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Resuscitation research trials must have adequate scientific basis, sound ethics, feasibility, and potential impact on health care. The organization and methodology of the Pittsburgh-based Brain Resuscitation Clinical Trials (BRCT I) are reviewed in detail. This type of international collaborative study will be useful for evaluation of new cardiopulmonary-cerebral resuscitation therapies.

Twenty-four-hour, four-hour (8 to 12 am), and overnight urine collections were examined for their ability to detect microalbuminuria in 292 patients with insulin-dependent diabetes mellitus (IDDM). Albumin excretion rate (AER) was measured and also estimated from the product of the urinary albumin/creatinine ratio (A/C) and the calculated 24-hour creatinine excretion. The fractional excretion of albumin (FEA) was also determined in aliquots from each urine sample. The correlation coefficients between measured 24-hour AER and estimated AER were 0.940 and 0.956 for four-hour and overnight collections, respectively (significance of each correlation, P less than 0.001). There was no advantage in using the FEA over the A/C ratio in predicting measured AER. Urinary A/C ratios (mg/mg) between 0.03 and 0.31 in the four-hour collections were highly predictive of microalbuminuria and of measured AER in the 24-hour collections: AER24-h (microgram/min/1.73 m2) = 2.74 + 0.870 x A/C4-h (all log10 values). In a subgroup of 175 patients having all three collections validated, 34 (20%) had microalbuminuria defined as AER 20 to 200 micrograms/min/1.73 m2 in at least two of the three samples and 44 (25%) had overt nephropathy (greater than 200 micrograms/min/1.73 m2). The ability of the AER in one urine collection to predict microalbuminuria in at least one of the other two collections was assessed in these 175 patients. Compared with the overnight urine collection, the four-hour collection had greater sensitivity while affording similar specificity and positive predictive value. Based on these data, the A/C ratio from a morning urine sample following initial AM voiding would seem adequate for the detection and monitoring of microalbuminuria in patients with IDDM.

Because CABG results in a significantly higher morbidity and prolonged hospitalization in the older patient group, PTCA is an attractive alternative for providing myocardial revascularization in the small group of older patients with appropriate lesions for dilation. This analysis of the results of PTCA in 370 older patients in the NHLBI PTCA Registry reveals that PTCA can be performed with acceptably low mortality and morbidity. Therefore, PTCA may offer an alternative to CABG in the highly selected symptomatic older patient.

Epidemiologic investigations have shown that low socioeconomic status is related to ischemic coronary heart disease mortality in men and women as well as to major risk factors for coronary heart disease, predominantly in men. The present study investigated the associations between educational attainment and biologic and behavioral risk factors for coronary heart disease in a community sample of 2,138 middle-aged women residing in Allegheny County, Pennsylvania. The women were contacted between 1983 and 1985 to determine eligibility for a study of risk factor changes during the perimenopausal period. Eligibility criteria included age 42 to 50 years, premenopausal status, diastolic blood pressure less than 100 mmHg, and nonuse of medications known to influence risk factors. Among the 541 eligible participants, the less education the women reported, the more atherogenic was their risk factor profile, including higher systolic blood pressure, low density lipoprotein (LDL) cholesterol, apolipoprotein B, triglycerides, fasting and two-hour glucose values, two-hour insulin values, body mass indices, and lower high density lipoprotein (HDL) cholesterol and HDL/LDL ratio; the more often they reported being cigarette smokers, taking little physical exercise, and consuming alcohol less than one day a week; the more often they reported on standardized psychologic tests being Type B, angry, pessimistic, depressed, and dissatisfied with paid work, and having little social support and self-esteem (all p values less than 0.01). Similar associations were obtained between educational attainment and risk factors reported by the 1,588 nonparticipants during the telephone screening interview. These results suggest many biologic and behavioral factors by which women with little education are at elevated risk for coronary heart disease. To the extent that advanced education protects women against coronary heart disease, a potentially important public health intervention for women is education.

Because noncontraceptive hormone use is not randomly distributed in the population, selection factors for hormone use need to be critically examined to clarify the nature of the relationship between hormone exposure and disease endpoints. The characteristics of hormone users were examined using sociodemographic and health-related information obtained in a telephone survey of 2,137 women (ages 40-52), randomly selected from a driver's license list of Pittsburgh area women. Results showed that 6% of the women surveyed reported current noncontraceptive hormone use, and that 71% of the users had undergone hysterectomy and/or oophorectomy, hereafter called the surgical group. Among all women, hormone users were older and thinner than nonusers, and the frequency of use was two times as high among whites than among blacks. Because rates of use varied dramatically by surgical status, separate univariate and multivariate analyses were conducted for women with and without a hysterectomy/oophorectomy. Body mass index was inversely related to hormone use, and alcohol consumption was positively related to hormone use among both groups. Whites had higher rates of hormone use than blacks among women with hysterectomy/oophorectomy, and a higher level of education was positively related to hormone use among nonsurgical women. The findings show that the distribution of hormone use varies markedly in the community by surgical status, body mass index, race, education, and alcohol use.

The need for a standardized and valid means of assessing diabetic neuropathy has been increasingly recognized. To identify potential components of such an assessment, interobserver variation (neurologist and internist) of a standard neurologic examination and the comparability of this examination with vibratory and thermal sensitivity testing was studied. The study population comprised the first 100 participants in a neuropathy substudy of 25- to 34-yr-old subjects with insulin-dependent diabetes mellitus taking part in a cohort follow-up study. Symptoms of dysesthesias, paresthesias, and burning, aching, or stabbing pain revealed good interobserver agreement. Signs of neuropathy, more prevalent in the great toe than index finger, showed poor interobserver agreement for vibration, but fair interobserver agreement for touch and pinprick. Mean quantitative sensory thresholds differed significantly by clinical category of abnormal vibratory and pinprick sensations. Threshold testing showed twice the prevalence of abnormality compared with clinical examination. It is concluded that components of the clinical examination can be identified that, along with quantitative sensory-threshold testing, may provide a satisfactory core assessment for use both in epidemiologic studies and incorporation into more in-depth protocols required for clinical research and practice. The clinical relevance of the greater prevalence of abnormalities on threshold testing will be established by long-term follow-up.

The NHLBI PTCA Registry collected clinical data on 3,101 PTCA procedures performed at 105 clinical centers between September 1977 and September 1981. To investigate the "learning curve" from introduction through the early application of this new therapy for revascularization, success rates and complication rates were examined by calendar year and according to investigator experience. Success rates improved by calendar year, from 54% in 1979 to 66% in 1981. Investigators with fewer than 50 cases had a success rate of 55%. After an investigator had performed 150 procedures, the success rate was 77%. The increase in success rate was largely the result of a dramatic increase in the ability to cross the narrowing with the catheter, and was accounted for by experience and improved equipment. Patient selection for PTCA was characterized by sex, age, previous CABG, number of diseased coronary arteries and stable Canadian Heart classification over time. Reflecting the increase in the success rate was the decrease in the need to perform elective CABG. Emergency CABG, death and MI rates were low (1% mortality, 5% nonfatal MI) and did not change significantly with time or with investigator experience.

Lipoprotein mass concentrations were measured by analytical ultracentrifugation in a subset of 57 hypercholesterolaemic male participants in the National Heart, Lung, and Blood Institute Type II Coronary Intervention Study. 2-year changes in levels of intermediate-density lipoproteins (IDL) of flotation rate 12-20 were strongly predictive of progression of coronary artery disease at 5 years. Changes in serum mass concentrations of low-density lipoproteins (LDL; flotation rate 0-12), very-low-density lipoproteins (VLDL; flotation rate 20-400), high-density lipoproteins (HDL), and the HDL2 and HDL3 subfractions did not differ significantly between men with and without definite progression of coronary artery disease. The relation of IDL mass to disease progression remained significant (p less than 0.05) after adjustment for group assignment to cholestyramine treatment or placebo and was only slightly reduced (p less than or equal to 0.06) by adjustment for changes in LDL mass concentrations. Changes in IDL mass and ratios of HDL-cholesterol to total-cholesterol or LDL-cholesterol were inversely correlated and had a similar ability to predict progression. The findings are consistent with earlier evidence that IDL are directly involved in the development of coronary artery disease and suggest that ratios of HDL-cholesterol to total-cholesterol or LDL-cholesterol may be indicators of coronary disease risk partly owing to relations with IDL metabolism.

In a secondary prevention trial conducted by the National Heart, Lung, and Blood Institute, the effect of lipid lowering by drug intervention on the progression of existing coronary artery disease (CAD) was evaluated in type II hyperlipidemic patients. This first randomized, secondary prevention trial compared the effect of cholestyramine and diet with that of placebo and diet in 143 patients over a 5-year period. End points evaluated were progression or regression of CAD, as demonstrated by angiographic changes compared with baseline angiograms. The cholestyramine-treated group demonstrated a significant reduction in total cholesterol and in low-density lipoprotein cholesterol (LDL) levels as compared with placebo, and an 8% increase in high-density lipoprotein cholesterol (HDL). A statistically significant result supporting the use of cholestyramine treatment was found in one category of CAD progression.

The Type II Coronary Intervention Study (Type II Study) is a double-blind, randomized, placebo-controlled clinical trial conducted by the Division of Intramural Research of the National Heart, Lung, and Blood Institute of Bethesda, Maryland. The study was designed to evaluate the 5-year treatment effect of cholestyramine on low density lipoprotein (LDL) cholesterol and on lesions in the coronary arteries. One hundred forty-three patients with Type II hyperlipoproteinemia (elevated LDL cholesterol) and coronary artery disease (CAD) were entered into the study between 1972 and 1976. Patients were stratified by sex and extent of coronary disease as defined angiographically and were randomly allocated to a daily dosage of 24 g cholestyramine and diet (treatment group) or placebo and diet (control group). Changes in the coronary arteries were evaluated by sequential coronary angiography carried out before and after five years of treatment. This report describes the trial design and baseline characteristics of the study patients.