Tissue lipoprotein lipase in normal individuals and in individuals with exogenous hypertriglyceridemia and the relationship of this enzyme to assimilation of fat.

Lipoprotein lipase activity (LLA) was measured in the adipose tissue of six healthy subjects and five members of a family in whom the trait for familial exogenous hypertriglyceridemia was segregating. The lipase activity measured was characteristic of lipoprotein lipase: increased by feeding, dependent on the presence of serum, and inhibited by sodium chloride and protamine sulfate. When compared with lipase activity in healthy individuals, LLA was grossly deficient in two siblings with postabsorptive chylomicronemia and was intermediate in both parents and one sibling, who had normal postabsorptive triglycerides. These findings are compatible with autosomal recessive inheritance. The hormone-sensitive lipolytic enzyme responsible for mobilization of free fatty acids from adipose storage was normal in the hyperlipemic subjects. After a 104-g fat meal, the serum triglyceride increased more in subjects heterozygotic for LLA deficiency than in the healthy subjects, and there was a relatively greater increase in chylomicrons and very low density lipoproteins in the affected individuals. These observations demonstrate the physiologic importance of lipoprotein lipase in removal of these lipoprotein groups and further clarify the differences between endogenous and exogenous hypertriglyceridemia.

Surface tension, metabolic activity, and lipid composition of alveolar cells in washings from normal dog lungs and after pulmonary artery ligation. Importance of a highly surface-active acellular layer.

Lung-washings from mammalian species are a rich source of surfactant and of cells, predominantly alveolar macrophages, that could be important in the metabolism of the surfactant. We obtained washings from normal dogs, and from dogs that had had one pulmonary artery (PA) ligated 1 or 2 days earlier. Centrifugation of wash (400 x g for 20 min) separated a sediment, made up of cells at the bottom and a white layer, largely acellular, from the supernatant. The volume of sediment averaged 2.1 +/- 1.4 ml,. 75% of which was white layer. The cells resembled the large alveolar (type II) cells found in the lung; however they differed by at least one major histochemical reaction. The white layer had greater surface activity than the cells or the supernate, and was richest in phospholipids and lecithin. The cells lost their surface activity when rinsed and resuspended. These observations suggest that surfactant is normally present, mainly in an acellular fraction and possibly at the surface of the alveolar cells. The alveolar macrophages may either store surfactant, rather than synthesize it, or simply acquire a coat of surfactant during sedimentation. After PA ligation, the earliest abnormality was a decrease in the white layer; the cells were fewer, smaller, and weaker in metabolic activity.

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.

Evaluation of physician assistants in rural primary care.

The advent of physician assistants raises questions regarding their appropriate utilization and monitoring. To determine practice patterns of physician assistants in settings independent of training programs, we studied 14 primary care practices in the rural southeast. Detailed observations, including appropriateness of medical care, were made on 788 outpatient-provider encounters. Physician assistants handled minor medical problems well and 61% of the patients observed in these practices fitted this category. Three practice patterns were observed: all patients were seen by the assistant initially, followed by the physician; patients managed concurrently by physician and assistant were not preselected; and patients with specific problems were assigned to the assistant. Properly managed, each of these patterns yielded competent care. Using these observations, proposed models of management and audit are presented for each practice pattern.

Echinocytes and acquired deficiency of plasma lipoproteins in burned patients.

Spiculated red blood cells (RBCs) (echinocytes) and decreased levels of plasma lipoproteins developed concomitantly in severely burned (more than 35% body surface burned) patients. The RBCs were characterized as flat cells with spicules evenly distributed over the surface, and the erythrocyte lipid content was slightly increased. No evidence of excessive hemolysis was found, although modest shortening of RBC life-span could not be excluded. Development of echinocytes presaged a poor prognosis similar to that observed with acanthocytosis in cirrhosis. Striking decreases in plasma alpha-lipoprotein, cholesterol, and phospholipid values were observed and could be explained in part by loss of alpha- and pre-beta-lipoproteins through damaged microvasculature as these were recovered from blister fluid. Decreased plasma lipoproteins and echinocyte development appeared to be temporally related; the degree of echinocytosis correlated with decreases in plasma lipid values and plasma protein values, but no causal relationship can be inferred because of the multiplicity of changes in severely burned patients.

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.

Blood pressure in childhood. The National Health Examination Survey.

Data were analyzed from the U.S. Health Examination Survey (Cycle II) to determine relationships between blood pressure and other characteristics. This survey examined a national probability sample of children aged 6-11 years. Significant relationships were found for blood pressure and the following variables: chronological and skeletal age, skinfold thickness (adiposity) and other anthropometric measurements, pulse rate, and systolic murmurs. These relationships may be interpreted as indicating important relationships between blood pressure and growth, adiposity, and hemodynamic manifestations of cardiac output. Data from this representative population portray blood pressure relationships in childhood.

Blood pressure in adolescence. The United States Health Examination survey.

A nationally representative sample of adolescents 12-17 years of age were examined in the U.S. Health Examination Survey and relationships between blood pressure and other variables were explored. During adolescence, blood pressure increases more rapidly in males than in females and only small racial differences are present. Weight has the strongest relationship to both systolic and diastolic pressure. Physiological maturation assessed by skeletal age and adiposity (skinfold thickness) are components of weight and each is also related to blood pressure. Although systolic murmurs are related to blood pressure at the time of examination, the murmurs are transitory and not predictive of future pressures. All factors were equally influential in each race-sex group. No significant relationships were found between geographic or demographic variables and blood pressure. These observations indicate the important relationships of physiological maturation and adiposity to adolescent blood pressure.

High blood pressure in older Americans. The First National Health and Nutrition Examination Survey.

Data from a representative sample of the U.S. adult population obtained during 1971-1975 were analyzed to provide a profile of blood pressure (BP) levels and related nutritional and sociodemographic factors. Older adults (aged 55-74 years) had a twofold greater prevalence of high BP than younger adults (25-54 years), and older black persons had the highest rates. Isolated systolic elevation was uncommon under 54 years of age, but occurred in 5% to 10% of adults over 55 years and was less common than systolic-diastolic elevation. In older adults, body mass (weight/height2) had the strongest relationship to BP of all the nutritional variables. Alcohol consumption and dietary calcium and phosphorus were associated with high BP, but dietary sodium and salt use were not. The serum calcium/phosphorus ratio and serum urate were significantly higher in older adults with high BP. In general, the variables associated with elevated BP in older adults were similar to those in younger adults, although the strengths of the associations differed. Associations of factors useful for nonpharmacologic prevention and management of high BP in older persons were suggested from this survey.

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.

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.

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.

Impact of an education program on perinatal care practices.

Education of health professionals has an important role in improving health care. A media-based, self-instructional, perinatal education program was developed and field tested in rural and urban regions of Michigan. Cognitive tests, chart audits, and consultation/referral times were used to measure the impact on education and patient care. The program effectively increased knowledge and improved patient care practices by physicians and nurses. This study presents evidence that a targeted educational program in a media-based format can significantly improve perinatal care.

Importance of baseline functional and socioeconomic factors for participation in cardiac rehabilitation.

Enrollment in cardiac rehabilitation has been reported to improve exercise capacity, psychological well-being, and survival. However, participation rates are low and the reasons for nonparticipation have not been adequately defined. The purpose of this study was to evaluate the major correlates of nonparticipation and to examine the level of participation of patients who stand to benefit most on the basis of preenrollment functional status and health behaviors. Three hundred ninety-three patients undergoing coronary artery bypass surgery (1) had baseline functional status and quality-of-life data collected, and (2) were recruited for participation in the Duke Center for Living comprehensive 3-week post-coronary bypass surgery rehabilitation program. Baseline demographic, clinical, catheterization, functional status, psychological status, and health behavior descriptors were analyzed to identify univariate and multivariable correlates of a patient's decision to participate in the program. At baseline, most clinical factors were similar in participants (n = 52) and nonparticipants (n = 341), but the nonparticipants were more often women (26% vs 12%, p = 0.02). Participants were also more likely to be employed (63% vs 45%, p = 0.02) and had a higher education and income distribution than nonparticipants (both p = 0.001). On 2 separate scales, nonparticipants had significantly more baseline functional impairment than participants (both p = 0.001). In multivariable analysis, the independent correlates of higher participation rates were: higher education (college graduates 71% more likely to participate than high school graduates) and better baseline Duke Activity Status Index (patients with mild functional impairment were at least 42% more likely to participate than patients with moderate impairment).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Serum cholesterol in patients undergoing cardiac catheterization for suspected coronary artery disease: diagnostic and prognostic implications.

The Duke Data Bank for Cardiovascular Diseases is an observational data bank capturing baseline, treatment, and follow-up information on patients referred for evaluation of suspected coronary artery disease. From 6829 patients referred between 1969 and 1990 for diagnostic angiography, baseline cholesterol levels were determined as part of the standard clinical procedure. Baseline total cholesterol values were found to be related to the presence of coronary disease in men and women, although in the elderly little evidence for a significant relationship was found. Formal tests for interactions revealed a significant interaction between age and cholesterol but not between gender and cholesterol. In subgroup analyses using the Cox proportional hazards model, no relationship was found between cholesterol and either cardiovascular death or total cardiac events (death or nonfatal myocardial infarction) in 2038 medically treated patients with 5 to 20 years of follow-up. In the subgroup of 1798 surgically treated patients, there was also no relationship between baseline cholesterol level and these end points. Finally, detailed lipid analysis was done at baseline and 6-month angiography in a second population of 759 patients undergoing percutaneous coronary angioplasty between 1986 and 1989. No substantial relationship between baseline or follow-up cholesterol, low-density or high-density lipoproteins, or triglyceride levels and restenosis was found.

Cholesterol and heart disease in older persons and women. Review of an NHLBI workshop.

The value of serum total cholesterol measurement in predicting coronary heart disease (CHD) is well established in middle-aged men, but has been questioned in middle-aged women and older people of both sexes. To address this, the most recent follow-up data from 25 populations in 22 US and international cohort studies were presented and analyzed at a recent National Heart, Lung, and Blood Institute (NHLBI) workshop. Crude relative and absolute excess risks of fatal CHD were determined for individual studies and pooled across studies to determine pooled risk estimates. Serum total cholesterol and low-density-lipoprotein (LDL) cholesterol levels predicted fatal CHD in middle-aged (< 65 years) and older (> or = 65 years) men and women, though the strength and consistency of these relationships in older women were diminished. High-density-lipoprotein (HDL) cholesterol levels inversely predicted CHD in middle-aged men and women and in older women, but not in older men. Data for minority groups and for overseas populations were similar to those for white people in the United States. Relative risk estimates were generally lower for older than for middle-aged subjects, but absolute excess risk was greater. Older people and middle-aged women with elevated cholesterol levels are clearly at increased risk of coronary disease; whether this risk can be modified by dietary or drug therapy, and at what level intervention is appropriate, must not be determined.

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.

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)