Electrophilic aromatic substitutions of silylated furans and thiophenes with retention of the organosilyl group.

The influence of trialkylsilyl groups on the nucleophilic reactivities of furans and thiophenes is determined by kinetic experiments.

Nocturnal penile tumescence activity unchanged after long-term intracavernous injection therapy.

PURPOSE: Anecdotal evidence suggests that some men have restored erectile function after long-term intracavernous injection therapy for erectile dysfunction. We objectively assessed this phenomenon using nocturnal penile tumescence testing. MATERIALS AND METHODS: In our retrospective study 19 men with a mean age of 53.5 years who had organic erectile dysfunction underwent nocturnal penile tumescence testing before and after prostaglandin E1 based intracavernous injection at least 6 months in duration. The nocturnal penile tumescence parameters measured included the number of erectile episodes, base and tip tumescence, and percent of time with rigidity greater than 70% at the penile base and tip. A 5-item questionnaire was given to all patients after the intracavernous injection period to assess subjective changes in erectile quality. RESULTS: Mean time on intracavernous injection was 2.42 years and mean injection frequency was 3.74 times monthly. Prostaglandin E1 only, and combined prostaglandin E1, phentolamine and papaverine were used in 7 and 9 cases, respectively. Nine patients believed that unaided erection improved after intracavernous injection and 6 achieved intercourse without injection who were unable to do so before injection. No statistically significant changes were noted in any of the 5 objectively measured nocturnal penile tumescence parameters. CONCLUSIONS: Long-term prostaglandin E1 based intracavernous injection may provide subjective improvement in erectile function in some men. However, as measured by nocturnal penile tumescence testing, no objective improvement in spontaneous erectile function occurs.

Cocaine associated priapism.

PURPOSE: Cocaine abuse is an ongoing epidemic in the United States. Priapism associated with cocaine use has been reported only twice in the urological literature. To our knowledge we report the first series of priapism associated with cocaine use and the first case associated with the use of this drug in its solid form, known as crack. MATERIALS AND METHODS: We retrospectively reviewed the presentation of 3 patients to our emergency department within the last year. Each patient presented with priapism and no identifiable predisposition other than the use of cocaine within 24 hours, as evident on positive urine toxicology. RESULTS: Each patient delayed seeking treatment, which added to the complexity of therapy. Intracavernosal aspiration and irrigations failed in all 3 cases. Cavernous spongiosal shunting failed in the first 2 cases. Cases 2 and 3 were complicated by the high flow variant of priapism. Case 1 ultimately required partial penectomy for infected, gangrenous, distal penile tissue. CONCLUSIONS: It appears that cocaine can be a cause of refractory priapism and treatment can be challenging. We suggest that urine toxicology screening be considered in such cases. The identification of underlying cocaine abuse is important in preventing priapism recurrence in these patients.

Loss of TGFbeta, Apoptosis, and Bcl-2 in Erectile Dysfunction and Upregulation of p53 and HIF-1alpha in Diabetes-Associated Erectile Dysfunction.

Vasculogenic erectile dysfunction (ED) is associated with collagen replacement of the cavernosal smooth muscle, mediated by an increase in transforming growth factor (TGF)-production secondary to hypoxemia. We tested the hypothesis that human ED is the result of an increase in apoptosis of the cavernosal smooth muscle cells with replacement by collagen, mediated by the TGFbeta upregulation. We also examined the tissue for proteins associated with apoptosis. Human cavernosal tissue was procured from impotent men at the time of prosthesis insertion. Normal corpous cavernosum served as a control. The TUNEL assay was used to assess apoptosis. Immunohistochemistry staining was used to detect TGFbeta and Bcl-2 expression, while Western blot analysis was used to detect expression of Bcl-2, p53, and hypoxia-inducible factor (HIF)-1a. Immunohistochemistry showed downregulation of TGFbeta protein expression in the corpus cavernosum of men with ED. Apoptotic nuclei were noted in cavernosal smooth muscle from a potent man but were not found in cavernosal tissue from men with ED. To gain insight into the possible mechanism of apoptosis in men with ED, the proto-oncogene Bcl-2, a potential inhibitor of apoptosis, was examined. Both immunohistochemistry and Western analysis revealed the presence of Bcl-2 in the cavernosal nerve of a potent man but its absence in cavernosal tissue from men with ED. Thus, loss of Bcl-2 expression correlated with the loss of apoptosis. In contrast, Western blotting demonstrated upregulation of p53 and HIF-1a expression in the cavernosal tissues from the men with ED and diabetes. Male ED follows an active process characterized by a loss of TGFb expression, apoptosis, and Bcl-2 expression. However, there is upregulation of p53 and HIF-1a in men with diabetes. These data support the possibility of hypoxia-mediated ED in diabetes via upregulation of p53 and HIF-1a but does not substantiate a role for TGFbeta in ED.

Current indications for open stone surgery in the treatment of renal and ureteral calculi.

PURPOSE: The development and advances in extracorporeal shock wave lithotripsy and endourological procedures have greatly diminished the need for open surgery in the treatment of renal and ureteral stones. We reviewed our experience with open stone surgery to determine the current indications and efficacy of this treatment modality. MATERIALS AND METHODS: Hospital and office charts, operative notes and records, and pertinent radiographic studies of all patients undergoing open stone surgery from January 1991 through December 1995 at 3 university affiliated hospitals were reviewed. Patient characteristics, stone burden, indications, surgical factors and outcomes were reviewed for each patient. RESULTS: Of 780 procedures performed for stone removal, 42 were open surgical procedures (5.4%) including pyelolithotomy in 15 (extended pyelolithotomy or pyelonephrolithotomy in 7), anatrophic nephrolithotomy in 14, ureterolithotomy in 7 and radial nephrolithotomy in 6. There were 24 men and 18 women ranging in age from 1 to 90 years (mean age 51.5). The most common indications for open surgery were complex stone burden (55%); failure of extracorporeal shock wave lithotripsy or endourological treatment (29%); anatomic abnormalities such as ureteropelvic junction obstruction, infundibular stenosis and/or renal caliceal diverticulum (24%); morbid obesity (10%) and co-morbid medical disease (7%). Mean estimated blood loss was 428 cc. Average hospital stay was 6.4 days. The stone-free rate after surgery was 93%. Five patients had minor postoperative complications that resolved with appropriate therapy. CONCLUSIONS: While most patients with renal and ureteral stones can be treated with less invasive techniques, open stone surgery continues to represent a reasonable alternative for a small segment of the urinary stone population.

Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase.

OBJECTIVES: To evaluate whether alterations in nitric oxide (NO) synthesis or activity contribute to age-related erectile dysfunction and to elucidate the mechanisms causing these alterations using the rabbit as our model of aging. METHODS: We compared the ability of the rabbit cavernosal smooth muscle to relax in the organ bath in response to acetylcholine (Ach, endothelium-dependent vasodilator), sodium nitroprusside (SNP, an NO donor), and A23187 (a calcium ionophore) in young (6 month old) and aged (2.5 to 3.5 year old) rabbits. In addition, the immunohistochemical expression of endothelial nitric oxide synthase (eNOS) in both young and aged rabbit cavernosal tissue was examined. Endothelial integrity was examined immunohistochemically with JC70. RESULTS: Ach-mediated relaxation of penile corporal tissue was significantly attenuated from a maximum of 68.39 +/- 6.27 (0.1 mM Ach, n = 4) in young rabbits to 39.02 +/- 4.88 (0.1 mM Ach, n = 6) in aged rabbits (P < 0.04). No statistically significant difference (P > 0.05) was noted between cavernosal relaxation to sodium nitroprusside between young rabbits (97.8%, 0.1 mM SNP, n = 5) and aged rabbits (76.1%, 0.1 mM SNP, n = 5). This suggested that the defect in the Ach-NO pathway was at the level of NO synthesis, not activity. Immunohistochemical staining for eNOS demonstrated upregulation in both the vascular endothelium and corporal smooth muscle of aged rabbit tissue compared with young rabbit cavernosal tissue (n = 5). Anatomic endothelial integrity was demonstrated in the young and aged rabbits by the presence of JC70. This suggested that the defect in the Ach-NO synthetic pathway was not at the level of eNOS and was not due to anatomic endothelial cell disruption. Finally, Ach-mediated cavernosal smooth muscle relaxation in the young rabbit was not significantly augmented (P > 0.05) in the presence of the calcium ionophore A23187 (10 microM). A23187, however, significantly augmented (P < 0.04) Ach-mediated relaxation in the aged rabbit from a maximum of 33.93 +/- 6.58 to 41.55 +/- 6.58 (10 microM Ach, n = 5). This suggested that a potential defect in the Ach-NO synthetic pathway was at the level of intracellular calcium flux and possibly at the level of the calcium-eNOS interaction. CONCLUSIONS: Endothelium-dependent relaxation is attenuated in the aging rabbit; eNOS is upregulated in the aging rabbit; and no difference is noted in response to direct NO donation between the young and aged rabbit. The endothelium is anatomically intact in both the young and aging rabbit. The calcium ionophore A23187 augmented the attenuated vasorelaxation in the aging rabbit cavernosum (although not to the levels seen in the young rabbit cavernosum) and had no effect on the young rabbit cavernosum. These data suggest that erectile dysfunction in the aging rabbit cavernosum appears to be related to endothelial dysfunction and is characterized by eNOS upregulation and aberrant intracellular calcium fluxes.

Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS.

OBJECTIVES: We hypothesized that advanced glycation end product (AGE) formation contributes to erectile dysfunction (ED) by quenching nitric oxide. Our first goal was to identify the specific AGE pentosidine in the diabetic human penis. Because AGE-mediated effects may involve inducible nitric oxide synthase (iNOS), we performed immunohistochemical and Western blot analysis of diabetic and nondiabetic human penile tissue for iNOS. Finally, because AGEs may act intracellularly to affect proteins, we set out to identify endothelial NOS (eNOS) in the human penis as an initial step in examining a possible intracellular interaction between eNOS and AGEs. METHODS: We performed high-performance liquid chromatographic analysis of diabetic human penile corpus cavernosum and serum for pentosidine and performed immunohistochemical, electron microscopic (EM), and Western blot analysis of the diabetic and nondiabetic penile corpus cavernosum and tunica for pyrraline, iNOS, and eNOS (and neural NOS [nNOS] for comparative purposes) via standard methods. RESULTS: We found a significant elevation of pentosidine in the penile tissue but not the serum of diabetic patients (average age 55.6 +/- 2.3 years) compared with that of nondiabetic patients (average age 61.8 +/- 3.6 years). Pentosidine was 117.06 +/- 9.19 pmol/mg collagen in the diabetic tunica versus 77.58 +/- 5.5 pmol/mg collagen in the nondiabetic tunica (P < 0.01) and 74.58 +/- 8.49 pmol/mg collagen in the diabetic corpus cavernosum versus 46.59 +/- 2.53 pmol/mg collagen in the nondiabetic corpus cavernosum (P < 0.01), suggesting a tissue-specific effect of the AGEs. We localized the site of deposition of the specific AGE pyrraline to the human penile tunica and the penile corpus cavernosum collagen. Immunohistochemical and EM analysis localized eNOS and iNOS to the cavernosal endothelium and smooth muscle. Western blot analysis in 6 patients revealed the following: iNOS, but no eNOS, in penile tissue from 1 insulin-dependent diabetic man; eNOS only in 1 man after radical prostatectomy; both eNOS and iNOS in 2 men with Peyronie's disease, as well as in 2 other men with impotence and hypertension. Finally, the specific iNOS inhibitor PNU-19451A significantly augmented relaxation of precontracted human cavernosal tissue, from 64.7% +/- 5.58 to 80.03% +/- 4.55 at 10 microM acetylcholine and 65.06% +/- 2.84 to 86.16% +/- 3.96 at 0.1 mM acetylcholine (n = 4, P < 0.002 and P < 0.02, respectively). CONCLUSIONS: AGEs are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum. We identified eNOS and iNOS in the human penile cavernosal smooth muscle and endothelium. The augmentation of cavernosal relaxation with a specific iNOS inhibitor, combined with the identification of iNOS protein, but not eNOS, in a patient with severe diabetes and ED, allows for speculation of a pathophysiologic mechanism for AGE-mediated ED via upregulation of iNOS and downregulation of eNOS. These data provide further insight into the mechanisms of advanced glycation end product-mediated ED and provide a foundation for further study.

Posterior urethral disruption associated with pelvic fracture: the place for delayed repair.

Posterior urethral injuries are most commonly associated with pelvic fractures. Retrograde urethrogram is the study of choice for evaluation of urethral injuries. Controversy exists between advocates of various methods of initial management. Simple suprapubic cystostomy placement with delayed urethral reconstruction is best reserved for patients with life-threatening, extensive injuries or for surgeons with limited experience in the management of this injury.

Age-related increase in an advanced glycation end product in penile tissue.

Nonenzymatic glycosylation (glycation) of proteins, often referred to as the Maillard reaction, has been proposed to play a role in age and diabetes-related processes by forming protein and DNA adducts and cross-links. These cross-links may contribute to erectile dysfunction by scavenging nitric oxide, which is needed for erection. As the basis for a possible role of the advanced Maillard reaction in age-related erectile dysfunction, we investigated the presence of the specific advanced glycation endproduct (AGE) pentosidine in penile corpus cavernosum tissue and penile tunica albuginea tissue as a function of age. A total of 23 penile tissue specimens were obtained at autopsy, from which 19 samples of tunica albuginea and 21 samples of corpus cavernosum were derived. In addition, 13 penile corporal and tunical specimens were procured at the time of insertion of a penile prosthesis, from which 12 tunica albugineal specimens and 10 samples of corpus cavernosum were derived. Collagen was extracted with acetic acid and pepsin digestion, and the final insoluble collagen product was acid-hydrolyzed with 6 N HCL for 24 h at 110 degrees C. Pentosidine was quantified by high-performance liquid chromatography using a reverse-phase column. The level of pentosidine (expressed in picomoles per milligram of insoluble collagen) was found to increase with age in cadaver as well as living penile corporal and tunical albugineal tissues. Best-fit analysis revealed an exponential increase in both types of cadaver penile tissue, with regression equations of y = 15.29 x 10(9.9e-3x), R2 = 0.79, being obtained in the tunica and y = 13.2 x 10(7.63e-3x), R2 = 0.56, in the corpora. These correspond to 6- and 4-fold increases in pentosidine levels from puberty to the age of 100 years (P < 0.05), respectively. Mean pentosidine levels were higher in the tunica than in the corpora. Comparison of pentosidine levels in the tunica versus the corpora revealed a weakly linear correlation (y = 24.88 + 1.08x, R2 = 0.32). Levels in the tunical and corporal specimens from the living human specimens fell with the predicted confidence intervals of the cadaveric tissue. Tunical specimens from patients who underwent repair or revision of a previously inserted penile prosthesis had very low levels of pentosidine. The exponential age-related increase in pentosidine observed in both types of penile tissue suggests an impairment of collagen turnover, which could be related to the advanced glycation reaction in aging. It is not known whether pentosidine itself is directly associated with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification. Formation of advanced Maillard reaction products, which is greatly accelerated in aging, diabetes, and uremia, could contribute to erectile dysfunction in these syndromes.

Malignant mesenchymoma of the prostate: immunohistochemical and ultrastructural observations.

A case of malignant mesenchymoma of the prostate is reported. Immunohistochemical and ultrastructural examination revealed malignant chondro-osteoblastic and rhabdomyoblastic features. A separate incidental prostatic adenocarcinoma was also seen. These lesions should be differentiated from carcinosarcoma in which adenocarcinoma is intermingled with malignant mesenchymal components.

Renal oncocytoma arising from a renal cyst: a case report and review of the literature.

Renal oncocytoma accounts for approximately 3 to 4% of all solid renocortical tumors. An unusual case of renal oncocytoma arising from the wall of a simple renal cyst is reported and the literature is reviewed.

Giant multilocular prostatic cystadenoma: a rare clinical entity and review of the literature.

Giant multilocular prostatic cystadenoma is a pathologically benign entity. To our knowledge only 3 cases have been reported in the literature, of which 2 were treated by means of pelvic exenteration. These lesions can occur in men of various ages, arise from the prostate and grow to massive proportions. Histologically the tumor is comprised of benign cysts lined with cuboidal and columnar epithelium. The lesions do not invade contiguous structures but they can be adherent to viscera in their proximity. Giant multilocular prostatic cystadenoma as demonstrated by our case is a benign entity that can be definitively treated by carefully planned complete surgical excision.

Urologic complications of spinal cord injury.

Spinal cord injuries in the past were associated with a very high mortality, predominantly from urologic complications and sepsis. Improvements in the urologic and medical management of these patients have significantly decreased the morbidity and mortality. Many complications may still develop during the urologic management, however. Periodic follow-up is thus essential to recognize and treat urologic complications in order to preserve renal function.

Spinal cord compression secondary to prostate carcinoma: treatment and prognosis.

Of 35 patients with prostate carcinoma and suspected spinal cord compression 26 (74%) had myelograms and/or magnetic resonance imaging studies demonstrating epidural spinal cord compression. In 5 of 26 patients (19%) spinal cord compression was the first indication of prostate cancer. All patients were initially treated with radiation, steroids and androgen deprivation therapy. Three patients underwent laminectomy. Of 12 patients (100%) ambulatory at presentation 12 remained ambulatory. Of 12 patients (83%) who were paraparetic at presentation 10 were ambulatory after treatment. However, 2 of these patients subsequently had recurrent compression and became paraplegic. Overall, 7 of 26 patients (27%) had recurrent compression. Of 5 patients who either presented with paraplegia or in whom paraplegia developed secondary to recurrent spinal cord compression 4 remained paraplegic despite treatment. The average survival of these 5 patients after treatment was 3.9 months versus 18 months for the group as a whole. In ambulatory or paraparetic patients radiation, androgen deprivation therapy and steroids are effective palliative therapy. However, patients who present with paraplegia or in whom paraplegia developed secondary to recurrent compression are often not palliated by this combination therapy. Prophylactic radiation of vertebral metastases discovered concurrently with compressive metastases may be valuable in preventing paraplegia.

Diagnosis and management of vesicoenteric fistulas.

Vesicoenteric fistulas represent challenging clinical problems and may be characterized by difficulty in diagnosis as well as controversy in management. We present our experience with 56 patients with vesicoenteric fistulas. The results of our series were compared with a report of 1,100 in the literature during the past 20 years. Fecaluria (48 per cent), abdominal pain (43 per cent) and pneumaturia (41 per cent) were the most common presenting symptoms among the patients we studied. Fistulas were most frequently attributable to diverticulitis (52 per cent), Crohn's disease (18 per cent), carcinoma of the colon (11 per cent) or other pelvic malignant conditions (9 per cent). The most accurate diagnostic modalities in our series were cystoscopy (88 per cent), cystography (56 per cent) and barium enema (32 per cent). The combined findings of these studies led to the diagnosis of a fistula in all patients. Intravenous urography, intestinal endoscopy and computed tomography were less useful, providing a diagnosis in only 5, 6 and 11 per cent, respectively. Surgical treatment was single staged in 57 per cent and multistaged in 35 per cent, while 8 per cent of the patients underwent intestinal diversion only. Comparison of the single versus multistaged approaches revealed that the total complication rate, frequency of additional procedures, rate of infectious complications and length of hospitalization were no higher for the single stage group. Based on these findings, we advocate single stage repair, except in those patients who have unusual complications.

Ureteral injuries complicating vascular surgery: is repair indicated?

We have managed 8 patients who sustained an iatrogenic ureteral injury during either placement or revision of a vascular graft. Primary repair was performed in all 5 patients diagnosed at injury. Persistent extravasation necessitating nephrectomy occurred in 2 of these patients. The diagnosis was delayed in 3 patients. Two patients underwent successful ureteral reconstruction and 1 required nephrectomy. Graft complications did not occur. Ureteral repair is recommended as the preferred method to manage ureteral injuries associated with vascular reconstruction.

Infected urachal cysts: a review of 10 cases.

Disorders of urachal remnants are uncommon. While a urachal cyst usually is asymptomatic, infection may mimic a variety of acute intra-abdominal or pelvic processes. We describe 10 patients in 2 distinct age groups (the young child and the young adult) with an infected urachal cyst. The presenting symptoms and signs in most patients included dysuria, severe lower abdominal pain and fever. In 7 patients the correct preoperative diagnosis was made. Diagnoses at referral included Crohn's disease, bladder carcinoma and pelvic inflammatory disease. A single procedure was performed in 7 cases and a staged technique was used in 3. The differential diagnosis of acute abdominal and pelvic pain or a midline lower abdominal mass in the pediatric or young adult age group should include infection of a urachal remnant.

Renal cell carcinoma presenting with gross hematuria from a solitary bladder metastasis.

Renal cell carcinoma commonly presents with gross hematuria. We report the first case in which the diagnosis of renal cell carcinoma was made following biopsy of an actively bleeding solitary bladder metastasis of a clear cell carcinoma of the kidney. The possible routes of metastasis of this uncommon lesion are discussed and a review of the literature is presented.