Inhibitory effects of L- and T-type calcium antagonists on contractions of human detrusor muscle.

The inhibitory and relaxant effects of the L-type calcium antagonists nifedipine, nimodipine, verapamil and diltiazem, and of the T-type calcium antagonist mibefradil, on contractions of isolated human detrusor muscle were investigated. The tissue was obtained from 10 patients undergoing cystectomy due to bladder cancer. Effects of the calcium antagonists at different concentrations on the concentration-response curves for carbachol were investigated. Furthermore, concentration-relaxation curves were performed using potassium-precontracted muscle strips. All L-type calcium antagonists suppressed the mean concentration-response curve of carbachol significantly at a concentration of 10(-6) M. Mibefradil up to 10(-5) M did not significantly suppress it. Nifedipine significantly reduced the carbachol-induced maximum contraction to 75% and 44%, verapamil to 75% and 67% of the appropriate control value at concentrations of 10(-7) and 10(-6) M, respectively. Diltiazem reduced it insignificantly to 96% and 71% at the above-mentioned concentrations. The concentration-relaxation experiments revealed following pD2-values and maximum relaxations of nifedipine, nimodipine, verapamil and diltiazem, respectively: 6.23, 6.37, 5.66, 5.81 and 85%, 83%, 82%, 90%. Maximum relaxations and pD2-values were not significantly different from each other. The lowest concentration, for which a significant effect compared to control in Student;s t-test was found, amounted to 10(-10) M, 10(-9) M, 10(-7) M, 10(-6.5) M and 10(-4) M for nimodipine, nifedipine, diltiazem, verapamil and mibefradil, respectively. L-type calcium antagonists are very potent relaxant agents of the human detrusor muscle in vitro.

Inhibitory effects of various L-type and T-type calcium antagonists on electrically generated, potassium-induced and carbachol-induced contractions of porcine detrusor muscle.

The inhibitory effects of different calcium antagonists on contractions of isolated porcine detrusor muscle were investigated. Suppression of the maximum potassium-induced contraction and electrically generated contractions by nifedipine, verapamil and diltiazem were investigated. Furthermore, concentration-response curves of carbachol after pretreatment with the L-type antagonists nifedipine, verapamil, diltiazem, nimodipine and the T-type antagonist mibefradil at different concentrations were performed. Nifedipine significantly reduced the potassium-induced maximum contraction to 89, 60, 21, 8 and 4% (10(-9)-10(-5) M). Verapamil and diltiazem significantly reduced it to 64, 30 and 5% (10(-7)-10(-5) M) or 79, 27, 7 and 1% (10(-7)-10(-4) M), respectively. Nifedipine, verapamil and diltiazem significantly reduced the electrically generated contraction to 55, 36, 34 and 25% (10(-7)-10(-4) M), 71, 32 and 2% (10(-6)-10(-4) M), 96, 78, 38 and 5% (10(-7)-10(-4) M), respectively. pD2 values of nifedipine, verapamil and diltiazem amounted to 7.07, 5.56 and 5.40 and differed significantly. After pretreatment with nifedipine at 10(-6) M, the concentration-response curve of carbachol was nearly suppressed. The effects of nimodipine, verapamil and diltiazem were smaller. Mibefradil caused only at 10(-5) M a significant reduction. All investigated L-type calcium antagonists were strong inhibitors of the examined contractions. Nifedipine showed the biggest inhibitory effect.

Low-power holmium:YAG laser urethrotomy for treatment of urethral strictures: functional outcome and quality of life.

PURPOSE: To evaluate the efficacy of endourethrotomy with the holmium:YAG laser as a minimally invasive treatment for urethral stricture. PATIENTS AND METHODS: Between January 2002 and January 2004, 32 male patients with symptomatic urethral strictures (8 bulbar, 9 penile, 9 combined) were treated with Ho:YAG-laser urethrotomy in our department. The stricture was iatrogenic in 60% (N = 18), inflammatory in 16.6% (N = 5), traumatic in 13.3% (N = 4), and idiopathic in 7% (N = 3). The stricture was incised under vision at the 12 o'clock location or the site of maximum scar tissue or narrowing in asymmetric strictures. Laser energy was set on 1200 to 1400 mJ with a frequency of 10 to 13 Hz. Postoperatively, drainage of the bladder was performed for 4 days using a 18F silicone catheter. Triamcinolone was instilled intraurethrally after removal of the catheter in all patients. Patients were followed up by mailed questionnaire, including International Prostate Symptom Score and quality of life. RESULTS: Retrograde endoscopic Ho:YAG laser urethrotomy could be performed in all 32 patients. Most patients (22; 68.7%) did not need any reintervention. Ten patients developed recurrent strictures that were treated by another laser urethrotomy in 4 patients (12.5%), while 6 patients (18.7%) needed open urethroplasty with buccal mucosa. Including 2 patients treated with repeat laser urethrotomy, 24 patients (75%) were considered successful after a mean follow-up of 27 months (range 13-38 months). No intraoperative complications were encountered, although in 5% of patients, a urinary-tract infection was diagnosed postoperatively. No gross hematuria occurred. CONCLUSIONS: The Ho:YAG laser urethrotomy is a safe and effective minimally invasive therapeutic modality for urethral stricture with results comparable to those of conventional urethrotomy. Further data from long-time follow-up are necessary to compare the success rate with that of conventional urethrotomy and urethroplasty. Nevertheless, the Ho:YAG laser urethrotomy might at least be an alternative to urethroplasty in patients with high comorbidity who are not suitable for open reconstruction.

Donor-site morbidity in buccal mucosa urethroplasty: lower lip or inner cheek?

OBJECTIVE: To evaluate donor-site complications of buccal mucosa urethroplasty and whether there is a difference in morbidity between harvesting the mucosa graft from the inner cheek or the lower lip. PATIENTS AND METHODS: Twenty-four consecutive patients with recurrent urethral strictures were treated with buccal mucosa urethroplasty in our department between September 2002 and April 2004. In 12 patients the graft was harvested from the lower lip or cheek and lower lip (group 1), and in 12 patients from the cheek (group 2). The mean (range) age of patients was 51 (26-66) years in group 1 and 53 (32-75) years in group 2. The mean (range) graft length was 6.2 (2-16) cm in group 1 and 5.7 (2-13) cm in group 2. All patients were followed up using a mailed questionnaire that asked about pain, numbness, difficulties in mouth opening or ingestion, and satisfaction, monthly for the first 3 months and then every 6 months. The mean (range) follow-up was 12.5 (6-23) months. RESULTS: There were no bleeding complications or disturbances in wound healing. All of the patients reported numbness in the area of the mental and buccal nerves, and graft-site tenderness after surgery. In group 1, the pain lasted for a mean (range) of 5.9 (0.5-22) months, compared to 1 (0.1-7) months in group 2 (P = 0.022). Perioral numbness lasted for a mean (range) of 10.3 (0.5-23) months in group 1 and 0.85 (0.1-3) months (P = 0.0027) in group 2. There were no statistically significant differences in problems with mouth opening or food intake between the two groups, but the patients in group 1 seemed to be less satisfied (6/12 patients satisfied) than those in group 2 (11/12 patients satisfied). CONCLUSIONS: Buccal mucosa graft harvesting from the lower lip and the inner cheek are both feasible, but harvesting from the lower lip resulted in a significantly greater long-term morbidity, which resulted in a lower proportion of satisfied patients. This seems to be due to a long-lasting neuropathy of the mental nerve. We therefore have changed our technique entirely from lower lip to inner cheek graft harvesting, whenever possible.

5-year-follow-up of patients with clinically insignificant residual fragments after extracorporeal shockwave lithotripsy.

OBJECTIVES: After SWL treatment, many patients have residual fragments in the kidney or ureter. Fragments 2 stones episodes. These patients and their referring urologist received follow-up questionnaires which contained questions about stone clearance, late complications, auxillary measures and dietary or drug metaphylaxis. RESULTS: Most residual stone fragments were located within the lower calyx (17%) and the renal pyelon (14%). Stone analysis was available in 142 patients with CIRF and revealed calciumoxalate calculi in 93.6% of the cases. In 78.6%, CIRF cleared spontaneously within few weeks and did not recur within 5 years. However, residual stones led to stone recurrence and need of re-treatment in 21.4%. Renal pyelon (23%) and calices showed comparable growth of former CIRF (lower calices 26.5%, middle calices 27%, upper calices 26%). Only 48% of the patients with recurrent stone formation followed dietary metaphylaxis. However, a significant correlation between a general or specific metaphylaxis and stone growth of CIRF could not be demonstrated. CONCLUSIONS: Most of the CIRF after SWL pass spontaneously without any complications. But considering that one fifth of the patients developed new stones at the side of residual fragments, it is obvious that close follow-up is required. Although we could not demonstrate a relation between metaphylaxis and stone re-growth, it is conceivable that adequate metaphylaxis can reduce stone recurrences.

Carboxyamido-triazole (CAI), a signal transduction inhibitor induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2.

Pro- and anti-apoptotic factors and intracellular signaling pathways are targets for therapeutic development of anticancer agents. Carboxyamido-triazole (CAI) is an inhibitor of transmembrane calcium influx and intracellular calcium-requiring signal transduction pathways. The present study investigates the effects of CAI on human transitional cancer cell (TCC) viability and apoptosis, and evaluates whether apoptotic resistance may be overcome pharmacologically. Both well-differentiated (RT4, RT112/grade 1) and poorly-differentiated (T24/grade 3; SUP/grade 4) human TCC lines were shown to express Fas. Upon exposure to agonistic monoclonal Fas antibody, only well-differentiated TCC lines underwent apoptotic cell death. CAI exposure reduced cell viability and caused an at least additive anti-apoptotic effect in combination with the Fas antibody in the Fas-insensitive TCC lines. Under the same conditions under which CAI treatment augmented Fas-mediated apoptosis, it was shown to reduce intracellular bcl-2 quantity. This response to CAI indicates that apoptotic cell death is enhanced by the reduction of bcl-2 protein expression. We suggest that the antitumor effect of CAI is at least partially based on restoring a pathway of apoptosis. It may cause transformation of cell homeostasis that leads to the alteration of apoptotic mechanisms, thus allowing highly malignant tumor cells to re-enter the physiological course of cell elimination.