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Biomedical subjects

L H Kuller

Publications and source records attributed to L H Kuller.

At least 361 records · Page 20Linked to original sources

Poisson regression modeling of temporal variation in incidence of childhood insulin-dependent diabetes mellitus in Allegheny County, Pennsylvania, and Wielkopolska, Poland, 1970-1985.

Contradictory observations have accumulated regarding a secular trend and/or an epidemic pattern in the incidence of insulin-dependent diabetes mellitus. In this study, insulin-dependent diabetes mellitus incidence below age 15 years was examined in Allegheny County, Pennsylvania, and in Wielkopolska, Poland, two areas diverse in terms of their geography and average risk for this disease. Numerator data were extracted from individual patient records, and annual denominator data were available for the years 1970-1985. Poisson regression models were used to disentangle the contributions of country, race, sex, age, period, and cohort effects to the observed variation in incidence. Poles and Allegheny County nonwhites were at greatly and moderately reduced risk, respectively, relative to Allegheny County whites. An increase in risk with age was significant and proportional in all three groups. There was significant time variability in Wielkopolska, where an epidemic began in 1982 and continued through 1985. This was a period rather than a cohort phenomenon and was a result of a recent outbreak of the disease rather than a long-term trend. In Allegheny County, changes in risk over the 16-year period were insignificant, although incidence doubled among whites aged 0-9 years during 1982-1983. The Poisson regression modeling provided a quantification and formal comparison of determinants of the incidence of insulin-dependent diabetes mellitus.

Adolescent↗

Clustering of premature mortality in 1,761 insulin-dependent diabetics and their family members.

The clustering of premature mortality was investigated in 1,761 insulin-dependent diabetics and their family members from the Children's Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus Registry from 1950-1981. At follow-up, 5% of the mothers and 13% of the fathers were deceased. Life table analyses revealed that fathers of deceased diabetics were significantly more likely to die prematurely than fathers of living diabetics (18% vs. 8% at age 55 years; p = 0.02). A father-diabetic son concordance of mortality appeared to be responsible for this effect. A similar overall trend was observed for maternal mortality, although the difference was not statistically significant. Cause-specific analyses revealed that the increased paternal mortality was primarily the result of cardiovascular disease. Overall mortality rates of parents of deceased diabetics were higher than those of the general population, reaching statistical significance in the age group 35-44 years (p less than 0.05). Mortality among diabetic siblings was also examined. Diabetic siblings of deceased diabetics had a markedly increased risk of dying compared with diabetic siblings of living diabetics (p = 0.001). These findings indicate that premature mortality among both diabetic and nondiabetic relatives of diabetics clusters in families in which there is a deceased insulin-dependent diabetic, and suggest that the marked increase in mortality among persons with insulin-dependent diabetes may be partly under familial control.

Actuarial Analysis↗

The epidemiology of serum sex hormones in postmenopausal women.

Serum sex hormones may be related to the risk of several diseases in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sex hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.

Aged↗

Educational attainment and behavioral and biologic risk factors for coronary heart disease in middle-aged women.

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.

Adult↗

Marked decline of coronary heart disease mortality in 35-44-year-old white men in Allegheny County, Pennsylvania.

Trends in coronary heart disease (CHD) mortality were examined among 35-44-year-old white men during 1970-1986. Death certificates were obtained for 1,216 cases. All were coroner-certified natural deaths and noncoroner-certified deaths due to vascular diseases and diabetes mellitus. Autopsy data, coroner's reports, hospital records, physician's reports, and informants were used to validate diagnoses. The reviewers rejected 73 of 805 CHD certifications, but they validated 54 cases not certified as CHD on the death certificate as CHD. The CHD mortality rate fell from 90.6/100,000/year in 1970-1972 to 40.3/100,000/year in 1985-1986. Approximately two thirds of the decline was related to a decline in sudden deaths including 41.6% due to incident sudden CHD death. The proportion of diabetics among validated CHD deaths rose dramatically from 6.5% in 1970-1972 to 23.0% in 1985-1986. The CHD mortality rate among diabetics apparently did not decline during the 17 years of the study. We conclude that primary prevention has contributed substantially to the CHD decline in the 35-44-year age group. Better diagnoses and treatment, especially of angina pectoris and of patients after a myocardial infarction, may also have been important. Control of CHD in diabetics must take high priority in further prevention strategies.

Adult↗

Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.

The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.

Antihypertensive Agents↗

The epidemiology of pulmonary function and COPD mortality in the multiple risk factor intervention trial.

The potential determinants of the changes in chronic obstructive pulmonary disease (COPD) mortality were evaluated using both the Multiple Risk Factor Intervention Trial (MRFIT) screenees, the longitudinal analysis of the participants, and the differences in special intervention (SI) and usual care (UC) groups. COPD was the underlying cause for only one third of all death certificates listing COPD. Small changes in classification will have a major impact on reported COPD death rates. Cigarette smoking is clearly the primary determinant of COPD mortality. Decreased pulmonary function is an independent risk factor for coronary heart disease (CHD) mortality. Smoking cessation results in a slower rate of decline in pulmonary function over time, especially among heavy smokers. Careful evaluation of smoking cessation, including repeat chemical measures, suggest that the percentage of long-term quitters, especially among heavy smokers has been overestimated. The low percentage of quitters substantially reduced the power to detect an intervention effect. The increased cigarette smoking among recent older cohorts, and failure to substantially reduce smoking, especially among heavy smokers, may be an important factor accounting for the failure to note a decline in COPD mortality among older persons.

Adult↗

Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study.

The natural history of diabetic neuropathy and its risk factors are not well understood, apart from the recognition that prevalence increases with duration and, in many studies, degree of glycemia. The role of potential risk factors was therefore evaluated in a cross-sectional analysis from the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study. We present results from the first 400 subjects seen at baseline examination. Neuropathy was determined by a trained internist with a standardized examination and was defined as the presence of at least two of three criteria: abnormal sensory or motor signs, symptoms consistent with neuropathy, and decreased tendon reflexes. The prevalence of neuropathy in this cohort was 34% (18%, 18-29 yr old, 58% greater than or equal to 30 yr old) with no difference by sex. By focusing on subjects greater than or equal to 18 yr old, all significant univariate variables (e.g., duration, glycosylated hemoglobin [HbA1]) were analyzed in 3 multiple logistic regression models: all subjects greater than or equal to 18 yr old and separating the same subjects into two groups based on age (18-29 and greater than or equal to 30 yr). Duration, HbA1, smoking status, and high-density lipoprotein cholesterol were found to be associated with neuropathy in the models for the greater than or equal to 18-yr-old group and the greater than or equal to 30-yr-old group. In the 18- to 29-yr-old group, duration, HbA1, and hypertension status were found to be significantly associated with neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assessment of AlbuSure and its usefulness in identifying IDDM subjects at increased risk for developing clinical diabetic nephropathy.

This study, which included 154 participants in a 10-yr follow-up study of diabetes complications, was conducted to evaluate AlbuSure (a qualitative test designed to detect urinary albumin concentrations greater than 0.03 g/L) for its ability to discriminate between albumin concentrations above and below the manufacturer's concentration threshold and to identify individuals at increased risk for developing diabetic nephropathy (i.e., those with albumin excretion rate [AER] greater than 0.0288 g/24 h). The reproducibility of AlbuSure results was also evaluated. The results of these evaluations were examined by three different types of urine collections (24 h, overnight, and timed postclinic) and overall. AlbuSure's validity was examined by comparing its results to immunonephelometrically measured concentrations and AER. When compared to albumin concentration, AlbuSure had an overall sensitivity of 81.8%, specificity of 94.8%, and positive predictive value of 90.6%. AlbuSure's sensitivity was lower (71.4%) when compared with AER; however, this was higher than the sensitivity achieved by dipsticks against AER (50.7%). On testing urine samples stored for 3 days at 4 degrees C, AlbuSure results were 100% reproducible after 1 day and had an overall reproducibility of 92% after 3 days. When urine was retested after 3 and 15 mo of storage at -70 degrees C, AlbuSure was greater than or equal to 90% reproducible, with some of the differing results attributable to corresponding changes in albumin concentration. The overnight sample appeared to be the sample of choice for testing with AlbuSure in that it showed excellent reproducibility and the highest sensitivity (compared to both albumin concentration and AER).

Agglutination Tests↗

Obesity, obesity-related behaviors and coronary heart disease risk factors in black and white premenopausal women.

Obesity is more common in black women than in white women in the USA, but there are few studies comparing black and white females on behaviors related to obesity or on the relationship between obesity and cardiovascular risk factors. We studied 490 white and 48 black premenopausal, nondiabetic, nonhypertensive women, aged 42-50 years, who were participating in the Pittsburgh Healthy Women Study. Black women had a higher BMI than white women and had a higher suprailiac:triceps ratio, suggesting a more central distribution of body fat. Weight gain since age 20 was greater in black women than in white women. Blacks and whites did not differ in caloric intake, smoking or alcohol consumption. However, there were marked differences in physical activity, with blacks reporting significantly less activity than whites. Differences in body fat distribution, weight gain since age 20 and activity remained after adjusting for education. Blacks also had higher blood pressure and poorer glucose tolerance than whites. The low activity level of black women should be considered when designing weight loss interventions.

Adipose Tissue↗

Endogenous estrogen levels and calcium intakes in postmenopausal women. Relationships with cortical bone measures.

To examine the interactions between hormone levels and calcium with cortical bone, we have attempted to combine risk factors for the development of peak skeletal mass with factors that may be related to the maintenance of bone integrity after menopause. A total of 174 postmenopausal women participated in our study. There was little relationship found between androgen hormones and radial bone density. Estrone levels were independently related to radial bone density. Examination of the relationship of calcium intake to bone revealed a protective effect solely in women who reported high "lifetime" calcium intakes. Taking calcium and estrone together revealed an additive relationship between the two factors, in that women with high estrone and high calcium levels had significantly greater bone density than women with less calcium and/or estrone. The results suggest that a lifetime of adequate calcium intake coupled with adequate levels of serum estrogens could maximize bone density after menopause.

Age Factors↗

Breast cancer study.

In the report "Spacelab-2 plasma depletion experiments for ionospheric and radio astronomical studies" by M. Mendillo et al. (27 Nov., p. 1260), figure 5A (p. 1263) was misplaced with respect to figure 5B so that the scale of figure 5A was incorrectly represented. A correct figure 5 is printed below.

Breast Neoplasms↗

An epidemiologic approach to the study of retinopathy: the Pittsburgh diabetic morbidity and retinopathy studies.

Diabetic retinopathy was studied in two cohorts of insulin-dependent diabetics (IDDs) from the Children's Hospital of Pittsburgh. The first cohort (n = 696) consisted of IDDs of long duration. Severe retinopathy was self-reported in 70% of this cohort by 30 years duration of diabetes. Associations between severe retinopathy, hypertension and smoking were observed. In order to examine the relationship between metabolic control and early diabetic retinopathy, a second cohort of adolescent IDDs (n = 58) were referred for standardized fluorescein angiography. Sixty-four percent had early retinopathy. None had proliferative changes. Significant differences in individual mean whole blood glycosylated hemoglobin (GHb), averaged over 3 years before angiography, were consistently seen between those with and without early retinopathy. Also, the number of microaneurysms was positively correlated with individual mean GHb. Before the advent of GHb testing, those IDDs who later had retinopathy were more likely to have experienced at least one hospitalization for diabetic ketoacidosis. These observations provide strong support that poor metabolic control preceded the development of diabetic retinopathy. Results are consistent with the hypothesis that improvement of metabolic control early in the course of IDDM may prevent or delay the development of the early changes of diabetic retinopathy.

Adolescent↗

Characteristics of noncontraceptive hormone users.

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.

Adult↗

Serum level changes after administration of a pharmacologic dose of beta-carotene.

Results from a pilot study to assess the feasibility of conducting a full-scale lung-cancer-prevention trial using pharmacologic beta-carotene are reported. Participants in the study were randomized in a double-blind fashion to receive either 15 mg orally of beta-carotene or placebo daily. Findings for the first 300 men to complete 1 y on study are presented. After 10 mo of treatment, serum levels in the placebo group showed essentially no change whereas levels in the treated group increased almost 10-fold after 4 mo of treatment. The relationship between change in serum levels are evaluated in regard to body mass index, alcohol consumption, amount of smoking, lipids, and other variables. The results to date clearly indicate that substantial serum response can be achieved with only 15 mg/d and that with this dosage no skin discoloration or other toxicities are observed.

Alcohol Drinking↗