Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates.

Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were obtained with iterative two-stage Bayesian fitting (MW\PHARM 3.30) as with a non-parametric maximization algorithm (NPEM2). The effect of various covariates on drug disposition was investigated retrospectively using multiple regression analysis. Predictive power for Kel increases with rising gestational age. For neonates 28.5 weeks and 30.9 weeks (r2 = 0.482), with gestational age, postnatal age, and Apgar score at 5 minutes being predictors. A very strong correlation existed between volume of distribution and weight (r2 = 0.83). Volume as a function of weight could be described with low predictivity by gestational age and to a lesser degree by Apgar score at 5 minutes (r2 = 0.298). The developed models need appropriate prospective clinical validation.

Bilateral asynchronous Sertoli cell tumor in a boy with the Peutz-Jeghers syndrome.

A rare type of Sertoli cell tumor with features of a large cell calcifying Sertoli cell tumor and a sex cord tumor with annular tubules developed in a boy with the Peutz-Jeghers syndrome. A similar tumor had been removed from the contralateral testicle 9 years previously. The clinical and pathological findings in our case are compared to 3 similar cases reported in the literature.

Fluorescence in situ hybridization analysis of 8p allelic loss and chromosome 8 instability in human prostate cancer.

Cytogenetic and molecular biological studies have demonstrated deletion of sequences that map to the short arm of chromosome 8 (8p) in tumors from several organ systems, including sequences that map within or near 8p22 in human prostate tumors. Recent studies in our laboratory have suggested that deletion of sequences on 8p may be concurrent with alterations in dosage for chromosome 8. In order to further investigate this finding, the present study has applied fluorescence in situ hybridization (FISH) techniques to determine the status of chromosome 8 in prostate tumors that have undergone deletion of sequences at 8p22. Dosage of 8p22 sequences was assayed utilizing unique sequence cosmid DNA probes by FISH and confirmed by amplification of microsatellite sequences by polymerase chain reaction (PCR). Chromosome 8 dosage was assayed by FISH utilizing both unique sequence cosmid probe DNA (specific to the 8q13.1-q13.3 chromosomal region) and pericentromeric probe DNA. FISH analysis of 10 specimens of normal or benign prostatic hyperplasia tissues paired with 9 tumor and one prostatic intraepithelial neoplasia tissues from the same patients for dosage at 8p, 8cen, and 8q, and PCR analysis for dosage at 8p, demonstrated that (a) FISH provided a more precise means of evaluating allelic loss than PCR in prostate tissue; (b) 8p22 sequence losses occurred frequently in prostate tumors; (c) 8p22 sequence losses were most often detected in the absence of 8cen or 8q sequence dosage alterations, although they were sometimes accompanied by gain or loss of 8cen or 8q sequences; and (d) the pattern of 8p22 sequence losses was most often widespread rather than focal. This study is the first to describe FISH analysis of interphase nuclei within tissue sections using cosmid probe DNAs.

Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine.

The aim of this study was to investigate the new synthetic HMG-CoA reductase inhibitor, fluvastatin, for efficacy, safety and tolerability in comparison to cholestyramine. One hundred fifty one primary hypercholesterolaemic patients participated in this double-blind, parallel-group, randomized study. During the first 12 weeks of the study, fluvastatin (20 mg and 40 mg daily) was compared with cholestyramine (16 g per day). In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed. Fluvastatin (40 mg) reduced LDL cholesterol by 28.0%, triglycerides by 10.5% and increased HDL cholesterol by 3.7%. Cholestyramine (16 g) reduced LDL cholesterol by 35.0%, but raised triglycerides and HDL cholesterol by 12.3% (p < 0.01) and 3.7% respectively. The combination of fluvastatin 20 mg and cholestyramine (4 g, 8 g and 16 g) induced the following reductions in LDL cholesterol: 30.4%, 35.6% and 46.6% respectively. There was no significant change in triglycerides in either group although HDL cholesterol was raised by 4.9%, 8.3% and 7.2% respectively. One patient treated with fluvastatin and two treated with cholestyramine were withdrawn from the study due to elevation of liver transaminases. The most frequent subjective adverse effects in both treatment groups were mild, transient gastrointestinal complaints. Thus, fluvastatin was effective as a lipid-lowering agent; the effect was further enhanced when fluvastatin was combined with cholestyramine.

Complications of intravesical bacillus Calmette-Guerin: a case report.

Bacillus Calmette-Guerin (BCG) is the most effective agent currently available to treat superficial bladder cancer. However, this form of therapy is not without potential serious or fatal complications. In addition to the potentially toxic systemic side effects attributed to hematogenous absorption of the bacillus, direct upper tract seeding may occur in patients with vesicoureteral reflux. We report on a patient treated with intravesical BCG for bladder cancer in whom unilateral necrotizing granulomatous pyelonephritis developed. Although severe, this complication is rare and we conclude that reflux is not a contraindication for intravesical BCG therapy.

A new technique for ureteral stent placement during pregnancy using endoluminal ultrasound.

Endoluminal sonography using the IVUS is a minimally invasive procedure performed using a flexible 6.2F catheter with a 20 megahertz transducer that can easily be passed endoscopically to image the urethra, bladder, ureter and renal pelvis. In the current study, a woman patient in her third trimester of pregnancy with a renal pelvic stone and persistent colic was safely treated with placement of an indwelling ureteral stent. Because it is minimally invasive and does not require the use of roentgenograms, we believe the IVUS will be a useful tool to assist with the management of ureteral colic in patients who are pregnant in whom intervention is required.