Pelvic organ prolapse is associated with alteration of sphingosine-1-phosphate/Rho-kinase signalling pathway in human vaginal wall.

Pelvic organ prolapse (POP) is a debilitating condition of unknown aetiology affecting > 50% of women over 40 years of age. In POP patients, the vaginal walls are weakened allowing descent of pelvic organs through the vagina. We sought to determine if sphingosine-1-phosphate (S1P) signalling, which regulates smooth muscle contractility and apoptosis via the RhoA/Rho-kinase (ROK) pathway, is altered in the vagina of women with POP. Utilising anterior vaginal wall specimens, we provide novel demonstration of the S1P pathway in this organ. Additionally, comparing specimens from women having pelvic reconstructive surgery for POP and control subjects, we reveal increases in mRNA expression of the three major mammalian S1P receptors (S1P1-S1P3), and RhoA and the ROK isoforms: ROKα and ROKß in POP patients, which correlates with a decrease in elastic fibre assembly pathway constituents. Taken together, our data suggest the S1P/ROK pathway as a novel area for future POP research and potential therapeutic development.

Effect of once-daily tadalafil on confidence and perceived difficulty in performing sexual intercourse in men who were incomplete responders to as-needed PDE5 inhibitor treatment.

INTRODUCTION: For men with erectile dysfunction (ED), the expectation of difficulty and level of confidence in achieving and maintaining an erection have an impact on sexual performance. OBJECTIVE AND METHODS: This 12-week, double-blind study investigated once-daily tadalafil (2.5 mg titrated to 5 mg or 5 mg) (n = 176) or placebo (n = 79) on confidence and perceived difficulty in performing sexual intercourse in men with ED who were incomplete responders to as-needed phosphodiesterase-5 inhibitor therapy. The Confidence in Performing Sexual Intercourse Questionnaire (CPSIQ) and Difficulty in Performing Sexual Intercourse Questionnaire (DPSIQ) were administered at baseline and 12 weeks. RESULTS: The mean change in CPSIQ for the tadalafil group was 1.8, which represents a shift from 'very low' to 'moderate' sexual confidence vs. a mean change of 0.5 in the placebo group (p < 0.0001). The mean change in DPSIQ for tadalafil was 1.6, which represents a shift from 'very difficult' to 'moderately' or 'slightly difficult' sexual performance vs. a mean change of 0.4 in the placebo group (p < 0.0001). Among men receiving tadalafil with an International Index of Erectile Function-Erectile Function (IIEF-EF) end-point score of ≥ 26 or who achieved a minimal clinically important difference in IIEF-EF score at end-point, the mean changes in CPSIQ were 3.0 and 2.4, respectively (both p < 0.0001). CONCLUSION: Once-daily tadalafil vs. placebo improves confidence and decreases difficulty in performing sexual intercourse for men with ED who were incomplete responders to as-needed PDE5 inhibitor therapy.

Coexisting lower urinary tract symptoms and erectile dysfunction: a systematic review of epidemiological data.

OBJECTIVE: Assess and categorise the available prevalence data on coexistent LUTS and ED in the general population and among individuals consulting a healthcare provider for any reason or when seeking treatment for LUTS and/or ED. METHODS: Literature search of English-language articles published during the last 15 years. RESULTS: Of 23 relevant studies identified, 12 used both the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF) as assessment tools and 11 used alternative approaches. In studies using both IPSS and IIEF, overall prevalence of coexistent LUTS/ED of any severity was not assessable for men in the general population, but rates ranged from 14-37% based on alternative assessments. In the general male population, 13-29% had moderate to severe LUTS and 8-35% had moderate to severe ED. In studies using both IPSS and IIEF, overall prevalence of coexistent LUTS and ED of any severity was 71-80% among men seeking treatment for LUTS, and 74% based on alternative assessments. Among men who sought treatment for either condition, 67-100% had moderate to severe LUTS and 43-59% had moderate to severe ED. Coexistence of LUTS and ED increased with age, ranging from 59-86% among men aged 40s to 60s in primary care to 79-100% in treatment-seeking men with LUTS aged 50s to 70s. Impact on QoL varied, but health-related QoL was generally worse in treatment-seeking men compared with men in the general population. CONCLUSIONS: Although less than one-third of middle-aged and older men in the general population have coexisting LUTS and ED, most men seeking treatment for either LUTS or ED have both conditions. Symptom severity and impact on QoL in each condition increase when LUTS and ED coexist.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Erectile dysfunction and testosterone screening with prostate specific antigen screening at age 40: are these three gender specific determinants additive for overall men's heath and do they improve traditional non-gender specific determinants to lessen cardiovascular risk and all-cause mortality?

AIMS: Assess support for a recommendation to add screening for both erectile dysfunction (ED) and hypogonadism to the initial medical evaluation of young-to-middle aged (≥ 40 years of age) men in light of recent guidelines suggesting prostate-specific antigen screening occur at that age. METHODS: A search of literature published from 1998 to 2009 was performed. Search terms included: ED combined with coronary artery disease (CAD), metabolic syndrome and hypogonadism, hypogonadism and ED, hypogonadism, ED and mortality. Articles were evaluated according to the Center of Evidence-Based Medicine. RESULTS: Both retrospective and prospective evaluations have demonstrated a strong relationship between ED, established cardiovascular risk factors, CAD and the potential occurrence of cardiovascular events. Low testosterone levels are associated with ED. Low serum total testosterone is an independent risk factor for both metabolic syndrome and type 2 diabetes and all-cause mortality. CONCLUSION: Traditionally, ED and testosterone levels have been considered mainly, if not exclusively, in the context of sexual health. The results briefly summarised herein and other recent reviews suggest that ED and hypogonadism are signals of future all-cause mortality and overall health status and thus move these evaluations into the broader arena of public health. Screening for ED and hypogonadism provide 'gender-specific determinants' to assess general metabolic and cardiovascular health risks in men. It is the opinion of the authors that this screening be performed in addition to the well-established non-gender-specific screening tests of lipids, blood pressure, obesity and serum glucose.

Benign prostatic hyperplasia evaluation, treatment and association with sexual dysfunction: practice patterns according to physician specialty.

AIMS: Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are a common problem in ageing men and are accompanied by sexual dysfunction (SD) in 40-70% of men evaluated in large-scale epidemiological studies. One year after the 2003 American Urological Association (AUA) guideline on BPH management was published, a survey of US urologists (UROs) and primary care physicians (PCPs) was conducted to ascertain physician knowledge of the AUA guideline and practice patterns regarding LUTS/BPH diagnosis, treatment and association with SD. METHODS: A 19-question qualitative survey, sponsored by the American Foundation of Urologic Disease, was mailed April 2004 to 7500 UROs and 17,500 PCPs, with responses collected until May 2004. RESULTS: A total of 788 surveys were returned (437 UROs; 351 PCPs). Only 62% of PCPs were aware of and only 41% of PCPs used the AUA-Symptom Index/International Prostate Symptom Score (AUA-SI/IPSS) to assess LUTS compared with 97% and 81% of UROs respectively. Alpha-blocker monotherapy was the treatment of choice for both UROs and PCPs. Compared with UROs, PCPs reported higher rates of SD in association with LUTS or BPH (37% vs. 27%) and BPH pharmacotherapy (27% vs. 21%). UROs and PCPs reported higher rates of SD side effects [ejaculatory dysfunction (EjD) and erectile dysfunction (ED)] for tamsulosin (EjD: UROs 22%, PCPs 12%; ED: UROs 7%, PCPs 10%) and doxazosin (EjD: UROs 14%, PCPs 10%; ED: UROs 7%, PCPs 12%) than for alfuzosin (EjD: UROs 6%, PCPs 4%; ED: UROs 4%, PCPs 5%). CONCLUSIONS: The results suggest that many PCPs are not using the AUA-SI/IPSS to assess LUTS in their ageing male patients. Both UROs and PCPs appear to be underestimating the prevalence of SD in men with LUTS/BPH relative to prevalence rates reported in large-scale epidemiological studies.

Sildenafil reduces bother associated with erectile dysfunction: pooled analysis of five randomized, double-blind trials.

Improvement in bother associated with erectile dysfunction (ED) is an important aspect of successful treatment of ED. Changes in erectile function and the bother associated with ED were assessed in this analysis of pooled data from five 12-week, multicenter, randomized, double-blind, placebo-controlled, flexible-dose studies of sildenafil. Men who received sildenafil (n=578, vs placebo, n=550) had significantly greater (least squares mean+/-s.e.) improvement in erectile function (EF) domain scores of the international index of erectile function (IIEF) (10.0+/-0.3 vs 1.0+/-0.3, P<0.0001) and in erection distress scale (EDS) total transformed score (18.8+/-0.8 vs 4.8+/-0.9, P<0.0001). Scores on individual questions of the EDS were 24-65% higher after treatment with sildenafil (vs 8-12%, for placebo). The change in EF domain score correlated positively with the change in total transformed EDS score (0.43, P<0.0001). Successful treatment of ED with sildenafil may reduce the bother associated with ED.

Male hypogonadism. Part I: Epidemiology of hypogonadism.

Male hypogonadism is a frequent and potentially undertreated condition. A number of longitudinal epidemiologic studies, including the Baltimore Longitudinal Study of Aging, the New Mexico Aging Process Study, and the Massachusetts Male Aging Study, have demonstrated age-related increases in the likelihood of developing hypogonadism. In addition to advancing age, increasing body mass index and/or type II diabetes mellitus may be associated with lower circulating androgen levels. Owing to the demographic trends toward increasing population age and life expectancy, together with the emerging pandemic of diabetes and recent trend toward an increasing prevalence of obesity in the United States, clinicians are likely to encounter increasing cases of hypogonadism in the near future.

Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors.

Potential pharmacokinetic interactions between dapoxetine, a serotonin transporter inhibitor developed for the treatment of premature ejaculation (PE), and the phosphodiesterase-5 inhibitors tadalafil and sildenafil, agents used in the treatment of erectile dysfunction (ED), were investigated in an open-label, randomized, crossover study (n=24 men) comparing dapoxetine 60 mg, dapoxetine 60 mg+tadalafil 20 mg, and dapoxetine 60 mg+sildenafil 100 mg. Plasma concentrations of dapoxetine, tadalafil, and sildenafil were determined by liquid chromatography-tandem mass spectrometry. Tadalafil did not affect the pharmacokinetics of dapoxetine, whereas sildenafil increased the dapoxetine AUCinf by 22%; these effects were deemed not clinically important. Dapoxetine did not appear to affect the pharmacokinetics of tadalafil or sildenafil. Most adverse events were mild in nature. Thus, dapoxetine has no clinically important pharmacokinetic interactions with tadalafil or sildenafil, and the combinations are well tolerated.

A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia.

The potential mechanisms underlying back pain and/or myalgia experienced by men taking tadalafil were investigated. An integrated analysis of 10 placebo-controlled tadalafil clinical trials (N=1846) showed that the incidence of back pain and/or myalgia was 9.4% in patients receiving tadalafil 10 mg (N=394), 8.3% in patients receiving tadalafil 20 mg (N=883) and 3.7% in placebo-treated patients (N=569). One (0.3%) patient receiving tadalafil 10 mg, six (0.7%) patients receiving tadalafil 20 mg, and no patients receiving placebo discontinued treatment due to back pain and/or myalgia. In a prospective study in healthy volunteers, no substantial changes were observed in laboratory markers indicative of inflammation or muscle damage, and tadalafil did not affect renal plasma flow nor produce lumbar or gluteal myositis by positron emission tomography scan or magnetic resonance imaging. Although the mechanism of back pain and/or myalgia remains unknown, these events appear to be self-limiting and a general effect of phosphodiesterase 5 inhibition.

Multi-institutional outcome study on the efficacy of closed-suction drainage of the scrotum in three-piece inflatable penile prosthesis surgery.

Infection is a devastating complication of penile prosthesis surgery that occurs in approximately 2-5% of all primary inflatable penile primary implants in most series. Prevention of hematoma and swelling with closed-suction drains has been shown not to increase infection rate and yield an earlier recovery time. Despite the intuitive advantages of short-term closed-suction drainage in reducing the incidence of postoperative scrotal swelling and associated adverse effects, many urologists are reluctant to drain the scrotum because of a theoretical risk of introducing an infection. In conclusion, this study was undertaken to evaluate the incidence of infection in three-piece penile prosthesis surgery with scrotal closed-suction drainage. A retrospective review of 425 consecutive primary three-piece penile prosthesis implantations was performed at three institutions in New Jersey, Ohio, and Arkansas from 1998 to 2002. Following the prosthesis insertion, 10 French Round Blake (Johnson & Johnson) or, in a few cases, 10 French Jackson Pratt, closed-suction drains were placed in each patient for less than 24 h. All subjects received standard perioperative antibiotic coverage. Average age at implant was 62 y (range 24-92 y). Operative time (incision to skin closure) was less than 60 min in the vast majority of cases. There were a total of 14 (3.3%) infections and three hematomas (0.7%) during an average 18-month follow-up period. In conclusion, this investigation revealed that closed-suction drainage of the scrotum for approximately 12-24 h following three-piece inflatable penile prosthesis surgery does not result in increased infection rate and is associated with a very low incidence of postoperative hematoma formation, swelling, and ecchymosis.

Adrenal metastases from renal cell carcinoma: role of ipsilateral adrenalectomy and definition of stage.

OBJECTIVES: We undertook this study to establish criteria for adrenalectomy in patients with renal cell carcinoma. METHODS: We retrospectively reviewed the records of 162 patients undergoing radical nephrectomy from 1979 to 1993 at University Hospitals of Cleveland. Simultaneous ipsilateral adrenalectomy was performed in 57 patients (35%). RESULTS: Three of these 57 patients (5.3%) had ipsilateral adrenal metastases. All 3 patients had large, left-sided, upper-pole tumors that extended through the renal capsule (Stage T3a). All 3 patients with adrenal metastases had progression to disseminated disease, with an average time to progression of 7.2 months, whereas only 13 (24%) of the 54 patients without adrenal metastases developed metastatic disease (none to adrenal), with an average time to progression of 27.6 months. No patient with organ-confined disease (Stage T1 or T2) or extracapsular disease in the midkidney or lower pole had adrenal metastases identified histologically. CONCLUSIONS: The prognosis is poor for renal cell carcinoma with ipsilateral adrenal involvement, even with complete removal. Because of this poor prognosis, we believe that adrenal involvement should constitute a separate stage category. We propose that patients with ipsilateral adrenal metastases via direct extension should be classified as having pathologic Stage pT3d. If the patient has an ipsilateral adrenal metastasis not via direct extension, contralateral adrenal metastasis, or bilateral adrenal metastases, the pathologic stage should be M1. Ipsilateral adrenalectomy should only be performed if a lesion is seen preoperatively on computed tomographic scan or if gross disease is seen at the time of nephrectomy although its removal may not benefit the patient.

Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury.

OBJECTIVES: To assess the efficacy of intraurethral prostaglandin E1 (alprostadil, MUSE) in treating erectile dysfunction in patients with spinal cord injury (SCI). METHODS: Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction. All patients were at least 1 year after injury, and all had previously used intracavernosal injections successfully (Schramek's grade 5 erection). The intraurethral drug was administered in the office, in the presence of a physician, with monitoring of blood pressure. If effective, the patient was then able to use MUSE at home. The first 3 patients underwent gradual dose escalation starting with 125 microg, without the use of a constriction ring. Because of hypotension, the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg. The quality of the erection was compared with that achieved with intracavernosal injections using Schramek's grading. RESULTS: The dose escalation (titration) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response. Transient hypotension was noted in these first 3 patients in whom the constricting band was not used. The highest dose of MUSE (1000 microg) was, therefore, used in the remaining 12 patients, with the constriction band. The quality of the erection varied and appeared to be less rigid in all patients (12 patients with grade 1 to 3; 3 patients with grade 4) than that noted with intracavernosal injection therapy (1 5 patients with grade 5). There was no incidence of priapism. The 3 patients with grade 4 erections tried the MUSE at home. All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy. CONCLUSIONS: MUSE appears to be somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction. It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension. Its ultimate use depends on the patient's level of satisfaction with the quality of the erection compared with intracavernosal injections.

Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase.

OBJECTIVES: To evaluate whether alterations in nitric oxide (NO) synthesis or activity contribute to age-related erectile dysfunction and to elucidate the mechanisms causing these alterations using the rabbit as our model of aging. METHODS: We compared the ability of the rabbit cavernosal smooth muscle to relax in the organ bath in response to acetylcholine (Ach, endothelium-dependent vasodilator), sodium nitroprusside (SNP, an NO donor), and A23187 (a calcium ionophore) in young (6 month old) and aged (2.5 to 3.5 year old) rabbits. In addition, the immunohistochemical expression of endothelial nitric oxide synthase (eNOS) in both young and aged rabbit cavernosal tissue was examined. Endothelial integrity was examined immunohistochemically with JC70. RESULTS: Ach-mediated relaxation of penile corporal tissue was significantly attenuated from a maximum of 68.39 +/- 6.27 (0.1 mM Ach, n = 4) in young rabbits to 39.02 +/- 4.88 (0.1 mM Ach, n = 6) in aged rabbits (P < 0.04). No statistically significant difference (P > 0.05) was noted between cavernosal relaxation to sodium nitroprusside between young rabbits (97.8%, 0.1 mM SNP, n = 5) and aged rabbits (76.1%, 0.1 mM SNP, n = 5). This suggested that the defect in the Ach-NO pathway was at the level of NO synthesis, not activity. Immunohistochemical staining for eNOS demonstrated upregulation in both the vascular endothelium and corporal smooth muscle of aged rabbit tissue compared with young rabbit cavernosal tissue (n = 5). Anatomic endothelial integrity was demonstrated in the young and aged rabbits by the presence of JC70. This suggested that the defect in the Ach-NO synthetic pathway was not at the level of eNOS and was not due to anatomic endothelial cell disruption. Finally, Ach-mediated cavernosal smooth muscle relaxation in the young rabbit was not significantly augmented (P > 0.05) in the presence of the calcium ionophore A23187 (10 microM). A23187, however, significantly augmented (P < 0.04) Ach-mediated relaxation in the aged rabbit from a maximum of 33.93 +/- 6.58 to 41.55 +/- 6.58 (10 microM Ach, n = 5). This suggested that a potential defect in the Ach-NO synthetic pathway was at the level of intracellular calcium flux and possibly at the level of the calcium-eNOS interaction. CONCLUSIONS: Endothelium-dependent relaxation is attenuated in the aging rabbit; eNOS is upregulated in the aging rabbit; and no difference is noted in response to direct NO donation between the young and aged rabbit. The endothelium is anatomically intact in both the young and aging rabbit. The calcium ionophore A23187 augmented the attenuated vasorelaxation in the aging rabbit cavernosum (although not to the levels seen in the young rabbit cavernosum) and had no effect on the young rabbit cavernosum. These data suggest that erectile dysfunction in the aging rabbit cavernosum appears to be related to endothelial dysfunction and is characterized by eNOS upregulation and aberrant intracellular calcium fluxes.

Hepatotoxicity related to intracavernous pharmacotherapy with papaverine.

OBJECTIVES: To determine the incidence of hepatotoxicity related to self-administration of intracavernous papaverine or papaverine/phentolamine (bimix). METHODS: From October 1994 through June 1996, we retrospectively reviewed the medical records of 71 consecutive patients diagnosed with organic erectile dysfunction (ED) and receiving intracavernous injection therapy. Inclusion criteria were documentation of normal baseline liver function tests (LFTs), a minimum of 6 months of follow-up that included LFTs, at least one self-injection every 2 weeks, and no other prior or concurrent treatment for ED. Thirty evaluable patients satisfied the inclusion criteria and formed group 1. Mean age was 63 years (range 40 to 77), mean follow-up was 18 months (range 6 to 32), and mean number of injections per month was 5.7 (range 3 to 12). An age-matched population of 20 patients (mean age 69 years, range 46 to 90) without ED but with similar comorbid risk factors formed the control group (group 2). All patients in group 2 had routine long-term follow-up of LFTs (mean 52 months, range 10 to 1 14). RESULTS: Two patients (6.67%) from group 1 had elevated LFTs during treatment: one experienced a mild elevation in alanine aminotransferase and the other developed transient elevations of total bilirubin and aspartate aminotransferase 6 months after beginning therapy. Both patients reported a history of alcohol abuse. Both patients remained asymptomatic. Neither patient required discontinuation of therapy. One patient (5%) from group 2 developed an elevation of total bilirubin at a follow-up of 12 months. CONCLUSIONS: Routine monitoring of LFTs is probably unnecessary during intracavernous pharmacotherapy. Patients with a history of alcohol abuse or liver disease, however, should be followed up more closely when papaverine is selected for intracavernous injection. In these patients, LFTs should be obtained before initiating treatment and at 6-month intervals.

Perineal abscess after embolization for high-flow priapism.

High-flow priapism is unusual and is most often due to blunt perineal trauma with resultant laceration of the cavernosal artery, creating an arteriocavernosal fistula. Although few cases have been reported, the consensus on management appears to be embolization of the fistula with autologous clot, alone or in combination with Gelfoam. We present a case of high-flow priapism treated in this manner. The embolized pseudoaneurysm evolved into an abscess that eventually spread to the perineum. The rarity of this entity and the postprocedural morbidity are reported.

EDITS: development of questionnaires for evaluating satisfaction with treatments for erectile dysfunction.

OBJECTIVES: To develop Patient and Partner versions of a psychometrically sound questionnaire, the EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction), to assess satisfaction with medical treatments for erectile dysfunction. METHODS: Treatment satisfaction differs from treatment efficacy as it focuses on a person's subjective evaluation of treatment received. Twenty-nine items representing the domain of treatment satisfaction for men and 20 representing partner satisfaction were generated. Two independent samples of 28 and 29 couples completed all items at two points in time. Spearman rank-order correlations were derived to assess test-retest reliability and couple coefficients of validity. Internal consistency coefficients were calculated for both Patient and Partner versions and a content validity panel was used to analyze content validity. RESULTS: Only items that met all the following criteria were selected to comprise the final questionnaires: (a) range of response four or more out of five; (b) test-retest reliability greater than 0.70; (c) ratings by at least 70% of the content validity panel as belonging in and being important for the domain; and (d) significant correlation between the subjects' and partners' responses. Eleven patient items met criteria and formed the Patient EDITS; five partner items met criteria and formed the Partner EDITS. Scores on the two inventories were normally distributed with internal consistencies of 0.90 and 0.76, respectively. Test-retest reliability for the Patient EDITS was 0.98; for the Partner EDITS, it was 0.83. CONCLUSIONS: Reliability and validity were well established, enabling the EDITSs to be used to assess satisfaction with treatment modalities for erectile dysfunction and to explore the impact of patient and partner satisfaction on treatment continuation.

Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS.

OBJECTIVES: We hypothesized that advanced glycation end product (AGE) formation contributes to erectile dysfunction (ED) by quenching nitric oxide. Our first goal was to identify the specific AGE pentosidine in the diabetic human penis. Because AGE-mediated effects may involve inducible nitric oxide synthase (iNOS), we performed immunohistochemical and Western blot analysis of diabetic and nondiabetic human penile tissue for iNOS. Finally, because AGEs may act intracellularly to affect proteins, we set out to identify endothelial NOS (eNOS) in the human penis as an initial step in examining a possible intracellular interaction between eNOS and AGEs. METHODS: We performed high-performance liquid chromatographic analysis of diabetic human penile corpus cavernosum and serum for pentosidine and performed immunohistochemical, electron microscopic (EM), and Western blot analysis of the diabetic and nondiabetic penile corpus cavernosum and tunica for pyrraline, iNOS, and eNOS (and neural NOS [nNOS] for comparative purposes) via standard methods. RESULTS: We found a significant elevation of pentosidine in the penile tissue but not the serum of diabetic patients (average age 55.6 +/- 2.3 years) compared with that of nondiabetic patients (average age 61.8 +/- 3.6 years). Pentosidine was 117.06 +/- 9.19 pmol/mg collagen in the diabetic tunica versus 77.58 +/- 5.5 pmol/mg collagen in the nondiabetic tunica (P < 0.01) and 74.58 +/- 8.49 pmol/mg collagen in the diabetic corpus cavernosum versus 46.59 +/- 2.53 pmol/mg collagen in the nondiabetic corpus cavernosum (P < 0.01), suggesting a tissue-specific effect of the AGEs. We localized the site of deposition of the specific AGE pyrraline to the human penile tunica and the penile corpus cavernosum collagen. Immunohistochemical and EM analysis localized eNOS and iNOS to the cavernosal endothelium and smooth muscle. Western blot analysis in 6 patients revealed the following: iNOS, but no eNOS, in penile tissue from 1 insulin-dependent diabetic man; eNOS only in 1 man after radical prostatectomy; both eNOS and iNOS in 2 men with Peyronie's disease, as well as in 2 other men with impotence and hypertension. Finally, the specific iNOS inhibitor PNU-19451A significantly augmented relaxation of precontracted human cavernosal tissue, from 64.7% +/- 5.58 to 80.03% +/- 4.55 at 10 microM acetylcholine and 65.06% +/- 2.84 to 86.16% +/- 3.96 at 0.1 mM acetylcholine (n = 4, P < 0.002 and P < 0.02, respectively). CONCLUSIONS: AGEs are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum. We identified eNOS and iNOS in the human penile cavernosal smooth muscle and endothelium. The augmentation of cavernosal relaxation with a specific iNOS inhibitor, combined with the identification of iNOS protein, but not eNOS, in a patient with severe diabetes and ED, allows for speculation of a pathophysiologic mechanism for AGE-mediated ED via upregulation of iNOS and downregulation of eNOS. These data provide further insight into the mechanisms of advanced glycation end product-mediated ED and provide a foundation for further study.

Vasculogenic impotence and cavernosal oxygen tension.

AIMS OF THIS STUDY: To determine the associations, if any, of cavernosal oxygen tension with vasculogenic impotence. MATERIALS AND METHODS: We evaluated penile cavernosal blood gas levels in men with suspected vasculogenic impotence during penile duplex ultrasonography and/or dynamic infusion cavernosometry and cavernosography (DICC). Patients with suspected impotence were evaluated from 1992-1996. Patient ages ranged from 24-75 y (mean 48 y). Eighteen men had arteriogenic impotence diagnosed by abnormal penile duplex ultrasound after injection of a vasoactive agent, and 23 men had venous leakage diagnosed by DICC. RESULTS: Eighteen men with arteriogenic impotence had the following mean blood gas values: pH = 7.38+/-0.01, PCO2 = 45.50+/-0.94, PO2 = 65.17+/-2.16. Twenty-three men with venogenic (venous leak) impotence had the following mean cavernosal blood gas values: pH = 7.41+/-0.01, PCO2 = 42.26+/-0.83, PO2 = 74.17+/-2.51. The differences in PO2 were significant (P<0.05). A subgroup of men with severe venous leakage had PO2 values that were similar to the low arterial PO2 values. CONCLUSION: The low PO2 in patients with arteriogenic impotence, and the subset of men with severe venous leak impotence, support a global concept of low cavernosal PO2 as a mechanism for both arteriogenic and venogenic impotence.

Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.

PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.