[100 years urology--surgical techniques].
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Publications and source records attributed to M C Truss.
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Results from experimental studies suggested a significance of the nitric oxide (NO)-cGMP- and cAMP-pathways in the control of the function of the smooth musculature of the human prostate. In addition, it has also been assumed that the vasoconstrictory peptide endothelin-1(ET-1) may play a role in the dynamic component of benign prostatic hyperplasia (BPH) and the so-called lower urinary tract symptomatology (LUTS). Nevertheless, up till now, little is known as to potential interactions between the contraction of prostatic smooth muscle mediated by ET-1 and the relaxation induced by NO and cGMP. Thus, it was the aim of the study to elucidate the effects of drugs interfering with the cGMP-pathway on the tension induced by ET-1 of isolated human prostate tissue, as well as contractile responses of isolated strip preparations to ET-1 and angiotensin-II (AT-II). Macroscopically normal human prostate tissue from the transition zone was obtained from male patients who had undergone surgery for localized cancer of the prostate or urinary bladder. Using the organ bath technique, the ability of ET-1 and AT-II to contract isolated prostate strips was evaluated. In another set-up, the effects of the NO-donor S-nitrosogluthatione (GSNO) and C-type natriuretic peptide(CNP), known as an endogenous ligand of the membrane bound guanylyl cyclase, (1 nM-1/10 microM) on the tension induced by 0.1 microM ET-1 of human prostate strips were investigated. The adenylyl cyclase stimulating agents forskolin and NO-donor natrium nitroprusside (NNP) were used as reference compounds. While AT-II failed to contract the prostate tissue, ET-1 induced stable and reproducible contractions of the tissue strips. The tension induced by 0.1 microM ET-1 was dose-dependently reversed by the drugs. The rank order of efficacy was forskolin >NNP>CNP(1 microM)>GSNO. R(max) values ranged from 55% (forskolin) to 35% (GSNO). Forskolin was the only compound which reached an EC50 value. Our results demonstrate that drugs in terfering with the cGMP- and cAMP-pathways can reverse the tension induced by ET-1. These findings are in support of the hypothesis that both cGMP and cAMP contribute to the control of the prostate smooth muscle tension and may provide new strategies for the future pharmacotherapy of LUTS und BPH.
During the last decade laparoscopy has become the standard technique in the urologist's armamentarium due to constant technological advancements and refinements. Laparoscopic radical prostatectomy (LRPE), although technically demanding and associated with a considerable learning curve, has become the operative procedure of choice for patients with clinically localized prostate cancer in selected and specialized urologic centers around the globe. However, a major drawback of LRPE is the transperitoneal route of access to the extraperitoneal organ of the prostate. The principal disadvantages of LRPE are potential intraperitoneal complications. Endoscopic extraperitoneal radical prostatectomy (EERPE) is a further advancement of minimally invasive surgery as it overcomes the limitations of LRPE by the strictly extraperitoneal route of access. Based on our growing experience with this procedure we introduce several technical modifications, improvements, and refinements including a nerve-sparing, potency-preserving approach (nEERPE) in an effort to further improve this minimally invasive procedure. We report our short-term follow-up results after 300 procedures. The mean operative times were 115 min without and 150 min with lymph node dissection, in total 140 min (range: 60-260 min). There was no conversion and the transfusion rate was 1.3%. There were three early reinterventions (two bleeding and one hematoma) and five late reinterventions (four symptomatic lymphoceles and one colostomy due to a rectal fistula). Pathological stage was pT2a in 54 patients (18%), pT2b in 87 patients (29%), pT3a in 115 patients (38.3%), pT3b in 40 patients (13.3%), and pT4 in 4 patients (1.3%). Positive surgical margins were found in 9.2% (13/141) of patients with pT2 tumor and 30.3% (47/155) of patients with pT3 tumor. The mean catheterization time was 6.9 days. Six and twelve months postoperatively 86.3 and 89.6% of the patients were completely continent; 9.2% of patients needed 1-2 pads per day and 4.5 and 1.2% of patients needed more than 2 pads per day, respectively. Short-term oncological and functional results of EERPE are at least as favorable as in LRPE while operative times are shorter and complication rates are low. EERPE is a technical advancement because it combines the advantages of a totally extraperitoneal access with the advantages of a minimally invasive procedure.
Female sexual dysfunction and even female sexual function are widely unknown. We therefore evaluated the sexual behaviour of younger and older women using a questionnaire. A total of 998 young women entered the study at Hannover Medical school. They were between 19 and 43 years old (median 24 years), and 64% answered the questionnaire. A total of 97.1% of the female students were heterosexual, 1.6% were lesbians and 1.3% were bisexual. Lack of sexual intercourse in the previous month was recorded by 21.1%, while 21.3% recorded intercourse 1-3 times a month, 46.8% 1-3 times a week and 5.5% daily. Adverse reactions to sexual situations were reported by 25% of the women, 20.5% had a negative perception for special partners or circumstances. Some 55% of the evaluated women were satisfied with their sexual life in the last month, 20% were fairly satisfied and 21% were un-satisfied. This study of a selected population of medical students shows a wide variety of sexual problems with a high prevalence of different disorders.
Today, the classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis, chancroid and inguinal granuloma, only account for a small proportion of all known sexually transmitted diseases (STDs). Other bacteria and viruses as well as yeasts, protozoa and epizoa must also be regarded as causative organisms of STD. Taken together, all sexually transmitted infections comprise more than 30 relevant STD pathogens. However, not all pathogens that can be sexually transmitted manifest diseases in the genitals and not all infections of the genitals are exclusively sexually transmitted. Concise information and tables summarising the diagnostic and therapeutic management of STDs in the field of urology allow a synoptic overview, and are in agreement with the recent international guidelines of other specialist areas. Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and recommended regimens are presented.
During the last decade laparoscopy has become a standard technique available to the urologist, through constant technological advances and refinements. The progress of laparoscopic/endoscopic techniques allows the indications for this surgery to include complex oncological procedures like radical prostatectomy. Since the first description of laparoscopic radical prostatectomy (LRP) in the early 1990s the technique has undergone significant technical modifications. Transperitoneal LRP is now a standard procedure and can be used successfully and reproducibly, giving results comparable with those from the open retropubic procedure. Despite many advantages, transperitoneal laparoscopy is associated with potential intraperitoneal complications. Because of the limitations inherent in the transperitoneal route, a totally extraperitoneal endoscopic radical prostatectomy (EERPE) has been developed. The totally extraperitoneal endoscopic access provides a safe and minimally invasive approach to various urological procedures, including prostatectomy. This technical improvement completely obviates intra-abdominal complications. EERPE combines the advantages of minimally invasive laparoscopy and the open retropubic approach. We review the surgical techniques of LRP and EERPE, and highlight the indications, contraindications and outcomes.
Disturbance of sexual function and sexual perceptions in the aging often have a significant negative impact on overall quality of life. Epidemiological data on this phenomenon are sparse. Recently, however, more investigations have been undertaken to improve diagnostic and therapeutic approaches. First scientific concepts are now emerging that will allow better patients care in the future.
The development of new imaging techniques and the refinement of established methods in uroradiological imaging is proceeding rapidly. In the last few years several important developments have been implemented in the routine diagnostic evaluation of urological patients.A milestone is the recent advent of multidetector helical computed tomography (CT), enabling the radiologist to provide the clinician with high-quality three-dimensional (3-D) reconstructions of the urological organs. Powerful workstations are an indispensable tool in the post-processing of CT and magnetic resonance imaging (MRI)data. Significant advances in imaging were obtained in the fields of oncological imaging (e.g. prostate MRI and spectroscopic imaging), paediatric uroradiology(e.g. MR urography) and the evaluation of stone disease by unenhanced helical CT.
Anticholinergic drugs are currently the therapy of choice to treat urgency and urge incontinence. However, muscarinergic receptor blockers with adequate selectivity for detrusor smooth muscle are not available. Also, in contrast to the normal detrusor, the unstable detrusor neurotransmission seems to be at least partially regulated by non-cholinergic (NANC) pathways. These factors may explain the common side effects and the limited clinical efficacy of these compounds. Specific modulation of intracellular second messenger pathways offers the possibility of organ selective manipulation of tissue function, specifically contraction and relaxation of smooth musculature. Because of their central role in the intracellular regulation of smooth muscle tone phosphodiesterases (PDEs) are an attractive pharmacological targets. The PDE 5 specific inhibitor sildenafil (Viagra) has revolutionized the treatment of patients with erectile dysfunction. Numerous other PDE inhibitors are currently under investigation for the treatment of various disorders. We investigated the role of PDEs in human detrusor smooth muscle. Our data demonstrate the presence of five PDE isoenzymes in human detrusor and suggest, for the first time, that the cAMP pathway and the calcium/calmodulin-stimulated PDE (PDE 1) are of functional importance in the intracellular regulation in this tissue in vitro. In addition. initial clinical data with the PDE 1 inhibitor vinpocetine in patients not responding to standard anticholinergic therapy indicate a possible role for vinpocetine in the treatment of urgency, urge incontinence and, possibly, low compliance bladder and interstitial cystitis. The results of a larger randomized, double-blind, placebo-controlled, multicenter trial with vinpocetine show a tendency in favor of vinpocetine over placebo; however, statistically significant results were documented for one parameter only. This might be due to the rather low dosage chosen and the small sample size. Further studies are necessary and currently underway to delineate the optimal dosage, indications and patient population. Modulation of intracellular key enzymes effecting second messenger metabolism, i.e. isoenzyme-selective PDE inhibition is a novel approach which possibly avoids the limitations of anticholinergic therapy in patients with lower urinary tract dysfunction.
Tolterodine has emerged as a new anticholinergic drug to treat detrusor instability in recent years. This substance and its major metabolite DD01 exhibit a favourable effect-to-side-effect ratio for the bladder. Several clinical studies demonstrated the drug's efficacy in reducing the symptoms of an overactive bladder (urgency, urge incontinence and high micturition frequency) and in increasing functional bladder volume. With a clinical effectiveness comparable to oxybutynin, the side effect-profile measures up favourably to oxybutynin. Consequently, though some limitations need to be addressed, tolterodine can be regarded as the drug of first choice to treat overactive bladders in a variety of patient groups: the young (and otherwise healthy), the elderly, as well as in patients with renal and hepatic insufficiency. A new extended release formula of tolterodine has been launched that may improve patients' compliance.
OBJECTIVES: To examine the functional effects of bradykinin (BK) and angiotensin II (AN II) on isolated human cavernous tissue and to detect any changes in the AN II levels in cavernous and peripheral blood samples taken from healthy volunteers at different functional conditions of the penile erectile tissue. Metabolites of the renin-angiotensin system and endothelium-derived vasoactive substances are known to be involved in the regulation of arterial vascular tone. The human corpus cavernosum (HCC), consisting of endothelial and smooth muscle cells, can be regarded as a compartment comparable to the vascular system. METHODS: The relaxing and contracting properties of BK and AN II on isolated HCC were investigated using the organ bath technique. Tissue levels of adenosine-3,5-cyclic monophosphate (cAMP) and guanosine-3,5-cyclic monophosphate (cGMP) were determined using specific radioimmunoassays, after exposing isolated HCC strips in a dose-dependent manner to BK, forskolin, and sodium nitroprusside. Blood samples were drawn simultaneously from the corpus cavernosum and cubital vein of 34 healthy volunteers at stages of penile flaccidity, tumescence, rigidity, and detumescence. Penile erection was induced by audiovisual and tactile stimulation. AN II levels were determined using a radioimmunoassay. RESULTS: In vitro, BK, forskolin, and sodium nitroprusside elicited dose-dependent relaxation of norepinephrine-induced tension of isolated HCC, and AN II evoked dose-dependent contraction of the HCC strips. The relaxing potency of BK was paralleled by its ability to elevate the intracellular levels of cAMP and cGMP. In vivo, the AN II levels in the cavernous plasma increased from 21.8 +/- 4.6 pg/mL in the flaccidity phase to 27.9 +/- 10 pg/mL in the detumescence phase. In the peripheral plasma, the AN II levels were 17.2 +/- 6.2 to 19.5 +/- 6.5 pg/mL in the respective penile stages. Thus, the mean AN II levels in the cavernous blood were about 30% higher than in the blood samples taken from the cubital vein. In the cavernous blood, the increase in the AN II plasma levels in the detumescence phase (27.9 +/- 10 pg/mL) was statistically significant. CONCLUSIONS: Our results suggest that penile cavernous smooth muscle tone is partially balanced by kinin-induced relaxation and AN II-induced contraction. Since the tissue and plasma levels of both peptides are regulated by the activity of the angiotensin-converting enzyme, there might be a rationale for the use of angiotensin-converting enzyme inhibitors in the treatment of erectile dysfunction associated with arterial hypertension.
The role of the sympathetic adrenergic nerves 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 transmitters are involved in this process. The peptide endothelin-1 (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated by various authors that ET-1 might be involved in the pathophysiology of erectile dysfunction. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels registered in systemic and cavernous blood cavities taken from healthy males and patients with ED during different penile conditions (flaccidity, tumescence/rigidity, detumescence). Thirty-two healthy adult males and 25 patients were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1/-2 was determined in plasma aliquots by means of an enzyme-linked immunoassay (ELISA). Mean systemic and cavernous plasma level of ET-1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernous blood during penile tumescence, rigidity and detumescence. In the group of patients, mean plasma ET-1/-2 levels in the phase of penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernous blood (flaccidity: 0.52+/-0.38 fmol/ml vs. 0.48+/-0.46 fmol/ml, respectively; detumescence: 0.53+/-0.33 fmol/ml vs. 0.27+/-0.11 fmol/ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and psychogenic etiology of ED. In the phase of detumescence, the mean ET-1/-2 level was lower in the cavernous blood cavities taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-1/-2 registered in the cavernous blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seems to be of no physiological significance, our data counteract the hypothesis of an ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding an involvement of ET-1 in the pathophysiology of erectile dysfunction.
The role of the sympathetic adrenergic nerves 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 transmitters are involved in this process. The peptide endothelin-l (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated that ET-1 might be involved in the pathophysiology of penile erection. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels recorded in systemic and cavernosal blood taken from healthy males and patients with erectile dysfunction (ED) during different penile conditions (flaccidity, tumescence/rigidity, detumescence). The study groups comprised 33 healthy adult males and 25 patients. The subjects were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET- 1/-2 was determined in plasma aliquots by means of an enzyme-linked immunosorbent assay (ELISA). Mean systemic and cavernosal plasma levels of ET- 1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernosal blood during penile tumescence, rigidity and detumescence. In the patients, mean plasma ET-1/-2 levels during penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernosal blood (flaccidity 0.52 +/- 0.38 fmol/ml vs 0.48 +/- 0.46 fmol/ml, respectively: detumescence 0.53 +/- 0.33 fmol/ml vs 0.27 +/- 0.11 fmol/ ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and those with a psychogenic aetiology of ED. During detumescence, the mean ET-1/-2 level was lower in the cavernosal blood taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-l/-2 in the cavernosal blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seemed to be of no physiological significance, our findings contradict the hypothesis of the ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding the involvement of ET-1 in the pathophysiology of erectile dysfunction.
Androgens influence important central and peripheral mechanisms of the erectile system. The relevance of a moderate decrease of serum testosterone level for erectile dysfunction (ED) has not been clarified so far. The aim of our study was to offer an easy transcutaneous method of androgen application. A previous study on the pharmacokinetic profile of the testosterone gel applied, showed marked elevation of the serum levels of testosterone. In our study, 46 hypogonadal patients with ED and total lack of vaginal penetration applied testosterone gel (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6-8 weeks, after a run-in period with placebo gel of 2 weeks. All patients showed decreased testosterone serum levels (<3 ng/ml) in at least two morning samples over a period of 3 weeks before treatment. Psychogenic etiology was excluded by a sexual psychologist. Patient age was 37-69 years (mean 53.5). Three patients (6.5%) responded to placebo in the run-in phase and were withdrawn from further treatment. Fifteen patients (32.6%) showed improved erection, allowing penetration and sexual intercourse. Twenty-eight patients (60.9%) did not respond to therapy. Local genital skin irritation was not observed. Elevation of peripheral testosterone was not correlated to a positive therapy response. A success-rate of 32.6% in this group of patients after exclusion of psychogenic patients and placebo-responders seems to justify further investigations. A medication period of 6-8 weeks is most probably too short to induce imaginable regenerative effects of testosterone on the erectile system. We therefore suggest that future double-blind and placebo-controlled studies should be designed for a minimum of 3 months. Testosterone gel may be a cost effective form of androgen administration.
Current pharmacological treatment modalities for urge incontinence and low compliance bladder are limited by a low clinical efficacy and the significant side effects of the standard drugs available. Previous in vitro studies indicated a possible functional relevance of the intracellular phosphodiesterase (PDE)-1 isoenzyme in the regulation of human detrusor smooth muscle contractility. We therefore investigated the effect of the PDE-1 inhibitor vinpocetine in nonresponders to standard pharmacological therapy. In 11/19 patients (57.9%) clinical symptoms and/or urodynamic parameters were improved. Although these initial data are preliminary, they represent the first evidence that isoenzyme-selective PDE inhibition may be a novel approach to the treatment of lower urinary tract disorders.
Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide turnover and, thus, smooth muscle tension. Recent reports have indicated the presence of PDE isoenzymes 1, 2, 4, and 5 in cytosolic supernatants prepared from human ureteral smooth muscle homogenates and the ability of second-generation inhibitors of PDE 3, 4, and 5 to relax KCl-induced tension of human ureteral muscle in vitro. The aim of the present study was to evaluate the functional effects of recently developed, third-generation isoenzyme-selective PDE inhibitors, the nitric oxide (NO)-donating agents sodium nitroprusside (SNP) and dihydropyridine (DHP), which is also described as an antagonist of L-type calcium channels, and the adenylyl cyclase-stimulating drug forskolin on tissue tension and cyclic nucleotide levels of human ureteral smooth muscle segments in vitro. Relaxant responses of human ureteral smooth muscle were investigated in vitro using the organ bath technique. Cyclic nucleotides cAMP and cGMP were determined by specific radioimmunoassay following time and dose-dependent incubation of the ureteral tissue with the drugs. The most pronounced relaxing effects on KCl-induced tension of ureteral smooth muscle were exerted by nitrovasodilator SNP, PDE4 inhibitor rolipram, and PDE5 inhibitors E 4021 and morpholinosulfonyl-pyrazolopyrimidine (MSPP). Relaxing potency of the drugs was paralleled by their ability to elevate intracellular levels of cGMP and cAMP, respectively. Our data suggest the possibility of using selective inhibitors of PDE isoenzymes 4 and 5 in the treatment of ureteral stones and ureteral colic.
The discovery of endocrine therapy of diseases of the prostate can be regarded as one of the most important events in the history of medicine and in urology in particular. This article delivers an overview about scientists and clinicians involved in this work during the last 200 years. A close historical relation between the endocrine therapy of benign prostatic hyperplasia and prostate cancer can be recognized. The historical framework between the work of John Hunter in the late eighteenth century, that of Charles Brenton Huggins in the late 1930s, and that of Andrew Schally in the 1970s has been assembled herein. With respect to all the other men who contributed greatly to this medical achievement, e.g., Edward L. Keyes and Russell S. Ferguson, with their first report on radioorchiectomy for the treatment of metastatic prostate cancer in 1936, this historical vignette is intended to make them part of the historical record.
The role of the sympathetic adrenergic nerves 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 transmitters might be involved in this process. Endothelin 1 (ET-1), a 21-amino-acid peptide with potent and long-lasting vasoconstrictor activity, may be one of the factors contributing to such control. The present study was undertaken to determine whether plasma levels of ET-1 changed during flaccidity, tumescence, rigidity, and detumescence. We determined plasma levels of ET-1 in the peripheral and cavernosal blood of 32 potent adult male volunteers, in whom penile tumescence and erection were elicited by exposure to visual and tactile erotic stimuli. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1 was quantified in plasma aliquots obtained from the blood samples. Using the organ bath technique, we evaluated the contractile effects of ET-1 and norepinephrine (NE) on isolated human corpus cavernosum musculature. No significant change in ET-1 levels was observed in the peripheral or cavernosal blood in the process of developing erection, rigidity, or detumescence. The mean plasma level of ET-1 was 0.2-0.7 fmol/ml. In the organ bath, ET-1 elicited concentration-dependent contractions of isolated human corpus cavernosum, which were much more pronounced than those evoked by the adrenergic agonist NE. Our data indicate that despite the in vitro efficacy of ET-1 in stimulating contractile activity in isolated human cavernous smooth muscle, the peptide may not be of ultimate importance for the mechanism of flaccidity and detumescence in healthy males. Nevertheless, the exact role of ETs in the control of penile smooth muscle tone remains to be established.