Penile enhancement using a porcine small intestinal submucosa graft in a rat model.

Several biodegradable materials have been experimented for penile enhancement, but none show the potential for clinical use. This study was designed to use porcine small intestinal submucosa (SIS) augmenting the normal tunica albuginea to increase the functional girth of the rat penis. In all, 20 adult male Sprague-Dawley rats constituted the study population. The animals were divided into two groups: group 1 consisted of the control (n=10) and group 2 (n=10) consisted of rats that underwent penile enhancement by a longitudinal I-shaped incision of the tunica albuginea on both sides, and the dissection of the plane between tunica albuginea and cavernosal tissue was carried out (n=10). The incision was then patched with a 3 x 10 mm2 piece of SIS, using a 6/0 nylon suture material. The penile length and mid-circumference were then measured using a Vernier Caliper before and 2 months after surgery. All rat penises underwent histological examination using Masson's trichome and Verhoff's van Giesen's stain for collagen and elastic fibers. The penile length, mid-circumference and degree of fibrosis score were expressed as mean+/-s.e. (standard error) and analyzed using a Wilcoxon rank-sum test. A statistical significance was accepted at P-value < or =0.05. Our results showed similar preoperative penile length and circumference in both groups. However, 2 months after the surgery, the mean penile circumference of the SIS group has grown significantly larger than the control group, while the mean penile length remained unchanged. The histological study of the rat penises revealed minimal amounts of fibrosis under the graft, and the elastic fibers of the graft showed orientation in a circular manner. In conclusion, SIS appears promising for material use in a penile enhancement.

Long-term follow-up on use of pericardial graft in the surgical management of Peyronie's disease.

We have previously reported on the use of Tutoplast cadaveric pericardium as an alternative material for grafting the tunica albugineal defect after Peyronie's plaque excision with satisfactory results in 11 patients. We now review long-term outcomes in this cohort of men. Eleven patients with significant penile curvature interfering with sexual intercourse were evaluated after at least 12 months of conservative therapy. All patients underwent pre-operative evaluation, including penile duplex Doppler ultrasound studies. Chemically processed and gamma-irradiated pericardium (Biodynamics International, Parsippany, NJ) was used to graft the cavernosal defect after surgical excision of the penile plaque. Three patients simultaneously underwent placement of penile prostheses secondary to documented erection problems identified at duplex Doppler ultrasound evaluation. The long-term postoperative complications and erectile function were evaluated with a mean follow-up of 30 months (range 25-35 months). All patients reported resolution of penile curvature allowing for normal sexual function after a mean follow-up of the first 14 months. Thirty months after placement of cadaveric pericardium, the three prosthetic patients still reported excellent sexual function. For the eight patients who did not undergo placement of a prosthesis, three with small to medium plaque size (<2 x 5 cm) continued to do well. The remaining five patients with a large plaque size (>2 x 5 cm) did well initially, but later reported difficulty maintaining erection due to venous leakage, thus they are currently using either a vacuum constriction device or an Actis ring. Three out of these five venous leakage patients had ventral plaques; two had dorsal plaques, one of significant size (4 x 5 cm). We conclude that for those patients who do not undergo placement of a prosthesis, a better long-term outcome is observed when the plaque is small to medium in size (<2 x 5 cm) and dorsally located. Patients with ventral plaque, extreme curvature, or plaque size >4 x 5 cm were more likely to have venoocclusive dysfunction, necessitating further intervention.

Antimicrobial activity of antibiotic-soaked, Resist-coated Bioflex.

This study investigates whether a hydrophilic coating (Resist), designed to inhibit bacterial adherence, applied to inflatable penile prostheses can prolong the effect of intraoperative antibiotics. The activity of antibiotic-soaked Bioflex (penile prosthetic substrate material) discs with and without Resist was examined by measuring the zone of inhibition following in vivo exposure in four groups of rabbits: 1, 2, 3 and 5 days' duration of disc implantation. Coated and uncoated discs were soaked in an aqueous solution of gentamicin and bacitracin. The implanted antibiotic-soaked discs were extracted, and the zone of inhibition against four microorganisms in vitro demonstrated that the Resist coating was especially effective against Staphylococcus epidermidis, and statistically significant improvements were observed for the coated over the uncoated substrate up to 3 days following implantation. This effect, and the anti-adherence properties of Resist, may prevent adhesion and colonization of some microorganisms to penile implants and reduce chances for infection.

Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats.

Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administered sildenafil demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal. STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone.

Intracavernosal injection and intraurethral therapy for erectile dysfunction.

Although the search for newer and more effective oral therapies is continually expanding, intracavernosal and intraurethral treatments continue to keep pace and are expected to remain in the clinician's armamentarium in the years to come. Unless there are contraindications, oral therapies are effective, have minimal side effects, and are first-line treatment. Some patients who have failed intraurethral and intracavernosal injection therapies previously have been shown to have successful outcomes with oral sildenafil in 56% to 57% of cases. If oral therapies are ineffective or have undesirable side effects, the intraurethral or intracavernosal routes are the next approach that should be prescribed.

Evaluation of nitric oxide synthase and arginase in the induction of a Peyronie's-like condition in the rat.

Peyronie's disease is an idiopathic, localized connective tissue disorder of the penis, involving the tunica albuginea of the corpus cavernosum and adjacent areolar space. Current proposals as to the origin of Peyronie's disease suggest that fibrosis and collagen changes of the tunica are the result of an inflammatory process following vascular trauma. Our laboratory and other investigators have recently proposed an animal model for the study of Peyronie's disease. When transforming growth factor-beta1 (TGF-beta1) was injected into the rat tunica albuginea, tissue fibrosis was observed at 6 weeks. Therefore, our aim was to assess arginase II, endothelial and inducible nitric oxide synthase isoforms, and nitrotyrosine levels--all factors involved in inflammatory reactions--in the cavernosal tissue of saline-injected and TGF-beta1-injected rats after 6 weeks in order to evaluate the roles these enzymes may play in the induction of a Peyronie's-like condition in the rat. To examine the expression of endothelial nitric oxide synthase (eNOS), iNOS, and arginase II protein, and mRNA in the corpus cavernosum, immunoblot analysis, and reverse transcriptase-polymerase chain reaction were performed. We also determined immunohistochemically the expression of nitrotyrosine, a marker of peroxynitrite formation, in the rat penis. After 6 weeks, iNOS protein and gene expression was up-regulated and eNOS protein and gene expression was down-regulated in the corpora cavernosa of the TGF-beta1-injected penises. Furthermore, arginase II protein expression as well as immunohistochemical localization of nitrotyrosine was significantly higher in the TGF-beta1-injected corpora cavernosa. These results suggest that iNOS is the key control element for peroxynitrite formation, arginase II expression, and eNOS down-regulation in the induction of a Peyronie's-like condition in the rat.

The current therapy of urinary calculi in Thailand.

The paper analyses the impact of modern therapy of urinary calculi in Thailand since the introduction of ESWL and endourology (PCNL and URS) in 1988. Up to then, conservative and open surgical measures had been the standard procedures. The study covers 12 medical centres in the north, northeast, south and central parts of the country between 1988 and 1997. Approximately 40 ESWL machines have been in use. ESWL was used in 66.1 per cent and 20.8 per cent of patients with renal and ureteric calculi respectively. Only 1.1 per cent of the patients had PCNL. URS was used in 20.8 per cent of patients with ureteric calculi. Open operations were required in 32.6 per cent and 53.6 per cent of patients with renal and ureteric calculi respectively. Nephrectomy was required in 4.8 per cent--16.0 per cent of patients with renal calculi. Certain considerations have been put forward to appraise the situation concerning urinary stone therapy in Thailand.

The urological complications of renal transplantation: an 11-year-experience at Ramathibodi Hospital.

From February 1986 to December 1996, renal transplantation was performed on 344 patients at Ramathibodi Hospital. The urological complications were retrospectively analyzed in 335 patients (338 renal transplants), 9 patients were lost to follow-up. There were 227 males and 108 females with age ranging from 15 to 62 years (mean age 40.28 years). There were 207 cadaveric and 131 living-related graft donors. The ureteroneocystostomy was performed either by modified Politano-Leadbetter (93 cases) or extravesical technique (245 cases). There were 23 cases of urological complications: ureterovesical anastomotic leakage 6, ureteric obstruction 6, vesicoureteric reflux 4, significant bleeding from ureterovesical anastomosis 3, renal infarction with fistulas 2, hydronephrosis due to blood clot retention and swelling of the anastomosis, requiring temporary double J stenting 2. The analysis was done by dividing the patients into 3 groups, the first and second groups consisted of 100 cases each and the third group consisted of 138 cases. The urological complications in the groups were 10 per cent, 9 per cent and 2.89 per cent respectively. There was a statistically significant difference between the first two groups combined and the third group in terms of complications (p < 0.025). The urological complications of living-related cases were 9 (6.87%), and of cadaveric cases were 14 (6.76%). There was no significant difference of the complications between living-related and cadaveric transplants (p < 0.05). The comparative results of the ureteric complications of the extravesical technique were significantly less than the modified Politano-Leadbetter technique (4.49% vs 10.75%), (p < 0.05). In conclusion, the extravesical technique of ureterovesical anastomosis was superior than the modified Leadbetter-Politano technique in terms of post-operative ureteral complications.

The organization of Kidney Transplantation Services at Ramathibodi Hospital: fourteen years experience on waiting list, kidney donors and kidney transplantation.

The Kidney Transplantation Program at Ramathibodi Hospital was established in 1985. By the end of 1998, there were 1,614 patients on the cumulative waiting list. The first kidney transplantation (KT) was started in 1986 by using kidney from living-related donor (LD) while cadaveric KT (CD-KT) was started in 1987. A total of 528 KT were done, 278 cases (52.7%) were CD-KT and 250 cases (47.3%) were LD-KT. Six patients had two kidney transplants. 278 kidneys were donated from 189 cadaveric donors. Fifty cadaveric donors (26.4%) were from Ramathibodi Hospital while the rest were from other hospitals and the Organ Donation Center, Thai Red Cross Society. For LD, 233 out of 250 (93.2%) were from living-related, more than 50 per cent of these donors were from siblings. 17 spousal donors have been accepted for KT at Ramathibodi Hospital since 1997. Concerning the recipient pools, 522 patients (32.3%) were transplanted, 123 patients (7.6%) died without KT, 111 patients (6.9%) underwent KT at other hospitals, and 78 patients (4.8%) changed to waiting lists at other hospitals. The rest were lost to follow-up. At present, only 265 patients are still actively waiting (send serum every month). The number of KT and living donors has gradually increased, whereas, the number of cadaveric donors has decreased. However, cooperation with the "Organ Donation Center" has improved the number of cadaveric donation in the last two years. Sufficient organ donations and an active working team will provide a good kidney transplant service for the patients.

Irrigation of the distal vas deferens during vasectomy: does it accelerate the post-vasectomy sperm-free rate?

A prospective, non-randomized, partially blinded, controlled trial was conducted to evaluate the efficacy of irrigation with normal saline solution (NSS) during no-scalpel vasectomy (NSV) compared with NSV alone in 62 men. In the NSS irrigation group, an Angiocath 24-gauge needle was inserted into the distal vas lumen, and 20 mL NSS solution was used to irrigate the vas manually on both sides. Post-operative follow-up included urine samples collected immediately and semen samples for sperm count at 2, 6 and 12 weeks post-vasectomy. The difference in the number of spermatozoa appearing in the post-vasectomy urine samples and the mean urine sperm count in both groups were significantly different ( p < 0.0001 and p < 0.01, respectively). The numbers of post-operative ejaculations, the mean sperm concentration, and the number of patients who achieved sterility (defined as no motile spermatozoa in the ejaculate) in both groups at 2, 6 and 12 weeks were similar ( p > 0.05). It is concluded that although irrigation of the distal vas with NSS was successful in removing a large number of spermatozoa from the tract, this procedure did not significantly accelerate the rate of achieving absence of motile spermatozoa in the ejaculate.

Evaluation of cadaveric pericardium in the rat for the surgical treatment of Peyronie's disease.

OBJECTIVES: To evaluate the intermediate-term efficacy of cadaveric pericardium (Tutoplast) as a grafting material in the surgical correction of Peyronie's disease using a rat model. Peyronie's disease is a connective tissue disorder of the tunica albuginea. When less invasive modalities fail to correct the penile deformity, surgical excision of the plaque and coverage with various grafting materials has been advocated. MFETHODS:Twenty male Sprague-Dawley rats (300 to 325 g) constituted the study population. The animals were divided into two groups: group 1, control rats (n = 10) and group 2, rats that underwent wedge excision of the tunica albuginea and replacement with cadaveric pericardial grafts (n = 10). All rats underwent electrical stimulation of the cavernosal nerve to assess erectile function after 4 months. Tissues obtained after death were stained with trichrome and Verhoff's van Giesen for collagen and elastic fibers. RESULTS: Erectile function as studied by cavernosal nerve stimulation was not significantly different in either group (P >0.05), and histologic studies of penile cross sections of the pericardial graft group revealed a mild to moderate degree of fibrosis surrounding the patch at 4 months. CONCLUSIONS: We found that pericardial cadaveric grafts in a rat model are a suitable tunica albuginea substitute. They allow for penile expansion after cavernosal nerve stimulation and are strong enough to withstand normal intracorporeal pressures. Our early experimental data in the rat support the use of pericardial cadaveric material for coverage of excised Peyronie's plaques. However, long-term follow-up in humans is mandatory.

Comparison of cadaveric pericardial, dermal, vein, and synthetic grafts for tunica albuginea substitution using a rat model.

OBJECTIVE: To evaluate in an animal model the intermediate and long-term efficacy of cadaveric pericardium, dermis, vein and Gore-Tex per thousand as grafting materials for tunica albuginea substitution after plaque excision for Peyronie's disease. MATERIALS AND METHODS: The study comprised 100 male Sprague-Dawley rats (300-325 g) divided into five equal groups: group 1, sham-operated controls; and groups 2-5 which underwent wedge excision of the tunica albuginea and replacement with either cadaveric pericardium, dermis, vein or Gore-Tex grafts. Ten rats in each group had the cavernosal nerve stimulated electrically to assess erectile function at 4 months, and the remaining 10 rats at 6 months. After death the sampled tissues were fixed in 10% formalin, paraffin-embedded, and stained with Masson's trichrome and Verhoff's van Giesen for collagen and elastic fibres. RESULTS: Erectile function, assessed by cavernosal nerve stimulation, did not differ significantly in any of the groups (P > 0.05). The histological assessment of penile cross-sections showed minimal fibrosis surrounding the patch in the dermal and vein grafts, and moderate to severe fibrosis in the Gore-Tex graft at 4 and 6 months. In the pericardial graft there was a moderate degree of fibrosis at 4 months with only minimal fibrosis at 6 months. CONCLUSIONS: These results show that cadaveric pericardium allows complete penile expansion and is strong enough to withstand normal intracorporal pressures. There was minimal fibrosis in the pericardial, dermal and vein grafts, and moderate fibrosis in the Gore-Tex graft at 6 months. The pericardial graft is a satisfactory grafting material when used for tunica albuginea substitution, including the surgical management of Peyronie's disease.

Localization of peripheral dopamine D1 and D2 receptors in rat corpus cavernosum.

OBJECTIVE: To detect and locate anatomically peripheral dopamine D1 and D2 receptors in rat cavernosa, as dopamine is important in sexual drive and penile erection through receptors located in the central nervous system. MATERIALS AND METHODS: Corpora cavernosa were obtained from Sprague-Dawley rats; total RNA and membrane proteins were extracted and cryostat sections prepared. The rat brain hypothalamus was used as a control for dopamine D1 and D2 receptors. The presence and expression of peripheral dopamine D1 and D2 receptor mRNAs in rat corpus cavernosa was assessed using reverse transcription and polymerase chain reaction (RT-PCR), and Northern blot hybridization using (32)P-UTP-labelled RNA probes. Concurrently, corresponding proteins from D1 and D2 receptors were assayed and detected by a Western blotting technique. The anatomical location of dopamine D1 and D2 receptor mRNAs in rat penile tissues was identified by in situ hybridization using (35)S-UTP-labelled RNA probes in cryostat sections. Immunohistochemical staining was used to locate peripheral dopamine D1 and D2 receptor proteins in rat corpora cavernosa. RESULTS: Dopamine D1 and D2 receptor gene expression was detected in rat corpora cavernosa. In situ hybridization signals for dopamine D1 and D2 receptor mRNAs were localized to corpus cavernosal tissues and dorsal vessels in the rat penis. Western blot analyses showed peripheral dopamine D1 and D2 receptor proteins in rat corpora cavernosa. Immunohistochemically, peripheral dopamine D1 and D2 receptor proteins were detected in dorsal nerves, dorsal vessels and corpus cavernosal smooth muscle of the rat penile tissues. CONCLUSIONS: Peripheral dopamine D1 and D2 receptors are present in the corpora cavernosa of rats. The functional significance of these receptors and signal transduction pathways in modulating the vascular tone of the penis warrants further investigation.