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The purpose of this study was to determine how well men recall reproductive information. By using a questionnaire, the authors surveyed men who had undergone orchiopexy for undescended testes and a group of matched control men, all of whom had had surgery at the Children's Hospital of Pittsburgh in Pittsburgh, Pennsylvania (n = 77), and their spouses. Subjects were a random subset of a larger (n = 1,212) male fertility study, which has been ongoing since 1992. In 1994, the spouses of men who participated in the study completed a short telephone survey that contained questions previously asked of their partners. Pearson correlations and kappa statistics were calculated to evaluate the accuracy of male recall of reproductive information. For the continuous measures, such as time to conception and frequency of intercourse, the correlations were high to moderate (r = 0.84 (p < 0.001) and r = 0.45 (p < 0.001), respectively). Agreement between the men and their spouses on the majority of bivariate (yes/no) questions, such as those concerning the use of birth control, as measured by the kappa statistic, was moderate to very good (K ranged from 0.14 to 0.69). Statistics were similar for formerly cryptorchid and control men. Male participants' responses to questions about their reproductive histories were accurate as compared with the responses given by their spouses. In this sample from a large cohort study, men appeared to recall reproductive information with acceptable accuracy.

Capture-recapture methods were employed to determine the most accurate and efficient approaches to monitor adolescent injuries. Multiple sources were used to ascertain cases of adolescent injuries that occurred between September 1 and December 31, 1991, in a single school district in metropolitan Pittsburgh, Pennsylvania. Eliminating the duplicate cases between the sources revealed 144 verified injuries; 127 (88.2%) were identified by student monthly recalls, 33 (22.9%) by daily attendance records, 58 (40.3%) by medical excuses, and 72 (50.0%) by a 4-month student recall. Capture-recapture analyses were undertaken to assess potential dependencies between the sources, to estimate the degree of underascertainment in the population, and to evaluate the efficiency of the individual sources and the combinations between them. It was estimated that 91% of the cases in the population were ascertained when all four methods of case finding were utilized. Furthermore, the analysis indicated that accurate injury estimates could be achieved using combinations of only two or three of the sources. An analysis of the efficiency of the methods of ascertainment revealed a trade-off between effort (the number of hours needed to identify cases) and the precision (coefficient of variation) of the injury estimates. Capture-recapture analysis not only provided an approach to evaluate and adjust for undercount but also offered a formal means to evaluate the most efficient combination of the sources to maximize completeness while minimizing effort. The use of these techniques has the potential to evaluate and improve injury surveillance as well as other disease monitoring systems.

The reproducibility and validity of a past year physical activity questionnaire was determined in a sample of 100 adolescents aged 15-18 years, randomly selected from a population-based cohort. Subjects completed four 7-day recalls of activity approximately 3 months apart. The average of the four 7-day recalls of activity was utilized as the "gold standard" against which the past year questionnaire was compared to evaluate validity. The questionnaire was also validated against objective measures, such as physical fitness and body mass index. Interscholastic team rosters were utilized to directly validate the reporting of specific activities. One-month and one-year test-retest reproducibility of the questionnaire were determined. For different measures of activity, the Spearman correlations between the questionnaire and the average of the 7-day recalls ranged from 0.55 to 0.67 in males and 0.73 to 0.83 in females, all significant at p < 0.01. In general, although there was no association between the past year activity questionnaire results and objective measures, there was a significant, albeit weak association between the physical activity questionnaire and time to complete a 1-mile (1.61-km) run (r = -0.47) in females. Subjects reported participating in specific interscholastic sports with an accuracy of 100%, 86%, and 95% for the fall, winter, and spring sports, respectively. Test-retest reproducibility was higher over one month (r = 0.79) than over one year (r = 0.66). These data provide evidence that the questionnaire yields a reasonable estimate of past year or "habitual" physical activity in adolescents.

The beneficial effect of physical activity in the general population is well known, but, to the authors' knowledge, has not been reported for persons with insulin-dependent diabetes mellitus. In a cohort of 548 diabetes patients followed as part of the Pittsburgh Insulin-dependent Diabetes Mellitus Morbidity and Mortality Study, physical activity was ascertained by survey in 1981, and mortality was ascertained through January 1, 1988. Cases were also compared with non-diabetic sibling controls. Activity level among cases varied inversely with the occurrence of diabetic complications. Overall activity level was inversely related to mortality risk. Sedentary males (< 1,000 kcal/week) were three times more likely to die than active males (> 2,000 kcal/week). A similar, but statistically nonsignificant, relation was seen in females. Cox proportional hazards analysis controlling for potential confounders (age, body mass index, insulin dose, reported diabetes complications, cigarette smoking, and current alcohol drinking) similarly revealed that activity level was inversely associated with mortality risk. Comparison of cases with non-diabetic sibling controls identified similar activity levels for the two groups. The results suggest that activity is not detrimental with regard to mortality, and may in fact provide a beneficial effect in terms of longevity in diabetes patients.

The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules.

The authors compared the epidemiology of childhood insulin-dependent diabetes mellitus in Estonia during 1980-1989 between native Estonians and an immigrant group that consisted mainly of Russians. The average annual incidence of diabetes mellitus was significantly higher in Estonians (11.8 per 100,000 children aged less than 15 years; 95% confidence interval (CI) 10.4-13.3) than in non-Estonians (7.6 per 100,000 children aged less than 15; 95% CI 6.2-9.4). This difference appeared in both sexes. The highest incidence in both Estonians and non-Estonians was recorded in 1982, when the incidence in the immigrant population was twice as high as the baseline level. These data indicate that immigrant populations need not acquire the same risk of insulin-dependent diabetes as the native population.

Proportional hazards models measuring the effect of age at onset of insulin-dependent diabetes mellitus on mortality risk are presented. The study population consisted of 924 insulin-dependent diabetic patients who were seen within 1 year of diagnosis at Children's Hospital of Pittsburgh between 1950 and 1981 and were more than 20 years old at follow-up. Age at diabetes onset was categorized as prepubertal or pubertal, defined by age. Individuals with pubertal onset of diabetes had a significantly higher risk of mortality compared with those with prepubertal onset by diabetes duration but not by attained age. It is proposed that age at onset is an independent determinant of mortality in diabetic individuals and may represent either heterogeneity within insulin-dependent diabetes mellitus with respect to long-term prognosis or an interactive effect of diabetes duration and puberty on prognosis.

High density lipoprotein cholesterol (HDL-chol) is negatively associated with coronary heart disease. Environmental heart disease risk factors may partially be related to coronary heart disease through alterations in HDL-chol concentrations. Little is known about the underlying mechanisms by which environmental factors are related to HDL-chol. The authors investigated a possible mechanism: changes in liver function as a mediating link between risk factors and HDL-chol concentrations in marathon runners, alcoholics, and participants in the Multiple Risk Factor Intervention Trial. Liver function, as measured by liver enzymes, was related to both coronary heart disease risk factors and alcohol consumption, suggesting that the increased levels of HDL-chol associated with alcohol were primarily the result of changes in liver function. The relationship of obesity to HDL-chol could not be explained by the alterations in liver function.

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.

Multivariate models for the risk of insulin-dependent diabetes mellitus for siblings of patients with insulin-dependent diabetes were developed using logistic regression analysis. The individuals studied in this report are full siblings of the insulin-dependent diabetic patients diagnosed at Children's Hospital of Pittsburgh between 1964 and 1982. For all siblings considered together, the sharing of two (but not one) HLA haplotypes, the presence of insulin-dependent diabetes in a parent, and being relatively young at the time the proband in the family was diagnosed were significantly associated with increased risk. On the other hand, B7 + siblings had a significantly decreased risk compared to B7--siblings, indicating the presence of an HLA-linked protective gene for the development of the disease. There was a significant interaction between sharing two HLA haplotypes and maternal age at the time of birth; for non-HLA-identical siblings, risk increased with increased maternal age, but maternal age had little or no effect on the risk for HLA-identical siblings. When non-HLA-identical siblings (0 or 1 HLA haplotypes shared) were analyzed separately, only the presence of insulin-dependent diabetes in one of the parents and increased maternal age at the time of birth of the sibling were found to be significantly associated with increased risk. Both of the totally non-HLA-identical diabetic siblings (neither HLA haplotype shared) in this data set had a parent with insulin-dependent diabetes, indicating that at least one HLA haplotype must be inherited in common with an affected family member for diabetes to develop. For HLA-identical siblings, the significant variables were the age of the sibling when the proband was diagnosed, the possession of B7, and maternal age at the time of birth of the sibling, and all three were negatively associated with risk.

Several diseases, e.g., coronary heart disease, cancer, etc., have been related to sex hormones. Thus, research on the epidemiology of sex hormones may be productive. The epidemiologic study of testosterone has been limited due to the circadian and circannual variations and the wide interindividual variability. The authors evaluated the reliability and repeatability of a single blood draw to measure individual plasma testosterone levels in three pilot studies. The results indicated that the measurements of the hormone level are highly repeatable and a single morning specimen appeared to be sufficient for characterization of individual testosterone levels. Research then focussed on 243 men in the Multiple Risk Factor Intervention Trial to investigate the determinants of plasma testosterone level. The results indicated that age and obesity were significantly correlated with plasma testosterone level. (The multiple R of these two variables in the multiple regression analysis for plasma total testosterone was 0.32.) Smoking was positively related to testosterone through a relationship with age. Daily physical activity, history of alcohol intake, and behavior factors of A and B behavior types were not found to be related to testosterone concentrations.

The relationship of endogenous concentrations of estrogen, in particular estrone, to the dominant radial bone density and bone area was examined in 78 normal postmenopausal women (mean age 57 years). The women were a subset of a population participating in a clinical trial designed to determine the effects of walking on bone loss. The data reported here were collected at baseline prior to randomization. Radial cortical bone density and bone area were measured at 30 per cent of the distance between the wrist and the elbow in the dominant arm. Estrone levels obtained by extraction and column chromatography were measured by radioimmunoassay. Estrone concentrations were cross-sectionally related to both radial bone density (r = 0.39, p less than 0.001) and bone area (r = 0.39, p less than 0.001). This relationship was independent of age, number of years since onset of menopause, and degree of obesity. In multiple regression analysis, estrone levels accounted for 15 per cent of the variance in bone density and bone area in this population. These results suggest that measurement of estrone in normal postmenopausal women may assist in the identification of women who are at high risk for osteoporosis and, thus, possible candidates for estrogen replacement therapy.

The incidence of insulin dependent diabetes mellitus, as determined from the Pittsburgh Insulin Dependent Diabetes Mellitus Registry, was examined in relationship to social class. The registry consists of all Allegheny County, Pennsylvania, cases of insulin dependent diabetes diagnosed under age 20 years in 1965-1976. Analyses of the registry data revealed little relationship between incidence, age at onset and social class. The lack of a strong relationship to social class indicates that the epidemiology of insulin dependent diabetes is not similar to those of polio or Hodgkin's disease, in which social class is strongly related to incidence and age at onset.

The aim of the present research was to determine the association between historical physical activity and baseline bone measurements in a group of 223 postmenopausal women participating in a clinical trial in Pittsburgh, Pennsylvania, from 1981 to 1986 by evaluating the effect of moderate physical activity on bone loss. Historical physical activity was assessed by a survey which divided the life span into four time periods (14-21, 22-34, 35-50, and 50+ years) and inquired about participation in leisure time physical activities for each period. From the responses, kilocalories of energy expenditure were calculated. Cortical bone density and area were measured in the radius with a computerized tomography scanner. The historical physical activity survey was administered a second time two to three months after the initial test to a 10% random sample of the women in order to determine the test-retest reliability of the instrument. Since the measurements of historical physical activity proved to be reliable, estimates of kilocalories determined for the entire population of women were correlated with bone area and density. A significant relation was found to exist between historical physical activity and dimensions of adult bone, particularly bone area. This association remained significant after adjustment for potential confounding variables and seemed to be strongest in the earlier age periods. To the authors' knowledge, this is the first report of a significant association between historical physical activity and bone.

Telecommunication will revolutionize how international medical research is completed. It is faster, more accurate, less expensive, and potentially more accessible than all other existing modes of communication. It is time for medical scientists to come into the age of electronic communication.

A major problem in the epidemiologic investigation of early fetal losses has been incomplete or biased ascertainment. In order to assess early fetal losses more accurately, one must first develop a simple method to identify early pregnancy. This study, conducted at the University of Pittsburgh from October 1985 through October 1986, has developed such a method through the use of monoclonal antibody urine pregnancy testing kits. A total of 88 volunteers collected urine samples beginning on the seventh postovulatory day and continued until either menses occurred or a serum radioimmunoassay pregnancy test was performed on day 16. If pregnancy was diagnosed, all of the participants' urine specimens from that menstrual cycle were analyzed by five monoclonal antibody tests. A total of 34 pregnancies were diagnosed, six (18%) of which resulted in early fetal losses. Pregnancy was first detectable between eight and 18 days postovulation. The mean time to the first positive test was 14 days for all five kits. The results indicate that it is possible to diagnose early pregnancy with urine testing and that this method is likely to prove acceptable for use in large-scale prospective studies.

The development of a device is reported called the Large-scale integrated Motor Activity Monitor to examine physical activity during individuals' normal daily lives. The unit which is slightly larger than a wrist watch records body movement when worn at various body locations. Two population studies were conducted to evaluate the units. Experiment 1 examined 20 male graduate students for a two-day period. The data indicated that the units were sensitive to individual differences in physical activity and did not interfere with normal activities. Experiment 2 compared 10 Physical Education majors with 10 non-Physical Education majors by having individuals log activities and record movement counts for a two-day period. The movement data revealed that the monitors significantly discriminated between the two populations. The energy expenditure derived from the specific loggings was highly related (r = +.69) to the trunk movements, indicating that the movement counts are an accurate estimate of physical activity. The high relationship to energy analysis, the sensitivity of the units and the ease of implementation indicate that the units may be useful in relating normal activity to acute heart disease and to risk factors such as obesity and lipoproteins.

Alcohol consumption is one of the major determinants of serum high density lipoprotein (HDL) cholesterol. Very few studies have examined the correlation between alcohol consumption and high density lipoprotein subclasses. It has been suggested that HDL2 is probably the fraction that is associated with reduced coronary heart disease. The current research investigated the relationship between alcohol consumption and HDL2 and HDL3 cholesterol among 234 alcoholics who were admitted for abstinence. The results indicated that the elevated serum HDL cholesterol concentrations among alcoholics were a combination of an increase in both HDL2 and HDL3 cholesterol. HDL cholesterol and HDL2 cholesterol increased with more alcohol consumption until about 450 ml of ethanol consumption per day when serum HDL cholesterol and HDL2 cholesterol decreased. HDL3 cholesterol showed a similar trend but was not statistically significant. In addition, the serum concentrations of HDL cholesterol and subclasses were positively correlated with liver enzymes. Those with alcohol-related liver disease had significantly higher HDL and HDL2 cholesterol levels than those without. Both HDL cholesterol and subclasses decreased concomitantly with the decline in liver enzymes within one month of abstinence. The possible biologic mechanisms linking alcohol drinking with HDL cholesterol through liver induction and sex hormone changes are discussed.

Racial differences in the incidence and natural history of insulin-dependent diabetes mellitus were evaluated in Allegheny County, Pennsylvania. The yearly incidence rate for whites was approximately 1.5 times that for blacks. The cumulative risk of developing insulin-dependent diabetes prior to age 20 was greater for whites (3.1/1,000, males; 2.8/1,000, females) than for blacks (1.7/1,000, males; 2.0/1,000, females). There was a slight excess risk for white males versus white females (relative risk = 1.09, p = 0.04), while no sex differential in risk was noted for blacks. The temporal trends and seasonal patterns were similar. Blacks more frequently possessed human lymphocyte antigen (HLA)-DR3/X and whites DR4/X; however, the risks associated with these antigens were similar by race. At onset, blacks had evidence of greater immunologic disturbance and less frequently reported infection than whites, although blacks more often had evidence of previous coxsackie viral infections. Evaluation of mortality patterns by race revealed that blacks had a higher mortality rate than whites. By 20 years duration of diabetes, blacks had a 2.4-fold increase in the risk of mortality compared with whites.

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.