Gout and urie acid lithiasis are known to have affected mankind for thousands of years. It is only recently, however, that great progress has been made in the understanding of the processes involved in purine metabolism and its disorders in man. The key enzymes active in the various pathways of purine synthesis and degradation have become known and their properties are the subject of intensive study. Major contributions to the knowledge of normal purine metabolism in man have derived from the study of inborn errors in patients with purine disorders, specifically complete and partial hypoxanthine-guanine phosphoribosyltransferase deficiency. Mutations of other enzymes involved in purine metabolism are being discovered. A great step forward has been made in the treatment of gout with the introduction of uricosuric drugs and more recently of the hypoxanthine analogue allopurinol, a synthetic xanthine oxidase inhibitor. Furthermore, the complex nature of the renal handling of urie acid excretion, although still posing difficult problems, appears to approach clari­ fication.

Inhalt

of Volume 41B.- Gout.- The Kinetics of Intramolecular Distribution of 15N in Uric Acid Following Administration of 15N-Glycine: Preferential Labeling of N?(3+9) of Uric Acid in Primary Gout and a Reappraisal of the "Glutamine Hypothesis".- Hyperglutamatemia in Primary Gout.- Reduced Renal Ammoniagenesis in Primary Gout.- The Uptake of Glycine-14C into the Adenine and Guanine of DNA and Insoluble RNA of Human Leukocytes.- On the Problem of Hyperuricemia in Certain Physiological Stress Conditions.- Uric Acid Metabolism Following Acute Myocardial Infarction.- The Effect of Weight Reduction on Urate Metabolism.- Diet and Gout.- Effect of Ribomononucleotides Given Orally on Uric Acid Production in Man.- Relationship between Gout and Arterial Hypertension.- Studies on the Mechanism of Fructose-Induced Hyperuricemia in Man.- Observations of Altered Intracellular Phosphoribosylpyrophosphate (PP-Ribose-P) in Human Disease.- Human Erythrocyte Phosphoribosylpyrophosphate Content and "Generation" During a Constant Rate Infusion of Xylitol.- Diabetes and Uric Acid - A Relationship Investigated by the Epidemiological Method.- Metabolic and Glucose Load Studies in Uric Acid, Oxalic and Hyperparathyroid Stone Formers.- Observations Concerning the Incidence of Disturbance of Lipid and Carbohydrate Metabolism in Gout.- Gout and Hyperlipidaemia.- Lipid and Purine Metabolism in Benign Symmetric Lipomatosis.- An Integrative Hypothesis for the Renal Disease of Urate Overproduction.- Acute Intratubular Crystal Deposition Causing Permanent Renal Damage in the Pig.- Analysis of Treatment Results in Uric Acid Lithiasis with and without Hyperuricemia.- Isolation of a Red Pigment from the Uric Acid Calculi.- Concentration of Urate by Differential Diffusion: A Hypothesis for Initial Urate Deposition.- Experimental Hyperuricemia in Rats.- The Binding of Urate to Plasma Proteins.- Pharmacology.- Efficacy of Single Daily Dose Allopurinol in Gouty Hyperuricemia.- Withdrawal of Allopurinol in Patients with Gout.- Effect of Long-Term Allopurinol Administration on Serial GFR in Normotensive and Hypertensive Hyperuricemic Subjects.- Metabolic Studies of Thiopurinol in Man and the Pig.- Effects of Allopurinol and Oxipurinol on Pyrimidine Biosynthesis in Man.- The Molecular Basis for the Effects of Allopurinol on Pyrimidine Metabolism.- Purine and Pyrimidine Biosynthesis in Neurospora Crassa and Human Skin Fibroblasts. Alteration by Ribosides and Ribotides of Allopurinol and Oxipurinol.- Effects of Allopurinol and Oxonic Acid on Pyrimidine Metabolism in the Pig.- Ribonucleotides of Allopurinol and Oxipurinol in Rat Tissues and Their Significance in Purine Metabolism.- The Effect of Allopurinol on Oral Purine Absorption and Excretion in the Pig.- Allopurinol and Thiopurinol: Effect in vivo on Urinary Oxypurine Excretion and Rate of Synthesis of Their Ribonucleotides in Different Enzymatic Deficiencies.- Urinary Excretion of 6 Hydroxylated Metabolite and Oxypurines in a Xanthinuric Man Given Allopurinol or Thiopurinol.- Acute Renal Failure During Adenine Therapy in Lesch-Nyhan Syndrome.- Behavioural Changes During Adenine Therapy in Lesch-Nyhan Syndrome.- Treatment of Gout and Hyperuricaemia by Benzbromarone, Ethyl 2 (Dibromo-3,5 Hydroxy-4 Benzoyl)-3 Benzofuran.- The Pig As an Animal Model for Purine Metabolic Studies.- Influence of a Uricosuric Drug on Connective Tissue Metabolism.- The Synthesis and Immuno-Enhancing Activity of 3-Butylazathioprine.- Renal Handling of Urate.- The Clinical Significance of Hypouricemia.- Hypouricemia, Hypercalciuria, and Decreased Bone Density. A New Hereditary Syndrome.- Suppression of Uric Acid Secretion in a Patient with Renal Hypouricemia.- Evidence for a Urate Reabsorptive Defect in Patients with Wilson's Disease.- Reevaluation of the Pyrazinamide Suppression Test.- Evidence for a Post-Secretory Reabsorptive Site for Uric Acid in Man.- Uric Acid Excretion in Infancy.- Renal Handling of Uric Acid in Sickle Cell Anemia.- Hyperuricemia Induced by Ethambutol.- Uricosuric Effect of an Anti-Cholinergic Agent in Hyperuricemic Subjects.- Effects of Benzofuran Derivatives on Tubular Permeability to Urate-2-14C in the Rat Nephron.- The Effect of Glucose upon Reabsorptive Transport of Urate by the Kidney.- Mechanisms of Renal Excretion of Urate in the Rat.- Methodology.- Immunoadsorbent Chromatography of Hypoxanthine-Guanine Phosphoribosyltransferase.- The Use of High Pressure Liquid Chromatography to Monitor Nucleotide Levels in Cells.- Electrophoretic Separation of Normal and Mutant Phosphoribosylpyrophosphate Synthetase.- Development of a Micro HGPRT Activity Assay: Preliminary Complementation Studies with Lesch-Nyhan Cell Strains.- Comment on the Assay of Purine Phosphoribosyltransferases in Cultured Human Fibroblasts.- Significance of Staining Uric Acid Crystals with Natural and Synthetic Dyes.