Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial

Context  Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use. Objective  To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography. Design, Setting, and Patients  The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada. Interventions  Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo. Main Outcome Measure  Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome. Results  The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P = .17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P = .32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P = .045), and suggested an increased risk in the active vitamin group (P = .09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions. Conclusion  In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.      

贴报-P2临床毒理学、药理学和疗效研究

5-Flourouracil（5-FU） is one of well known anti-cancer drugs, but its toxicity in normal lymphocytes remains a major problem in chemotherapy. The eastern traditional drug, Bupleuri radix（BR）, has been used for the treatment of liver diseases and contains series of triterpene saponins.     

Roxatidine versus ranitidine in the treatment of duodenal ulcers: A randomized double-blind controlled multicentre study in Singapore

Roxatidine acetate, a new H₂ receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine.     

计算机程序化的初均速法测定双黄连注射液的稳定性

用计算机程序化的初均速法,测定了双黄连溶液中3种主要成分——绿原酸、黄苓甙、连翘甙的活化能及室温贮存期。该方法简便、快速、结果准确。对临床应用有一定价值。     

Induction of unscheduled DNA synthesis in suspensions of rat hepatocytes by an environmental toxicant, 3,3'4,4'-tetrachloroazobenzene.

Unscheduled DNA synthesis was induced by 3,3'4,4'-tetrachloroazobenzene (TCAB)) in freshly isolated suspensions of rat hepatocytes. A dose-dependent response was demonstrated. Hepatocellular DNA was obtained after the chloroform-isoamyl alchohol-phenol extraction of the isolated nuclei. The induction of unscheduled DNA synthesis was measured by the incorporation of [3H]-thymidine in the presence of hydroxyurea as determined by the scintillation counting assay. DNA repair data obtained in this study on benzo[a]pyrene and methyl methanesulfonate are comparable to a previous report using primary cultures of hepatocytes and cesium chloride gradients. Hence, the present method offers promise as a rapid and sensitive screen for chemical carcinogens.