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Biomedical subjects

W R Harlan

Publications and source records attributed to W R Harlan.

At least 19 recordsLinked to original sources

Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop.

Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.

Cardiomyopathy, Dilated

Restenosis after coronary angioplasty: an overview.

Despite substantial basic and clinical efforts to address the problem of restenosis after percutaneous coronary intervention, effective preventive therapies have not yet been developed. Nevertheless, the accumulated information has provided much insight into the process of restenosis in addition to allowing standards to be developed for adequate clinical trials. The pathophysiology of restenosis increasingly appears to be distinct from that of primary atherosclerosis. Restenosis involves elastic recoil, incorporation of thrombus into the lesion and fibrocellular proliferation in varying degrees in different patients. Lack of an animal model that satisfactorily mimics restenosis is a major impediment to further understanding of the process. Clinical studies are hampered by difficulties in finding a single unifying definition of restenosis and by variable methods of reporting follow-up. Reporting of clinical outcomes of all patients in angiographic substudies would allow a more satisfactory interpretation of the results of clinical trials. Current noninvasive test results are not accurate enough to substitute for angiographic and clinical outcome data in intervention trials. In the majority of observational studies, only diabetes and unstable angina have emerged as consistently associated with restenosis; whereas most of the standard risk factors for atherosclerosis have a less consistent relation. Disappointingly, the new atherectomy and laser technologies have not affected restenosis rates. The one possible exception is coronary stenting, as a result of the larger luminal diameter achieved by the placement of the stent. In conclusion, although substantial continued effort is necessary to explore the basic aspects of cellular proliferation and mechanical alteration of atherosclerotic vessels, attention to the principles of clinical trials and observation are required to detect the impact of risk factors and interventions on the multifactorial problem of restenosis. Adequate sample sizes, collection of clinical and angiographic outcomes and factorial study designs hold promise for unraveling this important limitation of percutaneous intervention.

Angioplasty, Balloon, Coronary

Racial and ethnic diversity in obesity and other risk factors for cardiovascular disease: implications for studies and treatment.

This review summarizes current knowledge about differences in cardiovascular disease and its risk factors among minorities in the US population. The limited information available about differences in the association of obesity with cardiovascular disease risk factors in minorities is described. Our thesis is that environment and its evolutionary influence are important in risk-factor changes, although genetic characteristics moderate the impact of these factors. This review attempts to illustrate how studies of minority groups can help us to understand the importance and interaction of factors leading to increased cardiovascular disease risk. We suggest guidelines for the design of studies that will help us to better explain differences in cardiovascular disease and its risk factors among minorities and to improve therapy for this common disorder. Because diabetes is a major topic of the First International Conference on Race, Ethnicity, and Health, data on this disease are used in many of the examples presented.

Cardiovascular Diseases

The economic impact of injuries: a major source of medical costs.

Data from the 1980 National Medical Care Utilization and Expenditure Survey were analyzed to place the costs for injuries in the context of all medical costs and to describe the distribution by demographic and diagnostic groups. For the non-institutionalized population, injuries, which include intentional and unintentional, were the second leading cause of direct medical costs, accounting for $16,745 million in medical care expenditures and a major contributor to work loss and disability in the US. For the working-age population (17-64 years) injuries were the leading cost category ($11,341 million) and the third most costly category for persons 65 years of age and over ($3,479 million). The preponderance of costs were attributable to hospital-based care. Direct medical costs were disproportionately greater for males, White and other persons, and for those with household incomes less than $5,000. Injury morbidity also accounts for major indirect costs. Fractures accounted for the highest direct medical costs, greatest per capita charges (based on those with charges), and largest number of restricted activity days. These national estimates document the economic importance of injuries and direct public attention to policy imperatives related to research and prevention.

Absenteeism

Economic considerations that influence health policy and research.

Cardiovascular conditions account for more medical costs than any other diagnostic category in the United States. Increasingly, economic constraints will shape policy related to health care and research. Hypertension is the most common cardiovascular condition, and despite low unit health care costs, the aggregate costs are considerable. However, the unit and aggregate costs of the complications of hypertension are fourfold greater and, in this economic perspective, aggressive approaches are warranted to prevent complications. Treatment and research strategies should be identified that could have considerable potential economic impact. Several strategies are suggested as a prospective guide to policy development. Economic considerations will be important and should be incorporated in the planning of hypertension care and research.

Antihypertensive Agents

Secular trends in body mass index and skinfold thickness with socioeconomic factors in young adult women.

Secular trends in the relationship of body mass index (BMI) and skinfold thickness to educational and income levels were examined for white and black women aged 18-34 y over the period 1960-80 with data from three successive national surveys: NHES Cycle I, NHANES I, and NHANES II. Statistical models were fitted to assess the variability in mean BMI over time within levels of education or income. Mean BMI and skinfold thickness were negatively associated with both education and income. Over the 20-y period mean BMI increased for both white and black women at all levels of income and education. Because the increase in mean BMI was greater at lower educational levels, the differentiation of BMI by educational level increased over time, yielding a stronger negative association. In contrast differentiation of BMI by income category decreased over time. Black-white differences in mean BMI at comparable educational and income levels persisted over this period.

Adult

Secular trends in body mass index and skinfold thickness with socioeconomic factors in young adult men.

Secular trends in the relationship of body mass index (BMI) and skinfold thickness to educational and income levels were examined for white and black men aged 18-34 y over the period 1960-80 with data from three successive national surveys: NHES Cycle I, NHANES I, and NHANES II. Statistical models were fitted to assess the variability in mean BMI over time within levels of education or income. There were few secular changes in mean BMI. In both white and black men a secular change from a slight positive association between mean BMI and education to a negative association was characterized chiefly by an increase in mean BMI at the lowest educational level. A slight positive association between income level and mean BMI persisted almost unchanged over this period. Mean BMI was similar for black and white men. These findings are compared and contrasted with those from a similar study for young women.

Adult

Secular trends in body mass in the United States, 1960-1980.

Data from four National Health Examination Surveys conducted of the US population from 1960 to 1980 were analyzed to determine secular trends in obesity for white and for black adolescents and young adults of both sexes. Body mass index was categorized into four levels using cut points determined by the 50th, 75th, and 85th percentiles at the first survey in 1960-1962. The weighted proportions of persons in these body mass categories were determined, and statistical models were developed to describe secular trend and race effects. No consistent secular trends were found for white or black youths aged 12-17 years. No significant secular trends in obesity were found for white or black young males aged 18-34 years. Both for white and for black adult females, there were significant secular increases in the proportion of adult females in each of the successively heavier categories of body mass index. These increases were identical for white and for black adult females on the log-odds scale, but black adult females were already significantly heavier at the first survey. This race effect persisted throughout the entire time interval.

Adolescent

Activity-induced adaptations in skeletal muscles of iron-deficient rabbits.

The purpose of this study was to determine whether severe iron deficiency alters the adaptive response of skeletal muscle fibers to a sustained increase in tonic contractile activity. Seven weanling rabbits consumed a low iron diet and underwent phlebotomy twice weekly for 6 mo, resulting in severe anemia (mean Hb 5.5 g/dl). Compared with control animals, tibialis anterior skeletal muscles of iron-deficient animals exhibited reduced concentrations of cytochrome c (4.4 +/- 0.7 vs. 8.6 +/- 0.7 nmol/g tissue; P less than 0.01), and reduced activities of citrate synthase (83 +/- 10 vs. 133 +/- 13 mU/mg protein; P less than 0.01) and cytochrome-c oxidase (2.2 +/- 0.2 vs. 3.6 +/- 0.5 U/mg protein; P less than 0.05). In these muscles mitochondria were swollen and displayed deformed cristae. Less severe biochemical abnormalities were observed in cardiac and soleus skeletal muscles. Ten days of continuous electrical stimulation of the motor nerve supplying anterior compartment muscles of iron-deficient rabbits increased expression of mitochondrial proteins: cytochrome c was increased to 154% of control levels (P less than 0.05), and cytochrome-c oxidase and citrate synthase activities were increased to 199 and 272% of control levels, respectively (P less than 0.005). In addition, electrical pacing increased the fractional volume of mitochondria observed by electron microscopy and reduced the activity of aldolase A by 28% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

The relationship of blood lead levels to blood pressure in the U.S. population.

Numerous observations have indicated a relationship between moderate or heavy lead exposure and high blood pressure. To determine whether low-level lead exposure is related to blood pressure in the U.S. population, we analyzed data from the National Health and Nutrition Examination Survey II for persons 12 to 74 years of age. Significant correlations were found between blood lead and blood pressure for each race-gender group, and blood lead levels were significantly higher in groups with high diastolic blood pressure (greater than 90 mm Hg). Multiple stepwise regression models were developed to predict blood pressure. After adjusting for age, race, and body mass index, blood lead levels were significantly related to systolic and diastolic pressures in males but not in females. These findings and those from other studies confirm the relationship of blood lead and blood pressure at relatively low levels commonly observed in the general population. The strength and importance of this relationship require further study through epidemiologic and metabolic investigations.

Adolescent

Factors associated with glucose tolerance in adults in the United States.

Glucose tolerance data from the second National Health and Nutrition Examination Survey were analyzed to determine factors predicting fasting plasma glucose levels and glucose tolerance in a representative US population. Central adiposity (subscapular skinfolds), age, and family history of diabetes were the major predictors of fasting levels and of glucose tolerance. For women, having a diabetic mother was significantly related to fasting glucose and glucose tolerance, but for men the proportion of siblings with diabetes was positively related. Multiple regression analyses, after adjustment for age and subscapular skinfolds, identified white cell count, systolic blood pressure, natural logarithm total iron binding capacity, and family history variables as being significant predictors of glucose tolerance in both sexes. In addition, several other variables were predictive for men or women, but not for both. These data confirm the importance of the major predictors of glucose tolerance and suggest provocative new associations in the general population.

Adult

An epidemiological perspective on dietary electrolytes and hypertension.

This review of epidemiological studies has several general implications. First, the most relevant population data for extrapolation in providing public health or medical advice should come from intra-population studies, either observational or interventional. Second, the observational studies require follow-up with long-term intervention trials in representative segments of the population before broad pronouncements are made. Third, not all people respond uniformly to changes in the intake of a single electrolyte, at the levels that can be safely achieved in our society. Finally, there are clear indications of useful directions in which to alter dietary electrolytes, either singly or multiply, but the most effective, safe and achievable combinations of dietary change remain to be defined and tested over prolonged periods in naturalistic settings.

Calcium, Dietary

The dissemination of new medical information.

Dissemination of new medical information to the practicing physician is a complex and often faulty process. To examine the magnitude of this problem, we surveyed primary care physicians to determine their knowledge of the results of the cooperative trial of photocoagulation in diabetic retinopathy. Despite the acknowledge relevance to their practice, only 28% (38/137) of family physicians and 46% (42/91) of internists were aware of the study results (P less than .001). Respondents were asked to manage two patient problems involving diabetic retinopathy. Only 33% (75/229) handled both correctly, although the retinopathy photocoagulation study had been published 18 months earlier. These findings indicate that results from clinical trials may not be disseminated to practicing physicians and, therefore, not incorporated into practice. Greater attention should be directed toward making findings from clinical trials available to practitioners.

Diabetic Retinopathy

A longitudinal study of body fatness in childhood and adolescence.

Data from the United States Health Examination Surveys were analyzed to determine changes in body fatness between childhood and adolescence. A national probability sample (2,177 children) was examined in both Cycle II (6 to 11 years) and Cycle III (12 to 17 years) of these surveys and comprised the study cohort. The interval between examinations was three or four years. Adiposity was measured as skinfold thickness and correlations between childhood and adolescent adiposity were explored. High rank-order correlations were found between the two examinations for each race-sex group (P less than 0.001). The relationship between childhood and adolescent fatness was independent of stature, skeletal and sexual maturation, and economic status. Childhood fatness was the most predictive factor for adolescent fatness. This strong relationship indicates that the potentially obese adolescent can be identified during childhood.

Adolescent

Secondary sex characteristics of boys 12 to 17 years of age: the U.S. Health Examination Survey.

Data from the United States Health Examination Survey, Cycle III, were used to describe secondary sexual characteristics and their relationship to skeletal age in a representative sample of adolescent males aged 12 to 17 years. This survey utilized a national probability sample of youths selected to represent the U.S. population with respect to age, race, sex, geographic region, and socioeconomic status. Good concordance was found between Tanner stages for pubic hair and for genitalia. Sexual characteristics developed similarly for white and black boys, and socioeconomic status did not influence this development. Skeletal age and serum urate levels were closely related to development of pubic hair and genitalia. These data permit the physician to compare the development of individual patients with a representative sample of contemporaneous U.S. boys.

Adolescent

Antecedent renal disease and the outcome of pregnancy.

We assessed the effect of "healed" childhood renal disease on subsequent pregnancies by following-up a cohort of 224 children initially hospitalized with kidney disease. The pregnancy experience in this cohort was compared to two "control" cohorts comprising 81 female siblings and 191 age-matched female patients hospitalized contemporaneously for respiratory infection. The incidence of spontaneous abortion, stillbirth, and pregnancy-associated hypertension was not different among the cohorts; however, the incidence of infants with low birth weights was significantly greater in the renal and respiratory disease groups. Childhood kidney disease followed by impaired renal function (serum creatinine greater than 1.5 mg/dL) was associated with greater maternal and fetal morbidity. Kidney disease in childhood followed by apparent healing and no functional renal impairment does not have an adverse effect on maternal welfare, although the incidence of infants with low birth weight is apparently increased.

Abortion, Spontaneous

Physiologic determinants of serum urate levels in adolescence.

During adolescence, serum urate increases and adult levels are achieved. Physiologic factors related to serum urate were investigated in a nationally representative population of 6,768 youths aged 12 to 17 years (the US Health Examination Survey). Serum urate concentration increases markedly from ages 12 to 14 years in males, and levels were related to sexual and skeletal maturation. Although similar relationships were observed in females, the association is less striking, probably because of earlier pubescence, which was not captured in this study, and a pronounced androgenic response. In the later stages of adolescence (ages 15 to 17 years for males and 13 to 17 years for females), body composition (body mass index and skinfold thickness), blood pressure, and hematocrit have stronger relationships than sexual and somatic maturation. These latter relationships are similar to those in adults. This survey affords a portrayal of physiologic interrelationships with serum uric acid during adolescence.

Adolescent