Urinary 5-Methoxytryptamine in Patients With Rheumatic Fever*

Abstract

No specific diagnostic test for rheumatic fever has been available to date (1). The tryptophannicotinic acid metabolic series was studied exhaustively in the present work. This investigation was based on a previous observation that the tetrahydrofurfuryl ester of nicotinic acid elicited a different response in the skin of patients suffering from active rheumatic fever than in the skin of nonrheumatic patients (2). The reaction was attributed to nicotinic acid, a member of the tryptophan metabolic series.The present report describes an abnormal product of tryptophan metabolism isolated from the urine of rheumatic subjects. MATERIALS AND METHODSStudies in human subjects. Three groups of subjects were used in this study. The first two consisted of both male and female children between 3 and 16 years of age.Group I consisted of inpatients at the National Children's Cardiac Hospital with inactive rheumatic heart disease,' inactive rheumatic fever,' or congenital heart disease, and group II, of young subjects from other places who had either active or inactive rheumatic heart disease, or rheumatic fever. These two groups were considered separately because any uniform dietary and environmental effects observable among group I subj ects were balanced by dietary and environmental differences among group II subjects. Studies requiring large quantities of urine necessarily excluded group II patients. Group III consisted of adult male patients at the Veterans Administration Hospital, Coral Gables, Florida, with Hodgkin's disease or mutiple myeloma.Normal control subjects were also studied. As controls for groups I and II, urines were collected from local children of comparable ages and sex with no known diseases; as controls for group III, urine weas obtained from adult males with no known diseases.In all subjects, 24-or 48-hour urine samples were collected with toluene as a preservative and were refrigerated as soon as possible after collection. Urine specimens were * Supported by grants from the Florida Heart Association and the Heart Association of Greater Miami, Fla. ' In this report, "rheumatic heart disease" and "rheumatic fever" are distinguished by the presence or absence of heart involvement, respectively. analyzed for products in the tryptophan-nicotinic acid metabolic series.In some instances, "tryptophan loading" tests w,ere done. Five g of L-tryptophan suspended in 200 ml of orange juice was administered orally. The urinary excretion of 5-hydroxyindoleacetic acid and related compounds was measured during the subsequent 24 hours and compared with the amounts excreted over the same interval on the previous day, when only orange juice was fed.Chemical analytical mtiethods. Tryptophan was determined by the p-dimethylaminobenzaldehyde method of Spies and Chambers (3). Indoxylsulfate and tryptamine were determined by use of a modified Ehrlich's reagent (4). Kynurenic acid and xanthurenic acid were measured by the fluorometric method of Satoh and Price (5). Kynurenine was converted to o-acetophenone, which wvas measu...

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