Retrospective evaluation of the efficacy of daily paroxetine/tadalafil combination in patients with premature ejaculation and erectile dysfunction.

OBJECTIVE: Premature ejaculation (PE) and erectile dysfunction (ED) are sexual dysfunction diseases affecting males. The phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are used to treat ED whereas selective serotonin reuptake inhibitors (SSRIs) are preferred for PE. Most of the patients with ED also suffer from PE simultaneously. The combined drug therapies are commonly preferred as they favor elevated intra-vaginal ejaculation latency time (IELT) scores and improved sexual function. The study aimed to evaluate the efficacy and safety of daily paroxetine and tadalafil combination therapy in patients with PE and ED. PATIENTS AND METHODS: A total of 81 PE patients with ED were enrolled in the study. Patients were treated with daily paroxetine 20 mg and tadalafil 5 mg for 4 weeks. Pre- and post-treatment IELT, premature ejaculation profile (PEP), and International Index of Erectile Function-Erectile Function (IIEF-EF) scores of the patients were analyzed. RESULTS: The mean IELT and PEP index scores, and mean IIEF-EF values improved after combination therapy (p<0.001 for each). When lifelong and acquired PE+ED patients were compared, significant improvements were observed in IELT, PEP, and IIEF-EF scores in both groups (p<0.001). CONCLUSIONS: Even though the treatment methods are different, combined therapies to treat simultaneous PE and ED presence are effective compared to monotherapies. However, there is still no definitive treatment that can cure all subtypes of PE or ED.

Incidence of urological cancers in neurological patients: a review of the literature from the EAU Young Academic Urologist Functional Group.

INTRODUCTION: Urological cancers can be challenging in the diagnosis and treatment of patients with neurological diseases. As a result, there are still uncertainties regarding the incidence and risk factors favouring the development of urological cancers in these patients. The aim of this study was to review the available evidence regarding the incidence for the development of urological cancers in neurological patients to provide a basis for future recommendations and research. EVIDENCE ACQUISITION: A narrative review of the literature in Medline and Scopus up to June 2019 was performed. EVIDENCE SYNTHESIS: After screening 1729 records, 30 retrospective studies were retained. For bladder cancer (BC), 21 articles were identified, including a total of 673,663 patients. Among these patients, 4744 had a diagnosis of BC (1265 females, 3214 males, gender not reported in 265). In this group, 2514 were diagnosed with BC associated with a neurological disease. For prostate cancer (PC), 14 articles were identified, including a total of 831,889 men. Among these patients, 67,543 had a diagnosis of PC and 1457 had PC and a neurological disease. Two articles reported kidney cancer (KC), one reported testicular cancer (TC) and none described penile cancer or urothelial carcinomas of the upper urinary tract in neurological patients. CONCLUSIONS: The incidence of urological cancers, especially BC and PC, in patients with neurological diseases appears comparable to the general population. However due to the paucity of studies, specific recommendations for the management are lacking in neurologically disabled patients. In this report we investigated the frequency of urinary tract cancers in patients with neurological diseases. We conclude that urological cancers, especially bladder and prostate cancer, in patients with neurological diseases occur with similar frequency as in the general population.

Exclusive manual perineal rehabilitation with lidocaine 2% gel in the treatment of provoked vestibulodynia: results from a single-arm interventional study.

As of now, there is no adequate therapeutic strategy for provoked vestibulodynia (PVD). Pelvic Floor Muscle Therapy (PFMT) is a widely used technique in general pelvic floor rehabilitation. The objective of this study is to examine the effects of exclusive manual perineal rehabilitation with lidocaine 2% gel on PVD. During the first session, recruited patients (n = 68; mean age 31 ± 8.6; range: 18-52) received a questionnaire (Q1) on general well-being and health, pain of the genital area, sexual function, and symptoms during vaginal penetration. This questionnaire was based on a generalised questionnaire on the quality of life, the Medical Outcomes Study 36-item (SF-36), the Female Sexual Function Index (FSFI), and the Visual Analogue Scale (VAS). A second identical questionnaire with an additional set of open-ended questions concerning the assessment of the treatment was collected after treatment (Q2). A total of 45 questionnaires were completed. Statistical results showed a significant improvement of all items before and after treatment (p < 0.001): perceived general well-being and health, perceived vulvar pain, perceived sexual function, and perceived vaginal penetration. In conclusion, exclusive manual perineal rehabilitation using lidocaine 2% gel seems to be a safe and effective treatment option for vulvodynia in women.

Modelo novedoso basado en los parámetros de la tomografía para predecir el éxito de la litotricia por ondas de choque en los cálculos ureterales de diferentes localizaciones / A novel model using computed tomography parameters to predict shock wave lithotripsy success in ureteral stones at different locations

ObjetivoIncorporar los parámetros basados en la tomografía computarizada sin contraste (TCSC) a las características de los cálculos y de los pacientes comúnmente asociadas con el éxito de la litotricia por ondas de choque (LEOCH) para evaluar la efectividad de este nuevo modelo en la predicción del éxito de LEOCH en cálculos ureterales únicos situados en diferentes localizaciones.Materiales y métodosSe revisaron retrospectivamente los datos de los pacientes tratados con LEOCH por un único cálculo ureteral entre enero de 2017 y enero de 2019. Los parámetros basados en la TCSC se evaluaron junto con los parámetros demográficos de los pacientes y las características de los cálculos. Los parámetros basados en TCSC incluyeron la presencia o ausencia de hidronefrosis, trabeculación de la grasa perirrenal, edema periureteral, diámetro del uréter proximal, grosor de la pared ureteral (GPU) en el sitio del cálculo ureteral. Se utilizó el método de regresión logística para desarrollar un modelo predictivo útil. Posteriormente, se utilizó la curva ROC para determinar los puntos de corte, y se desarrolló un sistema de puntuación para la predicción del éxito de LEOCH.ResultadosLa tasa libre de cálculos fue del 77,1% (267/346) en toda la cohorte. El análisis univariante reveló que la edad, el volumen de los cálculos, la densidad, la trabeculación perirrenal, el diámetro del uréter proximal y el GPU se asociaron con el éxito de la LEOCH. En el análisis multivariante, la localización del cálculo ureteral proximal, el volumen del cálculo, la densidad y el GPU fueron predictores independientes del éxito de la LEOCH. La fórmula utilizada en el análisis de regresión logística fue: 1/[1+exp {-8,856+0,008(volumen del cálculo)+0,002 (densidad del cálculo)+0,673 (GPU)+1026 (cálculo ureteral proximal)}]. Las puntuaciones de 0, 1, 2, 3 y 4 se asociaron con un 97,8%, 83,4%, 60,8%, 33,2% y 11,1% de éxito, respectivamente, en el modelo de predicción basado en estos parámetros.

ObjectiveTo combine non-contrast computerized tomography (NCCT)-based parameters with stone and patient characteristics that are already known to affect shock wave lithotripsy (SWL) success and assess this novel model's effectiveness in predicting SWL success for single ureteral stones in different locations.Materials and methodsData of patients treated by SWL for a single ureteral stone between January 2017 and January 2019 were retrospectively reviewed. Demographic parameters of patients and stone characteristics were combined with NCCT-based parameters. NCCT-based parameters included the presence or absence of hydronephrosis, perinephric stranding, periureteral edema, diameter of the proximal ureter, ureteral wall thickness (UWT) at ureteral stone site. The logistic regression method was used for the development of a useful predictive model. Subsequently, the receiver operating curve was used to determine cut-off levels, and a scoring system was developed for prediction of SWL success.ResultsStone-free rate was 77,1% (267/346) in the entire cohort. Univariate analysis revealed that age, stone volume, density, perinephric stranding, diameter of proximal ureter, and UWT, were associated with SWL success. In multivariate analysis, proximal ureteral stone location, stone volume, density, and UWT were independent predictors of SWL success. The formula used during logistic regression analysis was: 1/[1+exp {-8.856+0.008(stone volume)+0.002 (stone density)+0.673 (UWT)+1026 (proximal ureteral stone)}]. The scores of 0, 1, 2, 3 and 4 were associated with 97,8%, 83,4%, 60,8%, 33,2% and 11,1% success rates, respectively, in the prediction model based on these parameters.ConclusionWe conclude that our model can facilitate decision-making for SWL treatment of ureteral stones in different locations (AU)

A novel model using computed tomography parameters to predict shock wave lithotripsy success in ureteral stones at different locations.

OBJECTIVE: To combine non-contrast computerized tomography (NCCT)-based parameters with stone and patient characteristics that are already known to affect shock wave lithotripsy (SWL) success and assess this novel model's effectiveness in predicting SWL success for single ureteral stones in different locations. MATERIALS AND METHODS: Data of patients treated by SWL for a single ureteral stone between January 2017 and January 2019 were retrospectively reviewed. Demographic parameters of patients and stone characteristics were combined with NCCT-based parameters. NCCT-based parameters included the presence or absence of hydronephrosis, perinephric stranding, periureteral edema, diameter of the proximal ureter, ureteral wall thickness (UWT) at ureteral stone site. The logistic regression method was used for the development of a useful predictive model. Subsequently, the receiver operating curve was used to determine cut-off levels, and a scoring system was developed for prediction of SWL success. RESULTS: Stone-free rate was 77,1% (267/346) in the entire cohort. Univariate analysis revealed that age, stone volume, density, perinephric stranding, diameter of proximal ureter, and UWT, were associated with SWL success. In multivariate analysis, proximal ureteral stone location, stone volume, density, and UWT were independent predictors of SWL success. The formula used during logistic regression analysis was: 1/[1 + exp {-8.856 + 0.008 (stone volume) + 0.002 (stone density) + 0.673 (UWT) + 1026 (proximal ureteral stone)}]. The scores of 0, 1, 2, 3 and 4 were associated with 97,8%, 83,4%, 60,8%, 33,2% and 11,1% success rates, respectively, in the prediction model based on these parameters. CONCLUSION: We conclude that our model can facilitate decision-making for SWL treatment of ureteral stones in different locations.

Êxpression of inducible nitric oxide synthase (iNOS) in the azoospermic human testis.

Azoospermia, which is the absence of spermatozoa in the ejaculate, is not a rare cause of male infertility. Inducible nitric oxide synthase (iNOS) is a calcium-independent NOS, which is present in the testis and involved in spermatogenesis, and apoptosis of Sertoli and germ cells. Twenty idiopathic infertile men presenting nonobstructive azoospermia were enrolled in this study, and testicular sperm extraction procedures were performed. Tissue extracts were dissected, and the fluid samples were investigated to determine the presence of spermatozoa. Histologic evaluation of the spermatozoa-present samples revealed that seminiferous tubules were normal and were lined by Sertoli cells and spermatogenic cells. However, in the spermatozoa-absent samples, the diameter of the seminiferous tubules was small, and Sertoli-cell-only syndrome was determined in most of the tubules. iNOS expression was very weak in Sertoli cells, germ cells, and in Leydig cells in the spermatozoa-present group. In the spermatozoa-absent group, the immunostaining was very intense in Sertoli and Leydig cells. Electron microscopy findings were supported the histologic results. In conclusion, complete germ cell loss and intense expression of iNOS in the Sertoli and Leydig cells in the spermatozoa-absent groups of azoospermic human testis suggest an essential role of iNOS in spermatogenesis.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in patients with familial multiple cerebral cavernous malformations.

Cavernous malformations can occur in both sporadic and autosomal dominant forms. The aim of this study was to investigate the potential role of insertion/deletion (I/D) polymorphisms of the angiotensin-converting enzyme (ACE) gene in the development of cerebral cavernous malformations (CCM). Forty-one members of two families affected by familial CCM were included in this study. DNA was isolated from peripheral venous blood, and polymerase chain reaction analysis was used to detect I/D polymorphisms of the ACE gene, using HACE3s and HACE3as as primers. Only 10 participants had MRI-confirmed CCM. Of these 10 subjects, seven had the I/D, two had the D/D, and one had the I/I genotype. Of the remaining 31 subjects, 14 had the I/I, 13 had the I/D, and four had the D/D genotype. There was a greater proportion of subjects with the D allele among those with MRI-confirmed CCM than among those without (p<0.05). These results suggest that the D polymorphism of the ACE gene may be involved in the pathogenesis of familial CCM.

Testicular oxidative stress. Effects of experimental varicocele in adolescent rats.

OBJECTIVE: This present study was undertaken to determine the levels of malondialdehyde (MDA), nitric oxide (NO) and total antioxidant status (TAS) in testes of adolescent rats with experimental bilateral varicocele and to determine the effects of oxidative stress on testis produced by varicocele. METHODS: 6-week-old, male Wistar rats, weighing 146-334 g (228.37 +/- 41.34 g), were randomly allocated into two groups. The first group underwent selective and bilateral partial ligation of the spermatic vein (n = 28), and the second group underwent a sham operation and served as the controls (n = 15). Animals were sacrificed 12 weeks after surgery and dilatation of the spermatic veins was observed in the first study group. Bilateral orchiectomy was performed in all rats, and MDA, NO and TAS levels were measured. RESULTS: In the study group, the mean MDA (SEM) level was 15.58 +/- 6.07 micromol/g protein, and in the control group, it was 11.59 +/- 3.86 micromol/g protein, respectively; this difference was statistically significant (p < 0.05). The mean NO level was 82.73 +/- 77.84 nmol/g protein in the study group, whereas 28.65 +/- 20.18 nmol/g protein in the control group, this difference was also statistically significant (p < 0.005). The mean TAS levels of the study and control groups were 0.91 +/- 0.32 and 1.78 +/- 0.46 nmol/g tissue, respectively, and this difference was also statistically significant (p < 0.001). But there was no correlation between these three parameters (MDA<-->TAS: r = -0.103, p > 0.05; MDA<-->NO: r = -0.104, p > 0.05; NO<-->TAS: r = -0.123, p > 0.05). CONCLUSION: These findings suggest that varicocele may change the testicular oxidative status and may play a role in testicular dysfunction that causes infertility.

Prosthesis culture 6 months after implantation and the effect of haematogenous seeding in a rat model.

The aim of this study was to investigate the role of haematogenous seeding in late prosthesis infection. In all, 45 male Wistar albino rats were divided into three equal groups. A small piece of silicone prosthesis was implanted into the scrotum of all rats under sterile condition and antibiotic prophylaxis. In the first group, all silicones were removed after 6 months without any complication and were cultured for bacterial growth. In the second group, a disc, which was saturated with Staphylococcus epidermidis, was inoculated subcutaneously in the legs of the rats in the 6th month, revealing a nodule formation 4-5 days after the inoculation and treated with an appropriate antibiotic after the nodule formation. In the third group, the same disc was inoculated, but all rats were treated immediately from the inoculation time onwards. The silicones of the second and third group were also removed at the end of the 6th month and were cultured to observe the bacterial growth. There was no evidence of prosthesis infection in any of the three groups. In the first group, three cultures were positive and revealed approximately 10 000 colonies of S. epidermidis in two and Proteus mirabilis in the remaining. Three and four cultures were positive in the second and third group, respectively. Low colonies of four different organisms (Escherichia coli, S. aureus, S. epidermidis, Pseudomonas aeruginosa) were identified in these cultures. There was no statistical significance of positive cultures in the three groups. Based on our results, there does not appear to be a true significance of haematogenous seeding on late prosthesis infection.

Gastrocystoplasty in pigs and effect of selective antral vagotomy on acid secretion of the reconstructed bladder.

INTRODUCTION: The aim of this study was to investigate the outcome of gastrocystoplasty and the effects of selective antral vagotomy (SAV) on the postprandial gastrin secretion from the antrum as well as on the acid secretion from the augmented bladder. MATERIALS AND METHODS: In this study on 12 male pigs, we applied subtotal cystectomy plus gastric augmentation plus SAV to the study group and the same procedure without SAV to the control group. The animals were followed up for 3 months with respect to feeding, weight, and urine output. The urine pH levels and the gastrin levels of the pigs in the two groups were then followed up and compared. RESULTS: The use of gastric segments in bladder reconstruction was found to be appropriate in terms of both gastric function and urinary system function. Nevertheless, regarding the effect of SAV, the differences between either the urinary pH levels or the gastrin levels of the pigs in the two groups were statistically significant. CONCLUSIONS: Although gastric segments in the bladder reconstruction were found to be appropriate in terms of both gastric function and urinary system function, SAV did not prevent postprandial gastrin secretion and the resulting increase of the urine acidity.

Covalently bound ionene polyelectrolyte-silica gel stationary phases for HPLC.

Micelle-mimetic ionene-based stationary phases for high-performance liquid chromatography (HPLC) are prepared by attaching [3,16]- and [3,22]-ionenes to aminopropyl silica through a carbon-nitrogen bond. These [x,y]-ionenes are polyelectrolytic molecules consisting of dimethylammonium charge centers interconnected by alternating alkyl chain segments containing x and y methylene groups, some of which can form aggregate species whose properties mimic those of conventional surfactant micelles. These ionene-bonded stationary phases were characterized using different recommended HPLC test mixtures. Test solute chromatographic behavior on the ionene phases was found to be similar to that of intermediate oligomeric or polymeric C-18 and/or phenyl phases, depending upon the specific test mixture employed. In addition, the phases exhibit significant solute shape recognition ability. The ionene stationary phases were successfully employed for the separation of the components of the recommended ASTM reversed-phase test mixture, as well as for ortho-, meta- and para-disubstituted benzenes and other positional or geometric isomeric compounds. The ionene materials allow for chromatographic separations under either reversed-phase or ion-exchange conditions. The retention mechanism on these multimodal phases can occur by hydrophobic partitioning or electrostatic interactions, depending upon the characteristics of the components of the analyte mixture (neutral or anionic). The effects of alteration of the percent organic modifier, flow rate and temperature of the mobile phase on chromatographic retention and efficiency on these phases were briefly examined.

Selectivity in capillary electrochromatography using native and single isomer anionic cyclodextrin reagents.

Separations of naphthalene compounds that differ in position of substitution and type of substituent were accomplished using cyclodextrin distribution capillary electrochromatography. Separation systems composed of running buffers containing mixtures of native neutral and single isomer anionic cyclodextrins (CDs) were employed yielding efficiencies of approximately 200,000 plates/meter. Solute migration rates and relative orders can be readily modified by changing CD types and concentrations. Experiments were performed to determine distribution coefficients between each of the CDs used in these studies and an aqueous running buffer. For this work, naphthalene-CD cavity inclusion is assumed to be the principal mode of interaction. The distribution coefficients for carboxymethyl-beta-cyclodextrin (CM-beta-CD), degree of substitution 1, were 10-70% larger than those for native beta-CD and 75-1800% large than those for gamma-CD. The CM-beta-CD was singly charged and yielded a narrow elution window. Nevertheless, baseline resolution was achieved for several substituted naphthalene compounds using CM-beta-CD in conjunction with beta-CD or gamma-CD. Under certain conditions, the gamma-CD system yielded an elution order that differed from that of the beta-CD system. Heptakis-(2,3-dimethyl-6-sulfato)-beta-CD with its -7 charge produced a much larger elution window. The extensive substitution with sulfonic groups at the truncated bottom of the CD seemed to inhibit inclusion as the distribution coefficients for the naphthalene compounds were generally more than an order of magnitude smaller than those for CM-beta-CD. Moreover, there was evidence that this sulfato-CD interacted with both the capillary wall and neutral beta-CD. This work differs from prior uses of CDs in that relatively complicated mixtures of neutral, achiral compounds are separated using combinations of recently developed single-isomer CDs as running-buffer additives. The single-isomer CDs, as opposed to most highly complex derivatized CD products, facilitate predictions of separation performance for multicomponent samples. In this manner, the ability to use knowledge of distribution coefficients to predict elution characteristics for a ternary CD system is demonstrated.

The role of intraoperative antibiotic irrigation and postoperative antibiotic therapy for contaminated implantable prosthesis: in a rat model in vivo.

The aim of this study was to determine the usefulness of intraoperative antibiotic irrigation solution and long-term effective antibiotic therapy for the infected prostheses. Forty-five male Wistar albino rats were divided into three equal groups and a small piece of silicone prosthesis contaminated with Staphylococcus epidermidis was implanted into the scrotum. In the first group, the silicone pieces were irrigated with an antibiotic solution intraoperatively and antibiotic therapy was applied for 20 days postoperatively. The second group underwent only antibiotic therapy. In the third group (control) neither intraoperative irrigation nor postoperative antibiotic therapy was applied. Postoperative clinical infection was determined as follow-up. All implants were extracted 20 days after the implantation and cultured to observe the bacterial growth. In the first group, in 13 rats the cultures were negative and in two rats, the cultures revealed positive bacterial growth. In the second group, in four rats the cultures were negative, in five rats the cultures were positive and six rats revealed infectious findings. In the third group, 13 rats revealed infectious findings, and in the remaining two rats the cultures were positive. The differences between three groups are statistically significant (P < 0.05). We conclude that intraoperative antibiotic irrigation and postoperative antibiotic therapy are highly beneficial in the infected prosthesis surgery.

Diphallus with urethral duplications.

We report a case of glandular diphallus with incomplete urethral duplication associated with rotation anomaly in the right kidney, complete ureteral duplication and ectopic ureteral orifice in the left. The bladder was single with good sphincter control. At operation, the hypoplastic glans was resected and the urethra opening into this glans was anastomosed side by side with the other urethra. Diphallus and incomplete urethral duplication are discussed in the light of evidence in the literature.

Patient-partner satisfaction with intracavernous medication supported with oral agents in selected cases of Peyronie's disease. A ten-month follow-up study.

We attempted to find the most adequate treatment option for some selected cases of Peyronie's disease. Between 1993 and 1996, 38 patients with Peyronie's disease and erectile dysfunction were treated with intracavernous medication, supported with oral colchicine and vitamin E. None of the cases had severe angulation of penis and intolerable pain during erection. Quality of sexual life was assessed by CWRU questionnaire. After ten-month follow-up we found improvement in all parameters, in CWRU. The symptoms of 24 cases diminished. The 21 partners examined were also satisfied with the therapy. We conclude that intracavernous medication combined with oral agents is a useful alternative treatment in selected cases of Peyronie's disease.

Priapism induced by chlorpromazine.

Priapism is a pathologically prolonged and painful penile erection, usually unassociated with sexual desire or intercourse. Causes include certain oral medications, although the mechanism for drug-induced priapism is unknown. We describe two cases of priapism attributed to chlorpromazine who have presented within the past two years.

Cobb's collar and syringocele with stone.

We report a case of unusual syringocele with a stone and Cobb's collar. Tubular or cystic dilatation of Cowper's gland duct has been called a syringocele. Congenital urethral narrowing is known as Cobb's collar. This paper presents a rare case of adult syringocele with stone and Cobb's collar. We analysed the clinical, radiological and therapeutic aspects of this entity.

Comparison of testicular volumes before and after varicocelectomy.

We attempted to determine the testicular volume changes in patients with unilateral varicocele, before and after varicocelectomy. Testicular volume differences were correlated for each group of varicocele grade. 123 men with a unilateral left varicocele were presented for surgery: 36 had grade I, 49 had grade II, and 38 had grade III varicoceles. A Prader orchidometer was used for testicular volume determination before and after varicocelectomy in each patient. Both left and right testicular volumes were compared. After the repair of grade I varicoceles, an improvement in testicular volumes was noticed, but the difference was not statistically significant (p > 0.05). Both right and left testicular volumes increased significantly after operation in patients with grades II and III varicoceles (p < 0.001). Right testicular volume improved more than left in most of the patients. Men with large varicocele had significantly decreased testicular volumes than men with small varicocele before operation. So testicular growth arrest was more significant in patients with large varicocele and postoperative results indicated a more dramatic improvement.

The relationship between diabetes mellitus, impotence and veno-occlusive dysfunction in Peyronie's disease patients.

Peyronie's disease is an ill-defined condition that often leads to severe penile deformity and sometimes erectile dysfunction. Penile Doppler studies indicate veno-occlusive dysfunction as the principal cause of poor rigidity in Peyronie's disease patients. Diabetes mellitus is also a known cause of impotence and its prevalence tended to be higher in patients with Peyronie's disease. We evaluated 143 patients with Peyronie's disease, also 92 impotent men (37 diabetic, 55 nondiabetic) as control group. Penile vascular studies were performed on each group. Diabetes mellitus was also investigated in patients with Peyronie's disease. Veno-occlusive dysfunction was found as the main cause of impotence in both groups (81.1% in diabetic, 89% in nondiabetic control group and 88.8% in Peyronie's disease patients). In our study group the prevalence of diabetes mellitus tended to be higher than in the control population but it did not alter the ratio of veno-occlusive dysfunction and impotence in Peyronie's disease patients. We believe there is a close relationship between diabetes mellitus and Peyronie's disease, considering our high incidence. We also conclude that diabetes mellitus is not the main cause of impotence in patients with Peyronie's disease.