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Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.
Second line therapies include: mycophenolate mofetil (cellcept) which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement.
Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (>90%) With this treatment most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%) and have elimination of peripheral blood DNTs. Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin and it has not been reported to cause hypogammaglobulinemia. Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires therapeutic drug monitoring. It is the second most commonly used agent in patients that require chronic therapy. It is mostly well tolerated (though side effects include mucositis, diarrhea, hyperlipidemia, delayed wound healing) with drug-drug interactions. It has better activity against autoimmune disease and lymphoproliferation than mycophenolate mofetil and other drugs; however, sirolimus requires therapeutic drug monitoring and can cause mucositis. A risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence. Its mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. The Goal serum trough is 5-15 ng/ml and can consider PCP prophylaxis but usually not needed.
Other treatments may include drugs like Fansidar, mercaptopurine: More commonly used in Europe. Another is rituximab but this can cause lifelong hypogammaglobulinemia and a splenectomy but there is a >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis
Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.
RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare genetic disorder of the immune system. RALD is characterized by lymphadenopathy, splenomegaly, autoimmunity, and elevation in granulocytes and monocytes. It shares many features with autoimmune lymphoproliferative syndrome and is caused by somatic mutations in NRAS or KRAS. This was first described by investigators João Oliveira and Michael Lenardo from the National Institutes of Health.
Autoimmune lymphoproliferative syndrome (ALPS), also known as Canale-Smith syndrome, is a form of lymphoproliferative disorder (LPDs). It affects lymphocyte apoptosis. It is a RASopathy.
It is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Normally, after infectious insult, the immune system down-regulates by increasing Fas expression on activated B and T lymphocytes and Fas-ligand on activated T lymphocytes. Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, autoimmune disease, and secondary cancers.
An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.
An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:
- By the component(s) of the immune system affected
- By whether the immune system is overactive or underactive
- By whether the condition is congenital or acquired
According to the International Union of Immunological Societies, more than 150 primary immunodeficiency diseases (PIDs) have been characterized. However, the number of acquired immunodeficiencies exceeds the number of PIDs.
It has been suggested that most people have at least one primary immunodeficiency. Due to redundancies in the immune system, though, many of these are never detected.
Iodine deficiency is treated by ingestion of iodine salts, such as found in food supplements. Mild cases may be treated by using iodized salt in daily food consumption, or drinking more milk, or eating egg yolks, and saltwater fish. For a salt and/or animal product restricted diet, sea vegetables (kelp, hijiki, dulse, nori (found in sushi)) may be incorporated regularly into a diet as a good source of iodine.
The recommended daily intake of iodine for adult women is 150–300 µg for maintenance of normal thyroid function; for men it is somewhat less at 150 µg.
However, too high iodine intake, for example due to overdosage of iodine supplements, can have toxic side effects. It can lead to hyperthyroidism and consequently high blood levels of thyroid hormones (hyperthyroxinemia). In case of extremely high single-dose iodine intake, typically a short-term suppression of thyroid function (Wolff–Chaikoff effect) occurs. Persons with pre-existing thyroid disease, elderly persons, fetuses and neonates, and patients with other risk factors are at a higher risk of experiencing iodine-induced thyroid abnormalities. In particular, in persons with goiter due to iodine deficiency or with altered thyroid function, a form of hyperthyroidism called Jod-Basedow phenomenon can be triggered even at small or single iodine dosages, for example as a side effect of administration of iodine-containing contrast agents. In some cases, excessive iodine contributes to a risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease).
In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed.
Vaccination after exposure, PEP, is highly successful in preventing the disease if administered promptly, in general within 6 days of infection. Begun with little or no delay, PEP is 100% effective against rabies. In the case of significant delay in administering PEP, the treatment still has a chance of success.
Five of the first 43 patients (12%) treated with the Milwaukee protocol survived, and those receiving treatment survived longer than those not receiving the treatment.
Treatment after exposure can prevent the disease if administered promptly, generally within 10 days of infection. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is effective in reducing the number of viral particles. Povidone-iodine or alcohol is then recommended to reduce the virus further.
In the US, the Centers for Disease Control and Prevention recommends people receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a 14-day period. The immunoglobulin dose should not exceed 20 units per kilogram body weight. HRIG is expensive and constitutes most of the cost of post exposure treatment, ranging as high as several thousand dollars. As much as possible of this dose should be injected around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site.
The first dose of rabies vaccine is given as soon as possible after exposure, with additional doses on days 3, 7 and 14 after the first. Patients who have previously received pre-exposure vaccination do not receive the immunoglobulin, only the postexposure vaccinations on days 0 and 3.
The pain and side effects of modern cell-based vaccines are similar to flu shots. The old nerve-tissue-based vaccinations that require multiple painful injections into the abdomen with a large needle are inexpensive, but are being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens.
Intramuscular vaccination should be given into the deltoid, not the gluteal area, which has been associated with vaccination failure due to injection into fat rather than muscle. In infants, the lateral thigh is recommended.
Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is an indication for post-exposure prophylaxis (PEP). The recommendation for the precautionary use of PEP in bat encounters where no contact is recognized has been questioned in the medical literature, based on a cost–benefit analysis. However, a 2002 study has supported the protocol of precautionary administering of PEP where a child or mentally compromised individual has been alone with a bat, especially in sleep areas, where a bite or exposure may occur without the victim being aware. Begun with little or no delay, PEP is 100% effective against rabies. In the case in which there has been a significant delay in administering PEP, the treatment should be administered regardless, as it may still be effective. Every year, more than 15 million people get vaccination after potential exposure. While this works well, the cost is significant.
There is preliminary evidence that iodine deficiency enhances the sensitivity of breast tissue to estrogen. In rats treated with estradiol, iodine deficiency has been shown to lead to changes similar to benign breast changes that are reversible by increased iodine in the diet. In a few studies, iodine supplementation had beneficial effects (such as reducing the presence of breast cyst, fibrous tissue plaques and breast pain) in women with fibrocystic breast changes.
Protective effects of iodine on breast cancer have been postulated from epidemiologic evidence and described in animal models. In view of the antiproliferative properties of iodine in breast tissue, molecular iodine supplementation has been suggested as an adjuvant in breast cancer therapy.
Radon has been produced commercially for use in radiation therapy, but for the most part has been replaced by radionuclides made in accelerators and nuclear reactors. Radon has been used in implantable seeds, made of gold or glass, primarily used to treat cancers.
The gold seeds were produced by filling a long tube with radon pumped from a radium source, the tube being then divided into short sections by crimping and cutting. The gold layer keeps the radon within, and filters out the alpha and beta radiations, while allowing the gamma rays to escape (which kill the diseased tissue). The activities might range from 0.05 to 5 millicuries per seed (2 to 200 MBq). The gamma rays are produced by radon and the first short-lived elements of its decay chain (Po, Pb, Bi, Po).
Radon and its first decay products being very short-lived, the seed is left in place. After 12 half-lives (43 days), radon radioactivity is at 1/2000 of its original level. At this stage, the predominant residual activity is due to the radon decay product Pb, whose half-life (22.3 year) is 2000 times that of radon (and whose activity is thus 1/2000 or radon's), and its descendants Bi and Po, totalizing 0.03% of the initial seed activity.
Radioactive water baths have been applied since 1906 in Jáchymov, Czech Republic, but even before radon discovery they were used in Bad Gastein, Austria. Radium-rich springs are also used in traditional Japanese onsen in Misasa, Tottori Prefecture. Drinking therapy is applied in Bad Brambach, Germany. Inhalation therapy is carried out in Gasteiner-Heilstollen, Austria, in Kowary, Poland and in Boulder, Montana, United States. In the United States and Europe there are several "radon spas", where people sit for minutes or hours in a high-radon atmosphere in the belief that low doses of radiation will invigorate or energize them.
The 2007 Tour de France was affected by a series of scandals and speculations related to doping. By the end of the Tour, two cyclists were dismissed for failing tests and the wearer of the yellow jersey was voluntarily retired by his team for lying about his whereabouts and missing doping tests. A fourth rider was confirmed to having used doping while in a training session prior to the 2007 Tour and a fifth rider failed tests late in the race, with his result being officially announced just after the end of the Tour. During the competition, two teams were asked to withdraw after at least one member was found to have doped.
The events generated criticism and a general distrustful attitude toward the sport of professional cycling from media and public opinion. The doping allegations also resulted in several team sponsors threatening to retire their support if events advanced further. Some media such as German TV channels ARD and ZDF left the Tour once the first scandals broke. Following the Tour's conclusion, the sport's governing bodies spoke out about ways to combat the prevalence of doping in cycling and key team sponsors elected to withdraw their support due to the reputational damage caused by the scandals. The 2007 Tour de France has been referred to as one of the most controversial Tours. After the end of the Tour, "The Times" of London ranked it 4th in its list of the top 50 sporting scandals.
For much of the second phase of his career, Cyclist Lance Armstrong faced constant allegations of doping. Armstrong consistently denied allegations of doping until a partial confession during a broadcast interview with Oprah Winfrey in January 2013.
Coenurosis (a.k.a. Caenurosis and Coenuriasis, gid or sturdy in the vernacular) is a parasitic infection that develops in the intermediate hosts of some tapeworm species ("Taenia multiceps", "T. serialis, T. brauni," or "T. glomerata") and are caused by the coenurus, the larval stage of these worms. This disease occurs mainly in sheep and other ungulates, but occasionally can occur in humans too by accidental ingestion of worms' eggs.
Adult worms of these species develop in the small intesine of the definitive hosts (dogs, foxes, and other canids), causing a disease from the group of taeniasis. Humans cannot be definitive hosts for these species of tapeworms.
Although coenurosis is more commonly associated with domestic animals, it has also been documented in wildlife. It has been found in mountain ungulates in the French Alps. It is believed that the ungulates are being contaminated by infected sheepdogs. Understanding how this disease is transmitted from sheepdogs to wild animals is important in managing the spread of this potentially dangerous zoonotic disease. A potential management strategy would be for farmers to properly dispose of carcasses that they find on their land. In wild gelada monkeys in Ethiopia, coenurosis was found to affect the fitness of these primates. Mortality increased and fertility was inhibited. The disease has also been documented in wild sheep and other ruminants and rarely documented in rodents, horses, and cats. Very few cases have been identified but this could be due to limited research on wild coenurosis. Animals infected with this disease tend to hide or take cover from predators and therefore may not be seen by humans. However, coenurosis has been known to increase mortality and decrease fertility in wild animal populations.
Since the introduction of doping tests in 1964, many cyclists were caught in the Tour de France. In recent years, 1996 Tour de France winner Bjarne Riis and points classification winner Erik Zabel, along with most of their Team Telekom team-mates, confessed to using erythropoietin (EPO). In 1997, former points classification winner Djamolidine Abdoujaparov was disqualified from the Tour de France for doping use. In 1998, the Festina affair had several main contenders removed from the race. In the next years, several riders were removed from the Tour de France for doping (see List of doping cases in cycling).
In addition, several riders were not allowed to start the previous Tour, including Jan Ullrich and Ivan Basso because of their involvement in the Operación Puerto doping case, a Spanish investigation against doctor Eufemiano Fuentes and a number of accomplices accused of administering prohibited doping products to approximately two hundred professional athletes, to enhance their performance.
After the completion of the 2006 Tour, winner Floyd Landis was found to have an elevated testosterone to epitestosterone ratio on a sample taken following Stage 17 of the race, and at the time of the 2007 Tour prologue. Since the results of an independent arbitration hearing were still pending Landis was prevented from defending his title. He was stripped of his 2006 Tour title in September 2007.
Armstrong has been criticized for his disagreements with outspoken opponents of doping such as Paul Kimmage and Christophe Bassons. Bassons wrote a number of articles for a French newspaper during the 1999 Tour de France which made references to doping in the peloton. Subsequently, Armstrong had an altercation with Bassons during the 1999 Tour de France where Bassons said Armstrong rode up alongside on the Alpe d'Huez stage to tell him "it was a mistake to speak out the way I (Bassons) do and he (Armstrong) asked why I was doing it. I told him that I'm thinking of the next generation of riders. Then he said 'Why don't you leave, then?'"
Armstrong later confirmed Bassons's story. On the main evening news on TF1, a French television station, Armstrong said: "His accusations aren't good for cycling, for his team, for me, for anybody. If he thinks cycling works like that, he's wrong and he would be better off going home". Kimmage, a professional cyclist in the 1980s who later became a sports journalist, referred to Armstrong as a "cancer in cycling". He also asked Armstrong questions in relation to his "admiration for dopers" at a press conference at the Tour of California in 2009, provoking a scathing reaction from Armstrong. This spat continued and is exemplified by Kimmage's articles in "The Sunday Times".
Another notable critic of Armstrong was David Walsh, also a reporter for "The Sunday Times". Referred to as a "little troll" by Armstrong, Walsh revealed in a 2001 "Sunday Times" story that he had ties to controversial Italian doctor Michele Ferrari. Two years later, Walsh's book "L.A. Confidentiel" alleged, based on testimony by Armstrong's former masseuse Emma O'Reilly, that clandestine trips were made to pick up and deliver doping products to Armstrong's team.
Until his 2013 admission, Armstrong continually denied using illegal performance-enhancing drugs and described himself as the most tested athlete in the world. However, a 1999 urine sample showed traces of corticosteroid; a medical certificate showed he used an approved cream for saddle sores which contained the substance. O'Reilly claimed that team officials conspired with a compliant doctor to falsify Armstrong's prescription, and that Armstrong never had the condition. She also claimed that, on other occasions, she was asked to dispose of used syringes for Armstrong and pick up strange parcels for the team.
From his return to cycling in the fall of 2008 through March 2009, Armstrong submitted to twenty-four unannounced drug tests by various anti-doping authorities. All of the tests were negative for performance-enhancing drugs.
U.S. federal prosecutors pursued allegations of doping by Armstrong from 2010–2012. The effort convened a grand jury to investigate doping charges, including taking statements under oath from Armstrong's former team members and other associates; met with officials from France, Belgium, Spain, and Italy; and requested samples from the French anti-doping agency. The investigation was led by federal agent Jeff Novitzky, who also investigated suspicions of steroid use by baseball players Barry Bonds and Roger Clemens. The probe was terminated on February 3, 2012 with no charges filed.
Tyler Hamilton, a professional cyclist who rode as Lance Armstrong's principal Domestique on the U.S. Postal Cycling team from 1999 through 2001, has extensively documented the history and methods of doping by Armstrong, himself, and others in "The Secret Race", a book co-authored with Daniel Coyle and published in 2012. The book also describes the investigation by Jeff Novitzky and the Food and Drug Administration and Hamilton's befuddlement that the investigation was dropped.