Circulating concentrations of adrenocorticotrophin in rheumatic fever

Western Society for Clinical Research measurement of these hormones accurately reflects adrenal function. Five to 10 mg. of FF given as an eight hour intravenous drip, or 1 to 2 mg. by mouth every six hours, markedly suppress adrenal cortical output. Studies of the pituitary-adrenal relation in normal as well as abnormal states of adrenal cortical function will be presented. Preliminary results from a study of urinary metabolites of FF indicate that degradation and conjugation are similar to that of hydrocortisone. These findings, in conjunction with the observed high topical potency, support the conclusion that the potentiality of action affected by halogen substitution probably occurs at the cellular level in the target tissues. CIRCULATING CONCENTRATIONS OF ADRENOCORTICOTROPHININ RHEUMATIC FEVER. A. Bertrand Brill, Robert S. Ely * and Vincent C. Kelley, *

Univ. Utah School Medicine, Salt Lake City, Utah. A satisfactory determination of endogenous ACTH levels in blood has become possible only recently. Development of the adrenal ascorbic acid depletion method for assaying the ACTH content of blood has been applied in investigations with animals and more recently in clinical investigations in occasional patients. This method allows assessment of pituitary function permitting a separate analysis of the factors involved in the pituitary-adrenal glands. In the present study endogenous ACTH activity was determined in the blood of forty children. These included normal control groups, subjects in various stages of rheumatic fever and its therapy and patients with Sydenham’s chorea. In the group of normal children, ACTH concentrations were not detectable. In rheumatic fever patients, before administration of hormone therapy, high levels of circulating ACTH were found which varied with the acuteness of the disease. Subsequently these levels were influenced by the type of therapy administered. ERYTHROCYTE CARBOHYDRATE METABOLISM IN HEREDITARY HEM~LYTIC ANEMIAS. A. G. Motulsky, B. W. Gabrio, * J. Burkhardt and C. A. Finch. *

Dept. Medicine, Univ. Washington, Seattle, Wash. Most hereditary hemolytic anemias are characterized by non-specific morphologic red cell anomalies. Abnormal shape may be absent as in hereditary non-spherocytic altogether, hemolytic disease. Structural changes fail to AUGUST,

1955

explain increased destruction in most instances. Since glucose is the prime source of energy of the red cell, an investigation of carbohydrate metabolism of abnormal erythrocytes appeared desirable. Methods included measurements of erythrocyte glycolytic rates, P3* uptake and analysis of non-radioactive and tagged phosphorylated intermediates by differential hydrolysis and by paper clectrophoresis and chromatography. Radioautographs of paper strips allowed ready screening, visualization and densitometric quantitation of metabolic abnormalities. Total P3* uptake and glycolytic rates of mature cells were normal in hereditary nonspherocytic hemolytic disease and in hereditary spherocytosis as well as in all other hemolytic anemias studied. Disturbed intracellular distribution of phosphorylated intermediates was detected in several cases of hereditary nonspherocytic disease and in hereditary spherocytosis. In the former condition, increases of 2,3_diphosphoglycerate were found, while the defect in hereditary spherocytosis consisted of accumulation of intraerythrocytic inorganic phosphate during incubation with P3*. Glucose and adenosine in vitro corrected the latter abnormality. The abnormal pattern showed little intrafamilial variability but differed from family to family. Incubation of hereditary spherocytes for twenty-four hours at 37”~. causes marked increases in osmotic fragility. Such a metabolic stress test demonstrated the biochemical defect in another manner since glucose, adenosine and related nucleosides tended to correct the abnormal fragility. These studies demonstrate the existence of apparently genetically controlled metabolic lesions in abnormal red cells. It has been shown that a reversible erythrocytic defect produced by red cell storage seriously interferes with viability of normal stored cells. It is suggested that the demonstrated lesions in hereditary hemolytic anemias may similarly be significant in producing the shortened red cell life span of abnormal cells. DESTRUCT~ONOFROVINEANTIHEMOPHILICFACTOR BY A COMPONENT OF HUMAN PLASMA. Theodore H. Spaet * and Evelyn J. Garner. Stanford Univ.

School Medicine,

San Francisco,

Although the antihemophilic human plasma is storage-labile,

Calif. factor (AHF) of bovine AHF is