Louis E. Schaefer

Adrenal Cortex and Lipid Metabolism Effects of Cortisone and Adreno-corticotropin (ACTH) on Serum Lipids in Man

Summary This investigation indicates that cortisone produced well-characterized changes of serum lipids in man. The effects of ACTH on the serum lipids were less pronounced.

Heredity, Environment, and Serum Cholesterol A Study of 201 Healthy Families

Serum cholesterol levels of 1,236 healthy persons, including 775 members of 201 families, were analyzed in the investigation of the genetic control of serum cholesterol. It was concluded that there is an important genetic component in the determination of this level in healthy persons, that the gene is probably not sex-linked, and that environmental factors seem to play a lesser role.

The effect of phenformin hydrochloride on serum cholesterol and triglyceride levels of the stable adult diabetic

Abstract Study of a randomly selected sample of 202 stable ketoacidosis-resistant diabetics aged 35–80 revealed that, subjects receiving phenformin hydrochloride (DBI) alone or in combination therapy had significantly lower serum cholesterol and triglyceride levels than matched diabetics treated with insulin or tolbutamide alone. A prospective study of 60 additional diabetics previously treated with diet or tolbutamide or untreated showed that phenformin as the sole therapeutic agent produced a 12 per cent fall in cholesterol, a 40 per cent fall in triglycerides, an 11 per cent fall in fasting blood sugar and a weight loss of 3 4 to 1 pound/month (average values). The average dose of phenformin was 85 mg. daily and the average period of treatment was 26 weeks. These findings were interpreted in light of current concepts of the interrelationship of disorders of carbohydrate and lipid metabolism and the mechanism of action of phenformin was considered.

Genetic studies on hypercholesteremia: Frequency in a hospital population and in families of hypercholesteremic index patients☆

Abstract Hypercholesteremia appears to be a common denominator for most patients with early coronary atherosclerosis. The frequency of the occurrence of this disorder and its possible genetic relationship become, therefore, important points in any studies designed to further our knowledge of coronary artery disease, particularly that occurring in the younger age groups. This report summarizes studies of hypercholesteremia in 250 men and 250 women, consecutive admissions to the Mount Sinai Hospital, New York, and an analysis of families of fifty-nine of the seventy-five probands who were found to have idiopathic hypercholesteremia. Serum cholesterol determinations were performed by the method of Schoenheimer and Sperry on blood drawn from patients who had fasted 12 hours. Hypercholesteremia was considered to be present if the serum cholesterol was 280 mg. per 100 ml. or greater. The age of the 250 men in the index group averaged 50.9 years, and their serum cholesterol averaged 215 mg. per 100 ml. The 250 women averaged 48.1 years, and their cholesterol 230 mg. per 100 ml. Ninetyseven of these 500 probands (41 men and 56 women) were hypercholesteremic. This group averaged 52.8 years of age, and 348 mg. per 100 ml. of serum cholesterol. Twenty-two of these ninety-seven patients were suffering from diseases associated with hypercholesteremia and were excluded from further consideration. Of the remaining 478 probands thirty-two of the 242 men (13.2 per cent) and forty-three of the 236 women (18.2 per cent) were hypercholesteremic. The frequency of hypercholesteremia was not significantly different between the two sexes. A thorough attempt was then made to examine the immediate relatives of the seventy-five hypercholesteremic probands. No relatives of sixteen of these patients could be examined. This was usually due to the fact that there was no living family member, or that those living were scattered throughout the world and therefore unavailable. Ninety-seven siblings and 110 children of the remaining fifty-nine hypercholesteremic probands were examined. The frequency of hypercholesteremia among the siblings was 51.5 per cent and among the children 29.4 per cent. Both these frequencies are significantly higher than those found among the 478 patients. Since the definition of hypercholesteremia used in the preceding calculations did not take into account the fact that serum cholesterol varies with age, the analyses were repeated using data of Keys and associates 11a in which age is taken into consideration; in these two age groups women have significantly higher cholesterol levels than men. Again it was found that the values for men and women are fairly close, differing at the 5 per cent level for only two age groups, 58 to 62 and 63 to 67. Keys and associates published serum cholesterol values which are expected to be exceeded by only 5 per cent of the population in each age group. The frequency of hypercholesteremia for the total usable sample, according to this method of analysis, was 12.0 per cent; the frequency among the siblings of the hypercholesteremic probands was 36.2 per cent and among the children 34.0 per cent. These frequencies, again, are significantly greater than those found for the index patients; but are not significantly different from the corresponding values obtained when levels of cholesterol above 279 mg. per 100 ml. were considered to represent hypercholesteremia. Of the 478 probands 266 were Jewish and 212 were non-Jewish. Hypercholesteremia was significantly more frequent among the Jewish probands (21 per cent versus 9 per cent), but the frequency among siblings and children was not different when Jewish hypercholesteremic probands and families were compared with non-Jewish. The mode of inheritance of idiopathic hypercholesteremia remains to be worked out. The finding that hypercholesteremia is as frequent among the siblings and children of the non-Jewish hypercholesteremic probands as compared with the Jewish may indicate that environmental factors are not of too great importance in determining the presence of hypercholesteremia. The validity of these tentative conclusions awaits the completion of a study now being done in a more representative and complete population group. However, even these preliminary observations shed some light on the complicated error of metabolism involved in hypercholesteremia and predisposition to early atherosclerosis.

Steroid Diabetes In Man: The Development of Diabetes During Treatment with Cortisone and Corticotropin

Observations on the development of diabetes have been made in five cases in which corticotropin (ACTH) and/or cortisone were used for the treatment of the basic disease. A detailed analysis of the diabetes, observed with a follow up on its subsequent course lasting up to iVz years, is presented. Special attention is devoted to a comparison of the features of the diabetes with those previously described as steroid diabetes in animals 1-4 and man.-

Tissue Permeability--a Factor in Atherogenesis: Studies with Cortisone and Hyaluronidase

Cortisone has a retarding effect on atherogenesis in cholesterol-fed rabbits, despite higher plasma cholesterol levels. This effect of cortisone is prevented by administration of hyaluronidase. The latter intensifies atherosclerosis and deposition of cholesterol in the liver.

Sodium Gentisate in the Treatment of Acute Rheumatic Fever

Five patients with acute rheumatic fever were treated with gentisate, the biologic oxidation product of salicylate. The clinical course of this group was contrasted with that of five patients who received salicylate. It was found that, in the doses employed, gentisate had an effect on the symptoms of acute rheumatic fever equal to that of salicylate, but that it produced none of the toxic reactions which were commonly found after salicylate administration. An oral dose of 2.0 Gm. of gentisate, every three hours, continued for at least ten days after the temperature became normal, was sufficient to control the symptoms of the disease.

Serum Phospholipids Genetic and Environmental Influences

Serum phospholipid levels were determined in 1,067 healthy persons aged 2 to 77 years. Phospholipid levels increased with age but in a different way for each of the sexes. The age-sex changes of serum phospholipids were similar to those observed for serum cholesterol. Correlation coefficients in members of 156 families indicated that the genetic factor is of importance in determining the serum phospholipid level in health. Because of the age-sex variations of serum phospholipid and serum cholesterol levels, no single arbitrary line can be drawn between normal and abnormally elevated levels of these 2 serum lipid fractions.

An Effect of Growth Hormone on Hexose Phosphate Metabolism.

Summary Glucose- and fructose-6-phosphate were assayed in the skeletal muscle of normal and hypophysectomized female rats, with and without growth hormone treatment, one hour after a glucose injection. The results show a statistically significant increase in the glucose-6-phosphate content of the muscle of rats receiving GH when compared to glucose-6-phosphate levels in controls, as well as less striking increases in fructose-6-phosphate levels.