The study of gouty arthritis has provided a common meeting ground for the research interests of both the basic scientist and the clinician. The interest of the chemist in gout began 1776 with the isolation of uric acid from a concretion of the urinary tract by the Swedish chemist SCHEELE. The same substance was subsequently extracted from a gouty tophus by the British chemist WOLLASTONE in 1797 and a half century later the cause of the deposits of sodium urate In such tophi was traced to a hyperuricemia in the serum of gouty patients by the British physician Alfred Baring GARROD who had also received training in the chemical laboratory and was therefore a fore-runner of many of today's clinician-investigators. The recent surge of progress in understanding of some of the causes of gout in terms of specific enzyme defects marks the entrance of the biochemist into this field of investigation. The identification of the first primary defect of purine metabolism associated with over-production of uric acid, a severe or partial deficiency of the enzyme hypoxanthine-guanine phospho­ ribosyl transferase was achieved less than a decade ago. The knowledge of the mechanism of purine over-production that it generated led shortly to the identification of families carrying a dominantly (possibly X-linked) inherited increase in the activity of the enzyme phosphoribosylpyrophosphate synthetase as a cause of purine over-production. Yet this is only a start as these two types of enzyme defects account for less than five per cent of gouty patients.

Inhalt

of Volume 76 B.- Renal Handling of Urate.- Renal Handling of Uric Acid.- Renal Handling of Urate in Man.- The Effect of Urine Flow Rate on Urate Clearance.- Effects of Vitamins on the Renal Handling of Uric Acid.- The Uricosuric Action of Amino Acids in Man.- Urate Excretion in Normal and Gouty Men.- The Effect of Acid Loading on Renal Excretion of Uric Acid and Ammonium in Gout.- Evidence for Two Secretory Mechanisms for Organic Acid Transport in Man.- Classification of Uricosuric States Based upon Response to Pharmacologic Inhibitors of Urate Transport.- Familial Renal Hypouricemia due to Isolated Tubular Defect.- Isolation and Characterization of Uricine.- Uricine - Uric Acid Interactions.- Urinary Excretion of Uricine.- Renal Handling of Urate in Animals.- Sites of Urate Transport in the Rat Nephron.- Factors Affecting Urate Reabsorption in the Rat Kidney.- Some Characteristics of Uric Acid Uptake by Separated Renal Tubules of the Rabbit.- Effects of Drugs on the Uptake of Uric Acid by Separated Renal Tubules of the Rabbit.- Tubular Handling of Allantoin in the Rat Kidney.- Biochemistry of Purine Transport.- Control of Net Cellular Uptake of Adenosine from the Lumen Side of the Guinea Pig Jejunal Epithelium.- Uptake of Hypoxanthine in Human Erythrocytes.- Incorporation of Purine Bases by Intact Red Blood Cells.- Uric Acid Transport Characteristics in Human Erythrocytes.- A Relationship Between Free Urate, Protein-bound Urate, Hyperuricemia and Gout in Caucasians and Maoris.- Biochemical Pharmacology.- Influence of Allopurinol on the Genetic Materials of Ehrlich Ascites Tumor Cells.- 6-Azauridine, an Inhibitor of the Purine Salvage Pathway.- Suppression of Experimental Urate Nephropathy by Salicylate.- Physiological Characteristics of Various Experimental Models for the Study of Disorders in Purine Metabolism.- In Vitro Investigations on the Influence of Antirheumatic Drugs on Purine Phosphoribosyltransferases and Their Possible Clinical Consequence.- Mechanism of Gouty Inflammation.- Influence of Urate on Connective Tissue Metabolism.- Protein Binding to Monosodium Urate Crystals and its Effect on Platelet Degranulation.- Protein Adsorption to Monosodium Urate Crystals: Differential Responses of Human Peripheral Blood Neutrophils.- Clinical Aspects of Purine Metabolism.- Serum Uric Acid Levels in England and Scotland.- Gout Disease. Its Natural History Based on 1,000 Observations.- Hyperuricemia as a Risk Factor in Coronary Heart Disease.- Hyperuricemia and other Cardiovascular Risk Factors.- Recurrent Gouty Phlebitis without Articular Gout.- Alterations of Human Purine Metabolism in Megaloblastic Anemia.- Typing of Uric Acid Level in Cerebrospinal Fluid in Neurological and Psychiatric Diseases.- Renal Tubular Transport of Urate in Fanconi Syndrome.- Nutritional State and Purine Metabolism.- Nutritional State and Purine Metabolism.- The Effect of Different Purines and Pyrimidines on Human Pyrimidine Biosynthesis.- The Effect of Weight Loss on Plasma and Urinary Uric Acid and Lipid Levels.- Pathogenesis of "Fasting Hyperuricemia" and its Prophylaxis.- Therapeutic Aspects of Disorders in Purine Metabolism.- The Treatment of Acute Gouty Arthritis.- Multi-Centre Trial of Naproxen and Phenylbutazone in Acute Gout.- The Influence of Allopurinol in Customary and in Slow Release Preparation on Different Parameters of Purine and Pyrimidine Metabolism.- Purine Excretion in Complete Adenine Phosphoribosyltransferase Deficiency: Effect of Diet and Allopurinol Therapy.- Thiopurinol: Dose-Related Effect on Urinary Oxypurine Excretion.- Dose-Response Relationship of a Uricosuric Diuretic.- The Pharmacology of the Hypouricemic Effect of Benzbromarone.- The Metabolic Effects of Tienilic Acid, a New Diuretic with Uricosuric Properties in Man and Dog.- Hyperuricemia as a Risk Factor.- Panel Discussion.- Author Index.