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Biomedical subjects

W Voyles

Publications and source records attributed to W Voyles.

6 recordsLinked to original sources

A factor analytic study of physical risk variables for CHD.

The scores of 40 hospitalized male coronary heart disease (CHD) patients, for seven traditionally employed physical CHD risk factors, were subjected to a confirmatory factor analysis that employed a LISREL program. An attempt was made to confirm a two-factor solution that involved family history as one factor, and smoking, serum cholesterol level, blood pressure, physical exercise, diet, and weight control as the second. The obtained goodness-of-fit index (.84) suggests that the two-factor solution is a moderately valid one. These findings raise the question whether many of the physical risk factors for CHD simply may be manifestations of a single behavioral characteristic, perhaps best described as "lack of self-control."

Adult↗

Long-term bepridil monotherapy for angina pectoris.

The long-term efficacy of bepridil as once-a-day monotherapy was studied in 19 men with stable angina pectoris. After 2 weeks of single-blind placebo therapy and a 12-week parallel placebo-controlled, dose-response study, each patient received open-label bepridil. After a dose-titration period of 3 months, patients received bepridil (100 to 400 mg once a day, mean 290 mg) for 24 months. The response to treatment was assessed by patient diaries and serial treadmill exercise testing 24 hours after dose administration, every 3 months. Only 2 patients were released from the study due to therapeutic failure. Compared with placebo, 3 months of bepridil therapy resulted in a significant reduction in the weekly frequency of angina from 10.3 +/- 9.1 to 1.8 +/- 3.5 (p less than 0.002) and nitroglycerin consumption from 5.0 +/- 5.4 to 1.4 +/- 2.3 (p less than 0.01). In addition, there was a simultaneous significant increase in the walking time to angina from 5.2 +/- 2.3 to 7.9 +/- 2.6 minutes (p less than 0.001) and total exercise time from 7.1 +/- 2.2 to 8.8 +/- 1.9 minutes (p less than 0.001). These favorable effects were sustained throughout the 24 months of the study. Although resting QTc interval was prolonged by 36 to 42 ms (p less than 0.001) during bepridil therapy, ventricular dysrhythmias were not observed immediately before or during exercise testing and were not manifested by symptoms. Neurologic and gastrointestinal side effects of mild to moderate severity were observed, but none required discontinuation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Usefulness of twice-daily isosorbide-5-mononitrate in preventing development of tolerance in angina pectoris.

Development of tolerance to nitrates during long-term therapy is a major concern. It has been suggested that isosorbide-5-mononitrate (IS-5MN), an active metabolite of isosorbide dinitrate, administered twice daily 12 hours apart does not lead to development of tolerance. The duration of effects of IS-5MN at a dose of 20 and 40 mg and of placebo was studied in patients with angina pectoris who responded to nitrates after the first dose (n = 12) and after 1 week of twice-daily therapy (n = 9). The study was double-blind, randomized and crossover in design. Compared with placebo values, after the first dose of 20 and 40 mg IS-5MN, exercise duration was higher at 2 hours (p less than 0.001) and 6 hours (p less than 0.02). After 1 week of twice-daily therapy at these doses, exercise duration increased at 2 hours (p less than 0.05) but not at 6 or 10 hours after the dose. After the first dose of 20 and 40 mg IS-5MN, standing systolic blood pressure decreased at 2 hours (p less than 0.02). Blood pressure did not change significantly after chronic therapy. Tolerance to antianginal effects during twice-daily therapy with 20 and 40 mg of IS-5MN developed despite higher plasma IS-5MN concentrations at 2 and 6 hours during twice-daily therapy than after the first dose. The tolerance during twice-daily therapy with IS-5MN was characterized by a reduced peak effect at 2 hours and shortened duration of action compared with first-dose effects.

Aged↗

Duration of effects and tolerance of slow-release isosorbide-5-mononitrate for angina pectoris.

Isosorbide-5-mononitrate (IS-5MN) is an active metabolite of isosorbide dinitrate, but unlike its parent compound, is nearly 100% bioavailable after oral administration. Once-a-day therapy with a slow-release formulation of IS-5MN is used widely in Europe for 24-hour prophylaxis of angina pectoris. In a randomized, crossover, double-blind, placebo-controlled study, the duration of effects of 50 and 100 mg of slow-release IS-5MN were evaluated after the first dose and after once-a-day therapy for 1 week in 9 patients with stable angina pectoris. Compared with placebo values, standing blood pressure decreased (p less than 0.001) and exercise time to the onset of angina and total exercise duration increased (p less than 0.008 and p less than 0.003) at 4 hours, but not at 20 or 24 hours after first dose of 50 and 100 mg of slow-release IS-5MN. After once-a-day therapy for 1 week, no improvement in exercise duration or reduction in ST-segment depression was seen after 50 or 100 mg of slow-release IS-5MN at 4, 20 or 24 hours despite high plasma IS-5MN concentrations. Thus, despite therapeutic plasma concentrations, 50 and 100 mg of slow-release IS-5MN did not exert antianginal or anti-ischemic effects at 20 and 24 hours after the first dose and at 4, 20 and 24 hours after sustained once-a-day therapy for 1 week.

Adult↗

Transdermal nitroglycerin patches in angina pectoris. Dose titration, duration of effect, and rapid tolerance.

The duration of effect of transdermal nitroglycerin patches was studied in 14 patients with angina pectoris. By titrating the dose to achieve specific circulatory effects, we chose a patch size that produced a consistent fall in systolic blood pressure of 10 mm Hg or greater for each patient (10 cm2 in 7 patients, 20 cm2 in 5, and 40 cm2 in 2; releasing 5, 10, and 20 mg of nitroglycerin per 24 hours, respectively). The effects of these individualized patches were compared with those of placebo patches. Compared with placebo, nitroglycerin patches increased exercise duration to the onset of angina (257 +/- 72 compared with 383 +/- 130 seconds, p less than 0.0001) and total exercise time (338 +/- 89 compared with 456 +/- 119 seconds, p less than 0.0001) and decreased ST segment depression (1.0 +/- 0.5 compared with 0.6 +/- 0.4 mm, p less than 0.05) at 4 hours but not at 24 and 48 hours. We conclude that nitroglycerin patches do not show objective evidence of antianginal or antiischemic effects for 24 hours. Tolerance to the circulatory and antianginal effects probably develops within 24 hours of patch application.

Administration, Topical↗

Lack of significant arrhythmogenicity from chronic theophylline and beta-2-adrenergic combination therapy in asthmatic subjects.

We monitored 14 asthmatic subjects (aged 18 to 60 years), with multiple 24-hour electrocardiogram (Holter) recordings, who were taking continuous sustained-release theophylline and beta-2-adrenergic therapy for control of their symptoms. All of the patients were enrolled in an efficacy study for the antiasthmatic drug lodoxamide. No patient demonstrated intrinsic cardiac disease by history or by a standard 12-lead electrocardiogram recording prior to entry into the study. All of the patients were stable at the beginning of the study while on therapeutic theophylline concentrations and inhaled and oral beta-2-adrenergics. Attempts were made to decrease the theophylline dosage by sequentially reducing the dose each week to one-half, one-quarter, and discontinuation. Holter monitoring was repeated at the end of each week of a new dose level. Five patients were able to reduce dosage and eight were able to discontinue theophylline completely. Theophylline therapy was associated with a higher mean heart rate (85.4 vs 79.9 bpm). The combination of theophylline and beta-2-adrenergics therapy was not associated with quantitative or qualitative changes in atrial or ventricular ectopic activity over beta-2-adrenergic therapy alone.

Adolescent↗