Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin, one of the most widely used drugs in the world, consistently produces gastric mucosal injury, but the pathogenic mechanisms are incompletely understood. The present study was designed to determine the role of neutrophils in aspirin-induced acute gastric mucosal injury. Gastric mucosal lesions induced by acidified aspirin (300 mg/kg) were completely prevented in rats that had been rendered profoundly neutropenic by anti-neutrophil serum. Aspirin-induced acute gastric mucosal lesions were also significantly, albeit incompletely, reduced in rats that had been rendered moderately neutropenic by methotrexate. Moreover, in the methotrexate-induced neutropenia model, the neutropenia-associated mucosal protection against aspirin-induced injury could be reversed by leucovorin rescue. Aspirin caused a marked and statistically significant reduction in gastric mucosal 6-ketoprostaglandin F1 alpha synthesis, but no significant changes in gastric mucosal leukotriene synthesis. Thus no gastric mucosal lesions were observed in profoundly neutropenic rats that were treated with aspirin, despite the marked inhibition of prostaglandin synthesis. These findings demonstrate that aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process.
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PMID:Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats. 147 99

Aspirin (acetylsalicylic acid) is effective in reducing vascular outcome events in patients with atherosclerosis: a relative risk reduction of about 30% for stroke, 22% for stroke and death, and 15% for vascular mortality. It is probable that low and high dose aspirin are similar in efficacy. Complications are more frequent with high dose aspirin than with low doses. Four randomised trials evaluating sulfinpyrazone vs placebo, and 3 trials evaluating sulfinpyrazone vs aspirin, showed more cerebrovascular events in the sulfinpyrazone group than in the aspirin and placebo groups. One small trial comparing dipyridamole with placebo in patients with cerebrovascular disease found no difference between the 2 groups in outcome. No other studies have compared dipyridamole alone with placebo or aspirin. The European Stroke Prevention Study II is currently in progress and is comparing dipyridamole + aspirin, dipyridamole, aspirin, and placebo. In the first year, the Ticlopidine Aspirin Stroke Study (TASS) showed a 42% risk reduction for stroke and death using the efficacy analysis and a 47% risk reduction for stroke and stroke death. Ticlopidine was more effective than aspirin in reducing stroke in both males and females. Apart from a reversible severe neutropenia in 0.86% of patients, ticlopidine-related adverse effects were relatively benign and reversible. The Canadian-American Ticlopidine Study (CATS) compared ticlopidine with placebo in patients with completed major strokes. The cumulative event rates for the primary outcome events of stroke, myocardial infarction and vascular death, using the efficacy approach, show clear evidence of separation almost immediately after randomisation, consistent with a constant risk reduction of about 30% in the ticlopidine group. These data provide strong evidence that ticlopidine conveys a clinically important reduction in the risk of thromboembolic events in patients with a history of completed thromboembolic stroke. In conclusion, aspirin is effective in preventing atherothrombotic morbidity and mortality. It reduces the overall vascular event rate by about 25%. Sulfinpyrazone and dipyridamole appear to add nothing important over aspirin alone. Ticlopidine is more effective than aspirin in preventing stroke. The modest, reversible risk of neutropenia, affecting less than 1% of patients, makes the benefit: risk ratio a reasonable one.
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PMID:Antiplatelet therapy in the prevention of stroke. 172 15

We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater.
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PMID:A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. 230 95

Human recombinant interleukins 1 alpha and 1 beta (rIL-1 alpha and -1 beta) both induced monophasic peripheral neutrophilia and lymphopenia in Lewis rats 1.5 hr after i.v. injection. The kinetics of rIL-1 alpha- and -1 beta-induced neutrophilia were similar to those induced by human monocyte-derived IL-1, IL-1 alpha, and IL-1 beta, and the peripheral neutrophilia was accompanied by a marked decrease in marrow neutrophils. Arachidonic acid metabolites are implicated as biochemical intermediates in the production of the neutrophilia but not lymphopenia, since indomethacin and dexamethasone both completely abrogated IL-1-induced neutrophilia but did not affect the IL-1-induced lymphopenia. Acetylsalicylic acid, a cyclooxygenase inhibitor, did not inhibit IL-1-induced neutrophilia, suggesting that products of the lipoxygenase rather than the cyclooxygenase pathway of arachidonate metabolism may contribute to the neutrophilia. Human recombinant tumor necrosis factor-alpha (rTNF) administered i.v. to Lewis rats induced peripheral neutropenia, two peaks of neutrophilia, and lymphopenia. A wide range of doses of rTNF resulted in an initial neutropenia at 0.5 hr after injection followed by a first peak of neutrophilia at 1.5 hr and a second peak of neutrophilia at 6 hr. The initial neutropenia and the first peak of neutrophilia were not inhibited by pretreatment of rats with dexamethasone, indomethacin, or aspirin. The second peak of neutrophilia was inhibited by both dexamethasone and indomethacin, but was not at all inhibited by aspirin, suggesting that the second peak of neutrophilia is mediated by the release of endogenous cytokines, especially by IL-1, since exogenous IL-1-induced neutrophilia is also completely inhibited by dexamethasone and indomethacin but not by aspirin. The TNF-induced peripheral neutrophilia is also accompanied by a significant depletion of bone marrow neutrophils, indicating that the source of increased circulating neutrophils is, at least in part, via recruitment of marrow neutrophils. Systemic blood pressure was not affected by IL-1 or rTNF at the dosages employed, showing that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic change-related release of adrenal hormones. Adrenalectomy did not alter the IL-1- or rTNF-induced neutrophilia or lymphopenia, also demonstrating that neither monokine mediates its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes. 331 83

Patients with atherosclerotic carotid artery stenosis commonly have arterial disease elsewhere, especially coronary artery disease. The aim of the medical treatment is to reduce the incidence of stroke, myocardial infarction and vascular death. Both primary and secondary prevention of these vascular events requires control of vascular risk factors, particularly lowering elevated blood pressure, lowering of elevated blood cholesterol and stopping smoking. Aspirin and ticlopidine are effective in reducing vascular events in patients with atherosclerosis, with a relative reduction of about 25% for the composite outcome event "stroke, myocardial infarction or vascular death". Whether low dose (less than 100 mg/d), medium (300 mg/d) or high dose (1,000 mg/d or more) of aspirin confer the same degree of protection against vascular events is unclear. The gastrointestinal side effects are greater for the high dose than for the medium dose, but the difference between the medium dose and the low dose is very small. Ticlopidine conveys a modest risk of reversible severe neutropenia and is often used as a second-line drug, but this is a controversial issue. Heparin is often used as a short-term preventive treatment in patients with transient ischaemic attacks or minor stroke, especially in those with "crescendo" transient ischaemic attacks, progressing stroke, severe carotid stenosis or intraluminal thrombus.
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PMID:[Medical treatment of atherosclerotic carotid stenoses]. 815 33

Aspirin in doses of 325 mg to 1,300 mg per day is the drug of choice for prophylactic therapy in cerebrovascular disease. Ticlopidine, a platelet antagonist, is available for use in patients who cannot tolerate aspirin or who have not had success with aspirin therapy. Although ticlopidine is more effective than aspirin in preventing stroke, its use may be somewhat limited due to cost and the uncommon but serious side effect of neutropenia. Low-dose warfarin remains the drug of choice for the prevention of cardioembolic stroke. The role of warfarin in ischemic cerebrovascular disease is unknown.
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PMID:Prophylactic drug therapy in cerebrovascular disease. 832 47

We analyzed the efficacy of ticlopidine and aspirin in the non-white subgroup of patients from the Ticlopidine Aspirin Stroke Study. In this double-blind, randomized, multicenter study, patients received either ticlopidine 250 mg (312 non-white patients) or aspirin 650 mg (291 non-white patients) twice a day. The 1-year cumulative event rate per 100 patients for nonfatal stroke or death from any cause was 5.5 for ticlopidine and 10.6 for aspirin--an apparent 48.1% reduction in risk with ticlopidine relative to aspirin. The 1-year cumulative event rate for fatal or non-fatal stroke was 3.7 for ticlopidine and 9.4 for aspirin--an apparent 60.8% reduction in risk with ticlopidine relative to aspirin. The cumulative event rates for both endpoints also were lower in ticlopidine-treated patients after the 2nd and 3rd years. These reductions were not significantly different between treatment groups, but were of the same order of magnitude as previously found for the total series, which did attain statistical significance (p = 0.048), and the frequency of adverse events was not significantly different between the two treatment groups. Severe neutropenia, the most serious adverse event associated with ticlopidine use, did not occur in non-white patients. These results suggest that ticlopidine is superior to aspirin for stroke prevention in non-whites.
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PMID:The efficacy and safety of ticlopidine and aspirin in non-whites: analysis of a patient subgroup from the Ticlopidine Aspirin Stroke Study. 842 6

The aim of platelet inhibitory therapy in cardiology is to prevent undesired thrombus formation and, thus, to prevent complications of cardiovascular diseases. In Germany, 5 substances are approved for antiplatelet therapy. Acetylsalicylic acid, an inhibitor of platelet cyclooxygenase, has been shown to be effective at both high and low doses in the secondary prevention of myocardial infarction, coronary heart disease, and cerebrovascular disease. In addition, acetylsalicylic acid is effective in reducing the complications of unstable angina pectoris and coronary angioplasty, and in reducing the occlusion rate of aortocoronary bypass grafts. The addition of dipyridamole to acetylsalicylic acid has not been shown to result in any additional benefit in many clinical studies. Ticlopidine, an antagonist of ADP-induced platelet aggregation has been similarly effective as acetylsalicylic acid in the treatment of coronary heart disease. The principal side effect of the drug, the occurrence of neutropenia in about 1% of treated patients, makes regular blood cell counts mandatory during treatment. In the secondary prevention of cerebrovascular disease, the drug may be superior to acetylsalicylic acid. Trapidil is an anti-platelet substance which acts on platelets through various mechanisms including inhibition of the release of "platelet derived growth factor". In 3 smaller randomized studies, trapidil has been found to reduce the restenosis rate after coronary angioplasty. Abciximab, the Fab-fragment of an antibody against the platelet fibrinogen receptor glycoprotein 11b/IIIa has been shown to be effective in the prevention of acute and long-term complications of high-risk coronary angioplasty.
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PMID:-New aspects in antithrombotic therapy--platelet inhibitors-. 864 75

Secondary prevention of arteriosclerosis tries to inhibit progression of the atherosclerotic process. Therapeutic measures focus on modification of cardiovascular risk factors and antithrombotic treatment. Hypercholesterolemia is the main risk factor for coronary artery disease. The risk of a coronary event is correlated to the plasma cholesterol level. Lowering plasma cholesterol results in reduction of vascular morbidity and mortality. Cigarette smoking is the predominant risk factor for peripheral arterial occlusive disease (PAOD). Smoking cessation reduces progression of PAOD and lowers cardiovascular morbidity and mortality. The preventive effect of antihypertensive therapy in hypertensive patients is most pronounced for cerebrovascular events. Antihypertensive measures improve prognosis after stroke and myocardial infarction. The increased cardiovascular risk in diabetics is in part explained by hyperglycemia and hyperinsulinemia, but also depends on coexisting dyslipidemia and hypertension. Intensive treatment of elevated blood glucose levels, dyslipidemia and hypertension are important preventive measures. Aspirin is highly effective in secondary prevention of vascular events. For the coronary arteries, low-dose aspirin is well established. Whether low-dose aspirin is equally effective for reducing progression of arteriosclerosis in the cerebrovascular and in the peripheral vessels is questionable. Ticlopidine serves as an alternative to aspirin; however, neutropenia may occur, which requires supervision of the patient.
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PMID:[Secondary prevention of arteriosclerosis]. 892 4

The antipyretic efficacy of propacetamol, an intravenous prodrug of paracetamol, was evaluated in two pediatric prospective randomized studies. In the first, we-compared one standard intravenous dose of propacetamol (30 mg/kg) to one standard intravenous dose of acetylsalicylic acid (ASA, 15 mg/kg) in 10 nononcologic patients with bacterial illnesses. In the second study, we compared two intravenous doses of propacetamol (30 mg/kg versus 15 mg/kg) in 24 oncologic patients with fever and neutropenia. No statistically significant differences in antipyretic efficacy were found between standard doses of propacetamol and ASA; even when half-doses of propacetamol (15 mg/kg) were used, good antipyretic efficacy was observed, which was not statistically different from that observed with the full dose. The use of propacetamol seems promising for patients (such as oncologic patients) who cannot receive enteral paracetamol formulas.
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PMID:Antipyretic effect of parenteral paracetamol (propacetamol) in pediatric oncologic patients: a randomized trial. 902 13


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