We have studied both central and peripheral hemodynamic changes induced by infusion of nitroglycerin (55 micrograms/kg per minute) over a 15-min period in conscious dogs to clarify its mechanism of ...action. Dogs were prepared with an electromagnetic flow probe positioned at the root of the aorta, and microspheres (9 microns) were used to measure regional blood flow distribution before and after 15 min of infusion. Controlled hypotension (-15 to -20 mmHg (1 mmHg = 133.322 Pa)) was maintained throughout the infusion period and this hypotensive state was associated with a significant decrease in stroke volume (-30%), cardiac index (-20%), and left ventricular work (-43%). Regional blood flow studies showed that at the 15th min of infusion, nitroglycerin induced significant decrease in blood flow to all components of the myocardium (range -12 to -20%) while their vascular resistances were not affected significantly. Blood perfusion to liver (hepatic artery), spleen, and intestine was also modified significantly (-22, -18, and -16%, respectively) while their vascular resistances remained close to control values. By the time measurements were made, blood flow and vascular resistance of cerebral and renal tissues remained normal. For each organ studied, blood perfusion was uniform. These results indicate that nitroglycerin elicits both central and peripheral hemodynamic changes and that local reflex adjustments modify the vasodilator effect of the drug in most vascular beds that we have studied.
Probucol 4,4-(isopropylidendithio bis)(2,6-di-t-butylphenol), as as an adjunct to diet, was evaluated for its effect on lowering the plasma cholesterol level in patients with familial ...hypercholesterolemia (type II). The trial had a double-blind, placebo-controlled, crossover design. About half of the 30 patients responded to a low-cholesterol modified-fat diet with a decrease in the plasma cholesterol level of approximately 13%. When probucol was added to the diet of the responders, their plasma cholesterol level was lowered a further 13%. Patients who did not respond to the diet did show reduced plasma cholesterol concentrations when receiving probucol plus the diet. Analysis of the cholesterol content of the various lipoprotein fractions showed that the low-density lipoproteins accounted for most of the total plasma cholesterol level decrease. There was, as expected, no effect on plasma triglyceride concentrations. Neither the 7-dehydrocholesterol nor the desmosterol level was increased in the plasma of patients treated with probucol for three months. Probucol is useful as an adjunct to diet in lowering plasma cholesterol levels in patients with familial hypercholesterolemia. The drug was well tolerated by all patients.
Summary
Background Lately, the number of systematic reviews published has increased substantially. Many systematic reviews exclude trials published in languages other than English. However, there is ...little empirical evidence to support this action. We looked for differences in the completeness of reporting between trials published in other languages and those published in English, to see whether the exclusion of trials published in other languages is justified.
Methods We compared completeness of reporting, design characteristics, and analytical approaches of 133 randomised controlled trials (RCTs) published in English between 1989 and 1994 and 96 published in French, German, Italian, or Spanish during the same time. RCTs were identified by hand searching of journals (seven in English and six in the other languages).
Findings We found no significant differences between trials published in English and other-language trials for any single item in the completeness of reporting scale (randomisation, double-blinding, withdrawals), or for the overall score (percentage of maximum possible score 51·0% for trials in English, 46·2% for trials in other languages; 95% Cl for difference -1·1 to 10·5). Other-language trials were more likely than English-language trials to have adult participants, to use two or more interventions, and to compare two or more active treatments without an untreated control group. Trials in other languages were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation.
Interpretation These results provide evidence for inclusion of all trial reports, irrespective of the language in which they are published, in systematic reviews. Their inclusion is likely to increase precision and may reduce systematic errors. We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic reviews.
To compare the hypnotic effects of a bedtime dose of zolpidem, triazolam, and placebo.
Double-blind, randomized, placebo- and active-controlled, parallel-group trial.
Six Canadian hospitals.
357 ...patients (aged 19 to 71 years) hospitalized the night before a surgical procedure.
At bedtime, each patient received either zolpidem 10 mg, triazolam 0.25 mg, or placebo, and was allowed to sleep for a maximum of 8 hours.
Outcome measures were subjective in nature and included a morning questionnaire, visual analog scales, and observation forms by study personnel. All continuous variables were analyzed by analysis of variance. All categorical data were compared using the Cochran-Mantel-Haenszel (CMH) test, and the percentage of patients asleep was compared using a CMH chi-square analysis. When significant overall treatment effects were observed, pairwise comparisons were undertaken. Compared with the placebo group, the following parameters were significantly (p < 0.001) different in the zolpidem and triazolam groups: sleep latency was shorter, total sleep time was longer, patients fell asleep more easily, and the number of patients awake 2 hours after drug administration was lower. There were no differences between any groups in next-morning somnolence or ability to concentrate. Both drugs were well tolerated, with adverse event incidence rates nearly identical to placebo.
In patients suffering from transient insomnia, a single dose of zolpidem 10 mg was as effective as triazolam 0.25 mg, and both were more effective than placebo and were well tolerated.
