Biomedical subjects

Udo Jonas

Publications and source records attributed to Udo Jonas.

54 records · Page 3Linked to original sources

PubMed2003

Effects of visual sexual stimuli and apomorphine SL on cerebral activity in men with erectile dysfunction.

PURPOSE: The present study investigates whether cerebral activation during visually evoked sexual arousal is different in patients with erectile dysfunction (ED) compared to the known pattern observed in healthy men, and additionally how cerebral activity during visual sexual stimulation is modified by treatment with apomorphine SL and whether the observed cerebral activity correlates with penile rigidity. PATIENTS AND METHODS: Cerebral activity was measured before and after treatment in 12 patients with erectile dysfunction randomised to receive either apomorphine SL or placebo using [15O]H(2)O-PET. Two PET scans were performed prior to administration of the study medication, the first after a neutral audiovisual stimulus and the second following a sexually stimulating audiovisual presentation. After receiving the study medication, patients were subjected to two additional scans each preceded by a sexually stimulating stimulus. Penile rigidity was assessed with the RigiScan device. Evaluation for significant regional cerebral activation was performed using statistical parametric mapping (SPM99). RESULTS: Cerebral activity increased significantly after the sexually stimulating video sequence compared to the neutral one in the inferior frontal cortex (Brodmann areas [BA] 47, 10, 11) and the rostral anterior cingulate (BA 32), and cerebral activity was observed to decrease in both inferior temporal cortices (BA 20). 4 out of 6 patients showed significant penile rigidity after apomorphine SL and in none of those receiving placebo. Apomorphine SL was observed to increase cerebral activity in the right superior prefrontal area (BA 6) that was not seen with placebo, while neither apomorphine SL nor placebo produced decreased cerebral activity. Penile rigidity correlated with increased cerebral activity in the anterior cingulum and right prefrontal cortex, and with decreased activity in the temporal cortex. CONCLUSIONS: In patients with erectile dysfunction, the pattern of increased and decreased cerebral activity in response to visual sexual stimuli in this study is similar to that reported in the literature in healthy men. Apomorphine SL appears to induce additional cerebral activity in the right prefrontal cortex, an area previously shown to be associated with sexual arousal in male volunteers during orgasm. This increased cerebral activity was associated with penile rigidity, further supporting the conclusion that apomorphine SL improves erectile function in men with ED by enhancing the natural central erectile signals that normally occur during sexual stimulation.

Adult↗

PubMed2003

Endoscopic extraperitoneal radical prostatectomy: initial experience after 70 procedures.

PURPOSE: After our initial experience with 70 transperitoneal laparoscopic radical prostatectomies we developed a totally extraperitoneal retropubic approach to radical prostatectomy using laparoscopic instruments. We report our initial experience with 70 endoscopic extraperitoneal radical prostatectomy procedures. MATERIALS AND METHODS: A total of 70 patients underwent endoscopic extraperitoneal radical prostatectomy. Mean patient age was 63.4 years (range 49 to 76). Mean preoperative prostate specific antigen was 12.48 ng./ml. (range 1.4 to 50.7). There were no specific selection criteria for the procedure. The steps of the procedure are preparation of the preperitoneal space with the help of a balloon trocar, trocar placement (a 3 x 5 and a 2 x 12 mm. port), pelvic lymph node dissection, exposure of the prostate and the bladder neck, incision of the endopelvic fascia, ligation of Santorini's plexus, bladder neck dissection, mobilization of the seminal vesicles, incision of Denonvilliers' fascia, sectioning of the prostatic pedicles with or without preservation of the neurovascular bundles, dissection of Santorini's plexus and apex, urethrovesical anastomosis with 7 to 9 interrupted sutures and removal of the specimen via an extraction bag. During the 70 endoscopic prostatectomies 11 hernia defects were treated in 9 patients concomitantly. RESULTS: There was no conversions and no re-interventions. Mean operative time was 155 minutes (range 90 to 260). One patient required transfusion with 2 units of blood cells. Pathological stage was pT2a in 19 patients, pT2b in 14, pT3a in 25, pT3b in 9 and pT4 in 3. Positive surgical margins were found in 2 of the 33 patients (6.1%) with pT2 tumors and in 13 of the 37 (35.1%) with pT3 and pT4 tumors. Postoperatively edema and hematoma of the penis in 10 cases was treated conservatively. Furthermore, 4 patients had asymptomatic lymphoceles, 1 required lymphocele drainage and 2 had partial obturator nerve paralysis, which resolved spontaneously. In 1 patient deep venous thrombosis developed. CONCLUSIONS: The preliminary results of this series are promising. Operative and perioperative morbidity was low. Functional results and oncological control were similar to the results of laparoscopic radical prostatectomy. The data demonstrate that endoscopic extraperitoneal radical prostatectomy can be performed with efficacy and results equal to those of laparoscopic radical prostatectomy, while providing the benefits of a totally extraperitoneal approach. Therefore, totally endoscopic extraperitoneal radical prostatectomy represents a technical improvement of laparoscopic technique because it completely obviates intra-abdominal complications and combines the advantages of minimally invasive laparoscopy and the retropubic open approach.

Aged↗

PubMed2003

Current and future trends in the oral pharmacotherapy of male erectile dysfunction.

The promising clinical data on the use of the first orally active phosphodiesterase inhibitor sildenafil citrate (Viagra) for treatment of male erectile dysfunction have been accompanied by an increase in research activities on the physiology of the male erectile mechanism. This included both peripheral intracellular signal transduction in the corpus cavernosum as well as central brain and spinal cord pathways that control penile erection. This work provided the basis for the development and introduction of several new therapeutic modalities into the management of erectile dysfunction that is now offered to the patients. Since the concept of 'taking a pill' as a cure for an illness or the relief of symptoms of a disease has become widely accepted by consumers, the pharmacological treatment of erectile dysfunction has primarily focused on selective, orally available drugs that act via influencing intracellular or central regulatory mechanisms, combining a high response rate and the advantage of an 'on-demand' intake. These agents are regarded as more efficacious, have a faster onset of drug action in the target tissue and an improved effect-to-side effect ratio than sildenafil. The purpose of this review is to describe the major novel and evolving pharmacological advances in the field of oral pharmacotherapy for the treatment of male erectile dysfunction.

Administration, Oral↗

PubMed2002

Oxytocin plasma levels in the systemic and cavernous blood of healthy males during different penile conditions.

It is well established that transmitters of the nonadrenergic-noncholinergic (NANC) system are involved in the control of sexual arousal and penile erection in healthy males. The proerectile activity of dopamine D1/D2 receptor agonist apomorphine-HCl (IXENSE, UPRIMA) involves oxytocinergic pathways descending from the hypothalamus to the brain stem and spinal autonomic centers. Although it has been demonstrated that injection of oxytocin into the paraventricular nucleus and the hippocampus produces penile erection in rats, the significance of the peptide in the control of sexual arousal and penile erection in man has been, up until now, only poorly evaluated. The present study was undertaken to determine whether oxytocin (OT) plasma levels alter in the systemic and cavernous blood of healthy males under different penile conditions (flaccidity, tumescence, rigidity, detumescence). Twenty-five healthy adult males were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and rigid erection. Blood was taken from the corpus cavernosum (CC) and the cubital vein (CV) during penile flaccidity, tumescence, rigidity and detumescence. Following extraction from plasma aliqouts, oxytocin was measured by means of a radioimmunoassay. An increase was observed in the mean OT plasma levels in the systemic and cavernous blood when the flaccid penis became tumescent (CC: from 66.7+/-34 to 75+/-44 pg/ml; CV: from 71+/-41 to 79+/-49.5 pg/ml). From tumescence to rigidity, OT further rose in the cavernous blood (to 81+/-58 pg/ml), whereas it remained unaltered in the systemic circulation. During detumescence, oxytocin plasma levels dropped in the cavernous but again increased in the systemic blood (to 94+/-49 pg/ml). Our results support the hypothesis of a pivotal role of OT in the mechanism of male sexual arousal and penile erection and provide a rationale for the use of apomorphine in the treatment of erectile dysfunction.

Adult↗

PubMed2002

The impact of extracorporal circulation on therapy-related mortality and long-term survival of patients with renal cell cancer and intracaval neoplastic extension.

In approximately 4%-10% of patients presenting with renal cell cancer, the transluminal propagation of a tumour thrombus into the vena cava inferior or the right atrium comes to diagnosis. Recent investigations have indicated that the presence of neoplastic extension into the venous system does not reveal independent prognostic value regarding the clinical course of the disease. Although the complete surgical removal of vena cava thrombosis in patients without simultaneously occurring regional lymph node or distant metastases has become a well established treatment modality, several questions concerning this surgical strategy still remain the subject of ongoing discussions. In the present investigation that included 92 patients with renal cell cancer and intracaval neoplastic extension, it was clearly demonstrated that using cardiopulmonary bypass, deep hypothermia and circulatory arrest - preferably, during the removal of intracaval thrombosis extending into the right atrium - does not result in a substantially increased treatment-related intra- or postoperative mortality. However, in contrast to a previously reported observation, this treatment option did not reveal any substantial impact on the long-term survival of the patients following surgical therapy. Accordingly, the cranial extension of intracaval thrombosis was not identified as a biological variable of any prognostic importance for renal cell cancer patients.

Adult↗

PubMed2002

Possible role of bioactive peptides in the regulation of human detrusor smooth muscle - functional effects in vitro and immunohistochemical presence.

Results from basic research implicate a role for bioactive peptides in controlling the mammalian lower urinary tract. Although various peptides are assumed to be involved in the potentiaton or inhibition of cholinergic or purinergic activity in the urinary bladder, there is still much controversy regarding the mode of action and functional significance of such peptides in detrusor smooth muscle. Thus, we evaluated the functional effects of atrial natriuretic peptide (ANP), calcitonin gene related peptide (CGRP), endothelin 1 (ET-1), substance P (SP) and vasoactive intestinal polypeptide (VIP) on isolated strip preparations of human detrusor smooth muscle and determined the presence of those peptides in the human detrusor by means of immunohistochemistry. The effects of peptides on isometric tension of isolated detrusor strip preparations and on tissue levels of cyclic nucleotides cAMP and cGMP were compared to those of adenylyl cyclase activator forskolin (F), nitric oxide donor Na(+)-nitroprusside (SNP) and non-specific phosphodiesterase (PDE) inhibitor papaverine (P). The effects of the compounds on isometric tension of isolated human detrusor smooth muscle were examined using the organ bath technique. To determine time- and dose-dependent effects on cyclic nucleotide levels, bladder strips were exposed to increasing doses of F, SNP, P, ANP, CGRP and VIP, then rapidly frozen in liquid nitrogen and homogenised in the frozen state. cAMP and cGMP were extracted and assayed using specific radioimmunoassays. The presence of peptides was investigated by light microscopy using the Avidin-Biotin-Complex (ABC) method. F, P and VIP most effectively reversed the carbachol-induced tension of isolated human detrusor strips. Relaxing effects of ANP, CGRP and SNP were negligible. In contrast, ET-1 and SP elicited dose-dependent contractions of the tissue. The relaxing effects of F, P and VIP were accompanied by an increase in cAMP and cGMP levels, respectively. Light microscopy revealed positive immunostaining for CGRP, ET 1, VIP and SP in sections of the detrusor muscle coat. Our results suggest a possible importance of ET 1, SP and VIP in regulating detrusor smooth muscle contraction and relaxation. Even if a peptide is not synthesised, stored or released in a smooth muscle tissue and is, therefore, unable to reach its target cells under physiologic conditions, a functional effect on the tissue might be mediated by peptide-binding to specific cell surface receptors.

Atrial Natriuretic Factor↗

PubMed2002

Homologous acellular matrix graft for vaginal repair in rats: a pilot study for a new reconstructive approach.

The purpose of this paper is to investigate using an acellular matrix graft of vagina (VAMG) or bladder (BAMG) in vaginal reconstruction. In 18 rats, vaginal length was measured and a hysterectomy performed. In three control animals, the vaginal stump was closed. In eight rats, the vagina was augmented with a VAMG; in seven, a BAMG was used. After 2-12 weeks, the animals were sacrificed, the vaginal length was reevaluated, and the vaginas were prepared for histologic evaluation. In the controls, the vagina was markedly shorter postoperatively. In the grafted animals, vaginal length was not significantly less than preoperative values with either matrix. Epithelialization, vascularization, and alpha-actin expression in the grafts were consistently observed. Regeneration appeared to be slightly greater in the organ-specific vagina matrix. With either matrix, however, although the vaginal stump remained open, the grafts lost most of the lumen. Vaginal reconstruction with a vagina acellular matrix graft is technically feasible. If further experiments can address the problem of luminal collapse - with, for instance, tissue expanders in the matrix - this technique may offer an alternative to the complex therapeutic options currently available.

Animals↗

PubMed2002

Increase in detrusor wall thickness indicates bladder outlet obstruction (BOO) in men.

Detrusor wall thickness decreases continuously while the bladder fills to 50% of its capacity and then remains constant until 100%. Therefore, detrusor wall measurements were performed in patients when the bladder was filled to maximum capacity only. Mean detrusor wall thickness for unobstructed (n = 14), equivocal (n=23) and obstructed patients (n=33) were 1.33, 1.62 and 2.4 mm, respectively (P <0.001). With increasing CHESS letters and CHESS numbers, the thickness of the detrusor wall increased as well (P< 0.001). The positive predictive value of detrusor wall measurement (95.5% for a cut-off value greater than or equal to 2 mm) was superior to all other predictors investigated. The thickness of the detrusor wall increases depending on the extent of BOO. Both constrictive and compressive BOO lead to an increase in detrusor wall thickness. BOO is found in 95.5% of men with a detrusor wall thickness greater than or equal to 2 mm. Measuring the thickness of the detrusor wall can be used as a screening test to detect BOO.

Adolescent↗

PubMed2002

Systemic and cavernous plasma levels of vasoactive intestinal polypeptide during sexual arousal in healthy males.

Results from basic research scrutiny indicate a role for non-adrenergic, non-cholinergic transmitters, among which there are various peptides, in the physiology of normal male sexual function. Nevertheless, it is not yet known which particular peptides are essentially involved in maintaining sexual arousal and regulating penile tumescence and rigidity in adult males. Vasoactive intestinal polypeptide (VIP), a peptide with smooth muscle relaxing properties, is considered to be one of the factors that contributes to such control. The present study was performed to evaluate the significance of VIP in normal male sexual function. We determined the plasma levels of VIP in the systemic and cavernous blood of 54 healthy adult male volunteers, who were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and erection. Whole blood was aspirated from the corpus cavernosum and the cubital vein during penile flaccidity, tumescence, rigidity and detumescence, and VIP was quantified in plasma aliquots by means of a radioimmunoassay. Of the 54 volunteers, 16 were permitted to masturbate and ejaculate, and blood was then again withdrawn from the cavernous meshwork and the cubital vein in order to measure VIP. All VIP levels were registered within the normal physiological range from 3.0-30 pmol/l. No increase in median VIP plasma levels was observed in the systemic and cavernous blood when the flaccid penis became rigid. During penile detumescence, mean cavernous VIP level increased to 11.9+/-7.8 pmol/l (baseline: 8.6+/-3.0 pmol/l), whereas VIP remained unaltered in the systemic circulation. Following ejaculation, mean VIP level in the cavernous blood was elevated to 25.3+/-10.9 pmol/l, whereas, in the systemic blood, no significant changes were registered. Our results support the hypothesis that VIP plays a functional role in the mechanism of male sexual arousal. Nevertheless, our data indicate that the peptide is not the main non-adrenergic, non-cholinergic mediator of penile tumescence and rigidity in human males.

Adult↗

PubMed2002

Some historical reflections on the ageing male.

Throughout the early history of medicine, discourses on the "ageing male" can be found, although most authors addressed the aspect of old age rather than the early onset and beginnings of this period of life. With reference to the typical climacteric changes in women, the term "climacteric disease" in males was coined by H. Halford in 1813 and finally reintroduced into modern medical terminology in the 1930s by A. A. Werner. In between, several authors have described this clinical entity, often called "climacterium virile", by considering hormonal and neurological changes to be the underlying causes. All these early writings should be of certain interest to those who are dealing with modern aspects of the ageing male and are reflected in this article.

Aging↗

PubMed2002

Cavernous and systemic plasma levels of norepinephrine and epinephrine during different penile conditions in healthy men and patients with erectile dysfunction.

OBJECTIVES: To examine and compare the courses of norepinephrine (NE) and epinephrine (E) plasma levels in the systemic and cavernous blood taken during different penile conditions from healthy men and a group of patients with erectile dysfunction (ED). Knowledge concerning the neurophysiology of penile erection has improved tremendously during the past two decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out to date. METHODS: Fifty-three healthy adult male subjects and 47 patients with ED of different etiologies were exposed to erotic stimuli to elicit penile tumescence and, in the group of healthy subjects, rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Plasma levels of NE and E were determined by means of a radioimmunoassay. RESULTS: In the healthy subjects, a significant reduction of NE in cavernous plasma was detected from flaccidity (362 +/- 173 pg/mL) to rigidity (248 +/- 122 pg/mL), followed by an increase in the detumescence phase (336 +/- 199 pg/mL). Changes in NE levels in the peripheral plasma were less pronounced. Cavernous E levels significantly increased from flaccidity (47 +/- 41 pg/mL) to tumescence (130 +/- 106 pg/mL) and dropped from rigidity (113 +/- 67 pg/mL) to detumescence (76 +/- 57 pg/mL). The course of systemic E plasma levels was similar to that in the cavernous blood. In contrast, median NE levels in the systemic and cavernous blood of the ED group slightly increased from flaccidity to tumescence (from 199 +/- 88 pg/mL to 210 +/- 99 pg/mL and from 273 +/- 140 pg/mL to 278 +/- 118 pg/mL, respectively). CONCLUSIONS: In healthy men, penile erection is accompanied by a reduction of NE in the cavernous blood and a rise in E levels in the peripheral and cavernous blood. That NE levels in the cavernous and systemic blood increase during sexual arousal in patients with ED might be an indication of a somatic dysregulation in sympathetic transmission or alterations of NE reuptake mechanisms as a cause of impaired erectile function.

Adult↗

PubMed2002

Serum levels of human growth hormone during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction.

OBJECTIVES: To detect changes in growth hormone (GH) serum levels during different penile conditions in the cavernous and systemic blood of patients with erectile dysfunction and compare them with the course of GH registered in healthy men. It has been suggested that human GH is involved in sexual maturation and plays a regulatory role in male reproductive function. Deficiency may result in fatigability, loss of sexual desire and erection, or oligospermia or azoospermia. It is assumed that the biologic effects of GH include insulin-like growth factor 1-mediated stimulation of endothelial nitric oxide formation. It has recently been demonstrated that GH serum levels in the systemic and cavernous blood of healthy men increases during developing penile erection. METHODS: Thirty-five healthy adult men and 45 patients with erectile dysfunction of either organogenic or psychogenic etiology were exposed to visual and tactile erotic stimuli to elicit penile tumescence and, in the group of healthy subjects, rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during the different functional conditions of the penis. Serum levels of GH were determined by means of an immunoradiometric assay. RESULTS: In the healthy subjects, systemic GH serum levels significantly increased during penile tumescence, followed by a transient decline from tumescence to rigidity and detumescence. In the unselected patients, the mean GH levels during penile flaccidity were determined to be about sevenfold lower than those registered in the blood of the healthy men. During penile tumescence, the mean increase in the GH levels in the systemic and cavernous blood of psychogenic patients was comparable to that seen in healthy men, but, in the group of organogenic patients, this increase was found to be negligible. CONCLUSIONS: We believe our data provide strong evidence that GH may be of major importance in the maintenance of male erectile capability-probably through a stimulating effect on cyclic guanosine monophosphate generation in human cavernous smooth muscle-and that a decline in GH release may contribute to the manifestation of erectile dysfunction.

Adult↗

PubMed2002

Detection of low-molecular-mass plasma peptides in the cavernous and systemic blood of healthy men during penile flaccidity and rigidity--an experimental approach using the novel differential peptide display technology.

OBJECTIVES: To use Differential Peptide Display (DPD) technology to evaluate the patterns of low-molecular-mass peptides and small proteins in the systemic and cavernous blood taken from healthy adult male volunteers during the penile stages of flaccidity and rigidity. Results from basic research implicate a role of various peptides in the control of mammalian penile erectile tissue. Nevertheless, it is not yet known which particular peptides are essential in the regulation of penile flaccidity, tumescence, rigidity, and detumescence. METHODS: Five healthy male subjects were exposed to visual and tactile erotic stimuli to elicit penile erection. Whole blood was simultaneously aspirated from the corpus cavernosum and cubital vein during penile flaccidity and rigidity. Plasma aliquots were subjected to DPD analysis by means of matrix-assisted-laser-desorption-ionization mass mapping and electrospray-ionization quadrupole--time-of-flight mass spectrometry. RESULTS: High-resolution two-dimensional peptide mass mapping revealed differences in the systemic and cavernous plasma samples related to penile flaccidity and rigidity. Distinct signals were recognized in the cavernous but not in the systemic plasma obtained during flaccidity. These signals were not registered in the plasma samples obtained from the corpus cavernosum during rigid erection. Although one signal was identified as the blood coagulation-activating peptide XIIIa, the remaining two signals could not be related to any known peptide. These signals may represent unknown local peptidergic factors that might be involved in the regulation of penile flaccidity. CONCLUSIONS: Our study demonstrates that DPD is a feasible method for detecting differences in the cavernous and systemic blood in relation to the different functional conditions of the penile erectile tissue. Additional studies using DPD should include the analysis of blood samples taken from the cavernous meshwork of healthy subjects during penile tumescence and detumescence to establish DPD as a valuable tool in contemporary corpus cavernosum basic research.

Adult↗

PubMed2002

Effects of various nitric oxide donating agents on the contractility and cyclic nucleotide turnover of human seminal vesicles in vitro.

OBJECTIVES: To evaluate the effects of the nitric oxide (NO)-donating drugs sodium nitroprusside, S-nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteineetylester (SNACET), and linsidomine (SIN-1), as well as the adenylyl cyclase-stimulating agent forskolin, on electrically induced contractions and on tissue levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) of isolated human seminal vesicle strip preparations. The significance of the L-arginine-NO-cGMP pathway in the regulation of smooth muscle tone in the human genitourinary tract has been well established; however, information on the relevance of NO-mediated signal transduction in the functional control of mammalian seminal vesicles is still sparse. METHODS: Seminal vesicle strip preparations were applied to an organ bath system under standard conditions. Phasic contractions were induced by electrical field stimulation (frequency 80 Hz, amplitude 10 V, single pulse 1 ms, total pulse duration 1 second, pause 90 seconds). After stable contraction amplitudes had been reached, the drugs were added in a cumulative manner (0.001 to 10 microM), and the isometric responses were registered. After drug exposure, freezing, tissue homogenization, and extraction of cyclic nucleotides, cAMP and cGMP were measured by means of enzyme-linked immunosorbent assays. RESULTS: Electrical field stimulation-induced amplitudes were attenuated by the drugs in a dose-dependent manner. The rank order of potency was GSNO > sodium nitroprusside > forskolin > SNACET > or = SIN-1. The relaxing effect of GSNO was antagonized in the presence of 10 microM of guanylyl cyclase inhibitor methylene blue. The inhibitory effects of GSNO, sodium nitroprusside, and forskolin on the contractile activity were paralleled by an increase in tissue cGMP (2 to 100-fold) and cAMP (7 to 9-fold). CONCLUSIONS: Our results strongly support the hypothesis that the contractility of human seminal vesicles is in part regulated by the NO-cGMP-cascade. This may give a rationale for the use of S-nitrosothiols, such as GSNO, in the pharmacotherapy of hyperexcitatory disturbances of ejaculation.

Aged↗

PubMed2002

Long-term follow-up after surgery for advanced colorectal carcinoma involving the urogenital tract.

OBJECTIVES: Advanced colorectal carcinomas frequently involve the urogenital tract. In the following we evaluate the long-term survival after radical surgical extirpation and the prognostic significance of involvement of specific urological organs. METHODS: Between January 1985 and April 1996, 101 patients underwent interdisciplinary tumour extirpation of an advanced colorectal carcinoma involving the urogenital tract. RESULTS: Of 68 men and 33 women, 40 presented with primary and 61 with recurrent carcinoma. As far as urological organs are concerned, the ureter was removed in 82 patients, followed by bladder (n=52), seminal vesicles (n=25), prostate (n=22), kidney, testicle and penis. Histology revealed cancerous infiltration in 52% of the organs resected. A negative surgical margin was obtained in 54% of the patients, 43% showed positive lymph nodes. There was a 41% peri-operative complication with a mortality rate of 5%. Five year overall survival was 24.4% (median 23 months) with prognostic factors being type of tumour (primary versus recurrent), surgical margin and lymph node status. Stratification according to these factors showed removal of bladder and prostate to be a favourable and ureteral removal to be an omnious factor. CONCLUSION: We conclude that multivisceral extirpation of advanced colorectal carcinomas involving the urogenital tract should be recommended in selected patients. Our data showed it to be a safe surgical procedure, which is associated with favourable long-term outcome in non-metastatic patients in whom complete surgical resection could be achieved.

Adult↗

PubMed2002

In vitro effects of a novel class of nitric oxide (NO) donating compounds on isolated human erectile tissue.

OBJECTIVES: The discovery of nitric oxide (NO) as one of the major effectors in penile erectile function has led to the development of various drugs which are able to elevate intracellular levels of cGMP. Recently, a novel class of NO donors have been developed, exemplified by S-nitroso-glutathione (GSNO) and S-nitroso-N-acetylcysteine-ethylester (SNACET), as well as compounds combining both phosphodiesterase inhibitory and NO donating activity, such as NCX 911 (sildenafil nitrate). In our study, we assessed the effects of GSNO, SNACET and NCX 911 on adrenergic tension and electrically induced relaxation of isolated human corpus cavernosum (HCC) and the in vitro formation of cGMP. Effects were compared to those of sodium nitroprusside (SNP) and sildenafil citrate. MATERIALS AND METHODS: Using the organ bath technique, drug effects were investigated on norepinephrine-induced tension and electrically induced relaxation of HCC. HCC strips were exposed to increasing concentrations of the compounds (0.01/0.1-10/100 microM) and the accumulation of cGMP was determined by means of a radioimmunoassay. RESULTS: Relaxation of HCC induced by means of electrical field stimulation (EFS) was abolished by tetrotodoxin, guanylyl cyclase inhibitor ODQ and nitric oxide synthase inhibitor L-NNA. Adrenergic tension of HCC strips was dose-dependently reversed by the drugs. The rank order of potency was: SNP > GSNO > NCX911 > sildenafil > SNACET. Compounds also dose-dependently increased EFS-induced amplitudes of relaxation (SNP > NCX911 > sildenafil > SNACET/GSNO). Relaxing effects of the drugs were paralleled by an increase in tissue levels of cGMP. CONCLUSION: Our results provide a rationale for future use of NCX 911 and S-nitrosothiols in the pharmacotherapy of erectile dysfunction (ED). Since the compounds are assumed to exert no considerable hemodynamic effects, they might be developed into new oral treatments for ED.

Adult↗

PubMed2002

Alfuzosin: a clinically uroselective alpha1-blocker.

A once-daily (o.d.) formulation of alfuzosin has recently been developed in order to improve the convenience of dosing and to provide optimal pharmacokinetic coverage over a 24-h period. The results of two double-blind, placebo-controlled phase III studies of similar design that included 983 patients with LUTS that suggested BPH have confirmed that alfuzosin 10 mg o.d. is a 24-h effective treatment for both symptoms and flow rates, and that there is no additional benefit in using a higher dosage. In addition, alfuzosin is the only alpha1-blocker that has demonstrated a significant decrease in post-void residual urine, a known risk factor for acute urinary retention, as well as the incidence of acute urinary retention in comparison with a placebo. Administered without an initial dose titration, alfuzosin 10 mg o.d. is well tolerated, with a low incidence of postural hypotension (< 1%) and no significant changes in blood pressure compared with a placebo, even in elderly and hypertensive patients. Ejaculation disorders were rarely reported and did not show an evident causal relationship to treatment. Alfuzosin 10 mg o.d. also exhibits an excellent sexual side-effect profile, with no deleterious impact on this important aspect of quality of life for BPH patients.

Administration, Oral↗

PubMed1999

Sacral electrical neuromodulation as an alternative treatment option for lower urinary tract dysfunction.

Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.

Journal Article↗