Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress.

INTRODUCTION: The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic. AIM: To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial cells. METHODS: Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 µM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10-15 Gy. Generation of reactive oxygen species (ROS) was studied. Extracellular hydrogen peroxide (H2O2) was measured using the Amplex Red assay and intracellular H2O2 using a fluorescent sensor. In addition, ROS superoxide (O2•-) was measured using a O2•- chemiluminescence enhancer. Both H2O2 and O2•- are known to reduce the bioavailability of nitric oxide, which is the most significant chemical mediator of penile erection. Generation of cellular peroxynitrite (ONOO-) was measured using a chemiluminescence assay with the PNCL probe. Subsequently, we measured the activation of acid sphingomyelinase (ASMase) enzyme by radioenzymatic assay using [14C-methylcholine] sphingomyelin as substrate, and the generation of the proapoptotic C16-ceramide was assessed using the diacylglycerol kinase assay. Endothelial cells apoptosis was measured as a readout of these cells' dysfunction. MAIN OUTCOME MEASURES: Single high-dose radiation therapy induced NADPH oxidases (NOXs) activation and ROS generation via the proapoptotic ASMase/ceramide pathway. The radio-protective effect of sildenafil on BAECs was due to inhibition of this pathway. RESULTS: Here, we demonstrate for the first time that radiation activated NOXs and induced generation of ROS in BAECs. In addition, we showed that sildenafil significantly reduced radiation-induced O2•- and as a result there was reduction in the generation of peroxynitrite in these cells. Subsequently, sildenafil protected the endothelial cells from radiation therapy-induced apoptosis. STRENGTHS AND LIMITATIONS: This is the first study demonstrating that single high-dose radiation therapy induced NOXs activation, resulting in the generation of O2•- and peroxynitrite in endothelial cells. Sildenafil reduced ROS generation by inhibiting the ASMase/ceramide pathway. These studies should be followed in an animal model of ED. CONCLUSIONS: This study demonstrated that sildenafil protects BAECs from radiation-induced oxidative stress by reducing NOX-induced ROS generation, thus resulting in decreased endothelial dysfunction. Therefore, it provides a potential mechanism to better understand the atherogenic etiology of postradiation ED. Wortel RC, Mizrachi A, Li H, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med 2019;16:1721-1733.

Impact of cardiovascular risk factors and related comorbid conditions and medical therapy reported at baseline on the treatment response to tadalafil 5 mg once-daily in men with lower urinary tract symptoms associated with benign prostatic hyperplasia: an integrated analysis of four randomised, double-blind, placebo-controlled, clinical trials.

PURPOSE: The influence of cardiovascular risk factors/comorbidities on response to oral once-daily tadalafil 5 mg was explored in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). METHODS: This post hoc analysis pooled data from four double-blind studies in which 1498 men with > 6-mo history of LUTS/BPH were randomised and received either once-daily placebo (n = 746) or tadalafil 5 mg (n = 752) for 12 weeks. Descriptive statistics were reported for changes in total International Prostate Symptom Score (IPSS), IPSS voiding and storage subscores, and IPSS quality-of-life (QoL) index. Treatment group differences by baseline clinical and cardiovascular factors and medical therapies were examined using analysis of covariance. RESULTS: Tadalafil was effective in men with LUTS/BPH and cardiovascular risk factors/comorbidities except for patients receiving > 1 antihypertensive medication. Placebo-adjusted least squares (LS) mean improvements in total IPSS were -1.2 (95% CI: -2.5 to -0.0) in men taking > 1 antihypertensive medication vs. -3.3 (95% CI: -4.4 to -2.1) in men taking one medication (interaction p = 0.020). In addition, placebo-adjusted LS mean improvements in total IPSS were -0.2 (95% CI, -2.1 to 1.7) in men who reported use of diuretics vs. -2.8 (95% CI, -3.7 to -1.9) in men who reported taking other antihypertensive medications vs. -2.3 (95% CI, -3.2 to -1.5) in men who reported not using any antihypertensive drug (p-value for interaction = 0.053). CONCLUSIONS: Once-daily tadalafil 5 mg improved LUTS/BPH, regardless of severity, in men with coexisting cardiovascular risk factors/comorbidities, except for patients with history of > 1 drug for arterial hypertension. Use of diuretics may contribute to patients' perception of a negated efficacy of tadalafil on LUTS/BPH. Comorbidities should be considered when choosing the optimal medicine to treat men with LUTS/BPH.

Erectile function recovery in patients after non-nerve sparing radical prostatectomy.

Few studies have looked at erectile function recovery (EFR) rates in men undergoing non-nerve sparing resection during radical prostatectomy (RP). Existing studies show great variation in EFR rates owing to multiple factors that minimize their utility in counselling RP patients. We investigated the EFR rate and its predictors in unilateral cavernous nerve resection and bilateral cavernous nerve resection patients 24 months after RP. We conducted a population-based, prospective cohort study of 966 patients who underwent RP at a tertiary cancer centre from 2008 to 2012. Cavernous nerve condition was evaluated on a 4-point nerve sparing score and assigned to one of three groups: bilateral sparing, unilateral resection (UNR) and bilateral nerve resection (BNR). EF was assessed pre-RP and 24-30 months post-op using a validated 5-point patient-reported scale (1 = fully rigid; 5 = no tumescence). EFR was defined as a post-op EF grade of 1-2. Statistical analysis included descriptive statistics, anova, chi-square, Fisher's exact test and logistic regression. Mean baseline EF was 1.84 ± 1.3 and 2.74 ± 1.5 for UNR and BNR patients respectively. Thirty-three percent of UNR patients and 13% of BNR patients exhibited EFR. Age, baseline EF were predictors of EFR. Multivariable analysis showed baseline EF was a significant predictor of EFR at 24 months for UNR. For BNR patients, pre-RP EF was the only factor predictive of EFR. Patients undergoing nerve resection still have a significant chance of achieving true EFR, with UNR surgery patients showing more potential for improvement than patients undergoing BNR surgery. Age and baseline EFR characterize recovery prospects in these two groups. Physicians should thus measure and account for baseline EF in addition to age and the degree of nerve resection when advising patients about expectations for successful EF following RP.

Enlarging the scope of managing benign prostatic hyperplasia: addressing sexual function and quality of life.

Benign prostatic hyperplasia is a common genitourinary disorder that increases in incidence with age. Symptoms of this condition include a weak urinary stream, hesitancy, intermittency and sensations of incomplete emptying, as well as frequency, urgency, urge incontinence and nocturia. These symptoms can be ameliorated successfully by a variety of medical treatments - such as alpha(1)-adrenergic blockade and 5-alpha-reductase inhibition - and surgical therapies - including transurethral resection of the prostate and less-invasive procedures. However, many of the treatments are known to result in sexual dysfunction, which can have a negative impact on the patient's quality of life. This must be considered when the physician seeks to determine the appropriate treatment for an individual patient. Current reports suggest that alpha(1)-adrenergic blockade is most likely to improve lower urinary tract symptoms while resulting in the fewest sexual side-effects; 5-alpha-reductase inhibitors appear to be particularly appropriate in men with large prostates. Among surgical therapies, transurethral resection of the prostate remains the gold standard, but is associated with a high incidence of sexual side-effects, especially retrograde ejaculation. Transurethral incision of the prostate, which is an endoscopic procedure, may be as effective as transurethral resection, but results in fewer side-effects. Minimally invasive procedures, including laser ablation or resection of the prostate, transurethral microwave thermotherapy and transurethral needle ablation, are rapidly evolving technologies that have demonstrated promising results, at least in the short term.

Congruence between veno-occlusive parameters during dynamic infusion cavernosometry: assessing the need for cavernosography.

While dynamic infusion cavernosometry (DIC) is being performed with increasing rarity, some centers continue to use this investigation modality. Cavernosography may be utilized to identify the location of patent venous channels in men with venous leak. In an era when venous ligation surgery is being performed with less frequency, the role of cavernosography has been questioned. This study was conducted to define the congruence between the three parameters (flow-to-maintain (FTM), pressure decay (PD) and cavernosography) used in the diagnosis of venous leak during DIC. Established values for the three parameters were utilized and the diagnosis of venous leak was based upon the FTM measurement. All studies were performed using a vasoactive agent-redosing schedule. Cavernosography was conducted using a nonionic contrast agent at an intracorporal pressure of 90 mmHg. In patients with an elevated FTM value, 24% had a normal PD recorded, all of whom had FTM values <10 ml/min. The Pearson correlation coefficient for the relationship between FTM and PD was 0.58 (P=0.025). In all, 36 patients (54%) had an abnormal cavernosogram (CG). All patients who had positive findings on CG had elevated FTM values. On the other hand, 46% of patients with abnormal FTM values had a normal CG. This analysis indicates that almost one-half of men with venous leak diagnosed at the time of DIC based on FTM measurement will fail to have any veins visualized on cavernosography. These data further undermine the value of cavernosography, particularly in men with low-grade venous leak.

Peyronie's disease fibroblasts demonstrate tumorigenicity in the severe combined immunodeficient (SCID) mouse model.

Peyronie's disease is a localized connective tissue disorder, caused by trauma to the erect penis, which results in cellular proliferation and excess extracellular matrix production within the tunica albuginea of the penis. We have previously demonstrated that cells derived from Peyronie's disease plaque tissue demonstrate increased cell growth, increased S-phase on flow cytometry, stabilization and inactivation of p53, and consistent morphologic transformation, all suggesting that these cells are biologically transformed. Severe combined immunodeficient (SCID) mice have been used extensively to study the pathobiology of malignant and benign tissue and cells. This study was undertaken to determine if Peyronie's derived fibroblasts had the potential to demonstrate tumorigenicity in the SCID mouse model, thus confirming their biologically transformed nature. Cultured fibroblasts were derived from three sources, namely, plaque tissue excised from men with Peyronie's disease, tunical tissue excised from young men with congenital penile curvature and neonatal foreskins. BALB/C SCID mice were divided into three groups and each group was inoculated with cultured fibroblasts from each of the three different sources. All animals were evaluated regularly and maintained in isolation for a period of 3 months following inoculation. All SCID mice inoculated with cells derived from Peyronie's disease plaque tissue (n=10) developed subcutaneous nodules at a mean time period of 2.5+/-0.5 months following injection. The mean maximum dimension and weight of the nodules at the time of killing the animal was 1.1+/-0.2 cms and 0.6+/-0.2 g, respectively. Histologically, the nodules were composed of large pleomorphic epithelioid cells with a high mitotic activity, which were negative for cytokeratin but positive for vimentin. None of the SCID mice inoculated with cells cultured from either normal tunica (n=5) or foreskin (n=5) developed subcutaneous nodules. In conclusion, the tumorigenic nature of Peyronie's disease plaque-derived fibroblasts sheds further light on the pathobiologic characteristics of these cells. Specifically, these data confirm that cells cultured from Peyronie's disease plaque are biologically transformed. Future refinement and study of this animal model may permit a more complete understanding of the pathophysiology of Peyronie's disease and fibromatoses in general. Furthermore, such an animal model may, in the future, allow a more ready evaluation of the therapeutic interventions for Peyronie's disease.

Chromosomal instability is demonstrated by fibroblasts derived from the tunica of men with Peyronie's disease.

Peyronie's disease is a fibrotic disorder, a condition characterized by cellular proliferation and excess extracellular matrix production. Previous work in related conditions has demonstrated chromosomal instability. This investigation was undertaken to analyze fibroblasts derived from Peyronie's disease tunical tissue for abnormalities of chromosome number and progression of cytogenetic aberrations during cell culture. Tunical tissue was excised from men with Peyronie's disease from both plaque and nonplaque tissue and cells were explanted in culture. Control cells were derived from both neonatal foreskins and normal tunica from men with congenital penile curvature. Fluorescent in situ hybridization was used to probe for chromosomes 7, 8, 17, 18, X and Y. Control cells demonstrated normal copy number for all chromosomes analyzed. In contrast, Peyronie's disease plaque-derived fibroblasts demonstrated frequent aneusomies in chromosomes 7, 8, 17, 18 and X and recurrent deletions of chromosome Y. Peyronie's disease nonplaque tunica-derived fibroblasts demonstrated infrequent chromosomal changes early in culture; however, with repeated passaging the majority of cell cultures demonstrated aneusomies in at least one chromosome. These data indicate that Peyronie's disease plaque-derived fibroblasts have consistent aneusomies even at early passage and that nonplaque tunica-derived cells from men with Peyronie's disease also demonstrate chromosomal instability. This suggests that the tunica albuginea of men with Peyronie's disease may be predisposed to undergoing unregulated fibrosis. These findings confirm the transformed nature of the Peyronie's disease tunical fibroblasts studied in this analysis. While the etiology of these findings is not clear, it is likely that these pathobiological characteristics contribute to the pathophysiology of this disease process.

The impact of sildenafil citrate on sexual satisfaction profiles in men with a penile prosthesis in situ.

OBJECTIVE: To assess the efficacy of sildenafil in increasing penile glans tumescence and improving patient satisfaction in men with a penile prosthesis, as this remains a major treatment for erectile dysfunction but a common complaint is the lack of glans engorgement. PATIENTS AND METHODS: To determine whether sildenafil combined with a penile prosthesis improves satisfaction, patients used an implant alone for at least 1 month, after which they completed the International Index of Erectile Function (IIEF) questionnaire. The same patients were then given sildenafil citrate and completed the IIEF questionnaire after using the sildenafil/implant combination. RESULTS: Patients who responded to sildenafil with glans engorgement reported significantly greater satisfaction scores than with an implant alone. CONCLUSION: We currently offer sildenafil citrate after implantation to all men who have a penile prosthesis placed.

The potential value of erectile dysfunction inquiry and management.

Erectile dysfunction (ED) is a serious condition that becomes more common as men age. Many older men, however, report satisfactory erectile capacity and enjoy satisfying sexual relationships. Physicians have been slow to discuss ED with patients even in the presence of multiple risk factors. New information provides strong reasons for ED inquiry and management in the primary care physician's office. The presence of ED can reveal as yet undiscovered neurovascular and psychological disorders including diabetes, hypertension, dyslipidaemia, depression and anxiety as well as early neuromuscular disorders. By inquiring about ED, physicians can better decrease iatrogenic sexual dysfunction caused by certain commonly used medications. The successful management of ED, made much easier by the development of phosphodiesterase type 5 inhibitors, has additional potential benefits including improvement of quality of life for both the patient and his partner; decreasing the symptoms of depression in depressed men who also have ED; improving relationships, a significant factor related to good health; and enhancing overall patient health. Other potential values for the physician include a better clinician-patient and increased physician work satisfaction. Primary care physicians need to recognise the value of ED inquiry and management and integrate these activities into practice.

Expanding the paradigm for plaque development in Peyronie's disease.

Despite centuries of recognition, Peyronie's disease remains somewhat of an enigma. Conventional wisdom suggests that trauma to the erect or semierect penis is the inciting event that sets off a cascade of events at the cellular level that results in localized fibrosis of the tunica albuginea. However, many questions remain unanswered at this juncture among the most important of which are why do so few men manifest this condition? Why is there such an ethnic predilection? What are the cofactors that along with penile trauma lead to plaque development. Historically, cytokine overexpression, autoimmune and genetic factors have been cited as contributors. This treatise endeavors to conduct an evidence-based assessment of the literature as it pertains to the pathophysiology of Peyronie's disease. Furthermore, an effort is made to evaluate contemporary literature pertaining to novel concepts in Peyronie's disease pathogenesis including NOS alterations, free radical generation, microarray analysis, pathogen involvement and animal model development. In conclusion, it is likely that in the near future we will see dramatic developments in our understanding of this condition.

Peyronie's disease cell culture models: phenotypic, genotypic and functional analyses.

Peyronie's disease is a fibromatosis of the tunica albuginea. While trauma is believed to be the inciting event, the exact pathophysiology of this condition is unknown. In vitro analysis of cell biology can shed light on the pathogenesis of medical conditions and has been used for many decades as a research tool. We have established a cell culture model, which we have used to study the pathobiology of cells derived from Peyronie's disease plaque tissue. In 10 separate cell cultures derived from different individuals, these cells have demonstrated consistent phenotypic, genotypic and functional alterations. In neither of the control cell cultures, neonatal foreskin fibroblasts and normal tunica-derived fibroblasts have any of the above aberrations been demonstrated. The cells studied have been shown to be fibroblasts in nature with a sub-population of myofibroblasts present in culture. The Peyronie's disease plaque tissue-derived fibroblasts have demonstrated (i) consistent morphologic transformation (ii) increased S-phase on flow cytometry (iii) decreased dependence on culture medium (iv) cytogenic instability (v) excess production of fibrogenic cytokines and (vi) stabilization and dysfunctionalization of p53. Further refinement of this model and future analyses may permit an increased understanding of the pathogenesis of this condition and allow the development of therapeutic strategies.

An open-label, uncontrolled dose-optimization study of sublingual apomorphine in erectile dysfunction.

BACKGROUND: Because apomorphine is a dopamine agonist that acts on areas of the central nervous system believed to mediate penile erection, its use in erectile dysfunction (ED) has been investigated. However, it also produces nausea by dopamine-receptor stimulation of the chemotrigger zone in the brain. Therefore, a low plasma concentration, achieved rapidly, would be selective for the desired erectile response but would be below the dopamine threshold for nausea. OBJECTIVE: We evaluated the efficacy and tolerability of a dose-optimized regimen of a sublingual formulation of apomorphine (apomorphine SL) in the treatment of ED. METHODS: This was a multicenter, open-label, uncontrolled, Phase III dose-optimization study of apomorphine SL in heterosexual men with ED. The 2-week screening period, during which baseline severity of ED was determined using the International Index of Erectile Function, was followed by a 3-week dose-optimization period beginning at a dose of 2 mg. Patients were to make at least 2 attempts at intercourse per week throughout the study, placing 1 apomorphine tablet under the tongue beforehand. At the end of the first week, the dose could be increased to 3 mg at the discretion of the investigator; at the end of the second week, the dose could be increased to a maximum of 4 mg or decreased as needed. In the following 4-week treatment period, patients took their individual optimal doses. The primary efficacy variable was the percentage of attempts resulting in erections firm enough for intercourse, as assessed by investigators' review of data from patients' diaries. Secondary variables included the percentage of attempts resulting in successful intercourse, time to erection, and duration of erection. Information about adverse events, including their severity and relation to treatment, was determined on the basis of direct questioning, spontaneous reports, and review of patient diaries. RESULTS: The study enrolled 849 heterosexual men whose ages ranged from 31 to 78 years (mean, 58.1 years). They had a mean 5.7-year history of ED of varbus causes. ED was mild in 11.5% of the men, moderate in 23.8 c, and severe in 48.1%. When results of the last 8 attempts were pooled, representing the period during which patients were taking their optimal doses of apomorphine SL, the mean percentage of attempts resulting in erections firm enough for intercourse was 39.4%, compared with 13.1% at baseline; attempts resulting in intercourse increased from a mean of 12.7% at baseline to 38.3% with treatment. The average median time to erection was 23 minutes, and the average median duration of erection was 13 minutes. Nausea, the most common treatment-related adverse event (11.7%). was dose related and diminished with continued dosing. One patient had a single syncopal episode that was judged to be related to apomorphine SL. CONCLUSIONS: In the present study, a dose-optimization regimen of apomorphine SL-with dosing initiated at 2 mg and adjusted up to a maximum of 4 mg as needed-was effective and well tolerated in the treatment of ED, regardless of its cause or severity.

Analysis of the consistency of intraurethral prostaglandin E(1) (MUSE) during at-home use.

OBJECTIVES: To determine the consistency of a successful response to intraurethral prostaglandin E(1) (MUSE), an effective treatment for a proportion of patients with erectile dysfunction, during at-home use in men who had a successful response in the office, to define the factors that correlated with the consistency of the response, and to determine whether patients continued long-term use. METHODS: The study group consisted of men with documented erectile dysfunction who had a successful response (grade 3 or 4 erection) to MUSE during an initial in-office dose. All enrollees completed a home diary assessing the treatment success during at least five medication administrations. Factors such as patient age, vascular risk factor status, and degree of in-office response were prospectively evaluated as correlates of response consistency. Finally, patient follow-up was conducted in an attempt to define how many patients were continuing to use this medication as a long-term treatment modality. RESULTS: Two hundred twelve patients underwent screening and 72 (34%) patients had in-office success. The overall per patient at-home consistency rate was 51%. None of the aforementioned factors correlated with the consistency of the response. At a mean of 9 months after beginning treatment, only 31% of the in-office responders were continuing to use MUSE. CONCLUSIONS: Although MUSE is an appropriate and safe treatment for many patients with erectile dysfunction, the lack of consistency is a significant consideration. Clinicians should pay close attention to patient education in an effort to promote realistic expectations for MUSE therapy. Furthermore, the lack of consistency may significantly lower the patient's interest in continuing this treatment long term.

Development of a mathematical model for the prediction of the area of venous leak.

Erectile dysfunction (ED) is an increasingly prevalent medical problem, affecting up to 50% of men aged between 40 and 70-y-old. Many cases are vasculogenic and some of these stem from the inability of the penis to store blood during erection due to leak into the venous system, termed corporo-venocclusive dysfunction (CVOD). The area of leakage during erection could be the most direct measure of erectile function but has not been investigated before. We have developed a simple mathematical model to determine the area of leak during erection and have tested it on data from both normal men (n=3) and men with venogenic impotence (n=16) undergoing dynamic infusion cavernosometry (DIC). The area of leak in the impotent group is significantly greater than in normal men at intracorporal pressures above 30 mmHg and reaches a plateau between 60 and 90 mmHg. Based on this study, we suggest that it may be necessary only to perform DIC at intracorporal pressures between 60 and 90 mmHg.

Improving the accuracy of vascular testing in impotent men: correcting hemodynamic alterations using a vasoactive medication re-dosing schedule.

PURPOSE: Arteriogenic or venogenic vascular insufficiency is the most common pathophysiology of organic erectile dysfunction. While vascular insufficiency may be suspected on history and physical examination, the definitive diagnosis is made by vascular testing. Dynamic infusion cavernosometry is a recognized technique for evaluating the hemodynamics of erection. Assigning the correct vascular diagnosis during testing is important. Complete corporeal smooth muscle relaxation is essential for obtaining accurate data. Previously others have suggested that repeat dosing with vasoactive medication may improve the diagnostic accuracy of vascular testing. We investigated the hemodynamic effect of repeat doses of medication. MATERIALS AND METHODS: Data were prospectively obtained on men undergoing dynamic infusion cavernosometry. When veno-occlusive parameters were abnormal, the intracavernous vasoactive agent dose was repeated to a maximum of 3 doses. Standard dynamic infusion cavernosometry criteria were used for diagnosing arteriogenic and venogenic erectile dysfunction. We analyzed the proportion of men in whom the vascular diagnosis was altered using this regimen. RESULTS: Of 420 men undergoing dynamic infusion cavernosometry, 70% warranted re-dosing based on abnormal veno-occlusive parameters. Of these 294 men veno-occlusive values were corrected by repeat medication in 32% and, therefore, they would have been falsely diagnosed with venous leakage during vascular evaluation. Half of all corrections occurred with the second dose, while half of the patients required a third dose of medication. CONCLUSIONS: These data should encourage clinicians to consider re-dosing during the vascular evaluation of men in whom incomplete corporeal smooth muscle relaxation is suspected. In this way a false diagnosis of venous leakage may be avoided in a significant number of cases.

Should all infertile males undergo urologic evaluation before assisted reproductive technologies? Two cases of testicular cancer presenting with infertility.

OBJECTIVE: To report two cases of testicular cancer in patients presenting with infertility. DESIGN: Case reports. SETTING: University-affiliated urology practice. PATIENT(S): Two men presenting with infertility. INTERVENTION(S): Complete history and physical, hormonal assays, semen analysis, scrotal ultrasound, radical orchiectomy. MAIN OUTCOME MEASURE(S): Testicular pathology specimens. RESULT(S): Testicular cancer was diagnosed in two men sent to a urology clinic for infertility treatment. CONCLUSION(S): A thorough evaluation should be completed in all males in couples presenting with infertility.

Reconstructing penile supersonic transporter (SST) deformity using glanulopexy (glans fixation).

After penile prosthesis insertion, men may develop a disabling supersonic transporter deformity from any one of several causes. We describe the results of surgical treatment in 10 such patients in whom sexual relations were restored by reconstructive glanulopexy. All procedures were performed on an outpatient basis using local anesthesia.

Basic fibroblast growth factor expression in Peyronie's disease.

PURPOSE: Peyronie's disease is a fibromatosis resulting in scarring of the tunica albuginea. While the inciting event is believed to be trauma to the erect penis, little is understood about the cascade of cellular events that leads to the formation of the plaque. Dysregulated wound healing serves as a paradigm for the study of this condition. Previous work has demonstrated a role for fibrogenic cytokines in wound healing, fibromatoses, including Peyronie's disease. We analyze the expression of the fibrogenic cytokine, basic fibroblast growth factor (FGF), by fibroblasts derived from Peyronie's disease tissue. MATERIALS AND METHODS: Patients with Peyronie's disease undergoing either penile prosthesis insertion or Nesbit penile plication surgery had biopsy specimens removed from the plaque and from normal tunical tissue remote from the plaque. Cell cultures were derived from these specimens. Cultured cells were characterized using immunofluorescence staining and immunosorbent digital imaging. The cell culture supernatants were analyzed using an enzyme-linked immunosorbent assay for the production of basic FGF. Foreskin tissue from men without Peyronie's disease was used as control cells. RESULTS: Five independent cell lines were established from plaque tissue and 4 independent cell lines were established from normal tunica from the same subjects. Intracellular antigen expression was consistent with the cells being myofibroblasts. Production of basic FGF by the plaque derived myofibroblasts was significantly greater compared to production by normal tunical myofibroblasts and foreskin fibroblasts. CONCLUSIONS: These data demonstrate the successful establishment of cell lines from plaque tissue and normal tunica from men with Peyronie's disease. The findings indicate a potential role for basic FGF over expression in the tunical fibrosis that occurs in this condition. This information may allow a better understanding of the basic mechanisms involved in the development of this disease. Furthermore, it may permit the elaboration of therapeutic strategies to prevent or reduce tunical scarring and plaque formation.