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)

The Canadian American Ticlopidine Study (CATS) is a randomised, double-blind, placebo-controlled trial to assess the effect of ticlopidine (250 mg twice daily) in reducing the rate of subsequent occurrence of stroke, myocardial infarction, or vascular death in patients who have had a recent thromboembolic stroke. Twenty-five centres entered 1072 patients into the study between 1 week and 4 months after their qualifying stroke. The patients were treated and followed for up to 3 years (mean 24 months). In the efficacy analysis, the event rate per year for stroke, myocardial infarction or vascular death, considered together, was 15.3% in the placebo group and 10.8% in the ticlopidine group, representing a relative risk reduction with ticlopidine of 30.2% (95% confidence interval 7.5-48.3%; p = 0.006). Ticlopidine was beneficial for both men and women (relative risk reductions 28.1%, p = 0.037, and 34.2%, p = 0.045, respectively). Analysis by intention-to-treat gave a smaller estimate of risk reduction (23.3%, p = 0.020) for stroke, myocardial infarction, or vascular death. Adverse experiences associated with ticlopidine included neutropenia (severe in about 1% of cases) and skin rash and diarrhoea (severe in 2% of cases each); all were reversible. This study provides evidence of a beneficial effect of ticlopidine in both men and women with a recent thromboembolic stroke.
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PMID:The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. 256 17

Five cases (3.5%) of reversible cephapirin-induced neutropenia were observed in 132 patients receiving this antibiotic. The disorder was severe (agranulocytosis) in 3 cases. Simultaneous maculopapular rash was observed in all of them and in 4 cases fever occurred. All the cases observed were female (p not significant). Neutropenia developed only after administration of high doses of the antibiotic for a prolonged period of time. In contrast to another 127 patients treated with cephapirin who did not develop neutropenia, neutropenic patients had received a mean daily dose, total dose, mean daily dose per kilogram and total dose per kilogram of body weight significantly larger (p = 0.05, 0.02, 0.001 and 0.001, respectively). The duration of therapy was significantly longer in the neutropenic group (p = 0.001). Neutropenia did not occur below 90 g of total dose, but when this amount was exceeded, the incidence of the disorder reached 26.3% (p less than 0.001). We conclude that when this drug must be used either for long periods of time or at high doses, a hematologic vigilance is recommendable.
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PMID:Cephapirin-induced neutropenia. 261 33

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

Nephrotoxicity related to vancomycin hydrochloride therapy has been reported at overall rates of 7% to 16% and as high as 35% when combined with an aminoglycoside antibiotic. We conducted a prospective study in older men. A group that received vancomycin was compared with a control group to determine the incidence of nephrotoxicity secondary to vancomycin therapy alone and in combination with aminoglycosides, to identify possible risk factors associated with nephrotoxicity, and to determine the incidence of other adverse effects associated with vancomycin use. Nephrotoxicity occurred in 11 (17%) of 66 patients receiving vancomycin and in 3 (5%) of 57 controls overall. Stepwise logistic-regression analysis failed to identify underlying illnesses or concurrent risks that may have contributed to the development of nephrotoxicity associated with vancomycin. Adverse effects, including phlebitis (14%), neutropenia (1%), rash (0%), and red neck syndrome (0%), occurred at rates similar to previous reports.
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PMID:Mild nephrotoxicity associated with vancomycin use. 276 51

Fifty patients with posttraumatic tibial nonunion complicated by chronic refractory osteomyelitis were treated with intravenous antibiotics. Fifteen patients (30%) experienced 18 episodes of leukopenia; seven of these patients became neutropenic and three became severely neutropenic. No patient became neutropenic prior to the 20th day of antibiotic therapy. The classic findings of fever, pruritus, maculopapular rash, and eosinophilia did not correlate with either the onset or the severity of the neutropenia. Neutropenia can develop precipitously. Prevention of neutropenia is difficult in a patient population receiving long-term antibiotic therapy. Regular monitoring of the white blood cell count and differential cell count minimizes the risk of developing prolonged, severe neutropenia with potential complications. No patient in this series had any serious or infectious complication secondary to neutropenia.
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PMID:Neutropenia complicating parenteral antibiotic treatment of infected nonunion of the tibia. 281 86

A total of 314 immunocompromised patients with serious cytomegalovirus (CMV) infection treated with ganciclovir administered intravenously were studied. Rates of favorable clinical response among evaluatable patients were 91 (84%) of 108 for CMV retinitis, 35 (83%) of 42 for gastrointestinal CMV infection, and 26 (72%) of 36 for CMV pneumonia. Of 167 treated patients who had AIDS, improvement or stabilization of CMV disease occurred in 83% as compared with 13% of 39 untreated, historical control patients with AIDS and similar CMV disease (P less than or equal to .004). Virologic response was noted in 111 (92%) of 121 patients who had sequential cultures of blood, urine, or throat washings for CMV. In an attempt to prevent relapse of CMV disease after discontinuation of ganciclovir, maintenance treatment was evaluated in a group of 61 patients with AIDS and CMV retinitis who had received an initial dosage of greater than or equal to 7.5 mg/(kg.d) for greater than or equal to 10 days. Median time to relapse of retinitis was 47 days in patients not receiving maintenance treatment as compared with 105 days in patients treated with 25-35 mg/(kg.w) (P = .0002). Adverse effects of treatment included neutropenia (42%), thrombocytopenia (19%), central nervous system effects (18%), nausea (6%), fever (6%), rash (6%), vomiting, diarrhea, infusion site reactions, and anemia (4% each). It was concluded that ganciclovir has clinical efficacy against CMV disease, as well as an in vivo antiviral effect, and that this agent reduces morbidity of serious CMV infections in immunocompromised patients.
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PMID:Ganciclovir treatment of life- or sight-threatening cytomegalovirus infection: experience in 314 immunocompromised patients. 284 86

Trimetrexate glucuronate (TMTX), a nonclassical folate antagonist, has been evaluated clinically on several schedules. We have studied TMTX administered as an iv bolus for 5 consecutive days every 3 weeks in 35 patients with advanced solid tumors. Drug was given at doses ranging from 7.6 to 18.8 mg/m2. The maximal tolerated dose was 13.1 mg/m2 per day x 5 for patients without prior myelotoxic treatment and 7.6 mg/m2 per day x 5 for previously treated patients. Because of wide individual differences in drug tolerance, dose escalation in 25% increments is recommended for patients not experiencing toxic effects. The dose-limiting toxicity was neutropenia. Rash and mucositis were also significant. TMTX concentrations were measured 1 and 24 hours after each dose, and the data were fit by use of a one-compartment pharmacokinetic model. With this simplified sampling and modeling scheme, the mean total body clearance (+/- SD) of trimetrexate was 31 +/- 20 mL/min per m2 and the volume of distribution was 13 +/- 7 L/m2. Mean plasma concentrations 1 hour after a dose were 1.12, 2.43, 3.33, and 3.25 mumol/L at 7.6, 9.1, 10.9, and 13.1 mg/m2, respectively. The mean TMTX concentration (+/- SD) 24 hours after a dose was 114 +/- 87 nmol/L. The mean area under the concentration-versus-time curve at 13.1 mg/m2 was 2,266 mumol.min/L. The drug concentration 1 hour after the first dose and the area under the concentration-versus-time curve were highly correlated with leukopenia and thrombocytopenia (r = .6 and .65 and P = .0007 and .0001, respectively). The maximal tolerated dose on the daily x 5 schedule was 30% of the dose tolerated on an iv bolus schedule. The choice of drug schedule for clinical trials when murine and human pharmacokinetics differ is discussed. Phase II trials are under way with both the iv bolus and the daily x 5 schedules.
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PMID:Phase I trial of trimetrexate glucuronate on a five-day bolus schedule: clinical pharmacology and pharmacodynamics. 290 52

Many of the adverse reactions produced by penicillamine and other compounds with an active sulfhydryl group form a distinctive pattern when viewed as a class. Alterations in taste perception, mucocutaneous lesions, proteinuria due to immune-complex membranous glomerulopathy, and pemphigus are adverse reactions that have been encountered with all of the compounds discussed herein. Hematologic reactions such as neutropenia and thrombocytopenia occur rarely and with variable frequency. The angiotension converting enzyme inhibitor captopril has an active sulfhydryl group. When it was first given in high doses to patients with severe hypertension, adverse effects similar in pattern to those just outlined were reported. With reduced doses and more careful patient selection, the more serious reactions are no longer found, but disturbances of taste perception, rash, and oral mucosal ulcers are still encountered.
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PMID:Adverse effects profile of sulfhydryl compounds in man. 293 93

We studied D-penicillamine toxicity in 259 patients with systemic sclerosis treated since 1972. The average daily dose of 635 mg was given for a mean of 1.8 years. Of patients with systemic sclerosis, 47% has side effects from D-penicillamine treatment, similar to the 56% of 807 patients with rheumatoid arthritis in seven separate series. Individual manifestations of toxicity included rash, proteinuria, gastrointestinal symptoms, dysgeusia, oral ulcers, thrombocytopenia, and neutropenia. Four episodes each of myasthenia gravis and pemphigus occurred in our patients; both were reported rarely in patients with rheumatoid arthritis. Adverse effects occurred more frequently after rapid increases in dosage. Treatment had to be discontinued due to toxicity in 29% of patients with systemic sclerosis and in 33% of those with rheumatoid arthritis. Although toxic, with a high frequency of adverse effects, D-penicillamine can be used safely in the treatment of systemic sclerosis. Pemphigus and myasthenia gravis may occur more frequently with therapy for systemic sclerosis than with that for rheumatoid arthritis.
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PMID:The toxicity of D-penicillamine in systemic sclerosis. 293 30

The effectiveness of piperacillin was investigated in 30 children operated upon for peritonitis: 13 had acute appendicitis with puriform peritoneal reaction, or a recently perforated appendix; 5 had generalized peritonitis of appendicular origin, and 13 had intraperitoneal abscess. In the 12 children who underwent right iliac appendicectomy (with post-operative drainage in 3), piperacillin was administered alone during 5 days; clinical and bacteriological cure was obtained in all cases; the mean duration of stay in hospital was 7 days. The 5 cases of generalized peritonitis required drainage; piperacillin was given alone in 4 of them and combined with an aminoglycoside and metronidazole in one who was in poor general condition. Bacteriology showed a predominance of Escherichia coli alone or associated with other organisms. Clinical and bacteriological cure was obtained in 3 patients; the mean duration of stay in hospital was 12 days. Seven of the 13 cases of intraperitoneal abscess needed drainage. Piperacillin was administered alone for 7 days on average in 10 cases and combined with an aminoglycoside and metronidazole in 2 cases. Eight patients had a favourable course, 5 developed complications. In all 3 groups piperacillin was tell tolerated. A patch of urticaria was noted in 2 cases and a transient skin rash in 2 other cases. No neutropenia was observed in these children whose treatment never exceeded 10 days.
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PMID:[Effectiveness of piperacillin in the antibacterial treatment of intra-abdominal infections in children]. 294 82


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