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A dysregulation of the TH1 T cell response is present in inflammatory bowel disease, especially Crohn s disease One of the key proinflammatory cytokines in the TH1 response is TNF- Several antibodies to TNF currently are available or in clinical testing for the treatment of inflammatory bowel disease Infliximab is an immunomodulating agent that represents a major advance in the treatment of patients with moderate to severe Crohn s disease and ulcerative colitis who are unresponsive to conventional therapy Infliximab is a chimeric (human/ mouse) IgG monoclonal antibody that binds with high specificity to membrane-associated TNF- on monocytes and activated T lymphocytes, promoting apoptosis and cell death Infliximab is administered by intravenous infusion The halflife of infliximab after intravenous infusion is 8 10 days; however, therapeutic serum concentrations persist for approximately 8 weeks A three-dose regimen of 5 mg/kg administered at 0, 2, and 6 weeks is recommended for acute induction, followed by infusions every 8 weeks for maintenance therapy Acute infusion reactions occur in 5% of infusions but occur less commonly in patients receiving concomitant immunomodulators (ie, azathioprine or methotrexate) Most are mild or moderate (nausea; headache; dizziness; urticaria; diaphoresis; or mild cardiopulmonary symptoms that include chest tightness, dyspnea, or palpitations) and can be treated by slowing the infusion rate and administering acetaminophen and diphenhydramine Severe reactions (hypotension, severe shortness of breath, rigors, severe chest discomfort) occur in less than 1% and may require oxygen, diphenhydramine, hydrocortisone, and epinephrine Delayed serum sickness-like reactions occur in 1% With repeated, intermittent intravenous injections, antibodies to infliximab (ATI) develop in up to 40% of patients, which are associated with a shortened duration or loss of response and increased risk of acute infusion reactions Giving infliximab in a regularly scheduled maintenance therapy (eg, every 8 weeks), concomitant use of infliximab with other immunomodulating agents (azathioprine, mercaptopurine, or methotrexate), or preinfusion treatment with corticosteroids (intravenous hydrocortisone 200 mg) significantly reduces the development of ATI Serious infections may occur in 2 5% of patients, including sepsis, pneumonia, abscess, and cellulitis; however, controlled studies suggest the increased risk may be attributable to increased severity of disease and concomitant use of corticosteroids Patients treated with infliximab are at increased risk for the development of disseminated tuberculosis as well as other opportunistic infections (Pneumocystis jiroveci, listeriosis, histoplasmosis, aspergillosis, varicella) Prior to use of infliximab, patients should be screened for latent tuberculosis with PPD testing and a chest radiograph Antinuclear and anti-DNA antibodies occur in a large percentage of patients; however, the development of drug-induced lupus is rare Infliximab may cause severe hepatic reactions leading to acute.



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Creating PDF documents with jsPDF | Tizen Developers
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Mercaptopurine and azathioprine are thiopurine drugs that are used in many patients with Crohn s disease and ulcerative colitis who are corticosteroid-dependent in an attempt to reduce or withdraw the corticosteroids and to maintain patients in remission Azathioprine is converted in vivo to mercaptopurine It is believed that the active metabolite of mercaptopurine is 6-thioguanine Monitoring of 6-thioguanine levels is performed in some research settings but is of unproven value in the management of most patients Allergic and nonallergic side effects of mercaptopurine and azathioprine occur in 10% of patients, including pancreatitis, bone marrow suppression, infections, hepatitis or cholestatic jaundice and, potentially, a higher risk of neoplasm Three competing enzymes are involved in the metabolism of mercaptopurine to its active (6-thioguanine) and inactive metabolites About 1 person in 300 has a homozygous mutation of one of the enzymes that metabolizes thiopurine methyltransferase (TPMT), placing them at risk for profound immunosuppression; 1 person in 9 is heterozygous for TPMT, resulting in intermediate enzyme activity Measurement of TPMT functional activity is recommended prior to initiation of therapy Treatment should be withheld in patients with absent TPMT activity The most effective dose of mercaptopurine is 1 15 mg/kg or of azathioprine is 2 3 mg/kg daily For patients with normal TPMT activity, both drugs may be initiated at the weightcalculated dose A complete blood count should be obtained weekly for 4 weeks, biweekly for 4 weeks, and then every 1 3 months for the duration of therapy Liver function tests should be measured periodically Some clinicians prefer gradual dose-escalation, especially for patients with intermediate TPMT activity or in whom TPMT measurement is not available; both drugs may be started at 25 mg/d and increased by 25 mg every 1 2 weeks while monitoring for myelosuppression until the target dose is reached If the white blood count falls below 3000 4000/mcL or the platelet count falls below 100,000/mcL, the medication should be held for at least 1 week before reducing the daily dose by 25 50 mg Methotrexate is used in the treatment of patients with inflammatory bowel disease, especially patients with Crohn s disease who are intolerant of mercaptopurine Methotrexate is an analog of dihydrofolic acid Although at high doses it interferes with cell proliferation through inhibition of nucleic acid metabolism, at low doses it has anti-inflammatory properties, including inhibition of expression of tumor necrosis factor- (TNF- ) in monocytes and macrophages Methotrexate may be given intramuscularly, subcutaneously, or orally Side effects of methotrexate include nausea, vomiting,.

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hepatic failure; liver enzymes should be monitored routinely during therapy It is speculated but unproven that infliximab may increase the risk of lymphoproliferative malignancies Rare cases of multiple sclerosis have been reported Infliximab may worsen congestive heart failure in patients with cardiac disease

Lichtenstein G et al American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease Gastroenterology 2006 Mar;130(3):935 9 [PMID: 16530531]

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The subtransient fault current at the Mallee bus for a single-line-to-ground fault is I = 2512 875 pu , f and the transient fault current at the Mallee bus for a single-line-to-ground fault is I f = 2372 877 pu (b) If the generators are solidly grounded, their zero sequence impedances will become just Z g 0 This smaller zero sequence impedance will result in a much higher fault current for a single-line-to-ground fault The input file required for program faults is:

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