Aims of the study: The aim of this double-blind, randomised, prospective, multicentre trial was to evaluate the ecacy of propiverine in patients suering from detrusor hyperre¯exia caused by spinal cord injury in comparison to placebo. Study design: The treatment period of 14 days comprised visits at baseline (V1) and after 14 days treatment (V2). Fifteen mg propiverine t.i.d. or placebo t.i.d. were administered as medication. The following ecacy parameters were adopted: the urodynamic parameters maximal cystometric bladder capacity, bladder volume on onset of the ®rst as well as duration and amplitude of the maximum detrusor contraction, bladder compliance and residual urine, and subjective assessment of ecacy by physicians. For the evaluation of the safety of propiverine the incidence rate of adverse events by directly questioning as well as laboratory parameters were investigated. For biometrical evaluation t-test for independent groups was applied. Results: One hundred and thirteen patients were investigated. The maximal cystometric bladder capacity increased signi®cantly in the propiverine group, on average by 104 ml (V1: 262+132 ml. V2: 366+143 ml, P50.001). The changes in bladder capacity during the ®rst contraction and the maximum detrusor contraction in the verum group were both statistically signi®cant. The bladder compliance documented a more pronounced increase under propiverine in comparison to placebo. Residual urine increased by 37+71 ml in the propiverine group, signi®cantly more than in the placebo group (P=0.01). Sixty-three per cent of the patients expressed subjectively an improvement under propiverine in comparison with 23% of the placebo group. Expected anticholinergic adverse events occurred: dryness of the mouth (37% in the verum and 8% in the placebo group), accommodation disorders (28% and 2% respectively). Nausea, constipation, headache, dizziness, tiredness and palpitations were reported in almost comparable incidence rates between 3 and 13% in both treatment groups.Eight drop-outs were registered in the propiverine group (®ve due to adverse events) and three in the placebo group (one due to adverse events). The laboratory parameters revealed no changes. Conclusion: Propiverine proved its ecacy in detrusor hyperre¯exia with regard to the urodynamic parameters of the maximal cystometric bladder capacity and detrusor contractility. Anticholinergic adverse events such as dryness of the mouth and accommodation disorders were considered being tolerable. The increase in residual urine re¯ects the therapeutically desired eect of detrusor relaxation because the majority of patients normally practise intermittent catheterisation for bladder emptying.

Despite their traditional popularity in many European countries and their increasing use as dietary supplements in the United States, the role of phytotherapeutic agents in treating lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) is continuously debated. If strict criteria of evidence-based medicine are applied, the available data have not yet provided clear evidence of efficacy for most phytotherapeutic preparations. Different extraction procedures used by the different manufacturers, the variations of the raw products (plants) used and the fact that the potentially active component(s) of the final product and its (their) mechanism(s) of action are still under investigation make comparisons between the various products impossible. Thus, one product might have clinical efficacy while another might not. Therefore, as long as the composition of the final product of the various preparations is not proven to be identical, each manufacturer's preparation must be evaluated separately, using the gold standard of placebo-controlled studies according to accepted guidelines. Conclusions of meta-analyses that include products from different plants undergoing different extraction procedures and that are used in different dosages may be misleading. A number of short-term randomised trials and some metaanalyses in the recent literature suggest clinical efficacy and good tolerability for some preparations, mainly extracts from Serenoa repens and also Pygeum africanum, products with high concentrations of beta-sitosterol, and pumpkin seeds. It is also claimed that the efficacy of an extract from S. repens is comparable to that of finasteride and alpha-blockers. However, as has been demanded by the International Consultations on BPH, additional randomised, placebo-controlled trials are needed before phytotherapeutic agents can be recommended as an effective option in treating LUTS and BPH.

No abstract

Glutathione S-transferase (GST, E.C. 2.5.1.18) comprises a family of isoenzymes that play a key role in the detoxification of such exogenous substrates as xenobiotics, environmental substances, and carcinogenic compounds. At least five mammalian GST gene families have been identified to be polymorphic, and mutations or deletions of these genes contribute to the predisposition for several diseases, including cancer. The gene cluster of GSTM1–GSTM5 has been reported to be localized on chromosome 1p and spans a length of nearly 100 kb. One mutation of the GSTM3 gene generates a recognition site for the transcription factor yin yang 1. As a result of this mutation, the expression of GSTM3 can be influenced. The mutated GSTM3 gene has been reported to be involved in increased susceptibility for the development of cancer, but no information is available concerning its role in bladder cancer. We have identified patients with a heterozygous GSTM3 geno- type who carry a significantly increased risk for the development of bladder cancer. Here we report that the mutation of intron 6 of GSTM3 increases the risk for bladder cancer (odds ratio: 2.31; 95% confidence interval [CI], 1.79–2.82). We developed a procedure to identify heterozygous or homozygous carriers of the GSTM1 alleles. Heterozygous carriers of the GSTM1 null genotype have a significantly elevated risk of developing bladder cancer. We calculated an odds ratio of 3.54 (95% CI, 2.99–4.11) for this genotype. These observations lead to the assumption that the lack of detoxification by glutathione conjugation predispose to bladder cancer when at least one of two alleles is affected. Furthermore, individuals presenting the homozygous wild type of GSTM1 and GSTM3 are significantly protected against bladder cancer.