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Biomedical subjects

David J Ralph

Publications and source records attributed to David J Ralph.

At least 19 recordsLinked to original sources

The penile suspensory ligament: abnormalities and repair.

OBJECTIVE: To assess men presenting with abnormalities of the penile suspensory ligament (PSL) and its correction. PATIENTS AND METHODS: In all, 35 men presenting with abnormalities of the PSL that were subsequently repaired were included in this series. The causes included; sexual trauma (15 men), congenital absence of the PSL/congenital penile curvature (14), and two each with venogenic erectile dysfunction, Peyronie's disease and penile dysmorphic disorder. The diagnosis was made clinically by the presence of a palpable gap between the symphysis pubis and the penis, together with medical history and examination of penile torsion or instability. The surgical repair used nonabsorbable sutures placed between the symphysis pubis and the tunica albuginea of the penis. RESULTS: A 'good' surgical outcome was defined as correction of the penile deformity or instability and achieving normal sexual function. There was a good surgical outcome in 91% of men as defined, and 86% of the men were happy with the outcome. There were no significant complications, but three men needed a repeat PSL repair. CONCLUSION: Men with abnormalities of the PSL can present with a variety of clinical symptoms, but when correctly diagnosed the repair is a simple technique with a successful cosmetic and functional outcome.

Adolescent↗

Penile suspensory ligament division for penile augmentation: indications and results.

OBJECTIVE: This study assessed the management of patients requesting penile length enhancement by division of the penile suspensory ligament. METHODS: From September 1998 to January 2005, 42 patients with a variety of etiologies were included; all underwent division of the penile suspensory ligament. The outcome was assessed objectively based on increase in flaccid stretched penile length (SPL) and subjectively using the rates of patient satisfaction. RESULTS: The mean increase in SPL was 1.3+/-0.9 cm (range, -1 to +3 cm), with the addition of a silicone spacer placed between the pubis and penis giving a better outcome (p<0.05). The overall patient satisfaction rate was 35% but lower in the group with penile dysmorphic disorder at 27%. CONCLUSION: Division of the penile suspensory ligament or other augmentation techniques may increase penile length but usually not to a degree that satisfies the patient. Men with penile dysmorphic disorder often have unrealistic expectations regarding the outcome of surgical intervention and should be encouraged to seek psychological help primarily, with surgery reserved as the last resort.

Adolescent↗

Reconstructive surgery of the penis.

PURPOSE OF REVIEW: Diseases of the penis are common, and the aim now is the preservation of function and cosmesis of the penis using modern penile reconstructive techniques. Penile cancer, Peyronie's disease and trauma are the three pathologies assessed. RECENT FINDINGS: Modern conservative organ-sparing surgery in penile cancer has shown that good oncological control can be gained by 2 mm margins that allow preservation of sexual function. Early intervention in the traumatic penis gives better results whereas the Nesbit operation is still the gold standard for Peyronie's disease as the quest for an alternative graft to saphenous vein continues. SUMMARY: The current operations of choice in penile reconstruction are glansectomy and skin grafting to fashion a neoglans in penile cancer and the Nesbit operation or saphenous grafting for Peyronie's disease.

Humans↗

Outcome of penile prosthesis implantation for treating erectile dysfunction: experience with 504 procedures.

OBJECTIVE: To evaluate the outcome of penile prosthesis surgery for different types of prosthesis. PATIENTS AND METHODS: The notes of 447 men who had 504 penile prosthesis implanted between August 1975 and December 2000 were evaluated. Of the prostheses inserted, 393 were malleable, 81 were three-piece inflatable and 30 were self-contained hydraulic prostheses. The mean (range) age of the men was 52 (21-78) years; 404 men had primary implants and 43 had revision surgery after operations at other institutions. The mean follow-up was 50 (1-297) months. RESULTS: Of the 447 men, 22 were lost to follow-up immediately after surgery. The most serious postoperative complications were infection (8%) and erosion (5%), which was more common in diabetic patients (10%) and after pelvic trauma with a urethral injury (21%). Of 482 prostheses, 21 failed mechanically (4%) and revision surgery was needed for 5% of the prostheses inserted (24/482). Overall, 89% (377/425) of men could have sexual intercourse and 344 (81%) were satisfied with the results. CONCLUSIONS: Of the men implanted with a penile prosthesis, 81% were satisfied with the outcome and an even higher proportion were satisfied with the inflatable prostheses. Dissatisfaction was mainly due to complications that resulted in removal of the prosthesis.

Adult↗

Venogenic erectile dysfunction in Klippel-Trenaunay syndrome.

OBJECTIVE: To report the management of erectile dysfunction (ED) secondary to Klippel-Trenaunay syndrome (KTS), a rare congenital vascular disease. PATIENTS AND METHODS: Three men (mean age 33 years) with vasogenic ED secondary to KTS underwent venous ligation surgery of the affected veins. These men had tried various treatments for their ED, including phosphodiesterase type 5 inhibitors and intracavernosal injection therapy, with little success. RESULTS: There was abnormal penile venous drainage in all three men, probably associated with congenital vascular malformation from KTS. After venous ligation the men were followed for 5 years and all reported good quality erections satisfactory for sexual intercourse. CONCLUSION: ED in men with KTS may be due to venous drainage anomalies and if confirmed, venous ligation surgery should be performed as this gives the best chance of a complete resolution.

Adult↗

Plaque incision and fascia lata grafting in the surgical management of Peyronie's disease.

OBJECTIVE: To assess the outcome of using modified human fascia lata (Tutoplast, Mentor Corp, Santa Barbara, CA, USA) in the surgical management of Peyronie's disease (PD), as the penile deformity associated with PD can be corrected by plaque incision and saphenous vein grafting (Lue procedure). PATIENTS AND METHODS: In all, 14 patients (mean age 51 years, range 34-59) with PD had their penile deformity corrected by plaque incision and Tutoplast grafting. Three patients had a previous unsuccessful Nesbit operation. The mean (range) penile deformity before surgery was 67.2 (20-90) degrees and the mean follow-up was 31 (17-37) months. RESULTS: Using set criteria, 13 patients were satisfied (excellent or satisfactory) with the results of surgery. The penis was completely straight in 11 of 14 patients. One patient developed de novo erectile dysfunction after surgery. In 10 patients there was no penile shortening, whereas four reported penile shortening of >1 cm. CONCLUSION: Fascia lata Tutoplast grafts provide a reliable and well tolerated biomaterial for penile reconstruction in PD. The outcome of using Tutoplast is similar to that from saphenous vein but without the morbidity associated with the donor site. However, there remains a significant risk of penile shortening and development of erectile dysfunction.

Adult↗

Evaluation of the Sexual Assessment Monitor, a diagnostic device used to electronically quantify ejaculatory latency time: findings from three studies.

OBJECTIVE: To validate the Sexual Assessment Monitor (SAM), a novel apparatus designed to collect electronic data on ejaculatory latency time (ELT) for diagnosing premature ejaculation (PE), and for accurately measuring treatment outcomes in clinical trials. PATIENTS, SUBJECTS AND METHODS: Men with PE, and healthy volunteers aged 18-75 years, were enrolled in three open-label studies, conducted in the UK. The SAM, which consists of a control box with two front attachments, a vibrator and sensor, was attached to the penis. The vibrator, which provides stimulation, was positioned at the frenulum using a soft cuff; the vibrator intensity was set at 80 units for most subjects. The sensor is an indium-gallium elasticated loop, which was positioned around the base of the penis to detect ejaculatory pulses. These pulses were transmitted to a data recorder in the control box. The data, which are displayed graphically as traces, were automatically classified by a computer-generated algorithm to quantify ELT. RESULTS: In all, 53 healthy volunteers and 58 men with PE provided 213 and 195 evaluable records, respectively. Most were complete records (99% and 96%). The pooled data showed that the ELT was much higher for healthy volunteers than for men with PE (geometric means: 687 vs 169 s, respectively), with a healthy volunteer to PE patient ratio of 2.87 (P < 0.001). Only 6.3% of subjects reported mild adverse events, which were unrelated to the SAM. CONCLUSIONS: These open-label studies show that the SAM can consistently and safely measure times to erection (from the start of vibration) and ejaculation, and ELT in healthy volunteers and men with PE. These findings show that the SAM has the potential to become the 'gold standard' in the diagnosis of PE and in clinical trials design.

Adolescent↗

A prospective study of 100 cases of penile cancer managed according to European Association of Urology guidelines.

OBJECTIVE: To prospectively assess the outcome of patients treated according to the European Association of Urology (EAU) guidelines on the management of penile cancer, a system originally based on retrospective series. PATIENTS AND METHODS: Between 2002 and 2005, 100 consecutive patients (median age 62 years) with penile cancer were treated at one institution; all were categorized and treated according to EAU guidelines. Data were analysed using the z-test, with significance defined as P < 0.05. RESULTS: Survival curves were limited to those with >12 months of follow-up (mean 29); the survival of the whole group was 92%. Of men with palpable nodes, 72% had lymph node involvement, whereas 18% of those with impalpable nodes who had lymphadenectomy according to the guidelines had lymph node disease. The grade of the primary tumour was more predictive than T stage for lymph node involvement and survival. The 3-year disease-specific survival for N0, N1 and N2 disease was 100%, 100% and 73%, respectively, and survival at 12 months for N3 disease was 67%. The median survival for those with metastases was 3 months. CONCLUSION: The overall survival of men with penile cancer is high, with a clear benefit for early lymphadenectomy in men with positive nodal disease. However, the current EAU guidelines are limited in predicting those patients with micrometastatic disease, with the result that 82% of patients undergo unnecessary prophylactic lymphadenectomy. There is a need to identify more accurate molecular markers for predicting lymph node disease, or the role of novel staging techniques must be assessed.

Adult↗

Normal erectile function.

A complex interaction of neural, vascular, and biomolecular activity results in normal erectile function. Two chambers in the penis, the corpus cavernosa, contain sinusoids, which fill with blood and expand to become rigid when smooth muscle is relaxed. Blood flow out of the penis is temporarily stopped (veno-occlusion) to maintain the erection. Neural control is complex but, in general, the sympathetic nervous system inhibits, and the parasympathetic system excites erectile function. The central nervous system can induce erections without peripheral stimuli, e.g. in nocturnal erections. In general, there are 5 recognized phases in erectile response: latent, tumescent, full erection, rigid erection, and detumescent. The key biochemical event in erectile function is an increase in levels of cyclic guanosine monophosphate, which causes smooth-muscle relaxation and allows an erection to occur. This process is mediated by nitric oxide, produced by neurons and elsewhere, which acts as a gaseous messenger molecule.

Central Nervous System↗

Reconstructive surgery in penile trauma and cancer.

This article provides an overview of the current concepts in reconstructive surgery following penile trauma, penile fracture and penile cancer. It covers the initial management of penile trauma, with the aim of preservation of as much viable tissue as is practical, and also provides advice on dealing with penile avulsion and amputation injuries. The best treatment for penile fracture-immediate surgical exploration and repair-is outlined and discussed. Finally, penile cancer management is reviewed, from initial biopsy to definitive treatment of the penile lesion-including wide excision, partial glansectomy, total glansectomy, and partial and total penectomy. It is concluded that appropriate surgery in all these conditions reduces subsequent long-term problems in sexual function, cosmesis, psychology, and (in cancer cases) longevity. The same reconstructive techniques can be applied for different penile conditions, and it is suggested that surgeons become experienced in genital surgery as a whole, rather than in oncology or trauma alone.

Humans↗

Pedicled pubic phalloplasty in females with gender dysphoria.

OBJECTIVE: To describe a novel phalloplasty technique and to study the results and complications in female patients with gender dysphoria. PATIENTS AND METHODS: Between 1989 and 2000, 85 female-to-male transsexual patients had a phalloplasty fashioned from suprapubic abdominal wall flap that was tubed to form the phallus, and which incorporated the neourethra made from a pedicled tube of labial skin. The complete neourethral reconstruction was in one stage in 32 patients and in two in 48; five patients did not wish to have the neourethra fashioned. RESULTS: The cosmetic appearance of the phallus was considered good in 68% of the patients. The major complications (in 60 patients) were related to the neourethra (75%) with stricture formation (64%) and/or fistulae (55%) predominating. This complication rate was significantly less (P < 0.001) when the neourethra was created in two stages. Once the neourethra was completed, patients were then offered both penile and testicular prostheses. Sexual intercourse was possible with no prosthesis in 16 patients. CONCLUSIONS: The pubic phalloplasty offers an acceptable neophallus without disfiguring the donor skin site. The main complications stem from creating the neourethra and these may be reduced by a two-stage procedure.

Adolescent↗

A nitric oxide-releasing PDE5 inhibitor relaxes human corpus cavernosum in the absence of endogenous nitric oxide.

INTRODUCTION: In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic approach in such cases. AIM: We therefore aimed to compare sildenafil and NO-releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence or presence of endogenous NO. METHODS: The two compounds were compared in reducing the phenylephrine-induced tone of human corpus cavernosum in the presence or absence of an inhibitor of NO synthase (L-NAME; 500 microM) or an inhibitor of soluble guanylate cyclase (ODQ, 10 microM). RESULTS: NCX-911 was as potent as sildenafil in control conditions (EC(50) = 733.1 +/- 94.4 nM and 800.7 +/- 155.8 nM, respectively). The potency of NCX-911 was not altered but that of sildenafil decreased significantly in the presence of L-NAME (EC(50) = 980.4 +/- 106.7 nM and 2446.7 +/- 256.8 nM, respectively; P < 0.001 for sildenafil vs. control). Both compounds below 1 microM failed to induce relaxation in the presence of ODQ (EC(50) = 6,578 +/- 1150 nM and 6,488 +/- 938 nM for NCX-911 and sildenafil, respectively). CONCLUSION: These results show that the potency of NCX-911 was maintained unlike sildenafil in the absence of endogenous NO confirming the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions.

Erectile Dysfunction↗

A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats.

We compared the effects of a nitric oxide (NO)-releasing sildenafil (NCX-911), NO-independent soluble guanylate cyclase activator (BAY41-2272) and sildenafil on the anococcygeus muscle from streptozotocin-induced 16-weeks diabetic rats. NCX-911, BAY41-2272 and sildenafil reduced the phenylephrine-induced tone in the control group (EC50=1088.8+/-165.0, 151.6+/-9.3 and 827.1+/-167.3 nM, respectively). The potencies of NCX-911 and BAY41-2272 were not altered, but that of sildenafil was significantly reduced in the diabetic group. EC50 values for NCX-911, BAY41-2272 and sildenafil in the diabetic group were 1765.9+/-303.5, 209.7+/-27.3 and 2842.2+/-640.3 nM, respectively (P<0.05 for sildenafil). Nitrergic relaxation responses were significantly decreased in the diabetic group. The remaining nitrergic relaxation responses were potentiated by BAY41-2272 but not by sildenafil or NCX-911. These results confirm that endogenous NO derived from nitrergic nerves is significantly decreased in diabetes, and suggest that NO-releasing PDE5 inhibitors and NO-independent soluble guanylate cyclase activators could be more useful than PDE5 inhibitors in the treatment of ED in long-term diabetes.

Adrenergic alpha-Agonists↗

Plaque incision and grafting as a salvage after a failed Nesbit procedure for Peyronie's disease.

OBJECTIVE: To analyse the outcome of plaque incision and grafting in patients who have a residual penile deformity after a Nesbit procedure for Peyronie's disease, as a further Nesbit procedure may present difficulties in dissection at the previous operative site, and may result in further penile shortening. PATIENTS AND METHODS: Over a 5-year period, 15 patients (mean age 58 years, range 34-66) presented with a residual penile deformity after a Nesbit procedure. All the patients had painless and stable Peyronie's disease. All patients had the Peyronie's plaque incised and grafted with either saphenous vein (12) or modified human fascia lata (three). The outcome was assessed using criteria which recorded the degree of penile shortening, quality of erections and penile angulation. RESULTS: Before surgery the mean (range) angle of deformity was 56 (40-90) degrees ; at a mean follow-up of 10 (3-16) months 11 patients had a straight penis, three a residual angle of 10-30 degrees and one had no change in angle. Two patients reported penile shortening and one a new onset of erectile dysfunction. Overall, 14 patients reported either an excellent or satisfactory result. CONCLUSIONS: These results indicate that plaque incision and grafting is an effective salvage operation to correct a residual penile deformity after a failed Nesbit procedure in patients with Peyronie's disease.

Adult↗