Introduction The implantation of inflatable penile prosthesis (IPP) with simultaneous manual penile remodeling allows for men to undergo a single procedure aimed at correcting both the penile deformity/curvature and erectile dysfunction (ED). Aim To evaluate the clinical outcomes and patient satisfaction in men with Peyronie's disease (PD) and ED who underwent AMS 700™ CX and the newer Coloplast™ Titan inflatable penile prosthesis (IPP) implant. Main Outcome Measures Patient demographics, type of IPP, clinical outcomes, post-implant sexual characteristics, and overall patient satisfaction. Methods A single-center retrospective review of clinical database and prospective telephone survey were conducted in all men with PD who underwent IPP between January 2006 and November 2010. Results A total of 138 patients with an average age of 57.7 (32 to 80) underwent AMS 700 CX (88 patients) and Coloplast Titans (50 patients) IPP implantation during the 5-year period. The majority of patients (91%) had only one IPP implantation. The IPP clinical outcomes include eight (6%) revision surgery for device malfunction and three (2%) device explantation for prosthesis infection. While there was no statistically significance in device survival between the two devices, the trend favored AMS 700 CX over Titan (5-year Kaplan-Meier estimates of mechanical survival were 91% vs. 87%, P > 0.05) and both IPPs provided similar penile straightening without the need for revision surgery. Most men (79%) reported great satisfaction following CX or Titan implants with greater than two thirds of men reported greater self-confidence and 82% of patients would undergo the same operation again. Conclusions AMS 700™ CX and Coloplast™ Titan IPP implantation and penile remodeling appeared to provide permanent penile straightening and high patient satisfaction without an increase risk of revision surgery.

Introduction Effective oral medication for use in men with Peyronie's disease (PD) has been an area of interest of the medical community and lay public for decades. Isolated septal scars (ISS) without evidence of penile deformity is a relatively new clinical entity, and at present, there is paucity in the published literature regarding its treatment. Current research into the use of phosphodiesterase type 5 (PDE5) inhibitors in regulating penile erectile response has revealed an alternative role for PDE5 inhibitors in decreasing oxidative stress-associated inflammatory change as seen in PD. Aim To examine the presence of ISS and assess the efficacy of PDE5 inhibitor use in septal scar remodeling. Methods Retrospective review of prospective database on all men who underwent penile Doppler ultrasound between December 2007 and December 2009. Main Outcome Measures Of the 65 men with ultrasonographic-confirmed ISS, 35 men received tadalafil 2.5 mg daily over a 6-month period. The clinical outcomes between the two groups were compared using International Index of Erectile Function (IIEF)-5 score and 6 months penile Doppler ultrasound follow up. Results The mean age for the tadalafil group was 43.2 (20–65) years, similar to the control group at 44.2 (34–72) years. The length of time from onset to presentation was 22 (6 to 40) months. The majority of ultrasonographic-proven ISS was not clinically palpable and complaint of decreased penile rigidity (66%) was the predominant feature. Treatment with low-dose daily tadalafil did not result in any significant side effects (such as headache and flushing) or discontinuation. The tadalafil group reported higher IIEF-5 score (pretreatment 11/25 to post-treatment 18/25) (P  < 0.01) and resolution of septal scar were recorded in 24 patients (69%) compared to three patients (10%) in the control group. Conclusion Low-dose daily tadalafil is a safe and effective treatment option in septal scar remodeling.

Little is known of the excitatory mechanisms that contribute to the tonic contraction of the corpus cavernosum smooth muscle in the flaccid state. We used patch-clamp electrophysiology to investigate a previously unidentified inward current in freshly isolated rat and human corporal myocytes. Phenylephrine (PE) contracted cells and activated whole cell currents. Outward current was identified as large-conductance Ca(2+)-activated K(+) current. The inward current elicited by PE was dependent on the Cl(-) gradient and was inhibited by niflumic acid, indicative of a Ca(2+)-activated Cl(-) (Cl(Ca)) current. Furthermore, spontaneous transient outward and inward currents (STOCs and STICs, respectively) were identified in both rat and human corporal myocytes and derived from large-conductance Ca(2+)-activated K(+) and Cl(Ca) channel activity. STICs and STOCs were inhibited by PE and A-23187, and combined 8-bromoadenosine cAMP and 8-bromoadenosine cGMP decreased their frequency. When studied in vivo, chloride channel blockers transiently increased intracavernosal pressure and prolonged nerve-evoked erections. This report reveals for the first time Cl(Ca) current in rat and human corpus cavernosum smooth muscle cells and demonstrates its key functional role in the regulation of penile erection.

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Diminished vascular endothelial function results in decreased vasodilator capacity and is associated with erectile dysfunction (ED) in patients afflicted with type 2 diabetes. The current study was designed to evaluate whether daily use of sildenafil could alter endothelial function and improve penile rigidity in a group of patients with diabetic ED. A double-blind, placebo-controlled, prospective trial was conducted with 24 men with type 2 diabetes who were randomized into 2 groups: one receiving daily sildenafil (50 mg, n 5 12) and the other placebo (n 5 12) for 10 weeks. Erectile function was captured subjectively using the International Index of Erectile Function (IIEF-5), and endothelial function was objectively monitored via brachial artery flow-mediated dilation. Among the placebo and sildenafil groups, there were no significant differences in average patient age, time from type 2 diabetes diagnosis, duration of ED, or baseline IIEF-5 scores. Past medical histories, including smoking, alcohol consumption, hypertension, and hyperlipidemia, were also similar. At the conclusion of the 10-week trial, patients who received daily sildenafil had significantly improved erectile rigidity as captured by IIEF-5 (P , .001) and increased endothelial function via brachial artery flow-mediated dilation (P , .01). Endothelial function in men with type 2 diabetes was enhanced with daily sildenafil. Improved erectile rigidity and enhanced vascular circulation was noted after 10 weeks of daily sildenafil use.

]i was reversibly inhibited by 27 Ϯ 7% (n ϭ 21, P Ͻ 0.005) in rat and by 55 Ϯ 15% (n ϭ 9, P Ͻ 0.01) in human SMCs. SNAP and SIL also reduced the contractile response to PE. To investigate the mechanism, we applied mediators alone or in combination. The soluble guanylyl cyclase inhibitor ODQ reduced the effect of SNAP and SIL. SIL, cGMP analogs, and NO donors without SIL did not reduce the PE-induced rise of [Ca 2ϩ ]i. However, the combination of 8-bromocGMP with SNAP reduced the Ca 2ϩ peak by 42 Ϯ 9% (n ϭ 22, P Ͻ 0.01). Our results demonstrate that NO and cGMP act synergistically to reduce Ca 2ϩ release from intracellular stores. Reduction of intracellular Ca 2ϩ release may contribute to relaxation of the corpus cavernosum, leading to erection. calcium stores; nitric oxide; sildenafil citrate; inositol 1,4,5-trisphosphate receptor THE TONE OF VASCULAR SMOOTH MUSCLE in the corpus cavernosum regulates penile tumescence: tonic contraction maintains the flaccid state, and relaxation leads to erection. Contractility of penile smooth muscle cells (SMCs) is modulated by various neurotransmitters and locally produced vasoactive substances. Considerable evidence suggests that norepinephrine is primarily responsible for tonic contraction of corpus cavernosum SMCs through activation of ␣-adrenergic receptors (1). Agonist binding to ␣-adrenergic receptors activates a G proteincoupled pathway increasing intracellular inositol 1,4,5-trisphosphate (IP 3 ) and activation of IP 3 receptors, followed by Ca 2ϩ release (3). Nitric oxide (NO), which is released by both endothelial cells and nonadrenergic, noncholinergic nerves, leads to relaxation of corpus cavernosum and is necessary for erection (6,28). NO has a variety of cellular effects including direct effects on ion channels and activation of soluble guanylyl cyclase (sGC), which converts GTP to cGMP (4, 26). cGMP in turn activates cGMP-dependent ion channels, cGMP-dependent protein kinase (PKG), and cGMP-regulated phosphodiesterases (PDEs). It has been suggested that, in vascular smooth muscle, most of the cGMP effects are mediated by PKG, because in PKG-1-deficient mice, aortic and corpus cavernosum smooth muscles fail to relax upon activation of the NO/cGMP pathway (16,27). PKG has a variety of effects in smooth muscle, including inhibition of the IP 3 receptor (30) and regulation of the Ca 2ϩ sensitivity of contractile proteins (23). Specific PKG mechanisms contributing to the regulation of SMC tone almost certainly vary from tissue to tissue, and the identity of specific targets involved in relaxation of corpus cavernosum SMCs remains uncertain.PDE types 2, 3, 5, and 11 are expressed in corpus cavernosum SMCs, although the main PDE activity is due to PDE5, which hydrolyzes cGMP (5, 10, 25). Sildenafil citrate (Viagra) acts by enhancing NO-mediated smooth muscle relaxation by competitive inhibition of PDE5, thereby maintaining elevated intracellular cGMP levels (2, 5).We investigated the effect of NO on adrenergically stimulated changes in intracellular Ca 2ϩ concentrat...

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Men aged ≥75 years reported satisfactory outcome with IPP surgery with no statistical significant difference identified across device survival and satisfaction rates compared to men aged <75 years.