Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.     

Effects of rifampicin on the peripheral turnover kinetics of thyroid hormones in mice and in men

The induction of mixed function hepatic oxygenases by rifampicin is known to increase the metabolic clearance rate (MCR) of T4. By performing T3 and rT3 kinetics we have shown that rifampicin also increases the MCR of T3 and rT3. Using the fall of serum T4 during TSH suppression as an indirect marker of the production rate (PR) of T4, we have demonstrated that there was no major change in monodeiodination nor any shift to either 5'- or 5-monodeiodination. Rifampicin stimulates in mice the mixed function hepatic oxygenases. However, we were unable to increase hepatic deiodinase activity (deiodinase type I) in this species. It is therefore possible that the increased MCR of T4 in man is not mediated by an increased conversion rate either. As mixed function hepatic oxygenases are known to increase hepatic conjugation it is suggested that rifampicin increases the biliary excretion of iodothyronine conjugates.     

Effects on ingestive behavior in rats of the alpha 1-adrenoceptor agonist cirazoline.

Microinjections of various alpha 1-adrenoceptor agonists including phenylephrine and phenylpropanolamine into the paravenricular hypothalamic nucleus (PVN) suppress food intake in rats, suggesting that this receptor type might act in opposition to previously identified facilatory PVN alpha 2-adrenoceptors in the modulation of feeding. In the present experiments, we examine the effects on food and water intake of intra-PVN as well as systemic injection of cirazoline, a highly potent alpha 1-adrenoceptor agonist. In Experiment 1, intra-PVN microinjection of cirazoline (0, 3, 6, 12 and 24 nmol) suppressed food intake (ED50 = 23.4 nmol) without significant effects on water intake. In Experiment 2, systemic injection of cirazoline (0, 0.05, 0.1, 0.2, 0.4 mg/kg) also markedly suppressed food intake (ED50 = 0.05 mg/kg i.p.), with a less potent action on water intake (ED50 = 0.22 mg/kg i.p.). The results of this study as well as our previous investigations strongly support the notion that alpha 1-adrenoceptors within rat PVN act to reliably suppress food intake.     

Electrosurgery in restorative Dentistry: 2. Clinical applications.

Electrosurgery techniques have been used in dentistry as an aid to soft tissue management for nearly 60 years. However, it was not until the late 1960s that the principles of electrosurgery were understood and improved equipment became available. Part 1 of the two-part series covered the theory behind using this technique. Part 2 will now discusses the clinical applications.     

Overnight and basal metabolic rates in men and women

The FAO/WHO/UNU recommendations for energy requirements assume that the energy cost of sleep is equal to the basal metabolic rate (BMR). We have tested the validity of this assumption by analysing overnight and BMR measurements made by whole-body indirect calorimetry. Data from 80 healthy subjects measured on a total of 246 occasions have been used. In a subgroup of 40 normal lean subjects the mean ratio of overnight metabolic rate (Overnight MR): BMR was 0.95 (range 0.85 - 1.02, s.d. 0.04). The mean ratio of lowest sleeping metabolic rate (Lowest SMR): BMR was 0.88 (range 0.83 - 0.96, s.d. 0.04). Ratios of Overnight MR: BMR were not significantly affected by different levels of exercise on the preceding day. This ratio was significantly higher for subjects who were obese, late pregnant or attached to ECG electrodes. With the exception of the late pregnant subjects these groups had the same Lowest SMR:BMR ratios as the normal lean subjects, indicating that the higher Overnight MR was caused by disturbed sleep. The data suggest that the use of BMR to estimate overnight energy expenditure would introduce an average overestimate of approximately 5 per cent during the actual hours of sleep, but that when applied over 24 h the error becomes negligible.