SummaryDiogenes is a Pan-European, randomized, controlled dietary intervention study investigating the effects of dietary protein and glycaemic index on weight (re)gain, metabolic and cardiovascular risk factors in obese and overweight families in eight European centres. The article is methodological in character, and the presentation of 'results' will be limited to baseline characteristics of the study populations included. A total of 891 families with at least one overweight/obese parent underwent screening. The parents started an initial 8-week low-calorie diet and families with minimum one parent attaining a weight loss of Ն8%, were randomized to one of five energy ad libitum, low-fat (25-30 E%) diets for 6 or 12 months: low protein/low glycaemic index, low protein/high glycaemic index, high protein/ low glycaemic index, high protein/high glycaemic index or control (national dietary guidelines). At two centres the families were provided dietary instruction plus free foods for 6 months followed by 6-month dietary instruction only. At the remaining six centres the families received dietary instruction only for 6 months. The median weight loss during the low-calorie diet was 10.3 kg (inter-quartile range: 8.7-12.8 kg, n = 775). A total of 773 adults and 784 children were randomized to the 6-month weight (re)gain prevention phase. Despite major cultural and dietary regional differences in Europe, interventions addressing effects of dietary factors are feasible with a reasonable attrition.

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The pharmacokinetics of verapamil was studied in patients with end-stage chronic renal failure and in normal subjects after i.v. injection of 3 mg and a single oral dose of 80 mg. Plasma levels of verapamil and its active metabolite norverapamil were measured by HPLC. After i.v. injection, the terminal phase half-life and total plasma clearance of verapamil in both groups were similar. Haemodialysis did not change the time course of plasma verapamil levels after i.v. administration. After a single oral dose, the plasma levels of verapamil and norverapamil in both groups of subjects were similar. Subsequently, normal volunteers and patients with renal failure were treated for 5 days with oral verapamil 80 mg t.d.s. There was no difference between the 2 groups of subjects in the trough and peak levels of verapamil or of norverapamil. Intravenous and oral administration of the calcium channel blocking agent had similar effects on blood pressure, heart rate and the PR-interval in the electrocardiogram in both groups. The study demonstrated that the disposition of verapamil was similar in normal subjects and in patients with renal failure.

The acute and long-term effects of the beta 1-adrenoceptor blocking agent metoprolol on blood pressure and maximal aerobic power (Wmax) were studied in 10 healthy subjects. Progressive maximal bicycle ergometer tests were performed after intravenous administration of placebo and metoprolol (0.15 mg . kg-1 and 0.30 mg . kg-1), and at the end of 4-week treatment periods with placebo, conventional metoprolol (C-M) and slow-release metoprolol (SR-M). The reduction in maximal exercise heart rate (HRmax) was correlated with the log plasma metoprolol concentration. Despite a reduction in HRmax of 23 beats/min after 0.15 mg . kg-1 metoprolol, Wmax was unaffected. After 0.30 mg . kg-1 HRmax was reduced by 40 beats/min and Wmax by 5.0%. During chronic treatment, the reductions in HRmax and Wmax were 48 beats/min and 7.5% (C-M) and 45 beats/min and 6.9% (SR-M), respectively. Resting systolic blood pressure was not changed after acute administration of metoprolol but it was reduced during chronic beta-blocker treatment. Resting diastolic blood pressure was not affected after acute or chronic treatment. Exercise systolic blood pressure remained unchanged after 0.15 mg . kg-1 metoprolol i.v. The fall in exercise systolic pressure after 0.30 mg . kg-1 metoprolol i.v. (18 +/- 5 mmHg) was significantly smaller than that during chronic treatment (30 +/- 6 mmHg C-M; 30 +/- 6 mmHg, SR-M). During chronic metoprolol treatment a certain % HRmax corresponded to a higher % Wmax than during placebo treatment, but the shift appeared to be of minor practical importance.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of antituberculosis drugs on the plasma level of verapamil was studied after its oral and intravenous administration. Six patients who had been treated for at least 6 months with a combination of rifampicin, ethambutol and isoniazid received a single oral dose of 40 mg verapamil. As compared to untreated subjects, the antituberculosis drugs greatly reduced the bioavailability of the calcium antagonist. Studies in patients in whom treatment with ethambutol and isoniazid had been discontinued revealed that the effect was due to rifampicin. The drugs for tuberculosis had no influence on the plasma level of verapamil when it was given intravenously. The findings can be explained by the induction of verapamil metabolizing liver enzymes in patients treated with rifampicin.