Theodor Klotz

The prevalence of Peyronie's disease: results of a large survey

Objectives To determine the prevalence of Peyronies disease, a localized connective tissue disorder of the penile tunica albuginea, the symptoms of which include palpable plaque, painful erections and curvature of the penis, in a large sample of men in Germany.

Distribution of nitric oxide synthase implies a regulation of circulation, smooth muscle tone, and secretory function in the human prostate by nitric oxide

Nitric oxide (NO) is suggested as a mediator involved in the regulation of smooth muscle tone, blood flow, and secretory function of the genitourinary tract and originates from different NO synthase (NOS) isoforms located in endothelial, neuronal, and epithelial structures. The aim of the present study was to determine the location of endothelial and neuronal NOS in the human prostate.

Localization of constitutive nitric oxide synthase isoforms and the nitric oxide target enzyme soluble guanylyl cyclase in the human bladder

PURPOSE Nitric oxide is a free radical gas synthesized from L-arginine by a family of isoenzymes called nitric oxide synthase that has an important role in smooth muscle relaxation. L-arginine, the substrate for nitric oxide synthase, may be beneficial under pathophysiological conditions in the bladder, as in interstitial cystitis. We determined the localization of nitric oxide synthase and the target enzyme of NO, soluble guanylyl cyclase, in the human bladder. MATERIALS AND METHODS Benign bladder tissues were obtained from 18 patients with localized superficial bladder tumors undergoing transurethral bladder resection. Histochemical nicotinamide adenine dinucleotide phosphate-diaphorase staining, nitric oxide synthase immunohistochemical testing and soluble guanylyl cyclase immunoreactivity studies were performed in all benign tissue specimens. RESULTS A different pattern of nitric oxide synthase expression was confirmed by nicotinamide adenine dinucleotide phosphate-diaphorase staining and immunohistochemical testing for endothelial and neuronal nitric oxide synthase. In addition to endothelial nitric oxide synthase expression, detrusor smooth muscle was recognized as an important location of endothelial nitric oxide synthase, while the urothelium had only small endothelial nitric oxide synthase positive cell clusters. Neuronal nitric oxide synthase expression was only found in nitrinergic fibers of the submucosal surface and between muscle cells. Detrusor and vascular smooth muscle as well as interstitial cells, nerve fibers and transitional epithelium were recognized as targets of nitric oxide, as shown by soluble guanylyl cyclase expression. CONCLUSIONS The distribution of constitutive nitric oxide synthase isoforms and soluble guanylyl cyclase provides evidence of nitric oxide-cyclic guanosine monophosphate mediated regulation of detrusor smooth muscle relaxation, neurotransmission and blood flow. Furthermore, the urothelium may also be a target of nitric oxide.

Effectiveness of Oral L-Arginine in First-Line Treatment of Erectile Dysfunction in a Controlled Crossover Study

Background and Aims: Relaxation of cavernous smooth muscle is a parasympathetic and non-adrenergic, non-cholinergic mediated process which requires nitric oxide (NO). NO is synthesized from L-arginine by NO synthase (NOS). Some studies report good clinical results under oral L-arginine medication in the treatment of erectile dysfunction. We examined the effectiveness and safety of L-arginine in the treatment of mixed-type impotence. Methods: 32 patients (mean age 51.6 years) with mixed-type impotence diagnosed according to the results of sexual history and urological examination were enrolled in a randomized, placebo-controlled, crossover comparison of an oral placebo with 3 × 500 mg L-arginine/day. A validated questionnaire (KEED) was used to define the grade of impotence with a score. The treatment consisted of two 17-day courses (50 tablets). After a 7-day washout period the patients who initially received the placebo for 17 days were switched to L-arginine and vice versa. We assessed the efficacy with the validated questionnaire at the end of each drug period. Results: 30 patients (94%) completed the whole treatment schedule. Five (17%) patients reported a significant improvement in erectile function at the end of the L-arginine phase and 6 (20%) patients after the placebo period. 17 (56%) patients showed little improvement with L-arginine and 13 (43%) with placebo. In 8 patients (27%) of the verum group there was either no change in the ED score or even a slight worsening. No statistical difference in the impotence scores were found. No drug-related adverse effects occurred with L-arginine treatment. Conclusion: Oral L-arginine 3 × 500 mg/day is not better than placebo as a first-line treatment for mixed-type impotence.

Evidence for the involvement of endothelial nitric oxide synthase from smooth muscle cells in the erectile function of the human corpus cavernosum

Abstract Nitric oxide (NO) is an important mediator in the relaxation of cavernosal smooth muscle. The present study examines the existence and location of the constitutive isoform eNOS (endothelial NO synthase) accompanying the already substantiated neurogenic NOS (nNOS) in the human corpus cavernosum of men with and without erectile dysfunction. Activities of NOS enzymes were examined in specimens of 11 potent and nine long-term impotent patients by means of light and electron microscopy using NADPH-diaphorase staining and immunohistochemical eNOS-specific, smooth muscle actin-specific and nNOS-specific markers. Cavernosal smooth muscle shows a distinct expression of eNOS. In contrast to the weaker expression of eNOS and nitrinergic innervation found in larger veins, the small intracavernosal helicine arteries express large quantities of eNOS and possess a dense nitrinergic innervation. Long-term impotent patients display a broad heterogeneity in eNOS expression and nitrinergic innervation while no overall correlation between NOS expression and erectile function was observed. The expression of eNOS indicates eNOS as a main source of NO alongside nNOS. The differentiated localization of eNOS supports at least a role of this isoform in vascular regulation.

Nitric Oxide Based Influence of Nitrates on Micturition in Patients with Benign Prostatic Hyperplasia

AbstractBackground: Nitric oxide (NO) is involved in the physiologic regulation of smooth muscle relaxation in the prostate. Organic nitrates act as NO donors. In this prospective open study we prove the influence of orally given nitrates on micturition. Methods: Thirty-two patients underwent a urological medical check-up prior to starting nitrate medication for cardiovascular disease. We examined peak flow rates, residual urine, IPS-score, PSA level and prostate volume. Exact inclusion and exclusion criteria were defined. Fifteen patients suffered from obstructive symptoms, 17 patients reported no subjective micturition problems. Urological re-evaluation was performed two weeks and three months after nitrate medication. Results: A significant improvement of peak urinary flow rates (+3.1 ml/s; p<0.05), IPS score and significant decrease of residual urine volume (-22 ml; p<0.05) were found in the symptomatic patients. No significant changes of micturition parameters were found in asymptomatic patients. PSA levels and prostate volumes did not change in either groups. Conclusions: Organic nitrates influence micturition parameters in patients with obstructive benign prostatic hyperplasia. This might be explained by the known mechanism of NO donation (smooth muscle relaxation) of nitrates. More functional controlled studies are necessary to describe the grade of influence of nitrates on the prostate. Concomitant oral medication with nitrates must be considered as a relevant bias factor on BPH in future clinical studies.

Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05).

To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine‐kinase inhibitor, compared with chemotherapy alone as first‐line treatment in advanced urothelial cancer.

MEASUREMENT OF VAGINAL AND MINOR LABIAL OXYGEN TENSION FOR THE EVALUATION OF FEMALE SEXUAL FUNCTION

PURPOSE Female sexual dysfunction is a new, rapidly expanding area of sexual medicine. Female sexual arousal disorder may, in part, be due to decreased pelvic blood flow. Therefore, we developed a simple noninvasive reproducible technique to measure vaginal and minor labial blood flow. MATERIALS AND METHODS The study included 12 healthy young women able to have orgasm through self-stimulation. Observations at orgasm were recorded in the 12 subjects after self-stimulation. Measurements were obtained intravaginally and on the minor labia using a modified Clark oxygen electrode to obtain partial oxygen pressure (pO(2)). RESULTS Mean basal vaginal value was 3.8 +/- 0.9 mm Hg and mean basal pO(2) on the minor labia was 18.3 +/- 3.7 mm. Hg. As soon as self-stimulation was initiated an increase in oxygen tension occurred and continued during sexual stimulation. Just before orgasm a further increase was noted with peak values measured immediately after the orgasm began (pO(2) 28.6 +/- 3.1 mm Hg intravaginally and 47.3 +/- 4.1 labial). Labial pO(2) measurement decreased relatively rapidly soon after orgasm. The time to return to basal vaginal values after orgasm varied from 20 to 30 minutes. CONCLUSIONS Previously, changes in female sexual arousal responses have been difficult to evaluate and quantify clinically. We developed a simple noninvasive reproducible technique to measure vaginal and minor labial blood flow. Age based and cycle dependent normograms now can be produced for vaginal and labial blood flow using this method.

Erectile Dysfunction in Cyclists

Objective: Perineal compression during bicycling appears to be responsible for some cases of erectile dysfunction. Material and Methods: In 46 healthy athletic men transcutaneous penile oxygen pressure (tpO2) at the glands of the penis was measured, using a transcutaneous measurement device. It has been shown that the tpO2 levels measured at the glans correlate with the penile blood flow. Our measurements were performed before, during and after cycling in an upright and a reclining position in a crossover study. Results: The mean transcutaneous pO2 at the glans in a standing position before biking was 60.5±8.1 mm Hg. It decreased after sitting on the saddle in an upright position to 17.9±3.9 mm Hg. Continued cycling in a seated upright position showed pO2 levels of 18.3±5.2 mm Hg, with a full return to normal pO2 values after a 10–min recovery period in a standing position. Cycling in a reclining position resulted in pO2 levels of 59.4±4.2 mm Hg, a similar level to that obtained before exercising. Conclusions: The results of the present study demonstrated that there is a defiency in penile perfusion caused by perineal arterial compression. Cycling in a reclining position – in which no perineal compression was seen – caused no alteration in penile blood flow during exercising. Therefore, we suggest cycling in a reclining position to avoid health hazards – such as penile numbness and hypoxygenation of the corpora cavernosa, which can result in impotency.

Nitric oxide pathways in human bladder carcinoma. The distribution of nitric oxide synthases, soluble guanylyl cyclase, cyclic guanosine monophosphate, and nitrotyrosine.

Nitric oxide (NO) is produced by a group of synthase enzymes (NOS). By means of different pathways, NO exerts several functions in benign and malignant human bladder tissues. The current paper describes the NO/guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) and the NO/oxidative pathways in human bladder tissues.