[Gout]. / Gicht.

In most cases gout is the clinical manifestation of familial hyperuricemia. Pathogenesis of hyperuricemia, clinical manifestations, diagnosis and differential diagnosis of hyperuricemia and gout are described. Treatment of hyperuricemia consists of dietary measurements and administration of uric acid lowering drugs, such as allopurinol or uricosuric agents. Nonsteroidal antiinflammatory drugs, colchicine and glucocorticosteroids are the treatment of choice for the acute gout attack. Prophylaxis of acute uric acid nephropathy consists of hydration, urine alkalinization and administration of allopurinol or rasburicase. For treatment of acute uric acid nephropathy rasburicase is the drug of choice.

Disease-specific noncompliance with drug treatment as a cause of persistent hyperuricemia and gout in anorexia nervosa.

A 49 year old female patient with anorexia nervosa was admitted to the hospital because of treatment-refractory hyperuricemia and gout. Medical history and clinical findings were compatible with primary gout and uric acid nephropathy. The patient stated that she regularly took allopurinol. In the hospital she initially received 300 mg allopurinol daily after breakfast. In order to ensure allopurinol ingestion and absorption the plasma concentrations of both allopurinol and its active metabolite oxipurinol were determined in addition to serum uric acid and further clinical chemistry data. Despite allopurinol treatment no decrease of serum uric acid was observed for three days. Therefore the head nurse was instructed to supervise the intake of allopurinol carefully. During the following days serum uric acid decreased and plasma oxipurinol concentrations rose. On day 9 of treatment serum uric acid fell into the upper normal range. Therefore the patient was allowed to leave the hospital within a few days. However serum uric acid thereafter increased again while plasma oxipurinol declined. Later on it became evident that the patient had vomited self-induced approximately 15 minutes after allopurinol intake. In the meantime her husband had urged her to return home. Starting with day 18 benzbromarone treatment was added. Combined therapy with 400 mg allopurinol and 50 mg benzbromarone daily finally resulted in a serum uric acid concentration of 4.5 mg/dl at discharge from the hospital. About three weeks later the private physician again diagnosed hyperuricemia with serum uric acid values between 10 and 12 mg/dl. Meanwhile the patient needs to be dialysed due to end stage renal disease. Our observations show that self-induced vomiting to prevent effective treatment may be a disease-specific pattern of noncompliance with drug therapy in anorexia nervosa.

A study of dose-response relationships of allopurinol in the presence of low or high purine turnover.

Effects of allopurinol (125-500 mg/m2 body surface) were studied in normal subjects during periods of 18 days both during a purine-free, isoenergetic liquid formula diet and additional intake of ribonucleic acid, 4 g/day. Plasma uric acid and renal excretion of uric acid, oxypurines (hypoxanthine plus xanthine) and orotic acid were measured and total purine excretion calculated. Effects of allopurinol were evaluated by comparison of the results obtained in the steady state during diet alone (average of days 7-10) with those during allopurinol administration (days 16-18). During the purine-free diet, plasma uric acid was lowered more than urinary uric acid by allopurinol on doses of 250-500 mg/m2 (44%-54% of control values on 500 mg/m2), demonstrating an increase in renal clearance. At the same dose, the uric acid lowering effect of allopurinol was more pronounced with than without purine loads (plasma 41%, urine 32% of control on 500 mg/m2 during purine intake), while renal uric acid clearance was decreased. The more pronounced reduction of uric acid excretion during purine administration was balanced to the greater part by a more pronounced increase in oxypurine excretion. Total purine excretion was reduced by about 20% during the purine-free diet irrespective of dose. The size of this purine deficit was doubled, but was also independent of dose during addition of purines. Orotic acid excretion increased with dose during allopurinol treatment and was reduced by addition of purines.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of dietary purines and pyrimidines on human pyrimidine biosynthesis]. / Der Einfluss von Nahrungspurinen und -pyrimidinen auf die Pyrimidinsynthese des Menschen.

Young healthy volunteers received a purine-free, isoenergetic formula diet over a period of 28 to 32 days. After a short time under formula diet alone 400 mg allopurinol were administered daily. After a further 10 days each volunteer received daily, in addition, either 4 g RNA, 4 g RNA-hydrolysate, 1 g guanosine-5-monophosphate (GMP), 1 or 3 g adenosine-5-monophosphate (AMP), uridine-5-monophosphate (UMP), cytidine-5-monophosphate (CMP) or adenosine, guanosine, uridine, cytidine, guanine, hypoxanthine, xanthine, cytosine and uracil. Finally the allopurinol was omitted. The renal excretion of total orotic acid (orotic acid and orotidine), uric acid and creatinine was determined daily; serum uric acid concentrations and the enzyme activities of orotidine-5-phosphate-decarboxylase (ODCase) and hypoxanthine-guanine-phosphoribosyltransferase (HGPRTase) from erythrocytes were determined every other day. The results show that RNA, RNA-hydrolysate, purine- and pyrimidine-nucleotides and -nucleotides as well as hypoxanthine, and to a lesser extent adenine, diminish allopurinol-induced orotaciduria. This is compatible with an influence of dietary purines and pyrimidines on human pyrimidine biosynthesis.