Sildenafil citrate efficacy 8 h postdose in men with mild to moderate erectile dysfunction.

In two randomized, double-blind, placebo-controlled trials of 100 mg sildenafil citrate, men (N=601) with mild to moderate erectile dysfunction (ED) attempted intercourse 8 h (range, 7-9 h) postdose. The baseline to end-of-treatment improvement in the sildenafil groups vs placebo was greater (P<0.001) for the per-patient proportion (PPP) of 'yes' responses to the Sexual Encounter Profile question 3 (SEP3: successful intercourse (primary outcome)) (odds ratio (OR)=3.2 (trial 1), 7.6 (trial 2) and 5.6 (pooled data)); PPP of erection hardness score 4 (EHS 4, completely hard and fully rigid) (OR=6.2 (trial 1) and 10.9 (trial 2)); scores on the International Index of Erectile Function; and other EHS and SEP outcomes. Two to three times as many men were satisfied with sildenafil vs placebo treatment (Erectile Dysfunction Inventory of Treatment Satisfaction Index >50). Thus, responsiveness to 100 mg sildenafil may persist for 8 h postdose in men with mild to moderate ED.

Early sildenafil dose optimization and personalized instruction improves the frequency, flexibility, and success of sexual intercourse in men with erectile dysfunction.

We investigated the effect of early sildenafil dose optimization and personalized instructions on sexual intercourse success in 1109 men beginning sildenafil therapy for erectile dysfunction. In phase 1 (4 weeks), patients followed the instructions contained in the sildenafil (50 mg) sample pack and had 1.4 sexual intercourse attempts per week with 82% success. Patients (17%) had a second intercourse attempt (80% successful): 58% occurred within 4 h, 20% within 5-8 h, and 22% within 9-24 h of the first attempt. In phase 2 (4 weeks), sildenafil was adjusted as needed (53% to 100 mg, and 2% to 25 mg), and investigators provided personalized instructions to facilitate patient success. Sexual intercourse attempts increased to 1.7 per week, with 91% success, and 18% were followed by a second attempt, of which 91% were successful. Most patients requested the 100-mg dose, which helped improve sexual intercourse frequency, flexibility and success.

Tadalafil dosed once a day in men with erectile dysfunction: a randomized, double-blind, placebo-controlled study in the US.

The efficacy and safety of tadalafil, dosed once a day for the treatment of erectile dysfunction, was assessed in a randomized, double-blind, placebo-controlled, parallel-design study at 15 US centers. Following a 4-week treatment-free run-in period, patients (>or=18 years of age) were randomly assigned to 24 weeks treatment with tadalafil 2.5 mg, tadalafil 5 mg or placebo. Primary efficacy endpoints were change at 24 weeks in International Index of Erectile Function Erectile Function (EF) Domain score and mean per-patient percentage 'yes' responses to Sexual Encounter Profile diary questions 2 and 3. Tadalafil significantly improved erectile function compared with placebo for all three co-primary efficacy endpoints. Few patients discontinued because of adverse events (2.1%, placebo; 6.3%, tadalafil 2.5 mg; 4.1%, tadalafil 5 mg). Common treatment-emergent adverse events (>or=5%) were nasopharyngitis, influenza, viral gastroenteritis and back pain. Tadalafil 2.5 mg and 5 mg, dosed once a day for 24 weeks, was well tolerated and significantly improved erectile function.

Long-term results of the FemSoft urethral insert for the management of female stress urinary incontinence.

A 5-year ongoing, controlled multicenter study enrolled 150 women. Outcome measures included pad weight tests (PWT), voiding diary (VD), quality of life (QOL) and satisfaction questionnaires. Outcome measures during the baseline period were compared to evaluations during follow-up. Concurrent evaluations with and without device use were also performed. Safety evaluations included urinalysis and culture, leak-point pressure (LPP) and cystoscopy. Adverse events (AE) were recorded throughout the study. One to 2 years of follow-up were collected on all study participants (mean 15 months). Statistically significant reductions in overall daily incontinence episodes (P<0.001) and PWT urine loss (P<0.001) were observed with the device at all follow-up intervals, and 93% of women had a negative PWT at 12 months. Women were satisfied with ease of use of the device, comfort and dryness, and significant improvements in QOL were observed (P<0.001). Subgroup analysis revealed that the insert was effective, despite the presence of urgency, low LPP, failed surgery and advanced age. AE included symptomatic urinary tract infection in 31.3%, mild trauma with insertion in 6.7%, hematuria in 3.3%, and migration in 1.3% of women. The results of PWT and VD demonstrated device efficacy. Women were satisfied and significant improvements in QOL were observed. AE were transient and required minimal or no treatment. The urethral insert should be considered as an option for the management of SUI.

Characterization of type I 5 alpha-reductase activity in DU145 human prostatic adenocarcinoma cells.

The conversion of testosterone (T) to dihydrotestosterone (DHT) has been demonstrated to be catalysed by at least two isoforms of human steroid 5 alpha-reductase, designated types I and II. Type II 5 alpha-reductase expression predominates in human accessory sex tissues, localized to the fibromuscular stromal compartment. The type I isoform predominates in skin, prostatic epithelia and, to a lesser extent, in prostatic fibromuscular stroma. The significance of the type I isoform to prostatic cellular growth and function remains undefined. In cultured DU145 cells, we evaluated the metabolism of [14C]-T and demonstrated the time-dependent formation of [14C]-DHT. Oxidative metabolism (conversion of [14C]-T to [14C]-androstenedione) and the formation of conjugated androgen metabolites occurred at a relatively low rate in the DU145 cells. Using human type I 5 alpha-reductase cDNA, Northern blot analysis of DU145 cell mRNA revealed high levels of type I isoform expression. Analogous probing of the DU145 cells with a human 5 alpha-reductase II cDNA failed to reveal expression of the type II isoform. The expression of functional type I activity has been confirmed pharmacologically using isoform-selective 5 alpha-reductase inhibitors. Reductive metabolism of [3H]-T in the DU145 cells was inhibited in a concentration-dependent manner by LY306089, a potent non-steroidal type I-selective inhibitor (IC50 = 10.0 nM). SKF105657, a steroidal type II-specific inhibitor was distinctly less active at inhibiting [3H]-DHT formation. LY306089 was a non-competitive inhibitor of type I 5 alpha-reductase in DU145 cellular homogenates with an apparent Ki value of 4.0 nM. These studies have identified and pharmacologically defined type I 5 alpha-reductase activity in an androgen-insensitive prostatic cancer cell line and provide the basis for additional investigations into the significance of type I 5 alpha-reductase to human prostatic pathophysiology.

Urinary incontinence: the basics.

Urinary incontinence (UI) is a widely prevalent problem that affects people of all ages and levels of physical health, both in healthcare settings and in the community. Contributing to the problem are that many practitioners remain uneducated about this condition, individuals are often too ashamed or embarrassed to seek professional help, and there are significant variations in diagnostic and treatment practices. Five types of UI are stress, urge, overflow, functional and manufactured incontinence. Stress, urge and overflow are caused by factors within the urinary tract and will be concentrated on in this article. To diagnose UI a three-part assessment should be conducted, including the patient history, physical examination, and urinalysis. A behavioral program should be designed which incorporates identification and education for both patient and clinician. Treatment options include pelvic floor exercises (Kegel), vaginal cones, bladder training (retraining), habit training (timed voiding), electrostimulation and biofeedback, clean intermittent catheterization, indwelling catheters, medications, collagen injections, surgery, and absorption products. Most patients can be helped dramatically or cured with the appropriate treatment.

Achieving a state of urinary continence for residents of nursing facilities. Part III: Manufactured incontinence.

The recognition and treatment of manufactured incontinence requires a thorough understanding of the pathogenesis of urinary incontinence. It is important to realize that is frequently not only what is done to the patient but what is not done or even what is overlooked.

The roles of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in the management of pyelocaliceal diverticula.

Various combinations of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous nephrostolithotomy were used in the treatment of 40 stone-containing caliceal diverticula in 39 patients (16 men and 23 women). Only 1 of 26 patients (4%) treated with ESWL as a single modality became stone-free, although 9 (36%) became asymptomatic. Ten patients undergoing ESWL primarily eventually required percutaneous nephrostolithotomy due to persistence of symptoms and all became stone-free. A total of 14 patients underwent a percutaneous approach as a single modality, and the diverticula in 13 of these patients became stone-free, although 2 patients did have residual parenchymal fragments. Therefore, 21 of 24 patients (87.5%) became completely free of stones using the percutaneous approach. All patients managed with percutaneous nephrostolithotomy became free of symptoms. The complex nature of access during percutaneous nephrostolithotomy favors a 1-stage approach with direct puncture into the stone-containing diverticulum. Simultaneous fulguration of the diverticulum at percutaneous nephrostolithotomy is favored, since all 17 patients in whom this technique was used had complete obliteration of the diverticulum on followup contrast studies. These data suggest that caliceal diverticula should be managed with percutaneous nephrostolithotomy, since ESWL monotherapy is unlikely to produce a stone-free or symptom-free status.

Transverse colon-gastric tube composite reservoir.

We describe our technique for a new form of continent urinary diversion. This reservoir includes a detubularized segment of transverse colon to provide low pressure urine storage, tunneled ureteral reimplants to prevent reflux, and a tubularized gastric segment used as a continent catheterizable efferent limb. This technique provides a new option for continent diversion in a variety of patients.

Bradykinin-induced contractions of canine prostate and bladder: effect of angiotensin-converting enzyme inhibition.

Alpha-adrenergic, cholinergic, and serotonergic receptor-mediated contractile responses have been well characterized in the genitourinary tissues of several mammalian species. The present study characterizes the in vitro contractile responsiveness of canine bladder and prostate to the peptides, bradykinin, angiotensin I, and angiotensin II. All preparations contracted to 0.15 M KCl. Bradykinin elicited contractile responses in both prostate (10(-10) to 10(-7) M) and bladder (10(-10) to 10(-6) M). In both tissues, angiotensin II produced minimal responses and angiotensin I failed to elicit contractions. The potent angiotensin converting enzyme (ACE) inhibitor, enalaprilic acid [MK-422] (10(-6) M) increased the contractile response to the prostate to bradykinin two-fold while having no effect on bradykinin-induced contractions in the bladder. Enalaprilic acid did not affect the contractile responses of the two tissues to angiotensin I or angiotensin II. The canine urogenital tissue contractile responses to bradykinin, angiotensin I, and angiotensin II may have relevance to human physiology. Previous studies have demonstrated that human prostatic tissue, specifically benign prostatic hyperplasia (BPH), has the highest concentration of ACE activity of tissues evaluated. Bradykinin is a potent peptidergic contractile agent in canine bladder and prostate. The activity of enalaprilic acid to amplify the bradykinin-induced contractions in the canine prostate is consistent with high levels of ACE in the tissue. These data confirm the sensitivity of the canine prostate to bradykinin and report for the first time, the ability of bradykinin to induce contractions in the prostate. These studies support the possibility that bradykinin may be involved in mediating micturition under normal and pathological states such as infravesical obstruction secondary to BPH. Furthermore, the results from these investigations in canine urogenital tissues, if applicable to humans, suggest that urinary function be closely monitored in patients receiving ACE inhibitor therapy.

Use of magnetic resonance imaging to determine surgical approach to renal cell carcinoma with vena caval extension.

Extension of renal cell carcinoma into the vena cava is found in 4 to 10 percent of patients. One key to successful surgical management is defining the superior extent of the thrombus. Currently, this is accomplished by using inferior venacavography. The limitations of this imaging technique include difficulty in defining the superior extent of the thrombus and determining the presence of hepatic vein involvement. We report our experience using magnetic resonance imaging (MRI) in 9 patients to stage the thrombus and to determine the operative approach. We believe that MRI supplants other imaging techniques for staging tumor thrombi in renal cell carcinoma.

Ectopic ureter presenting as a psoas abscess.

Psoas abscesses are uncommon infections whose etiology may be primary or secondary. We report on a boy with ureteral ectopia presenting as a secondary psoas abscess. The diagnosis of a psoas abscess is protean and should be considered in all patients, particularly children, who present with acute thigh or hip pain and fever.

Erosion of penile prostheses: a complication of urethral catheterization.

We studied 9 patients with indwelling urethral catheters or who were using intermittent clean catheterization and who had received a penile prosthesis. A 56 per cent (5 of 9) incidence of urethral erosion was found in this population. Urethral erosion was a late complication, 80 per cent (4 of 5) of the time in our series, that usually presented several months after implantation of the prosthesis. We believe that the etiological factors that contributed to this disastrous complication were the friction and inflammation associated with catheterization. We currently construct a perineal urethrostomy in patients who desire a penile prosthesis and who perform intermittent catheterization. If intermittent catheterization is not feasible, insertion of a suprapubic tube is recommended. We additionally recommend insertion of an inflatable penile prosthesis, since this type is relatively soft most of the time and will not cause as much pressure at the end of the penis. Since instituting these procedures we have not encountered any erosion.

Creation of a transverse colon--gastric composite reservoir: a new technique.

All existing continent urinary reservoirs utilize cecum and/or varying lengths of ileum. In patients who have received prior pelvic radiation therapy, continent diversion has not been feasible because those segments of bowel lie within the field of irradiation. We describe a new technique of continent diversion utilizing only bowel outside the field of pelvic irradiation. A urinary reservoir is constructed from reconfigured transverse colon. A tubularized segment of stomach is implanted beneath the taenia of the reservoir to provide a continent, catheterizable stoma. We describe this technique in detail and report our results in five dogs followed for a mean of 59 days.

Endoluminal radio-frequency electrocautery for permanent ureteral occlusion in swine.

An animal experiment was undertaken to assess the feasibility of using radio-frequency current-mediated thermal injury of the ureter to produce ureteral occlusion by means of an endoluminal approach. Through open pyelotomies, balloon angioplasty catheters coated with gold bipolar electrodes were introduced into the ureters. Doses (at 650 kHz) were delivered for specific energy totals in 13 of 15 ureters in eight pigs. Two ureters served as controls (balloon inflation without current application). In six experimental animals not killed immediately after the procedure, postoperative ureteral manometric studies and nephrostography were performed and nephrostomy drainage was maintained until death (1-8 weeks). Treatment with 200-400 J produced safe, reliable occlusion by 4 weeks. At histopathologic study at 4 and 8 weeks, necrotic muscularis propria had been replaced by fibrous tissue. Cardiac rhythm was not affected during treatment.

Comparative contractile responses among ventral, dorsal, and lateral lobes of the rat prostate.

Prostatic zonal heterogeneity as a factor influencing urogenital smooth muscle contractile mechanisms was evaluated in the dorsal, lateral, and ventral lobes of the sexually mature rat. Additionally, using the ventral lobe, we assessed the role of the prostatic capsule to determine its contribution to tissue contractility. Smooth muscle contractile responses were determined for the alpha-adrenergic agonists norepinephrine and methoxamine; the cholinergic agonist carbamylcholine; the alpha 2-adrenergic agonist UK-14,304; serotonin; and potassium chloride. The dorsal, lateral, and ventral lobes contracted in response to all agonists. In the three lobes, norepinephrine was the most potent contractile agent; alpha 2 receptor activation with UK-14,304 resulted in the lowest maximum response. Carbamylcholine and serotonin were only weak contractile agonists in all three lobes. Maximum contractile responses to alpha agonists were greatest in the ventral prostate relative to the other two lobes, based on contractile responses to norepinephrine and methoxamine relative to KCl. The contractions of the ventral lobe in the presence and absence of the capsule were similar; thus the observed responses were not enhanced by the capsule but were attributable primarily to the presence of prostatic smooth muscle. Insofar as these studies with anatomically distinct lobes in the rat may reflect zonal homology in other species, these results support the contention that all zones may contribute to prostatic contractility.

Symphyseal diastasis in the absence of the exstrophy-epispadias complex.

Symphyseal diastasis in the absence of exstrophy or epispadias is rare. We reviewed 11 reported cases and present 2 of our own. Based upon our findings, we recommend a thorough physical examination in all patients. A voiding cystourethrogram in those with the radiographic finding of symphyseal diastasis in the absence of exstrophy or epispadias may be helpful. A significant number of patients have associated congenital anomalies.