Dosage prescribing and plasma oxipurinol levels in patients receiving allopurinol therapy.

This study examined dosage prescribing patterns and steady-state oxipurinol plasma concentrations in 66 patients receiving chronic allopurinol therapy. Most patients (65%) were taking 300 mg allopurinol daily, although renal impairment was common. Using published guidelines, it was estimated that 35% of patients were receiving excessive dosages of allopurinol. Consequently, the plasma oxipurinol concentrations were often very high (mean (SD) was 156 (109) mumol.l-1). Accumulation of oxipurinol was inversely related to renal function. Plasma concentrations of oxipurinol and urate were not significantly related. However, most patients with oxipurinol concentrations of up to 100 mumol.l-1 had urate concentrations within the normal reference range.

Chronic strongyloidiasis in Tasmanian veterans--clinical diagnosis by the use of a screening index.

Chronic infection with Strongyloides stercoralis presents a diagnostic problem because of the low recovery of the organism from stools and the insensitivity of current serological tests. Of 150 former Far East POWs, 26 (17%) had S. stercoralis in stools. The clinical features in 18 stool-positive patients were compared to those in 24 stool-negative patients and showed that strongyloidiasis was associated with a higher frequency of alteration in bowel habit, upper abdominal discomfort, rash and eosinophilia. On the basis of these features, a screening index was devised which largely separated stool-positive and stool-negative patients and led to helpful therapy in three of four patients with compatible symptoms who lacked a definitive diagnosis. Treatment with thiabendazole appeared to be superior to treatment with mebendazole.

Intraocular pressure following systemic administration of cannabinoids.

Various cannabinoids have been tested for activity compared to delta 9-THC in reducing intraocular pressure after intravenous administration in rabbits at 0.1 mg or 1 mg/animal. Comparison of l-delta 9-, delta 8-, 11-OH-delta 9- and 11-OH- delta 8-THC indicates that minor configurational changes have only a small influence on activity with regard to induction of a fall in intraocular pressure, although 11-OH-delta 8-THC has increased activity. 8 alpha-OH-, 8 alpha-diOH- and 8 beta-diOH-delta 9-THC have little or no activity but 8 beta-OH-delta 9-THC is as active as delta 9-THC indicating that the hydroxyl group in the beta-position does not influence activity. Modification of the C5H11 alkyl side chain (3'-OH-delta 9-THC) reduced activity to 20% relative to delta 9-THC. Cannabidiol (CBD), cannabichromene, cannabigerol and olivetol had no activity, but 10-OH-CBD had some activity at 2 mg/animal. Cannabinol (CBN) had about half the activity of delta 9-THC and activity was reduced further with 1'-OH-CBN, indicating that side chain modification reduced activity. Neither delta 9-THC, nor cannabigerol, had any effect on intraocular pressure or total outflow facility in the rhesus monkey, suggesting species differences in ocular responses to cannabinoids. Further studies on modification of these compounds is warranted in order to further delineate the structure-activity relationships.

Plasma angiotensin II, renin, renin-substrate and aldosterone concentrations in acute renal failure in man.

Plasma concentrations of angiotensin II, renin, renin-substrate and aldosterone were measured in cases of acute renal failure. Angiotensin II, and renin levels were abnormally high on at least one occasion in nearly all patients. Mean angiotensin II and renin levels were highest in the first ten days of the disease. There was a highly significant positive correlation between concurrent estimations of renin and angiotensin II. Renin-substrate was also frequently elevated, but the correlations with renin and angiotensin II were not statistically significant. Despite the frequently marked elevation of plasma angiotensin II, only 2 of 17 measurements of plasma aldosterone were abnormally high. There was no significant relationship between aldosterone and plasma concentrations of angiotensin II, renin, sodium or potassium. The data are discussed in relation to current hypotheses implicating renin and angiotensin in the pathogenesis of acute circulatory renal failure.