Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

AIMS: To study the impact of glycaemic control on urinary incontinence in women who participated in the Diabetes Control and Complications Trial (DCCT; 1983-1993) and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC; 1994-present). METHODS: Study participants were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC follow-up, the urological assessment questionnaire (UroEDIC). Urinary incontinence was defined as self-reported involuntary leakage of urine that occurred at least weekly. Incident urinary incontinence was defined as weekly urinary incontinence present at EDIC year 17 but not at EDIC year 10. Multivariable regression models were used to examine the association of incident urinary incontinence with comorbid prevalent conditions and glycaemic control (mean HbA1c over the first 10 years of EDIC). RESULTS: A total of 64 (15.3%) women with Type 1 diabetes (mean age 43.6 ± 6.3 years at EDIC year 10) reported incident urinary incontinence at EDIC year 17. When adjusted for clinical covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), the mean EDIC HbA1c was associated with increased odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01-1.06 per mmol/mol increase; odds ratio 1.41, 95% CI 1.07-1.89 per % HbA1c increase). CONCLUSIONS: Incident urinary incontinence was associated with higher HbA1c levels in women with Type 1 diabetes, independent of other recognized risk factors. These results suggest the potential for women to modify their risk of urinary incontinence with improved glycaemic control. (Clinical Trials Registry no: NCT00360815 and NCT00360893).

Men with diabetes may require more aggressive treatment for erectile dysfunction.

Diabetes mellitus (DM) and erectile dysfunction (ED) are common health problems that markedly increase in prevalence and incidence with advancing age. DM is a known risk factor for developing ED; however, among men with ED it is unknown if DM alters the need for more invasive therapies. We sought to determine whether DM is associated with increased ED severity, reduced effectiveness of first-line (oral) therapies, and therefore higher utilization of second- and third-line therapies. The Inovus I3 database was queried to identify men with ED. Claims were followed for 48 months. Men with incomplete follow-up data and those diagnosed with DM after ED diagnosis were excluded from analysis. Rates of second-line (penile suppositories or injectables) and third-line (penile prostheses) ED therapies were compared between men with and without preexisting DM. Risk of progressing to second- and third-line therapies associated with DM was assessed with logistic regression and Kaplan-Meier analysis. From 1 January 2002 to 31 December 2006, 136 306 men were identified with prevalent and incident ED. Among this group, 19 236 men had DM that preceded their ED diagnosis. Men with DM were more than 50% more likely to be prescribed secondary ED treatments over the 2-year observation period, and more than twice as likely to undergo penile prosthesis surgery. Among a large population-based cohort of men with ED, those with DM are more likely to require more aggressive treatments. These data suggest that ED among men with diabetes may be less responsive to first-line treatments (oral agents), worsen more rapidly, or both.

Effect of endothelial cell-based iNOS gene transfer on cavernosal eNOS expression and mouse erectile responses.

Inducible nitric oxide synthase (iNOS) gene transfer is reported to augment erectile responses in rats, although it is also shown to impair vasorelaxation in cerebral arteries. We investigated the effect of endothelial cell-based iNOS gene transfer on endothelial NOS (eNOS) expression and mouse erectile responses. Human coronary artery endothelial cells (EC) transduced with empty vector (control) or iNOS were grown in culture and transplanted into the corpus cavernosum of severe combined immunodeficient mice. Endothelial NOS expression was compared in control and iNOS-transduced cells grown in the presence or absence of a selective iNOS inhibitor, L-N6- (1-iminoethyl) lysine hydrochloride (L-NIL). At 3-5 days after cell transplantation, we recorded intracorporal pressure (ICP) responses to cavernosal nerve stimulation and measured cavernosal total NO and eNOS protein expression. In this study, EC transduced with iNOS produced significantly more NO than controls but exhibited a twofold downregulation of eNOS protein and mRNA. This effect was reversed by L-NIL. In vivo, the cell-based gene transfer of iNOS led to significantly increased ICP responses, compared to mice transplanted with control ECs. Consistent with the in vitro data, cavernosal lysates had significantly reduced eNOS expression. In conclusion, EC gene transfer of iNOS downregulates EC expression of eNOS by an NOS-dependent mechanism. In the cavernosum of mice transplanted with Inos-transduced EC, nerve-stimulated erectile responses were augmented by the short-term gene transfer. However, our findings suggest that iNOS gene transfer may have deleterious effects on endothelial function if used as a treatment for erectile dysfunction.

Melanocortinergic control of penile erection.

Melanocortin receptors in the forebrain and spinal cord can be activated by endogenous or synthetic ligands to induce penile erection in rats and human subjects. To better understand how melanocortin circuits play a role in sex behavior, we review the contribution of melanocortin receptors and/or neurons in the hypothalamus, hindbrain, spinal cord and peripheral nerves to erectile function. New information regarding neuropeptides that mediate penile erection has extended our understanding of the central control of sex behavior, and melanocortin agonists may provide alternatives to existing treatment for highly prevalent problems including erectile dysfunction.

Evaluation and management of renal injuries: consensus statement of the renal trauma subcommittee.

OBJECTIVE: To determine the optimal evaluation and management of renal injuries by review of the world's English-language literature on the subject. METHODS: A consensus conference convened by the World Health Organization and the Societé Internationale d'Urologie met to critically review reports of the diagnosis and treatment of renal trauma. The English-language literature about renal trauma was identified using Medline, and additional cited works not detected in the initial search obtained. Evidence-based recommendations for the diagnosis and management of renal trauma were made with reference to a five-point scale. RESULTS: There were many Level 3 and 4 citations, few Level 2, and one Level 1 which supported clinical practice patterns. Findings of nearly 200 reviewed citations are summarized. CONCLUSIONS: Published reports on renal trauma still rely heavily on expert opinion and single-institution retrospective case series. Prospective trials of the most significant issues, when possible, might improve the quality of evidence that dictates the behaviour of practitioners.

Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors.

Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracavernous pressure nor augmented neurostimulated erectile responses. We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.

Pilot study of changes in stretched penile length 3 months after radical retropubic prostatectomy.

OBJECTIVES: To evaluate changes in stretched penile length after radical retropubic prostatectomy (RRP) in a prospective penile measurement study because an occasional complaint from patients after RRP is that their penis is shortened. METHODS: Thirty-one patients undergoing RRP by one surgeon were enrolled. The same physician completed measurements with a paper ruler to the nearest 0.5 cm. The stretched penile length was measured from the tip of the glans to the pubopenile skin junction. The measurements were taken in the preoperative holding area before the patient received anesthetic medication for the RRP and again 3 months postoperatively. The reliability and reproducibility of this measurement were confirmed. RESULTS: All 31 patients were measured at 3 months postoperatively. Of the 31 patients, 22 (71%) had a decrease in stretched penile length (range 0.5 to 4.0 cm). Seven were shortened 0.5 cm, 11 were shortened 1.0 to 2.0 cm, and 4 were shortened more than 2.0 cm. Five patients had no change, and in four the penile length was longer (range 0.5 to 1.0 cm). CONCLUSIONS: The results of this pilot study appear to show that the stretched penile length decreases after RRP at 3 months of follow-up in most men; 48% (15 of 31) had considerable shortening greater than 1.0 cm. If confirmed by other investigators, the cause of this change needs to be elucidated.

Smoking and erectile dysfunction: evidence based analysis.

PURPOSE: We examined available evidence concerning the role of smoking in the development of erectile dysfunction. This task involved a complete review of the smoking literature as it pertained to erectile dysfunction and select endothelial diseases. MATERIALS AND METHODS: We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings relevant to smoking, erectile dysfunction and endothelial diseases. The quality of the evidence was assessed by methods used to develop clinical practice guidelines. Our review involved an objective evaluation of the basic science literature and clinical studies. When necessary, we examined studies of endothelial diseases other than erectile dysfunction because of obvious gaps in the literature. RESULTS: There are strong parallels and shared risks among smoking, coronary artery disease, atherosclerosis and erectile dysfunction. Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection by the impairment of endothelium dependent smooth muscle relaxation. The association of erectile dysfunction with risk factors such as coronary artery disease and hypertension appears to be amplified by cigarette smoking. Smoking may increase the likelihood of moderate or complete erectile dysfunction 2-fold. The prevalence of erectile dysfunction in former smokers was no different from that in individuals who had never smoked, implying that smoking cessation may decrease the risk of erectile dysfunction. Case studies and retrospective series have shown an association of smoking with erectile dysfunction. CONCLUSIONS: Available evidence on the association of smoking with erectile dysfunction is not complete insofar as association linking factors are concerned. However, the evidence of such an association is likely due to the consistency of the relationship of smoking and endothelial disease, and the strength of the association of erectile dysfunction with other endothelial diseases.

Effect of incision and saphenous vein grafting for Peyronie's disease on penile length and sexual satisfaction.

PURPOSE: We determined the effect of incision and saphenous vein grafting on penile length, erectile function and overall sexual satisfaction in men with Peyronie's disease. MATERIALS AND METHODS: A total of 24 consecutive men underwent plaque incision and saphenous vein grafting with postoperative daily use of a vacuum erection device. Erect penile length, pain, curvature and erectile function were assessed before and after surgery, and overall sexual satisfaction was scored from 1 to 5 by a validated instrument. RESULTS: Of the 22 patients in whom adequate followup data were available mean penile length was increased 2.1 cm. as a result of surgery (p <0.001). Median score of overall satisfaction with sex life was 4 or moderately satisfied. Of the 86% of men who achieved sexual intercourse after surgery 54% used no erectile aids and 32% required sildenafil or intracavernous injection. Complete erectile dysfunction was present in 14% of cases. Patients who reported erectile difficulty preoperatively were significantly more likely to have erectile dysfunction postoperatively that required erectile aids. Arterial insufficiency on duplex Doppler ultrasound was associated with a higher likelihood of complete erectile dysfunction. Complications in 33% of patients included complete erectile dysfunction in 3 and significant persistent penile curvature in 1. CONCLUSIONS: Incision and venous grafting of plaque leads to statistically and clinically significant increases in penile length in men with Peyronie's disease. Preoperative erectile dysfunction and cavernous arterial insufficiency were associated with a higher risk of postoperative erectile dysfunction. Nevertheless, patients reported a high degree of satisfaction with their overall sex life.

Use of tolterodine in children with dysfunctional voiding: an initial report.

PURPOSE: Tolterodine was recently approved for the treatment of incontinence and overactive bladder in adults, and has fewer side effects than oxybutynin. We evaluated the safety and efficacy of tolterodine in children with dysfunctional voiding. MATERIALS AND METHODS: We retrospectively reviewed our experience with 30 pediatric patients treated with tolterodine for a primary diagnosis of dysfunctional voiding. Patients were treated with adult doses of tolterodine and behavioral modifications. Standard definitions determined by the International Children's Continence Society were adapted to designate final treatment outcomes on medication as cured-greater than 90% reduction in wetting episodes, improved-greater than 50% reduction or failed-less than 50% reduction. RESULTS: The children were 4 to 17 years old (mean age 8.7) and were treated with tolterodine for an average of 5.2 months. The final dose was 1 mg. twice daily in 1, 2 mg. twice daily in 27 and 4 mg. twice daily in 2 patients. Wetting episodes were cured in 10 (33%), improved in 12 (40%), and failed to show improvement in 8 (27%) cases. Four patients (13.3%) reported side effects and only 1 discontinued the medication due to diarrhea. There were no reports of hyperpyrexia, flushing or intolerance to sunshine and outdoor temperature. CONCLUSIONS: Our results demonstrate that tolterodine at adult doses without titration can be used safely to decrease wetting episodes in children with dysfunctional voiding. Controlled clinical trials should be completed to evaluate further efficacy and safety in children.

Comparison of open and endoscopic treatment of posttraumatic posterior urethral strictures.

The purpose of this study was to compare the invasiveness, morbidity, and outcomes of open versus endoscopic treatment of posttraumatic posterior urethral strictures. We compared two groups of men with strictures of the posterior urethra after pelvic fracture: Group I (n = 6) underwent cut-to-the-light procedures before 1995, and group II (n = 9) underwent perineal anastomotic urethroplasty after 1995. The operating time and blood loss were lower in the endoscopic group, but no other significant differences in morbidity or invasiveness were found. All six patients in group I required multiple secondary procedures: Three reached a stable voiding pattern after a mean of three interventions, two required subsequent urethroplasty, and one was lost to long-term follow-up. Normal voiding was achieved in all group II patients, although two (22%) required single internal urethrotomy within 3 months after surgery. The data show the comparable morbidity of open urethroplasty and cut-to-the-light procedures and support an aggressive surgical approach for the delayed treatment of posttraumatic posterior urethral strictures. Other than a reduced operating time, endoscopic procedures offered no compelling advantage over surgical reconstruction.

Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction.

OBJECTIVES: To assess the safety, erectogenic properties, and effect on sexual desire of Melanotan II, a synthetic melanotropic initiator of erection, in men with erectile dysfunction and organic risk factors. METHODS: Ten subjects were enrolled in a double-blind, placebo-controlled, crossover study. Melanotan II (0.025 mg/kg) and vehicle were each administered twice by subcutaneous injection; real-time RigiScan monitoring and a visual analog were used to quantify the erections during a 6-hour period. The level of sexual desire and side effects were recorded with a questionnaire. RESULTS: Melanotan II initiated subjectively reported erections in 12 of 19 injections versus only 1 of 21 doses of placebo. The mean rigidity score of the responders was 6.9 on a scale of 0 to 10. The mean duration of tip rigidity greater than 80% was 45.3 minutes with Melanotan II versus 1.9 for placebo (P = 0.047). The level of sexual desire after injection was significantly higher after Melanotan II administration than after placebo. Nausea and stretching/yawning occurred more frequently with Melanotan II, and 4 of 19 injections were associated with severe nausea. CONCLUSIONS: The erectogenic properties of Melanotan II are not limited to cases of psychogenic erectile dysfunction; men with a variety of organic risk factors developed penile erections. The finding of increased sexual desire warrants further investigation of centrally acting agents on disorders of sexual desire.

Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II.

We review our experience with Melanotan II, a non-selective melanocortin receptor agonist, in human subjects with erectile dysfunction (ED). Melanotan II was administered to 20 men with psychogenic and organic ED using a double-blind placebo-controlled crossover design. Penile rigidity was monitored for 6 h using RigiScan. Level of sexual desire and side effects were reported with a questionnaire. In the absence of sexual stimulation, Melanotan II led to penile erection in 17 of 20 men. Subjects experienced a mean of 41 min Rigiscan tip rigidity>80%. Increased sexual desire was reported after 13/19 (68%) doses of Melanotan II vs 4/21 (19%) of placebo (P<0.01). Nausea and yawning were frequently reported side effects due to Melanotan II; at a dose of 0.025 mg/kg, 12.9% of subjects had severe nausea. We conclude that Melanotan II is a potent initiator of penile erection in men with erectile dysfunction. Our findings warrant further investigation of melanocortin agonists and antagonists on penile erection. International Journal of Impotence Research (2000) 12, Suppl 4, S74-S79.

Complications related to the high lithotomy position during urethral reconstruction.

PURPOSE: We identified risk factors for complications of the lower extremities related to high lithotomy positioning during specific urethral reconstruction procedures in male patients. MATERIALS AND METHODS: Records from 185 open urethroplasties were evaluated for position related complications of the lower extremities (the compartmental syndrome, rhabdomyolysis, neurapraxia). Morphometric data (patient height, weight) and surgical details (duration of surgery and lithotomy positioning, types of repair and stirrups, stricture length and location) were assessed. RESULTS: In the 185 patients 18 position related complications (10%) were identified, 4 of which were severe. Univariate analysis showed length of stricture, and duration of surgery and lithotomy positioning to be statistically significant risk factors (p <0.05). Height, weight, body mass index and type of stirrups did not increase risk. Anterior end-to-end anastomosis and straightforward buccal mucosa patch grafts entailed negligible risk. Longer procedures (prostatomembranous and penile skin flap repairs) had higher complication rates (12% and 22%, respectively). Beginning penile skin flap procedures with patients in the supine position during flap harvesting followed by repositioning into high lithotomy for perineal flap transfer virtually eliminated the risk of severe complications. CONCLUSIONS: The risk of position related complications during urethral reconstruction is directly proportional to the duration of high lithotomy positioning. Procedures of less than 5 hours in duration had minimal risk. For complex flap procedures, we perform penile flap dissection with the patient supine and reposition for perineal flap transfer.