James R. Klinenberg

The Effectiveness of the Xanthine Oxidase Inhibitor Allopurinol in the Treatment of Gout

Excerpt The clinical benefits derived from controlling the hyperuricemia of patients with gouty arthritis have been well-established (1, 2). This has been achieved by using uricosuric drugs to incr...

Relationships between glycogen storage disease and tophaceous gout

Abstract Two patients with glucose-6-phosphatase deficiency glycogen storage disease and tophaceous gout have been studied in an effort to establish the possible relationships between the primary defect in carbohydrate metabolism and their hyperuricemia and gouty arthritis. The present studies support the view that lacticacidemia is a contributing factor to the hyperuricemia of these patients. However, hypoglycemia and ketonemia probably also contribute to the urate retention. The finding of an increased rate of urate biosynthesis in the one patient whose de novo purine biosynthesis was greater than normal points to an additional mechanism for the hyperuricemia found in this type of glycogen storage disease.

Altered immunoglobulin metabolism in systemic lupus erythematosus and rheumatoid arthritis

IgG and IgM metabolism was evaluated in 10 patients with systemic lupus erythematosus (SLE), 10 patients with rheumatoid arthritis (RA), and in seven normal volunteers. The biological half-lives of purified IgG and IgM, labeled with (131)I and (125)I, respectively, were determined by serial measurements of radioactivity in the blood and urine with a gamma well counter, and by serial counts of total body radioactivity in a total body counting chamber. The mean survival half-life for IgG in patients with SLE was 8.2 days as compared to an average of 18 days in normal controls. An average of 10.1% of total body IgG was catabolized daily compared to a mean of 3.9% in normal controls. Turnover of IgM in patients with SLE was, with very few exceptions, normal. In contrast, patients with rheumatoid arthritis revealed a milder abnormality of IgG metabolism, but markedly abnormal IgM catabolism with a mean half-life averaging 5.9 days as compared to 9.3 days in control subjects. An average of 14.2% of total body IgM was catabolized daily in patients with RA as compared to 8.1% in normal controls. Our data suggest that there are basic differences between patients with RA and SLE in the synthesis and catabolism of IgG and IgM not readily apparent from serum IgG and IgM concentration. Abnormal IgG and IgM metabolism may be related to underlying immunological mechanisms in these diseases. Immunoglobulin turnover studies appear to be an additional means for the characterization of rheumatic diseases.

Suppression of glycine-15N incorporation into urinary uric acid by adenine-8-13C in normal and gouty subjects

Adenine inhibited the de novo synthesis of purines in both normal and gouty man as shown by inhibition of the incorporation of glycine-(15)N into urinary uric acid without altering the incorporation of glycine-(15)N into urinary creatinine. The diminished purine synthesis did not result in a diminution in the 24 hr excretion of uric acid. This observation was explainable in part by the prompt conversion of adenine to uric acid. In addition to this direct conversion, adenine-8-(13)C provided a slow and prolonged contribution to urinary uric acid.A feedback inhibition of purine synthesis by nucleotides derived from adenine provides the best interpretation of these results.