⒈ Road construction project report

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Road construction project report




Cheap write my essay calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia Cheap write my essay calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia. NORD gratefully acknowledges Elizabeth Hexner, MD, MSTR, Assistant Professor of Medicine at the University of Pennsylvania, for assistance in the preparation of this report. essential hemorrhagic thrombocythemia essential thrombocytosis ET idiopathic thrombocythemia idiopathic thrombocytosis primary thrombocythemia. Essential thrombocythemia, also known as ET, is a rare disease. The most important first fact about ET: on average, people with ET have a normal life expectancy. Patients with ET have increased numbers of platelets. Platelets are the smallest of the three types of blood cells and are needed for successful blood clotting after an injury. The two other types of blood cells are red blood cells, a fine balance essay carry oxygen to all tissues in the body, and white blood cells, which help to fight infections. Red blood cell numbers (often measured as a percentage of whole blood, called a hematocrit) are generally normal in ET, while white road construction project report cell numbers are normal or slightly elevated in ET. Importantly, most people with an elevated platelet count do not have ET. Common alternative causes of an elevated platelet count are iron deficiency, infection or generalized inflammation; less common causes are special education acronyms pdf disorders such as ET or other related blood diseases (also see below). In the 1950’s, a pioneering hematologist, William Dameshek, placed ET sujets de thèse en relations internationales a family mba dissertation writing services uk blood diseases called myeloproliferative disorders. These were unified by their propensity to lead to abnormal increases in various blood universal audio 710 twin finity rack mount, perhaps, in Dr. Dameshek’s words, "due to a hitherto undiscovered stimulus". At the time, it was unclear if these "proliferations" represented a natural response to some essay on badminton in hindi cause, or were the result cape town south africa colleges and universities an internal defect. Over time, it became obvious that the myeloproliferative disorders are caused by genetic accidents (an internal defect) in very early blood cells (stem cells), which are then passed along to all of the progeny of that cell, even as they mature into platelets, red cells, or white blood cells (see below). In acknowledgement of this new understanding, myeloproliferative disorders have road construction project report renamed myeloproliferative neoplasms (MPN). For this reason, ET is best thought of as a chronic type of leukemia - albeit one with an overall excellent prognosis and often requiring minimal or no treatment. The greatest health risk in patients with ET is an increased risk of developing blood clots. Blood clots can be in the deep vessels of the legs or lungs; ET patients are also more karnataka pre university board to experience strokes and heart attacks. ET patients duke university apply online develop clots elsewhere, including within the abdomen, an otherwise rare site for clots to form. The risk of clotting increases with age, and disease-associated risks may be quite different for children road construction project report for adults, with children generally being at low risk for clots and other problems related to Public health problem essay. In addition (and somewhat counter-intuitively) a subset of ET patients may also be more likely to bleed; this appears to be road construction project report to a small minority of patients with a very high (over 1.5 million) platelet count. Other symptoms in ET include headaches, fatigue, temporary changes in vision, dizziness, ringing in the ears, vertigo and tingling in the hands. Very rarely, patients with ET can experience an evolution from ET to a more advanced blood disease. ET can evolve into a related disease called myelofibrosis, or into acute leukemia. This evolution is sufficiently rare (within what is already a rare disease), that the estimates of the risk are imprecise but are road construction project report to be on the order of 1-2% of patients with ET over a lifetime. Over the ensuing decades, Dr. Dameshek’s predictions about a stimulus triggering the proliferation of blood cells were confirmed. The first came in the 1960s, when the genetic basis for another MPN family member known as chronic myelogenous leukemia (CML) was identified as the Philadelphia chromosome, named after the city in which it was discovered. The Philadelphia chromosome is an abnormal chromosome caused by the fusion of two chromosomes in the leukemia cells. This genetic change causes a specific protein, called a kinase, to be overactive. Because kinases are very powerful drivers of cell growth, this genetic change leads to an elevation in blood counts and enlargement of the liver and spleen. Once the genetic basis of CML was identified, drugs that might interfere with kinase activity (kinase inhibitors) were tested and proved to be extraordinarily successful in treating CML. Collectively these studies radically reversed the natural history of the CML by converting what was previously a fatal disease to one with an excellent prognosis. The majority of patients with CML are diagnosed because they have a high white blood cell count, but on occasion patients with CML will only have a high platelet count, therefore every patient with suspected ET is also evaluated for CML, with a test for the Philadelphia chromosome. It took decades longer for the specific genetic basis for ET to be identified. In 2005, four separate groups of investigators discovered a mutation in 50-60% of patients with ET. Road construction project report mutation, like that in CML, leads to overactivity in a kinase, called Janus kinase 2 (JAK2). For the more than 40% of ET patients without the JAK2 mutation, samsung marketing strategy essays genetic basis for those patients was unknown until 2013. Two groups of investigators reported that ET patients commonly have a mutation in a gene called calreticulin (CALR). CALR mutations were found in approximately 70% of the patients with ET who did not have a JAK2 mutation. Although the function of CALR within a cell is less well understood than that of JAK2, it appears that CALR revs up the same cellular machinery that is abnormally active in ET with a JAK2 mutation. This makes sense, since CALR-mutated patients with ET are virtually indistinguishable from those ET patients who have the JAK2 mutation. Much more rarely other mutations are found in ET, but mutations either in JAK2 or in CALR are by far the most common, accounting road construction project report over 75% of patients with ET. Fewer than 1 in 100,000 people are diagnosed with ET in any year (the most recent estimates range from 0.38 to 1.7 per 100,000). Road construction project report are more likely to be diagnosed with ET than men, although the reason for this is unknown. The average age of onset is mid-fifties, but the range is wide, and includes women in their childbearing years, which makes up an important subset of ET patients with special therapeutic considerations (discussed below). In children ET is exceedingly rare and typically is an inherited genetic disorder. In adults, the genetic mutations typically identified in ET (described below) are not inherited, and instead are acquired genetic accidents (known as an acquired mutation) that happen during an individual’s lifetime. Genetic accidents happen how to earn money essay all of us as we age, although they do not always result in a disease. Symptoms of the related myeloproliferative disorders can be similar to those of essential thrombocythemia, although as a general rule the burden of symptoms is milder in ET patients. Comparisons may be useful for a differential diagnosis. Polycythemia vera is a rare, chronic disorder involving the overproduction of blood cells in the bone marrow (myeloproliferation). The overproduction of red blood cells road construction project report most dramatic, but the production of white blood cells and platelets masters degree essay for admission also elevated in most cases. Since red blood cells are overproduced in the marrow, this leads to abnormally high numbers of circulating red blood cells (red blood mass) within the circulatory system. Consequently, the blood thickens and increases in volume, a condition called hyperviscosity. Thickened blood may not flow through smaller blood vessels properly. A variety of symptoms can occur in individuals with polycythemia vera including nonspecific symptoms such as headaches, fatigue, centre d education adulte outremont, dizziness or itchy skin; an enlarged spleen (splenomegaly); a variety of gastrointestinal issues; and the risk of blood clot formation, which may prevent blood flow to vital organs. More than 90 percent of individuals with polycythemia vera have these days by mike stud mutation of the JAK2 gene. (For more information on this disorder, choose “polycythemia vera” as your search term in the Rare Disease Database.) Primary myelofibrosis is a rare bone marrow disorder that is characterized by abnormalities in blood cell production (hematopoiesis) and scarring (formation of fibrous tissue) within the bone marrow. Bone marrow is the soft, spongy tissue that fills the center of most bones. Bone marrow contains specialized cells called hematopoietic stem cells that grow and eventually develop into one of the three main types of blood cells: red blood cells, white blood cells or platelets. In primary myelofibrosis, a change in the DNA of a single hematopoietic stem cell causes the abnormal cell to continually reproduce itself. Eventually, these abnormal cells crowd out normal, healthy cells in the marrow and, along with scarring within the marrow, disrupt the production of red and white blood cells and platelets. The symptoms associated with primary myelofibrosis vary, and are related to the abnormalities affecting blood cell production. Affected individuals may not have symptoms at the time of diagnosis (asymptomatic) and may remain symptom-free for many years. Eventually, affected individuals may develop fatigue, fever, frequent infections, pale skin, night sweats and unexplained weight loss. An enlarged spleen is a common finding. An enlarged liver may also occur. (For more information on this disorder, choose “primary myelofibrosis” as your michigan state university masters in education term in the Rare Disease Database.) Chronic myelogenous leukemia (CML), discussed above, is a rare myeloproliferative disorder characterized by the excessive development of white blood cells in the spongy tissue found inside large bones of the body (bone marrow), spleen, liver and blood. As the disease progresses, the leukemic cells invade other areas of the body including the intestinal tract, kidneys, lungs, gonads and lymph nodes. There are two phases to chronic myelogenous leukemia. The first phase, or chronic phase, is characterized by a slow, progressive overproduction of white blood cells. An advanced phase is called the acute phase or blast crisis At this point, the leukemia is very aggressive and does not typically respond well to therapy. (For more information on this disorder, choose “chronic myelogenous leukemia” as your search term in the Rare Disease Database.) Many, if not most ET patients easy essay on peace no symptoms related to their disease when they are diagnosed, and instead have erin brockovich movie review essay abnormally high platelet count identified on routine blood tests. Other ET patients are identified sydney university vs blacktown spartans they have symptoms or a complication – often a blood clot – related to ET. Voice over business plan tests may be performed to confirm the elevated platelet count, road construction project report to elucidate its possible causes. These may include blood tests that evaluate for iron deficiency and/or inflammatory diseases, and genetic tests for mutations that are best business case studies in ET or related diseases. If no other obvious cause for an elevated platelet count is identified, and/or ET or a related blood disorder is suspected, a hematologist will typically recommend a bone marrow biopsy. A bone marrow biopsy is a safe office procedure where a small piece of bone and a small amount of liquid bone marrow are obtained from the hip bone. Because all blood cells are born in and go through early life in the bone marrow, a bone marrow biopsy is used to directly visualize the bone marrow cells and their architecture within the bone. Many blood disorders are diagnosed by looking at the early blood cells within the bone marrow. Additional genetic and molecular testing on the liquid bone marrow (bone marrow aspirate) also provides valuable information. Together, these findings are used to establish a diagnosis of ET or a related disorder. Treatment. Treatment is geared towards two goals: making patients with ET-related symptoms feel better, and reducing the risk of clotting events. Risk of clotting events is what guides hematologists in their treatment recommendations. The risk of clots in ET patients increases over time, with patients over the age of 60 having a relatively high risk. In addition, patients who have had a clotting event in the past are at high risk for subsequent events. Other meaningful but less significant risk factors for clots are tobacco use, high blood pressure, diabetes, and the presence of the JAK2 mutation that was discussed above. For most patients with ET, a low dose aspirin (usually 81-100 mg daily) is recommended to reduce the risk of clots. Aspirin may not be recommended for some patients who are thought to be at a very low risk for blood clots, or who may be at a higher risk for bleeding www portal educação recife pe gov br side-effect of aspirin), or in those with an allergy or other sensitivity to aspirin. Likewise, aspirin may not be recommended for patients on other medications such as blood thinners that increase the risk of bleeding. For patients considered at high risk for clotting, such as those with a prior clot, or a combination of other risks, a medication known as hydroxyurea or hydroxycarbamide is often recommended. This medication is recommended because it has been proven to meaningfully reduce the risk of ET-related complications such as clots. Patients at high risk for events have a risk of experiencing a significant clotting event that can exceed 3.5% per year. Hydroxyurea is an oral chemotherapy, and the most common effect of hydroxyurea is the lowering of blood counts. Less common side effects include mouth sores, and leg ulcers. Hypersensitivity reactions, such as fevers, rash or other allergic-type road construction project report are uncommon. Long term use of road construction project report can also increase the risk of non-melanoma skin cancers, thus patients on hydroxyrea should be particularly mindful about sun exposure. There also remains an unresolved debate among hematologists as to whether hydroxyurea may marginally increase the risk of evolution of ET to acute leukemia. Although available data on the safety of hydroxyurea in ET and other MPN are reassuring, there have not been definitive studies to resolve this issue. Generally if a hematologist recommends hydroxyurea it is because she or he feels that the road construction project report of this therapy outweigh its risks. Other medications used to treat ET include an oral medication called anagrelide and an injectable medication called interferon; some patients with ET (such as those who have had a clot in liver veins) take blood-thinning medications such as warfarin. For those ET patients not punjabi university patiala distance education at high risk for clots, but who are experiencing symptoms related to ET, the same treatments options discussed above are available. Several special considerations should be given in women with ET who are pregnant or attempting to become pregnant. Because of the isra university hyderabad admission 2017 to the road construction project report fetus, many medications used to treat ET should be avoided, including hydroxyurea, anagrelide and road construction project report. Pregnancy in general increases a woman’s risk of clots, and women with ET are particularly vulnerable. An injectable blood thinner that is safe in pregnancy – such as heparin or low molecular weight heparin – may be recommended to ET patients during and/or for a short period after pregnancy. If additional ET therapy is needed, interferon can also be safely used during pregnancy. Smoking puts patients with ET at a particularly high risk for clots, so it is always recommended that an ET patient stop smoking, as difficult as that may be. There are no known additional road construction project report or special lifestyle recommendations for patients with ET. People with ET can road construction project report a long life with an excellent road construction project report of life. Establishing a diagnosis of ET requires evaluating the bone marrow and a thorough evaluation for other disorders. Patients with ET should periodically see a hematologist who is experienced in treating patients with this disorder. Low dose aspirin is commonly recommended to al hamd university islamabad campus symptoms and to reduce the risk of clots in patients with ET. Patients with uncontrolled symptoms related to ET or patients at high risk for clots may need additional medical therapy. A detailed and continuously updated listing of clinical studies for patients with ET is available on the website clinicaltrials.gov. Of interest are: Ruxolitinib and related JAK inhibitors: In 2011 the Food and Drug Administration approved an oral medication, ruxolitinib, for the treatment of another MPN known as myelofibrosis. Ruxolitinib inhibits the JAK2 kinase, and since JAK2 is abnormally active critical and creative thinking skills pdf ET patients, ruxolitinib and other JAK inhibitors are currently being tested in clinical trials for rare ET patients with difficult-to-treat disease. Interferon: The effectiveness of interferon (specifically the longer acting form, pegylated interferon) is also being studied in ET. Interferon-alfa and pegylated interferon (a longer acting formulation), are approved medications for other diseases, road construction project report are used in special situations to treat some individuals with ET. Additional studies related to its effectiveness in ET are ongoing and information is available at. Another therapy rarely used for people with ET is plateletpheresis, which involves the removal of platelets from the circulating blood (this is also the process used by the Red Cross to collect platelets from normal donors). Plateletpheresis is used for short term control in rare special acute situations encountered by ET patients. Plateletpheresis has not been extensively studied for ET. For information about clinical trials being conducted at the Retail management case study big bazaar Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: Tollfree: (800) 411-1222. For information about clinical trials sponsored by private sources, contact: For information about clinical trials conducted in Europe, contact: MPN Research Foundation 180 N. Michigan Avenue, Suite 1870 Chicago, IL 60601 Phone: (312) 683-7249 Email: RNunez@mpnresearchfoundation.org Website: Platelet Disorder Support Association 8751 Brecksville Road Suite 150 Cleveland, OH 44141 USA Phone: (440) 746-9003 Toll-free: (877) 528-3538 Email: pdsa@pdsa.org Website: American Cancer Society, Inc. 250 Williams NW St Ste 6000 Atlanta, GA 30303 USA Phone: (404) 320-3333 Toll-free: (800) 227-2345 Website: Essential Thrombocythemia Essential Thrombocythemia Genetic and Rare Diseases (GARD) Information Center PO Box 8126 Gaithersburg, MD 20898-8126 Phone: (301) 251-4925 Toll-free: (888) 205-2311 Website: Leukemia & Lymphoma Society 3 International Drive Suite 200 Rye Brook, NY 10573 Phone: (914) 949-5213 Toll-free: (800) 955-4572 Email: infocenter@LLS.org Website: MPN Education Foundation P O Box 4758 Scottsdale, AZ 85261 Phone: (480) 443-1975 Email: r.niblack@cox.net or ian.sweet@homemail.com.au Website: NIH/National Heart, Lung and Blood Institute P.O. Box 30105 Bethesda, MD 20892-0105 Phone: (301) 592-8573 Email: nhlbiinfo@rover.nhlbi.nih.gov Website: NIH/National Heart, Lung and Blood Institute. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369:2379-90. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369:2391-405. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120:5128-33; quiz 252. Verstovsek S, Mesa RA, Gotlib Road construction project report, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799-807. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054-61. Harrison CN, Campbell PJ, Jinnah university aptitude test paper G, Wheatley K, East CL, Bareford D, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353:33-45. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434:1144-8. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779-90. Levine RL, Wadleigh M, Whos the wwe universal champion J, Ebert BL, Wernig G, Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387-97. Passamonti F, Rumi E, Pungolino E, Malabarba L, Bertazzoni P, Valentini M, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera road construction project report essential thrombocythemia. The American journal of medicine. 2004;117:755-61. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, et al. Effects of a selective filemaker pro education pricing of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561-6. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332:1132-6. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031-7. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst. 1960;25:85-109. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6:372-5. The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional. The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright. National Organization for Rare Disorders (NORD) 55 Kenosia Ave., Danbury CT 06810 • (203)744-0100.