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Biomedical subjects

F M Rasche

Publications and source records attributed to F M Rasche.

6 recordsLinked to original sources

High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up.

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.

Adult↗

Dose adjustment of ciprofloxacin in renal failure: reduce the dose or prolong the administration interval?

BACKGROUND: Dose adjustments of antimicrobial drugs are necessary in renal failure. One method of dose adjustment is to reduce the dose and the other is to prolong the administration interval in proportion to the reduced drug clearance. Pharmacokinetically, both methods involve an identical drug exposure but pharmacodynamically there may be differences. It is not known which dose adjustment method is preferable in patients with renal failure. METHODS: We performed simulations using a published mechanism-based pharmacokinetic/ pharmacodynamic model of ciprofloxacin effects on growth and death of Escherichia coli bacteria. Ciprofloxacin 500 mg every 12 hrs was selected as the standard dose. In renal failure either the dose was reduced (250 mg every 12 hrs) or the administration interval was prolonged (500 mg every 24 hrs) in proportion to the reduced ciprofloxacin clearance. Simulations were done with use of a commercial software package. RESULTS: In normal renal function, using the standard dose, bacterial eradication was predicted on day 3. In renal failure, bacterial eradication was predicted on day 3 when using the interval prolongation scheme but only on day 6 when using the dose reduction scheme. The relationship between the efficacies of these 3 dosage schemes could have been predicted by AUC above MIC and AUIC, but not by AUC/MIC or time above MIC. CONCLUSION: Prolongation of the administration interval may be the preferable dose adjustment method in renal failure with ciprofloxacin. We hypothesize that these results may be transferable to other so-called dose-dependent antimicrobial drugs.

Anti-Infective Agents↗

Pharmacokinetics and pharmacodynamics of lispro-insulin in hemodialysis patients with diabetes mellitus.

OBJECTIVE: Lispro-insulin, after subcutaneous injection in patients with normal renal function, is absorbed faster and has a faster onset of action when compared to regular insulin. However, the pharmacokinetics and pharmacodynamics of lispro-insulin in renal failure have not yet been investigated. PATIENTS AND METHODS: Eight patients with diabetes mellitus on long-term hemodialysis received an individualized dose of regular insulin or lispro-insulin in a crossover design. Blood glucose and insulin concentrations were measured before and after the subcutaneous insulin injections. RESULTS: Plasma insulin concentrations increased faster (time of maximum concentration tmax 20 vs 40 minutes, p = 0.01) and were higher (standardized maximum concentration Cmax/D 13.6 vs 6.1 microU/ml/U, p = 0.01) after lispro-insulin compared to regular insulin. The area under the curve, clearance and parameters of the hypoglycemic action for the 2 insulin products did not differ significantly, but there was a trend to minimum blood glucose level (time of the blood glucose minimum, Gtmin) to occur earlier with lispro-insulin (120 vs 210 minutes, p > 0.05). Differences in elimination half-life and volume of distribution were explained by flip-flop pharmacokinetics in the case of regular insulin. CONCLUSIONS: In hemodialysis patients with diabetes mellitus, lispro-insulin is absorbed faster than regular insulin. Differences in the effects of lispro-and regular insulin can be explained by the differences in pharmacokinetics.

Area Under Curve↗

Tonsillectomy does not prevent a progressive course in IgA nephropathy.

BACKGROUND: IgA nephropathy, or Berger's disease, is a primary mesangioproliferative glomerulonephritis, usually with a favourable prognosis. PATIENTS AND METHODS: To investigate the effect of tonsillectomy we conducted a retrospective investigation on renal outcome in 55 patients with IgA nephropathy in an outpatient university clinic between 1968 and 1994. Established risk factors for progressive IgA nephropathy were equally distributed in 16 patients subjected to tonsillectomy and in 39 patients without tonsillectomy. Renal survival and impact of risk factors were estimated by Kaplan-Meier analysis and Cox regression model. RESULTS: Seen in terms of the bivariate Kaplan-Meier analysis the probability of renal survival 10 years after biopsy was 0.37 for the 16 patients with tonsillectomy and 0.63 for the 39 patients without tonsillectomy (log-rank test p = 0.49, not significant). In the multivariate Cox regression model with 6 independent clinical covariates, initially high serum creatinine concentration had the strongest impact on renal outcome (p = 0.002), with a hazard ratio of 8.9 (95% CI: 2.3-35.0). Tonsillectomy had no significant influence in the Cox model (p = 0.37), displaying a hazard ratio of 1.7 (95% CI: 0.5-5.7). CONCLUSION: In conclusion, tonsillectomy does not reduce the risk of developing renal failure or prevent a progressive course of IgA nephropathy.

Adult↗