is lacking. Topical agents shown to be effective include antipyrine and benzocaine ear drops. Decongestants and antihistamines, either nasal or oral, are not recommended due to the lack of benefit and concerns regarding side effects. Half of cases of ear pain in children resolve without treatment in three days and 90% resolve in seven or eight days. The use of steroids is not supported by the evidence for acute otitis media. Antibiotics It is important to weigh the benefits and harms before using antibiotics for acute otitis media. As over 82% of acute episodes settle without treatment, about 20 children must be treated to prevent one case of ear pain, 33 children to prevent one perforation, and 11 children to prevent one opposite-side ear infection. For every 14 children treated with antibiotics, one child has an episode of either vomiting, diarrhea or a rash. If pain is present, pain medications may be used. For people requiring surgery to treat otitis media with effusion, preventative antibiotics may not help reduce the risk of post-surgical complications.For bilateral acute otitis media in infants younger than 24 months of age, there is evidence that the benefits of antibiotics outweigh the harms. A 2015 Cochrane review concluded that watchful waiting is the preferred approach for children over six months with non severe acute otitis media. Most children older than 6 months of age who have acute otitis media do not benefit from treatment with antibiotics. If antibiotics are used, a narrow-spectrum antibiotic like amoxicillin is generally recommended, as broad-spectrum antibiotics may be associated with more adverse events. If there is resistance or use of amoxicillin in the last 30 days then amoxicillin-clavulanate or another penicillin derivative plus beta lactamase inhibitor is recommended. Taking amoxicillin once a day may be as effective as twice or three times a day. While less than 7 days of antibiotics have fewer side effects, more than seven days appear to be more effective. If there is no improvement after 2–3 days of treatment a change in therapy may be considered. Azithromycin appears to have less side effects than either high dose amoxicillin or amoxicillin/clavulanate. Tympanostomy tube Tympanostomy tubes (also called "grommets") are recommended with three or more episodes of acute otitis media in 6 months or four or more in a year, with at least one episode or more attacks in the preceding 6 months. There is tentative evidence that children with recurrent acute otitis media (AOM) who receive tubes have a modest improvement in the number of further AOM episodes (around one fewer episode at six months and less of an improvement at 12 months following the tubes being inserted). Evidence does not support an effect on long-term hearing or language development. A common complication of having a tympanostomy tube is otorrhea, which is a discharge from the ear. The risk of persistent tympanic membrane perforation after children have grommets inserted may be low. It is still uncertain whether or not grommets are more effective than a course of antibiotics.Oral antibiotics should not be used to treat uncomplicated acute tympanostomy tube otorrhea. They are not sufficient for the bacteria that cause this condition and have side effects including increased risk of opportunistic infection. In contrast, topical antibiotic eardrops are useful. Otitis media with effusion The decision to treat is usually made after a combination of physical exam and laboratory diagnosis, with additional testing including audiometry, tympanogram, temporal bone CT and MRI. Decongestants, glucocorticoids, and topical antibiotics are generally not effective as treatment for non-infectious, or serous, causes of mastoid effusion. Moreover, it is recommended against using antihistamines and decongestants in children with OME. In less severe cases or those without significant hearing impairment, the effusion can resolve spontaneously or with more conservative measures such as autoinflation. In more severe cases, tympanostomy tubes can be inserted, possibly with adjuvant adenoidectomy as it shows a significant benefit as far as the resolution of middle ear effusion in children with OME is concerned. Chronic suppurative otitis media Topical antibiotics are of uncertain benefit as of 2020. Some evidence suggests that topical antibiotics may be useful either alone or with antibiotics by mouth. Antiseptics are of unclear effect. Topical antibiotics (quinolones) are probably better at resolving ear discharge than antiseptics. Alternative medicine Complementary and alternative medicine is not recommended for otitis media with effusion because there is no evidence of benefit. Homeopathic treatments have not been proven to be effective for acute otitis media in a study with children. An osteopathic manipulation technique called the Galbreath technique was evaluated in one randomized controlled clinical trial; one reviewer concluded that it was promising, but a 2010 evidence report found the evidence inconclusive. Outcomes Complications of acute otitis media consists of perforation of the ear drum, infection of the mastoid space behind the ear (mastoiditis), and more rarely intracranial complications can occur, such as bacterial meningitis, brain abscess, or dural sinus thrombosis. It is estimated that each year 21,000 people die due to complications of otitis media. Membrane rupture In severe or untreated cases, the tympanic membrane may perforate, allowing the pus in the middle-ear space to drain into the ear canal. If there is enough, this drainage may be obvious. Even though the perforation of the tympanic membrane suggests a highly painful and traumatic process, it is almost always associated with a dramatic relief of pressure and pain. In a simple case of acute otitis media in an otherwise healthy person, the bodys defenses are likely to resolve the infection and the ear drum nearly always heals. An option for severe acute otitis media in which analgesics are not controlling ear pain is to perform a tympanocentesis, i.e., needle aspiration through the tympanic membrane to relieve the ear pain and to identify the causative organism(s). Hearing loss Children with recurrent episodes of acute otitis media and those with otitis media with effusion or chronic suppurative otitis media have higher risks of developing conductive and sensorineural hearing loss. Globally approximately 141 million people have mild hearing loss due to otitis media (2.1% of the population). This is more common in males (2.3%) than females (1.8%).This hearing loss is mainly due to fluid in the middle ear or rupture of the tympanic membrane. Prolonged duration of otitis media is associated with ossicular complications and, together with persistent tympanic membrane perforation, contributes to the severity of the disease and hearing loss. When a cholesteatoma or granulation tissue is present in the middle ear, the degree of hearing loss and ossicular destruction is even greater.Periods of conductive hearing loss from otitis media may have a detrimental effect on speech development in children. Some studies have linked otitis media to learning problems, attention disorders, and problems with social adaptation. Furthermore, it has been demonstrated that individuals with otitis media have more depression/anxiety-related disorders compared to individuals with normal hearing. Once the infections resolve and hearing thresholds return to normal, childhood otitis media may still cause minor and irreversible damage to the middle ear and cochlea. More research on the importance of screening all children under 4 years old for otitis media with effusion needs to be performed. Epidemiology Acute otitis media is very common in childhood. It is the most common condition for which medical care is provided in children under five years of age in the US. Acute otitis media affects 11% of people each year (709 million cases) with half occurring in those below five years. Chronic suppurative otitis media affects about 5% or 31 million of these cases with 22.6% of cases occurring annually under the age of five years. Otitis media resulted in 2,400 deaths in 2013—down from 4,900 deaths in 1990. Etymology The term otitis media is composed of otitis, Ancient Greek for "inflammation of the ear", and media, Latin for "middle". References External links Neff MJ (June 2004). "AAP, AAFP, AAO-HNS release guideline on diagnosis and management of otitis media with effusion". American Family Physician. 69 (12): 2929–31. PMID 15222658.

Inguinal hernia

An inguinal hernia is a hernia (protrusion) of abdominal-cavity contents through the inguinal canal. Symptoms, which may include pain or discomfort especially with or following coughing, exercise, or bowel movements, are absent in about a third of patients. Symptoms often get worse throughout the day and improve when lying down. A bulging area may occur that becomes larger when bearing down. Inguinal hernias occur more often on the right than left side. The main concern is strangulation, where the blood supply to part of the intestine is blocked. This usually produces severe pain and tenderness of the area.Risk factors for the development of a hernia include: smoking, chronic obstructive pulmonary disease, obesity, pregnancy, peritoneal dialysis, collagen vascular disease, and previous open appendectomy, among others. Predisposition to hernias is genetic and they occur more often in certain families. Deleterious mutations causing predisposition to hernias seem to have dominant inheritance (especially for men). It is unclear if inguinal hernias are associated with heavy lifting. Hernias can often be diagnosed based on signs and symptoms. Occasionally medical imaging is used to confirm the diagnosis or rule out other possible causes.Groin hernias that do not cause symptoms in males do not need to be repaired. Repair, however, is generally recommended in females due to the higher rate of femoral hernias which have more complications. If strangulation occurs immediate surgery is required. Repair may be done by open surgery or by laparoscopic surgery. Open surgery has the benefit of possibly being done under local anesthesia rather than general anesthesia. Laparoscopic surgery generally has less pain following the procedure.In 2015 inguinal, femoral and abdominal hernias affected about 18.5 million people. About 27% of males and 3% of females develop a groin hernia at some time in their life. Groin hernias occur most often before the age of one and after the age of fifty. Globally, inguinal, femoral and abdominal hernias resulted in 60,000 deaths in 2015 and 55,000 in 1990. Signs and symptoms Hernias usually present as bulges in the groin area that can become more prominent when coughing, straining, or standing up. The bulge commonly disappears on lying down. Mild discomfort can develop over time. The inability to "reduce", or place the bulge back into the abdomen usually means the hernia is incarcerated which requires emergency surgery. As the hernia progresses, contents of the abdominal cavity, such as the intestines, can descend into the hernia and run the risk of being pinched within the hernia, causing an intestinal obstruction. Significant pain at the hernia site is suggestive of a more severe course, such as incarceration (the hernia cannot be reduced back into the abdomen) and subsequent ischemia and strangulation (when the hernia becomes deprived of blood supply). If the blood supply of the portion of the intestine caught in the hernia is compromised, the hernia is deemed "strangulated" and gut ischemia and gangrene can result, with potentially fatal consequences. The timing of complications is not predictable. Pathophysiology In males, indirect hernias follow the same route as the descending testes, which migrate from the abdomen into the scrotum during the development of the urinary and reproductive organs. The larger size of their inguinal canal, which transmitted the testicle and accommodates the structures of the spermatic cord, might be one reason why men are 25 times more likely to have an inguinal hernia than women. Although several mechanisms such as strength of the posterior wall of the inguinal canal and shutter mechanisms compensating for raised intra-abdominal pressure prevent hernia formation in normal individuals, the exact importance of each factor is still under debate. The physiological school of thought thinks that the risk of hernia is due to a physiological difference between patients who develop a hernia and those who do not, namely the presence of aponeurotic extensions from the transversus abdominis aponeurotic arch.Inguinal hernias mostly contain the omentum or a part of the small intestines, however, some unusual contents may be an appendicitis, diverticulitis, colon cancer, urinary bladder, ovaries, and rarely malignant lesions. Diagnosis There are two types of inguinal hernia, direct and indirect, which are defined by their relationship to the inferior epigastric vessels. Direct inguinal hernias occur medial to the inferior epigastric vessels when abdominal contents herniate through a weak spot in the fascia of the posterior wall of the inguinal canal, which is formed by the transversalis fascia. Indirect inguinal hernias occur when abdominal contents protrude through the deep inguinal ring, lateral to the inferior epigastric vessels; this may be caused by failure of embryonic closure of the processus vaginalis. In the case of the female, the opening of the superficial inguinal ring is smaller than that of the male. As a result, the possibility for hernias through the inguinal canal in males is much greater because they have a larger opening and therefore a much weaker wall through which the intestines may protrude. Inguinal hernias, in turn, belong to groin hernias, which also includes femoral hernias. A femoral hernia is not via the inguinal canal, but via the femoral canal, which normally allows passage of the common femoral artery and vein from the pelvis to the leg. In Amyands hernia, the content of the hernial sac is the vermiform appendix. In Littres hernia, the content of the hernial sac contains a Meckels diverticulum. Clinical classification of hernia is also important according to which hernia is classified into Reducible hernia: is one which can be pushed back into the abdomen by putting manual pressure to it. Irreducible/Incarcerated hernia: is one which cannot be pushed back into the abdomen by applying manual pressure.Irreducible hernias are further classified into Obstructed hernia: is one in which the lumen of the herniated part of intestine is obstructed. Strangulated hernia: is one in which the blood supply of the hernia contents is cut off, thus, leading to ischemia. The lumen of the intestine may be patent or not. Direct inguinal hernia The direct inguinal hernia enters through a weak point in the fascia of the abdominal wall, and its sac is noted to be medial to the inferior epigastric vessels. Direct inguinal hernias may occur in males or females, but males are ten times more likely to get a direct inguinal hernia.A direct inguinal hernia protrudes through a weakened area in the transversalis fascia near the medial inguinal fossa within an anatomic region known as the inguinal or Hesselbachs triangle, an area defined by the edge of the rectus abdominis muscle, the inguinal ligament and the inferior epigastric artery. These hernias are capable of exiting via the superficial inguinal ring and are unable to extend into the scrotum. When a patient develops a simultaneous direct and indirect hernia on the same side, it is called a pantaloon hernia or saddlebag hernia because it resembles a pair of pants with the epigastric vessels in the crotch, and the defects can be repaired separately or together. Another term for pantaloon hernia is Rombergs hernia. Since the abdominal walls weaken with age, direct hernias tend to occur in the middle-aged and elderly. This is in contrast to indirect hernias which can occur at any age including the young, since their etiology includes a congenital component where the inguinal canal is left more patent (compared to individuals less susceptible to indirect hernias). Additional risk factors include chronic constipation, being overweight or obese, chronic cough, family history and prior episodes of direct inguinal hernias. Indirect inguinal hernia An indirect inguinal hernia results from the failure of embryonic closure of the deep inguinal ring after the testicle has passed through it. It is the most common cause of groin hernia. A double indirect inguinal hernia has two sacs. In the male fetus, the peritoneum gives a coat to the testicle as it passes through this ring, forming a temporary connection called the processus vaginalis. In normal development, the processus is obliterated once the testicle is completely descended. The permanent coat of peritoneum that remains around the testicle is called the tunica vaginalis. The testicle remains connected to its blood vessels and the vas deferens, which make up the spermatic cord and descend through the inguinal canal to the scrotum. The deep inguinal ring, which is the beginning of the inguinal canal, remains as an opening in the fascia transversalis, which forms the fascial inner wall of the spermatic cord. When the opening is larger than necessary for passage of the spermatic cord, the stage is set for an indirect inguinal hernia. The protrusion of peritoneum through the internal inguinal ring can be considered an incomplete obliteration of the processus. In an indirect inguinal hernia, the protrusion passes through the deep inguinal ring and is located lateral to the inferior epigastric artery. Hence, the conjoint tendon is not weakened. There are three main types Bubonocele: in this case the hernia is limited in inguinal canal. Funicular: here the processus vaginalis is closed at its lower end just above the epididymis. The content of the hernial sac can be felt separately from the testis which lies below the hernia. Complete (or scrotal): here the processus vaginalis is patent throughout. The hernial sac is continuous with the tunica vaginalis of the testis. The hernia descends down to the bottom of the scrotum and it is difficult to differentiate the testis from hernia.In the female, groin hernias are only 4% as common as in males. Indirect inguinal hernia is still the most common groin hernia for females. If a woman has an indirect inguinal hernia, her internal inguinal ring is patent, which is abnormal for females. The protrusion of peritoneum is not called "processus vaginalis" in women, as this structure is related to the migration of the testicle to the scrotum. It is simply a hernia sac. The eventual destination of the hernia contents for a woman is the labium majus on the same side, and hernias can enlarge one labium dramatically if they are allowed to progress. Medical imaging A physician may diagnose an inguinal hernia, as well as the type, from medical history and physical examination. For confirmation or in uncertain cases, medical ultrasonography is the first choice of imaging, because it can both detect the hernia and evaluate its changes with for example pressure, standing and Valsalva maneuver.When assessed by ultrasound or cross sectional imaging with CT or MRI, the major differential in diagnosing indirect inguinal hernias is differentiation from spermatic cord lipomas, as both can contain only fat and extend along the inguinal canal into the scrotum.On axial CT, lipomas originate inferior or lateral to the cord, and are located inside the cremaster muscle, while inguinal hernias lie anteromedial to the cord and are not intramuscular. Large lipomas may appear nearly indistinguishable as the fat engulfs anatomic boundaries, but they do not change position with coughing or straining. Differential diagnosis Differential diagnosis of the symptoms of inguinal hernia mainly includes the following potential conditions: Femoral hernia Epididymitis Testicular torsion Lipomas Inguinal adenopathy (Lymph node Swelling) Groin abscess Saphenous vein dilation, called Saphena varix Vascular aneurysm or pseudoaneurysm Hydrocele Varicocele Cryptorchidism (Undescended testes) Management Conservative There is currently no medical recommendation about how to manage an inguinal hernia condition in adults, due to the fact that, until recently, elective surgery used to be recommended. The hernia truss (or hernia belt) is intended to contain a reducible inguinal hernia within the abdomen. It is not considered to provide a cure, and if the pads are hard and intrude into the hernia aperture they may cause scarring and enlargement of the aperture. In addition, most trusses with older designs are not able effectively to contain the hernia at all times, because their pads do not remain permanently in contact with the hernia. The more modern variety of truss is made with non-intrusive flat pads and comes with a guarantee to hold the hernia securely during all activities. They have been described by users as providing greater confidence and comfort when carrying out physically demanding tasks. However, their use is controversial, as data to determine whether they help prevent hernia complications are lacking. A truss also increases the probability of complications, which include strangulation of the hernia, atrophy of the spermatic cord, and atrophy of the fascial margins. This allows the defect to enlarge and makes subsequent repair more difficult. Their popularity is nonetheless likely to increase, as many individuals with small, painless hernias are now delaying hernia surgery due to the risk of post-herniorrhaphy pain syndrome. Elasticated pants used by athletes may also provide useful support for the smaller hernia. Surgical Surgical correction of inguinal hernias is called a hernia repair. It is not recommended in minimally symptomatic hernias, for which watchful waiting is advised, due to the risk of post herniorraphy pain syndrome. Surgery is commonly performed as outpatient surgery. There are various surgical strategies which may be considered in the planning of inguinal hernia repair. These include the consideration of mesh use (e.g. synthetic or biologic), open repair, use of laparoscopy, type of anesthesia (general or local), appropriateness of bilateral repair, etc. Mesh or non mesh repairs have both benefits in different areas, but mesh repairs may reduce the rate of hernia reappearance, visceral or neurovascular injuries, length of hospital stay and time to return to activities of daily living. Laparoscopy is most commonly used for non-emergency cases; however, a minimally invasive open repair may have a lower incidence of post-operative nausea and mesh associated pain. During surgery conducted under local anaesthesia, the patient will be asked to cough and strain during the procedure to help in demonstrating that the repair is without tension and sound.Constipation after hernia repair results in strain to evacuate the bowel causing pain, and fear that the sutures may rupture. Opioid analgesia makes constipation worse. Promoting an easy bowel motion is important post-operatively. Surgical correction is always recommended for inguinal hernias in children.Emergency surgery for incarceration and strangulation carry much higher risk than planned, "elective" procedures. However, the risk of incarceration is low, evaluated at 0.2% per year. On the other hand, surgery has a risk of inguinodynia (10-12%), and this is why males with minimal symptoms are advised to watchful waiting. However, if they experience discomfort while doing physical activities or they routinely avoid them for fear of pain, they should seek surgical evaluation. For female patients, surgery is recommended even for asymptomatic patients. Epidemiology A direct inguinal hernia is less common (~25–30% of inguinal hernias) and usually occurs in men over 40 years of age. Men have an 8 times higher incidence of inguinal hernia than women. See also Birkett hernia References External links Indirect Inguinal Hernia - University of Connecticut Health Center Media related to Inguinal hernia at Wikimedia Commons

Pharyngitis

Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoarse voice. Symptoms usually last 3–5 days. Complications can include sinusitis and acute otitis media. Pharyngitis is a type of upper respiratory tract infection.Most cases are caused by a viral infection. Strep throat, a bacterial infection, is the cause in about 25% of children and 10% of adults. Uncommon causes include other bacteria such as gonorrhea, fungus, irritants such as smoke, allergies, and gastroesophageal reflux disease. Specific testing is not recommended in people who have clear symptoms of a viral infection, such as a cold. Otherwise, a rapid antigen detection test (RADT) or throat swab is recommended. Other conditions that can produce similar symptoms include epiglottitis, thyroiditis, retropharyngeal abscess, and occasionally heart disease.NSAIDs, such as ibuprofen, can be used to help with the pain. Numbing medication, such as topical lidocaine, may also help. Strep throat is typically treated with antibiotics, such as either penicillin or amoxicillin. It is unclear whether steroids are useful in acute pharyngitis, other than possibly in severe cases, but a recent (2020) review found that when used in combination with antibiotics they moderately improved pain and the likelihood of resolution.About 7.5% of people have a sore throat in any 3-month period. Two or three episodes in a year are not uncommon. This resulted in 15 million physician visits in the United States in 2007. Pharyngitis is the most common cause of a sore throat. The word comes from the Greek word pharynx meaning "throat" and the suffix -itis meaning "inflammation". Classification Pharyngitis is a type of inflammation caused by an upper respiratory tract infection. It may be classified as acute or chronic. Acute pharyngitis may be catarrhal, purulent, or ulcerative, depending on the causative agent and the immune capacity of the affected individual. Chronic pharyngitis may be catarrhal, hypertrophic, or atrophic.Tonsillitis is a subtype of pharyngitis. If the inflammation includes both the tonsils and other parts of the throat, it may be called pharyngotonsillitis or tonsillopharyngitis. Another subclassification is nasopharyngitis (the common cold).Clergymans sore throat or clergymans throat is an archaic term formerly used for chronic pharyngitis associated with overuse of the voice as in public speaking. It was sometimes called dysphonia clericorum or chronic folliculitis sore throat. Cause Most cases are due to an infectious organism acquired from close contact with an infected individual. Viral These comprise about 40–80% of all infectious cases and can be a feature of many different types of viral infections. Adenovirus is the most common of the viral causes. Typically, the degree of neck lymph node enlargement is modest and the throat often does not appear red, although it is painful. The family Orthomyxoviridae which cause influenza are present with rapid onset high temperature, headache, and generalized ache. A sore throat may be associated. Infectious mononucleosis ("glandular fever") is caused by the Epstein–Barr virus. This may cause significant lymph-node swelling and an exudative tonsillitis with marked redness and swelling of the throat. The heterophile test can be used if this is suspected. Herpes simplex virus can cause multiple mouth ulcers. Measles Common cold: rhinovirus, coronavirus, respiratory syncytial virus, and parainfluenza virus can cause infection of the throat, ear, and lungs causing standard cold-like symptoms and often pain. Bacterial A number of different bacteria can infect the human throat. The most common is group A streptococcus (Streptococcus pyogenes), but others include Streptococcus pneumoniae, Haemophilus influenzae, Bordetella pertussis, Bacillus anthracis, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Fusobacterium necrophorum. Streptococcal pharyngitis Streptococcal pharyngitis or strep throat is caused by a group A beta-hemolytic streptococcus (GAS). It is the most common bacterial cause of cases of pharyngitis (15–30%). Common symptoms include fever, sore throat, and large lymph nodes. It is a contagious infection, spread by close contact with an infected individual. A definitive diagnosis is made based on the results of a throat culture. Antibiotics are useful to both prevent complications (such as rheumatic fever) and speed recovery. Fusobacterium necrophorumFusobacterium necrophorum is a normal inhabitant of the oropharyngeal flora and can occasionally create a peritonsillar abscess. In one out of 400 untreated cases, Lemierres syndrome occurs. DiphtheriaDiphtheria is a potentially life-threatening upper respiratory infection caused by Corynebacterium diphtheriae, which has been largely eradicated in developed nations since the introduction of childhood vaccination programs, but is still reported in the Third World and increasingly in some areas in Eastern Europe. Antibiotics are effective in the early stages, but recovery is generally slow. OthersA few other causes are rare, but possibly fatal, and include parapharyngeal space infections: peritonsillar abscess ("quinsy abscess"), submandibular space infection (Ludwigs angina), and epiglottitis. Fungal Some cases of pharyngitis are caused by fungal infection, such as Candida albicans, causing oral thrush. Noninfectious Pharyngitis may also be caused by mechanical, chemical, or thermal irritation, for example cold air or acid reflux. Some medications may produce pharyngitis, such as pramipexole and antipsychotics. Diagnosis Differentiating a viral and a bacterial cause of a sore throat based on symptoms alone is difficult. Thus, a throat swab often is done to rule out a bacterial cause.The modified Centor criteria may be used to determine the management of people with pharyngitis. Based on five clinical criteria, it indicates the probability of a streptococcal infection.One point is given for each of the criteria: Absence of a cough Swollen and tender cervical lymph nodes Temperature more than 38.0 °C (100.4 °F) Tonsillar exudate or swelling Age less than 15 (a point is subtracted if age is more than 44)The Infectious Disease Society of America recommends against empirical treatment and considers antibiotics only appropriate following positive testing. Testing is not needed in children under three, as both group A strep and rheumatic fever are rare, except if they have a sibling with the disease. Management The majority of the time, treatment is symptomatic. Specific treatments are effective for bacterial, fungal, and herpes simplex infections. Medications Pain medication, such as NSAIDs and acetaminophen (paracetamol), can help reduce the pain associated with a sore throat. Aspirin may be used in adults, but is not recommended in children due to the risk of Reye syndrome. Steroids (such as dexamethasone) may be useful for severe pharyngitis. Their general use, however, is poorly supported. Viscous lidocaine relieves pain by numbing the mucous membranes. Antibiotics are useful if a bacterial infection is the cause of the sore throat. For viral infections, antibiotics have no effect. In the United States, they are used in 25% of people before a bacterial infection has been detected. Oral analgesic solutions, the active ingredient is usually phenol, but also less commonly benzocaine, cetylpyridinium chloride, and/or menthol. Chloraseptic and Cepacol are two examples of brands of these kinds of analgesics. Alternative Gargling salt water is often suggested, but there is no evidence to support or discourage this practice. Alternative medicines are promoted and used for the treatment of sore throats. However, they are poorly supported by evidence. Epidemiology Acute pharyngitis is the most common cause of a sore throat and, together with cough, it is diagnosed in more than 1.9 million people a year in the United States. References == External links ==

Acanthosis nigricans

Acanthosis nigricans is a medical sign characterised by brown-to-black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the armpits, groin, navel, forehead and other areas.It is associated with endocrine dysfunction, especially insulin resistance and hyperinsulinaemia, as seen in diabetes mellitus. This activates the insulin-like growth factor receptors, which leads to proliferation of keratinocytes, fibroblasts and other cells in the skin. Activation of other growth factor receptors such as fibroblast growth factor receptors or epidermal growth factor receptor can also be responsible. Signs and symptoms Acanthosis nigricans may present with thickened, velvety, relatively darker areas of skin on the neck, armpit and in skin folds. Causes It typically occurs in individuals younger than age 40, may be genetically inherited and is associated with obesity or endocrinopathies, such as hypothyroidism, acromegaly, polycystic ovary syndrome, insulin-resistant diabetes or Cushings disease. Type I – familial Familial acanthosis: 86  may arise as a result of an autosomal dominant trait, presenting at birth or developing during childhood.: 506 : 676 Type II – endocrine Endocrine syndromes associated with acanthosis nigricans: 506–7  can develop in many conditions, particularly:: 978  : 86  starts with insulin resistance, such as diabetes mellitus and metabolic syndrome excess circulating androgens, particularly Cushings disease, acromegaly, polycystic ovary syndrome Addisons disease and hypothyroidism Rare diseases, including pinealoma, leprechaunism, lipoatrophic diabetes, pineal hyperplasia syndrome, pituitary basophilism, ovarian hyperthecosis, stromal luteoma, ovarian dermoid cysts, Prader-Willi syndrome, and Alström syndrome.Acanthosis nigricans associated with endocrine dysfunction is more insidious in its onset, is less widespread, and the patients are often concurrently obese.: 676 Type III – obesity and pseudoacanthosis nigricans In young persons, acanthosis nigricans is a visible marker which strongly suggests insulin resistance. Higher than normal insulin levels in the blood stream cause the growth of darkened skin over certain areas of the body. No skin treatment will get rid of AN. Acanthosis nigricans may lighten up and possibly go away by treating the root cause, insulin resistance, but it can take months or years to do so. Insulin resistance syndromes may be divided into type A (HAIR-AN) and type B syndromes.: 978 The majority of cases of acanthosis nigricans are associated with obesity and otherwise idiopathic. This is likely because of insulin resistance and more likely to occur in darker-skinned persons.: 968  This can also be referred to as pseudoacanthosis nigricans.: 86  In some cases, AN attributable to obesity and insulin resistance will occur on ones face. Most typically it will be present as a horizontal band on the forehead, but may also appear as perioral hyperpigmentation, periorbital hyperpigmentation, or generalized facial skin darkening. Type IV – drug-related Acanthosis nigricans has been linked to the use of nicotinic acid, glucocorticoid use, combined oral contraceptive pills, and growth hormone therapy.: 86 Type V – malignancy Malignant acanthosis nigricans: 86  refers to acanthosis nigricans occurring as a paraneoplastic syndrome associated with a cancer. Malignant acanthosis nigricans is most commonly associated with gastrointestinal adenocarcinomas, as well as genitourinary cancers such as those of the prostate, breast, and ovary. Other cancers, such as those of the lung, stomach, and lymphoma, are occasionally associated with acanthosis nigricans.: 86 This form of acanthosis nigricans is more likely to involve mucous membranes (25–50% of cases) Malignant acanthosis nigricans that may either precede (18%), accompany (60%), or follow (22%) the onset of an internal cancer.: 506  Malignancy-associated acanthosis nigricans is usually rapid in onset and may be accompanied by skin tags, multiple seborrheic keratoses, or tripe palms.: 676 Acral acanthotic anomaly Acral acanthotic anomaly refers to a variant of acanthosis nigricans limited to the elbows, knees, knuckles, and dorsal surfaces of the feet, in the absence of any other findings, in otherwise healthy individuals. While the etiology remains unknown, its presence does not suggest a likelihood of malignancy. Pathophysiology Acanthosis nigricans is caused by increased activation of growth factor receptor proteins, usually due to endocrine dysfunction. This is most commonly insulin-mediated activation of IGF receptors on keratinocytes, as a result of hyperinsulinaemia or insulin resistance, as seen in diabetes mellitus.Factors involved in the development of acanthosis nigricans include: Increased circulating insulin. This activates keratinocyte IGF receptors, particularly IGF-1. At high concentrations, insulin may also displace IGF-1 from insulin-like growth factor-binding protein (IGFBP). Increased circulating IGF may lead to keratinocyte and dermal fibroblast proliferation. In hereditary forms of acanthosis nigricans, fibroblast growth factor receptor (FGFR) defects Increased transforming growth factor (TGF), which appears to be the mechanism for malignancy-associated acanthosis nigricans. TGF acts on epidermal tissue via the epidermal growth factor receptor (EGFR).: 86 In conjunction with increased end levels of IGF, it is likely that perspiration and friction may be necessary predeterminants for lesions, since the level of insulin is usually not enough to activate IGF receptors across the body. Diagnosis Acanthosis nigricans is typically diagnosed clinically. A skin biopsy may be needed in unusual cases. If no clear cause is obvious, it may be necessary to search for one. Blood tests, an endoscopy, or X-rays may be required to eliminate the possibility of diabetes or cancer as the cause.: 87 On biopsy, hyperkeratosis, epidermal folding, leukocyte infiltration, and melanocyte proliferation may be seen.: 979 : 87 Differential diagnosis Acanthosis nigricans should be distinguished from the casal collar appearing in pellagra. Classification Acanthosis nigricans is conventionally divided into benign and malignant forms, although may be divided into syndromes according to cause:: 506  Benign This may include obesity-related, hereditary, and endocrine forms of acanthosis nigricans. Malignant. This may include forms that are associated with tumour products and insulin-like activity, or tumour necrosis factor.An alternate classification system still used to describe acanthosis nigricans was proposed in 1994. It delineates acanthosis nigricans syndromes according to their associated syndromes, including benign and malignant forms, forms associated with obesity and drugs, acral acanthosis nigricans, unilateral acanthosis nigricans, and mixed and syndromic forms. Treatment People with acanthosis nigricans should be screened for diabetes and, although rare, cancer. Controlling blood glucose levels through exercise and diet often improves symptoms. Topical fade creams (normally used for eliminating age spots) can lighten skin cosmetically in less severe cases. Selenium sulfide topical 2 percent applied in thin layer to dry skin ten minutes prior to bathing may clear symptoms. Selenium sulfide applied to dry scalp or skin is an inexpensive well tolerated treatment to balance skins biome and works by drying fungus like tinea versicolor that can coexist with acanthosis and exacerbate discoloration. Acanthosis nigricans maligna may resolve if the causative tumor is successfully removed. Prognosis Acanthosis nigricans is likely to improve in circumstances where a known cause is removed. For example, obesity-related acanthosis nigricans will improve with weight loss, and drug-induced acanthosis nigricans is likely to resolve when the drug is ceased. Hereditary variants may or may not fade with age, and malignancy-associated variants may, after a malignancy is removed, fade. : 87 References External links 00001 at CHORUS

Acute prostatitis

Acute prostatitis is a serious bacterial infection of the prostate gland. This infection is a medical emergency. It should be distinguished from other forms of prostatitis such as chronic bacterial prostatitis and chronic pelvic pain syndrome (CPPS). Signs and symptoms Men with acute prostatitis often have chills, fever, pain in the lower back, perineum, or genital area, urinary frequency and urgency often at night, burning or painful urination, body aches, and a demonstrable infection of the urinary tract, as evidenced by white blood cells and bacteria in the urine. Acute prostatitis may be a complication of prostate biopsy. Often, the prostate gland is very tender to palpation through the rectum. Diagnosis Acute prostatitis is relatively easy to diagnose due to its symptoms that suggest infection. The organism may be found in blood or urine, and sometimes in both. Common bacteria are Escherichia coli, Klebsiella, Proteus, Pseudomonas, Enterobacter, Enterococcus, Serratia, and Staphylococcus aureus. This can be a medical emergency in some patients and hospitalization with intravenous antibiotics may be required. A complete blood count reveals increased white blood cells. Sepsis from prostatitis is very rare, but may occur in immunocompromised patients; high fever and malaise generally prompt blood cultures, which are often positive in sepsis. A prostate massage should never be done in a patient with suspected acute prostatitis, since it may induce sepsis. Since bacteria causing the prostatitis is easily recoverable from the urine, prostate massage is not required to make the diagnosis. Rectal palpation usually reveals an enlarged, exquisitely tender, swollen prostate gland, which is firm, warm, and, occasionally, irregular to the touch. C-reactive protein is elevated in most cases.Prostate biopsies are not indicated as the (clinical) features (described above) are diagnostic. The histologic correlate of acute prostatitis is a neutrophilic infiltration of the prostate gland.Acute prostatitis is associated with a transiently elevated PSA, i.e., the PSA is increased during an episode of acute prostatitis and then decreases again after it has resolved. PSA testing is not indicated in the context of uncomplicated acute prostatitis. Other diagnostic method is sonography Treatment Antibiotics are the first line of treatment in acute prostatitis. Antibiotics usually resolve acute prostatitis infections in a very short time, however a minimum of two to four weeks of therapy is recommended to eradicate the offending organism completely. Appropriate antibiotics should be used, based on the microbe causing the infection. Some antibiotics have very poor penetration of the prostatic capsule, others, such as ciprofloxacin, trimethoprim/sulfamethoxazole, and tetracyclines such as doxycycline penetrate prostatic tissue well. In acute prostatitis, penetration of the prostate is not as important as for category II because the intense inflammation disrupts the prostate-blood barrier. It is more important to choose a bactericidal antibiotic (kills bacteria, e.g., a fluoroquinolone antibiotic) rather than a bacteriostatic antibiotic (slows bacterial growth, e.g. tetracycline) for acute potentially life-threatening infections.Severely ill patients may need hospitalization, while nontoxic patients can be treated at home with bed rest, analgesics, stool softeners, and hydration. Men with acute prostatitis complicated by urinary retention are best managed with a suprapubic catheter or intermittent catheterization. Lack of clinical response to antibiotics should raise the suspicion of an abscess and prompt an imaging study such as a transrectal ultrasound (TRUS). Prognosis Full recovery without sequelae is usual. References External links Prostatitis at Curlie

Alport syndrome

Alport syndrome is a genetic disorder affecting around 1 in 5,000-10,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect vision, except when changes to the lens occur in later life. Blood in urine is universal. Proteinuria is a feature as kidney disease progresses.The disorder was first identified in a British family by the physician Cecil A. Alport in 1927. Alport syndrome once also had the label hereditary nephritis, but this is misleading as there are many other causes of hereditary kidney disease and nephritis. Alport syndrome is caused by an inherited defect in type IV collagen—a structural material that is needed for the normal function of different parts of the body. Since type IV collagen is found in the ears, eyes, and kidneys, this explains why Alport syndrome affects different seemingly unrelated parts of the body (ears, eyes, kidneys, etc.). Depending on where the mutation is located in the genome, Alport syndrome can present itself in many forms. This includes X-linked Alport syndrome (XLAS), autosomal recessive Alport syndrome (ARAS), and autosomal dominant Alport syndrome (ADAS). Signs and symptoms These descriptions refer to classic Alport syndrome, which usually causes significant disease from young adult or late childhood life. Some individuals, usually with milder mutations or carrier status, develop disease later, or show only some of the features of classic disease. Chronic kidney disease Blood in urine is a usual feature of Alport syndrome from early infancy, identifiable on urine dipsticks. In young children, episodes of visible (macroscopic) haematuria may occur. Protein begins to appear in urine as the disease progresses. This is now regarded as an indication for treatment with ACE inhibitors. Progressive loss of kidney function (reflected clinically by increases in serum creatinine or decreases in estimated glomerular filtration rate) can occur and may require treatment with renal replacement: dialysis or a kidney transplant. Hearing loss Alport syndrome can also cause hearing loss although some patients are not affected. Hearing in Alport syndrome patients is normal at birth. Hearing loss in affected patients develops progressively, usually at the stage when kidney function is normal, but there is substantial proteinuria. However, in some patients, hearing loss is only noted after kidney function has been lost. Characteristically the early changes are reduced ability to hear high-frequency sounds, sensorineural deafness. This becomes more severe and affects lower frequencies too. Hearing loss is not usually complete in Alport syndrome; good communication is almost always possible with the use of hearing aids. Eye changes Various eye abnormalities are often seen including lenticonus, keratoconus, cataracts and corneal erosion as well as retinal flecks in the macula and mid-periphery. These rarely threaten vision. Lenticonus (cone-shaped lens) can be treated by replacement of the lens, as for cataracts. Mild keratoconus can be managed with hard, scleral, piggy-back or other specialty medical contact lenses; progressive cases may be halted with corneal collagen cross linking; and severe cases may require a corneal transplant. Macular abnormalities such as incomplete foveal hypoplasia or staircase foveopathy are common in Alport syndrome.It may also be associated with retinitis pigmentosa. Leiomyomatosis Diffuse leiomyomatosis of the oesophagus and tracheobronchial tree has been reported in some families with Alport syndrome. Symptoms usually appear in late childhood and include dysphagia, postprandial vomiting, substernal or epigastric pain, recurrent bronchitis, dyspnea, cough, and stridor. Leiomyomatosis is confirmed by computed tomography (CT) scanning or magnetic resonance imaging (MRI). Other abnormalities Aortic dissection has been described very rarely in patients with early-onset disease. Leiomyomas, tumours of smooth muscle affecting the oesophagus and female genital tract, may occur in a rare overlap syndrome involving the adjacent COL4A5 and COL4A6 genes. Pathophysiology Alport Syndrome is a relatively common genetic disorder affecting around 1 in 5,000-10,000 children, Genetics Alport syndrome is caused by mutations in COL4A3, COL4A4, and COL4A5, three of six human genes involved in basement membrane (type IV) collagen biosynthesis. Mutations in any of these genes prevent the proper production or assembly of the specialised type IV collagen 345 network which is an important structural component of basement membranes in the kidney, inner ear, and eye. It is also found in other locations, including the alveoli of the lungs. Basement membranes are thin, sheet-like structures that separate and support cells in many tissues. Type IV collagen 112 type is found in both vertebrates and invertebrates and is the major isoform in most human basement membranes. When mutations prevent the formation of 345 type IV collagen network in the glomerulus, the 112 network, which is formed in fetal development but usually replaced by 345, persists into adult life. Inheritance patterns Alport syndrome can have different inheritance patterns depending on which specific mutation is present. In most people with Alport syndrome (about 85%), the condition is inherited in an X-linked pattern, due to mutations in the COL4A5 gene. A condition is considered X-linked if the gene involved in the disorder is located on the X chromosome. In males, who have only one X chromosome, one altered copy of the COL4A5 gene is sufficient to cause severe Alport syndrome, explaining why most affected males eventually develop kidney failure. In females, who have two X chromosomes, a mutation in one copy of the COL4A5 gene usually results in blood in the urine, but most affected females do not develop kidney failure. Alport syndrome can also be inherited in an autosomal recessive pattern if both copies of the COL4A3 or COL4A4 gene, located on chromosome 2, have been mutated. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene. Past descriptions of an autosomal dominant form are now usually categorized as other conditions. Notably, conditions associated with giant platelets and associated with mutations of MYH9 are no longer considered to be Alport variants. However apparent autosomal dominant transmission of disease associated with mutations in COL4A3 and COL4A4 does occur.Clinical utility gene card for: Alport syndrome. Diagnosis The diagnosis can usually be made on a combination of clinical, family history, and biopsy criteria. Biopsy of kidneys or skin To be helpful, kidney biopsies need to be taken before the disease is too advanced. Changes on conventional (light) microscopy are not characteristic, and the possibility of other diagnoses, particularly focal segmental glomerulosclerosis (FSGS), may be raised. Electron microscopy shows a characteristic sequence of changes from thinning of the glomerular basement membrane (GBM), developing into areas of thinning and thickening, and finally into a complex appearance with apparent splitting, often described as a basketweave appearance. Early or very localised changes on this spectrum are not diagnostic, but the later changes are considered diagnostic.Immunohistochemistry or immunofluorescence studies to identify the COL3-4-5 proteins in GBM can be helpful. However, these studies may be normal in some patients with Alport syndrome, especially milder variants.The skin contains type IV collagen in a 556 network. Skin biopsies have been used to show the absence of the COL4A5 gene product, but these techniques are not straightforward, only apply to patients with severe COL4A5 mutations, and are not widely available. Genetic testing is now a better alternative if kidney biopsy is not possible. Family history A family history of end-stage renal disease with hearing impairment is suggestive of Alport syndrome, but other conditions can cause this combination of abnormalities. Most can be distinguished by clinical features. The finding of haematuria in relatives is suggestive. While X-linked inheritance is the most common pattern, genetic testing is revealing that atypical presentations may be more common than currently thought. Genetic testing Genetic testing plays an increasingly important role in confirming the diagnosis where the clinical features do not amount to proof. Other tests The use of eye examinations for screening has been proposed. Other tests may include a urine or blood test. Treatment Kidney disease and renal failure In addition to measures for chronic kidney disease (CKD) of any cause, there is evidence that ACE inhibitors can slow the deterioration of kidney function in Alport syndrome, delaying the need for dialysis or transplantation. The development of proteinuria has been recommended as an indication for commencing treatment.Once kidney failure has developed, patients usually do well on dialysis or with a kidney transplant. Transplantation can rarely be associated with the formation of antibodies to type IV collagen in the donor kidney resulting in progressive graft failure as a result of Goodpasture syndrome (Alport post-transplant anti-GBM disease).Gene therapy has been frequently discussed, but delivering it to the podocytes in the glomerulus that normally produce the type IV collagen in the glomerular basement membrane is challenging. Hearing loss It is not known whether ACE inhibitors or other treatments affect hearing loss. For those with classic Alport syndrome, hearing aids are often required in teenage or young adult years. Prognosis Studies of the life expectancy of patients with Alport syndrome are rare, but one 2012 study found that Alport patients receiving renal replacement therapy (dialysis or kidney transplantation) exhibited, on average, better survival compared with matched controls who had other renal diseases (and who also received renal replacement therapy). See also AMMECR1 Samoyed hereditary glomerulopathy, a disease shown to be a model for Alport syndrome. Fechtner syndrome Thin basement membrane disease References This article incorporates public domain material from the United States National Library of Medicine document: "Alport syndrome". (Genetics Home Reference) External links GeneReview/NIH/UW entry on Alport syndrome

Bronchiolitis

Bronchiolitis is inflammation of the small airways in the lungs. Acute bronchiolitis is due to a viral infection usually affecting children younger than two years of age. Symptoms may include fever, cough, runny nose, wheezing, and breathing problems. More severe cases may be associated with nasal flaring, grunting, or the skin between the ribs pulling in with breathing. If the child has not been able to feed properly, signs of dehydration may be present.Chronic bronchiolitis is the general term used for small airways disease in adults, notably in chronic obstructive pulmonary disease.Acute bronchiolitis is usually the result of infection by respiratory syncytial virus (72% of cases) or human rhinovirus (26% of cases). Diagnosis is generally based on symptoms. Tests such as a chest X-ray or viral testing are not routinely needed.There is no specific treatment. Symptomatic treatment at home is generally sufficient. Occasionally, hospital admission for oxygen, support with feeding, or intravenous fluids is required. Tentative evidence supports nebulized hypertonic saline. Evidence for antibiotics, antivirals, bronchodilators, or nebulized epinephrine is either unclear or not supportive.About 10% to 30% of children under the age of two years are affected by bronchiolitis at some point in time. It commonly occurs in the winter in the Northern Hemisphere. It is the leading cause of hospitalizations in those less than one year of age in the United States. The risk of death among those who are admitted to hospital is about 1%. Outbreaks of the condition were first described in the 1940s. Signs and symptoms Bronchiolitis typically presents in children under two years old and is characterized by a constellation of respiratory symptoms that consists of fever, rhinorrhea, cough, wheeze, tachypnea and increased work of breathing such as nasal flaring or grunting that develops over one to three days. Crackles or wheeze are typical findings on listening to the chest with a stethoscope. The child may also experience apnea, or brief pauses in breathing. After the acute illness, it is common for the airways to remain sensitive for several weeks, leading to recurrent cough and wheeze. Some signs of severe disease include: increased work of breathing (such as use of accessory muscles of respiration, rib & sternal retraction, tracheal tug) severe chest wall recession (Hoovers sign) presence of nasal flaring and/or grunting increased respiratory rate above normal hypoxia (low oxygen levels) cyanosis (bluish skin) lethargy and decreased activity poor feeding (less than half of usual fluid intake in preceding 24 hours) history of stopping breathing Causes The term usually refers to acute viral bronchiolitis, a common disease in infancy. This is most commonly caused by respiratory syncytial virus (RSV, also known as human pneumovirus). Other agents that cause this illness include human metapneumovirus, influenza, parainfluenza, coronavirus, adenovirus, rhinovirus and mycoplasma. Risk factors Children are at an increased risk for progression to severe respiratory disease if they have any of the following additional factors: Preterm infant (gestational age less than 37 weeks) Younger age at onset of illness (less than 3 months of age) Congenital heart disease Immunodeficiency Chronic lung disease Neurological disorders Tobacco smoke exposure Diagnosis The diagnosis is typically made by clinical examination. Chest X-ray is sometimes useful to exclude bacterial pneumonia, but not indicated in routine cases. Chest x-ray may also be useful in people with impending respiratory failure. Additional testing such as blood cultures, complete blood count, and electrolyte analyses are not recommended for routine use although may be useful in children with multiple comorbidities or signs of sepsis or pneumonia.Testing for the specific viral cause can be done but has little effect on management and thus is not routinely recommended. RSV testing by direct immunofluorescence testing on nasopharyngeal aspirate had a sensitivity of 61% and specificity of 89%. Identification of those who are RSV-positive can help for disease surveillance, grouping ("cohorting") people together in hospital wards to prevent cross infection, predicting whether the disease course has peaked yet, and reducing the need for other diagnostic procedures (by providing confidence that a cause has been identified). Identification of the virus may help reduce the use of antibiotics.Infants with bronchiolitis between the age of two and three months have a second infection by bacteria (usually a urinary tract infection) less than 6% of the time. When further evaluated with a urinalysis, infants with bronchiolitis had a concomitant UTI 0.8% of the time. Preliminary studies have suggested that elevated procalcitonin levels may assist clinicians in determining the presence of bacterial co-infection, which could prevent unnecessary antibiotic use and costs. Differential diagnosis There are many childhood illnesses that can present with respiratory symptoms, particularly persistent cough and wheezing. Bronchiolitis may be differentiated from some of these by the characteristic pattern of preceding febrile upper respiratory tract symptoms lasting for 1 to 3 days followed by the persistent cough, tachypnea, and wheezing. However, some infants may present without fever (30% of cases) or may present with apnea without other signs or with poor weight gain prior to onset of symptoms. In such cases, additional laboratory testing and radiographic imaging may be useful. The following are some other diagnoses to consider in an infant presenting with signs of bronchiolitis: Asthma and reactive airway disease Bacterial pneumonia Congenital heart disease Heart failure Whooping cough Allergic reaction Cystic fibrosis Chronic pulmonary disease Foreign body aspiration Vascular ring Prevention Prevention of bronchiolitis relies strongly on measures to reduce the spread of the viruses that cause respiratory infections (that is, handwashing, and avoiding exposure to those symptomatic with respiratory infections). Guidelines are mixed on the use of gloves, aprons, or personal protective equipment. In addition to good hygiene, an improved immune system is a great tool for prevention.One way to improve the immune system is to feed the infant with breast milk, especially during the first month of life. Respiratory infections were shown to be significantly less common among breastfed infants and fully breastfed RSV-positive hospitalized infants had shorter hospital stays than non or partially breastfed infants. Guidelines recommend exclusive breastfeeding for infants for the first 6 months of life.Palivizumab, a monoclonal antibody against RSV, can be administered to prevent bronchiolitis to infants less than one year of age that were born very prematurely or that have underlying heart disease or chronic lung disease of prematurity. Passive immunization therapy requires monthly injections during winter. Otherwise healthy premature infants that were born after a gestational age of 29 weeks should not be administered palivizumab as the harms outweigh the benefits. Passive protection through the administration of other novel monoclonal antibodies is also under evaluation.Immunizations for RSV are being developed but none are available currently outside of clinical trials.Tobacco smoke exposure has been shown to increase both the rates of lower respiratory disease in infants, as well as the risk and severity of bronchiolitis. Tobacco smoke lingers in the environment for prolonged periods and on clothing even when smoking outside the home. Guidelines recommend that parents be fully educated on the risks of tobacco smoke exposure on children with bronchiolitis. Management Treatment of bronchiolitis is usually focused on the hydration and symptoms instead of the infection itself since the infection will run its course and complications are typically from the symptoms themselves. Without active treatment, half of cases will go away in 13 days and 90% in three weeks. Children with severe symptoms, especially poor feeding or dehydration, may be considered for hospital admission. Oxygen saturation under 90%-92% as measured with pulse oximetry is also frequently used as an indicator of need for hospitalization. High-risk infants, apnea, cyanosis, malnutrition, and diagnostic uncertainty are additional indications for hospitalization.Most guidelines recommend sufficient fluids and nutritional support for affected children. Measures for which the recommendations were mixed include nebulized hypertonic saline, nebulized epinephrine, and nasal suctioning. Treatments which the evidence does not support include salbutamol, steroids, antibiotics, antivirals, heliox, continuous positive airway pressure (CPAP), chest physiotherapy, and cool mist or steam inhalation. Diet Maintaining hydration is an important part of management of bronchiolitis. Infants with mild pulmonary symptoms may require only observation if feeding is unaffected. However, oral intake may be affected by nasal secretions and increased work of breathing. Poor feeding or dehydration, defined as less than 50% of usual intake, is often cited as an indication for hospital admission. Guidelines recommend the use of nasogastric or intravenous fluids in children with bronchiolitis who cannot maintain usual oral intake. The risk of health care caused hyponatremia and fluid retention are minimal with the use of isotonic fluids such as normal saline, breast milk, or formula. Oxygen Inadequate oxygen supply to the tissue is one of the main concerns during severe bronchiolitis and oxygen saturation is often closely associated with both the need for hospitalization and continued length of hospital stay in children with bronchiolitis. However, oxygen saturation is a poor predictor of respiratory distress. Accuracy of pulse oximetry is limited in the 76% to 90% range and there is weak correlation between oxygen saturation and respiratory distress as brief hypoxemia is common in healthy infants. Additionally, pulse oximetry is associated with frequent false alarms and parental stress and fatigue. Clinicians may choose not to given additional oxygen to children with bronchiolitis if their oxygen saturation is above 90%. Additionally, clinicians may choose not to use continuous pulse oximetry in these people.When choosing to use oxygen therapy for a child with bronchiolitis, there is evidence that home oxygen may reduce hospitalization rate and length of stay although readmission rates and follow-up visits are increased. Also, the use of humidified, heated, high-flow nasal cannula may be a safe initial therapy to decrease work of breathing and need for intubation. However, evidence is lacking regarding the use of high-flow nasal cannula compared to standard oxygen therapy or continuous positive airway pressure. These practices may still be used in severe cases prior to intubation.Blood gas testing is not recommended for people hospitalized with the disease and is not useful in the routine management of bronchiolitis. People with severe worsening respiratory distress or impending respiratory failure may be considered for capillary blood gas testing. Hypertonic saline Guidelines recommend against the use of nebulized hypertonic saline in the emergency department for children with bronchiolitis but it may be given to children who are hospitalized.Nebulized hypertonic saline (3%) has limited evidence of benefit and previous studies lack consistency and standardization. A 2017 review found tentative evidence that it reduces the risk of hospitalization, duration of hospital stay, and improved the severity of symptoms. The majority of evidence suggests that hypertonic saline is safe and effective at improving respiratory symptoms of mild to moderate bronchiolitis after 24 hours of use. However, it does not appear effective in reducing the rate of hospitalization when used in the emergency room or other outpatient settings in which length of therapy is brief. Side effects were mild and resolved spontaneously. Bronchodilators Guidelines recommend against the use of bronchodilators in children with bronchiolitis as evidence does not support a change in outcomes with such use. Additionally, there are adverse effects to the use of bronchodilators in children such as tachycardia and tremors, as well as adding increased financial expenses.Several studies have shown that bronchodilation with β-adrenergic agents such as salbutamol may improve symptoms briefly but do not affect the overall course of the illness or reduce the need for hospitalization. However, there are conflicting recommendations about the use of a trial of a bronchodilator, especially in those with history of previous wheezing, due to the difficulty with assessing an objective improvement in symptoms. Bronchiolitis-associated wheezing is likely not effectively alleviated by bronchodilators anyway as it is caused by airway obstruction and plugging of the small airway diameters by luminal debris, not bronchospasm as in asthma-associated wheezing that bronchodilators usually treat well.Anticholinergic inhalers, such as ipratropium bromide, have a modest short-term effect at best and are not recommended for treatment. Epinephrine The current state of evidence suggests that nebulized epinephrine is not indicated for children with bronchiolitis except as a trial of rescue therapy for severe cases.Epinephrine is an α and β adrenergic agonist that has been used to treat other upper respiratory tract illnesses, such as croup, as a nebulized solution. A Cochrane meta-analysis in 2011 found no benefit to the use of epinephrine in the inpatient setting and suggested that there may be utility in the outpatient setting in reducing the rate of hospitalization. However, current guidelines do not support the outpatient use of epinephrine given the lack of substantial sustained benefit.A 2017 review found inhaled epinephrine with corticosteroids did not change the need for hospitalization or the time spent in hospital. Other studies suggest a synergistic effect of epinephrine with corticosteroids but have not consistently demonstrated benefits in clinical trials. Guidelines recommend against its use currently. Unclear evidence Currently other medications do not yet have evidence to support their use, although they have been studied for use in bronchiolitis. Experimental trials with novel antiviral medications in adults are promising but it remains unclear if the same benefit will be present. Surfactant had favorable effects for severely critical infants on duration of mechanical ventilation and ICU stay however studies were few and small. Chest physiotherapy, such as vibration or percussion, to promote airway clearance may slightly reduce duration of oxygen therapy but there is a lack of evidence that demonstrates any other benefits. People with difficulty clearing secretions due to underlying disorders such as spinal muscle atrophy or severe tracheomalacia may be considered for chest physiotherapy. Suctioning of the nares may provide temporarily relief of nasal congestion but deep suctioning of the nasopharynx has been shown prolong length of hospital stay in infants. Upper airway suctioning may be considered in people with respiratory distress, feeding difficulties, or infants presenting with apnea. Heliox, a mixture of oxygen and the inert gas helium, may be beneficial in infants with severe acute RSV bronchiolitis who require CPAP but overall evidence is lacking. DNAse has not been found to be effective but might play a role in severe bronchiolitis complicated by atelectasis. There are no systematic reviews or controlled trials on the effectiveness of nasal decongestants, such as xylometazoline, for the treatment of bronchiolitits. Overall evidence is insufficient to support the use of alternative medicine. There is tentative evidence for Chinese herbal medicine, vitamin D, N-acetylcysteine, and magnesium but this is insufficient to recommend their use. Non-effective treatments Ribavirin is an antiviral drug which does not appear to be effective for bronchiolitis. Antibiotics are often given in case of a bacterial infection complicating bronchiolitis, but have no effect on the underlying viral infection and their benefit is not clear. The risks of bronchiolitis with a concomitant serious bacterial infection among hospitalized febrile infants is minimal and work-up and antibiotics are not justified. Azithromycin adjuvant therapy may reduce the duration of wheezing and coughing in children with bronchiolitis but has not effect on length of hospital stay or duration of oxygen therapy. Corticosteroids, although useful in other respiratory disease such as asthma and croup, have no proven benefit in bronchiolitis treatment and are not advised. Additionally, corticosteroid therapy in children with bronchiolitis may prolong viral shedding and transmissibility. The overall safety of corticosteroids is questionable. Leukotriene inhibitors, such as montelukast, have not been found to be beneficial and may increase adverse effects. Immunoglobulins are of unclear benefit. Epidemiology Bronchiolitis typically affects infants and children younger than two years, principally during the autumn and winter. It is the leading cause of hospital admission for respiratory disease among infants in the United States and accounts for one out of every 13 primary care visits. Bronchiolitis accounts for 3% of emergency department visits for children under 2 years old. Bronchiolitis is the most frequent lower respiratory tract infection and hospitalization in infants worldwide. References External links Bronchiolitis. Patient information from NHS Choices "Bronchiolitis in children – A national clinical guideline" (PDF). Archived from the original (PDF) on 4 March 2016. Retrieved 6 December 2007. (1.74 MB) from the Scottish Intercollegiate Guidelines Network Ralston, SL; Lieberthal, AS; Meissner, HC; Alverson, BK; Baley, JE; Gadomski, AM; Johnson, DW; Light, MJ; Maraqa, NF; Mendonca, EA; Phelan, KJ; Zorc, JJ; Stanko-Lopp, D; Brown, MA; Nathanson, I; Rosenblum, E; Sayles S, 3rd; Hernandez-Cancio, S (27 October 2014). "Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis". Pediatrics. 134 (5): e1474–502. doi:10.1542/peds.2014-2742. PMID 25349312.

Carotid artery stenosis

Carotid artery stenosis is a narrowing or constriction of any part of the carotid arteries, usually caused by atherosclerosis. Signs and symptoms The common carotid artery is the large artery whose pulse can be felt on both sides of the neck under the jaw. On the right side it starts from the brachiocephalic artery (a branch of the aorta), and on the left side the artery comes directly off the aortic arch. At the throat it forks into the internal carotid artery and the external carotid artery. The internal carotid artery supplies the brain, and the external carotid artery supplies the face. This fork is a common site for atherosclerosis, an inflammatory build-up of atheromatous plaque inside the common carotid artery, or the internal carotid arteries that causes them to narrow.The plaque can be stable and asymptomatic, or it can be a source of embolization. Emboli break off from the plaque and travel through the circulation to blood vessels in the brain. As the vessels get smaller, an embolus can lodge in the vessel wall and restrict the blood flow to parts of the brain. This ischemia can either be temporary, yielding a transient ischemic attack (TIA), or permanent resulting in a thromboembolic stroke.Transient ischemic attacks are a warning sign and may be followed by severe permanent strokes, particularly within the first two days. TIAs by definition last less than 24 hours and frequently take the form of weakness or loss of sensation of a limb or the trunk on one side of the body or the loss of sight (amaurosis fugax) in one eye. Less common symptoms are artery sounds (bruits), or ringing in the ears (tinnitus).In asymptomatic individuals with a carotid stenosis, the risk of developing a stroke is increased above those without a stenosis. The risk of stroke is possibly related to the degree of stenosis on imaging. Some studies have found an increased risk with increasing degrees of stenosis while other studies have not been able to find such a relationship. Pathophysiology Atherosclerosis causes plaque to form within the carotid artery walls, usually at the fork where the common carotid artery divides into the internal and external carotid artery. The plaque build-up can narrow or constrict the artery lumen, a condition called stenosis. Rupture of the plaque can release atherosclerotic debris or blood clots into the artery. A piece of this material can break off and travel (embolize) up through the internal carotid artery into the brain, where it blocks circulation, and can cause death of the brain tissue, a condition referred to as ischemic stroke.Sometimes the stenosis causes temporary symptoms first, known as TIAs, where temporary ischemia occurs in the brain, or retina without causing an infarction. Symptomatic stenosis has a high risk of stroke within the next 2 days. National Institute for Health and Clinical Excellence (NICE) guidelines recommend that people with moderate to severe (50–99% blockage) stenosis, and symptoms, should have "urgent" endarterectomy within 2 weeks.When the plaque does not cause symptoms, people are still at higher risk of stroke than the general population, but not as high as people with symptomatic stenosis. The incidence of stroke, including fatal stroke, is 1–2% per year. The surgical mortality of endarterectomy ranges from 1–2% to as much as 10%. Two large randomized clinical trials have demonstrated that carotid surgery done with a 30-day stroke and death risk of 3% or less will benefit asymptomatic people with ≥60% stenosis who are expected to live at least 5 years after surgery. Surgeons are divided over whether asymptomatic people should be treated with medication alone or should have surgery.The common carotid artery is the large vertical artery in red. The blood supply to the carotid artery starts at the arch of the aorta (bottom). The carotid artery divides into the internal carotid artery and the external carotid artery. The internal carotid artery supplies the brain. Plaque often builds up at that division and causes a narrowing (stenosis). Pieces of plaque can break off and block the small arteries above in the brain, which causes a stroke. Plaque can also build up at the origin of the carotid artery at the aorta. Diagnosis Carotid artery stenosis is usually diagnosed by color flow duplex ultrasound scan of the carotid arteries in the neck. This involves no radiation, no needles and no contrast agents that may cause allergic reactions. This test has good sensitivity and specificity.Typically duplex ultrasound scan is the only investigation required for decision making in carotid stenosis as it is widely available and rapidly performed. However, further imaging can be required if the stenosis is not near the bifurcation of the carotid artery.One of several different imaging modalities, such as a computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA) may be useful. Each imaging modality has its advantages and disadvantages - Magnetic resonance angiography and CT angiography with contrast is contraindicated in patients with chronic kidney disease, catheter angiography has a 0.5% to 1.0% risk of stroke, MI, arterial injury or retroperitoneal bleeding. The investigation chosen will depend on the clinical question and the imaging expertise, experience and equipment available.For purpose of treatment, the degree of carotid stenosis is defined as: percent stenosis = ( 1 − ( minimum diameter within stenosis) / ( poststenotic diameter ) ) × 100%. Screening The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for carotid artery stenosis in those without symptoms as of 2021.While routine population screening is not advised, the American Heart Association and the Society for Vascular Surgery recommend screening in those diagnosed with related medical conditions or have risk factors for carotid artery disease. Screening is recommended for people who have: Vascular disease elsewhere in the body, including: Peripheral artery disease (PAD) Coronary artery disease (CAD) Atherosclerotic aortic aneurysm (AAA) Two or more of the following risk factors: High blood pressure (hypertension) High cholesterol (hyperlipidemia) Tobacco smoking Family history – First-degree relative diagnosed with atherosclerosis before age 60 or who had an ischemic strokeThe American Heart Association also recommends screening if a physician detects a carotid bruit, or murmur, over the carotid artery by listening through a stethoscope during a physical exam. For people with symptoms, the American Heart Association recommends initial screening using ultrasound. Treatment The goal of treating carotid artery stenosis is to reduce the risk of stroke. The type of treatment depends on the severity of the disease and includes: Lifestyle modifications including smoking cessation, eating a healthy diet and reducing sodium intake, losing weight, and exercising regularly. Medications to control high blood pressure and high levels of lipids in the blood. Surgical intervention for carotid artery revascularization. Medication Clinical guidelines (such as those of the American Heart Association (AHA) and National Institute for Clinical Excellence (NICE)) recommend that all patients with carotid stenosis be given medications to control their vascular risk factors, usually blood pressure lowering medications (if they have hypertension), diabetes medication (if they have diabetes), and recommend exercise, weight reduction (if overweight) and smoking cessation (for smokers). In addition, they would benefit from anti-platelet medications (such as aspirin or clopidogrel) and cholesterol lowering medication (such as statins, which were originally prescribed for their cholesterol-lowering effects but were also found to reduce inflammation and stabilize plaque). Revascularization According to the American Heart Association, interventions beyond medical management is based upon whether patients have symptoms: Asymptomatic patients: assessment of other medical conditions, life expectancy, and other individual factors; evaluation of the risks versus benefits; and patient preference are considered when determining whether surgical intervention should be performed. Symptomatic patients: it is recommended that patients who have experienced a transient ischemic attack or non-severely disabling acute ischemic stroke undergo surgical intervention, if possible.All interventions for carotid revascularization (carotid endarterectomy, carotid stenting, and transcarotid artery revascularization) carry some risk of stroke; however, where the risk of stroke over time from medical management alone is high, intervention may be beneficial. See also Ocular ischemic syndrome References == External links ==

Infectious mononucleosis

Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adults, the disease often results in fever, sore throat, enlarged lymph nodes in the neck, and tiredness. Most people recover in two to four weeks; however, feeling tired may last for months. The liver or spleen may also become swollen, and in less than one percent of cases splenic rupture may occur.While usually caused by the Epstein–Barr virus, also known as human herpesvirus 4, which is a member of the herpesvirus family, a few other viruses may also cause the disease. It is primarily spread through saliva but can rarely be spread through semen or blood. Spread may occur by objects such as drinking glasses or toothbrushes or through a cough or sneeze. Those who are infected can spread the disease weeks before symptoms develop. Mono is primarily diagnosed based on the symptoms and can be confirmed with blood tests for specific antibodies. Another typical finding is increased blood lymphocytes of which more than 10% are atypical. The monospot test is not recommended for general use due to poor accuracy.There is no vaccine for EBV, though promising vaccine research results exist. Infection can be prevented by not sharing personal items or saliva with an infected person. Mono generally improves without any specific treatment. Symptoms may be reduced by drinking enough fluids, getting sufficient rest, and taking pain medications such as paracetamol (acetaminophen) and ibuprofen.Mononucleosis most commonly affects those between the ages of 15 to 24 years in the developed world. In the developing world, people are more often infected in early childhood when there are fewer symptoms. In those between 16 and 20 it is the cause of about 8% of sore throats. About 45 out of 100,000 people develop infectious mono each year in the United States. Nearly 95% of people have had an EBV infection by the time they are adults. The disease occurs equally at all times of the year. Mononucleosis was first described in the 1920s and is colloquially known as "the kissing disease". Signs and symptoms The signs and symptoms of infectious mononucleosis vary with age. Children Before puberty, the disease typically only produces flu-like symptoms, if any at all. When found, symptoms tend to be similar to those of common throat infections (mild pharyngitis, with or without tonsillitis). Adolescents and young adults In adolescence and young adulthood, the disease presents with a characteristic triad: Fever – usually lasting 14 days; often mild Sore throat – usually severe for 3–5 days, before resolving in the next 7–10 days. Swollen glands – mobile; usually located around the back of the neck (posterior cervical lymph nodes) and sometimes throughout the body.Another major symptom is feeling tired. Headaches are common, and abdominal pains with nausea or vomiting sometimes also occur. Symptoms most often disappear after about 2–4 weeks. However, fatigue and a general feeling of being unwell (malaise) may sometimes last for months. Fatigue lasts more than one month in an estimated 28% of cases. Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks. Most people are able to resume their usual activities within 2–3 months.The most prominent sign of the disease is often the pharyngitis, which is frequently accompanied by enlarged tonsils with pus—an exudate similar to that seen in cases of strep throat. In about 50% of cases, small reddish-purple spots called petechiae can be seen on the roof of the mouth. Palatal enanthem can also occur, but is relatively uncommon.A small minority of people spontaneously present a rash, usually on the arms or trunk, which can be macular (morbilliform) or papular. Almost all people given amoxicillin or ampicillin eventually develop a generalized, itchy maculopapular rash, which however does not imply that the person will have adverse reactions to penicillins again in the future. Occasional cases of erythema nodosum and erythema multiforme have been reported. Seizures may also occasionally occur. Complications Spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination. Rarely the spleen may rupture. There may also be some enlargement of the liver. Jaundice occurs only occasionally.It generally gets better on its own in people who are otherwise healthy. When caused by EBV, infectious mononucleosis is classified as one of the Epstein-Barr virus-associated lymphoproliferative diseases. Occasionally the disease may persist and result in a chronic infection. This may develop into systemic EBV-positive T cell lymphoma. Older adults Infectious mononucleosis mainly affects younger adults. When older adults do catch the disease, they less often have characteristic signs and symptoms such as the sore throat and lymphadenopathy. Instead, they may primarily experience prolonged fever, fatigue, malaise and body pains. They are more likely to have liver enlargement and jaundice. People over 40 years of age are more likely to develop serious illness. (See Prognosis.) Incubation period The exact length of time between infection and symptoms is unclear. A review of the literature made an estimate of 33–49 days. In adolescents and young adults, symptoms are thought to appear around 4–6 weeks after initial infection. Onset is often gradual, though it can be abrupt. The main symptoms may be preceded by 1–2 weeks of fatigue, feeling unwell and body aches. Cause Epstein–Barr virus About 90% of cases of infectious mononucleosis are caused by the Epstein–Barr virus, a member of the Herpesviridae family of DNA viruses. It is one of the most commonly found viruses throughout the world. Contrary to common belief, the Epstein–Barr virus is not highly contagious. It can only be contracted through direct contact with an infected persons saliva, such as through kissing or sharing toothbrushes. About 95% of the population has been exposed to this virus by the age of 40, but only 15–20% of teenagers and about 40% of exposed adults actually become infected. Cytomegalovirus About 5% to 7% of cases of infectious mononucleosis is caused by human cytomegalovirus (CMV), another type of herpes virus. This virus is found in body fluids including saliva, urine, blood, and tears. A person becomes infected with this virus by direct contact with infected body fluids. Cytomegalovirus is most commonly transmitted through kissing and sexual intercourse. It can also be transferred from an infected mother to her unborn child. This virus is often "silent" because the signs and symptoms cannot be felt by the person infected. However, it can cause life-threatening illness in infants, people with HIV, transplant recipients, and those with weak immune systems. For those with weak immune systems, cytomegalovirus can cause more serious illnesses such as pneumonia and inflammations of the retina, esophagus, liver, large intestine, and brain. Approximately 90% of the human population has been infected with cytomegalovirus by the time they reach adulthood, but most are unaware of the infection. Once a person becomes infected with cytomegalovirus, the virus stays in their body fluids throughout the persons lifetime. Transmission Epstein–Barr virus infection is spread via saliva, and has an incubation period of four to seven weeks. The length of time that an individual remains contagious is unclear, but the chances of passing the illness to someone else may be the highest during the first six weeks following infection. Some studies indicate that a person can spread the infection for many months, possibly up to a year and a half. Pathophysiology The virus replicates first within epithelial cells in the pharynx (which causes pharyngitis, or sore throat), and later primarily within B cells (which are invaded via their CD21). The host immune response involves cytotoxic (CD8-positive) T cells against infected B lymphocytes, resulting in enlarged, atypical lymphocytes (Downey cells).When the infection is acute (recent onset, instead of chronic), heterophile antibodies are produced.Cytomegalovirus, adenovirus and Toxoplasma gondii (toxoplasmosis) infections can cause symptoms similar to infectious mononucleosis, but a heterophile antibody test will test negative and differentiate those infections from infectious mononucleosis.Mononucleosis is sometimes accompanied by secondary cold agglutinin disease, an autoimmune disease in which abnormal circulating antibodies directed against red blood cells can lead to a form of autoimmune hemolytic anemia. The cold agglutinin detected is of anti-i specificity. Diagnosis Diagnostic modalities for infectious mononucleosis include: Persons age, with highest risk at 10 to 30 years. Medical history, such as close contact with other people with infectious mononucleosis, and the presence and time of onset of "mononucleosis-like symptoms" such as fever and sore throat. Physical examination, including palpation of any enlarged lymph nodes in the neck, or enlarged spleen. The heterophile antibody test is a screening test that gives results within a day, but has significantly less than full sensitivity (70–92%) in the first two weeks after clinical symptoms begin. Serological tests take longer time than the heterophile antibody test, but are more accurate. Physical examination The presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes are the most useful to suspect a diagnosis of infectious mononucleosis. On the other hand, the absence of swollen cervical lymph nodes and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. The insensitivity of the physical examination in detecting an enlarged spleen means it should not be used as evidence against infectious mononucleosis. A physical examination may also show petechiae in the palate. Heterophile antibody test The heterophile antibody test, or monospot test, works by agglutination of red blood cells from guinea pigs, sheep and horses. This test is specific but not particularly sensitive (with a false-negative rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third). About 90% of diagnosed people have heterophile antibodies by week 3, disappearing in under a year. The antibodies involved in the test do not interact with the Epstein–Barr virus or any of its antigens.The monospot test is not recommended for general use by the CDC due to its poor accuracy. Serology Serologic tests detect antibodies directed against the Epstein–Barr virus. Immunoglobulin G (IgG), when positive, mainly reflects a past infection, whereas immunoglobulin M (IgM) mainly reflects a current infection. EBV-targeting antibodies can also be classified according to which part of the virus they bind to: Viral capsid antigen (VCA):Anti-VCA IgM appear early after infection, and usually, disappear within 4 to 6 weeks. Anti-VCA IgG appears in the acute phase of EBV infection, reaches a maximum at 2 to 4 weeks after onset of symptoms and thereafter declines slightly and persists for the rest of a person’s life.Early antigen (EA)Anti-EA IgG appears in the acute phase of illness and disappears after 3 to 6 months. It is associated with having an active infection. Yet, 20% of people may have antibodies against EA for years despite having no other sign of infection.EBV nuclear antigen (EBNA)Antibody to EBNA slowly appears 2 to 4 months after the onset of symptoms and persists for the rest of a person’s life.When negative, these tests are more accurate than the heterophile antibody test in ruling out infectious mononucleosis. When positive, they feature similar specificity to the heterophile antibody test. Therefore, these tests are useful for diagnosing infectious mononucleosis in people with highly suggestive symptoms and a negative heterophile antibody test. Other tests Epstein–Barr nuclear antigen detection. While it is not normally recognizable until several weeks into the disease and is useful for distinguishing between a recent-onset of infectious mononucleosis and symptoms caused by a previous infection. Elevated hepatic transaminase levels are highly suggestive of infectious mononucleosis, occurring in up to 50% of people. By blood film, one diagnostic criterion for infectious mononucleosis is the presence of 50% lymphocytes with at least 10% atypical lymphocytes (large, irregular nuclei), while the person also has fever, pharyngitis, and swollen lymph nodes. The atypical lymphocytes resembled monocytes when they were first discovered, thus the term "mononucleosis" was coined. A fibrin ring granuloma may be present. Differential diagnosis About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection. A differential diagnosis of acute infectious mononucleosis needs to take into consideration acute cytomegalovirus infection and Toxoplasma gondii infections. Because their management is much the same, it is not always helpful, or possible, to distinguish between Epstein–Barr-virus mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from toxoplasmosis is important, since it is associated with significant consequences for the fetus.Acute HIV infection can mimic signs similar to those of infectious mononucleosis, and tests should be performed for pregnant women for the same reason as toxoplasmosis.People with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the symptoms of fever, pharyngitis and adenopathy) and are given antibiotics such as ampicillin or amoxicillin as treatment.Other conditions from which to distinguish infectious mononucleosis include leukemia, tonsillitis, diphtheria, common cold and influenza (flu). Treatment Infectious mononucleosis is generally self-limiting, so only symptomatic or supportive treatments are used. The need for rest and return to usual activities after the acute phase of the infection may reasonably be based on the persons general energy levels. Nevertheless, in an effort to decrease the risk of splenic rupture experts advise avoidance of contact sports and other heavy physical activity, especially when involving increased abdominal pressure or the Valsalva maneuver (as in rowing or weight training), for at least the first 3–4 weeks of illness or until enlargement of the spleen has resolved, as determined by a treating physician. Medications Paracetamol (acetaminophen) and NSAIDs, such as ibuprofen, may be used to reduce fever and pain. Prednisone, a corticosteroid, while used to try to reduce throat pain or enlarged tonsils, remains controversial due to the lack of evidence that it is effective and the potential for side effects. Intravenous corticosteroids, usually hydrocortisone or dexamethasone, are not recommended for routine use but may be useful if there is a risk of airway obstruction, a very low platelet count, or hemolytic anemia.Antiviral agents act by inhibiting viral DNA replication. There is little evidence to support the use of antivirals such as aciclovir and valacyclovir although they may reduce initial viral shedding. Antivirals are expensive, risk causing resistance to antiviral agents, and (in 1% to 10% of cases) can cause unpleasant side effects. Although antivirals are not recommended for people with simple infectious mononucleosis, they may be useful (in conjunction with steroids) in the management of severe EBV manifestations, such as EBV meningitis, peripheral neuritis, hepatitis, or hematologic complications.Although antibiotics exert no antiviral action they may be indicated to treat bacterial secondary infections of the throat, such as with streptococcus (strep throat). However, ampicillin and amoxicillin are not recommended during acute Epstein–Barr virus infection as a diffuse rash may develop. Observation Splenomegaly is a common symptom of infectious mononucleosis and health care providers may consider using abdominal ultrasonography to get insight into the enlargement of a persons spleen. However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports. Prognosis Serious complications are uncommon, occurring in less than 5% of cases: CNS complications include meningitis, encephalitis, hemiplegia, Guillain–Barré syndrome, and transverse myelitis. Prior infectious mononucleosis has been linked to the development of multiple sclerosis. Hematologic: Hemolytic anemia (direct Coombs test is positive) and various cytopenias, and bleeding (caused by thrombocytopenia) can occur. Mild jaundice Hepatitis with the Epstein–Barr virus is rare. Upper airway obstruction from tonsillar hypertrophy is rare. Fulminant disease course of immunocompromised people are rare. Splenic rupture is rare. Myocarditis and pericarditis are rare. Postural orthostatic tachycardia syndrome Chronic fatigue syndrome Cancers associated with the Epstein-Barr virus include Burkitts lymphoma, Hodgkins lymphoma and lymphomas in general as well as nasopharyngeal and gastric carcinoma. Hemophagocytic lymphohistiocytosisOnce the acute symptoms of an initial infection disappear, they often do not return. But once infected, the person carries the virus for the rest of their life. The virus typically lives dormant in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the person is already carrying the virus dormant. Periodically, the virus can reactivate, during which time the person is again infectious, but usually without any symptoms of illness. Usually, a person with IM has few, if any, further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors, the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase, the virus can spread to others. History The characteristic symptomatology of infectious mononucleosis does not appear to have been reported until the late nineteenth century. In 1885, the renowned Russian pediatrician Nil Filatov reported an infectious process he called "idiopathic adenitis" exhibiting symptoms that correspond to infectious mononucleosis, and in 1889 a German balneologist and pediatrician, Emil Pfeiffer, independently reported similar cases (some of lesser severity) that tended to cluster in families, for which he coined the term Drüsenfieber ("glandular fever").The word mononucleosis has several senses, but today it usually is used in the sense of infectious mononucleosis, which is caused by EBV. The term "infectious mononucleosis" was coined in 1920 by Thomas Peck Sprunt and Frank Alexander Evans in a classic clinical description of the disease published in the Bulletin of the Johns Hopkins Hospital, entitled "Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis)". A lab test for infectious mononucleosis was developed in 1931 by Yale School of Public Health Professor John Rodman Paul and Walls Willard Bunnell based on their discovery of heterophile antibodies in the sera of persons with the disease. The Paul-Bunnell Test or PBT was later replaced by the heterophile antibody test. The Epstein–Barr virus was first identified in Burkitts lymphoma cells by Michael Anthony Epstein and Yvonne Barr at the University of Bristol in 1964. The link with infectious mononucleosis was uncovered in 1967 by Werner and Gertrude Henle at the Childrens Hospital of Philadelphia, after a laboratory technician handling the virus contracted the disease: comparison of serum samples collected from the technician before and after the onset revealed development of antibodies to the virus.Yale School of Public Health epidemiologist Alfred E. Evans confirmed through testing that mononucleosis was transmitted mainly through kissing leading to it being referred to colloquially as "the kissing disease". References External links Infectious mononucleosis at Curlie

Dental abscess

A dental abscess is a localized collection of pus associated with a tooth. The most common type of dental abscess is a periapical abscess, and the second most common is a periodontal abscess. In a periapical abscess, usually the origin is a bacterial infection that has accumulated in the soft, often dead, pulp of the tooth. This can be caused by tooth decay, broken teeth or extensive periodontal disease (or combinations of these factors). A failed root canal treatment may also create a similar abscess. A dental abscess is a type of odontogenic infection, although commonly the latter term is applied to an infection which has spread outside the local region around the causative tooth. Classification The main types of dental abscess are: Periapical abscess: The result of a chronic, localized infection located at the tip, or apex, of the root of a tooth. Periodontal abscess: begins in a periodontal pocket (see: periodontal abscess) Gingival abscess: involving only the gum tissue, without affecting either the tooth or the periodontal ligament (see: periodontal abscess) Pericoronal abscess: involving the soft tissues surrounding the crown of a tooth (see: Pericoronitis) Combined periodontic-endodontic abscess: a situation in which a periapical abscess and a periodontal abscess have combined (see: Combined periodontic-endodontic lesions). Signs and symptoms The pain is continuous and may be described as extreme, growing, sharp, shooting, or throbbing. Putting pressure or warmth on the tooth may induce extreme pain. The area may be sensitive to touch and possibly swollen as well. This swelling may be present at either the base of the tooth, the gum, and/or the cheek, and sometimes can be reduced by applying ice packs. An acute abscess may be painless but still have a swelling present on the gum. It is important to get anything that presents like this checked by a dental professional as it may become chronic later. In some cases, a tooth abscess may perforate bone and start draining into the surrounding tissues creating local facial swelling. In some cases, the lymph glands in the neck will become swollen and tender in response to the infection. It may even feel like a migraine as the pain can transfer from the infected area. The pain does not normally transfer across the face, only upwards or downwards as the nerves that serve each side of the face are separate. Severe aching and discomfort on the side of the face where the tooth is infected is also fairly common, with the tooth itself becoming unbearable to touch due to extreme amounts of pain. Complications If left untreated, a severe tooth abscess may become large enough to perforate bone and extend into the soft tissue eventually becoming osteomyelitis and cellulitis respectively. From there it follows the path of least resistance and may spread either internally or externally. The path of the infection is influenced by such things as the location of the infected tooth and the thickness of the bone, muscle and fascia attachments. External drainage may begin as a boil which bursts allowing pus drainage from the abscess, intraorally (usually through the gum) or extraorally. Chronic drainage will allow an epithelial lining to form in this communication to form a pus draining canal (fistula). Sometimes this type of drainage will immediately relieve some of the painful symptoms associated with the pressure. Internal drainage is of more concern as growing infection makes space within the tissues surrounding the infection. Severe complications requiring immediate hospitalization include Ludwigs angina, which is a combination of growing infection and cellulitis which closes the airway space causing suffocation in extreme cases. Also infection can spread down the tissue spaces to the mediastinum which has significant consequences on the vital organs such as the heart. Another complication, usually from upper teeth, is a risk of sepsis traveling through pathways to which it can possibly lead to endocarditis, brain abscess (extremely rare), or meningitis (also rare). Depending on the severity of the infection, the sufferer may feel only mildly ill, or may in extreme cases require hospital care. Diagnostic A periodontal abscess may be difficult to distinguish from a periapical abscess. Indeed, sometimes they can occur together. Since the management of a periodontal abscess is different from that of a periapical abscess, this differentiation is important to make. If the swelling is over the area of the root apex, it is more likely to be a periapical abscess; if it is closer to the gingival margin, it is more likely to be a periodontal abscess. Similarly, in a periodontal abscess pus most likely discharges via the periodontal pocket, whereas a periapical abscess generally drains via a parulis nearer to the apex of the involved tooth. If the tooth has pre-existing periodontal disease, with pockets and loss of alveolar bone height, it is more likely to be a periodontal abscess; whereas if the tooth has relatively healthy periodontal condition, it is more likely to be a periapical abscess. In periodontal abscesses, the swelling usually precedes the pain, and in periapical abscesses, the pain usually precedes the swelling. A history of toothache with sensitivity to hot and cold suggests previous pulpitis, and indicates that a periapical abscess is more likely. If the tooth gives normal results on pulp sensibility testing, is free of dental caries and has no large restorations; it is more likely to be a periodontal abscess. A dental radiograph is of little help in the early stages of a dental abscess, but later usually the position of the abscess, and hence indication of endodontal/periodontal etiology can be determined. If there is a sinus, a gutta percha point is sometimes inserted before the x-ray in the hope that it will point to the origin of the infection. Generally, periodontal abscesses will be more tender to lateral percussion than to vertical, and periapical abscesses will be more tender to apical percussion. Treatment Successful treatment of a dental abscess centers on the reduction and elimination of the offending organisms. This can include treatment with antibiotics and drainage, however, it has become widely recommended that dentists should improve the antibiotic prescribing practices, by limiting the prescriptions to the acute cases that suffer from the severe signs of spreading infection, in an attempt to overcome the development of antibiotic-resistant bacterial strains in the population. A 2018 Cochrane review has found insufficient evidence to rule out if patients with acute dental abscesses can benefit from antibiotic prescriptions.If the tooth can be restored, root canal therapy can be performed. Non-restorable teeth must be extracted, followed by curettage of all apical soft tissue. Unless they are symptomatic, teeth treated with root canal therapy should be evaluated at 1- and 2-year intervals after the root canal therapy to rule out possible lesional enlargement and to ensure appropriate healing. Abscesses may fail to heal for several reasons: Cyst formation Inadequate root canal therapy Vertical root fractures Foreign material in the lesion Associated periodontal disease Penetration of the maxillary sinusFollowing conventional, adequate root canal therapy, abscesses that do not heal or enlarge are often treated with surgery and filling the root tips; and will require a biopsy to evaluate the diagnosis. See also Barodontalgia Focal infection theory Intraoral dental sinus References == External links ==

Angular cheilitis

Angular cheilitis (AC) is inflammation of one or both corners of the mouth. Often the corners are red with skin breakdown and crusting. It can also be itchy or painful. The condition can last for days to years. Angular cheilitis is a type of cheilitis (inflammation of the lips).Angular cheilitis can be caused by infection, irritation, or allergies. Infections include by fungi such as Candida albicans and bacteria such as Staph. aureus. Irritants include poorly fitting dentures, licking the lips or drooling, mouth breathing resulting in a dry mouth, sun exposure, overclosure of the mouth, smoking, and minor trauma. Allergies may include substances like toothpaste, makeup, and food. Often a number of factors are involved. Other factors may include poor nutrition or poor immune function. Diagnosis may be helped by testing for infections and patch testing for allergies.Treatment for angular cheilitis is typically based on the underlying causes along with the use of a barrier cream. Frequently an antifungal and antibacterial cream is also tried. Angular cheilitis is a fairly common problem, with estimates that it affects 0.7% of the population. It occurs most often in people in their 30s to 60s, and is also relatively common in children. In the developing world, iron, vitamin B12, and other vitamin deficiencies are a common cause. Signs and symptoms Angular cheilitis is a fairly non specific term which describes the presence of an inflammatory lesion in a particular anatomic site (i.e. the corner of the mouth). As there are different possible causes and contributing factors from one person to the next, the appearance of the lesion is somewhat variable. The lesions are more commonly symmetrically present on both sides of the mouth, but sometimes only one side may be affected. In some cases, the lesion may be confined to the mucosa of the lips, and in other cases the lesion may extend past the vermilion border (the edge where the lining on the lips becomes the skin on the face) onto the facial skin. Initially, the corners of the mouth develop a gray-white thickening and adjacent erythema (redness). Later, the usual appearance is a roughly triangular area of erythema, edema (swelling) and breakdown of skin at either corner of the mouth. The mucosa of the lip may become fissured (cracked), crusted, ulcerated or atrophied. There is not usually any bleeding. Where the skin is involved, there may be radiating rhagades (linear fissures) from the corner of the mouth. Infrequently, the dermatitis (which may resemble eczema) can extend from the corner of the mouth to the skin of the cheek or chin. If Staphylococcus aureus is involved, the lesion may show golden yellow crusts. In chronic angular cheilitis, there may be suppuration (pus formation), exfoliation (scaling) and formation of granulation tissue.Sometimes contributing factors can be readily seen, such as loss of lower face height from poorly made or worn dentures, which results in mandibular overclosure ("collapse of jaws"). If there is a nutritional deficiency underlying the condition, various other signs and symptoms such as glossitis (swollen tongue) may be present. In people with angular cheilitis who wear dentures, often there may be erythematous mucosa underneath the denture (normally the upper denture), an appearance consistent with denture-related stomatitis. Typically the lesions give symptoms of soreness, pain, pruritus (itching) or burning or a raw feeling. Causes Angular cheilitis is thought to be multifactorial disorder of infectious origin, with many local and systemic predisposing factors. The sores in angular cheilitis are often infected with fungi (yeasts), bacteria, or a combination thereof; this may represent a secondary, opportunistic infection by these pathogens. Some studies have linked the initial onset of angular cheilitis with nutritional deficiencies, especially of the B (B2-riboflavin) vitamin and iron (which causes iron deficiency anemia), which in turn may be evidence of malnutrition or malabsorption. Angular cheilitis can be a manifestation of contact dermatitis, which is considered in two groups; irritational and allergic. Infection The involved organisms are: Candida species alone (usually Candida albicans), which accounts for about 20% of cases, Bacterial species, either: Staphylococcus aureus alone, which accounts for about 20% of cases, β-hemolytic streptococci alone. These types of bacteria have been detected in between 8–15% of cases of angular cheilitis, but less commonly are they present in isolation, Or a combination of the above organisms, (a polymicrobial infection) with about 60% of cases involving both C. albicans and S. aureus.Candida can be detected in 93% of angular cheilitis lesions. This organism is found in the mouths of about 40% of healthy individuals, and it is considered by some to be normal commensal component of the oral microbiota. However, Candida shows dimorphism, namely a yeast form which is thought to be relatively harmless and a pathogenic hyphal form which is associated with invasion of host tissues. Potassium hydroxide preparation is recommended by some to help distinguish between the harmless and the pathogenic forms, and thereby highlight which cases of angular cheilitis are truly caused by Candida. The mouth may act as a reservoir of Candida that reinfects the sores at the corners of the mouth and prevents the sores from healing. A lesion caused by recurrence of a latent herpes simplex infection can occur in the corner of the mouth. This is herpes labialis (a cold sore), and is sometimes termed "angular herpes simplex". A cold sore at the corner of the mouth behaves similarly to elsewhere on the lips, and follows a pattern of vesicle (blister) formation followed by rupture leaving a crusted sore which resolves in about 7–10 days, and recurs in the same spot periodically, especially during periods of stress. Rather than utilizing antifungal creams, angular herpes simplex is treated in the same way as a cold sore, with topical antiviral drugs such as aciclovir. Irritation contact dermatitis 22% of cases of angular cheilitis are due to irritants. Saliva contains digestive enzymes, which may have a degree of digestive action on tissues if they are left in contact. The corner of the mouth is normally exposed to saliva more than any other part of the lips. Reduced lower facial height (vertical dimension or facial support) is usually caused by edentulism (tooth loss), or wearing worn down, old dentures or ones which are not designed optimally. This results in overclosure of the mandible (collapse of the jaws), which extenuates the angular skin folds at the corners of the mouth, in effect creating an intertriginous skin crease. The tendency of saliva to pool in these areas is increased, constantly wetting the area, which may cause tissue maceration and favors the development of a yeast infection. As such, angular cheilitis is more commonly seen in edentulous people (people without any teeth). It is by contrast uncommon in persons who retain their natural teeth. Angular cheilitis is also commonly seen in denture wearers. Angular cheilitis is present in about 30% of people with denture-related stomatitis. It is thought that reduced vertical dimension of the lower face may be a contributing factor in up to 11% of elderly persons with angular cheilitis and in up to 18% of denture wearers who have angular cheilitis. Reduced vertical dimension can also be caused by tooth migration, wearing orthodontic appliances, and elastic tissue damage caused by ultraviolet light exposure and smoking.Habits or conditions that keep the corners of the mouth moist might include chronic lip licking, thumb sucking (or sucking on other objects such as pens, pipes, lollipops), dental cleaning (e.g. flossing), chewing gum, hypersalivation, drooling and mouth breathing. Some consider habitual lip licking or picking to be a form of nervous tic, and do not consider this to be true angular cheilitis, instead calling it perlèche (derived from the French word pourlècher meaning "to lick ones lips"), or "factitious cheilitis" is applied to this habit. The term "cheilocandidiasis" describes exfoliative (flaking) lesions of the lips and the skin around the lips, and is caused by a superficial candidal infection due to chronic lip licking. Less severe cases occur during cold, dry weather, and is a form of chapped lips. Individuals may lick their lips in an attempt to provide a temporary moment of relief, only serving to worsen the condition.The sunscreen in some types of lip balm degrades over time into an irritant. Using expired lipbalm can initiate mild angular cheilitis, and when the person applies more lipbalm to alleviate the cracking, it only aggravates it. Because of the delayed onset of contact dermatitis and the recovery period lasting days to weeks, people typically do not make the connection between the causative agent and the symptoms. Nutritional deficiencies Several different nutritional deficiency states of vitamins or minerals have been linked to AC. It is thought that in about 25% of people with AC, iron deficiency or deficiency of B vitamins are involved. Nutritional deficiencies may be a more common cause of AC in Third World countries. Chronic iron deficiency may also cause koilonychia (spoon shaped deformity of the fingernails) and glossitis (inflammation of the tongue). It is not completely understood how iron deficiency causes AC, but it is known that it causes a degree of immunocompromise (decreased efficiency of the immune system) which may in turn allow an opportunistic infection of candida. Vitamin B2 deficiency (ariboflavinosis) may also cause AC, and other conditions such as redness of mucous membranes, magenta colored glossitis (pink inflammation of the tongue). Vitamin B5 deficiency may also cause AC, along with glossitis, and skin changes similar to seborrhoeic dermatitis around the eyes, nose and mouth. Vitamin B12 deficiency is sometimes responsible for AC, and commonly occurs together with folate deficiency (a lack of folic acid), which also causes glossitis and megaloblastic anemia. Vitamin B3 deficiency (pellagra) is another possible cause, and in which other association conditions such as dermatitis, diarrhea, dementia and glossitis can occur. Biotin (vitamin B7) deficiency has also been reported to cause AC, along with hair loss (alopecia) and dry eyes. Zinc deficiency is known to cause AC. Other symptoms may include diarrhea, alopecia and dermatitis. Acrodermatitis enteropathica is an autosomal recessive genetic disorder causing impaired absorption of zinc, and is associated with AC.In general, these nutritional disorders may be caused by malnutrition, such as may occur in alcoholism or in poorly considered diets, or by malabsorption secondary to gastrointestinal disorders (e.g. Coeliac disease or chronic pancreatitis) or gastrointestinal surgeries (e.g. pernicious anemia caused by ileal resection in Crohns disease). Systemic disorders Some systemic disorders are involved in angular cheilitis by virtue of their association with malabsorption and the creation of nutritional deficiencies described above. Such examples include people with anorexia nervosa. Other disorders may cause lip enlargement (e.g. orofacial granulomatosis), which alters the local anatomy and extenuates the skin folds at the corners of the mouth. More still may be involved because they affect the immune system, allowing normally harmless organisms like Candida to become pathogenic and cause an infection. Xerostomia (dry mouth) is thought to account for about 5% of cases of AC. Xerostomia itself has many possible causes, but commonly the cause may be side effects of medications, or conditions such as Sjögrens syndrome. Conversely, conditions which cause drooling or sialorrhoea (excessive salivation) can cause angular cheilitis by creating a constant wet environment in the corners of the mouth. About 25% of people with Down syndrome appear to have AC. This is due to relative macroglossia, an apparently large tongue in a small mouth, which may constantly stick out of the mouth causing maceration of the corners of the mouth with saliva. Inflammatory bowel diseases (such as Crohns disease or ulcerative colitis) can be associated with angular cheilitis. In Crohns, it is likely the result of malabsorption and immunosuppressive therapy which gives rise to the sores at the corner of the mouth. Glucagonomas are rare pancreatic endocrine tumors which secrete glucagon, and cause a syndrome of dermatitis, glucose intolerance, weight loss and anemia. AC is a common feature of glucagonoma syndrome. Infrequently, angular cheilitis may be one of the manifestations of chronic mucocutaneous candidiasis, and sometimes cases of oropharyngeal or esophageal candidiasis may accompany angular cheilitis. Angular cheilitis may be present in human immunodeficiency virus infection, neutropenia, or diabetes. Angular cheilitis is more common in people with eczema because their skin is more sensitive to irritants. Other conditions possibly associated include plasma cell gingivitis, Melkersson–Rosenthal syndrome, or sideropenic dysphagia (also called Plummer–Vinson syndrome or Paterson–Brown–Kelly syndrome). Drugs Several drugs may cause AC as a side effect, by various mechanisms, such as creating drug-induced xerostomia. Various examples include isotretinoin, indinavir, and sorafenib. Isotretinoin (Accutane), an analog of vitamin A, is a medication which dries the skin. Less commonly, angular cheilitis is associated with primary hypervitaminosis A, which can occur when large amounts of liver (including cod liver oil and other fish oils) are regularly consumed or as a result from an excess intake of vitamin A in the form of vitamin supplements. Recreational drug users may develop AC. Examples include cocaine, methamphetamine, heroin, and hallucinogens. Allergic contact dermatitis Allergic reactions may account for about 25–34% of cases of generalized cheilitis (i.e., inflammation not confined to the angles of the mouth). It is unknown how frequently allergic reactions are responsible for cases of angular cheilitis, but any substance capable of causing generalized allergic cheilitis may present involving the corners of the mouth alone. Examples of potential allergens include substances that may be present in some types of lipstick, toothpaste, acne products, cosmetics, chewing gum, mouthwash, foods, dental appliances, and materials from dentures or mercury containing amalgam fillings. It is usually impossible to tell the difference between irritant contact dermatitis and allergic contact dermatitis without a patch test. Loss of lower facial height Severe tooth wear or ill fitting dentures may cause wrinkling at the corners of the lip that creates a favorable environment for the condition. This can be corrected with onlays or crowns on the worn teeth to restore height or new dentures with "taller" teeth. The loss of vertical dimension has been associated with angular cheilitis in older individuals with an increase in facial laxity. Diagnosis Angular cheilitis is normally a diagnosis made clinically. If the sore is unilateral, rather than bilateral, this suggests a local factor (e.g., trauma) or a split syphilitic papule. Angular cheilitis caused by mandibular overclosure, drooling, and other irritants is usually bilateral.The lesions are normally swabbed to detect if Candida or pathogenic bacterial species may be present. Persons with angular cheilitis who wear dentures often also will have their denture swabbed in addition. A complete blood count (full blood count) may be indicated, including assessment of the levels of iron, ferritin, vitamin B12 (and possibly other B vitamins), and folate. Classification Angular cheilitis could be considered to be a type of cheilitis or stomatitis. Where Candida species are involved, angular cheilitis is classed as a type of oral candidiasis, specifically a primary (group I) Candida-associated lesion. This form angular cheilitis which is caused by Candida is sometimes termed "Candida-associated angular cheilitis", or less commonly, "monilial perlèche". Angular cheilitis can also be classified as acute (sudden, short-lived appearance of the condition) or chronic (lasts a long time or keeps returning), or refractory (the condition persists despite attempts to treat it). Management There are four aspects to the treatment of angular cheilitis. Firstly, potential reservoirs of infection inside the mouth are identified and treated. Oral candidiasis, especially denture-related stomatitis is often found to be present where there is angular cheilitis, and if it is not treated, the sores at the corners of the mouth may often recur. This involves having dentures properly fitted and disinfected. Commercial preparations are marketed for this purpose, although dentures may be left in dilute (1:10 concentration) household bleach overnight, but only if they are entirely plastic and do not contain any metal parts, and with rinsing under clean water before use. Improved denture hygiene is often required thereafter, including not wearing the denture during sleep and cleaning it daily. For more information, see Denture-related stomatitis. Secondly, there may be a need to increase the vertical dimension of the lower face to prevent overclosure of the mouth and formation of deep skin folds. This may require the construction of a new denture with an adjusted bite. Rarely, in cases resistant to normal treatments, surgical procedures such as collagen injections (or other facial fillers such as autologous fat or crosslinked hyaluronic acid) are used in an attempt to restore the normal facial contour. Other measures which seek to reverse the local factors that may be contributing to the condition include improving oral hygiene, stopping smoking or other tobacco habits and use of a barrier cream (e.g. zinc oxide paste) at night.Thirdly, treatment of the infection and inflammation of the lesions themselves is addressed. This is usually with topical antifungal medication, such as clotrimazole, amphotericin B, ketoconazole, or nystatin cream. Some antifungal creams are combined with corticosteroids such as hydrocortisone or triamcinolone to reduce inflammation, and certain antifungals such as miconazole also have some antibacterial action. Diiodohydroxyquinoline is another topical therapy for angular cheilitis. If Staphylococcus aureus infection is demonstrated by microbiological culture to be responsible (or suspected), the treatment may be changed to fusidic acid cream, an antibiotic which is effective against this type of bacteria. Aside from fusidic acid, neomycin, mupirocin, metronidazole, and chlorhexidine are alternative options in this scenario. Finally, if the condition appears resistant to treatment, investigations for underlying causes such as anemia or nutrient deficiencies or HIV infection. Identification of the underlying cause is essential for treating chronic cases. The lesions may resolve when the underlying disease is treated, e.g. with a course of oral iron or B vitamin supplements. Patch testing is recommended by some in cases which are resistant to treatment and where allergic contact dermatitis is suspected. Prognosis Most cases of angular cheilitis respond quickly when antifungal treatment is used. In more long standing cases, the severity of the condition often follows a relapsing and remitting course over time. The condition can be difficult to treat and can be prolonged. Epidemiology AC is a relatively common condition, accounting for between 0.7 – 3.8% of oral mucosal lesions in adults and between 0.2 – 15.1% in children, though overall it occurs most commonly in adults in the third to sixth decades of life. It occurs worldwide, and both males and females are affected. Angular cheilitis is the most common presentation of fungal and bacterial infections of the lips. Etymology The term "angular cheilitis" is from Ancient Greek, χείλος meaning lip and -itis meaning inflammation. References == External links ==

Retinoblastoma

Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively found in young children.Though most children survive this cancer, they may lose their vision in the affected eye(s) or need to have the eye removed.Almost half of children with retinoblastoma have a hereditary genetic defect associated with retinoblastoma. In other cases, it is caused by a congenital mutation in the chromosome 13 gene 13q14 (retinoblastoma protein). Signs and symptoms Retinoblastoma is universally known as the most intrusive intraocular cancer among children. The chance of survival and preservation of the eye depends fully on the severity. Retinoblastoma is extremely rare as there are only about 200 to 300 cases every year in the United States. Looking at retinoblastoma globally, only 1 in about 15,000 children have this malignancy but these numbers continuously increase.Intraocular malignancies are more curable rather than extraocular malignancies due to early diagnosis and an early treatment prognosis. During infant screenings, if they incorporate an eye screening like they do a hearing screening, it can be detected at an earlier age, therefore, preventing its spread. Leucocoria is the primary indication of retinoblastoma and is when the cancer is still intraocular, meaning inside the eye. When light is reflected by the white tumor, the view of the red retina is blocked. Retinoblastoma can be curable after the initial sign and up to six months, if the tumor is intraocular. If you do not visit an ophthalmologist with signs of leucocoria within a reasonable amount of time, the delay in the diagnosis could lead to a more severe prognosis. Due to a delay in the diagnosis, it could result in proptosis which is then considered extraocular, the most severe.The most common and obvious sign of retinoblastoma is an abnormal appearance of the retina as viewed through the pupil, the medical term for which is leukocoria, also known as amaurotic cats eye reflex. Other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. Some children with retinoblastoma can develop a squint, commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). Retinoblastoma presents with advanced disease in developing countries and eye enlargement is a common finding.Depending on the position of the tumors, they may be visible during a simple eye exam using an ophthalmoscope to look through the pupil. A positive diagnosis is usually made only with an examination under anesthetic (EUA). A white eye reflection is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as Coats disease.The presence of the photographic fault red eye in only one eye and not in the other may be a sign of retinoblastoma. A clearer sign is "white eye" or "cats eye" (leukocoria). Cause Mutation of genes, found in chromosomes, can affect the way in which cells grow and develop within the body. Alterations in RB1 or MYCN can give rise to retinoblastoma. RB1 In children with the heritable genetic form of retinoblastoma, a mutation occurs in the RB1 gene on chromosome 13. RB1 was the first tumor suppressor gene cloned. Although RB1 interacts with over 100 cell proteins, its negative regulator effect on the cell cycle principally arises from binding and inactivation of the transcription factor E2F, thus repressing the transcription of genes which are required for the S phase.The defective RB1 gene can be inherited from either parent; in some children, however, the mutation occurs in the early stages of fetal development. The expression of the RB1 allele is autosomal dominant with 90% penetrance.Inherited forms of retinoblastomas are more likely to be bilateral. In addition, inherited uni- or bilateral retinoblastomas may be associated with pineoblastoma and other malignant midline supratentorial primitive neuroectodermal tumors (PNETs) with a dismal outcome; retinoblastoma concurrent with a PNET is known as trilateral retinoblastoma. A 2014 meta-analysis showed that 5-year survival of trilateral retinoblastoma increased from 6% before 1995 to 57% by 2014, attributed to early detection and improved chemotherapy.The development of retinoblastoma can be explained by the two-hit model. According to the two-hit model, both alleles need to be affected, so two events are necessary for the retinal cell or cells to develop into tumors. The first mutational event can be inherited (germline or constitutional), which will then be present in all cells in the body. The second “hit” results in the loss of the remaining normal allele (gene) and occurs within a particular retinal cell. In the sporadic, nonheritable form of retinoblastoma, both mutational events occur within a single retinal cell after fertilization (somatic events); sporadic retinoblastoma tends to be unilateral. Several methods have been developed to detect the RB1 gene mutations. Attempts to correlate gene mutations to the stage at presentation have not shown convincing evidence of a correlation. MYCN Not all retinoblastoma cases are with RB1 inactivation. There are cases reported with only one RB1 mutation or even two functional RB1 alleles, which indicates other oncogenic lesions of retinoblastoma. Somatic amplification of the MYCN oncogene is responsible for some cases of nonhereditary, early-onset, aggressive, unilateral retinoblastoma. MYCN can act as a transcription factor and promotes proliferation by regulating the expression of cell cycle genes. Although MYCN amplification accounted for only 1.4% of retinoblastoma cases, researchers identified it in 18% of infants diagnosed at less than 6 months of age. Median age at diagnosis for MYCN retinoblastoma was 4.5 months, compared with 24 months for those who had nonfamilial unilateral disease with two RB1 gene mutations. Diagnosis Screening for retinoblastoma should be part of a "well baby" screening for newborns during the first 3 months of life, to include: The red reflex: checking for a normal reddish-orange reflection from the eyes retina with an ophthalmoscope or retinoscope from about 30 cm or 1 foot, usually done in a dimly lit or dark room The corneal light reflex or Hirschberg test: checking for symmetrical reflection of beam of light in the same spot on each eye when a light is shined into each cornea, to help determine whether the eyes are crossed Eye examination: checking for any structural abnormalities Classification The two forms of the disease are a heritable form and nonheritable form (all cancers are considered genetic in that mutations of the genome are required for their development, but this does not imply that they are heritable, or transmitted to offspring). Around 55% of children with retinoblastoma have the nonheritable form. If no history of the disease exists within the family, the disease is labeled "sporadic", but this does not necessarily indicate that it is the nonheritable form. Bilateral retinoblastomas are commonly heritable, while unilateral retinoblastomas are commonly nonheritable.In about two-thirds of cases, only one eye is affected (unilateral retinoblastoma); in the other third, tumors develop in both eyes (bilateral retinoblastoma). The number and size of tumors on each eye may vary. In certain cases, the pineal gland or the suprasellar or parasellar region (or in very rare cases other midline intracranial locations) is also affected (trilateral retinoblastoma). The position, size, and quantity of tumors are considered when choosing the type of treatment for the disease. Differential diagnosis 1. Persistent hyperplastic primary vitreous is a congenital developmental anomaly of the eye resulting from failure of the embryological, primary vitreous, and hyaloid vasculature to regress, whereby the eye is shorter, develops a cataract, and may present with whitening of the pupil. 2. Coats disease is a typically unilateral disease characterised by abnormal development of blood vessels behind the retina, leading to blood vessel abnormalities in the retina and retinal detachment to mimic retinoblastoma. 3. Toxocariasis is a parasitic disease of the eye associated with exposure to infected puppies, which causes a retinal lesion leading to retinal detachment. 4. Retinopathy of prematurity is associated with low-birth-weight infants who receive supplemental oxygen in the period immediately after birth, and it involves damage to the retinal tissue and may lead to retinal detachment.If the eye examination is abnormal, further testing may include imaging studies, such as computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasound. CT and MRI can help define the structure abnormalities and reveal any calcium depositions. Ultrasound can help define the height and thickness of the tumor. Bone marrow examination or lumbar puncture may also be done to determine any metastases to bones or the brain. Morphology Gross and microscopic appearances of retinoblastoma are identical in both hereditary and sporadic types. Macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. Microscopically, both undifferentiated and differentiated elements may be present. Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include Flexner-Wintersteiner rosettes, Homer Wright rosettes, and fleurettes from photoreceptor differentiation. Genetic testing Identifying the RB1 gene mutation that led to a childs retinoblastoma can be important in the clinical care of the affected individual and in the care of (future) siblings and offspring. It may run in the family. Bilaterally affected individuals and 13-15% of unilaterally affected individuals, are expected to show an RB1 mutation in blood. By identifying the RB1 mutation in the affected individual, (future) siblings, children, and other relatives can be tested for the mutation; if they do not carry the mutation, child relatives are not at risk of retinoblastoma, so need not undergo the trauma and expense of examinations under anaesthetic. For the 85% of unilaterally affected patients found not to carry either of their eye tumor RB1 mutations in blood, neither molecular testing nor clinical surveillance of siblings is required. If the RB1 mutation of an affected individual is identified, amniotic cells in an at-risk pregnancy can be tested for the family mutation; any fetus that carries the mutation can be delivered early, allowing early treatment of any eye tumors, leading to better visual outcomes. For cases of unilateral retinoblastoma where no eye tumor is available for testing, if no RB1 mutation is detected in blood after high-sensitivity molecular testing (i.e. >93% RB1 mutation detection sensitivity), the risk of a germline RB1 mutation is reduced to less than 1%, a level at which only clinic examination (and not examinations under anaesthetic) is recommended for the affected individual and their future offspring (National Retinoblastoma Strategy, Canadian Guidelines for Care). Imaging Traditional ultrasound B scan can detect calcifications in the tumour while high-frequency ultrasound B scan is able to provide higher resolution than the traditional ultrasound and determine the proximity of the tumour with front portion of the eye. MRI scan can detect high-risk features such as optic nerve invasion; choroidal invasion, scleral invasion, and intracranial invasion. CT scan is generally avoided because radiation can stimulate the formation of more eye tumours in those with RB1 genetic mutation. Staging In order to properly diagnose retinoblastoma, there must be guidelines to follow to properly classify the risk of the tumor. The Reese Ellsworth Classification System, by Dr. Algernon Reese and Dr. Robert Ellsworth, is universally used to determine the size, location, and multi-focality of the tumor. The system was originally used to decide the best treatment result by using external beam radiotherapy, as well as, the likeliness of salvaging the globe of the eye. Due to chemotherapy not being part of the Reese Ellsworth Classification System, there needed to be an updated classification system to foresee the treatment outcomes of chemotherapy. The International Classification for Intraocular Retinoblastoma is now the current system being used, and it was created by Murphree and associates. According to Reese and Ellsworth, there were different groups that had various features in order to classify the globe salvage as very favorable to the category of very unfavorable. In order to salvage the affected eye, the disc diameter had to be around 4DD and behind the equator to have higher favorability. If the tumor was around ten in disc diameter and involved roughly 50% of the retina, it was considered unfavorable to salvage the globe which could result in enucleation. According to Murphree, the different groups were classified from very low risk to very high risk which was determined by features of the given tumor. Very low risk means that the tumor has to be less than 3mm and there must be no seeding of the vitreous or sub-retinal area. When a patient is very high risk, the tumor presents itself with multiple features and is going to have to be treated with conservative treatment modalities or enucleation. International Classification for Intraocular Retinoblastoma Treatment The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment depends on the individual case and is decided by the ophthalmologist in discussion with the paediatric oncologist. Correct treatment also depends on the mutation type, whether it is a germline RB1 mutation, a sporadic RB1 mutation or MYCN amplification with functional RB1. Children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies). The various treatment modalities for retinoblastoma includes: Enucleation of the eye – Most patients with unilateral disease present with advanced intraocular disease, so usually undergo enucleation, which results in a cure rate of 95%. In bilateral Rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision. External beam radiotherapy (EBR) – The most common indication for EBR is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies. However, patients with hereditary disease who received EBR therapy are reported to have a 35% risk of second cancers. Brachytherapy involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. It used as the primary treatment, or more frequently, in patients with small tumors or in those who had failed initial therapy including previous EBR therapy. Thermotherapy involves the application of heat directly to the tumor, usually in the form of infrared radiation. It is also used for small tumors. Laser photocoagulation is recommended only for small posterior tumors. An argon or diode laser or a xenon arc is used to coagulate all the blood supply to the tumor. Cryotherapy induces damage to the vascular endothelium with secondary thrombosis and infarction of the tumor tissue by rapidly freezing it. It may be used as primary therapy for small peripheral tumors or for small recurrent tumors previously treated with other methods. Systemic chemotherapy has become forefront of treatment in the past decade, in the search for globe-preserving measures and to avoid the adverse effects of EBR therapy. The common indications for chemotherapy for intraocular retinoblastoma include tumors that are large and that cannot be treated with local therapies alone in children with bilateral tumors. It is also used in patients with unilateral disease when the tumors are small, but cannot be controlled with local therapies alone. Intra-arterial chemotherapy – Chemotherapeutic drugs are administered locally by a thin catheter threaded through the groin, through the aorta, and the neck, directly into the optic vessels. Nanoparticulate chemotherapy – To reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents (carboplatin) has been developed, which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects. Chemoreduction is a combined approach using chemotherapy to initially reduce the size of the tumor, and adjuvant focal treatments, such as transpupillary thermotherapy, to control the tumor. Prognosis In the developed world, retinoblastoma has one of the best cure rates of all childhood cancers (95-98%), with more than 90% of sufferers surviving into adulthood. In the UK, around 40 to 50 new cases are diagnosed each year.Good prognosis depends upon early presentation of the child in health facility. Late presentation is associated with a poor prognosis.Survivors of hereditary retinoblastoma have a higher risk of developing other cancers later in life. Epidemiology Retinoblastoma presents with cumulative lifetime incidence rate of one case of retinoblastoma per 18000 to 30000 live births worldwide. A higher incidence is noted in developing countries, which has been attributed to lower socioeconomic status and the presence of human papilloma virus sequences in the retinoblastoma tissue.Almost 80% of children with retinoblastoma are diagnosed before three years of age and diagnosis in children above six years of age is extremely rare. In the UK, bilateral cases usually present within 14 to 16 months, while diagnosis of unilateral cases peaks between 24 and 30 months. See also Eye cancer Eye examination Retinoblastoma protein References External links Retinoblastoma information from MedlinePlus retinoblastoma at NIH/UW GeneTests RB1 Mutation Database Retinoblastoma at Curlie NCBI Genetic Testing Registry

Pityriasis rosea

Pityriasis rosea is a type of skin rash. Classically, it begins with a single red and slightly scaly area known as a "herald patch". This is then followed, days to weeks later, by an eruption of many smaller scaly spots; pinkish with a red edge in people with light skin and greyish in darker skin. About 20% of cases show atypical deviations from this pattern. It usually lasts less than three months and goes away without treatment. Sometimes malaise or a fever may occur before the start of the rash or itchiness, but often there are few other symptoms.While the cause is not entirely clear, it is believed to be related to human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7). It does not appear to be contagious. Certain medications may result in a similar rash. Diagnosis is based on the symptoms.Evidence for specific treatment is limited. About 1.3% of people are affected at some point in time. It most often occurs in those between the ages of 10 and 35. The condition was described at least as early as 1798. Signs and symptoms The symptoms of this condition include: Recent upper respiratory tract infections in 8–69% of patients have been reported by some studies. Occasionally, prodromal flu-like symptoms, including headache, joint pain, mild fever, and fatigue, as well as gastrointestinal symptoms such as nausea, diarrhea, or vomiting, and feeling generally unwell, precede other symptoms. In most cases, a single, 2 to 10 cm (1" to 4") oval red "herald" patch appears, classically on the trunk or neck, having an appearance similar to ringworm. Occasionally, the herald patch may occur in a hidden position (in the armpit, for example) and not be noticed immediately. The herald patch may also appear as a cluster of smaller oval spots, and be mistaken for acne. Rarely, it does not become present at all. After the herald patch appears, usually some days or weeks later, a rash of many small (5–10 mm; 1⁄4" to 1⁄2") pink or red, flaky, oval or round spots appear. They are mostly situated on the trunk and upper limbs. They follow the skins cleavage lines, which on the upper chest and back produce a characteristic "christmas-tree" distribution. In 6% of cases an "inverse" distribution may occur, with rash mostly on the extremities. In children, presentation can be atypical or inverse, and the course is typically milder. About one in four people with PR have mild to severe symptomatic itching. (Moderate itching due to skin over-dryness is much more common, especially if soap is used to cleanse the affected areas.) The itching is often non-specific, and worsens if scratched. This tends to fade as the rash develops and does not usually last through the entire course of the disease.About a fifth of cases have an atypical form, with significant variations in symptoms including the size, distribution, morphology, and evolution of the lesions. In addition to typical papules and scales, forms appearing as very large plaques (pityriasis rosea gigantea), urticaria, large blisters, patches resembling erythema multiforme, oral lesions, and various other appearances have been noted. A vesicular form can mimic chicken pox. Variations in distribution include inverted forms, with rashes on the face or extremities without appearing on the trunk, as well as more uncommon versions localized to the armpits, groin, or extremities (pityriasis rosea circinata et marginata of Vidal) or unilateral spread. Causes The cause of pityriasis rosea is not certain, but its clinical presentation and immunologic reactions suggest a viral infection as a cause. Some believe it to be a reactivation of herpes viruses 6 and 7, which cause roseola in infants, though some investigations have found no evidence of this. Diagnosis Experienced practitioners may make the diagnosis clinically. Classical symptoms are usually straightforward to recognize, but the wide range of atypical forms may cause difficulty for the clinician in diagnosing some cases. Misdiagnosis by nondermatologists is not uncommon. If the diagnosis is in doubt, tests may be performed to rule out similar conditions such as Lyme disease, ringworm, guttate psoriasis, nummular or discoid eczema, drug eruptions, other viral exanthems. The clinical appearance of pityriasis rosea in some cases is similar to that of secondary syphilis, and rapid plasma reagin testing should be performed if there is any clinical concern for syphilis. A biopsy of the lesions will show extravasated erythrocytes within dermal papillae and dyskeratotic cells within the dermis.A set of validated diagnostic criteria for pityriasis rosea is as follows: A patient is diagnosed as having pityriasis rosea if: On at least one occasion or clinical encounter, the patient has all the essential clinical features and at least one of the optional clinical features, and On all occasions or clinical encounters related to the rash, the patient does not have any of the exclusional clinical features.The essential clinical features are the following: Discrete circular or oval lesions, Scaling on most lesions, and Peripheral collarette scaling with central clearance on at least two lesions.The optional clinical features are the following: Truncal and proximal limb distribution, with less than 10% of lesions distal to mid-upper-arm and mid-thigh, Orientation of most lesions along skin cleavage lines, and A herald patch (not necessarily the largest) appearing at least two days before eruption of other lesions, from history of the patient or from clinical observation.The exclusional clinical features are the following: Multiple small vesicles at the centre of two or more lesions, Two or more lesions on palmar or plantar skin surfaces, and Clinical or serological evidence of secondary syphilis. Treatment The condition usually resolves on its own, and treatment is not required. Oral antihistamines or topical steroids may be used to decrease itching. Steroids do provide relief from itching, and improve the appearance of the rash, but they also cause the new skin that forms (after the rash subsides) to take longer to match the surrounding skin color. While no scarring has been found to be associated with the rash, scratching should be avoided. Its possible that scratching can make itching worse and an itch-scratch cycle may develop with regular scratching (that is, you itch more because you scratch, so you scratch more because you itch, and so on). Irritants such as soaps with fragrances, hot water, wool, and synthetic fabrics should be avoided. Lotions that help stop or prevent itching may be helpful.Direct sunlight makes the lesions resolve more quickly. According to this principle, medical treatment with ultraviolet light has been used to hasten resolution, though studies disagree whether it decreases itching or not. UV therapy is most beneficial in the first week of the eruption.A 2007 meta-analysis concluded that there is insufficient evidence for the effectiveness of most treatments. Oral erythromycin was found to be effective for treating the rash and relieving the itch based on one early trial; however, a later study could not confirm these results. Prognosis In most patients, the condition lasts only a matter of weeks; in some cases it can last longer (up to six months). The disease resolves completely without long-term effects. In a ten-year epidemiological study of 939 people in the United States, less than two percent had a recurrence. Epidemiology The overall prevalence of PR in the United States has been estimated to be 0.13% in men and 0.14% in women. It most commonly occurs between the ages of 10 and 35. It is more common in spring.PR is not viewed as contagious, though there have been reports of small epidemics in fraternity houses and military bases, schools and gyms. See also Pityriasis circinata - a localized form of pityriasis rosea that affects the axillae and groin Pityriasis - for list of similarly named flaky skin conditions List of cutaneous conditions References External links DermNet viral/pityriasis-roseaAmerican Academy of Dermatology - Pityriasis Rosea American Osteopathic College of Dermatology

Bowel obstruction

Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs and symptoms include abdominal pain, vomiting, bloating and not passing gas. Mechanical obstruction is the cause of about 5 to 15% of cases of severe abdominal pain of sudden onset requiring admission to hospital.Causes of bowel obstruction include adhesions, hernias, volvulus, endometriosis, inflammatory bowel disease, appendicitis, tumors, diverticulitis, ischemic bowel, tuberculosis and intussusception. Small bowel obstructions are most often due to adhesions and hernias while large bowel obstructions are most often due to tumors and volvulus. The diagnosis may be made on plain X-rays; however, CT scan is more accurate. Ultrasound or MRI may help in the diagnosis of children or pregnant women.The condition may be treated conservatively or with surgery. Typically intravenous fluids are given, a tube is placed through the nose into the stomach to decompress the intestines, and pain medications are given. Antibiotics are often given. In small bowel obstruction about 25% require surgery. Complications may include sepsis, bowel ischemia and bowel perforation.About 3.2 million cases of bowel obstruction occurred in 2015 which resulted in 264,000 deaths. Both sexes are equally affected and the condition can occur at any age. Bowel obstruction has been documented throughout history, with cases detailed in the Ebers Papyrus of 1550 BC and by Hippocrates. Signs and symptoms Depending on the level of obstruction, bowel obstruction can present with abdominal pain, swollen abdomen, abdominal distension, and constipation. Bowel obstruction may be complicated by dehydration and electrolyte abnormalities due to vomiting; respiratory compromise from pressure on the diaphragm by a distended abdomen, or aspiration of vomitus; bowel ischemia or perforation from prolonged distension or pressure from a foreign body.In small bowel obstruction, the pain tends to be colicky (cramping and intermittent) in nature, with spasms lasting a few minutes. The pain tends to be central and mid-abdominal. Vomiting may occur before constipation.In large bowel obstruction, the pain is felt lower in the abdomen and the spasms last longer. Constipation occurs earlier and vomiting may be less prominent. Proximal obstruction of the large bowel may present as small bowel obstruction. Causes Small bowel obstruction Causes of small bowel obstruction include: Adhesions from previous abdominal surgery (most common cause) Barbed sutures Pseudoobstruction Hernias containing bowel Crohns disease causing adhesions or inflammatory strictures Neoplasms, benign or malignant Intussusception Volvulus Superior mesenteric artery syndrome, a compression of the duodenum by the superior mesenteric artery and the abdominal aorta Ischemic strictures Foreign bodies (e.g. gallstones in gallstone ileus, swallowed objects such as expandable water toys) Intestinal atresiaAfter abdominal surgery, the incidence of small bowel obstruction from any cause is 9%. In those where the cause of the obstruction was clear, adhesions are the single most common cause (more than half). Large bowel obstruction Causes of large bowel obstruction include: Neoplasms / cancer Diverticulitis / Diverticulosis Hernias Inflammatory bowel disease Colonic volvulus (sigmoid, caecal, transverse colon) Adhesions Constipation Fecal impaction Fecaloma Colon atresia Intestinal pseudoobstruction Endometriosis Narcotic induced (especially with the large doses given to cancer or palliative care patients) Outlet obstruction Outlet obstruction is a sub-type of large bowel obstruction and refers to conditions affecting the anorectal region that obstruct defecation, specifically conditions of the pelvic floor and anal sphincters. Outlet obstruction can be classified into four groups. Functional outlet obstruction Inefficient inhibition of the internal anal sphincter Short-segment Hirschsprungs disease Chagas disease Hereditary internal sphincter myopathy Inefficient relaxation of the striated pelvic floor muscles Anismus (pelvic floor dyssynergia) Multiple sclerosis Spinal cord lesions Mechanical outlet obstruction Internal intussusception Enterocele Dissipation of force vector rectocele Descending perineum Rectal prolapse Impaired rectal sensitivity Megarectum Rectal hyposensitivity Diagnosis The main diagnostic tools are blood tests, X-rays of the abdomen, CT scanning, and ultrasound. If a mass is identified, biopsy may determine the nature of the mass.Radiological signs of bowel obstruction include bowel distension and the presence of multiple (more than six) gas-fluid levels on supine and erect abdominal radiographs. Ultrasounds may be as useful as CT scanning to make the diagnosis.Contrast enema or small bowel series or CT scan can be used to define the level of obstruction, whether the obstruction is partial or complete, and to help define the cause of the obstruction. The appearance of water-soluble contrast in the cecum on an abdominal radiograph within 24 hours of it being given by mouth predicts resolution of an adhesive small bowel obstruction with sensitivity of 97% and specificity of 96%.Colonoscopy, small bowel investigation with ingested camera or push endoscopy, and laparoscopy are other diagnostic options. Differential diagnosis Differential diagnoses of bowel obstruction include: Ileus Pseudo-obstruction or Ogilvies syndrome Intra-abdominal sepsis Pneumonia or other systemic illness Treatment Some causes of bowel obstruction may resolve spontaneously; many require operative treatment. In adults, frequently the surgical intervention and the treatment of the causative lesion are required. In malignant large bowel obstruction, endoscopically placed self-expanding metal stents may be used to temporarily relieve the obstruction as a bridge to surgery, or as palliation. Diagnosis of the type of bowel obstruction is normally conducted through initial plain radiograph of the abdomen, luminal contrast studies, computed tomography scan, or ultrasonography prior to determining the best type of treatment.Further research is needed to find out if parenteral nutrition is of benefit to people with an inoperable blockage of the bowel caused by advanced cancer. Small bowel obstruction In the management of small bowel obstructions, a commonly quoted surgical aphorism is: "never let the sun rise or set on small-bowel obstruction" because about 5.5% of small bowel obstructions are ultimately fatal if treatment is delayed. Improvements in radiological imaging of small bowel obstructions allow for confident distinction between simple obstructions, that can be treated conservatively, and obstructions that are surgical emergencies (volvulus, closed-loop obstructions, ischemic bowel, incarcerated hernias, etc.).A small flexible tube (nasogastric tube) may be inserted through the nose into the stomach to help decompress the dilated bowel. This tube is uncomfortable but relieves the abdominal cramps, distention, and vomiting. Intravenous therapy is utilized and the urine output is monitored with a catheter in the bladder.Most people with SBO are initially managed conservatively because in many cases, the bowel will open up. Some adhesions loosen up and the obstruction resolves. The patient is examined several times a day, and X-ray images are made to ensure he or she is not getting clinically worse.Conservative treatment involves insertion of a nasogastric tube, correction of dehydration and electrolyte abnormalities. Opioid pain relievers may be used for patients with severe pain. Antiemetics may be administered if the patient is vomiting. Adhesive obstructions often settle without surgery. If the obstruction is complete surgery is usually required. Most patients improve with conservative care in 2–5 days. When the obstruction is cancer, surgery is the only treatment. Those with bowel resection or lysis of adhesions usually stay in the hospital a few more days until they can eat and walk.Small bowel obstruction caused by Crohns disease, peritoneal carcinomatosis, sclerosing peritonitis, radiation enteritis, and postpartum bowel obstruction are typically treated conservatively, i.e. without surgery. Prognosis The prognosis for non-ischemic cases of SBO is good with mortality rates of 3–5%, while prognosis for SBO with ischemia is fair with mortality rates as high as 30%.Cases of SBO related to cancer are more complicated and require additional intervention to address the malignancy, recurrence, and metastasis, and thus are associated with poorer prognosis.All cases of abdominal surgical intervention are associated with increased risk of future small-bowel obstructions. Statistics from U.S. healthcare report 18.1% re-admittance rate within 30 days for patients who undergo SBO surgery. More than 90% of patients also form adhesions after major abdominal surgery. Common consequences of these adhesions include small-bowel obstruction, chronic abdominal pain, pelvic pain, and infertility. See also Impaction (animals) – A blockage of the intestines in animals Neonatal bowel obstruction – A blockage of the intestines in children References External links Obstruction, Small Bowel at eMedicine Obstruction, Large Bowel at eMedicine

Uterine prolapse

Uterine prolapse is when the uterus descends towards or through the opening of the vagina. Symptoms may include vaginal fullness, pain with sex, trouble urinating, urinary incontinence, and constipation. Often it gets worse over time. Low back pain and vaginal bleeding may also occur.Risk factors include pregnancy, childbirth, obesity, constipation, and chronic coughing. Diagnosis is based on examination. It is a form of pelvic organ prolapse, together with bladder prolapse, large bowel prolapse, and small bowel prolapse.Preventive efforts include managing chronic breathing problems, not smoking, and maintaining a healthy weight. Mild cases may be treated with a pessary together with hormone replacement therapy. More severe cases may require surgery such as a vaginal hysterectomy. About 14% of women are affected. It occurs most commonly after menopause. Causes The most common cause of uterine prolapse is trauma during childbirth, in particular multiple or difficult births. About 50% of women who have had children develop some form of pelvic organ prolapse in their lifetime. It is more common as women get older, particularly in those who have gone through menopause. This condition is surgically correctable. Pathophysiology The uterus (womb) is normally held in place by a hammock of muscles and ligaments. Prolapse happens when the ligaments supporting the uterus become so weak that the uterus cannot stay in place and slips down from its normal position. These ligaments are the round ligament, uterosacral ligaments, broad ligament and the ovarian ligament. The uterosacral ligaments are by far the most important ligaments in preventing uterine prolapse. In some cases of uterine prolapse, the uterus can be unsupported enough to extend past the vaginal wall for inches. Treatment Treatment is conservative, mechanical or surgical. Conservative Conservative options include behavioral modification and muscle strengthening exercises such as Kegel exercise. Pessaries are a mechanical treatment that supports the vagina and elevates the prolapsed uterus to its normal, correct position. Pessaries are frequently offered as a first-line treatment for uterine prolapse. Surgery Surgical options are many and may include a hysterectomy or a uterus-sparing technique such as laparoscopic hysteropexy, sacrohysteropexy or the Manchester operation. In the case of hysterectomy, the procedure can be accompanied by sacrocolpopexy. This is a mesh-augmented procedure in which the apex of the vagina is attached to the sacrum by a piece of medical mesh material.A Cochrane review found that sacral colpopexy was associated with lower risk of complications than vaginal interventions, but it was unclear what route of sacral colpopexy should be preferred. No clear conclusion could be reached regarding uterine preserving surgery versus vaginal hysterectomy for uterine prolapse. The evidence does not support use of transvaginal mesh (TVM) compared to native tissue repair for apical vaginal prolapse. The use of a transvaginal mesh is associated with side effects including pain, infection, and organ perforation. According to the FDA, serious complications are "not rare". Society and culture A number of class action lawsuits have been filed and settled against several manufacturers of TVM devices. References External links Illustrated description of Manchester Operation at atlasofpelvicsurgery.com Inverted uterus treatment, from Merck Professional

Occupational asthma

Occupational asthma is new onset asthma or the recurrence of previously quiescent asthma directly caused by exposure to an agent at workplace. It is an occupational lung disease and a type of work-related asthma. Agents that can induce occupational asthma can be grouped into sensitizers and irritants.Sensitizer-induced occupational asthma is an immunologic form of asthma which occurs due to inhalation of specific substances (i.e., high-molecular-weight proteins from plants and animal origins, or low-molecular-weight agents that include chemicals, metals and wood dusts) and occurs after a latency period of several weeks to years.Irritant-induced (occupational) asthma is a non-immunologic form of asthma that results from a single or multiple high dose exposure to irritant products. It is usually develops early after exposure; however can also develop insidiously over a few months after a massive exposure to a complex mixture of alkaline dust and combustion products, as shown in the World Trade Center disaster. Unlike those with sensitizer-induced occupational asthma, subjects with irritant-induced occupational asthma do not develop work-related asthma symptoms after re-exposure to low concentrations of the irritant that initiated the symptoms. Reactive airways dysfunction syndrome (RADS) is a severe form of irritant induced asthma where respiratory symptoms usually develop in the minutes or hours after a single accidental inhalation of a high concentration of irritant gas, aerosol, vapor, or smoke.Another type of work-related asthma is work-exacerbated asthma (WEA) which is asthma worsened by workplace conditions but not caused by it. WEA is present in about a fifth of patients with asthma and a wide variety of conditions at work, including irritant chemicals, dusts, second-hand smoke, common allergens that may be present at work, as well as other "exposures" such as emotional stress, worksite temperature, and physical exertion can exacerbate asthma symptoms in these patients. Both occupational asthma and work-exacerbated asthma can be present in an individual. A number of diseases have symptoms that mimic occupational asthma, such as asthma due to nonoccupational causes, chronic obstructive pulmonary disease (COPD), irritable larynx syndrome, hyperventilation syndrome, hypersensitivity pneumonitis, and bronchiolitis obliterans. Signs and symptoms Like other types of asthma, it is characterized by airway inflammation, reversible airways obstruction, and bronchospasm, but it is caused by something in the workplace environment. Symptoms include shortness of breath, tightness of the chest, coughing, sputum production and wheezing. Some patients may also develop upper airway symptoms such as itchy eyes, tearing, sneezing, nasal congestion and rhinorrhea.Symptoms may develop over many years as in sensitizer induced asthma or may occur after a single exposure to a high-concentration agent as in case of RADS. Risk factors At present, over 400 workplace substances have been identified as having asthmagenic or allergenic properties. Agents such as flour, diisocyanates, latex, persulfate salts, aldehydes, animals, wood dusts, metals, enzymes usually account for the majority cases, however, the distribution of causal agents may vary widely across geographic areas, depending on the pattern of industrial activities. For example, in France the industries most affected are bakeries and cake-shops, automobile industry and hairdressers, whereas in Canada the principal cause is wood dust, followed by isocyanates. Furthermore, the most common cause of occupational asthma in the workplace are isocyanates. Isocyanates are used in the production of motor vehicles and in the application of orthopaedic polyurethane and fibreglass casts.The occupations most at risk are: adhesive handlers (e.g. acrylate), animal handlers and veterinarians (animal proteins), bakers and millers (cereal grains), carpet makers (gums), electronics workers (soldering resin), forest workers, carpenters and cabinetmakers (wood dust), hairdressers (e.g. persulfate), health care workers (latex and chemicals such as glutaraldehyde), janitors and cleaning staff (e.g. chloramine-T), pharmaceutical workers (drugs, enzymes), seafood processors, shellac handlers (e.g. amines), solderers and refiners (metals), spray painters, insulation installers, plastics and foam industry workers (e.g. diisocyanates), textile workers (dyes) and users of plastics and epoxy resins (e.g. anhydrides)The following tables show occupations that are known to be at risk for occupational asthma, the main reference for these is the Canadian Centre for Occupational Health and Safety. Diagnosis To diagnose occupational asthma it is necessary to confirm the symptoms of asthma and establish the causal connection with the work environment. Various diagnostic tests can be used to aid in diagnoses of work related asthma.A spirometer is a device used to measure timed expired and inspired volumes, and can be used to help diagnose asthma. Peak expiratory flow rate (PEFR) is a hand held device which measures how fast a person can exhale and is a reliable test for occupational asthma. Serial PEFR can be measured to see if there is a difference in ability to exhale at work compared to that in a controlled environment. A non-specific bronchial hyperreactivity test can be used to support the diagnose occupational asthma. It involves measuring the forced expiratory volume in 1 second (FEV-1) of the patient before and after exposure to methacholine or mannitol. Presence of airway responsiveness i.e. significant drop in FEV-1 can be seen in patients with occupational asthma.Specific inhalation challenges test consist of exposing the subjects to the suspected occupational agent in the laboratory and/or at the workplace and assess for asthma symptoms as well as a reduction in FEV1.Other tests such as skin prick test, serum immunologic testing and measurement of sputum eosinophils can also be useful in establishing the diagnosis of occupational asthma. Prevention Several forms of preventive measures have been suggested to prevent development of occupational asthma and also detect risk or disease early to allow intervention and improve outcomes. These include: comprehensive programs, education and training, medical examinations, use of medications, reduction of exposures and elimination of exposures. Asthma symptoms and airway hyperresponsiveness can persist for several years after removal from the offending environment. Thus, early restriction from exposure to the trigger is advisable. Completely stopping exposure is more effective treatment than reducing exposure, but not always feasible. Management Medication Medications used for occupational asthma are similar to those used for other types of asthma such as short-acting beta-agonists like salbutamol or terbutaline, long-acting beta-agonists like salmeterol and formoterol and inhaled corticosteroids. Immunotherapy can also be used in some cases of sensitizer induced occupational asthma. Epidemiology Occupational asthma is one of the most common occupational lung disease. Approximately 17% of all adult-onset asthma cases are related to occupational exposures. About one fourth of adults with asthma have work-exacerbated asthma. Patients with work-related asthma are more likely to experience asthma attacks, emergency room visits, and worsening of their asthma symptoms compared with other adult asthma patients. Society and culture Compensation When a person is diagnosed with occupational asthma, it can result in serious socio-economic consequences not only for the workers but also for the employer and the healthcare system because the worker must change positions. The probability of being re-employed is lower for those with occupational asthma compared to those with normal asthma. The employer not only pays compensation to the employee, but will also have to spend a considerable amount of time and energy and funds for hiring and training new personnel. In the United States, it was estimated that the direct cost of occupational asthma in 1996 was $1.2 billion and the indirect cost $0.4 billion, for a total cost of $1.6 billion. In most cases, the employer could have saved more money by adhering to safety standards rather than causing employees to become injured. However, this can entail severe socio-economic consequences for the worker as well as the employer due to loss of job, unemployment, compensation issues, medical expenditures, and hiring and re-training of new personnel. See also Chronic obstructive pulmonary disease (COPD) Specific inhalation challenge Occupational safety and health National Institute of Occupational Safety and Health (NIOSH) Labor rights References External links NIOSH: Prevention of Occupational Asthma Occupational asthma and work aggravated asthma (UK) https://www.cdc.gov/niosh/topics/asthma/default.html

Asbestosis

Asbestosis is long-term inflammation and scarring of the lungs due to asbestos fibers. Symptoms may include shortness of breath, cough, wheezing, and chest tightness. Complications may include lung cancer, mesothelioma, and pulmonary heart disease.Asbestosis is caused by breathing in asbestos fibers. It requires a relatively large exposure over a long period of time, which typically only occur in those who directly work with asbestos. All types of asbestos fibers are associated with an increased risk. It is generally recommended that currently existing and undamaged asbestos be left undisturbed. Diagnosis is based upon a history of exposure together with medical imaging. Asbestosis is a type of interstitial pulmonary fibrosis.There is no specific treatment. Recommendations may include influenza vaccination, pneumococcal vaccination, oxygen therapy, and stopping smoking. Asbestosis affected about 157,000 people and resulted in 3,600 deaths in 2015. Asbestos use has been banned in a number of countries in an effort to prevent disease.Statistics from the Health and Safety Executive showed that in 2019, there were 490 asbestosis deaths. Signs and symptoms The signs and symptoms of asbestosis typically manifest after a significant amount of time has passed following asbestos exposure, often several decades under current conditions in the US. The primary symptom of asbestosis is generally the slow onset of shortness of breath, especially with physical activity. Clinically advanced cases of asbestosis may lead to respiratory failure. When a stethoscope is used to listen to the lungs of a person with asbestosis, they may hear inspiratory "crackles". The characteristic pulmonary function finding in asbestosis is a restrictive ventilatory defect. This manifests as a reduction in lung volumes, particularly the vital capacity (VC) and total lung capacity (TLC). The TLC may be reduced through alveolar wall thickening; however, this is not always the case. Large airway function, as reflected by FEV1/FVC, is generally well preserved. In severe cases, the drastic reduction in lung function due to the stiffening of the lungs and reduced TLC may induce right-sided heart failure (cor pulmonale). In addition to a restrictive defect, asbestosis may produce reduction in diffusion capacity and a low amount of oxygen in the blood of the arteries. Cause The cause of asbestosis is the inhalation of microscopic asbestos mineral fibers suspended in the air. In the 1930s, E. R. A. Merewether found that greater exposure resulted in greater risk. Pathogenesis Asbestosis is the scarring of lung tissue (beginning around terminal bronchioles and alveolar ducts and extending into the alveolar walls) resulting from the inhalation of asbestos fibers. There are two types of fibers: amphibole (thin and straight) and serpentine (curly). All forms of asbestos fibers are responsible for human disease as they are able to penetrate deeply into the lungs. When such fibers reach the alveoli (air sacs) in the lung, where oxygen is transferred into the blood, the foreign bodies (asbestos fibers) cause the activation of the lungs local immune system and provoke an inflammatory reaction dominated by lung macrophages that respond to chemotactic factors activated by the fibers. This inflammatory reaction can be described as chronic rather than acute, with a slow ongoing progression of the immune system attempting to eliminate the foreign fibers. Macrophages phagocytose (ingest) the fibers and stimulate fibroblasts to deposit connective tissue. Due to the asbestos fibers natural resistance to digestion, some macrophages are killed and others release inflammatory chemical signals, attracting further lung macrophages and fibrolastic cells that synthesize fibrous scar tissue, which eventually becomes diffuse and can progress in heavily exposed individuals. This tissue can be seen microscopically soon after exposure in animal models. Some asbestos fibers become layered by an iron-containing proteinaceous material (ferruginous body) in cases of heavy exposure where about 10% of the fibers become coated. Most inhaled asbestos fibers remain uncoated. About 20% of the inhaled fibers are transported by cytoskeletal components of the alveolar epithelium to the interstitial compartment of the lung where they interact with macrophages and mesenchymal cells. The cytokines, transforming growth factor beta and tumor necrosis factor alpha, appear to play major roles in the development of scarring inasmuch as the process can be blocked in animal models by preventing the expression of the growth factors. The result is fibrosis in the interstitial space, thus asbestosis. This fibrotic scarring causes alveolar walls to thicken, which reduces elasticity and gas diffusion, reducing oxygen transfer to the blood as well as the removal of carbon dioxide. This can result in shortness of breath, a common symptom exhibited by individuals with asbestosis. Those with asbestosis may be more vulnerable to tumor growth (mesothelioma) because asbestos decreases the cytotoxicity of natural killer cells and impairs the functioning of T helper cells, which detect abnormal cell growth. Diagnosis According to the American Thoracic Society (ATS), the general diagnostic criteria for asbestosis are: Evidence of structural pathology consistent with asbestosis, as documented by imaging or histology Evidence of causation by asbestos as documented by the occupational and environmental history, markers of exposure (usually pleural plaques), recovery of asbestos bodies, or other means Exclusion of alternative plausible causes for the findingsThe abnormal chest x-ray and its interpretation remain the most important factors in establishing the presence of pulmonary fibrosis. The findings usually appear as small, irregular parenchymal opacities, primarily in the lung bases. Using the ILO Classification system, "s", "t", and/or "u" opacities predominate. CT or high-resolution CT (HRCT) are more sensitive than plain radiography at detecting pulmonary fibrosis (as well as any underlying pleural changes). More than 50% of people affected with asbestosis develop plaques in the parietal pleura, the space between the chest wall and lungs. Once apparent, the radiographic findings in asbestosis may slowly progress or remain static, even in the absence of further asbestos exposure. Rapid progression suggests an alternative diagnosis. Asbestosis resembles many other diffuse interstitial lung diseases, including other pneumoconiosis. The differential diagnosis includes idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, sarcoidosis, and others. The presence of pleural plaques may provide supportive evidence of causation by asbestos. Although lung biopsy is usually not necessary, the presence of asbestos bodies in association with pulmonary fibrosis establishes the diagnosis. Conversely, interstitial pulmonary fibrosis in the absence of asbestos bodies is most likely not asbestosis. Asbestos bodies in the absence of fibrosis indicate exposure, not disease. Treatment There is no cure available for asbestosis. Oxygen therapy at home is often necessary to relieve the shortness of breath and correct underlying low blood oxygen levels. Supportive treatment of symptoms includes respiratory physiotherapy to remove secretions from the lungs by postural drainage, chest percussion, and vibration. Nebulized medications may be prescribed in order to loosen secretions or treat underlying chronic obstructive pulmonary disease. Immunization against pneumococcal pneumonia and annual influenza vaccination is administered due to increased sensitivity to the diseases. Those with asbestosis are at increased risk for certain cancers. If the person smokes, quitting the habit reduces further damage. Periodic pulmonary function tests, chest x-rays, and clinical evaluations, including cancer screening/evaluations, are given to detect additional hazards. Society and culture Legal issues The death of English textile worker Nellie Kershaw in 1924 from pulmonary asbestosis was the first case to be described in medical literature, and the first published account of disease attributed to occupational asbestos exposure. However, her former employers (Turner Brothers Asbestos) denied that asbestosis even existed because the medical condition was not officially recognised at the time. As a result, they accepted no liability for her injuries and paid no compensation, either to Kershaw during her final illness or to her family after her death. Even so, the findings of the inquest into her death were highly influential insofar as they led to a parliamentary enquiry by the British Parliament. The enquiry formally acknowledged the existence of asbestosis, recognised that it was hazardous to health and concluded that it was irrefutably linked to the prolonged inhalation of asbestos dust. Having established the existence of asbestosis on a medical and judicial basis, the report resulted in the first Asbestos Industry Regulations being published in 1931, which came into effect on 1 March 1932.The first lawsuits against asbestos manufacturers occurred in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the link between asbestos, asbestosis and mesothelioma became known (some reports seem to place this as early as 1898 in modern times). The liability resulting from the sheer number of lawsuits and people affected has reached billions of U.S. dollars. The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases. To date, about 100 companies have declared bankruptcy at least partially due to asbestos-related liability. In accordance with Chapter 11 and § 524(g) of the U.S. federal bankruptcy code, a company may transfer its liabilities and certain assets to an asbestos personal injury trust, which is then responsible for compensating present and future claimants. Since 1988, 60 trusts have been established to pay claims with about $37 billion in total assets. From 1988 through 2010, analysis from the United States Government Accountability Office indicates that trusts have paid about 3.3 million claims valued at about $17.5 billion. Notable people This is a partial list of notable people who have died from lung fibrosis associated with asbestos: Bernie Banton, social justice advocate Paul Gleason, Breakfast Club actor Stephen Jay Gould, Harvard University professor, paleontologist, evolutionary biologist, and historian Nellie Kershaw, first person diagnosed with asbestos-related disease, 1924 John MacDougall, politician Steve McQueen, actor Theodore Sturgeon, writer References External links "Asbestos Toxicity". ATSDR Case Studies in Environmental Medicine. U.S. Department of Health and Human Services. "Asbestos health and safety". British Government Health and Safety Executive. "Asbestos Exposure". National Cancer Institute, USA. 2017-06-15. "Environmental Health Guidance Note — Asbestos" (PDF). Queensland Health. May 2002. Archived from the original (PDF) on 2012-02-27. Retrieved 2011-12-03. "Asbestos". IRIS — Integrated Risk Information System. US Environmental Protection Agency. 2013-03-15. CASRN 1332-21-4.

Toxic multinodular goitre

Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism. It is a common cause of hyperthyroidism in which there is excess production of thyroid hormones from functionally autonomous thyroid nodules, which do not require stimulation from thyroid stimulating hormone (TSH).Toxic multinodular goiter is the second most common cause of hyperthyroidism (after Graves disease) in the developed world, whereas iodine deficiency is the most common cause of hypothyroidism in developing-world countries where the population is iodine-deficient. (Decreased iodine leads to decreased thyroid hormone.) However, iodine deficiency can cause goiter (thyroid enlargement); within a goitre, nodules can develop. Risk factors for toxic multinodular goiter include individuals over 60 years of age and being female. Signs and symptoms Symptoms of toxic multinodular goitre are similar to that of hyperthyroidism, including: heat intolerance muscle weakness/wasting hyperactivity fatigue tremor irritability weight loss osteoporosis increased appetite non-painful goitre (swelling of the thyroid gland) tachycardia (high heart rate - above 100 beats per minute at rest in adults) tracheal compression exophthalmos Causes Sequence of events: Iodine deficiency leading to decreased T4 production. Induction of thyroid cell hyperplasia due to low levels of T4. This accounts for the multinodular goitre appearance. Increased replication predisposes to a risk of mutation in the TSH receptor. If the mutated TSH receptor is constitutively active, it would then become toxic and produces excess T3/T4 leading to hyperthyroidism. Diagnosis Treatments Toxic multinodular goiter can be treated with antithyroid medications such as propylthiouracil or methimazole, radioactive iodine, or with surgery. Another treatment option is injection of ethanol into the nodules. History The usage of terminology for types of goiter has varied over the past century. Physicians and surgeons tend to differentiate among solitary-nodule goiter, multinodular goiter, and non-nodular goiter more thoroughly in recent decades than they formerly did. Thus some sources have described, or still describe, thyroid adenoma (toxic adenoma) as synonymous with toxic multinodular goiter, but other sources differentiate those two as single-nodule disease versus multinodular disease (respectively) with pathogenesis that is likely differing in most cases (e.g., single neoplastic cell clone versus multifocal or diffuse molecular metabolic change). The medical eponyms "Plummer disease" (named after American physician Henry Stanley Plummer) and "Parry disease" (named after English physician Caleb Hillier Parry) have been used to refer to toxic multinodular goiter, toxic adenoma, and toxic diffuse goiter (Graves disease); the specific entity in each patient/case is not always clear retrospectively, especially in older literature. This is logical given that advanced medical imaging that can show what is happening at various places within a thyroid gland inside a living person (such as nuclear medicine imaging of radioiodine tracer uptake) was not available until after the 1940s. References == External links ==

Anorectal abscess

Anorectal abscess (also known as an anal/rectal abscess, or perianal/perirectal abscess) is an abscess adjacent to the anus. Most cases of perianal abscesses are sporadic, though there are certain situations which elevate the risk for developing the disease, such as diabetes mellitus, Crohns disease, chronic corticosteroid treatment and others. It arises as a complication of paraproctitis. Ischiorectal, inter- and intrasphincteric abscesses have been described. Signs and symptoms Pain in the perianal area is the most common symptom of an anorectal abscess. The pain may be dull, aching, or throbbing. It is worst when the person sits down and right before a bowel movement. After the individual has a bowel movement, the pain usually lessens. Other signs and symptoms of anorectal abscess include constipation, drainage from the rectum, fever and chills, or a palpable mass near the anus. The condition can become extremely painful, and usually worsens over the course of just a few days. The pain may be limited and sporadic at first, but may worsen to a constant pain which can become very severe when body position is changed (e.g., when standing up, rolling over, and so forth). Depending upon the exact location of the abscess, there can also be excruciating pain during bowel movements, though this is not always the case. This condition may occur in isolation, but is frequently indicative of another underlying disorder, such as Crohns disease. Complications If left untreated, an anal fistula will almost certainly form, connecting the rectum to the skin. This requires more intensive surgery. Furthermore, any untreated abscess may (and most likely will) continue to expand, eventually becoming a serious systemic infection. Cause Abscesses are caused by a high-density infection of (usually) common bacteria which collect in one place or another for any variety of reasons. Anal abscesses, without treatment, are likely to spread and affect other parts of the body, particularly the groin and rectal lumen. All abscesses can progress to serious generalized infections requiring lengthy hospitalizations if not treated. Historically, many rectal abscesses are caused by bacteria common in the digestive system, such as E. coli. While this still continues often to be the case, there has recently been an increase in the causative organism being staphylococcus, as well as the difficult to treat community-acquired methicillin-resistant S. aureus. Because of the increasing appearance of more exotic bacteria in anal abscesses, microbiological examination will always be performed on the surgical exudate to determine the proper course of any antibiotic treatment. Diagnosis Diagnosis of anorectal abscess begins with a medical history and physical exam. Imaging studies which can help determine the diagnosis in cases of a deep non-palpable perirectal abscess include pelvic CT scan, MRI or trans-rectal ultrasound. These studies are not necessary, though, in cases which the diagnosis can be made upon physical exam. Classification Anorectal abscesses are classified according to their anatomic location and the following are the most common types: perianal abscess, ischiorectal abscess, intersphincteric abscess and supralevator abscess. Perianal abscess, which represents the most common type of anorectal abscesses accounting for about 60% of reported cases, are superficial collections of purulent material just beneath the skin of the anal canal.Ischiorectal abscess is formed when suppuration transverses the external anal sphincter into the ischiorectal space.Intersphincteric abscess results from suppuration contained between the internal and external anal sphincters.Supralevator abscess forms from cephalad extension of the intersphincteric abscess above the levator ani or from caudal extension of a suppurative abdominal process like appendicitis, diverticular or gynaecologic sepsis. Differential diagnosis This condition is often initially misdiagnosed as hemorrhoids, since this is almost always the cause of any sudden anal discomfort. The presence of the abscess, however, is suspected when the pain quickly worsens over one or two days and usual hemorrhoid treatments are ineffective in bringing relief. Furthermore, any serious abscess will eventually begin to cause signs and symptoms of general infection, including fever and nighttime chills. A physician can rule out a hemorrhoid with a simple visual inspection, and usually appreciate an abscess by touch. Treatment Anal abscesses are rarely treated with a simple course of antibiotics. In almost all cases surgery will need to take place to remove the abscess. Treatment is possible in an emergency department under local anesthesia, but it is highly preferred to be formally admitted to a hospital and to have the surgery performed in an operating room under general anesthesia. Generally speaking, a fairly small but deep incision is performed close to the root of the abscess. The surgeon will allow the abscess to drain its exudate and attempt to discover any other related lesions in the area. This is one of the most basic types of surgery, and is usually performed in less than thirty minutes by the anal surgical team. Generally, a portion of the exudate is sent for microbiological analysis to determine the type of infecting bacteria. The incision is not closed (stitched), as the damaged tissues must heal from the inside toward the skin over a period of time. The affected individual is often sent home within twenty-four hours of the surgery, and may be instructed to perform several sitz baths per day. These involve a small basin which is filled with warm water, and possibly with salts; usually fits over a toilet; and soaks the affected area for a period of time. Another method of recovery involves the use of surgical packing. The initial packing is inserted by the surgical team, with redressing generally performed by hospital staff or a district nurse. During the week following the surgery, many patients will have some form of antibiotic therapy, along with some form of pain management therapy, consistent with the nature of the abscess. It is unclear whether internal packing of the perianal abscess influences time taken for healing, wound pain, development of fistulae, or abscess recurrence.The patient usually experiences an almost complete relief of the severe pain associated to his/her abscess upon waking from anesthesia; the pain associated with the opening and draining incision during the post-operative period is often mild in comparison. Gallery References == External links ==

Tetralogy of Fallot

Tetralogy of Fallot (TOF), formerly known as Steno-Fallot tetralogy, is a congenital heart defect characterized by four specific cardiac defects. Classically, the four defects are: pulmonary stenosis, which is narrowing of the exit from the right ventricle; a ventricular septal defect, which is a hole allowing blood to flow between the two ventricles; right ventricular hypertrophy, which is thickening of the right ventricular muscle; and an overriding aorta, which is where the aorta expands to allow blood from both ventricles to enter.At birth, children may be asymptomatic or present with many severe symptoms. Later in infancy, there are typically episodes of bluish colour to the skin due to a lack of sufficient oxygenation, known as cyanosis. When affected babies cry or have a bowel movement, they may undergo a "tet spell" where they turn cyanotic, have difficulty breathing, become limp, and occasionally lose consciousness. Other symptoms may include a heart murmur, finger clubbing, and easy tiring upon breastfeeding.The cause of tetralogy of Fallot is typically not known. Risk factors include a mother who uses alcohol, has diabetes, is over the age of 40, or gets rubella during pregnancy.: 62  It may also be associated with Down syndrome and other chromosomal defects that cause congenital heart defects.TOF is typically treated by open heart surgery in the first year of life. The timing of surgery depends on the babys symptoms and size. The procedure involves increasing the size of the pulmonary valve and pulmonary arteries and repairing the ventricular septal defect. In babies who are too small, a temporary surgery may be done with plans for a second surgery when the baby is bigger. With proper care, most people who are affected live to be adults. Long-term problems may include an irregular heart rate and pulmonary regurgitation.The prevalence of TOF is estimated to be anywhere from 0.02 to 0.04%. Though males and females were initially thought to be affected equally, more recent studies have found males to be affected more than females. It is the most common complex congenital heart defect, accounting for about 10 percent of cases. It was initially described in 1671 by Niels Steensen. A further description was published in 1888 by the French physician Étienne-Louis Arthur Fallot, after whom it is named. The first total surgical repair was carried out in 1954. Signs and symptoms Tetralogy of Fallot results in low oxygenation of blood. This is due to a mixing of oxygenated and deoxygenated blood in the left ventricle via the ventricular septal defect (VSD) and preferential flow of the mixed blood from both ventricles through the aorta because of the obstruction to flow through the pulmonary valve. The latter is known as a right-to-left shunt.Infants with TOF – a cyanotic heart disease – have low blood oxygen saturation. Blood oxygenation varies greatly from one patient to another depending on the severity of the anatomic defects. Typical ranges vary from 60% to around 90%. Depending on the degree of obstruction, symptoms vary from no cyanosis or mild cyanosis to profound cyanosis at birth. If the baby is not cyanotic, then it is sometimes referred to as a "pink tet". Other symptoms include a heart murmur which may range from almost imperceptible to very loud, difficulty in feeding, failure to gain weight, retarded growth and physical development, labored breathing (dyspnea) on exertion, clubbing of the fingers and toes, and polycythemia. The baby may turn blue with breastfeeding or crying.Those born with tetralogy of Fallot are more likely to experience psychiatric disorders such as attention deficit hyperactivity disorder (ADHD) in later life, potentially due to underlying genetic changes that predispose to both conditions. Tet spells Infants and children with unrepaired tetralogy of Fallot may develop "tet spells". These are acute hypoxia spells, characterized by shortness of breath, cyanosis, agitation, and loss of consciousness.: 200  This may be initiated by any event – such as anxiety, pain, dehydration, or fever – leading to decreased oxygen saturation or that causes decreased systemic vascular resistance, which in turn leads to increased shunting through the ventricular septal defect. Typically, these spells decrease in frequency after the first four years of life.Clinically, tet spells are characterized by a sudden, marked increase in cyanosis followed by syncope.: 200 Older children will often squat instinctively during a tet spell. This increases systemic vascular resistance and allows for a temporary reversal of the shunt. It increases pressure on the left side of the heart, decreasing the right to left shunt, thus decreasing the amount of deoxygenated blood entering the systemic circulation. Cause While the specific causes of TOF have not been fully identified, there are various environmental or genetic factors that have been associated with TOF. So far, around 20% of overall CHD cases have been due to known causes such as genetic defects and teratogens which are various factors causing embryo development abnormalities or birth defects. However, the other 80% of cases have little known about their cause.Genetic factors linked to TOF include various gene mutations or deletions. Gene deletions associated with TOF include chromosome 22 deletion as well as DiGeorge syndrome.Specific genes associations with TOF include: JAG1 codes for ligands within the Notch family of proteins and is highly expressed in the developing heart. Mutations of the JAG1 gene can lead to abnormal heart development associated with TOF. NKX2-5 codes for cardiac morphogenesis regulators to allow for proper heart development. Defects in this gene typically causes septal defects and has been associated with around 4% of all TOF cases. ZFPM2 is another cardiac regulator involved in regulation of GATA4. Mutations of the ZFPM2 gene lead to reduced GATA production and have been seen in some TOF cases. VEGF a well-known endothelial growth factor involved in the vascularization of the heart. Decreased VEGF expression has been shown to be a modifier of TOF. NOTCH1 is involved in the vascularization of tissues and is the most common site of genetic variations involved with TOF, accounting for 7% of all TOF cases. TBX1 expresses progenitors involved with the development of the right ventricle. Chromosome 22q11 deletions also deleting TBX1 gene have been seen in 17% TOF cases. FLT4 gene expression leads to Vascular endothelial growth factor receptor 3 (VEGFR-3) which helps vascularization. Mutations of this gene have been associated with TOF, accounting for 2.4% of all cases. FOXC2 is another gene involved in embryonic development of the cardiac system. Mutations of this gene have been shown to result in dysfunctional lymphatic syndrome and TOF. GATA4 aids in cardiac development by helping increase the production of cardiomyocytes. Mutations of this gene have been seen in various familial TOF cases often lasting 2-3 generations. FLNA is a protein coded by the gene of the same name that crosslinks actin filaments into networks in cytoplasm and helps anchor membrane proteins for the actin cytoskeleton. Mutations of this gene were seen to cause TOF in some patients.The Environmental Factors that have been studied to potentially be associated TOF include: Maternal Alcohol consumption: During embryonic development, many of the body’s processing and filtration systems are not fully developed. Fetal body is unable to process alcohol as well as adults which can lead to improper development, including cardiogenesis. While no conclusive evidence has been found between effects of alcohol consumption and TOF, maternal alcohol consumption has been seen in various patients with TOF. Maternal smoking: Maternal smoking has been associated with various fetal complications such as premature delivery and low birth weight which can lead to TOF. In the famous Baltimore-Washington Study, it was reported that smoking more than one pack per day while pregnant was associated with two specific cardiac deflects, both part of TOF: pulmonary stenosis and transposition with VSD. Maternal diabetes: Maternal diabetes, diabetes Mellitus, and gestational diabetes are well-known risk factors of fetal CHD, including TOF. Maternal diabetes has been shown to increase the risk of cardiovascular deformations, namely the transposition of great arteries, one of the four deformations in TOF. Studies have also looked at whether diabetes increases the risk of malformation or poor sugar regulation and have found that sugar regulation does not significantly affect cardiac malformations. Retrospective studies have shown that diabetic mothers with good glucose control still retained the elevated CHD risk. Rubella: Rubella is characterized as mild, contagious viral disease with often unnoticed consequences. Infection with rubella during the first trimester has been seen to cause various fetal malformations, including TOF. Maternal Age: Older maternal age, especially after 35 can have various pregnancy risks due to existing co-morbidities such as hypertension, diabetes, hypothyroidism, and consanguinity. These risk factors can effect fetal development and lead to various fetal conditions such as CHD (including TOF), Down Syndrome and Autism.Embryology studies show that anterior malalignment of the aorticopulmonary septum results in the clinical combination of a ventricular septal defect (VSD), pulmonary stenosis, and an overriding aorta.: 200  Right ventricular hypertrophy develops progressively from resistance to blood flow through the right ventricular outflow tract. Pathophysiology In healthy individuals, the human heart develops around the 20th day of gestation, when the outer endocardial tubes merge into a single cardiac tube. Thereafter, the cardiac tube begins to fold, developing into the atrium and ventricle. The right ventricle is dominant prior to birth, receiving 65% of the venous return to the heart, and is the main contributor of blood flow to the lower part of the body, the placenta, and the lungs. Though the exact cause of TOF is unknown, an association that has been observed is an anterior deviation of the infundibular septum that results in a misaligned VSD, with an overriding aorta causing a subsequent right ventricular obstruction.Different factors such as pulmonary stenosis can also contribute with the right ventricular outflow obstruction. During tet spells, a decrease in systemic vascular resistance or an increase in pulmonary resistance would be physiologically observed. The main anatomic defect in TOF is the anterior deviation of the pulmonary outflow septum. This defect results in narrowing of the right ventricular outflow tract (RVOT), override of the aorta, and a VSD. Four malformations "Tetralogy" denotes four parts, here implying the syndromes four anatomic defects. This is not to be confused with the similarly named teratology, a field of medicine concerned with abnormal development and congenital malformations (including tetralogy of Fallot). Below are the four heart malformations that present together in tetralogy of Fallot: There is anatomic variation between the hearts of individuals with tetralogy of Fallot. Primarily, the degree of right ventricular outflow tract obstruction varies between patients and generally determines clinical symptoms and disease progression.Presumably, this arises from an unequal growth of the aorticopulmonary septum (aka pulmonary outflow septum).: 199  The aorta is too large, thus "overriding," and this "steals" from the pulmonary artery, which is therefore stenosed. This then prevents ventricular wall closure, therefore VSD, and this increases the pressures on the right side, and so the R ventricle becomes bigger to handle the work.: 199 Additional anomalies In addition, tetralogy of Fallot may present with other anatomical anomalies, including:: 66–8  stenosis of the left pulmonary artery, in 40% a bicuspid pulmonary valve, in 60% right-sided aortic arch, in 25% coronary artery anomalies, in 10% a patent foramen ovale or atrial septal defect, in which case the syndrome is sometimes called a pentalogy of Fallot an atrioventricular septal defect partially or totally anomalous pulmonary venous returnTetralogy of Fallot with pulmonary atresia (pseudotruncus arteriosus) is a severe variant in which there is complete obstruction (atresia) of the right ventricular outflow tract, causing an absence of the pulmonary trunk during embryonic development.: 67–8  In these individuals, blood shunts completely from the right ventricle to the left where it is pumped only through the aorta. The lungs are perfused via extensive collaterals from the systemic arteries, and sometimes also via the ductus arteriosus.: 67–8 Diagnosis There are three different useful diagnostic tests used for the diagnosis of tetralogy of Fallot. These include a chest radiograph, electrocardiogram, and echocardiogram. The echocardiography determines the final diagnosis and typically offers enough information for surgical treatment planning. About half of all patients are now diagnosed before they are born. Differential diagnosis is when physicians diagnose between two or more conditions for a persons symptoms and this can include primary pulmonary causes of cyanosis, cyanotic heart lesions, pulmonary stenosis and transposed arterial trunks. Chest radiograph Before more sophisticated techniques became available, chest X-ray was the definitive method of diagnosis. The abnormal "coeur-en-sabot" (boot-like) appearance of a heart with tetralogy of Fallot is classically visible via chest X-ray, although most infants with tetralogy may not show this finding. The boot like shape is due to the right ventricular hypertrophy present in TOF. Lung fields are often dark (absence of interstitial lung markings) due to decreased pulmonary blood flow.: 171–72 Electrocardiogram An electrocardiogram (ECG) is one of the most basic procedures for assessing the heart. Tiny electrodes are applied to specific areas on the body, near the chest, arm, and neck. Lead cables connect the electrodes to an ECG machine. The hearts electrical activity is then measured. Natural electrical impulses help maintain blood flowing properly by coordinating contractions in different areas of the heart. These impulses are recorded by an ECG, which shows how fast, the rhythm, intensity and timing of the electrical impulses as they travel through the heart.Electrocardiography shows right ventricular hypertrophy (RVH), along with right axis deviation. RVH is noted on EKG as tall R-waves in lead V1 and deep S-waves in lead V5-V6. Echocardiogram Congenital heart defects are now diagnosed with echocardiography, which is quick, involves no radiation, is very specific, and can be done prenatally.Echocardiography establishes the presence of TOF by demonstrating a VSD, RVH, and aortic override. Many patients are diagnosed prenatally. Color Doppler (type of echocardiography) measures the degree of pulmonary stenosis. Additionally, close monitoring of the ductus arteriosus is done in the neonatal period to ensure that there is adequate blood flow through the pulmonary valve.: 171–72 In certain cases, coronary artery anatomy cannot be clearly viewed using echocardiogram. In this case, cardiac catheterization can be done.: 37, 201 Genetics From a genetics perspective, it is important to screen for DiGeorge in all babies with TOF.: 37, 201 Treatment Tet spells Tet spells are defined as cyanotic spells occurring due to the obstruction right ventricular outflow. Tet spells can be triggered by various factors such as crying, progressive tachypnea, and deep breathing, with symptoms including but not limited to blue skin, nails and lips, profound crying and difficulty breathing.Tet spells may be treated with beta-blockers such as propranolol, but acute episodes require rapid intervention with morphine or intranasal fentanyl to reduce ventilatory drive, a vasopressor such as phenylephrine, or norepinephrine to increase systemic vascular resistance, and IV fluids for volume expansion.: 18, 201 Oxygen (100%) may be effective in treating spells because it is a potent pulmonary vasodilator and systemic vasoconstrictor. This allows more blood flow to the lungs by decreasing shunting of deoxygenated blood from the right to left ventricle through the VSD. There are also simple procedures such as squatting and the knee chest position which increase systemic vascular resistance and decrease right-to-left shunting of deoxygenated blood into the systemic circulation.: 18, 201 If the spells are refractory to the above treatments, people are usually intubated and sedated. The treatment of last resort for tet spells is extracorporeal membrane oxygenation (ECMO) along with consideration of Blalock Taussig shunt (BT shunt).: 18, 201 Total surgical repair Total surgical repair of TOF is a curative surgery. Different techniques can be used in performing TOF repair. However, a transatrial, transpulmonary artery approach is used for most cases.: 153  The repair consists of two main steps: closure of the VSD with a patch and reconstruction of the right ventricular outflow tract.This open-heart surgery is designed to relieve the right ventricular outflow tract stenosis by careful resection of muscle and to repair the VSD.: 154 The right ventricle outflow tract can be reconstructed using mainly 2 procedures: a transannular patch (TAP) or a pulmonary valve-sparing procedure (PVS). The decision on the type of the procedure depends on individual anatomy (especially the size of the pulmonary valve). PVS showed better overall survival, event-free survival and less pulmonary regurgitation at 10, 20 and 30 years after the operation. PVS can be performed with or without ventriculotomy. A study found similar overall and event-free survival and pulmonary regurgitation rate between patients who underwent PVS with ventriculotomy and the ones who did not.Additional reparative or reconstructive surgery may be done on patients as required by their particular cardiac anatomy.: 153 Timing of surgery in asymptomatic patients is usually between the ages of two months to one year.: 201–2  However, in symptomatic patients showing worsening blood oxygen levels, severe tet-spells (cyanotic spells), or dependence on prostaglandins from early neonatal period (to keep the ductus arteriosus open) need to be planned fairly urgently: 201–2 Potential surgical repair complications include residual ventricular septal defect, residual outflow tract obstruction, complete atrioventricular block, arrhythmias, aneurysm of right ventricular outflow patch, and pulmonary valve insufficiency.: 59  Long-term complications most commonly include pulmonary valve regurgitation, and arrhythmias.Total repair of tetralogy of Fallot initially carried a high mortality risk, but this risk has gone down steadily over the years. Surgery is now often carried out in infants one year of age or younger with less than 5% perioperative mortality.: 205  Post surgery, most patients enjoy an active life free of symptoms.: 205  Currently, long-term survival is close to 90%.: 167  Today the adult TOF population continues to grow and is one of the most common congenital heart defects seen in adult outpatient clinics.: 100–101 Palliative surgery Initially surgery involved forming a side to end anastomosis between the subclavian artery and the pulmonary artery -i.e. a systemic to pulmonary arterial shunt.: 57  This redirected a large portion of the partially oxygenated blood leaving the heart for the body into the lungs, increasing flow through the pulmonary circuit, and relieving symptoms. The first Blalock-Thomas-Taussig shunt surgery was performed on 15-month-old Eileen Saxon on November 29, 1944 with dramatic results.The Potts shunt and the Waterston-Cooley shunt are other shunt procedures which were developed for the same purpose. These are no longer used. Currently, palliative surgery is not normally performed on infants with TOF except for extreme cases.: 173  For example, in symptomatic infants, a two-stage repair (initial systemic to arterial shunt placement followed by total surgical repair) may be done. Potential complications include inadequate pulmonary blood flow, pulmonary artery distortion, inadequate growth of the pulmonary arteries, and acquired pulmonary atresia.: 59 Approaches to surgical repair After years of tetralogy of Fallot surgical repair expertise, the attention shifted to the emerging evidence that long-term pulmonary insufficiency is detrimental to right ventricular function and clinical prognosis. As a result, the hunt for surgical procedures to relieve right ventricular outflow tract obstruction while minimizing pulmonary regurgitation has intensified.A constrained right ventricular outflow tract reconstruction with a Dacron patch matched to a nominal pulmonary annulus expansion or an annulus-sparing approach yielded primary complete repair outcomes in 94 TOF infants. The pulmonary annulus size was larger in babies treated with the latter technique, as predicted. After an average follow-up of around eight years, the first group had a higher than moderate PR, yet there was no significant difference in independence from severe PR after ten years.Furthermore, there was no significant difference in right ventricular dilation between the two techniques. Finally, they found that reconstructing the pulmonary annulus in TOF with only a tiny transannular incision and a stiff Dacron patch to inhibit pulmonary annulus extension throughout the normal growing phase produces the same long-term benefits as preserving the full pulmonary annulus integrity. Complications Short-term Residual ventricular septal defects and persistent right ventricular outflow blockage are common problems in the immediate postoperative period. Arrhythmias such as ventricular tachycardia, atrial fibrillation/flutter, and intra-atrial re-entrant tachycardia can occur after tetralogy repair. With broad complex tachycardia, the ECG will likely show a right bundle branch block or left bundle branch block patterns. Patients who have had their hearts repaired may experience sudden cardiac death. Risk factors for abnormal heart rhythms include: Age (at repair) Male gender Transient complete heart block beyond post operative day three QRS duration greater than 180 milliseconds Long-term Adult patients with congenital cardiac disease are on the rise at a rate of about 5% per year, outpacing the pediatric population. Right ventricular volume overload form pulmonary insufficiency, right ventricular aneurysm from outflow patch or ventriculotomy, distal pulmonary artery obstruction, ventricular hypertrophy, chamber enlargement, biventricular dysfunction, and aortic root dilation and insufficient are all long-term complications seen in these patients. Arrhythmia, heart failure, and complications from reoperations are the three primary causes of death in individuals with corrected tetralogy of Fallot. QRS duration greater than 180 milliseconds, older age at repair (greater than three years), significant pulmonary valve or tricuspid valve regurgitation, history of syncope, multifocal premature ventricular contractions, and ventricular tachycardia are some of the factors associated with sudden death after 30 years of procedure. Pulmonary insufficiency is the most common reason for reoperation, and pulmonary valve replacement criteria have traditionally been based on the severity of the regurgitant fraction on a magnetic resonance or CT scan. Right and left ventricular end-systolic and end-diastolic volume indices, ejection fractions, and the existence of aneurysm generating obstructive outflow are all parameters seen in this research. Exercise intolerance, heart failure signs and symptoms, syncope, and prolonged ventricular tachycardia are all possible symptoms. A transcatheter pulmonary valve method can also be used to replace a pulmonary valve. Pregnancy In comparison to the general obstetric population, women who had their tetralogy of Fallot repaired completely have similar outcomes. The degree of pulmonary regurgitation with right or left ventricular dysfunction, as well as the level of pulmonary hypertension, are linked to an increased risk of pregnancy complications. Fetal death is more likely in women who have moderate right ventricular hypertension or who have undergone a palliative shunt. In comparison to 0.8% of the general population, offspring of women with tetralogy have a 3–5% chance of developing congenital cardiac disease. If the 22q11 deletion is present, there is a 50% chance of transferring the damaged chromosome, with a high risk of a congenital cardiac abnormality. Prognosis Untreated, tetralogy of Fallot rapidly results in progressive right ventricular hypertrophy due to the increased resistance caused by narrowing of the pulmonary trunk.: 199  This progresses to heart failure which begins in the right ventricle and often leads to left heart failure and dilated cardiomyopathy. Mortality rate depends on the severity of the tetralogy of Fallot. If left untreated, TOF carries a 35% mortality rate in the first year of life, and a 50% mortality rate in the first three years of life. Patients with untreated TOF rarely progress to adulthood.Patients who have undergone total surgical repair of tetralogy of Fallot have improved hemodynamics and often have good to excellent cardiac function after the operation with some to no exercise intolerance (New York Heart Association Class I-II). Long-term outcome is usually excellent for most patients, however residual post-surgical defects such as pulmonary regurgitation, pulmonary artery stenosis, residual VSD, right ventricular dysfunction, right ventricular outflow tract obstruction may affect life expectancy and increase the need for reoperation.: 205 Cardiovascular and cerebrovascular complications in patients with repaired CHD such as TOF occur earlier in life compared to healthy subjects. Chronic pulmonary regurgitation and right ventricular dilation and dysfunction is also common.Within 30 years after correction, 50% of patients will require reoperation. The most common cause of reoperation is a leaky pulmonary valve (pulmonary valve insufficiency). This is usually corrected with a procedure called pulmonary valve replacement.: 136 One common prognostic factor with TOF is the development of ischemia reperfusion injury. Insufficient myocardial protection is considered one of the main causes of death in the correction of TOF. Comorbidities There are many comorbid conditions that can occur with TOF that may exacerbate the condition. Often, TOF can present with low birth weight and prematurity. In both of these cases, mortality and morbidity were both seen to increase. Differences in right atrial and ventricular mechanics and liver stiffness was also observed in adults with repaired TOF, as well as pulmonary atresia and persistent pulmonary stenosis. In patients with pulmonary atresia, there is complete failure of forward flow from the right ventricle to the pulmonary arterial vasculature. As such, pulmonary blood flow is entirely dependent on shunting from the systemic circulation, typically through a patent ductus arteriosus. The pathophysiology of TOF together with pulmonary arteriosus is uniquely attributable to defects of the pulmonary arteries. Even after operative care, these patients remain at higher risk for pulmonary arterial stenoses and pulmonary hypertension.Danon disease, which is a rare genetic disorder, was also observed to complicate TOF. In particular, elongation of the QRS complex and a shortened PR interval. Genetic abnormalities found in TOF may lead to the earlier diagnosis of Danon disease, helping to improve prognostic outcomes. Epidemiology The prevalence of tetralogy of Fallot is estimated to be 0.02–0.04%, which corresponds to approximately 200 to 400 cases per million live births. It accounts for 7–10% of all congenital heart abnormalities, making it the most common cyanotic heart defect.: 100–101  Although males and females were initially believed to be affected equally, more recent studies have shown TOF affects males more than females. About 1 in 100 newborns is diagnosed with a congential heart defect, of which 10% are diagnosed with TOF. Genetically, it is most commonly associated with Down syndrome and DiGeorge syndrome. Down syndrome and other chromosomal disorders are known to occur alongside congential heart defects such as TOF. History Tetralogy of Fallot was initially described in 1671 by the Danish researcher Niels Steensen. Also referenced as Nicolaus Steno in Latin, Stensen was a pioneer in anatomy and geology. His work made significant contributions to the field of cardiac anatomy and pathology, which led to the condition initially being titled Steno-Fallot tetralogy. A further description was published in 1888 by the French physician Étienne-Louis Arthur Fallot, after whom it was ultimately named. In 1924, Maude Elizabeth Seymour Abbott, a pediatric cardiologist from Montreal, Canada, named it tetralogy of Fallot.The short paper "Dissection of a Monstrous Foetus in Paris" in 1671 first described the conditions that would later together be known as TOF. In particular, it highlighted the unusual formation of arteries, the stenosing of the pulmonary artery, the absence of the ductus arteriosus, an overriding aorta, and fetal cardiac circulation where blood was redirected to the aorta from the pulmonary artery. Over a hundred years later in 1777, Dutch physician Eduard Sandifort reported what he referred to as "the blue boy" patient. This patient, who was 16 months old, was initially thought to have asthma, though an autopsy postmortem revealed a cardiac malformation with no ductus arteriosus or ligamentum arteriosum, indicating that the child may have died from TOF. Another 13-year-old patient was reported by Scottish physician William Hunter in 1782. Hunter described the patient, along with three others, as suffering from cyanosis after a posthumous examination in 1774.Other cases, such as those presented by Pulteney (1785), Abernethy (1793), Bell (1797), Dorsey (1812), and Farre (1814) also contributed to modern understandings of TOF. The first reported case of TOF was in America at the University of Pennsylvania in 1816, with more cases being reported by Peacock (1858 and 1869), Widman (1881), and finally Fallot (1888), after whom the condition is named. Fallot was the first to elegantly describe the four key features that differentiate it from other cyanotic cardiac conditions, and was prominent in the disqualification of a patent foramen ovale as a fifth feature. Fallot initially referred to it as "La maladie bleue", which is French for "the blue disease" or "cyanose cardiaque", translating to "cardiac cyanosis".The first surgical repair was carried out in 1944 at Johns Hopkins. The procedure was conducted by surgeon Alfred Blalock and cardiologist Helen B. Taussig, with Vivien Thomas also providing substantial contributions and listed as an assistant. This first surgery was depicted in the film Something the Lord Made. It was actually Helen Taussig who convinced Alfred Blalock that the shunt was going to work. 15-month-old Eileen Saxon was the first person to receive a Blalock–Thomas–Taussig shunt. Furthermore, the Blalock-Thomas-Taussig procedure, initially the only surgical treatment available for tetralogy of Fallot, was palliative but not curative. The first total repair of tetralogy of Fallot was done by a team led by C. Walton Lillehei at the University of Minnesota in 1954 on an 11-year-old boy. Total repair on infants has had success from 1981, with research indicating that it has a comparatively low mortality rate. Today the adult TOF population continues to grow and is one of the most common congenital heart defect seen in adult outpatient clinics.: 100–101 Related disorders The following illnesses have symptoms that are comparable to tetralogy of Fallot. For a differential diagnosis, comparisons between these disorders provides valuable knowledge. Atrial septal defects Atrial septal defects (ASDs) are a kind of congenital heart abnormality in which a tiny opening exists between the two atria of the heart. The burden on the right side of the heart is increased as a result of these abnormalities, as is the blood flow to the lungs. This leads to excessive blood flow to the lungs and an increased workload on the right side of the heart. Another common finding associated with ASDs is right ventricular hypertrophy, also known as enlargement of the right ventricle. Ventricular septal defects Ventricular septal defects (VSDs) are a kind of congenital heart abnormality in which one of the ventricles is missing. Two atria and one big ventricle are common in infants with congenital abnormalities. Symptoms of these diseases include an unusually high rate of breathing (tachypnea), a blue hue to the skin (cyanosis), wheezing, a rapid heartbeat (tachycardia), and/or an abnormally enlarged liver, which are similar to those of other congenital heart problems (hepatomegaly). VSDs can also lead to a build-up of fluid around the heart, which can lead to congestive heart failure. Atrioventricular septal defect Atrioventricular septal defect (AVSD) is an uncommon congenital heart condition characterized by faulty development of the hearts septa and valves. Congestive heart failure is common in infants with the entire version of the condition. Fluid builds up in other parts of the body, particularly the lungs. Breathing difficulties may result from pulmonary congestion (dyspnea). Mitral valve stenosis Mitral valve stenosis is an uncommon cardiac abnormality that can occur at birth (congenital) or develop later in life (acquired). The aberrant narrowing of the mitral valves opening characterizes this condition. There are two versions of this condition known as congenital and acquired characterized by different symptoms. Congenital Mitral valve stenosis symptoms include a wide array such as respiratory infections, breathing difficulties, heart palpitations and coughing. Acquired mitral valve stenosis symptoms also include a wide array such as consciousness losses, angina, general weakness and abdominal discomfort. Notable cases Shaun White, American professional snowboarder and skateboarder Beau Casson, Australian cricketer Dennis McEldowney, New Zealand author and publisher Max Page, Volkswagens "Little Darth Vader" from the 2011 Super Bowl commercial Billy Kimmel, the son of talk show host Jimmy Kimmel; Billys diagnosis led Kimmel to discuss access to health care on his show Jimmy Kimmel Live! See also Trilogy of Fallot Congenital rubella syndrome References External links What Is Tetralogy of Fallot? at the National Institutes of Health Understanding your childs heart: Tetralogy of Fallot by the British Heart Foundation

Chronic granulomatous disease

Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds (most importantly the superoxide radical due to defective phagocyte NADPH oxidase) used to kill certain ingested pathogens. This leads to the formation of granulomas in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.This condition was first discovered in 1950 in a series of 4 boys from Minnesota, and in 1957 it was named "a fatal granulomatosus of childhood" in a publication describing their disease. The underlying cellular mechanism that causes chronic granulomatous disease was discovered in 1967, and research since that time has further elucidated the molecular mechanisms underlying the disease. Bernard Babior made key contributions in linking the defect of superoxide production of white blood cells, to the cause of the disease. In 1986, the X-linked form of CGD was the first disease for which positional cloning was used to identify the underlying genetic mutation. Symptoms and signs Classically, patients with chronic granulomatous disease will have recurrent bouts of infection due to the decreased capacity of their immune system to fight off disease-causing organisms. The recurrent infections they acquire are specific and are, in decreasing order of frequency: pneumonia abscesses of the skin, tissues, and organs septic arthritis osteomyelitis bacteremia/fungemia superficial skin infections such as cellulitis or impetigoMost people with CGD are diagnosed in childhood, usually, before age 5. Early diagnosis is important since these people can be placed on antibiotics to ward off infections before they occur. Small groups of CGD patients may also be affected by McLeod syndrome because of the proximity of the two genes on the same X-chromosome. Atypical infections People with CGD are sometimes infected with organisms that usually do not cause disease in people with normal immune systems. Among the most common organisms that cause disease in CGD patients are: Bacteria (particularly those that are catalase-positive)Staphylococcus aureus. Serratia marcescens. Listeria species. E. coli. Klebsiella species. Pseudomonas cepacia, a.k.a. Burkholderia cepacia. Nocardia. Fungi Aspergillus species. Aspergillus has a propensity to cause infection in people with CGD and of the Aspergillus species, Aspergillus fumigatus seems to be most common in CGD. Candida species.Patients with CGD can usually resist infections of catalase-negative bacteria but are susceptible to catalase-positive bacteria. Catalase is an enzyme that catalyzes the breakdown of hydrogen peroxide in many organisms. In infections caused by organisms that lack catalase (catalase-negative), the host with CGD is successfully able to "borrow" hydrogen peroxide being made by the organism and use it to fight off the infection. In infections by organisms that have catalase (catalase-positive), this "borrowing mechanism" is unsuccessful because the enzyme catalase first breaks down any hydrogen peroxide that would be borrowed from the organism. Therefore in the CGD patient, hydrogen peroxide cannot be used to make oxygen radicals to fight infection, leaving the patient vulnerable to infection by catalase-positive bacteria. Genetics Most cases of chronic granulomatous disease are transmitted as a mutation on the X chromosome and are thus called an "X-linked trait". The affected gene on the X chromosome codes for the gp91 protein p91-PHOX (91 is the weight of the protein in kDa; the gp means glycoprotein). CGD can also be transmitted in an autosomal recessive fashion (via CYBA, NCF1, NCF2 and NCF4) which affect other PHOX proteins. The type of mutation that causes both types of CGD are varied and may be deletions, frame-shift, nonsense, and missense.A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD. This has been reported in women who are homozygous for the genetic defect causing glucose-6-phosphate dehydrogenase deficiency (G6PD), which is characterised by reduced NADPH levels. Pathophysiology Phagocytes (i.e. neutrophils and macrophages) require an enzyme to produce reactive oxygen species to destroy bacteria after they are ingested (phagocytosis), a process known as the respiratory burst. This enzyme is termed "phagocyte NADPH oxidase" (PHOX). This enzyme oxidizes NADPH and reduces molecular oxygen to produce superoxide anions, a reactive oxygen species. Superoxide is then disproportionated into peroxide and molecular oxygen by superoxide dismutase. Finally, peroxide is used by myeloperoxidase to oxidize chloride ions into hypochlorite (the active component of bleach), which is toxic to bacteria. Thus, NADPH oxidase is critical for phagocyte killing of bacteria through reactive oxygen species.(Two other mechanisms are used by phagocytes to kill bacteria: nitric oxide and proteases, but the loss of ROS-mediated killing alone is sufficient to cause chronic granulomatous disease.)Defects in one of the four essential subunits of phagocyte NADPH oxidase (PHOX) can all cause CGD of varying severity, dependent on the defect. There are over 410 known possible defects in the PHOX enzyme complex that can lead to chronic granulomatous disease. Diagnosis When chronic granulomatous disease (CGD) is suspected, neutrophil-function testing should be carried out, and positive findings should be confirmed by genotyping. The p47phox mutation is due to a pseudogene conversion, hence it may not be detectable by standard sequencing; in these cases, an immunoblot or gene dose determination may be needed to confirm p47phox deficiency.Infections caused by the pathogens commonly associated with CGD should prompt functional or genetic screening; neonatal or early postnatal screening of potentially affected children is essential with a family history of CGD.Neutrophil function tests: These include nitroblue tetrazolium (NBT) reduction test, dihydrorhodamine (DHR) 123 test, direct measurement of superoxide production, cytochrome c reduction assay, and chemiluminescence. DHR test is usually preferred because it is easy to use, objective, and it is able to distinguish between X-linked and autosomal forms of CGD; furthermore, it allows to detect gp91phox carriers. The nitroblue-tetrazolium (NBT) test is the original and most widely known test for chronic granulomatous disease. It is negative in CGD, meaning that it does not turn blue. The higher the blue score, the better the cell is at producing reactive oxygen species. This test depends upon the direct reduction of NBT to the insoluble blue compound formazan by superoxide which is produced by normal peripheral blood neutrophils stimulated in vitro; NADPH oxidase catalyzes the aforementioned reaction and NADPH is oxidized in the same reaction. This test is simple to perform and gives rapid results but only tells whether or not there is a problem with the PHOX enzymes, not how much they are affected. Dihydrorhodamine (DHR) 123 test: In this test the respiratory burst of the neutrophils is stimulated with phorbol myristate acetate (PMA), resulting in oxidation of dihydrorhodamine 123 (nonfluorescent derivative of rhodamine) to rhodamine 123 (green fluorescent compound), which can be measured by flow cytometry. This test is abnormal in patients with chronic granulomatous disease (i.e., there is no shift in fluorescence with stimulation). Moreover, its quantitative nature allows to differentiate oxidase-positive from oxidase-negative phagocyte subpopulations in CGD carriers and identify deficiencies in gp91phox and p47phox. Modest residual production of reactive oxygen intermediates (ROI) as assessed by DHR 123 test, is associated with significantly less severe illness and a greater likelihood of long-term survival than patients with little residual ROI production. On the other hand, in the case of complete myeloperoxidase deficiency, DHR test gives abnormal results (false positive for CGD) because the DHR signal yielded by flow cytometry depends on intact NADPH oxidase activity as well as the presence of a myeloperoxidase (MPO); however, NBT test demonstrates normal production of superoxide.Genetic testing: Once CGD has been diagnosed based on abnormal neutrophil function tests, genetic testing should go next. As mentioned above, p47phox defect is usually difficult to identify genetically because it is caused by pseudogene conversion and may be missed in typical sequencing studies; in this case, immunoblotting or flow cytometry can show absence of protein.Prenatal testing: It is particularly useful when a family member has already been diagnosed with CGD. This test may be performed by analysis of NADPH oxidase activity of neutrophils from fetal blood. Samples from amniotic fluid or chorionic villi provides an earlier and more reliable diagnosis for families at risk. Classification Chronic granulomatous disease is the name for a genetically heterogeneous group of immunodeficiencies. The core defect is a failure of phagocytic cells to kill organisms that they have engulfed because of defects in a system of enzymes that produce free radicals and other toxic small molecules. There are several types, including: X-linked chronic granulomatous disease (CGD) autosomal recessive cytochrome b-negative CGD autosomal recessive cytochrome b-positive CGD type I autosomal recessive cytochrome b-positive CGD type II atypical granulomatous disease Treatment Management of chronic granulomatous disease revolves around two goals: 1) diagnose the disease early so that antibiotic prophylaxis can be given to keep an infection from occurring, and 2) educate the patient about his or her condition so that prompt treatment can be given if an infection occurs. Antibiotics Physicians often prescribe the antibiotic trimethoprim-sulfamethoxazole to prevent bacterial infections. This drug also has the benefit of sparing the normal bacteria of the digestive tract. Fungal infection is commonly prevented with itraconazole, although a newer drug of the same type called voriconazole may be more effective. The use of this drug for this purpose is still under scientific investigation. Immunomodulation Interferon, in the form of interferon gamma-1b (Actimmune) is approved by the Food and Drug Administration for the prevention of infection in CGD. It has been shown to reduce infections in CGD patients by 70% and to decrease their severity. Although its exact mechanism is still not entirely understood, it has the ability to give CGD patients more immune function and therefore, greater ability to fight off infections. This therapy has been the standard treatment for CGD for several years. Hematopoietic stem cell transplantation (HSCT) Hematopoietic stem cell transplantation from a matched donor is curative although not without significant risk. Prognosis There are currently no studies detailing the long term outcome of chronic granulomatous disease with modern treatment. Without treatment, children often die in the first decade of life. The increased severity of X-linked CGD results in a decreased survival rate of patients, as 20% of X-linked patients die of CGD-related causes by the age of 10, whereas 20% of autosomal recessive patients die by the age of 35. Recent experience from centers specializing in the care of patients with CGD suggests that the current mortality has fallen to under 3% and 1% respectively. CGD was initially termed "fatal granulomatous disease of childhood" because patients rarely survived past their first decade in the time before routine use of prophylactic antimicrobial agents. The average patient now survives at least 40 years. Epidemiology CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.Chronic granulomatous disease affects all people of all races, however, there is limited information on prevalence outside of the United States. One survey in Sweden reported an incidence of 1 in 220,000 people, while a larger review of studies in Europe suggested a lower rate: 1 in 250,000 people. History This condition was first described in 1954 by Janeway, who reported five cases of the disease in children. In 1957 it was further characterized as "a fatal granulomatosus of childhood". The underlying cellular mechanism that causes chronic granulomatous disease was discovered in 1967, and research since that time has further elucidated the molecular mechanisms underlying the disease. Use of antibiotic prophylaxis, surgical abscess drainage, and vaccination led to the term "fatal" being dropped from the name of the disease as children survived into adulthood. Research Gene therapy is currently being studied as a possible treatment for chronic granulomatous disease. CGD is well-suited for gene therapy since it is caused by a mutation in single gene which only affects one body system (the hematopoietic system). Viruses have been used to deliver a normal gp91 gene to rats with a mutation in this gene, and subsequently the phagocytes in these rats were able to produce oxygen radicals.In 2006, two human patients with X-linked chronic granulomatous disease underwent gene therapy and blood cell precursor stem cell transplantation to their bone marrow. Both patients recovered from their CGD, clearing pre-existing infections and demonstrating increased oxidase activity in their neutrophils. However, long-term complications and efficacy of this therapy were unknown.In 2012, a 16-year-old boy with CGD was treated at the Great Ormond Street Hospital, London with an experimental gene therapy that temporarily reversed the CGD and allowed him to overcome a life-threatening lung disease. References == External links ==

Laryngomalacia

Laryngomalacia (literally, "soft larynx") is the most common cause of chronic stridor in infancy, in which the soft, immature cartilage of the upper larynx collapses inward during inhalation, causing airway obstruction. It can also be seen in older patients, especially those with neuromuscular conditions resulting in weakness of the muscles of the throat. However, the infantile form is much more common. Laryngomalacia is one of the most common laryngeal congenital disease in infancy and public education about the signs and symptoms of the disease is lacking. Signs and symptoms In infantile laryngomalacia, the supraglottic larynx (the part above the vocal cords) is tightly curled, with a short band holding the cartilage shield in the front (the epiglottis) tightly to the mobile cartilage in the back of the larynx (the arytenoids). These bands are known as the aryepiglottic folds. The shortened aryepiglottic folds cause the epiglottis to be curled on itself. This is the well known "omega shaped" epiglottis in laryngomalacia. Another common finding of laryngomalacia involves the posterior or back part of the larynx, where the arytenoid cartilages or the mucosa/tissue over the arytenoid cartilages can collapse into the airway and cause airway obstruction.Laryngomalacia results in partial airway obstruction, most commonly causing a characteristic high-pitched squeaking noise on inhalation (inspiratory stridor). Some infants have feeding difficulties related to this problem. Rarely, children will have significant life-threatening airway obstruction. The vast majority, however, will only have stridor without other more serious symptoms such as dyspnea (difficulty breathing). Causes Although laryngomalacia is not associated with a specific gene, there is evidence that some cases may be inherited. Relaxation or a lack of muscle tone in the upper airway may be a factor. It is often worse when the infant is on his or her back, because the floppy tissues can fall over the airway opening more easily in this position. Diagnosis The physician will ask some questions about the babys health problems and may recommend a flexible laryngoscopy to further evaluate the infants condition. Additional testing can be done to confirm the diagnoses including; flexible fiberoptic laryngoscopy, airway fluoroscopy, direct laryngoscopy and bronchoscopy. Treatment Time is the only treatment necessary in more than 90% of infant cases. In other cases, surgery may be necessary. Most commonly, this involves cutting the aryepiglottic folds to let the supraglottic airway spring open. Trimming of the arytenoid cartilages or the mucosa/ tissue over the arytenoid cartilages can also be performed as part of the supraglottoplasty. Supraglottoplasty can be performed bilaterally (on both the left and right sides at the same time), or be staged where only one side is operated on at a time.Treatment of gastroesophageal reflux disease can also help in the treatment of laryngomalacia, since gastric contents can cause the back part of the larynx to swell and collapse even further into the airway. In some cases, a temporary tracheostomy may be necessary. Prognosis Laryngomalacia becomes symptomatic after the first few months of life (2–3 months), and the stridor may get louder over the first year, as the child moves air more vigorously. Most of the cases resolve spontaneously and fewer than 15% of the cases will need surgical intervention. Parents need to be supported and educated about the condition. Epidemiology Although this is a congenital lesion, airway sounds typically begin at age 4–6 weeks. Until that age, inspiratory flow rates may not be high enough to generate the sounds. Symptoms typically peak at age 6–8 months and remit by age 2 years. Late-onset laryngomalacia may be a distinct entity, which can present after age of 2 years. References == External links ==

Reactive arthritis

Reactive arthritis, also known as Reiters syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease. By the time the patient presents with symptoms, often the "trigger" infection has been cured or is in remission in chronic cases, thus making determination of the initial cause difficult. The arthritis often is coupled with other characteristic symptoms; this has been called Reiters syndrome, Reiters disease or Reiters arthritis. The term "reactive arthritis" is increasingly used as a substitute for this designation because of Hans Reiters war crimes with the Nazi Party. The manifestations of reactive arthritis include the following triad of symptoms: an inflammatory arthritis of large joints, inflammation of the eyes in the form of conjunctivitis or uveitis, and urethritis in men or cervicitis in women. Arthritis occurring alone following sexual exposure or enteric infection is also known as reactive arthritis. Patients can also present with mucocutaneous lesions, as well as psoriasis-like skin lesions such as circinate balanitis, and keratoderma blennorrhagicum. Enthesitis can involve the Achilles tendon resulting in heel pain. Not all affected persons have all the manifestations. The clinical pattern of reactive arthritis commonly consists of an inflammation of fewer than five joints which often includes the knee or sacroiliac joint. The arthritis may be "additive" (more joints become inflamed in addition to the primarily affected one) or "migratory" (new joints become inflamed after the initially inflamed site has already improved).Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis often precipitated by genitourinary or gastrointestinal infections. The most common triggers are intestinal infections (with Salmonella, Shigella or Campylobacter) and sexually transmitted infections (with Chlamydia trachomatis); however, it also can happen after group A streptococcal infections.It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population. It can occur in epidemic form. Patients with HIV have an increased risk of developing reactive arthritis as well. Numerous cases during World Wars I and II focused attention on the triad of arthritis, urethritis, and conjunctivitis (often with additional mucocutaneous lesions), which at that time was also referred to as Fiessenger-Leroy-Reiter syndrome. Signs and symptoms Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic in reactive arthritis is "Cant see, cant pee, cant climb a tree." The classic triad consists of: Conjunctivitis Nongonococcal urethritis Asymmetric oligoarthritis Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease. The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination. Other urogenital problems may arise such as prostatitis in men and cervicitis, salpingitis and/or vulvovaginitis in women. It presents with monoarthritis affecting the large joints such as the knees and sacroiliac spine causing pain and swelling. An asymmetrical inflammatory arthritis of interphalangeal joints may be present but with relative sparing of small joints such as the wrist and hand. Patient can have enthesitis presenting as heel pain, Achilles tendinitis or plantar fasciitis, along with balanitis circinata (circinate balanitis), which involves penile lesions present in roughly 20 to 40 percent of the men with the disease. A small percentage of men and women develop small hard nodules called keratoderma blennorrhagicum on the soles of the feet and, less commonly, on the palms of the hands or elsewhere. The presence of keratoderma blennorrhagica is diagnostic of reactive arthritis in the absence of the classical triad. Subcutaneous nodules are also a feature of this disease. Ocular involvement (mild bilateral conjunctivitis) occurs in about 50% of men with urogenital reactive arthritis syndrome and about 75% of men with enteric reactive arthritis syndrome. Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision. Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go. Dactylitis, or "sausage digit", a diffuse swelling of a solitary finger or toe, is a distinctive feature of reactive arthritis and other peripheral spondylarthritides but can also be seen in polyarticular gout and sarcoidosis. Mucocutaneous lesions can be present. Common findings include oral ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. In the oral cavity, the patients may experience recurrent aphthous stomatitis, geographic tongue and migratory stomatitis in higher prevalence than the general population. Some patients experience serious gastrointestinal problems similar to those of Crohns disease. About 10 percent of people with reactive arthritis, especially those with a prolonged course of the disease, will develop cardiac manifestations, including aortic regurgitation and pericarditis. Reactive arthritis has been described as a precursor of other joint conditions, including ankylosing spondylitis. Causes Reactive arthritis is associated with the HLA-B27 gene on chromosome 6 and by the presence of enthesitis as the basic pathologic lesion and is triggered by a preceding infection. The most common triggering infection in the US is a genital infection with Chlamydia trachomatis. Other bacteria known to cause reactive arthritis which are more common worldwide are Ureaplasma urealyticum, Salmonella spp., Shigella spp., Yersinia spp., and Campylobacter spp. A bout of food poisoning or a gastrointestinal infection may also precede the disease (the last four genera of bacteria mentioned above are enteric bacteria). Shigella is the most common organism causing reactive arthritis following diarrhea. Chlamydia trachomatis is the most common cause of reactive arthritis following urethritis. Ureaplasma and mycoplasma are rare causes. There is some circumstantial evidence for other organisms causing the disease, but the details are unclear.Reactive arthritis usually manifests about 1–3 weeks after a known infection. The mechanism of interaction between the infecting organism and the host is unknown. Synovial fluid cultures are negative, suggesting that reactive arthritis is caused either by an autoimmune response involving cross-reactivity of bacterial antigens with joint tissues or by bacterial antigens that have somehow become deposited in the joints. Diagnosis There are few clinical symptoms, but the clinical picture is dominated by arthritis in one or more joints, resulting in pain, swelling, redness, and heat sensation in the affected areas. The urethra, cervix and the throat may be swabbed in an attempt to culture the causative organisms. Cultures may also be carried out on urine and stool samples or on fluid obtained by arthrocentesis. Tests for C-reactive protein and erythrocyte sedimentation rate are non-specific tests that can be done to corroborate the diagnosis of the syndrome. A blood test for the genetic marker HLA-B27 may also be performed. About 75 percent of all the patients with reactive arthritis have this gene. Diagnostic criteria Although there are no definitive criteria to diagnose the existence of reactive arthritis, the American College of Rheumatology has published sensitivity and specificity guidelines. Treatment The main goal of treatment is to identify and eradicate the underlying infectious source with the appropriate antibiotics if still present. Otherwise, treatment is symptomatic for each problem. Nonspecific urethritis may be treated with a short course of tetracycline. Analgesics, particularly NSAIDs, are used. Steroids, sulfasalazine and immunosuppressants may be needed for patients with severe reactive symptoms that do not respond to any other treatment. Local corticosteroids are useful in the case of iritis. Prognosis Reactive arthritis may be self-limiting, frequently recurring, chronic or progressive. Most patients have severe symptoms lasting a few weeks to six months. 15 to 50 percent of cases involve recurrent bouts of arthritis. Chronic arthritis or sacroiliitis occurs in 15–30 percent of cases. Repeated attacks over many years are common, and patients sometimes end up with chronic and disabling arthritis, heart disease, amyloid deposits, ankylosing spondylitis, immunoglobulin A nephropathy, cardiac conduction abnormalities, or aortitis with aortic regurgitation. However, most people with reactive arthritis can expect to live normal life spans and maintain a near-normal lifestyle with modest adaptations to protect the involved organs. Epidemiology Because women may be underdiagnosed, the exact incidence of reactive arthritis is difficult to estimate. A few studies have been completed, though. In Norway between 1988 and 1990, the incidence was 4.6 cases per 100,000 for chlamydia-induced reactive arthritis and 5 cases per 100,000 for that induced by enteric bacteria. In 1978 in Finland, the annual incidence was found to be 43.6 per 100,000. History When reactive arthritis appears in a triad that also includes ophthalmic and urogenital manifestations, the eponym "Reiters syndrome" is often applied; German physician Hans Conrad Julius Reiter described the condition in a soldier he treated during World War I. A number of physicians have suggested that the eponym is undeserved. Reiters Nazi Party affiliation, and in particular his involvement in forced human experimentation in the Buchenwald concentration camp (which, after his capture at the end of World War II, resulted in his prosecution in Nuremberg as a war criminal), have come to overshadow his medical accomplishments. Furthermore, he was not the first physician to make associations between the arthritis and other symptoms—the names arthritis urethritica, venereal arthritis and polyarteritis enterica had previously been applied—and the full triad was described by another physician in the 19th century. Notable cases It has been postulated that Italian-born explorer Christopher Columbus had reactive arthritis, dying from a heart attack caused by the condition. Pat Buchanan, American conservative political commentator, author, syndicated columnist, politician and broadcaster P. J. Gallagher Ian Murray, Scottish football player Mark St. John, one-time guitarist for Kiss Kirk Brandon, lead singer for Spear of Destiny Daniel Johns, Australian musician, lead singer for Silverchair Steve Walters, football player and survivor of sexual abuse by football trainer Barry Bennell See also List of medical eponyms with Nazi associations References External links eMedicine Questions and Answers about Reactive Arthritis - US National Institute of Arthritis and Musculoskeletal and Skin Diseases

Minimal change disease

Minimal change disease (also known as MCD, minimal change glomerulopathy, and nil disease, among others) is a disease affecting the kidneys which causes a nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema (soft tissue swelling) and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 6 years of age. MCD is responsible for 10–25% of nephrotic syndrome cases in adults. It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children. Signs and symptoms The clinical signs of minimal change disease are proteinuria (abnormal excretion of proteins, mainly albumin, into the urine), edema (swelling of soft tissues as a consequence of water retention), weight gain, and hypoalbuminaemia (low serum albumin). These signs are referred to collectively as nephrotic syndrome. The first clinical sign of minimal change disease is usually edema with an associated increase in weight. The swelling may be mild but patients can present with edema in the lower half of the body, periorbital edema, swelling in the scrotal/labial area and anasarca in more severe cases. In older adults, patients may also present with acute kidney injury (20–25% of affected adults) and high blood pressure. Due to the disease process, patients with minimal change disease are also at risk of blood clots and infections. Pathology For years, pathologists found no changes when viewing kidney biopsy specimens under light microscopy, hence the name "minimal change disease." Sometimes, the mesangium may have expanded, but otherwise there is no injury to kidney tissue itself.Under immunofluorescence, there are no immunoglobulins or complement deposits bound to kidney tissue.With the advent of electron microscopy, the changes now known as the hallmarks of the disease were discovered. These are diffuse loss of visceral epithelial cells foot processes (i.e., podocyte effacement), vacuolation, and growth of microvilli on the visceral epithelial cells, allowing for excess protein loss in the urine. Pathophysiology Proteinuria The cause and pathogenesis of the pathology is unclear and it is currently considered idiopathic. However, it does not appear to involve complement or immune complex deposition. Rather, an altered T cell-mediated immunologic response with abnormal secretion of lymphokines by T cells is thought to modify the glomerular basement membrane, specifically the podocytes, increasing permeability. This allows the leakage of albumin and other serum proteins into the urine. Also, the exact cytokine responsible has yet to be elucidated, with IL-12, IL-18 and IL-13 having been most studied in this regard, yet never conclusively implicated. Data from a longitudinal study (Nephrotic Syndrome Study Network – NEPTUNE) published in 2022 suggested that up to 29% of biopsy-confirmed, mixed pediatric and adult minimal change disease cases exhibited serum autoantibodies against nephrin, a structural protein located in the podocyte slit diaphragm.There has been discussion of B cell involvement in nephrotic syndrome, especially minimal change disease due to the success of immunotherapy that target both B and T cells, increased markers for B cell activation during a relapse of minimal change disease, and alterations in B cell sub-classes during minimal change disease remission. This hypothesis is supported by recent findings of anti-nephrin antibodies isolated in minimal change disease. Edema When albumin is excreted in the urine, its serum (blood) concentration decreases. Consequently, the plasma oncotic pressure reduces relative to the interstitial tissue. The subsequent movement of fluid from the vascular compartment to the interstitial compartment manifests as the soft tissue swelling referred to as edema. This fluid collects most commonly in the feet and legs, in response to gravity, particularly in those with poorly functioning valves. In severe cases, fluid can shift into the peritoneal cavity (abdomen) and cause ascites. As a result of the excess fluid, individuals with minimal change disease often gain weight, as they are excreting less water in the urine, and experience fatigue. Diagnosis As minimal change disease is a subset of nephrotic syndrome, diagnosis involves looking for a combination of edema, high amounts of protein in urine, low albumin and high serum cholesterol. Initial workup can include a urinalysis, kidney function tests, serum albumin level and a lipid panel. Microscopic amounts of blood are present in the urine of 10-30% adults with MCD.As MCD is the most common type of nephrotic syndrome in children, renal biopsy is not usually done in children under the age of 10 unless there are concerning features that are unusual for the disease (high blood pressure, bloody urine, renal dysfunction) and if they fail to respond to corticosteroid therapy. These would suggest that it may not be minimal change disease. In adults, a renal biopsy is required as there is a much wider differential for nephrotic syndrome. As the name suggests, the renal biopsy of a patient with minimal change disease would show minimal or no evidence of disease in light microscopy, which is unique among the causes of nephrotic syndrome. Treatment Children The first line therapy to minimal change disease is corticosteroids T.Prednisolone 60mg/sq.m/day or 2mg/kg/day. For those are who are unable to tolerate corticosteroid treatment, cyclosporine is an alternative; other immunosuppressants have also been used such as calcineurin inhibitor, mycophenolate mofetil, rituximab though studies on their effectiveness is fairly limited. There is no common consensus on how long the corticosteroid therapy should be, with treatment length ranging from 4–12 weeks. Along with corticosteroid therapy, acute symptomatic management involves salt and fluid restriction to control the swelling.For children who do not respond to corticosteroids (usually after a trial of 8 weeks), cyclosporine can be tried. Adults Treatment guidelines for adults are fairly limited, and are largely based on studies done on children. The mainline therapy is also corticosteroid therapy T.Prednisolone 1mg/kg/day with other immunosuppressants as possible alternatives, though there is very little data on these alternatives efficacy. Other medications such as ACE inhibitors to reduce the amount of protein in the urine or statins to decrease high levels of cholesterol seen with nephrotic syndrome are generally unnecessary. ACE inhibitors may be considered in people with MCD who also have high blood pressure. Prognosis Children Minimal change disease usually responds well to initial treatment with the first-line therapy: corticosteroids, with 95% responding. Younger children, who are more likely to develop minimal change disease, usually respond faster than adults with 50% of children having complete remission with 8 days of corticosteroid therapy and most other patients responding by the 4th week. Few do not respond to corticosteroids and have to rely on an alternative therapy. However, despite positive response to corticosteroids, relapses are common, requiring repeat treatment with corticosteroids. About 25% never relapse, another 25% relapse infrequently (one relapse within 6 months of initial response or 1–3 relapses in 12 months), and 50% relapse frequently (>2 relapses within 6 months of initial response or >4 relapses in 12 months). The relapse rate is the reason behind a discussion on continuing prednisone treatment to even beyond 12 weeks to possibly decrease relapse rate; several studies trying this have failed to show significant improvement. A majority of relapses seem to be triggered by respiratory infections. Long term, children can relapse several years after having no symptoms; though after 2 years, the risk is significantly lower.In most children with minimal change disease, particularly among those who respond typically, there is minimal to no permanent damage observed in their kidneys. Complications primarily arise from the side effects of therapy. Prolonged use of corticosteroids can lead to immunosuppression (leading to infection), growth complications, weight gain. Adults While most adults diagnosed with minimal change disease respond to corticosteroids, 25% fail to respond after 3–4 months of corticosteroid therapy; it is possible that these patients were incorrectly diagnosed, and do not have minimal change disease. Adults with MCD tend to respond more slowly to corticosteroid treatment, taking up to 3 or 4 months, than children do. Data in adults is less complete than for children, but relapses are fairly frequent with 56–76% of patients relapsing and needing further treatment with immunosuppressants such as ciclosporin, tacrolimus, mycophenolate, and rituximab. There is little evidence to support the use of azathioprine for MCD.As in children, complications primarily arise from the side effects of therapy. Prolonged use of corticosteroids can lead to immunosuppression (leading to infection), growth complications, weight gain. Epidemiology Minimal change disease is most common in very young children but can occur in older children and adults.It is by far the most common cause of nephrotic syndrome in children, accounting for 70–90% of children >1 year of age. After puberty, it is caused by minimal change disease about half the time. Among young children, boys seem to be more likely to develop minimal change disease than girls (about 2:1). Minimal change disease is seen in about 16 in every 100,000 children, being more common in South Asians and Native Americans, but rarer in African Americans.In adults, it accounts for less than 15% of adults diagnosed with nephrotic syndrome. Etymology Minimal change disease has been called by many other names in the medical literature, including minimal change nephropathy, minimal change nephrosis, minimal change nephrotic syndrome, minimal change glomerulopathy, foot process disease (referring to the foot processes of the podocytes), nil disease (referring to the lack of pathologic findings on light microscopy), nil lesions, lipid nephrosis, and lipoid nephrosis. References == External links ==

Placenta praevia

Placenta praevia is when the placenta attaches inside the uterus but in a position near or over the cervical opening. Symptoms include vaginal bleeding in the second half of pregnancy. The bleeding is bright red and tends not to be associated with pain. Complications may include placenta accreta, dangerously low blood pressure, or bleeding after delivery. Complications for the baby may include fetal growth restriction.Risk factors include pregnancy at an older age and smoking as well as prior cesarean section, labor induction, or termination of pregnancy. Diagnosis is by ultrasound. It is classified as a complication of pregnancy.For those who are less than 36 weeks pregnant with only a small amount of bleeding recommendations may include bed rest and avoiding sexual intercourse. For those after 36 weeks of pregnancy or with a significant amount of bleeding, cesarean section is generally recommended. In those less than 36 weeks pregnant, corticosteroids may be given to speed development of the babys lungs. Cases that occur in early pregnancy may resolve on their own.It affects approximately 0.5% of pregnancies. After four cesarean sections, however, it affects 10% of pregnancies. Rates of disease have increased over the late 20th century and early 21st century. The condition was first described in 1685 by Paul Portal. Signs and symptoms Women with placenta previa often present with painless, bright red vaginal bleeding. This commonly occurs around 32 weeks of gestation, but can be as early as late mid-trimester. More than half of women affected by placenta praevia (51.6%) have bleeding before delivery. This bleeding often starts mildly and may increase as the area of placental separation increases. Placenta praevia should be suspected if there is bleeding after 24 weeks of gestation. Bleeding after delivery occurs in about 22% of those affected.Women may also present as a case of failure of engagement of fetal head. Cause The exact cause of placenta previa is unknown. It is hypothesized to be related to abnormal vascularisation of the endometrium caused by scarring or atrophy from previous trauma, surgery, or infection. These factors may reduce differential growth of lower segment, resulting in less upward shift in placental position as pregnancy advances. Risk factors The following have been identified as risk factors for placenta previa: Previous placenta previa (recurrence rate 4–8%), caesarean delivery, myomectomy or endometrium damage caused by D&C. Women who are younger than 20 are at higher risk and women older than 35 are at increasing risk as they get older. Women who have had previous pregnancies (multiparity), especially a large number of closely spaced pregnancies, are at higher risk due to uterine damage. Smoking during pregnancy; cocaine use during pregnancy Women with a large placentae from twins or erythroblastosis are at higher risk. Race is a controversial risk factor, with some studies finding that people from Asia and Africa are at higher risk and others finding no difference. Placental pathology (velamentous insertion, succenturiate lobes, bipartite i.e. bilobed placenta etc.) Baby is in an unusual position: breech (buttocks first) or transverse (lying horizontally across the womb).Placenta previa is itself a risk factor of placenta accreta. Alcohol use during pregnancy was previously listed as a risk factor, but is discredited by this article. Classification Traditionally, four grades of placenta previa were used, but it is now more common to simply differentiate between "major" and "minor cases. Other than that placenta previa can be also classified as: Complete: When the placenta completely covers the cervix Partial: When the placenta partially covers the cervix Marginal: When the placenta ends near the edge of the cervix, about 2 cm from the internal cervical os Diagnosis History may reveal antepartum hemorrhage. Abdominal examination usually finds the uterus non-tender, soft and relaxed. Leopolds maneuvers may find the fetus in an oblique or breech position or lying transverse as a result of the abnormal position of the placenta. Malpresentation is found in about 35% cases. Vaginal examination is avoided in known cases of placenta previa. Confirmatory Previa can be confirmed with an ultrasound. Transvaginal ultrasound has superior accuracy as compared to transabdominal one, thus allowing measurement of distance between placenta and cervical os. This has rendered traditional classification of placenta previa obsolete.False positives may be due to following reasons: Overfilled bladder compressing lower uterine segment Myometrial contraction simulating placental tissue in abnormally low location Early pregnancy low position, which in third trimester may be entirely normal due to differential growth of the uterus.In such cases, repeat scanning is done after an interval of 15–30 minutes. In parts of the world where ultrasound is unavailable, it is not uncommon to confirm the diagnosis with an examination in the surgical theatre. The proper timing of an examination in theatre is important. If the woman is not bleeding severely she can be managed non-operatively until the 36th week. By this time the babys chance of survival is as good as at full term. Management An initial assessment to determine the status of the mother and fetus is required. Although mothers used to be treated in the hospital from the first bleeding episode until birth, it is now considered safe to treat placenta previa on an outpatient basis if the fetus is at less than 30 weeks of gestation, and neither the mother nor the fetus are in distress. Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother are in distress. Blood volume replacement (to maintain blood pressure) and blood plasma replacement (to maintain fibrinogen levels) may be necessary. Corticosteroids are indicated at 24–34 weeks gestation, given the higher risk of premature birth. Delivery The method of delivery is determined by clinical state of the mother, fetus and ultrasound findings. In minor degrees (traditional grade I and II), vaginal delivery is possible. RCOG recommends that the placenta should be at least 2 cm away from internal os for an attempted vaginal delivery. When a vaginal delivery is attempted, consultant obstetrician and anesthetists are present in delivery suite. In cases of fetal distress and major degrees (traditional grade III and IV) a caesarean section is indicated. Caesarian section is contraindicated in cases of disseminated intravascular coagulation. An obstetrician may need to divide the anterior lying placenta. In such cases, blood loss is expected to be high and thus blood and blood products are always kept ready. In rare cases, hysterectomy may be required. Complications Maternal Antepartum hemorrhage Malpresentation Abnormal placentation Postpartum hemorrhage Placenta previa increases the risk of puerperal sepsis and postpartum hemorrhage because the lower segment to which the placenta was attached contracts less well post-delivery. Fetal IUGR (15% incidence) Hypoxia Premature delivery Death Epidemiology Placenta previa occurs approximately one of every 200 births globally. It has been suggested that rates of placenta previa are increasing due to increased rate of Caesarian section. Reasons for regional variation may include ethnicity and diet. Africa Rates of placenta praevia in sub-Saharan Africa are the lowest in the world, averaging 2.7 per 1000 pregnancies. Despite a low prevalence, this disease has had a profound impact in Africa as it is linked with negative outcomes for both the mother and infant. The most common maternal outcome of placenta praevia is extreme blood loss before or after birth (antepartum hemorrhage and postpartum hemorrhage), which is a major cause of maternal and infant mortality in countries like Tanzania. Risk factors for placenta praevia among African women include prior pregnancies, prenatal alcohol consumption, and insufficient gynecologic care. In North Africa placenta praevia rates occur in 6.4 per 1000 pregnancies. Asia Mainland China has the highest prevalence of placenta praevia in the world, measuring at an average of 12.2 per 1000 pregnancies. Specifically, placenta praevia is most common in Southeast Asia, though the reason for this has not yet been investigated. There are many risk factors for placenta praevia in Asian women, of which include pregnancies occurring in women ages 35 and older (advanced maternal age) or in women who have had a prior Caesarean section, having multiple pregnancies, and experiencing either miscarriage or abortion in the past. In comparison with other Asian countries, placenta praevia is more common in Japan (13.9 per 1000) and Korea (15 per 1000). In the Middle East, placenta praevia rates are lower in both Saudi Arabia (7.3 per 1000) and Israel (4.2 per 1000). Australia The continent with the second highest rates for placenta praevia is Australia, where it affects about 9.5 out of every 1000 pregnant women. Researchers concerned with these rates have tested the specificity and sensitivity of fetal anomaly scans. In conclusion, it was determined the threshold that defines placenta praevia (based on proximity of placenta to cervix) must be reduced in order to improve the accuracy of diagnoses and to avoid false positives leading screenings. Europe Placenta praevia in Europe occurs in about 3.6 per 1000 pregnancies. Latin America In Latin America, placenta praevia occurs in about 5.1 per 1000 pregnancies. North America In North America placenta praevia occurs in 2.9 per 1000 pregnancies. Ethnic differences indicate White women are less likely to experience placenta praevia than Black women. Additionally, more cases of placenta praevia are found in women from low-income areas which are linked to insufficient pregnancy care. According to the socioeconomic demographic in North America, Black women are more likely to come from low income areas and are thus more likely to develop placenta praevia.In Nova Scotia, infants born to pregnant woman who experience placenta praevia have a mortality rate 3–4 times higher than normal pregnancies. A couple of factors contribute to this rate, including length of time fetus was in the womb and mothers age. Infants that did survive experienced increased rates of birth defects, breathing problems, and blood abnormalities.Research suggests that the incidence of placenta praevia in the U.S. is increasing as a result of the increased rate of Caesarian sections. References == External links ==

Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system (a hypersensitivity response) to the fungus Aspergillus (most commonly Aspergillus fumigatus). It occurs most often in people with asthma or cystic fibrosis. Aspergillus spores are ubiquitous in soil and are commonly found in the sputum of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses. ABPA causes airway inflammation, leading to bronchiectasis—a condition marked by abnormal dilation of the airways. Left untreated, the immune system and fungal spores can damage sensitive lung tissues and lead to scarring. The exact criteria for the diagnosis of ABPA are not agreed upon. Chest X-rays and CT scans, raised blood levels of IgE and eosinophils, immunological tests for Aspergillus together with sputum staining and sputum cultures can be useful. Treatment consists of corticosteroids and antifungal medications. Signs and symptoms Almost all patients have clinically diagnosed asthma, and present with wheezing (usually episodic in nature), coughing, shortness of breath and exercise intolerance (especially in patients with cystic fibrosis). Moderate and severe cases have symptoms suggestive of bronchiectasis, in particular thick sputum production (often containing brown mucus plugs), as well as symptoms mirroring recurrent infection such as pleuritic chest pain and fever. Patients with asthma and symptoms of ongoing infection, who do not respond to antibiotic treatment, should be suspected of ABPA. Pathophysiology Aspergillus spores are small (2–3 μm in diameter) and can penetrate deep into the respiratory system to the alveolar level. In healthy people, innate and adaptive immune responses are triggered by various immune cells (notably neutrophils, resident alveolar macrophages and dendritic cells) drawn to the site of infection by numerous inflammatory cytokines and neutrophilic attractants (such as CXCR2 receptor ligands). In this situation, mucociliary clearance is initiated and spores are successfully phagocytosed, clearing the infection from the host.In people with predisposing lung diseases—such as persistent asthma or cystic fibrosis (or rarer diseases such as chronic granulomatous disease or Hyper-IgE syndrome)—several factors lead to an increased risk of ABPA. These include immune factors (such as atopy or immunogenic HLA-restricted phenotypes), as well as genetic factors (such as CFTR gene mutations in both asthmatics and cystic fibrosis patients and a ZNF77 mutation resulting in a premature stop codon in asthmatics and ABPA patients). By allowing Aspergillus spores to persist in pulmonary tissues, it permits successful germination which leads to hyphae growing in mucus plugs. There are hypersensitivity responses, both a type I response (atopic, with formation of immunoglobulin E, or IgE) and a type III hypersensitivity response (with formation of immunoglobulin G, or IgG). The reaction of IgE with Aspergillus antigens results in mast cell degranulation with bronchoconstriction and increased capillary permeability. Immune complexes (a type III reaction) and inflammatory cells are deposited within the mucous membranes of the airways, leading to necrosis (tissue death) and eosinophilic infiltration. Type 2 T helper cells appear to play an important role in ABPA due to an increased sensitivity to interleukin (IL) 4 and IL-5. These cytokines up-regulate mast cell degranulation, exacerbating respiratory decline.Aspergillus also utilises a number of factors to continue evading host responses, notably the use of proteolytic enzymes that interrupt IgG antibodies aimed towards it. Another important feature is its ability to interact and integrate with epithelial surfaces, which results in massive pro-inflammatory counter-response by the immune system involving IL-6, IL-8 and MCP-1 (a CCL2 receptor ligand). Proteases released by both the fungus and neutrophils induce further injury to the respiratory epithelium, leading to initiation of repair mechanisms (such as an influx of serum and extracellular matrix (ECM) proteins) at the site of infection. Aspergillus spores and hyphae can interact with ECM proteins, and it is hypothesised that this process facilitates the binding of spores to damaged respiratory sites.As concentrations of Aspergillus proteases increase, the immunological effect switches from pro-inflammatory to inhibitory, and further reduces phagocytic ability to clear Aspergillus. Ultimately, repeated acute episodes lead to wider scale damage of pulmonary structures (parenchyma) and function via irreversible lung remodelling. Left untreated, this manifests as progressive bronchiectasis and pulmonary fibrosis that is often seen in the upper lobes, and can give rise to a similar radiological appearance to that produced by tuberculosis. Diagnosis The exact criteria for the diagnosis of ABPA are not yet universally agreed upon, though working groups have proposed specific guidelines. Minimal criteria include five factors: the presence of asthma and/or cystic fibrosis, a positive skin test to Aspergillus sp., total serum IgE > 416 IU/mL (or kU/L), an increased Aspergillus species–specific IgE and IgG antibodies, and the presence of infiltrates on a chest X-ray.ABPA should be suspected in patients with a predisposing lung disease—most commonly asthma or cystic fibrosis— and is often associated with chronic airway limitation (CAL). Patients generally present with symptoms of recurrent infection such as fever, but do not respond to conventional antibiotic therapy. Poorly-controlled asthma is a common finding, with a case series only finding 19% of ABPA patients with well-controlled asthma. Wheezing and hemoptysis (coughing up blood) are common features, and mucus plugging is seen in 31–69% of patients. Blood tests and serology The first stage involves exposing the skin to Aspergillus fumigatus antigens; an immediate reaction is hallmark of ABPA. The test should be performed first by skin prick testing, and if negative followed with an intradermal injection. The overall sensitivity of the procedure is around 90%, though up to 40% of asthmatic patients without ABPA can still show some sensitivity to Aspergillus antigens (a phenomenon likely linked to a less severe form of ABPA termed severe asthma with fungal sensitization (SAFS)).Serum blood tests are an important marker of disease severity and are also useful for the primary diagnosis of ABPA. When serum IgE is normal (and patients are not being treated by glucocorticoid medications), ABPA is excluded as the cause of symptoms. A raised IgE increases suspicion, though there is no universally accepted cut-off value. Values can be stated in international units (IU/mL) or ng/mL, where 1 IU is equal to 2.4 ng/mL. Since studies began documenting IgE levels in ABPA during the 1970s, various cut-offs between 833 and 1000 IU/mL have been employed to both exclude ABPA and to warrant further serological testing. The current consensus is that a cut-off of 1000 IU/mL should be employed, as lower values are encountered in SAFS and asthmatic sensitization.IgG antibody precipitin testing from serum is useful, as positive results are found in between 69 and 90% of patients, though also in 10% of asthmatics with and without SAFS. Therefore, it must be used in conjunction with other tests. Various forms exist, including enzyme-linked immunosorbent assay (ELISA) and fluorescent enzyme immunoassay (FEIA). Both are more sensitive than conventional counterimmunoelectrophoresis. IgG may not be entirely specific for ABPA, as high levels are also found in chronic pulmonary aspergillosis (CPA) alongside more severe radiological findings.Until recently, peripheral eosinophilia (high eosinophil counts) was considered partly indicative of ABPA. More recent studies show that only 40% of people with ABPA present with eosinophilia, and hence a low eosinophil count does not necessarily exclude ABPA; for example patients undergoing steroid therapy have lower eosinophil counts. Radiological investigation Consolidation and mucoid impaction are the most commonly described radiological features described in ABPA literature, though much of the evidence for consolidation comes from before the development of computed tomography (CT) scans. Tramline shadowing, finger-in-glove opacities and toothpaste shadows are also prevalent findings.When utilising high-resolution CT scans, there can be a better assessment of the distribution and pattern of bronchiectasis within the lungs, and hence this is the tool of choice in the radiological diagnosis of ABPA. Central (confined to medial two-thirds of the medial half of the lung) bronchiectasis that peripherally tapers bronchi is considered a requirement for ABPA pathophysiology, though in up to 43% of cases there is a considerable extension to the periphery of the lung.Mucoid impaction of the upper and lower airways is a common finding. Plugs are hypodense but appear on CT with high attenuation (over 70 Hounsfield units) in up to 20% of patients. Where present it is a strong diagnostic factor of ABPA and distinguishes symptoms from other causes of bronchiectasis.CT scans may more rarely reveal mosaic-appearance attenuation, centrilobular lung nodules, tree-in-bud opacities and pleuropulmonary fibrosis (a finding consistent with CPA, a disease with ABPA as a known precursor). Rarely other manifestations can be seen on CT scans, including military nodular opacities, perihilar opacities (that mimic hilar lymphadenopathy), pleural effusions and pulmonary masses. Cavitation and aspergilloma are rarer findings, not exceeding 20% of patients, and likely represent a shift from ABPA to CPA if accompanied by pleural thickening or fibrocavitary disease. Culture Culturing fungi from sputum is a supportive test in the diagnosis of ABPA, but is not 100% specific for ABPA as A. fumigatus is ubiquitous and commonly isolated from lung expectorant in other diseases. Nevertheless, between 40 and 60% of patients do have positive cultures depending on the number of samples taken. Staging New criteria by the ABPA Complicated Asthma ISHAM Working Group suggests a 6-stage criteria for the diagnosis of ABPA, though this is yet to be formalised into official guidelines. This would replace the current gold standard staging protocol devised by Patterson and colleagues. Stage 0 would represent an asymptomatic form of ABPA, with controlled asthma but still fulfilling the fundamental diagnostic requirements of a positive skin test with elevated total IgE (>1000 IU/mL). Stage 6 is an advanced ABPA, with the presence of type II respiratory failure or pulmonary heart disease, with radiological evidence of severe fibrosis consistent with ABPA on a high-resolution CT scan. It must be diagnosed after excluding the other, reversible causes of acute respiratory failure. Treatment Underlying disease must be controlled to prevent exacerbation and worsening of ABPA, and in most patients this consists of managing their asthma or CF. Any other co-morbidities, such as sinusitis or rhinitis, should also be addressed.Hypersensitivity mechanisms, as described above, contribute to progression of the disease over time and, when left untreated, result in extensive fibrosis of lung tissue. In order to reduce this, corticosteroid therapy is the mainstay of treatment (for example with prednisone); however, studies involving corticosteroids in ABPA are limited by small cohorts and are often not double-blinded. Despite this, there is evidence that acute-onset ABPA is improved by corticosteroid treatment as it reduces episodes of consolidation. There are challenges involved in long-term therapy with corticosteroids—which can induce severe immune dysfunction when used chronically, as well as metabolic disorders—and approaches have been developed to manage ABPA alongside potential adverse effects from corticosteroids.The most commonly described technique, known as sparing, involves using an antifungal agent to clear spores from airways adjacent to corticosteroid therapy. The antifungal aspect aims to reduce fungal causes of bronchial inflammation, whilst also minimising the dose of corticosteroid required to reduce the immune systems input to disease progression. The strongest evidence (double-blinded, randomized, placebo-controlled trials) is for itraconazole twice daily for four months, which resulted in significant clinical improvement compared to placebo, and was mirrored in CF patients. Using itraconazole appears to outweigh the risk from long-term and high-dose prednisone. Newer triazole drugs—such as posaconazole or voriconazole—have not yet been studied in-depth through clinical trials in this context.Whilst the benefits of using corticosteroids in the short term are notable, and improve quality of life scores, there are cases of ABPA converting to invasive aspergillosis whilst undergoing corticosteroid treatment. Furthermore, in concurrent use with itraconazole, there is potential for drug interaction and the induction of Cushing syndrome in rare instances. Metabolic disorders, such as diabetes mellitus and osteoporosis, can also be induced.In order to mitigate these risks, corticosteroid doses are decreased biweekly assuming no further progression of disease after each reduction. When no exacerbations from the disease are seen within three months after discontinuing corticosteroids, the patient is considered to be in complete remission. The exception to this rule is patients who are diagnosed with advanced ABPA; in this case, removing corticosteroids almost always results in exacerbation and these patients are continued on low-dose corticosteroids (preferably on an alternate-day schedule).Serum IgE can be used to guide treatment, and levels are checked every 6–8 weeks after steroid treatment commences, followed by every 8 weeks for one year. This allows for a determination of baseline IgE levels, though its important to note that most patients do not entirely reduce IgE levels to baseline. Chest X-ray or CT scans are performed after 1–2 months of treatment to ensure infiltrates are resolving. Epidemiology There are limited national and international studies into the burden of ABPA, made more difficult by a non-standardized diagnostic criteria. Estimates of between 0.5 and 3.5% have been made for ABPA burden in asthma, and 1–17.7% in CF. Five national cohorts, detecting ABPA prevalence in asthma (based on GINA estimates), were used in a recent meta-analysis to produce an estimate of the global burden of ABPA complicating asthma. From 193 million people with asthma worldwide, ABPA prevalence in asthma is estimated to be between 1.35 and 6.77 million people, using 0.7–3.5% attrition rates. A compromise at 2.5% attrition has also been proposed, placing global burden at around 4.8 million people affected. The Eastern Mediterranean region had the lowest estimated prevalence, with a predicted case burden of 351,000; collectively, the Americas had the highest predicted burden at 1,461,000 cases. These are likely underestimates of total prevalence, given the exclusion of CF patients and children from the study, as well as diagnostic testing being limited in less developed regions. References External links Fungal Research Trust Aspergillus Website Allergic Bronchopulmonary Aspergillosis — GP Notebook Medpix. ABPA radiology pictures

Polymorphous light eruption

Polymorphous light eruption (PLE), sometimes also called polymorphic light eruption (PMLE), is a non-life-threatening and potentially distressing skin condition that is triggered by sunlight and artificial UV exposure in a genetically susceptible person, particularly in temperate climates during the spring and early summer. Due to its many clinical appearances, it is named polymorphic or polymorphous and the terms are used interchangeably. The resulting itch can cause significant suffering.PLE is also defined as an idiopathic primary photodermatosis, in which the photosensitizer is unknown.Treatments include prevention with sun avoidance and supervised light therapy, and symptom control with topical steroids. Signs and symptoms Typically, the first episode develops in the spring following the first exposure to intense sun. Further episodes of the irritable rash occur several hours to days following subsequent sun exposure.PLE appears on areas of the skin newly exposed to sunlight such as the visible part of the neckline, backs of hands, arms and legs, and feet, but less commonly the face. At these areas, there may be feelings of burning and severe itching. Smooth red-topped small papules which merge into plaques, small fluid-filled blisters (papulovesicles) and less commonly target-shaped lesions which look like erythema multiforme may be visible. In addition, it may occur in other parts of the body in some people treated for inflammatory skin diseases with phototherapy.The rash is usually quite symmetrical and characteristic for each individual, appearing similar with each recurrence, but can look dissimilar in different people.Fever, fatigue and headaches have been previously associated with the eruption, but are rare.The rash may persist for many days to a couple of weeks, resolving spontaneously without scarring as long as further sunlight exposure is avoided.Recurring yearly, the eruption can sometimes last longer than a few days if persistent and repeated sun exposure occurs. However, the "hardening" effect, with respite during the later summer, frequently occurs with gradual exposure of sunlight, eventually leading to significant improvement. Causes The cause of PLE is not yet understood, but several factors may be involved. It is thought to be due to a type IV delayed-type hypersensitivity to an allergen produced in the body following sunlight exposure, in a genetically susceptible person. It is also thought that skin microbiome or microbial elements could be involved in pathogenesis of the disease UV exposure PLE can be provoked by UVA or UVB (chief cause of sunburn) rays, meaning it can be triggered even by sunlight through glass. UV-A is a major constituent of sunlight, can pass through glass, is relatively resistant to sunscreen and can cause light eruption without sunburn.Artificial UV light sources from tanning units and phototherapy treatment units can also trigger PLE. About three-quarters of patients acquire PLE after UV-A exposure only, one-tenth after UV-B exposure only, and the rest after a combination of UV-A and UV-B exposure.People vary in the amount of sun exposure needed to trigger the rash. Oxidative stress Oxidative stress and the modification of the redox status of the skin has been implicated in the expression of PLE. Photosensitizer It has been suggested that an undefined endogenous or exogenous photo-allergen may trigger a delayed immune reaction resulting in PLE. Genetics Half of patients have a family history of PLE, demonstrating a clear genetic influence. Oestrogen effect The preponderance in women with a decline in severity following menopause has been thought to be associated with oestrogen effects, A natural fall in oestrogens may account for the tendency to remit after the menopause. Diagnosis The diagnosis of PLE is typically made by assessing the history and clinical observations. Any investigations are usually to exclude other conditions, particularly lupus and porphyria.Blood tests are usually normal. However, positive antinuclear antibody and extractable nuclear antigen (anti-Ro/La) in low titre may be found, even in the absence of other criteria to suggest a diagnosis of lupus erythematosus. If clinical findings suggest a possibility of porphyria, urinary and red cell porphyrin screening may be performed and are negative in PLE.Photoprovocation tests are usually not required but may be undertaken by specialised centres in winter. When a decision to undertake this is made, a small area of the frequently affected skin is exposed to varying doses of UVA and minimal erythema dose (MED) (amount of UV radiation that will produce minimal redness of skin within a few hours following exposure) of broadband UVB for three consecutive days. An examination of the skin to detect the rash is made, however, up to 40% have false negative responses. Biopsy findings Depending on the clinical signs, histology of a skin biopsy may vary. There may be oedema in the epidermis with a dense superficial and deep lymphocytic infiltrate without vasculitis. Recently appearing lesions may show neutrophils. Spongiosis and vesicle formation may also be present. Direct immunofluorescence testing is negative. Differential diagnosis The photosensitivity connected with lupus erythematosus is the main condition that may appear like PLE. However, the rash of lupus is inclined to be more persistent. PLE does not increase the risk of lupus.Other similar appearing conditions are solar urticaria, which has a shorter duration, the eczema-like condition, photosensitive dermatitis, and photosensitivity drug reaction.Prickly heat, which is caused by warm weather or heat is not the same as PLE.Photosensitivity is also found in some of the porphyrias. Nearly all cases of porphyria cutanea tarda exhibit blister formation on the skin within 2–4 days of light exposure. Variegate porphyria and hereditary coproporphyria can also exhibit symptoms of light-induced blisters. Classification Sunlight has been documented to trigger numerous skin conditions and the confusing terminology and categorisation previously has made the correct diagnosis and subsequent treatment difficult.Variants of PLE have been described: Juvenile spring eruption is a cutaneous condition that affects the helices of the ears, particularly in boys, because their ears are relatively more exposed to sunlight. Benign summer light eruption is a cutaneous condition, and a name used in continental Europe, particularly France, to describe a clinically short-lived, itchy, papular eruption particularly affecting young women after several hours of sunbathing at the beginning of summer or on sunny vacations. Actinic Prurigo is a hereditary form of PLE occurring typically in Native Americans. Treatment Management entails regulating triggers whilst simultaneously inducing "hardening"; that is, steadily increasing exposure to sunlight, as light sensitivity is reduced with repeated sun exposureCovering up with densely woven clothing has also been shown to help, in addition to applying a broad-spectrum, water-resistant semi-opaque sun protection factor (SPF) 50+ sunblock cream before sun exposure and then every two hours thereafter confers some protection.The application of topical corticosteroids may lessen the redness and itch, and for preventing predictable holiday flare-ups, short courses of oral corticosteroids are sometimes considered.Another treatment option is a supervised course of low dose phototherapy, usually undertaken in winter. If resistant, the administration of hydroxychloroquine in early spring is sometimes considered.As sun exposure is avoided, vitamin D levels may fall and hence supplements are sometimes advised. Prognosis Generally, PLE resolves without treatment; also, PLE irritations generally leave no scar.There may be a possible link with autoimmune thyroid disease. Some progression to autoimmune disease has been observed. However, another study of people with elevated titres of antinuclear antibodies with PLE found no progression to lupus erythematosus after an 8-year follow-up. Epidemiology In the United States, whilst one-quarter of people being investigated for a photosensitivity disorder were diagnosed with PLE, the prevalence in the general population is 10 to 15% and may even be as high as 40% as suggested in one study of more than 2000 people. It is also particularly more prevalent in Central Europe and Scandinavia.PLE is more common in young adults and has a female preponderance with a ratio of 2:1 female-to-male. In Germany the female to male ratio has been cited as 9:1. It can, however, occur in all age groups and all skin types.Those experiencing sun exposure all year round seldom acquire PLE eruption. Hence, it is less common near the equator.The cases of this condition are most common between the spring and autumn months in the northern hemisphere and at higher altitudes. Society and culture Reports of psychological distress have been made in more than 40% of peoples with PLE. This includes emotional distress, anxiety and depression History Thomas Bateman, following on from findings of his predecessor, Robert Willan, first recorded a description of PLE in the nineteenth century, defining it as eczema solare with recurrent non scarring eczematous lesions triggered by sun exposure.Danish physician Carl Rasch first described the eczema-like polymorphic light eruption in 1900, following his interest in the effect of sunlight on the skin. He has since been credited with coining the term "polymorphic light eruption". See also Photosensitivity with HIV infection List of cutaneous conditions References External links www.emedicine.com

Infective endocarditis

Infective endocarditis is an infection of the inner surface of the heart, usually the valves. Signs and symptoms may include fever, small areas of bleeding into the skin, heart murmur, feeling tired, and low red blood cell count. Complications may include backward blood flow in the heart, heart failure – the heart struggling to pump a sufficient amount of blood to meet the bodys needs, abnormal electrical conduction in the heart, stroke, and kidney failure.The cause is typically a bacterial infection and less commonly a fungal infection. Risk factors include valvular heart disease, including rheumatic disease, congenital heart disease, artificial valves, hemodialysis, intravenous drug use, and electronic pacemakers. The bacteria most commonly involved are streptococci or staphylococci. Diagnosis is suspected based on symptoms and supported by blood cultures or ultrasound of the heart. There is also a noninfective form of endocarditis.The usefulness of antibiotics following dental procedures for prevention is unclear. Some recommend them for people at high risk. Treatment is generally with intravenous antibiotics. The choice of antibiotics is based on the results of blood cultures. Occasionally heart surgery is required.The number of people affected is about 5 per 100,000 per year. Rates, however, vary between regions of the world. Infective endocarditis occurs in males more often than in females. The risk of death among those infected is about 25%. Without treatment, it is almost universally fatal. Classification Infective endocarditis is divided into the three categories of acute, subacute, and chronic based on the duration of symptoms. Acute infective endocarditis refers to the presence of signs and symptoms of infective endocarditis that are present for days up to six weeks. If these signs and symptoms persist for more than six weeks but less than three months, this is subacute infective endocarditis. Chronic infective endocarditis refers to the presence of such signs and symptoms when they persist for more than three months. Subacute bacterial endocarditis (SBE) is often due to streptococci of low virulence (mainly viridans streptococci) and mild to moderate illness which progresses slowly over weeks and months (>2 weeks) and has low propensity to hematogenously seed extracardiac sites. Acute bacterial endocarditis (ABE) is a fulminant illness over days to weeks (<2 weeks), and is more likely due to Staphylococcus aureus, which has much greater virulence or disease-producing capacity and frequently causes metastatic infection.This classification is now discouraged, because the ascribed associations (in terms of organism and prognosis) were not strong enough to be relied upon clinically. The terms short incubation (meaning less than about six weeks) and long incubation (greater than about six weeks) are preferred. Culture results Infective endocarditis may also be classified as culture-positive or culture-negative. By far the most common cause of "culture-negative" endocarditis is prior administration of antibiotics.Sometimes microorganisms can take a longer period of time to grow in the culture media, for example Cutibacterium spp. and the HACEK bacteria group. Some organisms are said to be fastidious because they have demanding growth requirements. Some examples include pathogens like Aspergillus species, Brucella species, Coxiella burnetii, Chlamydia species. Due to delay in growth and identification in these cases, patients may be erroneously classified as "culture-negative" endocarditis. Heart side Endocarditis can also be classified by the side of the heart affected: People who intravenously inject opioids such as heroin or methamphetamine may introduce infection which can travel to the right side of the heart, classically affecting the tricuspid valve, and most often caused by S. aureus. Regardless of cause, left-sided endocarditis is more common in people who inject IV drugs and people who do not use substances than right-sided endocarditis. Infection setting Another form of endocarditis is healthcare-associated endocarditis when the infecting organism is believed to be transmitted in a health care setting like hospital, dialysis unit or a residential nursing home. Nosocomial endocarditis is a form of healthcare associated endocarditis in which the infective organism is acquired during a stay in a hospital and it is usually secondary to presence of intravenous catheters, total parenteral nutrition lines, pacemakers, etc. Valve type Finally, the distinction between native-valve endocarditis and prosthetic-valve endocarditis is clinically important. Prosthetic valve endocarditis can be early (< 60 days of valvular surgery), intermediate (60 days to 1 year) or late (> 1 year following valvular surgery). Early prosthetic valve endocarditis is usually due to intraoperative contamination or postoperative bacterial contamination which is usually nosocomial in nature. Late prosthetic valve endocarditis is usually due to community-acquired microorganisms.Prosthetic valve endocarditis is commonly caused by Staphylococcus epidermidis as it is capable of growing as a biofilm on plastic surfaces. Cutibacterium acnes almost exclusively causes endocarditis on prosthetic heart valves. Signs and symptoms Fever occurs in 97% of people; malaise and endurance fatigue in 90% of people. A new or changing heart murmur, weight loss, and coughing occurs in 35% of people. Vascular phenomena: septic embolism (a piece of infected debris or tissue breaking off and traveling through the bloodstream to a distant site) (causing thromboembolic problems such as a stroke or gangrene of the fingers), Janeway lesions (painless hemorrhagic cutaneous lesions on the palms and soles), bleeding in the brain, conjunctival hemorrhage, splinter hemorrhages, kidney infarcts, and splenic infarcts. Infective endocarditis can also lead to the formation of mycotic aneurysms. Immunologic phenomena: glomerulonephritis which allows for blood and albumin to enter the urine, Oslers nodes ("ephemeral spots of a painful nodular erythema, chiefly in the skin of the hands and feet"), Roths spots on the retina, positive serum rheumatoid factor Other signs may include night sweats, rigors, anemia, spleen enlargement Cause Many microorganisms can cause infective endocarditis. These are generally isolated by blood culture, where the patients blood is drawn and any growth is noted and identified. The term bacterial endocarditis (BE) commonly is used, reflecting the fact that most cases of IE are due to bacteria; however, infective endocarditis (IE) has become the preferred term. Bacterial Staphylococcus aureus is the leading cause of infective endocarditis in most parts of the world and is responsible for about 31% of cases. Staphylococcus aureus is the most common cause of endocarditis in people who use intravenous drugs. Viridans streptococci and Enterococci are the second and third most common organisms responsible for infective endocarditis. Viridans streptococci are a common cause of infective endocarditis in South America. Other Streptococci are also a frequent cause. Infective endocarditis due to Streptococcus bovis occurs more commonly in Europe than in North America. HACEK group of bacteria are also rare causes of infective endocarditis in North America.The viridans group includes S. oralis, S. mitis, S. sanguis, S. gordonii and S. parasanguis. The primary habitats for these organisms are the oral cavity and upper respiratory tract. These bacteria are present in the normal oral flora and enter the bloodstream due to disruption of tissues in the mouth when dental surgical procedures are performed (tooth extractions) or genitourinary manipulation. Similarly, HACEK organisms are a group of bacteria that live on the dental gums and can be seen with people who inject drugs who contaminate their needles with saliva. Patients may also have a history of poor dental hygiene or pre-existing valvular disease.Viridans alpha-hemolytic streptococci, that are present in the mouth, are the most frequently isolated microorganisms when the infection is acquired in a community setting. In contrast, Staphylococcus bloodstream infections are frequently acquired in a health care setting where they can enter the bloodstream through procedures that cause breaks in the integrity of skin, such as surgery, catheterization, or during access of long term indwelling catheters or secondary to intravenous injection of recreational drugs.Enterococcus can enter the bloodstream as a consequence of abnormalities in the gastrointestinal or genitourinary tracts.Some organisms, when isolated, give valuable clues to the cause, as they tend to be specific. Pseudomonas species, which are very resilient organisms that thrive in water, may contaminate street drugs that have been contaminated with drinking water. P. aeruginosa can infect a child through foot punctures, and can cause both endocarditis and septic arthritis. S. bovis and Clostridium septicum, which are part of the natural flora of the bowel, are associated with colon cancers. When they present as the causative agent in endocarditis, it usually prompts a colonoscopy to be done immediately due to concerns regarding spread of bacteria from the colon through the bloodstream due to the cancer breaking down the barrier between the inside of the colon (lumen) and the blood vessels which drain the bowel. Less commonly reported bacteria responsible for so called "culture negative endocarditis" include Bartonella, Chlamydia psittaci, and Coxiella. Such bacteria can be identified by serology, culture of the excised valve tissue, sputum, pleural fluid, and emboli, and by polymerase chain reaction or sequencing of bacterial 16S ribosomal RNA.Multiple case reports of infective endocarditis caused by unusual organisms have been published. Cutibacterium spp., which are normal skin flora, have been responsible for infective endocarditis, preferably in patients with prosthetic heart valves, in rare cases leading to death.Tropheryma whipplei has caused endocarditis without gastrointestinal involvement. Citrobacter koseri was found in an immunocompetent adult. Neisseria bacilliformis was found in a person with a bicuspid aortic valve. Fungal Fungal endocarditis (FE) is often fatal and one of the most serious forms of infective endocarditis. The types of fungi most seen associated with this disease are: Candida albicans is found as a spherical or oval budding yeast. It is associated with endocarditis in people who inject drugs, patients with prosthetic valves, and immunocompromised patients. It forms biofilms around thick-walled resting structures like prosthetic heart valves and additionally colonizes and penetrates endothelial walls. C. albicans is responsible for 24-46% of all the cases of FE, and its mortality rate is 46.6–50%.Other fungi demonstrated to cause endocarditis are Histoplasma capsulatum and Aspergillus. Aspergillus contributes to roughly 25% of FE cases. Endocarditis with Tricosporon asahii has also been reported in a case report. Risk factors Risk factors for infective endocarditis are based on the premise that in a healthy individual, bacteremia (bacteria entering the bloodstream) is cleared quickly with no adverse consequences. However, if a heart valve is damaged, the bacteria can attach themselves to the valve, resulting in infective endocarditis. Additionally, in individuals with weakened immune systems, the concentration of bacteria in the blood can reach levels high enough to increase the probability that some will attach to the valve. Some significant risk factors are listed here: Artificial heart valves Intracardiac devices, such as implantable cardioverter-defibrillators Unrepaired cyanotic congenital heart defects History of infective endocarditis Neoplastic disease Chronic rheumatic heart disease, which is an autoimmune response to repeated Streptococcus pyogenes infection (mostly in the developing world) Age-related degenerative valvular lesions Congenital heart valve abnormalities Hemodialysis, a medical procedure that filters the blood of individuals with kidney failure Poor oral hygiene Coexisting conditions, especially ones that suppress immunity. Diabetes mellitus, alcohol use disorder, chronic liver disease, HIV/AIDS, and intravenous drug use all fall in this categoryMore detailed descriptions of these and other risk factors are provided below. Other conditions that result in large numbers of bacteria entering into the bloodstream include colorectal cancer (mostly Streptococcus bovis), serious urinary tract infections (mostly enterococci), and drug injection (Staphylococcus aureus). With a large number of bacteria, even a normal heart valve may become infected. A more virulent organism (such as Staphylococcus aureus) can cause infective endocarditis by infecting even a normal heart valve.People who inject drugs tend to get their right-sided heart valves infected because the veins that are injected drain into the right side of the heart. In rheumatic heart disease, infection occurs on the aortic and the mitral valves on the left side of the heart.Other factors that increase the risk of developing infective endocarditis are low levels of white blood cells, immunodeficiency or immunosuppression, malignancy, diabetes mellitus, and excessive alcohol use. Dental operations In the past, one in eight cases of infective endocarditis was because of bacteremia caused by dental procedures (in most cases due to Streptococcus viridans, which reside in the oral cavity), such as cleaning or extraction of a tooth. This was thought to be more clinically significant than it actually was. However, it is important that a dentist or a dental hygienist be told of any heart problems before commencing treatment. Antibiotics are administered to patients with certain heart conditions as a precaution, although this practice has changed in the US, with new American Heart Association guidelines released in 2007, and in the UK as of March 2008 due to new NICE guidelines. Everyday tooth brushing and flossing will similarly cause bacteremia, so a high standard of oral health should be adhered to at all times.Although there is little evidence to support antibiotic prophylaxis for dental treatment, the current American Heart Association guidelines are highly accepted by clinicians and patients. Pathogenesis Damaged valves and endocardium contribute to the development of infective endocarditis. Specifically, the damaged part of a heart valve forms a local blood clot, a condition known as non-bacterial thrombotic endocarditis (NBTE). The platelet and fibrin deposits that form as part of the blood clotting process allow bacteria to take hold and form vegetations. As previously mentioned, the body has no direct methods of combating valvular vegetations because the valves do not have a dedicated blood supply. This combination of damaged valves, bacterial growth, and lack of a strong immune response results in infective endocarditis.Damage to the valves and endocardium can be caused by: Altered, turbulent blood flow. The areas that fibrose, clot, or roughen as a result of this altered flow are known as jet lesions. Altered blood flow is more likely in high pressure areas, so ventricular septal defects or patent ductus arteriosus can create more susceptibility than atrial septal defects. Catheters, electrodes, and other intracardiac prosthetic devices. Solid particles from repeated intravenous injections. Chronic inflammation. Examples include auto-immune mechanisms and degenerative valvular lesions.The risk factors for infective endocarditis provide a more extensive list of conditions that can damage the heart. Diagnosis In general, the Duke criteria should be fulfilled in order to establish the diagnosis of endocarditis. Although the Duke criteria are widely used, they have significant limitations. For example, the sensitivity of the Duke criteria for detecting infective endocarditis decreases when prosthetic heart valves are present.As the Duke criteria rely heavily on the results of echocardiography, research has addressed when to order an echocardiogram by using signs and symptoms to predict occult endocarditis among people who inject drugs and among non drug-abusing patients. However, this research is over twenty years old and it is possible that changes in the epidemiology of endocarditis and bacteria such as staphylococci make the following estimates incorrect. The blood tests C reactive protein (CRP) and procalcitonin have not been found to be particularly useful in helping make or rule out the diagnosis. Ultrasound Echocardiography is the main type of diagnostic imaging used to establish the diagnosis of infective endocarditis. There are two main types of echocardiography used to assist with the diagnosis of IE: transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE).The transthoracic echocardiogram has a sensitivity and specificity of approximately 65% and 95% if the echocardiographer believes there is probable or almost certain evidence of endocarditis. However, in endocarditis involving a prosthetic valve, TTE has a sensitivity of approximately 50%, whereas TEE has a sensitivity exceeding 90%. The TEE also has an important diagnostic role when the TTE does not reveal IE but diagnostic suspicion remains high, since TEE is more sensitive for infective endocarditis and is better able to characterize infection-related damage to the heart valves and surrounding tissues.Guidelines support the initial use of TTE over TEE in people with abnormal blood cultures, a new heart murmur, and suspected infective endocarditis. TEE is the preferred initial form of imaging in people with suspected infective endocarditis who have a moderate to high pretest probability of infective endocarditis, including people with prosthetic heart valves, blood cultures growing Staphylococcus, or have an intracardiac device (such as a pacemaker). Modified Duke criteria Established in 1994 by the Duke Endocarditis Service and revised in 2000, the Duke criteria are a collection of major and minor criteria used to establish a diagnosis of infective endocarditis. According to the Duke criteria, diagnosis of infective endocarditis can be definite, possible, or rejected. A diagnosis of infective endocarditis is definite if either the following pathological or clinical criteria are met: One of these pathological criteria: Histology or culture of cardiac vegetation, embolized vegetation, or intracardiac abscess from the heart finds microorganisms Active endocarditisOne of these combinations of clinical criteria Two major clinical criteria One major and three minor criteria Five minor criteriaDiagnosis of infective endocarditis is possible if one of the following combinations of clinical criteria is met: One major and one minor criteria Three minor criteria are fulfilled Major criteria Positive blood culture with typical IE microorganism, defined as one of the following: Typical microorganism consistent with IE from two separate blood cultures, as noted below: Viridans-group streptococci, or Streptococcus bovis including nutritional variant strains, or HACEK group, or Staphylococcus aureus, or Community-acquired enterococci, in the absence of a primary focus Microorganisms consistent with IE from persistently positive blood cultures defined as: Two positive cultures of blood samples drawn >12 hours apart, or Three or a majority of ≥four separate blood cultures (with first and last sample drawn at least one hour apart) Coxiella burnetii detected by at least one positive blood culture or IgG antibody titer for Q fever phase 1 antigen >1:800. This was previously a minor criterionEvidence of endocardial involvement with positive echocardiogram is defined as Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or Abscess, or New partial dehiscence of prosthetic valve or new valvular regurgitation (worsening or changing of preexisting murmur not sufficient) Minor criteria Predisposing factor: known cardiac lesion, recreational drug injection Fever >38 °C Vascular phenomena: arterial emboli, pulmonary infarcts, Janeway lesions, conjunctival hemorrhage Immunological phenomena: glomerulonephritis, Oslers nodes, Roths spots, Rheumatoid factor Microbiologic evidence: Positive blood culture (that doesnt meet a major criterion) or serologic evidence of infection with organism consistent with IE but not satisfying major criterion Risk Among people who do not use intravenous drugs and have a fever in the emergency department, there is a less than 5% chance of occult endocarditis. Mellors in 1987 found no cases of endocarditis nor of staphylococcal bacteremia among 135 febrile patients in the emergency room. The upper confidence interval for 0% of 135 is 5%, so for statistical reasons alone, there is up to a 5% chance of endocarditis among these patients. In contrast, Leibovici found that among 113 non-selected adults admitted to the hospital because of fever there were two cases (1.8% with 95%CI: 0% to 7%) of endocarditis.Among people who do use intravenous drugs and have a fever in the emergency department, there is about a 10% to 15% prevalence of endocarditis. This estimate is not substantially changed by whether the doctor believes the patient has a trivial explanation for their fever. Weisse found that 13% of 121 patients had endocarditis. Marantz also found a prevalence of endocarditis of 13% among such patients in the emergency department with fever. Samet found a 6% incidence among 283 such patients, but after excluding patients with initially apparent major illness to explain the fever (including 11 cases of manifest endocarditis), there was a 7% prevalence of endocarditis.Among people with staphylococcal bacteremia (SAB), one study found a 29% prevalence of endocarditis in community-acquired SAB versus 5% in nosocomial SAB. However, only 2% of strains were resistant to methicillin and so these numbers may be low in areas of higher resistance. Prevention Not all people with heart disease require antibiotics to prevent infective endocarditis. Heart diseases have been classified into high, medium and low risk of developing IE. Those falling into high risk category require IE prophylaxis before endoscopies and urinary tract procedures. Diseases listed under high risk include: Prior endocarditis Unrepaired cyanotic congenital heart diseases Completely repaired congenital heart disease in their first 6 months Prosthetic heart valves Incompletely repaired congenital heart diseases Cardiac transplant valvulopathyFollowing are the antibiotic regimens recommended by the American Heart Association for antibiotic prophylaxis: Oral amoxicillin one hour before the procedure Intravenous or intramuscular ampicillin one hour before the procedure In patients allergic to penicillins Azithromycin or clarithromycin orally one hour before the procedure Cephalexin orally one hour before the procedure Clindamycin orally one hour before the procedureIn the UK, NICE clinical guidelines no longer advise prophylaxis because there is no clinical evidence that it reduces the incidence of IE and there are negative effects (e.g. allergy and increased bacterial resistance) of taking antibiotics that may outweigh the benefits.Antibiotics were historically commonly recommended to prevent IE in those with heart problems undergoing dental procedures (known as dental antibiotic prophylaxis). There is, however, insufficient evidence to support whether antibiotics are effective or ineffective at preventing IE when given prior to a dental procedures in people at high risk. They are less commonly recommended for this procedure.In some countries e.g. the US, high risk patients may be given prophylactic antibiotics such as penicillin or clindamycin for penicillin-allergic people prior to dental procedures. Prophylactics should be bactericidal rather than bacteriostatic. Such measures are not taken in certain countries e.g. Scotland due to the fear of antibiotic resistance. Because bacteria are the most common cause of infective endocarditis, antibiotics such as penicillin and amoxicillin (for beta lactamase-producing bacteria) are used in prophylaxis. Treatment High-dose antibiotics are the cornerstone of treatment for infective endocarditis. These antibiotics are administered by the intravenous (IV) route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart. This is necessary because neither the heart valves nor the vegetations adhering to them are supplied by blood vessels. Antibiotics are typically continued for two to six weeks depending on the characteristics of the infection and the causative microorganisms. Antibiotic treatment lowers the risk of embolic complications in people with infective endocarditis.In acute endocarditis, due to the fulminant inflammation, empirical antibiotic therapy is started immediately after the blood has been drawn for culture to clarify the bacterial organisms responsible for the infection. This usually includes vancomycin and ceftriaxone IV infusions until the infecting organism is identified and the susceptibility report with the minimum inhibitory concentration becomes available. Once this information is available, this allows the supervising healthcare professional to modify the antimicrobial therapy to target the specific infecting microorganism. The routine use of gentamicin to treat endocarditis has fallen out of favor due to the lack of evidence to support its use (except in infections caused by Enterococcus and nutritionally variant streptococci) and the high rate of complications. In cases of subacute endocarditis, where the persons hemodynamic status is usually stable, antibiotic treatment can be delayed until the causative microorganism can be identified.Viridans group streptococci and Streptococcus bovis are usually highly susceptible to penicillin and can be treated with penicillin or ceftriaxone. Relatively resistant strains of viridans group streptococci and Streptococcus bovis are treated with penicillin or ceftriaxone along with a shorter two-week course of an aminoglycoside during the initial phase of treatment. Highly penicillin-resistant strains of viridans group streptococci, nutritionally variant streptococci like Granulicatella sp., Gemella sp., Abiotrophia defectiva, and Enterococci are usually treated with a combination therapy consisting of penicillin and an aminoglycoside for the entire duration of 4–6 weeks.Some people may be treated with a relatively shorter course of treatment (two weeks) with benzyl penicillin IV if infection is caused by viridans group streptococci or Streptococcus bovis as long as the following conditions are met: Endocarditis of a native valve, not of a prosthetic valve A MIC ≤ 0.12 mg/l A complication such as heart failure, arrhythmia, or pulmonary embolism occurs No evidence of extracardiac complication like septic thromboembolism No vegetations > 5 mm in diameter conduction defects Rapid clinical response and clearance of bloodstream infectionAdditionally, oxacillin-susceptible Staphylococcus aureus native valve endocarditis of the right side can also be treated with a short 2-week course of a beta-lactam antibiotic such as nafcillin with or without aminoglycosides. The main indication for surgical treatment is regurgitation or stenosis. In active infective endocarditis, the surgery should remove enough leaflet tissue to ensure eradication of the infectious process. Subsequent valve repair can be performed in limited disease. Replacement of the valve with a mechanical or bioprosthetic artificial heart valve is necessary in certain situations: Patients with significant valve stenosis or regurgitation causing heart failure Evidence of hemodynamic compromise in the form of elevated end-diastolic left ventricular or left atrial pressure or moderate to severe pulmonary hypertension Presence of intracardiac complications like paravalvular abscess, conduction defects or destructive penetrating lesions Recurrent septic emboli despite appropriate antibiotic treatment Large vegetations (> 10 mm) Persistently positive blood cultures despite appropriate antibiotic treatment Prosthetic valve dehiscence Relapsing infection in the presence of a prosthetic valve Abscess formation Early closure of mitral valve Infection caused by fungi or resistant Gram-negative bacteria.The guidelines were recently updated by both the American College of Cardiology and the European Society of Cardiology. There was a recent meta-analysis published that showed surgical intervention at seven days or less is associated with lower mortality. Prognosis Infective endocarditis is associated with 18% in-hospital mortality. As many as 50% of people with infective endocarditis may experience embolic complications. Epidemiology In developed countries, the annual incidence of infective endocarditis is 3 to 9 cases per 100,000 persons. Infective endocarditis occurs more often in men than in women. There is an increased incidence of infective endocarditis in persons 65 years of age and older, which is probably because people in this age group have a larger number of risk factors for infective endocarditis. In recent years, over one-third of infective endocarditis cases in the United States was healthcare-associated. Another trend observed in developed countries is that chronic rheumatic heart disease accounts for less than 10% of cases. Although a history of valve disease has a significant association with infective endocarditis, 50% of all cases develop in people with no known history of valvular disease. History Few diseases present greater difficulties in the way of diagnosis than malignant endocarditis, difficulties which in many cases are practically insurmountable. It is no disparagement to the many skilled physicians who have put their cases upon record to say that, in fully one-half the diagnosis was made post mortem. Lazare Riviére first described infective endocarditis affecting the aortic valve in 1616. In 1806, Jean-Nicolas Corvisart coined the term vegetation to describe collections of debris found on a mitral valve affected by infective endocarditis. The British physician Joseph Hodgson was the first to describe the embolic complications of infective endocarditis in 1815. It was not until 1878 that Theodor Klebs first suggested that infective endocarditis had a microbial infectious origin. In 1909, William Osler noted that heart valves that experienced degeneration and were sclerotic or poorly functioning had a higher risk of being affected. Later, in 1924, Emanuel Libman and Benjamin Sacks described cases of vegetative endocarditis that lacked a clear microbial origin and were often associated with the autoimmune condition systemic lupus erythematosus. In 1944, physicians reported on the first successful use of penicillin to treat a case of infective endocarditis. References External links Infective endocarditis at Curlie

De Quervains thyroiditis

De Quervains thyroiditis, also known as subacute granulomatous thyroiditis or giant cell thyroiditis, is a member of the group of thyroiditis conditions known as resolving thyroiditis. People of all ages and genders may be affected. Presentation Patients will experience a hyperthyroid period as the cellular lining of colloid spaces fails, allowing abundant colloid into the circulation, with neck pain and fever. Patients typically then become hypothyroid as the pituitary reduces TSH production and the inappropriately released colloid is depleted before resolving to euthyroid. The symptoms are those of hyperthyroidism and hypothyroidism. In addition, patients may suffer from painful dysphagia. There are multi-nucleated giant cells on histology. Thyroid antibodies can be present in some cases. The clinical presentation during the hyperthyroid phase can mimic those of Diffuse Toxic Goiter or Graves disease. In such cases, a radionuclide thyroid uptake and scan can be helpful, since subacute thyroiditis will result in decreased isotope uptake, while Graves disease will generally result in increased uptake. Distinguishing between these two types of disease is important, since Graves disease and Diffuse Toxic Goiter can be treated with radioiodine therapy, but subacute thyroiditis is usually self-limited and is not treated with radioiodine. Causes Some cases may be viral in origin, perhaps preceded by an upper respiratory tract infection. Viral causes include Coxsackie virus, mumps and adenoviruses. Some cases develop postpartum. Pathophysiology In the initial phase of damage to the gland, preformed thyroid hormone will fall out of the damaged cells. This leads to symptoms and biochemistry of an overactive thyroid (feels hot, trembly, anxious, loses weight, fast heart rate, sweaty, greasy hair), with raised free T3 and free T4, and a suppressed thyroid stimulating hormone (TSH) value. The damaged cells will no longer be able to take up iodine in order to manufacture further supplies of thyroid hormone, and thus in due course the patient comes to experience the symptoms of an underactive thyroid (feels cold, tired, depressed, gains weight, dry skin and hair) with low free T3 and free T4, and eventually increased TSH. Diagnosis With the standard overactive thyroid, iodine uptake into the thyroid is avid, whereas if the cells are damaged, then uptake is poor. In this way, if there is doubt about whether the patient has too much thyroid hormone because of de Quervains thyroiditis, then measuring radio-iodine uptake or technetium uptake gives a clear cut answer as it will be higher than normal in standard thyrotoxicosis and lower than normal in de Quervains. Treatment Treatment is beta blockers, aspirin, and NSAIDs (or corticosteroids if NSAIDs are ineffective). Eponym It is named for Fritz de Quervain. It should not be confused with De Quervain syndrome. Terminology It is sometimes called subacute thyroiditis, but there are other forms of subacute thyroiditis, subacute lymphocytic thyroiditis, postpartum thyroiditis, and autoimmune thyroiditis all of which, in contrast to de Quervains, are typically painless or "silent". It is also sometimes called "painful subacute thyroiditis". This is in contrast to subacute lymphocytic thyroiditis, which is also sometimes called "painless thyroiditis". References == External links ==

Rhinitis

Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip.The inflammation is caused by viruses, bacteria, irritants or allergens. The most common kind of rhinitis is allergic rhinitis, which is usually triggered by airborne allergens such as pollen and dander. Allergic rhinitis may cause additional symptoms, such as sneezing and nasal itching, coughing, headache, fatigue, malaise, and cognitive impairment. The allergens may also affect the eyes, causing watery, reddened, or itchy eyes and puffiness around the eyes. The inflammation results in the generation of large amounts of mucus, commonly producing a runny nose, as well as a stuffy nose and post-nasal drip. In the case of allergic rhinitis, the inflammation is caused by the degranulation of mast cells in the nose. When mast cells degranulate, they release histamine and other chemicals, starting an inflammatory process that can cause symptoms outside the nose, such as fatigue and malaise. In the case of infectious rhinitis, it may occasionally lead to pneumonia, either viral or bacterial. Sneezing also occurs in infectious rhinitis to expel bacteria and viruses from the respiratory tract. Rhinitis is very common. Allergic rhinitis is more common in some countries than others; in the United States, about 10–30% of adults are affected annually. Mixed rhinitis (MR) refers to patients with nonallergic rhinitis and allergic rhinitis. MR is a specific rhinitis subtype. It may represent between 50 and 70% of all AR patients. However, true prevalence of MR has not been confirmed yet. Types Rhinitis is categorized into three types (although infectious rhinitis is typically regarded as a separate clinical entity due to its transient nature): (i) infectious rhinitis includes acute and chronic bacterial infections; (ii) nonallergic rhinitis includes vasomotor, idiopathic, hormonal, atrophic, occupational, and gustatory rhinitis, as well as rhinitis medicamentosa (rebound congestion); (iii) allergic rhinitis, triggered by pollen, mold, animal dander, dust, Balsam of Peru, and other inhaled allergens. Infectious Rhinitis is commonly caused by a viral or bacterial infection, including the common cold, which is caused by Rhinoviruses, Coronaviruses, and influenza viruses, others caused by adenoviruses, human parainfluenza viruses, human respiratory syncytial virus, enteroviruses other than rhinoviruses, metapneumovirus, and measles virus, or bacterial sinusitis, which is commonly caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Symptoms of the common cold include rhinorrhea, sneezing, sore throat (pharyngitis), cough, congestion, and slight headache. Nonallergic rhinitis Nonallergic rhinitis refers to rhinitis that is not due to an allergy. The category was formerly referred to as vasomotor rhinitis, as the first cause discovered was vasodilation due to an overactive parasympathetic nerve response. As additional causes were identified, additional types of nonallergic rhinitis were recognized. Vasomotor rhinitis is now included among these under the more general classification of nonallergic rhinitis. The diagnosis is made upon excluding allergic causes. It is an umbrella term of rhinitis of multiple causes, such as occupational (chemical), smoking, gustatory, hormonal, senile (rhinitis of the elderly), atrophic, medication-induced (including rhinitis medicamentosa), local allergic rhinitis, non-allergic rhinitis with eosinophilia syndrome (NARES) and idiopathic (vasomotor or non-allergic, non-infectious perennial allergic rhinitis (NANIPER), or non-infectious non-allergic rhinitis (NINAR).In vasomotor rhinitis, certain nonspecific stimuli, including changes in environment (temperature, humidity, barometric pressure, or weather), airborne irritants (odors, fumes), dietary factors (spicy food, alcohol), sexual arousal, exercise, and emotional factors trigger rhinitis. There is still much to be learned about this, but it is thought that these non-allergic triggers cause dilation of the blood vessels in the lining of the nose, which results in swelling and drainage. Non-allergic rhinitis can co-exist with allergic rhinitis, and is referred to as "mixed rhinitis". The pathology of vasomotor rhinitis appears to involve neurogenic inflammation and is as yet not very well understood. The role of transient receptor potential ion channels on the non-neuronal nasal epithelial cells has also been suggested. Overexpression of these receptors have influence the nasal airway hyper-responsiveness to non-allergic irritant environmental stimuli (e.g., extremes of temperature, changes in osmotic or barometric pressure). Vasomotor rhinitis appears to be significantly more common in women than men, leading some researchers to believe that hormone imbalance plays a role. In general, age of onset occurs after 20 years of age, in contrast to allergic rhinitis which can be developed at any age. Individuals with vasomotor rhinitis typically experience symptoms year-round, though symptoms may be exacerbated in the spring and autumn when rapid weather changes are more common. An estimated 17 million United States citizens have vasomotor rhinitis.Drinking alcohol may cause rhinitis as well as worsen asthma (see alcohol-induced respiratory reactions). In certain populations, particularly those of East Asian countries such as Japan, these reactions have a nonallergic basis. In other populations, particularly those of European descent, a genetic variant in the gene that metabolizes ethanol to acetaldehyde, ADH1B, is associated with alcohol-induced rhinitis. It is suggested that this variant metabolizes ethanol to acetaldehyde too quickly for further processing by ALDH2 and thereby leads to the accumulation of acetaldehyde and rhinitis symptoms. In these cases, alcohol-induced rhinitis may be of the mixed rhinitis type and, it seems likely, most cases of alcohol-induced rhinitis in non-Asian populations reflect true allergic response to the non-ethanol and/or contaminants in alcoholic beverages, particularly when these beverages are wines or beers. Alcohol-exacerbated rhinitis is more frequent in individuals with a history of rhinitis exacerbated by aspirin.Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), particularly those that inhibit cyclooxygenase 1 (COX1), can worsen rhinitis and asthma symptoms in individuals with a history of either one of these diseases. These exacerbations most often appear due to NSAID hypersensitivity reactions rather than NSAID-induced allergic reactions.The antihistamine azelastine, applied as a nasal spray, may be effective for vasomotor rhinitis. Fluticasone propionate or budesonide (both are steroids) in nostril spray form may also be used for symptomatic treatment. The antihistamine cyproheptadine is also effective, probably due to its antiserotonergic effects. A systematic review on non-allergic rhinitis reports improvement of overall function after treatment with capsaicin (the active component of chili peppers). The quality of evidence is low, however. Allergic Allergic rhinitis or hay fever may follow when an allergen such as pollen, dust, or Balsam of Peru is inhaled by an individual with a sensitized immune system, triggering antibody production. These antibodies mostly bind to mast cells, which contain histamine. When the mast cells are stimulated by an allergen, histamine (and other chemicals) are released. This causes itching, swelling, and mucus production. Symptoms vary in severity between individuals. Very sensitive individuals can experience hives or other rashes. Particulate matter in polluted air and chemicals such as chlorine and detergents, which can normally be tolerated, can greatly aggravate the condition.Characteristic physical findings in individuals who have allergic rhinitis include conjunctival swelling and erythema, eyelid swelling, lower eyelid venous stasis, lateral crease on the nose, swollen nasal turbinates, and middle ear effusion.Even if a person has negative skin-prick, intradermal and blood tests for allergies, they may still have allergic rhinitis, from a local allergy in the nose. This is called local allergic rhinitis. Many people who were previously diagnosed with nonallergic rhinitis may actually have local allergic rhinitis.A patch test may be used to determine if a particular substance is causing the rhinitis. Rhinitis medicamentosa Rhinitis medicamentosa is a form of drug-induced nonallergic rhinitis which is associated with nasal congestion brought on by the use of certain oral medications (primarily sympathomimetic amine and 2-imidazoline derivatives) and topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoline nasal sprays) that constrict the blood vessels in the lining of the nose. Chronic atrophic rhinitis Chronic rhinitis is a form of atrophy of the mucous membrane and glands of the nose. Rhinitis sicca Chronic form of dryness of the mucous membranes. Polypous rhinitis Chronic rhinitis associated with polyps in the nasal cavity. Pathophysiology Most prominent pathological changes observed are nasal airway epithelial metaplasia in which goblet cells replace ciliated columnar epithelial cells in the nasal mucous membrane. This results in mucin hypersecretion by goblet cells and decreased mucociliary activity. Nasal secretion are not adequately cleared with clinical manifestation of nasal congestion, sinus pressure, post-nasal dripping, and headache. Over-expression of transient receptor potential (TRP) ion channels, such as TRPA1 and TRPV1, may be involved in the pathogenesis of non-allergic rhinitis. Association between rhinitis and asthma Neurogenic inflammation produced by neuropeptides released from sensory nerve endings to the airways is a proposed common mechanism of association between both allergic and non-allergic rhinitis with asthma. This may explain higher association of rhinitis with asthma developing later in life. Environmental irritants acts as modulators of airway inflammation in these contiguous airways. Development of occupational asthma is often preceded by occupational rhinitis. Among the causative agents are flours, enzymes used in processing food, latex, isocyanates, welding fumes, epoxy resins, and formaldehyde. Accordingly, prognosis of occupational asthma is contingent on early diagnosis and the adoption of protective measures for rhinitis. Diagnosis The different forms of rhinitis are essentially diagnosed clinically. Vasomotor rhinitis is differentiated from viral and bacterial infections by the lack of purulent exudate and crusting. It can be differentiated from allergic rhinitis because of the absence of an identifiable allergen. Prevention In the case of infectious rhinitis, vaccination against influenza viruses, COVID-19 virus, adenoviruses, measles, rubella, Streptococcus pneumoniae, Haemophilus influenzae, diphtheria, Bacillus anthracis, and Bordetella pertussis may help prevent it. Management The management of rhinitis depends on the underlying cause. For allergic rhinitis, intranasal corticosteroids are recommended. For severe symptoms intranasal antihistamines may be added. Pronunciation and etymology Rhinitis is pronounced , while coryza is pronounced .Rhinitis comes from the Ancient Greek ῥίς rhis, gen.: ῥινός rhinos "nose". Coryza has a dubious etymology. Robert Beekes rejected an Indo-European derivation and suggested a Pre-Greek reconstruction *karutya. According to physician Andrew Wylie, "we use the term [coryza] for a cold in the head, but the two are really synonymous. The ancient Romans advised their patients to clean their nostrils and thereby sharpen their wits." See also Infectious coryza in chickens References External links Sinus Infection And Allergic Rhinitis Specialist Library for ENT and Audiology Hay fever resources – online library of high quality research on hay fever and other ENT disorders

Ganglion cyst

A ganglion cyst is a fluid-filled bump associated with a joint or tendon sheath. It most often occurs at the back of the wrist, followed by the front of the wrist. Onset is often over several months, typically with no further symptoms. Occasionally, pain or numbness may occur. Complications may include carpal tunnel syndrome.The cause is unknown. The underlying mechanism is believed to involve an outpouching of the synovial membrane. Risk factors include gymnastics activity. Diagnosis is typically based on examination with light shining through the lesion being supportive. Medical imaging may be done to rule out other potential causes.Treatment options include watchful waiting, splinting the affected joint, needle aspiration, or surgery. About half the time, they resolve on their own. About three per 10,000 people newly develop ganglion of the wrist or hand a year. They most commonly occur in young and middle-aged females. Presentation The average size of these cysts is 2.0 cm, but excised cysts of more than 5 cm have been reported. The size of the cyst may vary over time and may increase after activity. Between 50 and 70% of all masses on the hand and wrist are expected to be ganglion cysts. Sites Ganglion cysts most frequently occur around the dorsum of the wrist and on the fingers. A common site of the occurrence is along the extensor carpi radialis brevis, as it passes over the dorsum of the wrist joint. Although most commonly found in the wrist, ganglion cysts also may occur in the foot.Ganglion cysts are "commonly observed in association with the joints and tendons of the appendicular skeleton, with 88% in communication with the multiple small joints of the hand and wrist and 11% with those of the foot and ankle". Wrist They commonly are found near the wrist joint, especially at the scapholunate area.Common wrist ganglions include: dorsal wrist ganglion volar wrist ganglion volar retinaculum ganglion extensor retinaculum ganglion occult ganglion intraosseous ganglion mucous cyst Foot In a 2007 study of patients in Glasgow whose foot lumps were removed surgically, 39 of 101 cases were ganglion cysts. The study replicated earlier findings that no ganglion cysts were found on the sole or heel. The authors wrote, "Although lumps in these areas may be ganglia, the surgeon should probably consider other diagnoses in the first instance." The researchers noted a preponderance of occurrence among females (85%) and that 11 of the other cases had been misdiagnosed as ganglion cysts before surgery.Ganglion cysts are not limited to the hands and feet. They may occur near the knee, commonly near the cruciate ligaments, but they may occur at the origins of the gastrocnemius tendon, and anteriorly on Hoffas infrapatellar fat pad. At the shoulder, they typically occur at the acromioclavicular joint or along the biceps tendon. Other From their common origin at a joint or tendon, ganglion cysts may form in a wide range of locations. Rarely, intraosseous ganglion cysts occur, sometimes in combination with a cyst in the overlying soft tissue. Rare cases of intramuscular ganglion cysts in the gastrocnemius muscle of the calf have been reported. It is possible for a cyst to be considerably displaced from the joint. In one extreme case, a ganglion cyst was observed to propagate extensively via the conduit of the common peroneal nerve sheath to a location in the thigh; in such cases surgery to the proximal joint to remove the articular connection may remove the need for a riskier, more extensive surgery in the neural tissue of the thigh. The cysts may intrude into the spine, which may cause pain and dysesthesia in distant extremities.Cystic adventitial disease, in which a cyst occurs within the popliteal artery near the knee, has been proposed recently to occur by an articular mechanism, with a conduit leading from the joint, similar to the development of ganglion cysts, that spreads within the peroneal nerve.Cysts that were compressing one or more nerves and causing bone erosions have been reported to occur near the shoulder joint. Causes The most commonly accepted probable cause of ganglion cysts is the "herniation hypothesis", by which they are thought to occur as "an out-pouching or distention of a weakened portion of a joint capsule or tendon sheath." This description is based on the observations that the cysts occur close to tendons and joints. The microscopic anatomy of the cyst resembles that of tenosynovial tissue. The fluid is similar in composition to synovial fluid. Dye injected into the joint capsule frequently ends up in the cyst, which may become enlarged after activity. Dye injected into the cyst rarely enters the joint, however, which has been attributed to the apparent formation of an effective and one-way "check valve", allowing fluid out of the joint, but not back in.In synovials, post-traumatic degeneration of connective tissue and inflammation have been considered as causes. Other possible mechanisms for the development of ganglion cysts include repeated mechanical stress, facet arthrosis, myxoid degeneration of periarticular fibrous tissues and liquefaction with chronic damage, increased production of hyaluronic acid by fibroblasts, and a proliferation of mesenchymal cells. Diagnosis Ganglion cysts are diagnosed easily, as they are visible and pliable to touch. Radiographs in anteroposterior and lateral views should be obtained to exclude any more serious underlying pathology. Ultrasonography (US) may be used to increase diagnostic confidence in clinically suspected lesions or to depict occult cysts, because intratendinous ganglia are readily distinguished from extratendinous ganglia during dynamic ultrasonography, as microscopically, ganglionic cysts are thin-walled cysts containing clear, mucinous fluid. Treatment If persons are not in pain, they should simply be reassured that the lump is not cancerous, and wait for the lump to disappear on its own. At least 33% resolve without treatment within six years, and 50% within 10 years.Surgical treatments remain the primary elective option for treatment of ganglion cysts. The progression of ganglion surgery worldwide is to use an arthroscopic or miniopening method. Alternatively, a hypodermic needle may be used to drain the fluid from the cyst (via aspiration) and a corticosteroid may be injected after the cyst is empty; however, if the fluid has thickened, owing to the passage of time, this treatment is not always effective. The recurrence rate is about 50% following needle drainage (via aspiration) of ganglion cysts. A historical method of treatment for a ganglion cyst was to strike the lump with a large and heavy book, causing the cyst to rupture and drain into the surrounding tissues. Historically, a Bible was the largest or only book in any given household, and was employed for this treatment. This led to the nickname of "Bible bumps" or "Gideons disease" for these cysts. This treatment risks injuring the person and thus is not recommended. Complications Complications of treatment may include joint stiffness and scar formation. Recurrence of the lesion is more common following excision of a volar ganglion cyst in the wrist. Incomplete excision that fails to include the stalk or pedicle also may lead to recurrence, as will failing to execute a layered closure of the incision. Prognosis Recurrence rate is higher in aspirated cysts than in excised ones. Ganglion cysts have been found to recur following surgery in 12% to 41% of patients. A six-year outcome study of the treatment of ganglion cysts on the dorsal wrist compared excision, aspiration, and no treatment. Neither excision nor aspiration provided long-term benefit better than no treatment. Of the untreated ganglion cysts, 58% resolved spontaneously; the postsurgery recurrence rate in this study was 39%. A similar study in 2003 of ganglion cysts occurring on the palmar surface of the wrist states: "At 2- and 5-year follow-up, regardless of treatment, no difference in symptoms was found, regardless of whether the palmar wrist ganglion was excised, aspirated, or left alone." Etymology Being a misnomer that has persisted into modern times, the ganglion cyst is unrelated to the neural "ganglion" or "ganglion cell"; its etymology traces back to the ancient Greek γάγγλιον, a "knot" or "swelling beneath the skin", which extends to the neural masses by analogy. Generally, Hippocrates is credited with the description of these cysts.The term "Bible cyst" (or "Bible bump") is derived from an urban legend or historical effort to hit the cyst with a Bible. Trying to treat the lesion by hitting it with a book, though, is discouraged. See also Ganglioneuroma References External links American Academy of Orthopaedic Surgeons - Ganglions cyst of the wrist Canadian Centre for Occupational Health and Safety - Ganglion cyst

Pseudohypoparathyroidism

Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Those with the condition have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is appropriately high (due to the low level of calcium in the blood). Its pathogenesis has been linked to dysfunctional G Proteins (in particular, Gs alpha subunit). Pseudohypoparathyroidism is a very rare disorder, with estimated prevalence between 0.3 and 1.1 cases per 100000 population depending on geographic location. Types Types include: Type 1a (OMIM 103580) Has a characteristic phenotypic appearance (Albrights hereditary osteodystrophy), including short fourth and fifth metacarpals and a rounded facies. It is most likely an autosomal dominant disorder. It is also associated with thyroid stimulating hormone resistance. Caused by GNAS1 mutation. Type 1b (OMIM 603233) Lacks the physical appearance of type 1a, but is biochemically similar. It is associated with a methylation defect in the A/B exon of GNAS1, caused by STX16 disruption. Type 2 (OMIM 203330) Also lacks the physical appearance of type 1a. Since the genetic defect in type 2 is further down the signalling pathway than in type 1, there is a normal cAMP response to PTH stimulation despite the inherent abnormality in calcium regulation. The specific gene is not identified.While biochemically similar, type 1 and 2 disease may be distinguished by the differing urinary excretion of cyclic AMP in response to exogenous PTH.Some sources also refer to a "type 1c" (OMIM 612462). The phenotype is the same as in type 1a, but red blood cells show normal Gs activity. As it is also caused by a GNAS mutation, it is not clear whether it should be considered an entity separate from Ia. Presentation Patients may present with features of hypocalcaemia including carpo-pedal muscular spasms, cramping, tetany, and if the calcium deficit is severe, generalized seizures. IQ is typically mildly depressed or unaffected. Additional characteristics include short stature, obesity, developmental delay, and calcification of the basal ganglia in the deep white matter of the brain.Type 1a Pseudohypoparathyroidism is clinically manifest by bone resorption with blunting of the fourth and fifth knuckles of the hand, most notable when the dorsum of the hand is viewed in closed fist position. This presentation is known as knuckle knuckle dimple dimple sign (Archibalds sign). This is as opposed to Turner syndrome which is characterized by blunting of only the fourth knuckle, and Down syndrome, which is associated with a hypoplastic middle phalanx. Related conditions The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal. Diagnosis Biochemical findings hypocalcemia hyperphosphatemia elevated parathyroid hormone (hyperparathyroidism) Suppressed calcitriol levels Treatment Calcium and Calcitriol supplements, the latter with a larger dose than for treatment of hypoparathyroidism. See also Hypoparathyroidism Pseudopseudohypoparathyroidism Hyperparathyroidism Rickets Hypervitaminosis D References Further reading Mantovani, G; Bastepe, M; Monk, D; de Sanctis, L; Thiele, S; Usardi, A; Ahmed, SF; Bufo, R; Choplin, T; De Filippo, G; Devernois, G; Eggermann, T; Elli, FM; Freson, K; García Ramirez, A; Germain-Lee, EL; Groussin, L; Hamdy, N; Hanna, P; Hiort, O; Jüppner, H; Kamenický, P; Knight, N; Kottler, ML; Le Norcy, E; Lecumberri, B; Levine, MA; Mäkitie, O; Martin, R; Martos-Moreno, GÁ; Minagawa, M; Murray, P; Pereda, A; Pignolo, R; Rejnmark, L; Rodado, R; Rothenbuhler, A; Saraff, V; Shoemaker, AH; Shore, EM; Silve, C; Turan, S; Woods, P; Zillikens, MC; Perez de Nanclares, G; Linglart, A (August 2018). "Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement" (PDF). Nature Reviews. Endocrinology. 14 (8): 476–500. doi:10.1038/s41574-018-0042-0. PMC 6541219. PMID 29959430. == External links ==

Foodborne illness

Foodborne illness (also foodborne disease and food poisoning) is any illness resulting from the spoilage of contaminated food by pathogenic bacteria, viruses, or parasites that contaminate food, as well as prions (the agents of mad cow disease), and toxins such as aflatoxins in peanuts, poisonous mushrooms, and various species of beans that have not been boiled for at least 10 minutes. Symptoms vary depending on the cause but often include vomiting, fever, and aches, and may include diarrhea. Bouts of vomiting can be repeated with an extended delay in between, because even if infected food was eliminated from the stomach in the first bout, microbes, like bacteria (if applicable), can pass through the stomach into the intestine and begin to multiply. Some types of microbes stay in the intestine. For contaminants requiring an incubation period, symptoms may not manifest for hours to days, depending on the cause and on quantity of consumption. Longer incubation periods tend to cause those affected to not associate the symptoms with the item consumed, so they may misattribute the symptoms to gastroenteritis, for example. Causes Foodborne illness usually arises from improper handling, preparation, or food storage. Good hygiene practices before, during, and after food preparation can reduce the chances of contracting an illness. There is a consensus in the public health community that regular hand-washing is one of the most effective defenses against the spread of foodborne illness. The action of monitoring food to ensure that it will not cause foodborne illness is known as food safety. Foodborne disease can also be caused by a large variety of toxins that affect the environment.Furthermore, foodborne illness can be caused by a number of chemicals, such as pesticides, medicines, and natural toxic substances such as vomitoxin, poisonous mushrooms or reef fish. Bacteria Bacteria are a common cause of foodborne illness. The United Kingdom, in 2000, reported the individual bacteria involved as the following: Campylobacter jejuni 77.3%, Salmonella 20.9%, Escherichia coli O157:H7 1.4%, and all others less than 0.56%. In the past, bacterial infections were thought to be more prevalent because few places had the capability to test for norovirus and no active surveillance was being done for this particular agent. Toxins from bacterial infections are delayed because the bacteria need time to multiply. As a result, symptoms associated with intoxication are usually not seen until 12–72 hours or more after eating contaminated food. However, in some cases, such as Staphylococcal food poisoning, the onset of illness can be as soon as 30 minutes after ingesting contaminated food. Most common bacterial foodborne pathogens are: Campylobacter jejuni which can lead to secondary Guillain–Barré syndrome and periodontitis Clostridium perfringens, the "cafeteria germ" Salmonella spp. – its S. typhimurium infection is caused by consumption of eggs or poultry that are not adequately cooked or by other interactive human-animal pathogens Escherichia coli O157:H7 enterohemorrhagic (EHEC) which can cause hemolytic-uremic syndromeOther common bacterial foodborne pathogens are: Bacillus cereus Escherichia coli, other virulence properties, such as enteroinvasive (EIEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroaggregative (EAEC or EAgEC) Listeria monocytogenes Shigella spp. Staphylococcus aureus Staphylococcal enteritis Streptococcus Vibrio cholerae, including O1 and non-O1 Vibrio parahaemolyticus Vibrio vulnificus Yersinia enterocolitica and Yersinia pseudotuberculosisLess common bacterial agents: Brucella spp. Corynebacterium ulcerans Coxiella burnetii or Q fever Plesiomonas shigelloides Enterotoxins In addition to disease caused by direct bacterial infection, some foodborne illnesses are caused by enterotoxins (exotoxins targeting the intestines). Enterotoxins can produce illness even when the microbes that produced them have been killed. Symptom appearance varies with the toxin but may be rapid in onset, as in the case of enterotoxins of Staphylococcus aureus in which symptoms appear in one to six hours. This causes intense vomiting including or not including diarrhea (resulting in staphylococcal enteritis), and staphylococcal enterotoxins (most commonly staphylococcal enterotoxin A but also including staphylococcal enterotoxin B) are the most commonly reported enterotoxins although cases of poisoning are likely underestimated. It occurs mainly in cooked and processed foods due to competition with other biota in raw foods, and humans are the main cause of contamination as a substantial percentage of humans are persistent carriers of S. aureus. The CDC has estimated about 240,000 cases per year in the United States. Clostridium botulinum Clostridium perfringens Bacillus cereusThe rare but potentially deadly disease botulism occurs when the anaerobic bacterium Clostridium botulinum grows in improperly canned low-acid foods and produces botulin, a powerful paralytic toxin. Pseudoalteromonas tetraodonis, certain species of Pseudomonas and Vibrio, and some other bacteria, produce the lethal tetrodotoxin, which is present in the tissues of some living animal species rather than being a product of decomposition. Emerging foodborne pathogens Aeromonas hydrophila, Aeromonas caviae, Aeromonas sobriaScandinavian outbreaks of Yersinia enterocolitica have recently increased to an annual basis, connected to the non-canonical contamination of pre-washed salad. Preventing bacterial food poisoning Prevention is mainly the role of the state, through the definition of strict rules of hygiene and a public services of veterinary surveying of animal products in the food chain, from farming to the transformation industry and delivery (shops and restaurants). This regulation includes: traceability: in a final product, it must be possible to know the origin of the ingredients (originating farm, identification of the harvesting or of the animal) and where and when it was processed; the origin of the illness can thus be tracked and solved (and possibly penalized), and the final products can be removed from the sale if a problem is detected; enforcement of hygiene procedures such as HACCP and the "cold chain"; power of control and of law enforcement of veterinarians.In August 2006, the United States Food and Drug Administration approved phage therapy which involves spraying meat with viruses that infect bacteria, and thus preventing infection. This has raised concerns, because without mandatory labelling consumers would not be aware that meat and poultry products have been treated with the spray.At home, prevention mainly consists of good food safety practices. Many forms of bacterial poisoning can be prevented by cooking food sufficiently, and either eating it quickly or refrigerating it effectively. Many toxins, however, are not destroyed by heat treatment. Techniques that help prevent food borne illness in the kitchen are hand washing, rinsing produce, preventing cross-contamination, proper storage, and maintaining cooking temperatures. In general, freezing or refrigerating prevents virtually all bacteria from growing, and heating food sufficiently kills parasites, viruses, and most bacteria. Bacteria grow most rapidly at the range of temperatures between 40 and 140 °F (4 and 60 °C), called the "danger zone". Storing food below or above the "danger zone" can effectively limit the production of toxins. For storing leftovers, the food must be put in shallow containers for quick cooling and must be refrigerated within two hours. When food is reheated, it must reach an internal temperature of 165 °F (74 °C) or until hot or steaming to kill bacteria. Mycotoxins and alimentary mycotoxicoses The term alimentary mycotoxicosis refers to the effect of poisoning by mycotoxins through food consumption. The term mycotoxin is usually reserved for the toxic chemical products produced by fungi that readily colonize crops. Mycotoxins sometimes have important effects on human and animal health. For example, an outbreak which occurred in the UK in 1960 caused the death of 100,000 turkeys which had consumed aflatoxin-contaminated peanut meal. In the USSR in World War II, 5,000 people died due to alimentary toxic aleukia (ALA). The common foodborne Mycotoxins include: Aflatoxins – originating from Aspergillus parasiticus and Aspergillus flavus. They are frequently found in tree nuts, peanuts, maize, sorghum and other oilseeds, including corn and cottonseeds. The pronounced forms of Aflatoxins are those of B1, B2, G1, and G2, amongst which Aflatoxin B1 predominantly targets the liver, which will result in necrosis, cirrhosis, and carcinoma. In the US, the acceptable level of total aflatoxins in foods is less than 20 μg/kg, except for Aflatoxin M1 in milk, which should be less than 0.5 μg/kg. The official document can be found at FDAs website. Altertoxins – are those of alternariol (AOH), alternariol methyl ether (AME), altenuene (ALT), altertoxin-1 (ATX-1), tenuazonic acid (TeA), and radicinin (RAD), originating from Alternaria spp. Some of the toxins can be present in sorghum, ragi, wheat and tomatoes. Some research has shown that the toxins can be easily cross-contaminated between grain commodities, suggesting that manufacturing and storage of grain commodities is a critical practice. Citrinin Citreoviridin Cyclopiazonic acid Cytochalasins Ergot alkaloids / ergopeptine alkaloids – ergotamine Fumonisins – Crop corn can be easily contaminated by the fungi Fusarium moniliforme, and its fumonisin B1 will cause leukoencephalomalacia (LEM) in horses, pulmonary edema syndrome (PES) in pigs, liver cancer in rats and esophageal cancer in humans. For human and animal health, both the FDA and the EC have regulated the content levels of toxins in food and animal feed. Fusaric acid Fusarochromanone Kojic acid Lolitrem alkaloids Moniliformin 3-Nitropropionic acid Nivalenol Ochratoxins – In Australia, The Limit of Reporting (LOR) level for ochratoxin A (OTA) analyses in 20th Australian Total Diet Survey was 1 µg/kg, whereas the EC restricts the content of OTA to 5 µg/kg in cereal commodities, 3 µg/kg in processed products and 10 µg/kg in dried vine fruits. Oosporeine Patulin – Currently, this toxin has been advisably regulated on fruit products. The EC and the FDA have limited it to under 50 µg/kg for fruit juice and fruit nectar, while limits of 25 µg/kg for solid-contained fruit products and 10 µg/kg for baby foods were specified by the EC. Phomopsins Sporidesmin A Sterigmatocystin Tremorgenic mycotoxins – Five of them have been reported to be associated with molds found in fermented meats. These are fumitremorgen B, paxilline, penitrem A, verrucosidin, and verruculogen. Trichothecenes – sourced from Cephalosporium, Fusarium, Myrothecium, Stachybotrys, and Trichoderma. The toxins are usually found in molded maize, wheat, corn, peanuts and rice, or animal feed of hay and straw. Four trichothecenes, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS), and deoxynivalenol (DON) have been most commonly encountered by humans and animals. The consequences of oral intake of, or dermal exposure to, the toxins will result in alimentary toxic aleukia, neutropenia, aplastic anemia, thrombocytopenia and/or skin irritation. In 1993, the FDA issued a document for the content limits of DON in food and animal feed at an advisory level. In 2003, US published a patent that is very promising for farmers to produce a trichothecene-resistant crop. Zearalenone Zearalenols Viruses Viral infections make up perhaps one third of cases of food poisoning in developed countries. In the US, more than 50% of cases are viral and noroviruses are the most common foodborne illness, causing 57% of outbreaks in 2004. Foodborne viral infection are usually of intermediate (1–3 days) incubation period, causing illnesses which are self-limited in otherwise healthy individuals; they are similar to the bacterial forms described above. Enterovirus Hepatitis A is distinguished from other viral causes by its prolonged (2–6 week) incubation period and its ability to spread beyond the stomach and intestines into the liver. It often results in jaundice, or yellowing of the skin, but rarely leads to chronic liver dysfunction. The virus has been found to cause infection due to the consumption of fresh-cut produce which has fecal contamination. Hepatitis E Norovirus Rotavirus Parasites Most foodborne parasites are zoonoses. Platyhelminthes:Diphyllobothrium sp. Nanophyetus sp. Taenia saginata Taenia solium Fasciola hepatica See also: Tapeworm and Flatworm Nematode:Anisakis sp. Ascaris lumbricoides Eustrongylides sp. Toxocara Trichinella spiralis Trichuris trichiura Protozoa:Acanthamoeba and other free-living amoebae Cryptosporidiosis Cyclospora cayetanensis Entamoeba histolytica Giardia lamblia Sarcocystis hominis Sarcocystis suihominis Toxoplasma Natural toxins Several foods can naturally contain toxins, many of which are not produced by bacteria. Plants in particular may be toxic; animals which are naturally poisonous to eat are rare. In evolutionary terms, animals can escape being eaten by fleeing; plants can use only passive defenses such as poisons and distasteful substances, for example capsaicin in chili peppers and pungent sulfur compounds in garlic and onions. Most animal poisons are not synthesised by the animal, but acquired by eating poisonous plants to which the animal is immune, or by bacterial action. Alkaloids Ciguatera poisoning Grayanotoxin (honey intoxication) Hormones from the thyroid glands of slaughtered animals (especially Triiodothyronine in cases of hamburger thyrotoxicosis or alimentary thyrotoxicosis) Mushroom toxins Phytohaemagglutinin (red kidney bean poisoning; destroyed by boiling) Pyrrolizidine alkaloids Shellfish toxin, including paralytic shellfish poisoning, diarrhetic shellfish poisoning, neurotoxic shellfish poisoning, amnesic shellfish poisoning and ciguatera fish poisoning Scombrotoxin Tetrodotoxin (fugu fish poisoning)Some plants contain substances which are toxic in large doses, but have therapeutic properties in appropriate dosages. Foxglove contains cardiac glycosides. Poisonous hemlock (conium) has medicinal uses. Other pathogenic agents Prions, resulting in Creutzfeldt–Jakob disease (CJD) and its variant (vCJD) "Ptomaine poisoning" Ptomaine poisoning was a myth that persisted in the public consciousness, in newspaper headlines, and legal cases as an official diagnosis, decades after it had been disproven scientifically in the 1910s.In the 19th century, the Italian chemist Francesco Selmi, of Bologna, introduced the generic name ptomaine (from Greek ptōma, "fall, fallen body, corpse") for alkaloids found in decaying animal and vegetable matter, especially (as reflected in their names) putrescine and cadaverine. The 1892 Mercks Bulletin stated, "We name such products of bacterial origin ptomaines; and the special alkaloid produced by the comma bacillus is variously named Cadaverine, Putrescine, etc." While The Lancet stated, "The chemical ferments produced in the system, the... ptomaines which may exercise so disastrous an influence." It is now known that the "disastrous... influence" is due to the direct action of bacteria and only slightly due to the alkaloids. Thus, the use of the phrase "ptomaine poisoning" is now obsolete. Tainted potato salad sickening hundreds at a Communist political convention in Massillon, Ohio, and aboard a Washington DC cruise boat in separate incidents during a single week in 1932 drew national attention to the dangers of so-called "ptomaine poisoning" in the pages of the American news weekly, Time. Another newspaper article from 1944 told of more than 150 persons being hospitalized in Chicago with ptomaine poisoning apparently from rice pudding served by a chain of restaurants. Mechanism Incubation period The delay between the consumption of contaminated food and the appearance of the first symptoms of illness is called the incubation period. This ranges from hours to days (and rarely months or even years, such as in the case of listeriosis or bovine spongiform encephalopathy), depending on the agent, and on how much was consumed. If symptoms occur within one to six hours after eating the food, it suggests that it is caused by a bacterial toxin or a chemical rather than live bacteria. The long incubation period of many foodborne illnesses tends to cause those affected to attribute their symptoms to gastroenteritis.During the incubation period, microbes pass through the stomach into the intestine, attach to the cells lining the intestinal walls, and begin to multiply there. Some types of microbes stay in the intestine, some produce a toxin that is absorbed into the bloodstream, and some can directly invade the deeper body tissues. The symptoms produced depend on the type of microbe. Infectious dose The infectious dose is the amount of agent that must be consumed to give rise to symptoms of foodborne illness, and varies according to the agent and the consumers age and overall health. Pathogens vary in minimum infectious dose; for example, Shigella sonnei has a low estimated minimum dose of < 500 colony-forming units (CFU) while Staphylococcus aureus has a relatively high estimate.In the case of Salmonella a relatively large inoculum of 1 million to 1 billion organisms is necessary to produce symptoms in healthy human volunteers, as Salmonellae are very sensitive to acid. An unusually high stomach pH level (low acidity) greatly reduces the number of bacteria required to cause symptoms by a factor of between 10 and 100. Gut microbiota unaccustomed to endemic organisms Foodborne illness often occurs as travelers diarrhea in persons whose gut microbiota is unaccustomed to organisms endemic to the visited region. This effect of microbiologic naivete is compounded by any food safety lapses in the foods preparation. Epidemiology Asymptomatic subclinical infection may help spread these diseases, particularly Staphylococcus aureus, Campylobacter, Salmonella, Shigella, Enterobacter, Vibrio cholerae, and Yersinia. For example, as of 1984 it was estimated that in the United States, 200,000 people were asymptomatic carriers of Salmonella. Infants Globally, infants are a group that is especially vulnerable to foodborne disease. The World Health Organization has issued recommendations for the preparation, use and storage of prepared formulas. Breastfeeding remains the best preventive measure for protection from foodborne infections in infants. United States In the United States, using FoodNet data from 2000 to 2007, the CDC estimated there were 47.8 million foodborne illnesses per year (16,000 cases for 100,000 inhabitants) with 9.4 million of these caused by 31 known identified pathogens. 127,839 were hospitalized (43 per 100,000 inhabitants per year). 3,037 people died (1.0 per 100,000 inhabitants per year). United Kingdom According to a 2012 report from the Food Standards Agency, there were around a million cases of foodborne illness per year (1,580 cases for 100,000 inhabitants). 20,000 were hospitalized (32 per 100,000 inhabitants); 500 people died (0.80 per 100,000 inhabitants). France This data pertains to reported medical cases of 23 specific pathogens in the 1990s, as opposed to total population estimates of all foodborne illness for the United States.In France, for 750,000 cases (1,210 per 100,000 inhabitants): 70,000 people consulted in the emergency department of a hospital (113 per 100,000 inhabitants); 113,000 people were hospitalized (182 per 100,000 inhabitants); 460 people died (0.75 per 100,000 inhabitants). Australia A study by the Australian National University, published in November 2014, found in 2010 that there were an estimated 4.1 million cases of foodborne gastroenteritis acquired in Australia on average each year, along with 5,140 cases of non-gastrointestinal illness. The study was funded by the Australian Department of Health, Food Standards Australia New Zealand and the NSW Food Authority.The main causes were Norovirus, pathogenic Escherichia coli, Campylobacter spp. and non-typhoidal Salmonella spp., although the causes of approximately 80% of illnesses were unknown. Approximately 25% (90% CrI: 13%–42%) of the 15.9 million episodes of gastroenteritis that occur in Australia were estimated to be transmitted by contaminated food. This equates to an average of approximately one episode of foodborne gastroenteritis every five years per person. Data on the number of hospitalisations and deaths represent the occurrence of serious foodborne illness. Including gastroenteritis, non-gastroenteritis and sequelae, there were an estimated annual 31,920 (90% CrI: 29,500–35,500) hospitalisations due to foodborne illness and 86 (90% CrI: 70–105) deaths due to foodborne illness circa 2010. This study concludes that these rates are similar to recent estimates in the US and Canada.A main aim of this study was to compare if foodborne illness incidence had increased over time. In this study, similar methods of assessment were applied to data from circa 2000, which showed that the rate of foodborne gastroenteritis had not changed significantly over time. Two key estimates were the total number of gastroenteritis episodes each year, and the proportion considered foodborne. In circa 2010, it was estimated that 25% of all episodes of gastroenteritis were foodborne. By applying this proportion of episodes due to food to the incidence of gastroenteritis circa 2000, there were an estimated 4.3 million (90% CrI: 2.2–7.3 million) episodes of foodborne gastroenteritis circa 2000, although credible intervals overlap with 2010. Taking into account changes in population size, applying these equivalent methods suggests a 17% decrease in the rate of foodborne gastroenteritis between 2000 and 2010, with considerable overlap of the 90% credible intervals.This study replaces a previous estimate of 5.4 million cases of foodborne illness in Australia every year, causing: 18,000 hospitalizations 120 deaths (0.5 deaths per 100,000 inhabitants) 2.1 million lost days off work 1.2 million doctor consultations 300,000 prescriptions for antibiotics.Most foodborne disease outbreaks in Australia have been linked to raw or minimally cooked eggs or poultry. The Australian Food Safety Information Council estimates that one third of cases of food poisoning occur in the home. Comparison between countries Outbreaks The vast majority of reported cases of foodborne illness occur as individual or sporadic cases. The origin of most sporadic cases is undetermined. In the United States, where people eat outside the home frequently, 58% of cases originate from commercial food facilities (2004 FoodNet data). An outbreak is defined as occurring when two or more people experience similar illness after consuming food from a common source.Often, a combination of events contributes to an outbreak, for example, food might be left at room temperature for many hours, allowing bacteria to multiply which is compounded by inadequate cooking which results in a failure to kill the dangerously elevated bacterial levels.Outbreaks are usually identified when those affected know each other. Outbreaks can also be identified by public health staff when there are unexpected increases in laboratory results for certain strains of bacteria. Outbreak detection and investigation in the United States is primarily handled by local health jurisdictions and is inconsistent from district to district. It is estimated that 1–2% of outbreaks are detected. Society and culture United Kingdom In postwar Aberdeen (1964) a large-scale (>400 cases) outbreak of typhoid occurred, caused by contaminated corned beef which had been imported from Argentina. The corned beef was placed in cans and because the cooling plant had failed, cold river water from the Plate estuary was used to cool the cans. One of the cans had a defect and the meat inside was contaminated. This meat was then sliced using a meat slicer in a shop in Aberdeen, and a lack of cleaning the machinery led to spreading the contamination to other meats cut in the slicer. These meats were then eaten by the people of Aberdeen who then became ill.Serious outbreaks of foodborne illness since the 1970s prompted key changes in UK food safety law. These included the death of 19 patients in the Stanley Royd Hospital outbreak and the bovine spongiform encephalopathy (BSE, mad cow disease) outbreak identified in the 1980s. The death of 21 people in the 1996 Wishaw outbreak of E. coli O157 was a precursor to the establishment of the Food Standards Agency which, according to Tony Blair in the 1998 white paper A Force for Change Cm 3830, "would be powerful, open and dedicated to the interests of consumers".In May 2015, for the second year running, Englands Food Standards Agency devoted its annual Food Safety Week to – "The Chicken Challenge". The focus was on the handling of raw chicken in the home and in catering facilities in a drive to reduce the high levels of food poisoning from the campylobacter bacterium. Anne Hardy argues that widespread public education of food hygiene can be useful, particularly through media (TV cookery programmes) and advertisement. She points to the examples set by Scandinavian societies. United States In 2001, the Center for Science in the Public Interest petitioned the United States Department of Agriculture to require meat packers to remove spinal cords before processing cattle carcasses for human consumption, a measure designed to lessen the risk of infection by variant Creutzfeldt–Jakob disease. The petition was supported by the American Public Health Association, the Consumer Federation of America, the Government Accountability Project, the National Consumers League, and Safe Tables Our Priority.None of the US Department of Health and Human Services targets regarding incidence of foodborne infections were reached in 2007.A report issued in June 2018 by NBCs Minneapolis station using research by both the CDC and the Minnesota Department of Health concluded that foodborne illness is on the rise in the U.S. Organizations The World Health Organization Department of Food Safety and Zoonoses (FOS) provides scientific advice for organizations and the public on issues concerning the safety of food. Its mission is to lower the burden of foodborne disease, thereby strengthening the health security and sustainable development of Member States. Foodborne and waterborne diarrhoeal diseases kill an estimated 2.2 million people annually, most of whom are children. WHO works closely with the Food and Agriculture Organization of the United Nations (FAO) to address food safety issues along the entire food production chain—from production to consumption—using new methods of risk analysis. These methods provide efficient, science-based tools to improve food safety, thereby benefiting both public health and economic development. International Food Safety Authorities Network (INFOSAN) The International Food Safety Authorities Network (INFOSAN) is a joint program of the WHO and FAO. INFOSAN has been connecting national authorities from around the globe since 2004, with the goal of preventing the international spread of contaminated food and foodborne disease and strengthening food safety systems globally. This is done by: Promoting the rapid exchange of information during food safety events; Sharing information on important food safety issues of global interest; Promoting partnership and collaboration between countries; and Helping countries strengthen their capacity to manage food safety risks.Membership to INFOSAN is voluntary, but is restricted to representatives from national and regional government authorities and requires an official letter of designation. INFOSAN seeks to reflect the multidisciplinary nature of food safety and promote intersectoral collaboration by requesting the designation of Focal Points in each of the respective national authorities with a stake in food safety, and a single Emergency Contact Point in the national authority with the responsibility for coordinating national food safety emergencies; countries choosing to be members of INFOSAN are committed to sharing information between their respective food safety authorities and other INFOSAN members. The operational definition of a food safety authority includes those authorities involved in: food policy; risk assessment; food control and management; food inspection services; foodborne disease surveillance and response; laboratory services for monitoring and surveillance of foods and foodborne diseases; and food safety information, education and communication across the farm-to-table continuum. Prioritisation of foodborne pathogens The Food and Agriculture Organization of the United Nations and The World Health Organization have published a global ranking of foodborne parasites using a multicriteria ranking tool concluding that Taenia solium was the most relevant, followed by Echinococcus granulosus, Echinococcus multilocularis, and Toxoplasma gondii. The same method was used regionally to rank the most important foodborne parasites in Europe ranking Echinococcus multilocularis of highest relevance, followed by Toxoplasma gondii and Trichinella spiralis. Regulatory steps Food may be contaminated during all stages of food production and retailing. In order to prevent viral contamination, regulatory authorities in Europe have enacted several measures: European Commission Regulation (EC) No 2073/2005 of November 15, 2005 European Committee for Standardization (CEN): Standard method for the detection of norovirus and hepatitis A virus in food products (shellfish, fruits and vegetables, surfaces and bottled water) CODEX Committee on Food Hygiene (CCFH): Guideline for the application of general principles of food hygiene for the control of viruses in food See also References This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. Further reading Periodicals International Journal of Food Microbiology, ISSN 0168-1605, Elsevier Foodborne Pathogens and Disease, ISSN 1535-3141, Mary Ann Liebert, Inc. Mycopathologia, ISSN 1573-0832 (electronic), ISSN 0301-486X (paper), Springer Books Hocking AD, Pitt JI, Samson RA, Thrane U (2005). Advances in Food Mycology. Springer. ISBN 978-0-387-28385-2. ISBN 978-0-387-28391-3 (electronic). Hobbs BC (1993). Food Poisoning and Food Hygiene. British Medical Bulletin. Vol. 7. Edward Arnold. pp. 167–70. doi:10.1093/oxfordjournals.bmb.a073825. ISBN 978-0-340-53740-4. PMID 14821218. Riemann HP, Cliver DO (2006). FoodBorne Infections and Intoxications. Academic Press. ISBN 978-0-12-588365-8. Smith JL (2005). Fratamico PM, Bhunia AK, Smith JL (eds.). Foodborne Pathogens: Microbiology And Molecular Biology. Horizon Scientific Press. ISBN 978-1-904455-00-4. External links Foodborne diseases, emerging, WHO, Fact sheet N°124, revised January 2002 Foodborne illness information pages, NSW Food Authority Food safety and foodborne illness, WHO, Fact sheet N°237, revised January 2002 UK Health protection Agency US PulseNet Food poisoning from NHS Direct Online Food Safety Network hosted at the University of Guelph, Canada. Food Standard Agency website

Primary ovarian insufficiency

Primary ovarian insufficiency (POI) (also called premature ovarian insufficiency, premature menopause, and premature ovarian failure) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of folliclular (egg producing area) dysfunction or early loss of eggs. POI can be seen as part of a continuum of changes leading to menopause that differ from age-appropriate menopause in the age of onset, degree of symptoms, and sporadic return to normal ovarian function. POI affects approximately 1 in 10,000 women under age 20, 1 in 1,000 women under age 30, and 1 in 100 of those under age 40. A medical triad for the diagnosis is amenorrhea, hypergonadotropism, and hypoestrogenism.Physical and emotional symptoms include hot flashes, night sweats, dry skin, vaginal dryness, irregular or absent menstruation, anxiety, depression, mental fog, irritability, nervousness, decreased libido, and increased autoimmune disruption. The sense of shock and distress on being informed of the diagnosis can be overwhelming. The general treatment is for symptoms, bone protection, and mental health. Although 5 to 10% of women with POI may ovulate sporadically and become pregnant without treatment, others may use assisted reproductive technology including in vitro fertilization and egg donation or decide to adopt or remain childless.The causes of POI are heterogeneous and are unknown in 90% of cases. It can be associated with genetic causes, autoimmune disease, enzyme deficiency, infection, environmental factors, radiation, or surgery in 10%. Two to 5% of women with POI and a premutation in FMR1, a genetic abnormality, are at risk of having a child with fragile X syndrome, the most common cause of inherited intellectual disability.The diagnosis is based on ages less than 40, amenorrhea, and elevated serum follicle-stimulating hormone (FSH) levels. Typical serum FSH levels in POI patients is in the post-menopausal range. Treatment will vary depending on the symptoms. It can include hormone replacement therapy, fertility management, and psychosocial support, as well as annual screenings of thyroid and adrenal function. Signs and symptoms The signs and symptoms of POI can be seen as part of a continuum of changes leading to menopause. POI contrasts with age-appropriate menopause in the age of onset, degree of symptoms and sporadic return to normal ovarian function. As some women retain partial ovarian function, symptoms may not be as severe as regular menopause. In others, particularly with coexistent depression, symptoms such as decreased quality of life can be severe.Hormonally, POI is defined by abnormally low levels of estrogen and high levels of FSH, which demonstrate that the ovaries are no longer responding to circulating FSH by producing estrogen and developing fertile eggs. The ovaries will likely appear smaller than normal. The age of onset can be as early as 11 years. POI can be seen as part of a continuum of changes leading to menopause that differ from age-appropriate menopause in the age of onset, degree of symptoms, and sporadic return to normal ovarian function. A contrasting problem can be when a girl never begins menstruation due to a genetic condition causing primary amenorrhea. Causes The cause of POI is idiopathic in 90% of cases. Some cases of POI are attributed to autoimmune disorders such as autoimmune oophoritis, Hashimoto thyroiditis, Addison disease, type I diabetes mellitus, pernicious anemia, genetic disorders such as Turner syndrome and Fragile X syndrome, metabolic defects, and enzyme defects. One study showed a strong correlation between incidence of POI and certain variants in the inhibin alpha gene. Chemotherapy and radiation treatments for cancer can sometimes cause POI. The effect of chemotherapy or radiation is variable and in a mouse model, with results consistent with observations in humans, cyclophosphamide can result in an 87% reduction in primordial follicles 72 hours after administration. Women who have had a hysterectomy tend to go through menopause early and have a nearly twofold increased risk of POI. Almost any pelvic surgery has the potential to damage the ovary by affecting its blood supply or causing inflammation in the area resulting in POI. Galactosemia Women who have inherited classic galactosemia (galactose intolerance) may develop primary ovarian insufficiency. Mechanism The pathogenic mechanisms of POI are highly heterogeneous and can be divided into four major categories: follicular migration defect early in embryogenesis; an early decrease in the primordial follicles; increased follicular death; and altered maturation or recruitment of primordial follicles. These result in a decrease of the ovaries general supply of eggs that normally lasts until an average age of 51 for age of age-appropriate menopause.Genetic causes such as Turner syndrome have initial ovarian development but then ovaries degenerate rapidly during prenatal life, often leading to gonadal dysgenesis with streak ovaries. In those cases where POI is associated with adrenal autoimmunity, histological examination almost always confirms the presence of an autoimmune oophoritis in which follicles are infiltrated by lymphocytes, plasma cells, and macrophages that attack mainly steroid-producing cells and eventually result in follicular depletion.In some women FSH may bind to the FSH receptor site, but be inactive. By lowering the endogenous FSH levels with ethinylestradiol (EE) or with a GnRH-a the receptor sites are free and treatment with exogenous recombinant FSH activates the receptors and normal follicle growth and ovulation can occur. (Since the serum Anti-Müllerian hormone (AMH) level is correlated with the number of remaining primordial follicles some researchers believe the above two phenotypes can be distinguished by measuring serum AMH levels.Genetic associations include genetic disorders, autoimmune diseases, enzyme defects, and resistant ovaries.Mutations in FOXL2 cause Blepharophimosis Ptosis Epicanthus inversus Syndrome (BPES). Premature ovarian failure is part of the BPES Type I variant of the syndrome but not of the BPES Type II variant. DNA repair deficiency BRCA1 protein plays an essential role in the repair of DNA double-strand breaks by homologous recombination. Women with a germline BRCA1 mutation tend to have premature menopause as evidenced by the final menorrhea appearing at a younger age. BRCA1 mutations are associated with occult POI. Impairment of the repair of DNA double-strand breaks due to a BRCA1 defect leads to premature ovarian aging in both mice and humans.In addition to BRCA1, the MCM8-MCM9 protein complex also plays a crucial role in the recombinational repair of DNA double-strand breaks. In humans, an MCM8 mutation can give rise to premature ovarian failure, as well as chromosomal instability. MCM9, as well as MCM8, mutations are also associated with ovarian failure and chromosomal instability. The MCM8-MCM9 complex is likely required for the homologous recombinational repair of DNA double-strand breaks that are present during the pachytene stage of meiosis I. In women homozygous for MCM8 or MCM9 mutations, failure to repair breaks apparently leads to oocyte death and small or absent ovaries. Diagnosis The diagnosis is based on age less than forty, amenorrhea for four months or more, and two elevated serum follicle-stimulating hormone (FSH) measurements at one-month intervals. The anterior pituitary secretes FSH and LH at high levels to try to increase the low estrogen levels that are due to the dysfunction of the ovaries. Typical FSH in POI patients is over 40 mlU/ml (post-menopausal range). Treatment Fertility Between 5 and 10 percent of women with POI may become pregnant with no treatment. As of 2016 no fertility treatment has been found to effectively increase fertility in women with POI, and the use of donor eggs with in-vitro fertilization (IVF) and adoption are a means of achieving parenthood for women with POI. Some women with POI choose to live child-free.Researchers have investigated the use of a hormone called dehydroepiandrosterone (DHEA) in women with POI to increase spontaneous pregnancy rates. Results from studies on DHEA in 2010 indicated that DHEA may increase spontaneously conceived pregnancies, decrease spontaneous miscarriage rates and improve IVF success rates in women with POI. This includes women referred for donor eggs or surrogacy in 2009. In 2018, there was no significant improvement in ovarian function by 12-month on DHEA supplementation in women with POI. Given the inconclusiveness of potential benefits and risks of testosterone and DHEA supplementation, longer-term, randomized studies are warranted for women and girls with POI.Ovarian tissue cryopreservation can be performed on prepubertal girls at risk for premature ovarian failure, and this procedure is as feasible and safe as comparable operative procedures in children.In 2013, Kawamura in Japan and his collaborators at Stanford University published treatment of infertility of POI patients by fragmenting ovaries followed by in vitro treatment of ovarian fragments with phosphatidylinositol-3 kinase activators to enhance the AKT pathway followed by autografting. They successfully promoted follicle growth, retrieved mature oocytes, and performed in vitro fertilization. Following embryo transfer, a healthy baby was delivered. A 2020 review covered variations including phosphatidylinositol-3 kinase activators to enhance the AKT pathway, fragmentation of ovarian cortex, combining those two into in-vitro activation (IVA), and drug-free IVA. Two laparoscopies are needed in conventional IVA and one with drug-free IVA. Hormonal replacement Women with POI can develop symptoms of estrogen deficiency, including vasomotor flushes and vaginal dryness that respond to physiologic replacement of hormones. Most authorities recommend that this hormone replacement continue until age 50 years, the normal age of menopause. The leading hormone replacement regimen recommended involves the administration of estradiol daily by either skin patch or vaginal ring. This approach reduces the risk of pulmonary embolism and deep venous thrombosis by avoiding the first pass effect on the liver that is induced by oral estrogen therapy. The transdermal estradiol patch also provides the replacement by steady infusion rather than by bolus when taking daily pills.Concerns of estrogen supplement are addressed in The US Medical Eligibility Criteria for Contraceptive Use, 2010 provides guidance for safety of contraceptive methods and include guidance for conditions associated with increased risk of thrombosis such as postpartum, history of thrombosis, thrombogenic mutations, systemic lupus erythematosus, diabetes, and hypertension. There is also an increased risk with valvular heart disease and cardiomyopathy.To avoid the development of endometrial cancer young women taking estradiol replacement need also to take a progestin in a regular cyclic fashion. The most evidence supports the use of medroxyprogesterone acetate per day for days one through 12 of each calendar month. This will induce regular and predictable menstrual cycles. It is important that women taking this regimen keep a menstrual calendar. If the next expected menses is late it is important to get a pregnancy test. It this is positive, the woman should stop taking the hormone replacement. Approximately 5 to 10% of women with confirmed POI conceive a pregnancy after the diagnosis without medical intervention. Prognosis Infertility can be a result of this condition and is the most discussed problem resulting from it, but there are additional health implications of the problem, and studies are ongoing. For example, osteoporosis (decreased bone density) affects almost all women with POI due to an insufficiency of estrogen. There is also an increased risk of heart disease, hypothyroidism such as Hashimotos thyroiditis, Addisons disease, and other autoimmune disorders. Emotional health The most common words women use to describe how they felt in the two hours after being given the diagnosis of POI are "devastated", "shocked," and "confused." The diagnosis is more than infertility and affects a womans physical and emotional well-being. Patients face the acute shock of the diagnosis, associated stigma of infertility, grief from the death of dreams, anxiety and depression from the disruption of life plans, confusion around the cause, shame, insecurity and lowered self-esteem, anger in reflection of being letdown by the medical system, symptoms of estrogen deficiency, worry over the associated potential medical sequelae such as reduced bone density and cardiovascular risk, and the uncertain future that all of these factors create. Women diagnosed with POI in their 20s have disproportionately reported experiencing dismissiveness, bias, and "not being taken seriously" by healthcare professionals.There is a need for an evidence-based integrative medicine program to assist women with POI. Presently such a program does not exist in the community, but a community of practice has formed to address this deficiency. Women with POI perceive lower social support than control women, so building a trusted community of practice for them would be expected to improve their well-being. Also, when having that social support, it often helps with reducing stress and having better coping skills. It is important to connect women with POI to an appropriate collaborative care team because the condition has been clearly associated with suicide related to the stigma of infertility. Suicide rates are known to be increased in women who experience infertility. Epidemiology The prevalence increases with age and is approximately 1 in 10,000 women under age 20, 1 in 1,000 women under age 30, and one percent by age of 40. History Fuller Albright et al. in 1942 reported a syndrome with amenorrhea, estrogen deficiency, menopausal FSH levels, and short stature. They used the term "primary ovarian insufficiency" to distinguished POI from ovarian insufficiency secondary to a primary failure of pituitary FSH and other hormonal secretion. POI has been described as a more accurate and less stigmatizing term than premature ovarian failure or premature menopause.Chapter 28 of the early Qing dynasty work Fù Qīngzhǔ Nǚkē (《傅青主女科》Fù Qīngzhǔs Gynecology) describes the cause and appropriate treatment for premature menopause. 年未老经水断 (niánwèilǎo jīngshuǐduàn) glosses as not yet old, menstrual water cut-off. References External links Primary Ovarian Insufficiency (POI): Overview National Institutes of Health

Osteochondritis dissecans

Osteochondritis dissecans (OCD or OD) is a joint disorder primarily of the subchondral bone in which cracks form in the articular cartilage and the underlying subchondral bone. OCD usually causes pain during and after sports. In later stages of the disorder there will be swelling of the affected joint which catches and locks during movement. Physical examination in the early stages does only show pain as symptom, in later stages there could be an effusion, tenderness, and a crackling sound with joint movement. OCD is caused by blood deprivation of the secondary physes around the bone core of the femoral condyle. This happens to the epiphyseal vessels under the influence of repetitive overloading of the joint during running and jumping sports. During growth such chondronecrotic areas grow into the subchondral bone. There it will show as bone defect area under articular cartilage. The bone will then possibly heal to the surrounding condylar bone in 50% of the cases. Or it will develop into a pseudarthrosis between condylar bone core and osteochondritis flake leaving the articular cartilage it supports prone to damage. The damage is executed by ongoing sport overload. The result is fragmentation (dissection) of both cartilage and bone, and the free movement of these bone and cartilage fragments within the joint space, causing pain, blockage and further damage. OCD has a typical anamnesis with pain during and after sports without any history of trauma. Some symptoms of late stages of osteochondritis dissecans are found with other diseases like rheumatoid disease of children and meniscal ruptures. However, the disease can be confirmed by X-rays, computed tomography (CT) or magnetic resonance imaging (MRI) scans. Non-surgical treatment is successful in 50% of the cases. If in late stages the lesion is unstable and the cartilage is damaged, surgical intervention is an option as the ability for articular cartilage to heal is limited. When possible, non-operative forms of management such as protected reduced or non-weight bearing and immobilization are used. Surgical treatment includes arthroscopic drilling of intact lesions, securing of cartilage flap lesions with pins or screws, drilling and replacement of cartilage plugs, stem cell transplantation, and in very difficult situation in adults joint replacement. After surgery rehabilitation is usually a two-stage process of unloading and physical therapy. Most rehabilitation programs combine efforts to protect the joint with muscle strengthening and range of motion. During an immobilization period, isometric exercises, such as straight leg raises, are commonly used to restore muscle loss without disturbing the cartilage of the affected joint. Once the immobilization period has ended, physical therapy involves continuous passive motion (CPM) and/or low impact activities, such as walking or swimming. OCD occurs in 15 to 30 people per 100,000 in the general population each year. Although rare, it is an important cause of joint pain in physically active children and adolescents. Because their bones are still growing, adolescents are more likely than adults to recover from OCD; recovery in adolescents can be attributed to the bones ability to repair damaged or dead bone tissue and cartilage in a process called bone remodeling. While OCD may affect any joint, the knee tends to be the most commonly affected, and constitutes 75% of all cases. Franz König coined the term osteochondritis dissecans in 1887, describing it as an inflammation of the bone–cartilage interface. Many other conditions were once confused with OCD when attempting to describe how the disease affected the joint, including osteochondral fracture, osteonecrosis, accessory ossification center, osteochondrosis, and hereditary epiphyseal dysplasia. Some authors have used the terms osteochondrosis dissecans and osteochondral fragments as synonyms for OCD. Signs and symptoms In osteochondritis dissecans, fragments of cartilage or bone become loose within a joint, leading to pain and inflammation. These fragments are sometimes referred to as joint mice. OCD is a type of osteochondrosis in which a lesion has formed within the cartilage layer itself, giving rise to secondary inflammation. OCD most commonly affects the knee, although it can affect other joints such as the ankle or the elbow.People with OCD report activity-related pain that develops gradually. Individual complaints usually consist of mechanical symptoms including pain, swelling, catching, locking, popping noises, and buckling / giving way; the primary presenting symptom may be a restriction in the range of movement. Symptoms typically present within the initial weeks of stage I; however, the onset of stage II occurs within months and offers little time for diagnosis. The disease progresses rapidly beyond stage II, as OCD lesions quickly move from stable cysts or fissures to unstable fragments. Non-specific symptoms, caused by similar injuries such as sprains and strains, can delay a definitive diagnosis.Physical examination typically reveals fluid in the joint, tenderness, and crepitus. The tenderness may initially spread, but often reverts to a well-defined focal point as the lesion progresses. Just as OCD shares symptoms with common maladies, acute osteochondral fracture has a similar presentation with tenderness in the affected joint, but is usually associated with a fatty hemarthrosis. Although there is no significant pathologic gait or characteristic alignment abnormality associated with OCD, the patient may walk with the involved leg externally rotated in an attempt to avoid tibial spine impingement on the lateral aspect of the medial condyle of the femur. Causes Despite much research, the causes remain unclear but include repetitive physical trauma, ischemia (restriction of blood flow), hereditary and endocrine factors, avascular necrosis (loss of blood flow), rapid growth, deficiencies and imbalances in the ratio of calcium to phosphorus, and problems of bone formation. Although the name "osteochondritis" implies inflammation, the lack of inflammatory cells in histological examination suggests a non-inflammatory cause. It is thought that repetitive microtrauma, which leads to microfractures and sometimes an interruption of blood supply to the subchondral bone, may cause subsequent localized loss of blood supply or alteration of growth.Trauma, rather than avascular necrosis, is thought to cause osteochondritis dissecans in juveniles. In adults, trauma is thought to be the main or perhaps the sole cause, and may be endogenous, exogenous or both. The incidence of repetitive strain injury in young athletes is on the rise and accounts for a significant number of visits to primary care; this reinforces the theory that OCD may be associated with increased participation in sports and subsequent trauma. High-impact sports such as gymnastics, soccer, basketball, lacrosse, football, tennis, squash, baseball and weight lifting may put participants at a higher risk of OCD in stressed joints (knees, ankles and elbows).Recent case reports suggest that some people may be genetically predisposed to OCD. Families with OCD may have mutations in the aggrecan gene. Studies in horses have implicated specific genetic defects. Pathophysiology Osteochondritis dissecans differs from "wear and tear" degenerative arthritis, which is primarily an articular surface problem. Instead, OCD is a problem of the bone underlying the cartilage, which may secondarily affect the articular cartilage. Left untreated, OCD can lead to the development of degenerative arthritis secondary to joint incongruity and abnormal wear patterns.OCD occurs when a loose piece of bone or cartilage partially (or fully) separates from the end of the bone, often because of a loss of blood supply (osteonecrosis) and decalcification of the trabecular bone matrix. The loose piece may stay in place or slide around, making the joint stiff and unstable. OCD in humans most commonly affects the knees, ankles, and elbow but can affect any joint.In skeletally immature individuals, the blood supply to the epiphyseal bone is good, supporting both osteogenesis and chondrogenesis. With disruption of the epiphyseal plate vessels, varying degrees and depth of necrosis occur, resulting in a cessation of growth to both osteocytes and chondrocytes. In turn, this pattern leads to disordered ossification of cartilage, resulting in subchondral avascular necrosis and consequently OCD.Four minor stages of OCD have been identified after trauma. These include revascularization and formation of granulation (scar) tissue, absorption of necrotic fragments, intertrabecular osteoid deposition, and remodeling of new bone. With delay in the revascularization stage, an OCD lesion develops. A lesion can lead to articular-surface irregularities, which in turn may cause progressive arthritic deterioration. Diagnosis To diagnose osteochondritis dissecans, an X-ray, CT scan or MRI scan can be performed to show necrosis of subchondral bone, formation of loose fragments, or both. Occasionally a nuclear medicine bone scan is used to assess the degree of loosening within the joint. Physical examination Physical examination often begins with examination of the patients gait. In OCD of the knee, people may walk with the involved leg externally rotated in an attempt to avoid tibial spine impingement on the lateral aspect of the medial condyle of the femur.Next, the examining physician may check for weakness of the quadriceps. This examination may reveal fluid in the joint, tenderness, and crepitus. The Wilson test is also useful in locating OCD lesions of the femoral condyle. The test is performed by slowly extending the knee from 90 degrees, maintaining internal rotation. Pain at 30 degrees of flexion and relief with tibial external rotation is indicative of OCD.Physical examination of a patient with ankle OCD often returns symptoms of joint effusion, crepitus, and diffuse or localized tenderness. Examination often reveals symptoms of generalized joint pain, swelling, and times with limited range of motion. Some with loose body lesions may report catching, locking, or both. The possibility of microtrauma emphasizes a need for evaluation of biomechanical forces at the knee in a physical examination. As a result, the alignment and rotation of all major joints in the affected extremity is common, as are extrinsic and intrinsic abnormalities concerning the affected joint, including laxity. Diagnostic imaging X-rays show lucency of the ossification on the anterior aspect of the knee in juvenile patients. In older people, the lesion typically appears as an area of osteosclerotic bone with a radiolucent line between the osteochondral defect and the epiphysis. The visibility of the lesion depends on its location and on the amount of knee flexion used. Harding described the lateral X-ray as a method to identify the site of an OCD lesion.Magnetic resonance imaging (MRI) is useful for staging OCD lesions, evaluating the integrity of the joint surface, and distinguishing normal variants of bone formation from OCD by showing bone and cartilage edema in the area of the irregularity. MRI provides information regarding features of the articular cartilage and bone under the cartilage, including edema, fractures, fluid interfaces, articular surface integrity, and fragment displacement. A low T1 and high T2 signal at the fragment interface is seen in active lesions. This indicates an unstable lesion or recent microfractures. While MRI and arthroscopy have a close correlation, X-ray films tend to be less inductive of similar MRI results.Computed tomography (CT) scans and Technetium-99m bone scans are also sometimes used to monitor the progress of treatment. Unlike plain radiographs (X-rays), CT scans and MRI scans can show the exact location and extent of the lesion. Technetium bone scans can detect regional blood flow and the amount of osseous uptake. Both of these seem to be closely correlated to the potential for healing in the fragment. Classification OCD is classified by the progression of the disease in stages. There are two main staging classifications used; one is determined by MRI diagnostic imaging while the other is determined arthroscopically. However, both stagings represent the pathological conditions associated with OCDs natural progression.While the arthroscopic classification of bone and cartilage lesions is considered standard, the Anderson MRI staging is the main form of staging used in this article. Stages I and II are stable lesions. Stages III and IV describe unstable lesions in which a lesion of the cartilage has allowed synovial fluid between the fragment and bone. Treatment Treatment options include modified activity with or without weight bearing; immobilization; cryotherapy; anti-inflammatory medication; drilling of subchondral bone; microfracture; removal or reattachment of loose bodies; mosaicplasty and osteoarticular transfer system (OATS) procedures. The primary goals of treatment are: Enhance the healing potential of subchondral bone; Fix unstable fragments while maintaining joint congruity; and Replace damaged bone and cartilage with implanted tissues or cells that can grow cartilage.The articular cartilages capacity for repair is limited: partial-thickness defects in the articular cartilage do not heal spontaneously, and injuries of the articular cartilage which fail to penetrate subchondral bone tend to lead to deterioration of the articular surface. As a result, surgery is often required in even moderate cases where the osteochondral fragment has not detached from the bone (Anderson Stage II, III). Non-surgical Candidates for non-operative treatment are limited to skeletally immature teenagers with a relatively small, intact lesion and the absence of loose bodies. Non-operative management may include activity modification, protected weight bearing (partial or non-weight bearing), and immobilization. The goal of non-operative intervention is to promote healing in the subchondral bone and prevent potential chondral collapse, subsequent fracture, and crater formation.Once candidates for treatment have been screened, treatment proceeds according to the lesions location. For example, those with OCD of the knee are immobilized for four to six weeks or even up to six months in extension to remove shear stress from the involved area; however, they are permitted to walk with weight bearing as tolerated. X-rays are usually taken three months after the start of non-operative therapy; if they reveal that the lesion has healed, a gradual return to activities is instituted. Those demonstrating healing by increased radiodensity in the subchondral region, or those whose lesions are unchanged, are candidates to repeat the above described three-month protocol until healing is noted. Surgery The choice of surgical versus non-surgical treatments for osteochondritis dissecans is controversial. Consequently, the type and extent of surgery necessary varies based on patient age, severity of the lesion, and personal bias of the treating surgeon—entailing an exhaustive list of suggested treatments. A variety of surgical options exist for the treatment of persistently symptomatic, intact, partially detached, and completely detached OCD lesions. Post-surgery reparative cartilage is inferior to healthy hyaline cartilage in glycosaminoglycan concentration, histological, and immunohistochemical appearance. As a result, surgery is often avoided if non-operative treatment is viable. Intact lesions If non-surgical measures are unsuccessful, drilling may be considered to stimulate healing of the subchondral bone. Arthroscopic drilling may be performed by using an antegrade (from the front) approach from the joint space through the articular cartilage, or by using a retrograde (from behind) approach through the bone outside of the joint to avoid penetration of the articular cartilage. This has proven successful with positive results at one-year follow-up with antegrade drilling in nine out of eleven teenagers with the juvenile form of OCD, and in 18 of 20 skeletally immature people (follow-up of five years) who had failed prior conservative programs. Hinged lesions Pins and screws can be used to secure flap (sometimes referred to as hinged) lesions. Bone pegs, metallic pins and screws, and other bioresorbable screws may be used to secure these types of lesions. Full thickness lesions The three methods most commonly used in treating full thickness lesions are arthroscopic drilling, abrasion, and microfracturing. In 1946, Magnusson established the use of stem cells from bone marrow with the first surgical debridement of an OCD lesion. These cells typically differentiate into fibrocartilage and rarely form hyaline cartilage. While small lesions can be resurfaced using this form of surgery, the repair tissue tends to have less strength than normal hyaline cartilage and must be protected for 6 to 12 months. Results for large lesions tend to diminish over time; this can be attributed to the decreased resilience and poor wear characteristics of the fibrocartilage.In attempts to address the weaker structure of the reparative fibrocartilage, new techniques have been designed to fill the defect with tissue that more closely simulates normal hyaline articular cartilage. One such technique is autologous chondrocyte implantation (ACI), which is useful for large, isolated femoral defects in younger people. In this surgery, chondrocytes are arthroscopically extracted from the intercondylar notch of the articular surface. The chondrocytes are grown and injected into the defect under a periosteal patch. ACI surgery has reported good to excellent results for reduced swelling, pain and locking in clinical follow-up examinations. However, some physicians have preferred to use undifferentiated pluripotential cells, such as periosteal cells and bone marrow stem cells, as opposed to chondrocytes. These too have demonstrated the ability to regenerate both the cartilage and the underlying subchondral bone.Similar to OATS, arthroscopic articular cartilage paste grafting is a surgical procedure offering cost-effective, long-lasting results for stage IV lesions. A bone and cartilage paste derived from crushed plugs of the non-weight-bearing intercondylar notch can achieve pain relief, repair damaged tissue, and restore function. Unstable lesions Some methods of fixation for unstable lesions include countersunk compression screws and Herbert screws or pins made of stainless steel or materials that can be absorbed by the body. If loose bodies are found, they are removed. Although each case is unique and treatment is chosen on an individual basis, ACI is generally performed on large defects in skeletally mature people. Rehabilitation Continuous passive motion (CPM) has been used to improve healing of the articular surface during the postoperative period for people with full-thickness lesions. It has been shown to promote articular cartilage healing for small (< 3 mm in diameter) lesions in rabbits. Similarly, Rodrigo and Steadman reported that CPM for six hours per day for eight weeks produced an improved clinical outcome in humans.A rehabilitation program often involves protection of the compromised articular surface and underlying subchondral bone combined with maintenance of strength and range of motion. Post-operative analgesics, namely a mix of opioids and NSAIDs, are usually required to control pain, inflammation and swelling. Straight leg raising and other isometric exercises are encouraged during the post-operative or immobilization period. A six to eight-week home or formal physical therapy program is usually instituted once the immobilization period has ended, incorporating range of motion, stretching, progressive strengthening, and functional or sport-specific training. During this time, patients are advised to avoid running and jumping, but are permitted to perform low impact activities, such as walking or swimming. If patients return to activity before the cartilage has become firm, they will typically complain of pain during maneuvers such as squatting or jumping. Prognosis The prognosis after different treatments varies and is based on several factors which include the age of the patient, the affected joint, the stage of the lesion and, most importantly, the state of the growth plate. It follows that the two main forms of osteochondritis dissecans are defined by skeletal maturity. The juvenile form of the disease occurs in open growth plates, usually affecting children between the ages of 5 and 15 years. The adult form commonly occurs between ages 16 to 50, although it is unclear whether these adults developed the disease after skeletal maturity or were undiagnosed as children.The prognosis is good for stable lesions (stage I and II) in juveniles with open growth plates; treated conservatively—typically without surgery—50% of cases will heal. Recovery in juveniles can be attributed to the bones ability to repair damaged or dead bone tissue and cartilage in a process called bone remodeling. Open growth plates are characterized by increased numbers of undifferentiated chondrocytes (stem cells) which are precursors to both bone and cartilaginous tissue. As a result, open growth plates allow for more of the stem cells necessary for repair in the affected joint. Unstable, large, full-thickness lesions (stage III and IV) or lesions of any stage found in the skeletally mature are more likely to fail non-operative treatment. These lesions offer a worse prognosis and surgery is required in most cases. Epidemiology OCD is a relatively rare disorder, with an estimated incidence of 15 to 30 cases per 100,000 persons per year. Widuchowski W et al. found OCD to be the cause of articular cartilage defects in 2% of cases in a study of 25,124 knee arthroscopies. Although rare, OCD is noted as an important cause of joint pain in active adolescents. The juvenile form of the disease occurs in children with open growth plates, usually between the ages 5 and 15 years and occurs more commonly in males than females, with a ratio between 2:1 and 3:1. However, OCD has become more common among adolescent females as they become more active in sports. The adult form, which occurs in those who have reached skeletal maturity, is most commonly found in people 16 to 50 years old.While OCD may affect any joint, the knee—specifically the medial femoral condyle in 75–85% of knee cases—tends to be the most commonly affected, and constitutes 75% of all cases. The elbow (specifically the capitulum of the humerus) is the second most affected joint with 6% of cases; the talar dome of the ankle represents 4% of cases. Less frequent locations include the patella, vertebrae, the femoral head, and the glenoid of the scapula.The oldest case of OCD was identified on the temporo-mandibular joint of the Qafzeh 9 fossil. History The condition was initially described by Alexander Monro (primus) in 1738. In 1870, James Paget described the disease process for the first time, but it was not until 1887 that Franz König published a paper on the cause of loose bodies in the joint. In his paper, König concluded that: Trauma had to be very severe to break off parts of the joint surface. Less severe trauma might contuse the bone to cause an area of necrosis which might then separate. In some cases, the absence of notable trauma made it likely that there existed some spontaneous cause of separation.König named the disease "osteochondritis dissecans", describing it as a subchondral inflammatory process of the knee, resulting in a loose fragment of cartilage from the femoral condyle. In 1922, Kappis described this process in the ankle joint. On review of all literature describing transchondral fractures of the talus, Berndt and Harty developed a classification system for staging of osteochondral lesions of the talus (OLTs). The term osteochondritis dissecans has persisted, and has since been broadened to describe a similar process occurring in many other joints, including the knee, hip, elbow, and metatarsophalangeal joints. Notable cases Michael Russell, American tennis player Kristina Vaculik, Canadian artistic gymnast Jonathan Vilma, American football linebacker Seo In-guk, Korean actor Veterinary aspects OCD also is found in animals, and is of particular concern in horses, as there may be a hereditary component in some horse breeds. Feeding for forced growth and selective breeding for increased size are also factors. OCD has also been studied in other animals—mainly dogs, especially the German Shepherd—where it is a common primary cause of elbow dysplasia in medium-large breeds.In animals, OCD is considered a developmental and metabolic disorder related to cartilage growth and endochondral ossification. Osteochondritis itself signifies the disturbance of the usual growth process of cartilage, and OCD is the term used when this affects joint cartilage causing a fragment to become loose.According to the Columbia Animal Hospital the frequency of affected animals is dogs, humans, pigs, horses, cattle, chickens, and turkeys, and in dogs the most commonly affected breeds include the German Shepherd, Golden and Labrador Retriever, Rottweiler, Great Dane, Bernese Mountain Dog, and Saint Bernard. Although any joint may be affected, those commonly affected by OCD in the dog are: shoulder (often bilaterally), elbow, knee and tarsus.The problem develops in puppyhood although often subclinically, and there may be pain or stiffness, discomfort on extension, or other compensating characteristics. Diagnosis generally depends on X-rays, arthroscopy, or MRI scans. While cases of OCD of the stifle go undetected and heal spontaneously, others are exhibited in acute lameness. Surgery is recommended once the animal has been deemed lame.Osteochondritis dissecans is difficult to diagnose clinically as the animal may only exhibit an unusual gait. Consequently, OCD may be masked by, or misdiagnosed as, other skeletal and joint conditions such as hip dysplasia. References External links Radiology MR and CT of OCD

Superior vena cava syndrome

Superior vena cava syndrome (SVCS), is a group of symptoms caused by obstruction of the superior vena cava ("SVC"), a short, wide vessel carrying circulating blood into the heart. The majority of cases are caused by malignant tumors within the mediastinum, most commonly lung cancer and non-Hodgkins lymphoma, directly compressing or invading the SVC wall. Non-malignant causes are increasing in prevalence due to expanding use of intravascular devices (such as permanent central venous catheters and leads for pacemakers and defibrillators), which can result in thrombosis. Other non-malignant causes include benign mediastinal tumors, aortic aneurysm, infections, and fibrosing mediastinitis.Characteristic features are edema (swelling due to excess fluid) of the face and arms and development of swollen collateral veins on the front of the chest wall. Shortness of breath and coughing are quite common symptoms; difficulty swallowing is reported in 11% of cases, headache in 6% and stridor (a high-pitched wheeze) in 4%. The symptoms are rarely life-threatening, though edema of the epiglottis can make breathing difficult, edema of the brain can cause reduced alertness, and in less than 5% of cases of SVCO, severe neurological symptoms or airway compromise are reported. Resolution of superior vena cava syndrome is directly related to the treatment of the underlying compression. Signs and symptoms Shortness of breath is the most common symptom, followed by face or arm swelling.Following are frequent symptoms: Difficulty breathing Headache Facial swelling Venous distention in the neck and distended veins in the upper chest and arms Migraines (especially if unusual to normal) Large decrease in lung capacity Facial swelling after bending/laying down Upper limb edema Lightheadedness Cough Edema (swelling) of the neck, called the collar of Stokes Pembertons signSuperior vena cava syndrome usually presents more gradually with an increase in symptoms over time as malignancies increase in size or invasiveness. Cause Over 80% of cases are caused by malignant tumors compressing the superior vena cava. Lung cancer, usually small cell carcinoma, comprises 75–80% of these cases and non-Hodgkin lymphoma, most commonly diffuse large B-cell lymphoma, comprises 10–15%. Rare malignant causes include Hodgkins lymphoma, metastatic cancers, leukemia, leiomyosarcoma of the mediastinal vessels, and plasmocytoma. Syphilis and tuberculosis have also been known to cause superior vena cava syndrome. SVCS can be caused by invasion or compression by a pathological process or by a deep vein thrombosis in the vein itself, although this latter is less common (approximately 35% due to the use of intravascular devices). Diagnosis The main techniques of diagnosing SVCS are with chest X-rays (CXR), CT scans, transbronchial needle aspiration at bronchoscopy and mediastinoscopy. CXRs often provide the ability to show mediastinal widening and may show the presenting primary cause of SVCS. However, 16% of people with SVC syndrome have a normal chest X-ray. CT scans should be contrast enhanced and be taken on the neck, chest, lower abdomen, and pelvis. They may also show the underlying cause and the extent to which the disease has progressed. Treatment Several methods of treatment are available, mainly consisting of careful drug therapy and surgery. Glucocorticoids (such as prednisone or methylprednisolone) decrease the inflammatory response to tumor invasion and edema surrounding the tumor. Glucocorticoids are most helpful if the tumor is steroid-responsive, such as lymphomas. In addition, diuretics (such as furosemide) are used to reduce venous return to the heart which relieves the increased pressure.In an acute setting, endovascular stenting by an interventional radiologist may provide relief of symptoms in as little as 12–24 hours with minimal risks.Should a patient require assistance with respiration whether it be by bag/valve/mask, bilevel positive airway pressure (BiPAP), continuous positive airway pressure (CPAP) or mechanical ventilation, extreme care should be taken. Increased airway pressure will tend to further compress an already compromised SVC and reduce venous return and in turn cardiac output and cerebral and coronary blood flow. Spontaneous respiration should be allowed during endotracheal intubation until sedation allows placement of an ET tube and reduced airway pressures should be employed when possible. Prognosis Symptoms are usually relieved with radiation therapy within one month of treatment. However, even with treatment, 99% of patients die within two and a half years. This relates to the cancerous causes of SVC found in 90% of cases. The average age of disease onset is 54 years. See also Pembertons sign References Further reading Wilson LD, Detterbeck FC, Yahalom J (May 2007). "Clinical practice. Superior vena cava syndrome with malignant causes". N Engl J Med. 356 (18): 1862–9. doi:10.1056/NEJMcp067190. PMID 17476012. Randolph HL Wong; Joshua Chai; Calvin SH Ng; et al. (2009). "Transvenous pacing lead-induced Superior Vena Cava Syndrome: What do we know?". Surgical Practice. 13 (4): 125–126. doi:10.1111/j.1744-1633.2009.00462.x. == External links ==

Periodic limb movement disorder

Periodic limb movement disorder (PLMD) is a sleep disorder where the patient moves limbs involuntarily and periodically during sleep, and has symptoms or problems related to the movement. PLMD should not be confused with restless legs syndrome (RLS). RLS is characterized by a voluntary response to an urge to move legs due to discomfort. PLMD on the other hand is involuntary, and the patient is often unaware of these movements altogether. Periodic limb movements (PLMS) occurring during daytime period can be found but are considered as a symptom of RLS. Only PLMS during sleep can suggest a diagnosis of PLMD.Periodic limb movement disorder is characterized by recurrent episodes of frequent limb movements while sleeping. It mostly happens in the lower parts of the body like the toes, ankles, knees and hips. It can also, in some cases, appear in the upper extremities of the body. These movements can lead the patient to wake up, and if so, sleep interruption can be the origin of excessive daytime sleepiness.PLMD is characterized by increased periodic limb movements during sleep (PLMS), which must coexist with a sleep disturbance or other functional impairment, in an explicit cause-effect relationship. Usually, these involuntary movements come from lower extremities (including toes, ankles, knees, and hips), although they can also be observed in upper extremities, occasionally. PLMS seem to be common features within many people, and identifying whether or not these movements are clinically relevant for a distinct diagnosis of PLMD remains a challenge for clinical and scientific fields. Moreover, diagnosis of PLMD cannot be used when narcolepsy, restless legs syndrome (RLS), REM sleep behaviour disorder (RBD) or untreated obstructive sleep apnea (OSA) is already diagnosed, since abnormal movements during sleep are frequent in these disorders. Signs and symptoms People with PLMD often have excessive daytime sleepiness (EDS), falling asleep during the day, trouble falling asleep at night, and difficulty staying asleep throughout the night. Patients also display involuntary limb movements that occur at periodic intervals anywhere from 20 to 40 seconds apart. They often only last the first half of the night during non-REM sleep stages. Movements do not occur during REM because of muscle atonia. PLMS can be unilateral or bilateral and not really symmetrical or simultaneous. PLMS is often a symptom of RLS but evidence for differences between those two sleep disorders was found in literature. Sleep structure differed, when RLS patients had significantly more REM sleep and less stage 1 sleep compared to PLMD patients. Besides, PLMI was significantly higher in patients with PLMD. Causes It is mostly unknown what causes PLMD, but in many cases the patient also has other medical problems such as Parkinsons disease or narcolepsy. Medical agents must be taken into consideration: several psychopharmacological drugs (serotonergic and tricyclic antidepressants, venlafaxine and mirtazapine) heighten the risk of PLMD. For women, the presence of musculoskeletal disease, heart disease, obstructive sleep apnea, cataplexy, doing physical activities close to bedtime and the presence of a mental disorder were significantly associated with having a higher risk of both PLMD and restless legs syndrome.PLMS seems to have an origin in the spinal cord. In fact, PLMS was suggested to be associated with increased spinal reflexes. Manifestations of PLMS seem to occur mostly in disorders associated with dopaminergic dysfunctions.Hypothesis of low ferritin levels in adult population was raised to explain PLMD where increased RLS severity and increased PLMS were significantly correlated with low ferritin levels. Research evidence suggested iron is possibly contributing to PLMD. Thus, lack of iron may induce inhibition of dopamine formation which might underlie PLMS. Diagnosis People with PLMD often do not know the cause of their excessive daytime sleepiness and their limb movements are reported by a spouse or sleep partner. PLMD cannot be diagnosed by polysomnogram (PSG) alone, it is necessary to obtain a full medical history and taking into account all available information.Polysomnography is recognized as the assessment method which brings most precise information on sleep quality, sleep structure and physiological parameters during sleep (respiration, heart rate, movements). Therefore, diagnostic of PLMD can usually be established only in laboratory settings. As people usually ignore the cause of their daytime impairments, PLMS during sleep are mostly found through laboratory examination rather than clinical complaints.Video-Polysomnography may be recommended to distinguish PLMS from other leg movements during sleep time which may be similar to PLMS when it comes to duration and pattern. Measures from PSG allocated to the diagnostic of PLMD are essentially based on electromyography (EMG) measuring muscle activity. EMG electrodes are usually placed on anterior tibialis muscle.Recent studies showed actigraphy may be combined to PSG as a screening tool for PLMD diagnosis. Actigraphs are watch-shaped devices - usually worn by adult population on the wrist - used to record sleep and wake periods for at least a week. Recent actigraphy devices allow more precise recordings which helps evaluating if actual movements meet diagnostic criteria for PLMD. Recent studies showed actigraph records reflect quite accurately PLMI criterion.Crucial for the diagnosis are the inter-movement intervals and the frequency of PLMS - each movement must happen within a 4 to 90 second interval from the previous movement. The periodic limb movement index (PLMI), which corresponds to the number of periodic limb movements per hour, must be more than 15 movements per hour in adults and 5 movements or more per hour in children. The diagnosis of PLMD requires a visible cause-effect relationship between PLMS and an observed sleep disturbance or daytime impairment (both disturbance and impairment have to be clinically significant).Other relevant causes of Insomnia and Hypersomnia have to be ruled out before diagnosing PLMD (most importantly anxiety, obstructive sleep apnea, and narcolepsy). Furthermore, symptoms can not be better explained by any other conditions.For the differential diagnosis it is important to differentiate PLMD from other leg movements during sleep, which are high-frequency: alternating leg movement activity (ALMA) are very similar events and could be mistaken for PLMS hypnagogic foot tremor (HFT) events are also very similar to PLMS and could be misdiagnosed excessive fragmentary myoclonus (EFM) events are shorter than PLMS Classification PLMD is classified in the third edition of the International Classification of Sleep Disorders (ICSD-3) which presents current sleep disorders nosology. ICSD-3 is divided in 7 sections and PLMD is classified in the Sleep-Related Movement Disorders section. There are some updates from ICSD-2. The diagnosis is more strict. A simple complaint is no longer enough: a significant clinical impairment is needed. Sleep impairments need to be clearly caused by PLMS and the symptoms also need to be explained solely by the PLMS. Treatment PLMD can be effectively treated with dopaminergic agents (pramipexole, ropinirole, cabergoline, and rotigotine) and it has been found that patients with a low ferritin level respond well to oral iron supplements. Adverse effects of these agents have been reported and include the occurrence of restless leg syndrome triggered by the medication, as well as cortical arousals, which are a cause of disturbed sleep. Patients must stay on these medications in order to experience relief, because there is no known cure for this disorder. PLMs tend to be exacerbated by tricyclic antidepressants, SSRIs, stress, and sleep deprivation. It is also advised not to consume caffeine, alcohol, or antidepressants as these substances could worsen the PLMD symptoms. Other medications aimed at reducing or eliminating the leg jerks or the arousals can be prescribed. Non-ergot derived dopaminergic medications (pramipexole and ropinirole) are preferred. Other dopaminergic agents such as co-careldopa, co-beneldopa, pergolide, or lisuride may also be used. These medications decrease or eliminate both the leg jerks and the arousals. These medications are also successful for the treatment of restless legs syndrome. In one study, co-careldopa was superior to dextropropoxyphene in decreasing the number of leg kicks and the number of arousals per hour of sleep. However, co-careldopa and, to a lesser extent, pergolide may shift the leg movements from the nighttime to the daytime.Clonazepam in doses of 1 mg has been shown to improve objective and subjective measures of sleep.Hypothesis was presented for supplementation of magnesium use for PLMD improvement due to evidence for therapeutic effects of magnesium on normal magnesium level patients with insomnia and RLS. Evidence of magnesium on pathomechanisms of PLMD has yet to be found. However, it remains insufficient evidences related to the efficacy of pharmacological treatment in PLMD, and its use has been based on the dopaminergic medication effect on RLS. Therefore, a careful clinical monitoring with any pharmacological use in PLMD is recommended. Epidemiology PLMD is estimated to occur in approximately 4% of adults (aged 15–100), but is more common in the elderly, especially females, with up to 11% experiencing symptoms. PLMD appears to be related to restless legs syndrome (RLS) - a study of 133 people found that 80% of those with RLS also had PLMS. However the opposite is not true: many people who have PLMS do not also have restless legs syndrome.PLMD is an uncommon childhood disorder. Based on adult criteria and PSG analysis, studies showed prevalence of isolated PLMD in children population with no other comorbidity about 1.2 to 1.5%. There was also evidence for 5.6 to 7.7% of children with PLMI > 5/hr. Periodic limb movements during sleep are associated with a lower quality of life in children with monosymptomatic nocturnal enuresis See also Hypnic jerk Restless legs syndrome References == External links ==

Pyelonephritis

Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may include pus around the kidney, sepsis, or kidney failure.It is typically due to a bacterial infection, most commonly Escherichia coli. Risk factors include sexual intercourse, prior urinary tract infections, diabetes, structural problems of the urinary tract, and spermicide use. The mechanism of infection is usually spread up the urinary tract. Less often infection occurs through the bloodstream. Diagnosis is typically based on symptoms and supported by urinalysis. If there is no improvement with treatment, medical imaging may be recommended.Pyelonephritis may be preventable by urination after sex and drinking sufficient fluids. Once present it is generally treated with antibiotics, such as ciprofloxacin or ceftriaxone. Those with severe disease may require treatment in hospital. In those with certain structural problems of the urinary tract or kidney stones, surgery may be required.Pyelonephritis affects about 1 to 2 per 1,000 women each year and just under 0.5 per 1,000 males. Young adult females are most often affected, followed by the very young and old. With treatment, outcomes are generally good in young adults. Among people over the age of 65 the risk of death is about 40%. Signs and symptoms Signs and symptoms of acute pyelonephritis generally develop rapidly over a few hours or a day. It can cause high fever, pain on passing urine, and abdominal pain that radiates along the flank towards the back. There is often associated vomiting.Chronic pyelonephritis causes persistent flank or abdominal pain, signs of infection (fever, unintentional weight loss, malaise, decreased appetite), lower urinary tract symptoms and blood in the urine. Chronic pyelonephritis can in addition cause fever of unknown origin. Furthermore, inflammation-related proteins can accumulate in organs and cause the condition AA amyloidosis.Physical examination may reveal fever and tenderness at the costovertebral angle on the affected side. Causes Most cases of community-acquired pyelonephritis are due to bowel organisms that enter the urinary tract. Common organisms are E. coli (70–80%) and Enterococcus faecalis. Hospital-acquired infections may be due to coliform bacteria and enterococci, as well as other organisms uncommon in the community (e.g., Pseudomonas aeruginosa and various species of Klebsiella). Most cases of pyelonephritis start off as lower urinary tract infections, mainly cystitis and prostatitis. E. coli can invade the superficial umbrella cells of the bladder to form intracellular bacterial communities (IBCs), which can mature into biofilms. These biofilm-producing E. coli are resistant to antibiotic therapy and immune system responses, and present a possible explanation for recurrent urinary tract infections, including pyelonephritis. Risk is increased in the following situations: Mechanical: any structural abnormalities in the urinary tract, vesicoureteral reflux (urine from the bladder flowing back into the ureter), kidney stones, urinary tract catheterization, ureteral stents or drainage procedures (e.g., nephrostomy), pregnancy, neurogenic bladder (e.g., due to spinal cord damage, spina bifida or multiple sclerosis) and prostate disease (e.g., benign prostatic hyperplasia) in men Constitutional: diabetes mellitus, immunocompromised states Behavioral: change in sexual partner within the last year, spermicide use Positive family history (close family members with frequent urinary tract infections) Diagnosis Laboratory examination Analysis of the urine may show signs of urinary tract infection. Specifically, the presence of nitrite and white blood cells on a urine test strip in patients with typical symptoms are sufficient for the diagnosis of pyelonephritis, and are an indication for empirical treatment. Blood tests such as a complete blood count may show neutrophilia. Microbiological culture of the urine, with or without blood cultures and antibiotic sensitivity testing are useful for establishing a formal diagnosis, and are considered mandatory. Imaging studies If a kidney stone is suspected (e.g. on the basis of characteristic colicky pain or the presence of a disproportionate amount of blood in the urine), a kidneys, ureters, and bladder x-ray (KUB film) may assist in identifying radioopaque stones. Where available, a noncontrast helical CT scan with 5 millimeter sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis. All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine. In patients with recurrent ascending urinary tract infections, it may be necessary to exclude an anatomical abnormality, such as vesicoureteral reflux or polycystic kidney disease. Investigations used in this setting include kidney ultrasonography or voiding cystourethrography. CT scan or kidney ultrasonography is useful in the diagnosis of xanthogranulomatous pyelonephritis; serial imaging may be useful for differentiating this condition from kidney cancer. Ultrasound findings that indicate pyelonephritis are enlargement of the kidney, edema in the renal sinus or parenchyma, bleeding, loss of corticomedullary differentiation, abscess formation, or an areas of poor blood flow on doppler ultrasound. However, ultrasound findings are seen in only 20% to 24% of people with pyelonephritis.A DMSA scan is a radionuclide scan that uses dimercaptosuccinic acid in assessing the kidney morphology. It is now the most reliable test for the diagnosis of acute pyelonephritis. Classification Acute pyelonephritis Acute pyelonephritis is an exudative purulent localized inflammation of the renal pelvis (collecting system) and kidney. The kidney parenchyma presents in the interstitium abscesses (suppurative necrosis), consisting in purulent exudate (pus): neutrophils, fibrin, cell debris and central germ colonies (hematoxylinophils). Tubules are damaged by exudate and may contain neutrophil casts. In the early stages, the glomerulus and vessels are normal. Gross pathology often reveals pathognomonic radiations of bleeding and suppuration through the renal pelvis to the renal cortex. Chronic pyelonephritis Chronic pyelonephritis implies recurrent kidney infections and can result in scarring of the renal parenchyma and impaired function, especially in the setting of obstruction. A perinephric abscess (infection around the kidney) and/or pyonephrosis may develop in severe cases of pyelonephritis. Xanthogranulomatous pyelonephritis Xanthogranulomatous pyelonephritis is an unusual form of chronic pyelonephritis characterized by granulomatous abscess formation, severe kidney destruction, and a clinical picture that may resemble renal cell carcinoma and other inflammatory kidney parenchymal diseases. Most affected individuals present with recurrent fevers and urosepsis, anemia, and a painful kidney mass. Other common manifestations include kidney stones and loss of function of the affected kidney. Bacterial cultures of kidney tissue are almost always positive. Microscopically, there are granulomas and lipid-laden macrophages (hence the term xantho-, which means yellow in ancient Greek). It is found in roughly 20% of specimens from surgically managed cases of pyelonephritis. Prevention In people who experience recurrent urinary tract infections, additional investigations may identify an underlying abnormality. Occasionally, surgical intervention is necessary to reduce the likelihood of recurrence. If no abnormality is identified, some studies suggest long-term preventive treatment with antibiotics, either daily or after sexual activity. In children at risk for recurrent urinary tract infections, not enough studies have been performed to conclude prescription of long-term antibiotics have a net positive benefit. Drinking cranberry juice does not appear to provide much if any benefit in decreasing urinary tract infections. Management In people suspected of having pyelonephritis, a urine culture and antibiotic sensitivity test is performed, so therapy can eventually be tailored on the basis of the infecting organism. As most cases of pyelonephritis are due to bacterial infections, antibiotics are the mainstay of treatment. The choice of antibiotic depends on the species and antibiotic sensitivity profile of the infecting organism, and may include fluoroquinolones, cephalosporins, aminoglycosides, or trimethoprim/sulfamethoxazole, either alone or in combination. Simple A 2018 systematic review recommended the use of norfloxacin as it has the lowest rate of side effects with a comparable efficacy to commonly used antibiotics.In people who do not require hospitalization and live in an area where there is a low prevalence of antibiotic-resistant bacteria, a fluoroquinolone by mouth such as ciprofloxacin or levofloxacin is an appropriate initial choice for therapy. In areas where there is a higher prevalence of fluoroquinolone resistance, it is useful to initiate treatment with a single intravenous dose of a long-acting antibiotic such as ceftriaxone or an aminoglycoside, and then continuing treatment with a fluoroquinolone. Oral trimethoprim/sulfamethoxazole is an appropriate choice for therapy if the bacteria is known to be susceptible. If trimethoprim/sulfamethoxazole is used when the susceptibility is not known, it is useful to initiate treatment with a single intravenous dose of a long-acting antibiotic such as ceftriaxone or an aminoglycoside. Oral beta-lactam antibiotics are less effective than other available agents for treatment of pyelonephritis. Improvement is expected in 48 to 72 hours. Complicated People with acute pyelonephritis that is accompanied by high fever and leukocytosis are typically admitted to the hospital for intravenous hydration and intravenous antibiotic treatment. Treatment is typically initiated with an intravenous fluoroquinolone, an aminoglycoside, an extended-spectrum penicillin or cephalosporin, or a carbapenem. Combination antibiotic therapy is often used in such situations. The treatment regimen is selected based on local resistance data and the susceptibility profile of the specific infecting organism(s).During the course of antibiotic treatment, serial white blood cell count and temperature are closely monitored. Typically, the intravenous antibiotics are continued until the person has no fever for at least 24 to 48 hours, then equivalent antibiotics by mouth can be given for a total of two–week duration of treatment. Intravenous fluids may be administered to compensate for the reduced oral intake, insensible losses (due to the raised temperature) and vasodilation and to optimize urine output. Percutaneous nephrostomy or ureteral stent placement may be indicated to relieve obstruction caused by a stone. Children with acute pyelonephritis can be treated effectively with oral antibiotics (cefixime, ceftibuten and amoxicillin/clavulanic acid) or with short courses (2 to 4 days) of intravenous therapy followed by oral therapy. If intravenous therapy is chosen, single daily dosing with aminoglycosides is safe and effective.Fosfomycin can be used as an efficacious treatment for both UTIs and complicated UTIs including acute pyelonephritis. The standard regimen for complicated UTIs is an oral 3g dose administered once every 48 or 72 hours for a total of 3 doses or a 6 grams every 8 hours for 7 days to 14 days when fosfomycin is given in IV form.Treatment of xanthogranulomatous pyelonephritis involves antibiotics as well as surgery. Removal of the kidney is the best surgical treatment in the overwhelming majority of cases, although polar resection (partial nephrectomy) has been effective for some people with localized disease. Watchful waiting with serial imaging may be appropriate in rare circumstances. Follow-up If no improvement is made in one to two days post therapy, inpatients should repeat an urine analysis and imaging. Outpatients should check again with their doctor. Epidemiology There are roughly 12–13 cases annually per 10,000 population in women receiving outpatient treatment and 3–4 cases requiring admission. In men, 2–3 cases per 10,000 are treated as outpatients and 1– cases/10,000 require admission. Young women are most often affected. Infants and the elderly are also at increased risk, reflecting anatomical changes and hormonal status. Xanthogranulomatous pyelonephritis is most common in middle-aged women. It can present somewhat differently in children, in whom it may be mistaken for Wilms tumor. Research According to a 2015 meta analysis, vitamin A has been shown to alleviate renal damage and/or prevent renal scarring. Terminology The term is from Greek πύελο|ς pýelo|s, "basin" + νεφρ|ός nepʰrós, "kidney" + suffix -itis suggesting "inflammation".A similar term is "pyelitis", which means inflammation of the renal pelvis and calyces. In other words, pyelitis together with nephritis is collectively known as pyelonephritis. Etymology The word pyelonephritis is formed by the Greek roots pyelo- from πύελος (púelos) renal pelvis and nephro- from νεφρός (nephrós) kidney together with the suffix -itis from -ῖτις (-itis) used in medicine to indicate diseases or inflammations. See also Interstitial nephritis Malakoplakia References External links NIDDK Atlas of Pathology

Abetalipoproteinemia

Abetalipoproteinemia (also known as: Bassen-Kornzweig syndrome, microsomal triglyceride transfer protein deficiency disease, MTP deficiency, and betalipoprotein deficiency syndrome) is a disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.It is a rare autosomal recessive disorder. Presentation Symptoms Often symptoms will arise that indicate the body is not absorbing or making the lipoproteins that it needs. These symptoms usually appear en masse.These symptoms come as follows: Failure to thrive (i.e. failure to grow in infancy) Steatorrhea (i.e. fatty, pale stools) Frothy stools Foul smelling stools Protruding abdomen Intellectual disability/developmental delay Developmental coordination disorder, evident by age ten Ataxia Muscle weakness Slurred speech (dysarthria) Scoliosis (curvature of the spine) Progressive decreased vision Balance and coordination problems Signs Acanthocytosis Retinitis pigmentosa Low blood cholesterol Features Abetalipoproteinemia affects the absorption of dietary fats, cholesterol, and certain vitamins. People affected by this disorder are not able to make certain lipoproteins, which are molecules that consist of proteins combined with cholesterol and particular fats called triglycerides. This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A, vitamin D, vitamin E, and vitamin K. However, many of the observed effects are due to vitamin E deficiency in particular. Signs and symptoms vary and present differently from person to person. In general, 80–99% of individuals exhibit malabsorption of fats and fat-soluble vitamins. Approximately 30%-79% of people with the disease display symptoms of abnormality of the retinal pigmentation, ataxia, muscular hypotonia or reduced tendon reflexes.The signs and symptoms of abetalipoproteinemia appear in the first few months of life (because pancreatic lipase is not active in this period). They can include failure to gain weight and grow at the expected rate (failure to thrive); diarrhea; abnormal spiny red blood cells (acanthocytosis); and fatty, foul-smelling stools (steatorrhea). The stool may contain large chunks of fat and/or blood. Infants often present with gastrointestinal problems caused by the poor fat absorption, which also contributes to steatorrhea. Other features of this disorder may develop later in childhood and often impair the function of the nervous system. They can include poor muscle coordination, difficulty with balance and movement (ataxia), and progressive degeneration of the retina (the light-sensitive layer in the posterior eye) that can progress to near-blindness (due to deficiency of vitamin A, retinol). Adults in their thirties or forties may have increasing difficulty with balance and walking. Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal column tracts. Genetics Mutations in the microsomal triglyceride transfer protein (MTTP) gene has been associated with this condition. (apolipoprotein B deficiency, a related condition, is associated with deficiencies of apolipoprotein B.)The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein, which is essential for creating beta-lipoproteins. These lipoproteins are both necessary for the absorption of fats, cholesterol, and fat-soluble vitamins from the diet and necessary for the efficient transport of these substances in the bloodstream. Most of the mutations in this gene lead to the production of an abnormally short microsomal triglyceride transfer protein, which prevents the normal creation of beta-lipoproteins in the body. MTTP-associated mutations are inherited in an autosomal recessive pattern, which means both copies of the gene must be faulty to produce the disease.The disease is extremely rare with approximately 100 reported cases worldwide since it was first identified by doctors Bassen and Kornzweig in 1950. Mechanism Abetalipoproteinemia effects multiple physiological systems, the two most common being the nervous and the skeletal. Disruption of nervous function includes loss of reflexes, speech impairments, tremors or involuntary motor tics, or peripheral neuropathy (damage to the nerves outside of the brain and spinal cord). Peripheral neuropathy causes loss of sensation, weakness or numbness and pain in the extremities through stabbing, burning, or tingling sensations. Skeletal system developments often include lordosis, kyphoscoliosis, or pes cavus. Individuals often have abnormal bleeding due to the difficulty of forming clots.Additional complications of the diseases if not properly treated include blindness, mental deterioration, ataxia, loss of peripheral nerve function. Diagnosis The initial workup of Abetalipoproteinemia typically consists of stool sampling, a blood smear, and a fasting lipid panel, though these tests are not confirmatory. As the disease is rare, though a genetics test is necessary for diagnosis, it is generally not done initially. However, prenatal testing may be available for pregnancies identified to be at an increased risk (if both parents are unaffected carrier or one parent is affected and the other in a carrier).Acanthocytes are seen on blood smear. Since there is no or little assimilation of chylomicrons, their levels in plasma remains low.The inability to absorb fat in the ileum will result in steatorrhea, or fat in the stool. As a result, this can be clinically diagnosed when foul-smelling stool is encountered. Low levels of plasma chylomicron are also characteristic.There is an absence of apolipoprotein B. On intestinal biopsy, vacuoles containing lipids are seen in enterocytes. This disorder may also result in fat accumulation in the liver (hepatic steatosis). Because the epithelial cells of the bowel lack the ability to place fats into chylomicrons, lipids accumulate at the surface of the cell, crowding the functions that are necessary for proper absorption.Multiple related disorders present with similar symptoms as abetalipoproteinemia that can provide a useful diagnosis through comparisons. Some of those disorders are: Treatment Treatment normally consists of rigorous dieting, involving massive amounts of vitamin E. High-dose Vitamin E therapy helps the body restore and produce lipoproteins, which people with abetalipoproteinemia usually lack. Vitamin E also helps keep skin and eyes healthy; studies show that many affected males will have vision problems later on in life. Common additional supplementation includes medium chain fatty acids and linoleic acid. Treatments also aim to slow the progression of nervous system abnormalities. Developmental coordination disorder and muscle weakness are usually treated with physiotherapy or occupational therapy. Dietary restriction of triglycerides has also been useful. Nutritionists often work with medical professionals to design appropriate dietary treatments for their patients. Prognosis Prognosis can vary heavily based on the severity of the neurological dysfunction. If treatment is initiated early in disease the neurologic sequelae may be reversed and further deterioration can be prevented. Long-term outlook is reasonably good for most people when diagnosed and treated early. A case study presented a female patient diagnosed at the age of 11. Despite the relatively late diagnosis, the patient married and at the age of 34, gave birth to a full-term healthy infant. Her medication included vitamin K 10 mg twice a week, beta-carotene 40,000 IU daily, vitamin A 10,000 IU daily, vitamin E 400 IU daily, vitamins B6 and B12, calcium, magnesium and eye drops.Prolonged vitamin deficiencies can further compromise health. Specifically, a prolonged vitamin E deficiency can lead to the development of limiting ataxia and gait disturbances. Some individuals may develop retinal degeneration and blindness. If left untreated, the condition may lead to death. Current Research The primary goal with Abetalipoproteinemia research is focused on supplying the fat-soluble vitamins the body lacks. Previous research considered the short term use of intravenous infusion of vitamins A and E. The goal was to determine whether these infusions would delay or counteract the symptoms in patients. No results were posted.More recent research has focused on different ways to supply the patient with Vitamin E. In 2018, the Journal of Lipid Research posted a study testing alternative forms of Vitamin E absorption. Currently, Vitamin E is most often supplemented in the fat-soluble form vitamin E acetate. Due to fat malabsorption, the intended supplementation is considerable compromised. Two different forms were tested: vitamin E tocofersolan and α-tocopherol acetate. The study concluded that plasma bioavailabilities were extremely low (2.8% and 3.1%, respectively. Additionally, plasma concentrations of tocopherol were not significantly different in patients.This study provides new insight in vitamin E supplementation and suggest further research is needed with different forms of Vitamin E as possible treatment options to abetalipoproteinemia.Currently, there is a clinical study recruiting abetalipoproteinemia patients to study inherited retinal degenerative disease. References External links Abetalipoproteinemia at NLM Genetics Home Reference

Atypical pneumonia

Atypical pneumonia, also known as walking pneumonia, is any type of pneumonia not caused by one of the pathogens most commonly associated with the disease. Its clinical presentation contrasts to that of "typical" pneumonia. A variety of microorganisms can cause it. When it develops independently from another disease, it is called primary atypical pneumonia (PAP). The term was introduced in the 1930s and was contrasted with the bacterial pneumonia caused by Streptococcus pneumoniae, at that time the best known and most commonly occurring form of pneumonia. The distinction was historically considered important, as it differentiated those more likely to present with "typical" respiratory symptoms and lobar pneumonia from those more likely to present with "atypical" generalized symptoms (such as fever, headache, sweating and myalgia) and bronchopneumonia. Signs and symptoms Usually the atypical causes also involve atypical symptoms: No response to common antibiotics such as sulfonamide and beta-lactams like penicillin. No signs and symptoms of lobar consolidation, meaning that the infection is restricted to small areas, rather than involving a whole lobe. As the disease progresses, however, the look can tend to lobar pneumonia. Absence of leukocytosis. Extrapulmonary symptoms, related to the causing organism. Moderate amount of sputum, or no sputum at all (i.e. non-productive). Lack of alveolar exudate. Despite general symptoms and problems with the upper respiratory tract (such as high fever, headache, a dry irritating cough followed later by a productive cough with radiographs showing consolidation), there are in general few physical signs. The patient looks better than the symptoms suggest. Cause The most common causative organisms are (often intracellular living) bacteria: Chlamydia pneumoniae Mild form of pneumonia with relatively mild symptoms. Chlamydia psittaci Causes psittacosis. Coxiella burnetii Causes Q fever. Francisella tularensis Causes tularemia. Legionella pneumophila Causes a severe form of pneumonia with a relatively high mortality rate, known as legionellosis or Legionnaires disease. Mycoplasma pneumoniae Usually occurs in younger age groups and may be associated with neurological and systemic (e.g. rashes) symptoms.Atypical pneumonia can also have a fungal, protozoan or viral cause.In the past, most organisms were difficult to culture. However, newer techniques aid in the definitive identification of the pathogen, which may lead to more individualized treatment plans. Viral Known viral causes of atypical pneumonia include respiratory syncytial virus (RSV), influenza A and B, parainfluenza, adenovirus, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), COVID-19 and measles. Diagnosis Chest radiographs (X-ray photographs) often show a pulmonary infection before physical signs of atypical pneumonia are observable at all. This is occult pneumonia. In general, occult pneumonia is rather often present in patients with pneumonia and can also be caused by Streptococcus pneumoniae, as the decrease of occult pneumonia after vaccination of children with a pneumococcal vaccine suggests.Infiltration commonly begins in the perihilar region (where the bronchus begins) and spreads in a wedge- or fan-shaped fashion toward the periphery of the lung field. The process most often involves the lower lobe, but may affect any lobe or combination of lobes. Epidemiology Mycoplasma is found more often in younger than in older people. Older people are more often infected by Legionella. Terminology "Primary atypical pneumonia" is called primary because it develops independently of other diseases.It is commonly known as "walking pneumonia" because its symptoms are often mild enough that one can still be up and about."Atypical pneumonia" is atypical in that it is caused by atypical organisms (other than Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). These atypical organisms include special bacteria, viruses, fungi, and protozoa. In addition, this form of pneumonia is atypical in presentation with only moderate amounts of sputum, no consolidation, only small increases in white cell counts, and no alveolar exudate.At the time that atypical pneumonia was first described, organisms like Mycoplasma, Chlamydophila, and Legionella were not yet recognized as bacteria and instead considered viruses. Hence "atypical pneumonia" was also called "non-bacterial".In literature the term atypical pneumonia is current, sometimes contrasted with viral pneumonia (see below) and sometimes, though incorrectly, with bacterial pneumonia. Many of the organisms causative of atypical pneumonia are unusual types of bacteria (Mycoplasma is a type of bacteria without a cell wall and Chlamydias are intracellular bacteria). As the conditions caused by the various agents have different courses and respond to different treatments, the identification of the specific causative pathogen is important. References == External links ==

Paraphimosis

Paraphimosis is an uncommon medical condition in which the foreskin of a penis becomes trapped behind the glans penis, and cannot be reduced (pulled back to its normal flaccid position covering the glans). If this condition persists for several hours or there is any sign of a lack of blood flow, paraphimosis should be treated as a medical emergency, as it can result in gangrene. Causes Paraphimosis is usually caused by medical professionals (iatrogenic) or parents who handle the foreskin improperly. The foreskin may be retracted during penile examination, penile cleaning, urethral catheterization, or cystoscopy; if the foreskin is left retracted for a long period, some of the foreskin tissue may become edematous (swollen with fluid), which makes subsequent reduction of the foreskin difficult. Prevention and treatment Paraphimosis can be avoided by bringing the foreskin back into its normal, forward, non-retracted position after retraction is no longer necessary (for instance, after cleaning the glans penis or placing a Foley catheter). Phimosis (both pathologic and normal childhood physiologic forms) is a risk factor for paraphimosis; physiologic phimosis resolves naturally as a child matures, but it may be advisable to treat pathologic phimosis via long-term stretching or elective surgical techniques (such as preputioplasty to loosen the preputial orifice or circumcision to amputate the foreskin tissue partially or completely).The foreskin responds to the application of tension to cause expansion by creating new skin cells though the process of mitosis. The tissue expansion is permanent. Non-surgical stretching of the foreskin may be used to widen a narrow, non-retractable foreskin. Stretching may be combined with the use of a corticosteroid cream. Beaugé recommends manual stretching for young males in preference to circumcision as a treatment for non-retractile foreskin because of the preservation of sexual sensation.Paraphimosis can often be effectively treated by manual manipulation of the swollen foreskin tissue. This involves compressing the glans penis and moving the foreskin back to its normal position, perhaps with the aid of a lubricant, cold compression, and local anesthesia as necessary. If this fails, the tight edematous band of tissue can be relieved surgically with a dorsal slit, or a circumcision. An alternative method, the Dundee technique, entails placing multiple punctures in the swollen foreskin with a fine needle, and then expressing the edema fluid by manual pressure. According to Ghory and Sharma, treatment by circumcision may be elected as "a last resort, to be performed by a urologist". Other experts recommend delaying elective circumcision until after paraphimosis has been resolved. References == External links ==

Budd–Chiari syndrome

Budd–Chiari syndrome is a very rare condition, affecting one in a million adults. The condition is caused by occlusion of the hepatic veins that drain the liver. It presents with the classical triad of abdominal pain, ascites, and liver enlargement. The formation of a blood clot within the hepatic veins can lead to Budd–Chiari syndrome. The syndrome can be fulminant, acute, chronic, or asymptomatic. Subacute presentation is the most common form. Signs and symptoms The acute syndrome presents with rapidly progressive severe upper abdominal pain, yellow discoloration of the skin and whites of the eyes, liver enlargement, enlargement of the spleen, fluid accumulation within the peritoneal cavity, elevated liver enzymes, and eventually encephalopathy. The fulminant syndrome presents early with encephalopathy and ascites. Liver cell death and severe lactic acidosis may be present as well. Caudate lobe enlargement is often present. The majority of patients have a slower-onset form of Budd–Chiari syndrome. This can be painless. A system of venous collaterals may form around the occlusion which may be seen on imaging as a "spiders web". Patients may progress to cirrhosis and show the signs of liver failure.On the other hand, incidental finding of a silent, asymptomatic form may not be a cause for concern. Causes The cause can be found in more than 80% of patients. Primary Budd–Chiari syndrome (75%): thrombosis of the hepatic vein Hepatic vein thrombosis is associated with the following in decreasing order of frequency:Polycythemia vera Pregnancy Postpartum state Use of oral contraceptives Paroxysmal nocturnal hemoglobinuria Hepatocellular carcinoma Lupus anticoagulantsSecondary Budd–Chiari syndrome (25%): compression of the hepatic vein by an outside structure (e.g. a tumor)Budd–Chiari syndrome is also seen in tuberculosis, congenital venous webs and occasionally in inferior vena caval stenosis. Often, the patient is known to have a tendency towards thrombosis, although Budd–Chiari syndrome can also be the first symptom of such a tendency. Examples of genetic tendencies include protein C deficiency, protein S deficiency, the Factor V Leiden mutation, hereditary anti-thrombin deficiency and prothrombin mutation G20210A. An important non-genetic risk factor is the use of estrogen-containing (combined) forms of hormonal contraception. Other risk factors include the antiphospholipid syndrome, aspergillosis, Behçets disease, dacarbazine, pregnancy, and trauma.Many patients have Budd–Chiari syndrome as a complication of polycythemia vera (myeloproliferative disease of red blood cells). People who have paroxysmal nocturnal hemoglobinuria (PNH) appear to be especially at risk for Budd–Chiari syndrome, more than other forms of thrombophilia: up to 39% develop venous thromboses, and 12% may acquire Budd-Chiari.A related condition is veno-occlusive disease, which occurs in recipients of bone marrow transplants as a complication of their medication. Although its mechanism is similar, it is not considered a form of Budd–Chiari syndrome.Other toxicologic causes of veno-occlusive disease include plant & herbal sources of pyrrolizidine alkaloids such as Borage, Boneset, Coltsfoot, Tu-san-chi, Comfrey, Heliotrope (sunflower seeds), Gordolobo, Germander, and Chaparral. Pathophysiology Any obstruction of the venous vasculature of the liver is referred to as Budd–Chiari syndrome, from the venules to the right atrium. This leads to increased portal vein and hepatic sinusoid pressures as the blood flow stagnates. The increased portal pressure causes increased filtration of vascular fluid with the formation of ascites in the abdomen and collateral venous flow through alternative veins leading to esophageal, gastric and rectal varices. Obstruction also causes centrilobular necrosis and peripheral lobule fatty change due to ischemia. If this condition persists chronically what is known as nutmeg liver will develop. Kidney failure may occur, perhaps due to the body sensing an "underfill" state and subsequent activation of the renin-angiotensin pathways and excess sodium retention. Diagnosis When Budd–Chiari syndrome is suspected, measurements are made of liver enzyme levels and other organ markers (creatinine, urea, electrolytes, LDH).Budd–Chiari syndrome is most commonly diagnosed using ultrasound studies of the abdomen and retrograde angiography. Ultrasound may show obliteration of hepatic veins, thrombosis or stenosis, spiderweb vessels, large collateral vessels, or a hyperechoic cord replacing a normal vein. Computed tomography (CT) or magnetic resonance imaging (MRI) is sometimes employed although these methods are generally not as sensitive. Liver biopsy is nonspecific but sometimes necessary to differentiate between Budd–Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia or Reyes syndrome. Evaluation for a JAK2 V617F mutation is recommended. Treatment A minority of patients can be treated medically with sodium restriction, diuretics to control ascites, anticoagulants such as heparin and warfarin, and general symptomatic management. However, the majority of patients require further intervention. Milder forms of Budd–Chiari may be treated with surgical shunts to divert blood flow around the obstruction or the liver itself. Shunts must be placed early after diagnosis for best results. The TIPS is similar to a surgical shunt: it accomplishes the same goal but has a lower procedure-related mortality, a factor that has led to a growth in its popularity. If all the hepatic veins are blocked, the portal vein can be approached via the intrahepatic part of inferior vena cava, a procedure called DIPS (direct intrahepatic portocaval shunt). Patients with stenosis or vena caval obstruction may benefit from angioplasty. Limited studies on thrombolysis with direct infusion of urokinase and tissue plasminogen activator into the obstructed vein have shown moderate success in treating Budd–Chiari syndrome; however, it is not routinely attempted.Liver transplantation is an effective treatment for Budd–Chiari. It is generally reserved for patients with fulminant liver failure, failure of shunts, or progression of cirrhosis that reduces the life expectancy to one year. Long-term survival after a transplant ranges from 69 to 87%. The most common complications of transplants are rejection, arterial or venous thromboses, and bleeding due to the need for anticoagulants. Up to 10% of patients may have a recurrence of Budd–Chiari syndrome after the transplant. Prognosis Several studies have attempted to predict the survival of patients with Budd–Chiari syndrome. In general, nearly 2/3 of patients with Budd–Chiari are alive at 10 years. Important negative prognostic indicators include ascites, encephalopathy, elevated Child-Pugh scores, elevated prothrombin time, and altered serum levels of various substances (sodium, creatinine, albumin, and bilirubin). Survival is also highly dependent on the underlying cause of the Budd–Chiari syndrome. For example, a patient with an underlying myeloproliferative disorder may progress to acute leukemia, independently of Budd–Chiari syndrome. Eponym It is named after George Budd, a British physician, and Hans Chiari, an Austrian pathologist. References External links Syndrome 10-138d.Budd–Chiari Syndrome at Merck Manual of Diagnosis and Therapy Home Edition

Fungal meningitis

Fungal meningitis refers to meningitis caused by a fungal infection. Signs and symptoms Symptoms of fungal meningitis are generally similar to those of other types of meningitis, and include: a fever, stiff neck, severe headache, photophobia (sensitivity to light), nausea and vomiting, and altered mental status (drowsiness or confusion). Causes Fungal meningitis may be caused by the following (and also other) types of fungi: Candida - C. albicans is the most common Candida species that causes infections of the central nervous system. Coccidioides - it is endemic to southwestern United States and Mexico. A third of patients presenting with disseminated coccidioidomycosis have developed meningitis. Histoplasma - occurs in bird and bat droppings and is endemic to parts of the United States, South, and Central America. Involvement of the central nervous system occurs in about 10-20% of cases of disseminated histoplasmosis. Blastomyces - occurs in soil rich in decaying organic matter in the Midwest United States. Meningitis is an unusual manifestation of blastomycosis and can be very difficult to diagnose. Cryptococcus (Cryptococcal meningitis) - it is thought to be acquired through inhalation of soil contaminated with bird droppings. C. neoformans is the most common pathogen to cause fungal meningitis. Aspergillus - Aspergillus infections account for 5% of fungal infections involving the central nervous system. Risk factors Individuals with a weak immune system are most at risk. This includes individuals taking immunosuppressive medication, cancer patients, HIV patients, premature babies with very low birth weight, the elderly, etc. People who are at an increased risk of acquiring particular fungal infections in general may also be at an increased risk of developing fungal meningitis, as the infection may in some cases spread to the central nervous system. People residing in the Midwestern United States, and Southwestern United States and Mexico are at an increased risk of infection with Histoplasma and Coccidioides, respectively. Diagnosis If suspected, fungal meningitis is diagnosed by testing blood and cerebrospinal fluid for pathogens. Identifying the specific pathogen is necessary to determine the proper course of treatment and the prognosis. Measurement of opening pressure, cell count with differential, glucose and protein concentrations, Grams stain, India ink, and culture tests should be performed on cerebrospinal fluid when fungal meningitis is suspected. Treatment Fungal meningitis is treated with long courses of high dose antifungal medications. The duration of treatment is dependent upon the causal pathogen and the patients ability to stave off the infection; for patients with a weaker immune system or diabetes, treatment will often take longer. Prognosis Prognosis depends on the pathogen responsible for the infection and risk group. Overall mortality for Candida meningitis is 10-20%, 31% for patients with HIV, and 11% in neurosurgical cases (when treated). Prognosis for Aspergillus and coccidioidal infections is poor. Outbreaks As of November 5, 2012, the CDC reported that 409 patients had laboratory-confirmed fungal meningitis caused by injections with contaminated medication. There had been 30 fatalities. A black mold, Exserohilum rostratum, was found in 45 of these cases. Aspergillus fumigatus was found in one case, and a Cladosporium species was found in one case.Aspergillus has been very rarely associated with meningitis while cases caused explicitly by Exserohilum in otherwise healthy individuals have not been previously reported. See also Meningitis Cryptococcal meningitis References == External links ==

Peutz–Jeghers syndrome

Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanosis). This syndrome can be classed as one of various hereditary intestinal polyposis syndromes and one of various hamartomatous polyposis syndromes. It has an incidence of approximately 1 in 25,000 to 300,000 births. Signs and symptoms The risks associated with this syndrome include a substantial risk of cancer, especially of the breast and gastrointestinal tracts. Colorectal is the most common malignancy, with a lifetime risk of 39 percent, followed by breast cancer in females with a lifetime risk of 32 to 54 percent.Patients with the syndrome also have an increased risk of developing carcinomas of the liver, lungs, breast, ovaries, uterus, testes, and other organs. Specifically, it is associated with an increased risk of sex-cord stromal tumor with annular tubules in the ovaries.Due to the increased risk of malignancies, direct surveillance is recommended.The average age of first diagnosis is 23. The first presentation is often bowel obstruction or intussuseption from the hamartomatous gastrointestinal polyps. Dark blue, brown, and black pigmented mucocutaneous macules, are present in over 95 percent of individuals with Peutz-Jeghers syndrome. Pigmented lesions are rarely present at birth, but often appear before 5 years of age. The macules may fade during puberty. The mealoncytic macules are not associated with malignant transformation.Complications associated with Peutz-Jeghers syndrome include obstruction and intussusception, which occur in up to 69 percent of patients, typically first between the ages of 6 and 18, though surveillance for them is controversial. Anemia is also common due to gastrointestinal bleeding from the polyps. Genetics In 1998, a gene was found to be associated with the mutation. On chromosome 19, the gene known as STK11 (LKB1) is a possible tumor suppressor gene. It is inherited in an autosomal dominant pattern, which means that anyone who has PJS has a 50% chance of passing the disease on to their offspring.Peutz–Jeghers syndrome is rare and studies typically include only a small number of patients. Even in those few studies that do contain a large number of patients, the quality of the evidence is limited due to pooling patients from many centers, selection bias (only patients with health problems coming from treatment are included), and historical bias (the patients reported are from a time before advances in the diagnosis of treatment of Peutz–Jeghers syndrome were made). Probably due to this limited evidence base, cancer risk estimates for Peutz–Jeghers syndrome vary from study to study. There is an estimated 18–21% risk of ovarian cancer, 9% risk of endometrial cancer, and 10% risk of cervical cancer, specifically adenoma malignum. Diagnosis The main criteria for clinical diagnosis are: Family history Mucocutaneous lesions causing patches of hyperpigmentation in the mouth and on the hands and feet. The oral pigmentations are the first on the body to appear, and thus play an important part in early diagnosis. Intraorally, they are most frequently seen on the gingiva, hard palate and inside of the cheek. The mucosa of the lower lip is almost invariably involved as well. Hamartomatous polyps in the gastrointestinal tract. These are benign polyps with an extraordinarily low potential for malignancy.Having 2 of the 3 listed clinical criteria indicates a positive diagnosis. The oral findings are consistent with other conditions, such as Addisons disease and McCune–Albright syndrome, and these should be included in the differential diagnosis. 90–100% of patients with a clinical diagnosis of PJS have a mutation in the STK11/LKB1 gene. Molecular genetic testing for this mutation is available clinically. Management Resection of the polyps is required only if serious bleeding or intussusception occurs. Enterotomy is performed for removing large, single nodules. Short lengths of heavily involved intestinal segments can be resected. Colonoscopy can be used to snare the polyps if they are within reach. Prognosis Most patients will develop flat, brownish spots (melanotic macules) on the skin, especially on the lips and oral mucosa, during the first year of life, and a patients first bowel obstruction due to intussusception usually occurs between the ages of six and 18 years. The cumulative lifetime cancer risk begins to rise in middle age. Cumulative risks by age 70 for all cancers, gastrointestinal (GI) cancers, and pancreatic cancer are 85%, 57%, and 11%, respectively.A 2011 Dutch study followed 133 patients for 14 years. The cumulative risk for cancer was 40% and 76% at ages 40 and 70, respectively. 42 (32%) of the patients died during the study, of which 28 (67%) were cancer related. They died at a median age of 45. Mortality was increased compared with the general population.A family with sinonasal polyposis were followed up for 28 years. Two cases of sinonasal type adenocarcinoma developed. This is a rare cancer. This report suggested that follow up of sinus polyps in this syndrome may be indicated. Monitoring Some suggestions for surveillance for cancer include the following: Small intestine with small bowel radiography every 2 years, Esophagogastroduodenoscopy and colonoscopy every 2 years, CT scan or MRI of the pancreas yearly, Ultrasound of the pelvis and testes yearly Mammography from age 25 annually Papanicolaou smear (Pap smear) annually beginning at age 18-20Follow-up care should be supervised by a physician familiar with Peutz–Jeghers syndrome. Genetic consultation and counseling as well as urological and gynecological consultations are often needed. Eponym First described in a published case report in 1921 by Jan Peutz (1886–1957), a Dutch Internist, it was later formalized into the syndrome by American physicians at Boston City Hospital, Harold Joseph Jeghers (1904–1990) and Kermit Harry Katz (1914–2003), and Victor Almon McKusick (1921–2008) in 1949 and published in the New England Journal of Medicine. See also List of cutaneous conditions Sex cord tumour with annular tubules References External links GeneReviews/NCBI/NIH/UW entry on Peutz-Jeghers syndrome Peutz-Jeghers syndrome – Genetics Home Reference

Umbilical hernia

An umbilical hernia is a health condition where the abdominal wall behind the navel is damaged. It may cause the navel to bulge outwards—the bulge consisting of abdominal fat from the greater omentum or occasionally parts of the small intestine. The bulge can often be pressed back through the hole in the abdominal wall, and may "pop out" when coughing or otherwise acting to increase intra-abdominal pressure. Treatment is surgical, and surgery may be performed for cosmetic as well as health-related reasons. Signs and symptoms A hernia is present at the site of the umbilicus (commonly called a navel or belly button) in newborns; although sometimes quite large, these hernias tend to resolve without any treatment by around the age of 2–3 years. Obstruction and strangulation of the hernia is rare because the underlying defect in the abdominal wall is larger than in an inguinal hernia of the newborn. The size of the base of the herniated tissue is inversely correlated with risk of strangulation (i.e., a narrow base is more likely to strangulate). Babies are prone to this malformation because of the process during fetal development by which the abdominal organs form outside the abdominal cavity, later returning into it through an opening which will become the umbilicus.Hernias may be asymptomatic and present only as a bulge of the umbilicus. Symptoms may develop when the contracting abdominal wall causes pressure on the hernia contents. This results in abdominal pain or discomfort. These symptoms may be worsened by the patient lifting or straining. Causes The causes of umbilical hernia are congenital and acquired malformation, but an apparent third cause is really a cause of a different type, a paraumbilical hernia. Congenital Congenital umbilical hernia is a congenital malformation of the navel (umbilicus). Among adults, it is three times more common in women than in men; among children, the ratio is roughly equal. It is also found to be more common in children of African descent. Acquired An acquired umbilical hernia directly results from increased intra-abdominal pressure caused by obesity, heavy lifting, a long history of coughing, or multiple pregnancies. Another type of acquired umbilical hernias are incisional hernias, which are hernia developing in a scar following abdominal surgery, e.g. after insertion of laparoscopy trocars through the umbilicus. Paraumbilical Importantly, an umbilical hernia must be distinguished from a paraumbilical hernia, which occurs in adults and involves a defect in the midline near to the umbilicus, and from omphalocele. Diagnosis Navels with the umbilical tip protruding past the umbilical skin ("outies") are often mistaken for umbilical hernias, which are a completely different shape. Treatment for cosmetic purposes is not necessary, unless there are health concerns such as pain, discomfort or incarceration of the hernia content. Incarceration refers to the inability to reduce the hernia back into the abdominal cavity. Prolonged incarceration can lead to tissue ischemia (strangulation) and shock when untreated. Umbilical hernias are common. With a study involving Africans, 92% of children had protrusions, 49% of adults, and 90% of pregnant women. However, a much smaller number actually had hernias: only 23% of children, 8% of adults, and 15% of pregnant women.When the orifice is small (< 1 or 2 cm), 90% close within 3 years (some sources state 85% of all umbilical hernias, regardless of size), and if these hernias are asymptomatic, reducible, and dont enlarge, no surgery is needed (and in other cases it must be considered). Treatment Children In some communities mothers routinely push the small bulge back in and tape a coin over the palpable hernia hole until closure occurs. This practice is not medically recommended as there is a small risk of trapping a loop of bowel under part of the coin resulting in a small area of ischemic bowel. This "fix" does not help and germs may accumulate under the tape, causing infection. The use of bandages or other articles to continuously reduce the hernia is not evidence-based.An umbilical hernia can be fixed in two different ways. The surgeon can opt to stitch the walls of the abdomen or he/she can place mesh over the opening and stitch it to the abdominal walls. The latter is of a stronger hold and is commonly used for larger defects in the abdominal wall. Most surgeons will not repair the hernia until 5–6 years after the baby is born. Most umbilical hernias in infants and children close spontaneously and rarely have complications of gastrointestinal-content incarcerations.How far the projection of the swelling extends from the surface of the abdomen (the belly) varies from child to child. In some, it may be just a small protrusion; in others it may be a large rounded swelling that bulges out when the baby cries. It may hardly be visible when the child is quiet and or sleeping.Normally, the abdominal muscles converge and fuse at the umbilicus during the formation stage, however, in some cases, there remains a gap where the muscles do not close and through this gap the inner intestines come up and bulge under the skin, giving rise to an umbilical hernia. The bulge and its contents can easily be pushed back and reduced into the abdominal cavity.In contrast to an inguinal hernia, the complication incidence is very low, and in addition, the gap in the muscles usually closes with time and the hernia disappears on its own. The treatment of this condition is essentially conservative: observation allowing the child to grow up and see if it disappears. Operation and closure of the defect is required only if the hernia persists after the age of 3 years or if the child has an episode of complication during the period of observation like irreducibility, intestinal obstruction, abdominal distension with vomiting, or red shiny painful skin over the swelling. Surgery is always done under anesthesia. The defect in the muscles is defined and the edges of the muscles are brought together with sutures to close the defect. In general, the child needs to stay in the hospital for 1 day and the healing is complete within 8 days.At times, there may be a fleshy red swelling seen in the hollow of the umbilicus that persists after the cord has fallen off. It may bleed on touch, or may stain the clothes that come in contact with it. This needs to be shown to a pediatric surgeon. This is most likely to be an umbilical polyp and the therapy is to tie it at the base with a stitch so that it falls off and there is no bleeding. Alternatively, it may be an umbilical granuloma that responds well to local application of dry salt or silver nitrate but may take a few weeks to heal and dry. Adults Many hernias never cause any problems, and do not require any treatment at all. However, because the risk of complications with age are higher and the hernia is unlikely to resolve without treatment, surgery is usually recommended.Usually hernia has content of bowel, abdominal fat or omentum, tissue that normally would reside inside the abdominal cavity if it wasnt for the hernia. In some cases, the content gets trapped in the hernia sac, outside the abdominal wall. The blood flow to this trapped tissue may be compromised, or the content even strangulated in some cases. Depending on the severity and duration of blood flow compromise, it can cause some pain and discomfort. Usually the situation resolves itself, when the protrusion of content is returned to the abdominal cavity. Sometimes this needs to be done by a doctor at the ICU.The hernia content becoming trapped combined with severe pain, inability to perform bowel movement or pass gas, swelling, fever, nausea and/or discoloration over the area could be signs of a prolonged compromise in blood flow of the hernia content. If so, emergency surgery is often required, since prolonged compromise in blood flow otherwise threatens organ integrity.If hernias are symptomatic and disturb daily activity or have had episodes of threatening incarceration, preventive surgical treatment can be considered. The surgery is performed under anaesthesia, while the surgeon identifies the edges of the defect and bring them together permanently using either suture or mesh. Small umbilical hernias are often successfully repaired with suture, while larger hernias may require a suitable mesh, although some surgeons advocate mesh treatment for most hernias. The most common complications for both techniques are superficial wound infections and recurrence of the hernia and some people experience pain at the surgical site. See also Fetal development Umbilicoplasty Paraumbilical hernia Omphalocoele References External links Overview at Cincinnati Childrens Hospital Medical Center Overview at Penn State