Alfred Steiner

Effect of Neomycin on Serum Cholesterol Level of Man.

Summary Oral administration of neomycin was associated with a significant decrease in serum cholesterol concentration of all of the 10 patients studied. On 1.5 to 2 g of neomycin daily, mean serum cholesterol level in each patient was decreased from 17 to 29%, average fall for the group was 22%. The fall in serum cholesterol level was maintained for the duration of drug administration which varied from 3 to 16 weeks. At a daily dose level of 0.5 to 1 g of neomycin similar but less marked falls in the serum cholesterol level resulted.

Production of arteriosclerosis in dogs by cholesterol and thiouracil feeding.

Abstract 1. 1. The production of arteriosclerosis in an omniverous mammal, the dog, by the feeding of cholesterol and thiouracil has been confirmed. 2. 2. The resultant arteriosclerotic lesions in the dog have the same anatomical distribution and sites of predilection as do lesions in man, including the occurrence of cerebral arteriosclerosis. 3. 3. The morphological features of the arteriosclerotic lesions in dogs resemble those of human arteriosclerosis in that infiltration of the intima with foam cells and proliferation of the endothelium of the intima occurs in the early lesions, while extension into the media, hyalinization, hemorrhage, and calcification develop in the more advanced placques. 4. 4. It has been demonstrated that thiouracil in the dosage used does not lead to arterial lesions. 5. 5. The feeding of 10 Gm. of cholesterol daily, in addition to the regular diet, containing less than 5.0 per cent fat, without thiouracil, resulted in a moderate hypercholesterolemia and early arteriosclerosis in one dog.

The Abnormal Serum Lipid Pattern in Patients with Coronary Arteriosclerosis

Studies in experimental arteriosclerosis have indicated that the relative level of serum lipid phosphorus may be as significant a factor as the absolute level of serum cholesterol in the production of arterial lesions. For this reason, the serum lipid pattern of 82 patients with coronary arteriosclerosis has been compared with that of 112 healthy adults. An elevation of the serum cholesterol, serum lipid phosphorus and the serum cholesterol-lipid phosphorus molar ratio has been found in most of the patients with coronary arteriosclerosis.

Effect of Estrogenic Hormone on Serum Lipids in Patients with Coronary Arteriosclerosis

The oral administration of large amounts of ethinyl estradial daily to patients with coronary arteriosclerosis and to control subjects consistently produced a favorable effect upon the serum lipid pattern. However, toxic effects of the estrogen prohibited its prolonged use. The clinical status of the patient as evidenced by the incidence of chest pain or the electrocardiogram were not altered during the period of the study.

The physiologic action of oxygen and carbon dioxide on the coronary circulation, as shown by blood gas and electrocardiographic studies

Abstract By means of blood gas and electrocardiographic observations, the physiologic action of oxygen and carbon dioxide on the coronary circulation was studied. When a deficiency of oxygen has been produced in the arterial blood by decreasing the oxygen concentration of inspired air, certain compensating mechanisms become manifest, such as an increase in pulmonary ventilation and circulation velocity. In cases of coronary sclerosis, the narrowed lumina of the coronary arteries impose a variable degree of obstruction to an increase in the flow of blood. The induction of oxygen want in the presence of this relative ischemia results in severe anoxia of the heart muscle, the consequences of which are (1) coronary insufficiency, with precordial pain and cardiac or peripheral circulatory failure, and (2) electrocardiographic changes, particularly lowering of the T wave or depression of the S-T segment. The increased pulmonary ventilation produced by acute anoxia engenders a disproportionate loss of dissolved carbon dioxide, with a shift in blood pH toward the alkaline side. Since alkalosis produced by hyperventilation has been shown to cause constriction of capillaries in other parts of the body, the possibility that it may have the same effect on the coronary circulation was investigated. The addition of small amounts of carbon dioxide, such as 2 to 3 per cent, to a low-oxygen mixture prevented the clinical and electrocardiographic signs of coronary insufficiency which have been described above. Although the inhalation of a low-oxygen carbon dioxide mixture in eight out of ten cases of coronary disease resulted in a higher arterial oxygen saturation than the inhalation of a comparable low-oxygen mixture, there were four cases in which the symptoms or electrocardiographic signs of coronary insufficiency either did not occur, or were diminished, in the presence of a comparable, severe arterial anoxemia, when carbon dioxide loss was prevented. The inhalation of high-oxygen concentrations is known to improve the function of the coronary circulation when it has been previously impaired. The electrocardiographic effects of the inhalation of approximately pure oxygen in thirty-two cases of coronary disease were studied. In twenty-seven cases, the T wave was rendered more upright. The addition of carbon dioxide to high-oxygen concentrations either had no effect, or, in six cases, diminished slightly the T-wave elevation produced by inhaling high-oxygen mixtures. Accepting Macleods thesis that one of the factors influencing the height of the T wave is the speed of recovery of cardiac muscle, we tentatively conclude that the evidence obtained in these studies suggests that the inhalation of low-oxygen mixtures prolongs the recovery period of heart muscle in patients with coronary disease, and that the inhalation of high-oxygen mixtures shortens the recovery period. In the presence of acute anoxia, the inhalation of small amounts of carbon dioxide shortens the recovery period of cardiac muscle, in part by increasing the arterial oxygen tension, and in part by preventing constriction of capillaries in the coronary circulation. The administration of carbon dioxide in the absence of alkalosis may in some cases delay the recovery period of heart muscle.

Effect of Antibiotics on the Serum Cholesterol Concentration of Patients with Atherosclerosis

Oral neomycin, at the dose level of 0.5 to 2 Gm. daily, produced a significant fall in the level of serum cholesterol in all of 29 periods in 20 patients studied. The effect reached a maximum in approximately 2 weeks and persisted for the duration of the experiments up to 9 months. After the medication was discontinued, the serum cholesterol levels returned to control values within 2 weeks. No significant toxic reaction to oral neomycin was discernible. Neomycin by injection in excess of the amount calculated to be absorbed from the gastrointestinal tract failed to lower the serum cholesterol level. The mechanism of action of neomycin was not determined, but it is thought to be a local effect in the gastrointestinal tract or its contents. Oral aureomycin and oral kanamycin had a similar but less marked and less consistent effect on the level of serum cholesterol in a number of patients. In a limited number of patients, oral achromycin, bacitracin, chloromycetin, streptomycin, and mycostatin did not have a significant effect on the serum cholesterol level; likewise, intramuscular penicillin and streptomycin failed to alter the serum cholesterol level. The prior lowering of the serum cholesterol concentration by a low-fat diet did not prevent a further decrease in the serum cholesterol by oral neomycin.

Production of Hyperlipemia and Early Atherosclerosis in Rabbits by a High Vegetable Fat Diet

Feeding of a high vegetable fat diet made up of ground peanuts and purina chow to rabbits resulted in an increase in the serum cholesterol, as well as other serum lipids, including β-lipoprotein fraction. Microscopic lipid deposits in the intima and underlying media of the ascending and thoracic aorta were present in 10 of 33 rabbits at the end of 5 to 12 months. Small areas of gross atherosclerosis of the aorta were found in two rabbits.

Effect of Saturated and Unsaturated Fats on the Concentration of Serum Cholesterol and Experimental Atherosclerosis

The feeding of a diet rich in unsaturated fats to rabbits produced no significant alteration of the serum cholesterol level, while the feeding of a diet rich in saturated fats produced an elevation of the serum cholesterol without the development of experimental atherosclerosis. The addition of unsaturated fats to a diet rich in cholesterol failed to prevent hypercholesterolemia and experimental atherosclerosis in rabbits.

Effect of Sitosterol on the Concentration of Serum Lipids in Patients with Coronary Atherosclerosis

The oral administration of large amounts of sitosterol to patients with coronary atherosclerosis has resulted in statistically significant decrease in serum cholesterol in one half of the trial periods. However, because of the fluctuation of the serum cholesterol that occurs in patients with coronary atherosclerosis, further study will be necessary to demonstrate that the decrease in serum cholesterol coincident with sitosterol administration is not due to the lability of the serum lipids in this group of individuals.

Effect of Feeding of “Soya Lecithin”∗ on Serum Cholesterol Level of Man.

Summary (1) Twenty-five grams of “soya lecithin” were fed to 8 patients for 6-week periods. (2) The serum cholesterol level in each instance was lowered significantly. The decline was maintained for only 5 weeks despite the maintenance of the “soya lecithin” regime. (3) The induced hypocholesterolemia was not associated with an increase in the basal metabolism.