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H W Schnaper

Publications and source records attributed to H W Schnaper.

106 records · Page 6Linked to original sources

Can dropout and other noncompliance be minimized in a clinical trial? Report from the Veterans Administrative National Heart, Lung and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

Long-term clinical trials must face the problem of participants who drop out before the study is closed or who in other ways do not comply with the protocol. In a joint Veterans Administration-National Heart, Lung and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups and followed for up to 30 months. The data were analyzed for factors related to dropout and to medication and visit noncompliance. Large differences in dropout and compliance rates were found by clinic and age but not by treatment allocations (active vs. placebo) nor race-sex. In addition, noncompliance was 78%-118% higher in participants who subsequently chose to drop out of the study. Indications were that the attitude of a clinic towards participant complaints, willingness to temporarily reduce medication and vigorous pursuit of those who failed to keep appointments were important factors in reducing dropout. Strategies for minimizing dropout and noncompliance must be part of the study protocol, clinic personnel should be trained in using such strategies, and both clinic and participant compliance should be centrally monitored.

Adult↗

Clinical program for screening and treatment of hypertension in veterans.

Hypertension clinics, in which primary care is provided by specially trained nonphysician therapists under physician supervision, can provide very effective and relatively inexpensive control of hypertension for large numbers of patients. Since 1972, 32 VA Hypertension Screening and Treatment Clinics have screened about 500,000 veterans, 29 percent of whom have had diastolic pressures of 90 mmHg or more and 13 percent of whom have had diastolic pressures of 105 mmHg or more. Of subjects who returned for a second visit, 77 percent continued to have diastolic pressures of 90 mmHg or more. Blacks had a higher percentage of severe hypertension than whites.Since treatment became available in these clinics in 1974, 25,000 veterans have been treated. Computerized data are available for 10,777 of them who began treatment during 1974, 1975, or 1976. Of those with at least five treatment visits during that period, half had diastolic pressures below 90 mmHg at their most recent visit, and 80 percent had diastolic pressures below 100 mmHg. Moreover visit adherence was high, with two thirds of those who began treatment in these clinics during their first six months of operation continuing that treatment for two and a half years.

Adult↗

Serum lipoprotein levels during chlorthalidone therapy. A Veterans Administration-National Heart, Lung, and Blood Institute cooperative study on antihypertensive therapy: mild hypertension.

In a joint Veterans Administration-National Heart, Lung, and Blood Institute study of mild hypertension, 1,012 men and women, 21 to 50 years of age and with diastolic pressure from 85 to 105 mm Hg, were randomized into two double-blind treatment groups. Subjects in the active group received chlorthalidone or chlorthalidone plus reserpine, while the other subjects received matching placebo tablets. After one year of treatment, the chlorthalidone group had increases of 10.0 +/- 1.8 (SE) mg/dL in total cholesterol level, 9.8 +/- 5.2 mg/dL in triglyceride level, and 12.6 +/- 3.4 mg/dL in low-density lipoprotein-cholesterol level above the changes in the placebo group. There was no difference in high-density lipoprotein changes between the two groups (0.1 +/- 0.8 mg/dL). The possible net effect on risk of increasing lipid values while lowering pressure in the long-term treatment of mild hypertension with thiazides or related diuretics must be further evaluated.

Adult↗

Double-blind studies of the clinical effectiveness of prazosin.

In separate double-blind trials, prazosin was compared with placebo and with methyldopa and placebo. In both, prazosin was well tolerated and succeeded in lowering blood pressure in patients with mild to moderate hypertension. The mean reductions with methyldopa were greater, but the difference was not statistically significant and a higher percentage of the patients in the prazosin group became normotensive.

Adult↗

Inhibition of interleukin 1 (IL-1)-elicited leukocytosis and LPS-induced fever by soluble immune response suppressor (SIRS).

IL-1-induced leukocytosis was inhibited or blocked in a dose-dependent manner by SIRS, an antigen-nonspecific suppressive lymphokine, when administered intravenously or per os to CBA mice. Timing experiments showed that SIRS effectively inhibited the leukocytosis when administered within 30 minutes of the IL-1. An antipyrogenic activity of SIRS was observed in rabbits injected intravenously with LPS. SIRS, given intravenously in one or two doses, markedly reduced LPS-induced fever. SIRS (2000 units) was a more effective antipyretic agent than aspirin (3 mg/kg body weight, intramuscularly). The results suggest that SIRS may be a potential drug for use in IL-1-mediated disorders.

Animals↗

The relationship between diuretics and serum cholesterol in Hypertension Detection and Follow-up Program participants.

The effect of diuretics, mainly chlorthalidone, on serum cholesterol was studied in 7,006 of the Hypertension Detection and Follow-up Program (HDFP) hypertensive patients not on antihypertensive medication at baseline. Several investigators have reported that diuretic therapy increases serum cholesterol in treated subjects. However, data from two long-term studies indicated that no increase in cholesterol occurred after two years of diuretic treatment. In the present study, yearly changes in serum cholesterol in hypertensives treated with diuretics were observed. The results were in agreement with those reported from both short-term and long-term studies, in that a significant increase in cholesterol was observed in six months to one year into the study but not from the second to the fifth year of therapy. In fact, the serum cholesterol levels were the same as baseline values after two years of drug treatment and decreased slightly thereafter. In the untreated group, no change or a decrease in serum cholesterol was observed during the course of the study. The possible causes for changes in serum cholesterol concentration such as regression to the mean, change in body weight, baseline cholesterol concentration, and the action mechanism of diuretic drugs are discussed.

Adult↗

Early markers of ventilator-induced lung injury in rats.

Positive pressure ventilation with hyperdistention of the lungs (PPVHDL) causes microscopic lung injury in rats and in mice. This study compared lung lavage and serum levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine phosphokinase (CPK), lung lavage and plasma endothelin-1 (ET-1) concentration, lung tissue ET-1 mRNA expression, angiotensin converting enzyme (ACE) activity of lung homogenates, and histology of the lung structure in control and PPVHDL rats. Rats were anesthetized with pentobarbital. While control rats were breathing spontaneously, the PPVHDL rats were ventilated with a rodent ventilator delivering 30 percent oxygen, a tidal volume of 18.6 +/- 4.5 ml/kg, and a respiratory rate of 55 to 60 per minute. End-tidal CO2 was maintained at 38-40 mm Hg. After seven hours, rats were killed and the lungs were lavaged. Red blood cells were present in the sediment of lavage fluid in PPVHDL rats and their lung structure showed severe congestion, alveolar septa filled with red cells, and extravasation of red blood cells and inflammatory cells into the alveolar space. Lung lavage fluid AST and LDH were significantly higher in the PPVHDL compared with the control group (P < 0.03 and P < 0.001, respectively). Electrophoresis of the lung lavage LDH showed increased peak-5 in the PPVHDL group. Serum LDH, CPK, AST, and potassium concentrations [K]+ were significantly higher in the PPVHDL rats whereas their serum total protein level was significantly lower than the control group (P < 0.001). Electrophoretic patterns of serum and lung lavage protein were similar in both groups indicating a transmural passage of serum protein from the intravascular to the intra-alveolar space. No significant difference was found in lung tissue ET-1 mRNA expression and lung protein concentration between the two groups. Lung ACE activity, in contrast, was significantly lower in PPVHDL rats. This study demonstrated that moderate alveolar hyperdistention caused significant structural lung damage accompanied by decreased ACE activity after seven hours of mechanical ventilation and that elevated lung lavage and serum LDH and AST levels in lung lavage and in serum might be early markers of ventilator-induced lung injury in this rat model.

Animals↗