The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.

We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.

Objective To determine the impact of post‐operative education about bladder cancer and topical immunotherapy on the physical, psychological and social well‐being of patients with superficial bladder cancer. Patients and methods Eighty‐five patients (mean age 59 years, range 26–85, 64 men and 21 women) receiving topical immunotherapy were questioned during the initial cycle of treatment and during maintenance therapy with bacille Calmette‐Guérin (BCG). Patients completed a questionnaire on their quality of life when they commenced treatment and twice more during maintenance therapy. Results Psychological distress and physical symptoms were intense when the diagnosis of bladder cancer was revealed to the patients, despite the knowledge that this cancer is usually curable. The overall quality of life, condition of health and sexual activity were mostly only moderate, were poor during initial therapy and better during 3‐monthly maintenance therapy. Conclusion In general, the quality of life of these patients is characterized by the disruption of their lifestyle and marked by change in their circumstances. It is the responsibility of the urologist to take the necessary time to educate, comfort and motivate such patients with superficial bladder cancer.

Fluorescence-optical measurements of the intracellular chloride concentration facilitate identification of chloride movements across the cell membrane of living cells. The two main dyes used for this purpose are 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ) and 6-methoxy-quinolyl acetoethyl ester (MQAE). The use of both substances is impaired by their poor membrane permeability and therefore limited loading of the cells to be studied. Here we report the use of 6-methoxy-N-ethylquinolinium iodide (MEQ), a chloride-sensitive dye for which a membrane-permeable form is easily prepared. This makes the loading procedure as easy as with the acetoxymethyl (AM) forms of other dyes for sensing intracellular ions. In addition, the original method, which described absolute concentration measurements of chloride in the cytosol, was modified in so far as only relative measurements were made. This avoids the known limitations of single wavelength excitation and emission dyes with respect to exact concentration measurements. Moreover, to enhance the signal-to-noise ratio the driving force for chloride was considerably increased by changing the original direction of the anion flux in the cells under investigation. We verified the method by using fibroblasts and activating ICln, a putative chloride channel cloned from epithelial cells and of paramount importance in the regulatory volume decrease in these cells. In the presence of SCN- the MEQ quench measured in NIH 3T3 fibroblasts is dramatically enhanced in hypotonically challenged cells compared with cells under isotonic conditions. Antisense oligodeoxynucleotides sensing ICln considerably impeded the swelling-induced chloride current (ICl) in NIH 3T3 fibroblasts. Accordingly, the chloride movement measured by the SCN- quench of the MEQ signal was significantly reduced. Similar results can be obtained in the presence of 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) or 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), two known blockers of chloride transport in the plasma membrane of a variety of cells. In conclusion, fluroscence-optical measurements using MEQ as the chloride-sensitive dye provide a reliable and easy-to-use method for measuring changes of the chloride flux across the cell membrane of living cells.

The present study assesses the clinical outcome of microsurgical subinguinal varicocelectomy in infertile men, especially with regard to sperm count, motility and fertility. Between June 1990 and October 1998, 272 patients had subinguinal microsurgical varicocelectomy operations for clinical varicoceles, and their long-term results were assessed. In nearly all the patients there was a significant improvement in sperm count and sperm motility after 3 and 6 months. Very few complications arose from this procedure. We concluded that microsurgical subinguinal varicocelectomy is an effective treatment for clinical varicoceles in infertile men. The significant improvement in the quality of spermatozoa, the low complication rates and the remarkably high pregnancy rates make this a valuable alternative to in vitro reproduction techniques.