Walter D. Block

Familial hypercholesterolemia, xanthomatosis and coronary heart disease☆

Abstract The mode of inheritance of familial hypercholesterolemia and its relation to coronary heart disease were studied in 268 persons belonging to a single family group which was heavily tainted with this abnormal trait. Analysis of the present data and those taken from the literature provided no firm basis for accepting without reservation any of the currently proposed genetic models of hypercholesterolemia. In particular, it was left open to question whether xanthomatosis resulted from the presence of a single gene or the concurrence of two abnormal alleles; it was suggested that the less severe degrees of hypercholesterolemia reflect not only the presence of a specific genetic abnormality but also the moderating influence of additional host and environmental factors. The disturbance related to elevated serum cholesterol levels was shown to be associated with increased susceptibility to the development of coronary heart disease, whether xanthomatosis is present or not, a finding at variance with a report based on a study of the same families ten years ago.

Hyperglycemia and Hypertriglyceridemia Among Persons with Coronary Heart Disease

Excerpt Coronary heart disease has been associated with a number of physiologic abnormalities, of which hypertension and hypercholesterolemia have been most clearly defined as risk factors. Regardl...

Comparison between free amino acid levels in plasma deproteinated with picric acid and with sulfosalicylic acid.

Summary A comparative study of 20% sulfosalicylic acid and of 1% picric acid in precipitating plasma proteins before analysis for free amino acids by ion-exchange chro-matography showed that both methods give values comparable in precision and accuracy. The sulfosalicylic acid method is less time-consuming, and requires fewer manipulations.

Effect of exercise training on glucose tolerance, in vivo insulin sensitivity, lipid and liproprotein concentrations in middle-aged men with mild hypertriglyceridemia

The effects of 9 weeks of aerobic exercise training with maintenance of stable body weight upon insulin sensitivity and upon glucose, lipid, and lipoprotein concentrations were studied in 10 middle-aged men with mild hypertriglyceridemia. Following training, mean maximum oxygen consumption improved from 33.5 +/- 1.9 to 39.3 +/- 1.9 mL/kg/min (means +/- SEM), (P less than 0.01). Glucose concentrations, both fasting and during oral glucose tolerance testing, remained stable but both fasting insulin concentrations and insulin responses to oral glucose decreased (P less than 0.1 and less than 0.01, respectively). In vivo insulin sensitivity improved 25 +/- 6.1% (P less than 0.01) following training. Exercise training resulted in decreases in fasting serum triglyceride concentrations from 203 +/- 12.6 to 126 +/- 9.0 mg/dL (P less than 0.01), primarily as a result of the reduction in VLDL-triglycerides (P less than 0.01). The magnitude in percentage decrease of VLDL-triglycerides was found to be significantly correlated (r = 0.71, P less than 0.05) with the magnitude in percent increase in max VO2. Serum cholesterol levels declined from 211 +/- 8.9 to 193 +/- 11.9 mg/dL (P less than 0.01), and the ratio of HDL-cholesterol to total cholesterol was improved. This study demonstrates that exercise training at a level of intensity feasible for many middle-aged men has beneficial effects on several factors that have been associated with an increased risk of cardiovascular disease.

The influence of physical training on glucose tolerance, insulin sensitivity, and lipid and lipoprotein concentrations in middle-aged hypertriglyceridaemic, carbohydrate intolerant men

SummaryThe effects of 9 weeks of moderate intensity exercise training while on a weight-maintaining diet were studied in 19 untrained middle-aged, hypertriglyceridaemic, carbohydrate intolerant men. Initial mean maximum oxygen consumption was low (29.7±1.0 ml-min−1 · kg−1; mean±SEM) and improved (34.2±1.4ml·min−1·kg−1, p<0.01) with exercise training. Fasting glucose, insulin, lipid and lipoprotein concentrations did not change. While the abnormal glucose response to oral glucose did not change with training, insulin concentrations were significantly (p<0.05) lower at 90 and 120 min during the final oral glucose tolerance test. Insulin mediated glucose uptake did not change, indicating that the degree of exercise training failed to improve in vivo insulin sensitivity. Significant associations were found between the following parameters measured: fasting concentrations of triglycerides and insulin, very low density lipoprotein-triglycerides and glucose, and measures of in vivo insulin resistance and fasting insulin levels, suggesting that insulin resistance in these glucose intolerant subjects may play a role in their hypertriglyceridaemia. These data indicate that moderate increases in physical training alone are not sufficient to improve the carbohydrate, insulin and lipid metabolism of hypertriglyceridaemic, glucose intolerant men.

The Tecumseh Study

The Tecumseh Community Health Study has been described in terms of its history, aims, design, conduct and current results, work in progress and future plans. This prospective epidemiological investigation of health and disease, especially cardiovascular disease and related disorders, in a total, natural community has its emphasis on the early detection of disease precursors in susceptible individuals, families, and other groups; the outlook is on prevention. An extensive and intensive study of this kind has been shown to be both feasible and productive. It represents what Dr. Thomas Francis, Jr., has called “clinical investigation on a community level,” including data on man and his environment. The key contribution of Dr. Francis in the establishment and conduct of the study is recalled and remembered with deep appreciation and respect.

Comparative effects of physical training and diet in normalizing serum lipids in men with Type IV hyperlipoproteinemia.

The effect mild physical training (PT) (group A), Type IV hyperlipoproteinemia (HLP) diet (group B), and PT plus Type IV HLP diet on serum lipids (group C) in 46 men with Type IV HLP was studied. Significant reductions in mean triglyceride (TG) levels from 163, 229, 196, to 136, 145, 116 mg/100 ml serum were found for groups A, B, and C, respectively. Following six weeks of intervention, cholesterol levels also dropped for all groups with the losses were found for all groups while groups A and C displayed significant reductions in body fatness, but both of these changes appeared independent of lipid reductions. It was concluded that either mild PT or HLP diet or both are effective means of lowering TG levels in Type IV HLP individuals. Furthermore, it appears that patients need to participate regularly in formal programs in order to maintain adherence to these interventions.

Amino acid content of rabbit urine and plasma.

Abstract The content of amino acids in plasma and urine from male albino rabbits was determined by ion-exchange chromatography and compared to values for other species. In general, the amino acids present in the plasma and urine of rabbits are those commonly found in other species. In contrast to human urine in which the content of histidine is usually greater than the two methylated derivatives, the content of histidine in rabbit urine is lower than either 1-methylhistidine or 3-methylhistidine. The plasma amino acid pattern is unusual in that glycine content is higher than alanine content; this is the reverse of the pattern in man and the cat. Fasting the rabbits for 88 hr. caused approximately a 66% decrease in the total amount of urinary amino acids. A 12- or 88-hr, fast caused the plasma total amino acid content to decrease approximately 30%. Valine, isoleucine, and leucine contents of the plasma, however, were increased.

Habitual Physical Activity and Glucose Tolerance: Males Age 16–64 in a Total Community

The data being reported are part of an epidemiologic study of health and disease in an entire community, Tecumseh, Michigan. Approximately 1,300 males age 16–65 were classified into three groups on the basis of their habitual leisure and occupational physical activity. A blood sample was drawn one hour after a glucose challenge and analyzed for glucose concentration. A measure of body fatness (sum of four skinfolds) was also available on the men. Glucose concentration of the three physical activity groups was compared by analyses of variance within narrow age groups. There was no significant relationship between glucose tolerance and habitual physical activity. There was a slight, but in some age groups significant, relationship between glucose tolerance and body fatness. The population was then divided within each age group into subgroups (thirds) by sum of skinfolds. The analysis was repeated in each age-fatness group. Glucose tolerance was better in the active men but only among the leanest subgroup of subjects.

Maximal oxygen uptake and blood lipids.

One thousand and sixty males and 119 females age 10-69, were tested on the treadmill as they walked at 3 mph (2 mph in subjects 60 yr and older). Every 3 min, the grade was increased 3%. Oxygen uptake and related measurements were recorded during the 3rd min .at each grade. Subjects, age 10-39, exercised to. exhaustion and maximal oxygen uptake (VOz max) was measured. In subjects age m9, VOz max was estimated from sub-max VO1 and heart rate. Serum cholesterol and serum triglyceride were determined in most of these subjects. After remov- ing the effects of age, wt and sum of four skinfolds, nonfasting values of cholesterol and triglycer- ide concentrations were unrelated to 90, max.