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991.
Wells-Knecht KJ Ott GR Cheng M Wells GJ Breslin HJ Gingrich DE Weinberg L Mesaros EF Huang Z Yazdanian M Ator MA Aimone LD Zeigler K Dorsey BD 《Chemical research in toxicology》2011,24(11):1994-2003
There are numerous published studies establishing a link between reactive metabolite formation and toxicity of various drugs. Although the correlation between idiosyncratic reactions and reactive metabolite formation is not 1:1, the association between the two is such that many pharmaceutical companies now monitor for reactive metabolites as a standard part of drug candidate testing and selection. The most common method involves in vitro human microsomal incubations in the presence of a thiol trapping agent, such as glutathione (GSH), followed by LC/MS analysis. In this study, we describe several 2,7-disubstituted-pyrrolotriazine analogues that are extremely potent reactive metabolite precursors. Utilizing a UPLC/UV/MS method, unprecedented levels of GSH adducts were measured that are 5-10 times higher than previously reported for high reactive metabolite-forming compounds such as clozapine and troglitazone. 相似文献
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Erik WMA Bischoff Tjard RJ Schermer Hans Bor Pete Brown Chris van Weel Wil JHM van den Bosch 《The British journal of general practice》2009,59(569):927-933
Background
Changes in the burden of chronic obstructive pulmonary disease (COPD) and its exacerbations on primary health care are not well studied.Aim
To identify trends in the prevalence of physician-diagnosed COPD and exacerbation rates by age, sex, and socioeconomic status in a general practice population.Design of study
Trend analysis of COPD data from a 27-year prospective cohort of a dynamic general practice population.Setting
Data were taken from the Continuous Morbidity Registration Nijmegen.Method
For the period 1980–2006, COPD and COPD exacerbation data were extracted for patients aged ≥40 years. Data were standardised for the composition of the Continuous Morbidity Registration population in the year 2000. Regression coefficients for trends were estimated by sex, age, and socioeconomic status. Rate ratios were calculated for prevalence differences in different demographic subgroups.Results
During the study period, the overall COPD prevalence decreased from 72.7 to 54.5 per 1000 patients per year. The exacerbation rate decreased from 44.1 to 31.5 per 100 patients, and the percentage of patients with COPD who had exacerbations declined from 27.6% to 21.0%. The prevalence of COPD increased significantly in women, in particular those aged ≥65 years with low socioeconomic status. Decreases in exacerbation rates and percentages of patients with exacerbations were independent of sex, age, and socioeconomic status.Conclusion
The decline in COPD prevalence and exacerbation rates suggests a reduction of the burden on Dutch primary care. The increase of the prevalence in women indicates a need to focus on this particular subgroup in COPD management and research. 相似文献995.
996.
Prediction of 1‐year mortality and impact of bivalirudin therapy according to level of baseline risk: A patient‐level pooled analysis from three randomized trials 下载免费PDF全文
Jennifer Yu MD Roxana Mehran MD FSCAI Tim Clayton MSC C. Michael Gibson MD Bruce R. Brodie MD Bernhard Witzenbichler MD A. Michael Lincoff MD Efthymios N. Deliargyris MD Bernard J. Gersh MB ChB DPhil Stuart J. Pocock PhD Gregg W. Stone MD FSCAI George D. Dangas MD PhD FSCAI 《Catheterization and cardiovascular interventions》2016,87(3):391-400
Objectives : We aimed to construct a predictive model for one‐year mortality in patients undergoing invasive coronary evaluation and to examine the impact of bivalirudin on survival according to the level of baseline risk. Background : Compared to heparin plus GP IIb/IIIa inhibitors (HEP/GPI), bivalirudin decreases bleeding complications in a range of clinical presentations. The impact of preprocedural risk assessment on survival and whether this is modified by bivalirudin, has not been investigated in detail. Methods : We examined patient‐level data from the REPLACE‐2, ACUITY, and HORIZONS‐AMI trials (n = 18,819) to construct a risk‐adjusted mortality model using baseline clinical variables. Results : One‐year mortality occurred in 287 patients (3.1%) assigned to bivalirudin and 336 patients (3.6%) assigned to HEP/GPI (HR 0.85; 95% CI, 0.73–1.00; P = 0.048). Using 11 highly significant predictors of mortality, we developed an integer‐risk score to classify patients into risk tertiles. High‐risk patients had a rate of 1‐year mortality over 9‐fold greater than low‐risk patients. Consequently, the absolute mortality reduction attributed to bivalirudin was more marked in high‐risk patients: 3.1% (?0.8% to 7.0%) in the overall cohort, 4.8% (0.5% to 9.2%) in the PCI cohort (P‐interaction versus intermediate and low risk categories, 0.09 and P = 0.02, respectively). Conclusions : In patients undergoing invasive coronary evaluation, 1‐year mortality can be predicted using baseline variables. Bivalirudin treatment (versus HEP/GPI) conferred a survival benefit. © 2015 Wiley Periodicals, Inc. 相似文献
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998.
Rezazadeh M Hajilooi M Haidari M Rafiei A Alavi SA Keramat F 《Scandinavian journal of infectious diseases》2006,38(11-12):1045-1049
A C-T substitution at position 590 in the interleukin-4 (IL-4) gene is associated with increased production of IL-4. We sought to determine the associations between this polymorphism and susceptibility to brucellosis. DNA was extracted from the whole blood of 163 control individuals and 282 patients with brucellosis. A polymorphism in the IL-4 gene at position 590 from the promoter site was determined using an allele-specific PCR method. The prevalence of the T allele of IL-4 polymorphism was significantly higher in the patients group than in controls (28.9% vs 11.4%, p<0.004). Patients with brucellosis had a higher frequency of intermediate producer genotype (CT) (53.5% vs 22.7%, p<0.001) while low producer genotype (CC) was higher in the control group (77.3% vs 44.4%). Multiple logistic regression analysis demonstrated that patients who were heterozygous (CT) for interleukin-4 promoter polymorphism had a significantly higher risk for brucellosis with an odds ratio of 4.2 (95% CI 2.7-6.6, p<0.0001). Our findings demonstrate for the first time an association between IL-4 590 promoter polymorphism and contracting brucellosis in the Iranian population. 相似文献
999.
Brodie BR Stone GW Cox DA Stuckey TD Turco M Tcheng JE Berger P Mehran R McLaughlin M Costantini C Lansky AJ Grines CL 《American heart journal》2006,151(6):1231-1238
1000.
The report of two cases with multiple sulfatase deficiency resulting from a rare similar gene mutation 下载免费PDF全文