Barker, Nelson W.

Abstract The deficiency in the conversion of prothrombin to thrombin which develops after administration of dicumarol appears to be due largely to decreased cothromboplastin activity. Both the development of this deficiency and the recovery from it tend to precede the accompanying changes in prothrombin itself, as measured by the two-stage method. In terms of deviation from normal, the deficiency in conversion often exceeds in magnitude the deficiency of prothrombin itself.

The clinical and follow-up data on 520 non-diabetic patients less than 60 years of age who had a clinical diagnosis of arteriosclerosis obliterans of the lower extremities made at the Mayo Clinic in the period 1939 through 1948 were reviewed from the standpoint of pathogenesis, prognosis, and clinical course of the disease. The ratio of males to females was 11 to 1, and the mean concentration of plasma cholesterol in the male patients with arteriosclerosis obliterans was approximately 50 mg. per 100 ml. greater than that of either of 2 control groups of men without clinical evidence of atherosclerosis. The incidence of smoking among the men with this disease was higher than in a comparable group of men without it. Obesity was not commonly associated with arteriosclerosis obliterans, while hypertension was associated with the disease about 3 times as often as in a control group without the disease. The survival rate for patients with arteriosclerosis obliterans was less favorable than that of a normal population of a similar age and sex distribution, and the survival rate for patients with atherosclerotic aorto-iliac occlusion was significantly less favorable than that of patients with atherosclerotic occlusion of the femoral artery. In approximately three fourths of the patients who died, the cause of death was thought to be disease of the coronary arteries. The presence of atherosclerosis elsewhere than in the arteries supplying the extremities, as manifested by clinical coronary artery or cerebrovascular disease at the time of diagnosis, had an adverse effect on survival. Four per cent of the patients required amputation of a leg shortly after the diagnosis of arteriosclerosis obliterans was made at the clinic, and an additional 4.9 per cent subsequently required amputation during the 5-year period following the initial examination. Only 3.0 per cent of patients with intermittent claudication as the only symptom of their disease required an amputation during this period. Eleven and three-tenths per cent of patients who continued to smoke, but none who abstained from smoking, had amputations within 5 years. Since all patients of the series were treated before the advent of direct arterial surgery for segmental arterial occlusion, it is believed that the subsequent course of the disease in these patients may be used as a basis for comparative evaluation of results in patients subjected to direct arterial surgical procedures.

The successful use of dicumarol in the prevention of intravascular thrombosis and subsequent embolism has led to the investigation of other coumarin compounds as therapeutic anticoagulants. 4-Hydroxycoumain anticoagulant No. 63 is such a compound. Like dicumarol, it induces hypoprothrombinemia and daily tests of prothrombin time are necessary as a guide to dosage. Our experience indicates that a less fluctuating and somewhat more consistent therapeutic hypoprothrombinemia can be established and maintained with anticoagulant No. 63 than with dicumarol. The potential disadvantage of the prolonged hypoprothrombinemia after administration is stopped is counter balanced by the strong and relatively rapid antagonistic effect of vitamin K 1 .

Heparin administered intravenously increases the translucence of plasma during alimentary lipemia. This apparently is solely a physical change. This article reports observations concerning this phenomenon in normal persons and atherosclerotic patients. For purposes of maximal sensitivity, exceedingly small amounts of heparin are used, and distinct differences between the normal and the atherosclerotic individuals are noted, with the atherosclerotic failing to clear well on the same empiric dose of heparin as the normal persons. An unexpected observation was that the normal men developed a significantly greater degree of lipemia than did normal women after ingestion of the same fat meal.

The anticoagulant drugs, heparin and dicumarol, have been of great value in the prevrention and treatment of peripheral thromboembolic disease. The use of both drugs requires individualization of dosage based on the results of the appropriate tests of their effect on coagulation. The risk of bleeding is very small if heparin and dicumarol are properly used. New anticoagulant drugs are being studied and evaluated clinically in an effort to increase even further the effectiveness and safety of anticoagulant therapy.

Cerebral infaretion currently is the third leading cause of death in the United States. Since atherosclerosis of the cerebral arteries is the basis for the majority of strokes, the authors undertook to define more accurately the distribution of such atherosclerosis, its relation to coronary atherosclerosis, and its relation to such other factors as hypertension, obesity, and cerebral infarction. The results of their study are presented here.

Nicotinic acid was administered orally to 33 patients with hypercholesterolemia in doses varying from 1.5 to 6.0 Gm. per day for periods of 3 months to 1½ years. Significant, sustained, and reproducible decreases in the concentration of cholesterol and total lipids in the plasma and of serum beta-lipoprotein cholesterol were observed in a majority of patients. This form of therapy appears to be effective, practical, and probably free from serious harmful effects.