We studied two sisters 29 and 31 years old who had skin and tendon xanthomas, corneal clouding, and severe coronary atherosclerosis. Histologic examination showed collections of lipid-laden histiocytes in the skin. The patients' plasma cholesterol concentrations were 177 and 135 mg per deciliter (4.58 and 3.49 mmol per liter). Levels of high-density-lipoprotein cholesterol were 4 and 7 mg per deciliter (0.1 and 0.2 mmol per liter). Only traces of apolipoprotein A-I were detected in whole plasma. The plasma density fraction from 1.06 to 1.21 g per milliliter contained no high-density lipoprotein on high-pressure liquid chromatography, no apolipoprotein A-I on sodium dodecyl sulfate electrophoresis, and only traces of apolipoprotein A-I on radioimmunoassay. Apolipoprotein C-III was also not detectable. The activity of lecithin-cholesterol acyltransferase was 40 per cent of normal. The half-life of infused normal high-density lipoprotein was three days (normal, 5.8 days). The parents and children of these two patients had low levels of high-density-lipoprotein cholesterol and apolipoprotein A-I. These cases support the hypothesis that low concentrations of high-density lipoprotein promote atherosclerosis.

A review of hereditary amyloidoses is provided by papers from a 1969 international symposium on primary amyloidosis. These discussions allow comparison of the amyloid neuropathy with onset in the lower extremities (POrtUgueseJapanese families), the neuropathy with onset in the upper extremities (Indiana-Maryland families), the neuropathy and nephropathy of the Iowa family, and the amyloidosis of familial Mediterranean fever. The importance of studies of genetic entities in understanding the pathogenesis of amyloidosis is emphasized.

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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.

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An anhydrous color reagent containing ferric chloride is pumped through Tygon tubing to a glass coil in a 95° heating bath. Manually prepared serum extracts (1:20 isopropanol dilution) are presented to the stream of preheated color reagent, and the two are passed through three mixing coils, connected in series. The absorbance of the resultant color is determined at 550 mµ in a 15 mm. tubular flow-cell. The improved N-automated procedure gave values of greater precision (5.6%) for total cholesterol determined in replicate samples from sera pools than the N-automated procedure which lacked precision (27.7%). The values found in 60 individual serums are within 6.0% of total cholesterol values determined by the Abell et al. method.

A modification of the Harvard Step Test was administered to approximately 4700 males and females, age 10-69 in Tecumseh, Michigan. Heart rate response to this standardized exercise test is an estimate of capacity for muscular work. A blood sample was drawn 1 h after a glucose challenge on the same day the exercise test was given. Four skinfolds were measured as an index of body fatnes. It was the purpose of this analysis to study the relationship of glucose tolerance to heart rate response to exercise. All analyses were done in age and sex-specific sub-groups. The correlation coefficients are low but positive in all but one sub-group and half of the coefficients are statistically significant. This suggests that poor fitness for work (high heart rate in response to exercise) was related, albeit weakly, to lowered glucose tolerance. However, there is a positive relationship between body fatness on the one hand and serum glucose and heart rate response to exercise on the other. When the effect of body fatness was eliminated the relationship of heart rate response to exercise ahd glucose tolerance remained about the same; low but statistically significant in some age groups.

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