Biomedical subjects

Udo Jonas

Publications and source records attributed to Udo Jonas.

At least 19 recordsLinked to original sources

PubMed2004

Interactions between cGMP- and cAMP-pathways are involved in the regulation of penile smooth muscle tone.

Nitric oxide (NO)/cyclic GMP (cGMP)-mediated mechanisms have a pivotal function in reducing the tone of the penile smooth musculature during normal erectile responses. The cyclic AMP (cAMP) signaling pathway is also involved in the adjustment of smooth muscle contractility, and suggestions for interactions between cGMP- and cAMP-mediated mechanisms have been presented. Using activators of the cGMP- or the cAMP-pathway, as well as inhibitors of protein kinase A (PKA; cAMP-dependent kinase) and protein kinase G (PKG; cGMP-dependent kinase), the present study was undertaken to further delineate the functional relation between these pathways in the penis. In addition, the distribution of PKA and some cAMP-binding phosphodiesterases (cAMP-PDEs) were investigated in human erectile tissue. Functional experiments were performed on isolated human corpus cavernosum (HCC). The effects of an inhibitor of the PKA, Rp-8CPT-cAMPS (10 microM), or the PKG, Rp-8-pCPT-cGMPS (10 microM), on relaxation induced by the cumulative administration of sodium nitroprusside (SNP), forskolin, sildenafil or tadalafil (IC351) were studied in preparations of HCC precontracted with 1 microM norepinephrine (NE). Using immunohistochemical procedures, the presence of immunoreactivity for cAMP-PDEs PDE3, PDE4, and PDE4A, as well as for PKA was investigated in specimens of HCC from which preparations were also used in the functional experiments. Forskolin, SNP, sildenafil, and IC 351 dose-dependently reversed NE-induced tension of isolated HCC preparations. The relaxing effects of SNP were significantly attenuated by Rp-8-pCPT-cGMPS, but not by Rp-8CPT-cAMPS. In contrast, relaxation induced by forskolin, sildenafil and tadalafil were significantly reversed by both Rp-8-pCPT-cGMPS and Rp-8CPT-cAMPS. Abundant immunoreactivity for PDE3 and PKA was observed in the corpus cavernosum smooth muscle cells. Immunoreactivity for PDE4 was also detected in the smooth musculature and in the cytoplasm of endothelial cells lining the cavernous sinusoids, as well as in nerve fibres interspersing the trabecular stroma. The present results support the hypothesis of interactions between cGMP- and cAMP-mediated signals in the HCC, and suggest that the effects of inhibitors of PDE5 on isolated erectile tissue may also partly or indirectly include actions of the cAMP second messenger system. The exact mechanism by which such an interaction occurs is not clear, but it may involve altered activity of the cGMP-inhibited PDE3 brought about by a change in the intracellular levels of cGMP by the inhibition of PDE5. This will in turn lead to increasing levels of cAMP, facilitating the interaction of cAMP with the PKA. The immunoreactivity specific for PDE3, PDE4, PDE4A and PKA registered in HCC section is also in support of an important role for the cAMP/PKA-system for penile smooth muscle function.

Adult↗

PubMed2004

Functional tissue engineering of autologous tunica albuginea: a possible graft for Peyronie's disease surgery.

OBJECTIVES: The aim of the present study was to generate a tissue engineered type of mechanically stable graft suitable for surgical replacement of the tunica albuginea penis. METHODS: Porcine fibroblasts isolated from open fascia biopsies were seeded on decellularized collagen matrices and then cultivated in a bioreactor under continuous multiaxial stress for up to 21 days (n=12). Static cultures without mechanical stress served as controls. Cell proliferation, cell alignment, and de novo synthesis of extracellular matrix proteins (proteoglycans, procollagen I, elastin) in these grafts was evaluated by hematoxylin-eosin, pentachrome, and immuno-staining. Additionally, the enzymatic isolation of porcine fibroblasts from X4mm skin punch biopsies (n=8) was evaluated. RESULTS: Mechanically strained cultures of fibroblasts showed a homogeneous multilayer matrix infiltration and a regular cell alignment in the direction of strain axis after 7 days, as well as a de novo production of extracellular matrix proteins compared to the static control. A large amount of viable fibroblasts was easily obtained from small skin punch biopsies. CONCLUSION: This study shows that continuous multiaxial stimuli improve proliferation and extracellular matrix synthesis of mature fibroblasts reseeded on a biological matrix making this a feasible autologous tissue engineered graft for penile surgery. For the clinical setting fibroblasts harvested from small skin biopsies can be a comfortable cell source.

Animals↗

PubMed2004

Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial.

OBJECTIVES: To examine the efficacy and tolerability of antimuscarinic therapy in women with urge-predominant mixed incontinence. METHODS: This was a double-blind, randomized, placebo-controlled trial comprising 854 women with urge-predominant mixed incontinence, including urge incontinence (five or more episodes per week), urinary frequency (eight or more micturitions on average in 24 hours), and urgency in combination with stress incontinence. Women received 8 weeks of treatment with tolterodine tartrate extended-release (ER) 4 mg or placebo once daily. The outcome measures included urge incontinence episodes per week, stress incontinence episodes per week, micturition frequency per 24 hours, urgency episodes per 24 hours, volume voided per micturition, patient perception of bladder condition, and assessment of treatment benefit. RESULTS: After 8 weeks, tolterodine ER produced a statistically significant decrease in the weekly urge incontinence episodes compared with placebo (-12.3 versus -8.0; P <0.0001). Other micturition variables improved significantly more with tolterodine ER. No difference was found between treatment groups regarding the change in the number of stress incontinence episodes. A significantly greater proportion of patients receiving tolterodine ER than those receiving placebo reported improvement in bladder condition (61% versus 46%; P <0.001) and treatment benefit (76% versus 55%; P <0.001). After 8 weeks, the tolterodine ER group had experienced statistically significant improvements compared with the placebo group in 9 of 10 quality-of-life domains. The frequency of adverse events was similar between treatment groups. CONCLUSIONS: Tolterodine ER is an effective treatment of urge urinary incontinence, frequency, and urgency in women with concomitant stress urinary incontinence. The efficacy of tolterodine ER in reducing urge incontinence episodes was unaffected by the presence of stress incontinence. The results of this study support the first-line use of antimuscarinic therapy to treat the urge incontinence component of urge-predominant mixed incontinence.

Adult↗

PubMed2004

Cytotoxicity of different intracavernous vasoactive drugs on cultured endothelial cells of human corpus cavernosum penis.

OBJECTIVES: To investigate the cytotoxic effect of prostaglandin E(1) (PGE(1)), a standard combination of papaverine/phentolamine, and a triple mixture of these agents on human cavernosal endothelial cells using a cell culture model. The endothelial layer of the corpus cavernosum plays an important role in signal transduction of penile erection and is directly exposed to vasoactive agents after intracavernous injection for erectile dysfunction. METHODS: Primary endothelial cells were obtained from the corpus cavernosum of 13 potent patients undergoing penile surgery. Cultured cells were exposed for 30 minutes to physiologic dilutions of 20 microg PGE(1), 30 mg papaverine/1 mg phentolamine, or the same dosages of the triple mixture of these agents, each dissolved in 5 to 50 mL sodium chloride. Lactate dehydrogenase release as a cytotoxicity marker was measured 6 hours after drug exposure, and the total cell metabolic activity was quantified after 48 hours with a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)-based assay. Additionally, the amount of viable cells was identified with a dual fluorescent staining procedure. RESULTS: The initial release of lactate dehydrogenase was elevated up to 3.2-fold in the concentrated papaverine/phentolamine and triple mixture group compared with PGE(1) and the control. After 48 hours, the papaverine-containing formulations led to a significant dose-dependent decrease in the viable cell count and metabolic activity of the cultures that was not noticed with PGE(1). CONCLUSIONS: These in vitro data strongly suggest an unfavorable effect of vasoactive agents containing papaverine on cavernosal endothelial cells. Before fibrotic changes of the smooth muscle stroma, the functionally important endothelium of the corpus cavernosum might suffer significantly from intracavernous injection therapy. Therefore, papaverine should no longer be used for this indication.

Alprostadil↗

PubMed2003

Androgen and estrogen receptors in the human corpus cavernosum penis: immunohistochemical and cell culture results.

Despite the central and peripheral effects of androgens on the nervous system, the local effects of androgens in the corpus cavernosum penis and their importance for erectile function is still unclear. In this study corpus cavernosum biopsies of eight adult potent patients, aged 19-63 years, undergoing penile deviation surgery (group A) and 12 patients undergoing male-to-female transsexual surgery (group B) were immunostained for nuclear androgen and estrogen-alpha receptors. Additionally, primary corpus cavernosum endothelial cell cultures were obtained from six transsexual patients and exposed to testosterone, dihydrotestosterone, estradiol and progesterone likewise for 7 days. Total cell count was performed and cell metabolic activity was measured by a tetrazolium salt-based assay. Androgen and estrogen-alpha receptors were detected in stromal as well as in endothelial cells. Of all cell nuclei, 74.9% (SD 16.4) in group A and 63.5% (SD 17.1) in group B were positively stained for androgen receptors. The respective percentage of estrogen receptors was 11% (SD 9.5) and 21.2% (SD 12.6). An age-dependent difference in receptor distribution was not observed in either group. In the cell culture system only cultures exposed to testosterone and dihydrotestosterone showed a dose-dependent increase of cell metabolic activity compared to the cultures supplemented with estradiol and progesterone. The significant and age-independent high androgen and low estrogen-alpha receptor distribution found in both groups suggests a possible peripheral effect of androgens at the level of the corpus cavernosum penis in adult humans. This is supported by the observed effect of testosterone and dihydrotestosterone on cell count and endothelial cell metabolism in our cell culture system. The role of estrogens remains unclear.

Adult↗

PubMed2003

Is there an inhibitory role of cortisol in the mechanism of male sexual arousal and penile erection?

BACKGROUND: It has been speculated for more than 2 decades whether there is a significance of adrenal corticosteroids, such as cortisol, in the process of normal male sexual function, especially in the control of sexual arousal and the penile erectile tissue. However, only few in vivo studies have been carried out up until now on the effects of cortisol on human male sexual performance and penile erection. In order to evaluate further the role of cortisol in male sexual activity, the present study was conducted to detect serum levels of cortisol in the systemic and cavernous blood taken during different penile conditions from healthy males. MATERIAL AND METHODS: The effects of cortisol derivative prednisolone, catecholamine norepinephrine (NE) and the peptide endothelin-1 (ET-1) on isolated human corpus cavernosum (HCC) were investigated using the organ bath technique. Fifty-four healthy adult male subjects were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Serum levels of cortisol (microg/dl) were determined by means of a radioimmunoassay (ELISA). RESULTS: In the healthy volunteers, cortisol serum levels significantly decreased in the systemic circulation and the cavernous blood with increasing sexual arousal, when the flaccid penis became rigid. During detumescence, the mean cortisol level remained unaltered in the systemic circulation, whereas in the cavernous compartment, it was found to decrease further. Under all penile conditions, no significant differences were registered between cortisol levels in the systemic circulation and in the cavernous blood. Cumulative addition of NE and ET-1 (0.001-10 microM) induced contraction of isolated HCC strips, whereas the contractile response to prednisolone was negligible. CONCLUSION: Our results strongly suggest an inhibitory role for cortisol in the mechanism of male sexual response and behaviour. These properties are mediated rather via an effect on central structures than on the penile erectile tissue. Future studies to include patients suffering from erectile dysfunction may reveal whether or not there are differences in the cortisol serum profiles of healthy subjects and patients under different stages of sexual arousal.

Adult↗

PubMed2003

Evolution of endoscopic extraperitoneal radical prostatectomy (EERPE)--technical improvements and development of a nerve-sparing, potency-preserving approach.

During the last decade, laparoscopy has become a standard technique in the armoury of the urologist due to constant technological advances and refinements. Laparoscopic radical prostatectomy (LRPE), although technically demanding and associated with a considerable learning curve, has become the surgical procedure of choice in selected and specialized urological centers around the globe for patients with clinically localized prostate cancer. However, a major drawback of LRPE is the transperitoneal route of access to the extraperitoneal prostate. The principal disadvantages of LRPE are potential intraperitoneal complications, such as bowel injury, ileus, intraperitoneal bleeding, intraperitoneal urinary leakage, intraperitoneal adhesion formation and concomitant small bowel obstruction. Endoscopic extraperitoneal radical prostatectomy (EERPE) is a further advancement of minimal invasive surgery as it overcomes the limitations of LRPE by the strictly extraperitoneal route of access combining the advantages of minimal invasive surgery with those of an extraperitoneal procedure. Based on our growing experience with this procedure, we have introduced several technical modifications, improvements and refinements including a nerve-sparing, potency-preserving approach (nEERPE) in an effort to further improve this minimally invasive procedure.

Adult↗

PubMed2003

Immunocytochemical distribution of nitric oxide synthase in the human seminal vesicle: a light and electron microscopical study.

Although nitric oxide (NO) has been proven to be one of the most important non-adrenergic, non-cholinergic mediators in the control of human reproductive tract organs, to date information on the significance of NO-mediated signal transduction in the control of human seminal vesicle (SV) function is still sparse.()Recent investigations have underlined the significance of NO in the maintenance of sperm capacitation and viscosity of the seminal plasma as well as in the control of mammalian seminal vesicle smooth muscle tone. In order to further investigate the functional impact of NO on the regulation of normal SV function, we examined the distribution of NADPH-diaphorase (NADPH-d), endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) in the cellular anatomy of human SV by means of light and electron microscopical immunocytochemistry (LM, EM) in combination with the tyramide signal amplification technique. Human SV were obtained from 15 patients who had undergone surgery for pelvic malignancies (carcinoma of the prostate or urinary bladder). SV specimens were fixed, sectioned and examined by LM and EM for the presence of NAPDH-d, eNOS and nNOS using specific antibodies and advanced staining procedures. LM revealed a dense NADPH-d reaction in glandular epithelial structures, whereas no substantial labeling was detected in the fibromuscular stroma. EM showed that the NADPH-d reaction product was abundantly detectable attached to membranes of the endoplasmic reticulum, mitochondria and the nuclei of glandular epithelial cells. nNOS staining was found in nerve fibers branching within the SV tissue. eNOS staining was present in small vessels but was only observed to a minor degree in glandular and subglandular structures and the smooth muscle stroma. Our results support the hypothesis that human SV is a site of NO production. The distribution of NADPH-d may give rise to the speculation that NO is mainly involved in the regulation of SV secretory activity. The sparse correlation between NADPH-d-, eNOS- and nNOS-staining might hint at the existence of a previously unidentified NOS isoform in human SV.

Adult↗

PubMed2003

Is serotonin significant for the control of penile flaccidity and detumescence in the human male?

For more then 15 years, there has been speculation on the significance of serotonergic pathways in the control of male sexual function, especially in the maintenance of penile flaccidity and the initiation of detumescence. However, only a few in vivo studies on peripheral serotonergic transmission have been carried out. The aim of the present study was to evaluate further the effects of serotonin (5-HT) on isolated human erectile tissue and to detect serum levels of 5-HT in the systemic and cavernous blood taken during different penile conditions from healthy males. The effects of 5-HT on isolated human corpus cavernosum (HCC) were investigated using the organ bath technique. A total of 41 healthy, adult male subjects were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Serum levels of 5-HT (ng/ml) were determined by means of an enzyme-linked immunosorbent assay. The cumulative addition of 5-HT (0.001-10 microM) induced contraction in the isolated HCC strips. The contractile response was abolished in the presence of 5-HT(1alpha)-receptor antagonist NAN-190. No attenuating effect of 5-HT was observed on electrically induced relaxation of the tissue. Moreover, amplitudes of relaxation remained unaltered in the presence of NAN-190. In the healthy volunteers, a significant increase in 5-HT levels was detected in the cavernous serum from flaccidity (113+/-62) to tumescence and rigidity (140+/-69 and 141+/-54, respectively), followed by a decrease in the detumescence phase (123+/-79). Changes in 5-HT levels in the systemic serum were less pronounced. Under all penile conditions, systemic 5-HT levels were higher than those registered in the cavernous serum. Although 5-HT does not appear to be involved in postsynaptic transmission in the HCC, our results may provide evidence for a physiological significance of 5-HT in the control of penile flaccidity and detumescence. Thus, our findings may give a rationale for the use of 5-HT antagonists in the pharmacotherapy of erectile dysfunction.

Adult↗

PubMed2003

Systemic and cavernous plasma levels of vasopressin in healthy males during different functional conditions of the penis.

The role of the sympathetic adrenergic system in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic-noncholinergic transmitters are involved in this process. Arginine-vasopressin (AVP, ADH), a pituitary peptide hormone with potent vasoconstrictor activity, may be one of the factors contributing to such control. The present study was undertaken to determine whether or not plasma levels of AVP change during penile flaccidity, tumescence, rigidity, and detumescence. We determined the plasma levels of AVP in the systemic as well as the cavernous blood of 25 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, and AVP was quantified in plasma aliquots obtained from the whole blood samples. A marked decline in mean AVP plasma levels from 5.4+/-2.7 ng/l during flaccidity to 2.9+/-2.5 ng/l during rigidity was registered in the systemic blood of the subjects. No further decline was observed when the rigid penis became detumescent. In contrast, no alterations in AVP plasma levels were detected in the cavernous blood under the different penile conditions. The results from our study are contrary to the hypothesis of a local release and uptake of AVP in the cavernous compartment in the control of penile flaccidity and detumescence. Moreover, our findings are not in favour of AVP as an important mediator involved in adrenergic neurotransmission in the corpus cavernosum penis. Nevertheless, our data indicate that the decrease in systemic AVP levels in response to sexual arousal might be a prerequisite to facilitate penile tumescence and rigidity in healthy males.

Adult↗

PubMed2003

Effects of various nitric oxide-donating drugs on adrenergic tension of human seminal vesicles in vitro.

OBJECTIVES: To evaluate the effects of the nitric oxide (NO)-donating compounds sodium nitroprusside (SNP), S-nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteine (SNAC), S-nitroso-N-acetylcysteine-ethylester (SNACET), and linsidomine (SIN-1) on the adrenergic tension of isolated human seminal vesicle strip preparations. The significance of the NO-cyclic guanosine monophosphate (cGMP) pathway in the regulation of smooth muscle tone in the human genitourinary tract has been well established. However, information on the significance of NO-mediated signal transduction in the functional control of the mammalian seminal vesicles is still sparse. METHODS: Seminal vesicle strip preparations were applied to an organ bath system under standard conditions. Tension was induced by the addition of 10 microM norepinephrine. After stable tension plateaus had been reached, the drugs were added in a cumulative manner (0.01 to 100 microM) and the isometric responses of the tissue registered. The effects of the compounds on the phasic contractility of the tissue preparations were also evaluated. The adenylyl cyclase-stimulating agent forskolin was used as a reference compound known to interfere with the cyclic adenosine monophosphate pathway. RESULTS: Adrenergic tension was dose dependently attenuated by the drugs. The rank order of potency, from greater to lesser, was GSNO, SNAC, SNP, SIN-1, forskolin, and SNACET. The rank order (from greater to lesser) with regard to the inhibitory effects of the compounds on the frequency of phasic contractions of the tissue induced by the addition of norepinephrine was GSNO, SNAC, SNP, and SIN-1; the effects of SIN-1, forskolin, and SNACET on the frequency of contractions were nearly equipotent. CONCLUSIONS: Our results strongly support the hypothesis that the contractility of the human seminal vesicle is under the control of the NO-cGMP pathway. This finding may give a rationale for the use of S-nitrosothiols, such as GSNO and SNAC, in the pharmacotherapy of hyperexcitatory disturbances of ejaculation (premature ejaculation).

Adrenergic alpha-Agonists↗

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↗