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Biomedical subjects

Udo Engelmann

Publications and source records attributed to Udo Engelmann.

13 recordsLinked to original sources
PubMed2007

Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial.

AIM: To test the hypothesis that sildenafil (50 mg nightly for one year) can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment. METHODS: In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function (IIEF EF) and the peak systolic velocity (PSV) of penile cavernous arteries were used to measure the efficacy. RESULTS: After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 (60.4%, 95% confidence interval [CI]: 45.3-74.2%) of the nightly group vs. 4 of 49 (8.2%, 95% CI: 2.3-19.6%) of the as-needed group. PSV improved by 11.2 cm/s (95% CI: 4.7-21.4; P=0.012) in the nightly group but only by 3.4 cm/s (-5.1-14.7; P=0.435) in the as-needed group. IIEF EF normalized in 1 of 18 (5.6%, 95% CI: 0.1-27.3%) non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most (28/29, 97%) nightly group men who had initially normalized. CONCLUSION: Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

Adult↗
PubMed2006

Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin.

The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH.

Adrenergic alpha-Antagonists↗
PubMed2005

Development and validation of a risk score for somatic erectile dysfunction: combined results from three cross-sectional surveys.

OBJECTIVES: Some men with erectile dysfunction (ED) have difficulties discussing their condition with their physicians. Existing screening and diagnostic tools for ED often require the administration of personal questions regarding the condition. We present a simple risk score to estimate the individual likelihood of somatic ED, based on age and existing health conditions. METHODS: Data from the Cologne Male Survey (n = 4396) were used to develop a multivariable logistic regression model for the individual ED likelihood. The regression equation was both internally and externally validated using data from a national study (Berlin study) and a multinational cross-sectional study (MALES study). RESULTS: A final regression equation including age, pelvic surgery, diabetes mellitus, arterial circulatory disorder, heart disease, smoking, and hypertension reached an area under the receiver operating characteristic curve of 0.84 (0.5 means random and 1.0 perfect discrimination). Internal validation did not indicate any relevant overfit and the external validation results (national data: AUC = 0.75; multinational data: AUC = 0.67) are similar to those of other popular risk scores. CONCLUSIONS: The validated ED risk score developed from the regression equation can be used as a screening tool to identify patients who are at a high risk of somatic ED. This tool can facilitate entering into discussions between physicians and patients regarding erectile function.

Adult↗
PubMed2005

Differential endostatin binding to bladder, prostate and kidney tumour vessels.

OBJECTIVES: To define the anti-angiogenic mechanism and causes of the heterogeneous influence of endostatin, one of a group of matrix-derived inhibitors of tumour angiogenesis of increasing significance in tumour treatment, on various tissue types. MATERIALS AND METHODS: Variations in the binding behaviour of endostatin with vessels were assessed in different tumours (bladder, prostate and kidney) and compared with benign tissue vessels. Biotinylated endostatin was used and detected using extravidin CY3 and extravidin-gold immunolabelling. RESULTS: There were significant differences in the number of vessels showing endostatin binding among benign and malignant bladder, prostate and kidney tissues. While there was distinct endostatin binding on a mean (sd) of 94.2 (3.0)% bladder and 73.8 (19.5)% prostate tumour vessels, there was less binding, at 11.32 (3.9)%, on kidney tumour vessels. There was less binding to vessels of benign bladder, prostate and kidney tissue, at 2.0 (1.5), 1.7 (1.7) and 1.5 (1.7)%, respectively. At the ultrastructural level, different binding sites were detected both inside and outside the endothelial cells. CONCLUSION: Endostatin binds more to all tumour tissues than to benign tissue, but the degree of binding in malignant kidney tissue was significantly less than that in malignant prostate and bladder tissues. These divergent vascular endostatin-binding patterns could be responsible for a tumour type-dependent anti-angiogenic effect attributable to endostatin. Such selective behaviour would have therapeutic consequences for future anti-angiogenic therapy, in which different kinds of tumours could be further classified into those responding to endostatin or not.

Aged↗
PubMed2004

Vessels in benign prostatic hyperplasia contain more binding sites for endostatin than vessels in normal prostate tissue.

OBJECTIVE: The angiogenic phenotype is an effect of a net balance of angiogenic and anti-angiogenic factors. Endostatin is one of a group of recently described matrix-derived inhibitors of tumour angiogenesis that have acquired increasing significance for tumour treatment. Endostatin's anti-angiogenic mechanism and the causes of its heterogenic influence on various tissue types have not yet been defined. METHODS: We investigated the variations in endostatin's binding behaviour to vessels in benign prostatic hyperplasia (BPH) compared to endostatin binding to vessels in normal prostate tissue. Biotinylated endostatin was used and was detected using Extravidin CY3. RESULTS: In BPH 89.12% +/- 10.72% of vessels showed endostatin binding. This was significantly more than observed for vessels in normal prostate tissue (1.66% +/- 1.66%). CONCLUSION: The strongly proliferative tissue of BPH may be a growth-limited cause of significantly more endostatin binding sites. The investigation indicates endostatin as a possible new target for BPH treatment.

Aged↗
PubMed2004

Future options for combination therapy in the management of erectile dysfunction in older men.

The prevalence of erectile dysfunction (ED) has dramatically increased in parallel with the aging of the Western industrialised population. The estimated prevalence of ED worldwide in 1995 was 152 million men. As the population in industrial nations ages, an estimated 322 million men will be affected by ED by the year 2025. Oral drug therapy with the phosphodiesterase (PDE) type 5 inhibitor sildenafil fails in some patients with ED; however, several different classes of drugs demonstrate efficacy in treating ED, creating the potential for pharmacological combination therapy. Pharmaceutical products that lead to the activation of or an increase in cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate), with or without nitric oxide donors or nitrates, as well as alpha-adrenoceptor antagonists, have been used to treat ED. Sildenafil has been used in combination with alprostadil (prostaglandin E1) and administered via intraurethral or intracavernous route. Successful intercourse using this combination of agents varies from 47% to 100% following failed monotherapy. Various combination therapies for ED are being studied using PDE5 inhibitors, together with other agents, alpha-adrenoceptor antagonists, and testosterone replacement therapy for men with hypogonadism. The combination of centrally acting agents with PDE5 inhibitors, e.g. a regimen of apomorphine plus PDE5 inhibitor, is an attractive approach because the two therapies target different mechanisms. New PDE5 inhibitors such as vardenafil should be tried first as therapy for sildenafil nonresponders before exploring any combination therapy options. Preliminary observations of combination therapy have been encouraging and provide a scientific rationale for prospective, randomised clinical trials with adequate numbers of patients.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2002

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

BACKGROUND: 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. METHODS: Bladder carcinoma tissues were collected from 18 patients by transurethral resection procedures. Normal benign vesical tissue specimens from a further eight patients with benign diseases served as controls. Immunohistochemistry was conducted for localization of sGC, cGMP, and nitrotyrosine in benign and malignant vesical tissues, evaluating two-three tissue sections per patient. RESULTS: Positive immunolabeling for sGC and cGMP was detected in vascular endothelial cells of normal and malignant vesical tissues. Those signals were most intense in bladder carcinoma tissues. Immunolabeling for sGC and cGMP was also detected in normal urothelial cells. In bladder carcinoma cells, a heterogeneous immunolabeling for sGC and cGMP was seen, with a wide spectrum of signal intensity. Positive immunostaining for sGC and cGMP was also observed in stromal round cells in benign and malignant bladder tissues. Immunolabeling for nitrotyrosine was mainly observed in endothelial cells, with a much stronger immunolabeling in bladder carcinoma tissues compared to normal benign controls. A weak immunolabeling for nitrotyrosine was also observed in bladder carcinoma cells. Normal urothelial cells did not show such nitrotyrosine expression. CONCLUSIONS: The current report provides evidences that NO play several roles through different pathways in benign and malignant vesical tissues. The influences generated by NO molecules can be divided into cGMP-mediated effects (those resulting from the NO/sGC/cGMP pathway) and non-cGMP-mediated effects (those resulting from the NO/oxidative pathway). Increased angiogenesis is a cGMP-mediated effect, while nitrotyrosine production is a non cGMP-mediated oxidative effect. Such an NO/oxidative pathway is observed more often in bladder carcinoma.

Aged↗
PubMed2002

Cycling and penile oxygen pressure: the type of saddle matters.

OBJECTIVES: Temporary genital numbness is a common side effect of long-distance cycling; cases of impotence have even been reported. Recent reports have shown that perineal compression leads to a decrease in penile blood flow. Reduced oxygen tension leads to penile fibrosis, which works counterproductively to the achievement of an erection. The shape of the bicycle saddle could be a factor affecting penile perfusion. The aim of this study is to find out the influence of different saddle designs on penile perfusion. MATERIAL AND METHODS: In 20 healthy athletic young men (mean age 26.8 years, range 21-31 years) without history of erectile dysfunction, transcutaneous oxygen pressure (PtcO2), which correlates with arterial and tissue PO2, was measured at the glans of the penis using a transcutaneous measurement device. All men were measured in a standing position before cycling, then during cycling in a seated position on a stationary bicycle. Four different bike saddle designs were used: (A) narrow heavily padded seat; (B) narrow seat with medium padding and a V-shaped groove in the saddle nose ("body geometry"); (C) wide unpadded leather seat; (D) women's special wide seat with medium padding and no saddle nose. RESULTS: During cycling in all seats a decrease in penile oxygen pressure could be observed, reflecting perineal compression. But the differences were unexpected: seat (A) mean PtcO2 11.8 mmHg, decrease in initial oxygen pressure 82.4%; seat (B) mean PtcO2 20.8 mmHg, decrease in initial oxygen pressure 72.4%; seat (C) mean PtcO2 25.3 mmHg, decrease in initial oxygen pressure 63.6%; seat (D) mean PtcO2 62.3 mmHg, decrease in initial oxygen pressure 20.3%. CONCLUSIONS: Cycling in a seated position leads to a compression of perineal arteries with a consequent significant decrease in penile perfusion. But, there are unexpected differences between different saddle types. It was possible to demonstrate that the most important factor in safeguarding penile perfusion is not the amount of padding, but rather a saddle width which prevents sufficiently the compression of the perineal arteries.

Adult↗
PubMed2002

Vardenafil Bayer Yakuhin.

Bayer is developing vardenafil, an orally active phosphodiesterase (PDE) 5 inhibitor for the potential treatment of erectile dysfunction (ED) [314382]. NDAs were filed in September 2001 in the US and Mexico [423096], and vardenafil was submitted for Canadian approval in October 2001. As of November 2001, Bayer was expecting a response from the FDA in the second half of 2002 [429499]; the EMEA accepted a filing in January 2002, following a December 2001 submission [438163]. By October 2000, phase III trials were underway in Japan [384751] and by December 2001, a Japanese NDA had been filed; at the same time an application was filed in South Africa [426526], [433060]. At this time Japanese launch was expected in 2003 [434758]. By February 2001, Bayer was also investigating a nasal formulation of vardenafil for the potential treatment of erectile dysfunction [397608]. In November 2001, Bayer and GlaxoSmithKline signed a worldwide copromotion agreement for vardenafil, under which Bayer was to be responsible for all regulatory work required to obtain approval [429499]. In February 1999, Lehman Brothers predicted a 10% probability that vardenafil would reach the market, with launch in 2002. Peak Japanese sales of US$600 million were predicted for 2014 [319225]. In May 2000, Bayer predicted peak sales of Euro900 million [397137]. In July 2001, Lehman Brothers predicted a 75% chance that vardenafil would reach the market, and forecast peak sales of US $0.85 billion worldwide; the analyst also speculated that Bayer would seek a comarketing partner [414766].

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

Detection of circulating tumor cells in patients with renal cell carcinoma by reverse transcriptase polymerase chain reaction for G250/MNCA-9: results of a prospective trial.

OBJECTIVES: Radical nephrectomy displays the standard procedure for patients with localized renal cell carcinoma. The transperitoneal approach is often favored compared to the retroperitoneal approach because of the early ligation of the renal vessels, thereby tumor cell shedding by manipulation of the tumor is thought to be avoided. The aim of our study was to investigate the influence of the surgical technique on intraoperative tumor cell shedding. Furthermore, we evaluated the clinical course of the patients being operated on with either method in terms of complications, postoperative recovery, and hospital stay. METHODS: A total of 55 consecutive patients with renal tumors suspicious for malignancies were evaluated for this study. Peripheral blood samples were obtained from 44 patients at admission, intraoperatively (before and after kidney removal), and before discharge. Ribonucleic acid was extracted, converted to complementary deoxyribonucleic acid, and reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for G250/MNCA-9 was performed. Data regarding the clinical course of the patients were analyzed retrospectively by reviewing patient files. RESULTS: The clinical course for patients undergoing retroperitoneal nephrectomy was statistically different compared to the transperitoneal approach group regarding operating time and duration of drains, favoring the retroperitoneal approach group. Evaluation of MNCA-9 RT-PCR revealed no difference according to operative technique, tumor-nodes-metastasis, or clinical tumor stage. Despite this result, we found positive RT-PCR signals for MNCA-9 in patients with transitional cell cancer of the renal pelvis and benign renal lesions. CONCLUSIONS: There is no clinical relevant difference between the transperitoneal and retroperitoneal approaches for radical nephrectomy. Furthermore, the retroperitoneal approach does not bear the risk of intraoperative tumor cell shedding by the handling of the tumor.

Aged↗