[TREATMENT OUTCOMES OF BLADDER NECK CONTRACTURE AFTER TRANSURETHRAL PROSTATE SURGERY].

(Introduction) A known complication of the surgical treatment of benign prostatic hyperplasia (BPH) is bladder neck contracture (BNC). BNC is often treated using transurethral incision of the bladder neck (TUI-BN); however, there are few reports on the outcomes of TUI-BN. Therefore, we examined the outcomes of patients who underwent TUI-BN after transurethral prostate surgery. (Material and methods) We retrospectively examined 25 patients who underwent TUI-BN between February 2015 and January 2021 for the following: (1) patients' characteristics; (2) the time from transurethral prostate surgery to TUI-BN; (3) the trigger of BNC diagnosis; (4) surgical procedure of BNC repair/perioperative course; (5) micturition function immediately after TUI-BN; and (6) Postoperative outcomes. (Results) The median age of the patients was 77 years, and the surgical procedures for BPH were transurethral resection of the prostate (TURP) in four cases, transurethral resection in saline plasma vaporization of the prostate (TURisP) in nine cases, and transurethral enucleation with bipolar (TUEB) in 12 cases. The median time to onset of BNC symptoms was 364 days, and 18 patients (72%) were diagnosed within 2 years. The trigger of BNC diagnosis was urinary symptoms in 21 cases, of which 16 patients had exacerbation of urination. The median duration of the surgical procedure of BNC repair was 14 min, and the incisions most frequently used (in 44% of cases) were at the 4 o'clock and 8 o'clock positions. Transient stress urinary incontinence was observed as a complication in three cases. In the 4 o'clock and 8 o'clock incisions, the maximum urine flow rate improved significantly (11.1 mL/s perioperatively vs. 20.9 mL/s postoperatively; P=0.004). These symptoms improved in 16 of the 21 symptomatic cases, and the maximum urine flow rate improved significantly (P< 0.01). The median observation period after surgery was 170 days; eight postoperative patients were lost to follow up. There were two cases of recurrence. (Conclusions) BNC is likely to develop within 2 years after transurethral prostate surgery. In this study, the success rate of the initial TUI-BN was 92%, as reoperation was required in two cases; however, the overall prognosis was good.

[OUTCOMES OF CHRONIC UNILATERAL HEMATURIA TREATED USING DIGITAL FLEXIBLE URETEROSCOPE].

(Objectives) We examined the treatment outcomes in cases of chronic unilateral hematuria treated using flexible ureteroscope for observation and hemostasis. (Methods) The study included 14 patients (7 men and 7 women) with a median age of 56.5 years who underwent ureteroscopy using a digital flexible ureteroscope for chronic unilateral hematuria between March 2014 and August 2019. All the patients presented with macroscopic hematuria as a clinical symptom, but in one patient, the hematuria was accompanied by anemia and required a blood transfusion. In addition, bleeding occurred on the left side in 8 patients and on the right side in 3 patients; however, for the remaining 3 patients, the affected side could not be identified. Fourteen patients were examined on the basis of the ureteroscopic findings, number of bleeding sites, hemostatic intervention, treatment effect, and presence or absence of recurrences. (Results) The ureteroscopic findings showed a hemangioma in 7 patients and minute venous rupture in 3, but the remaining 4 patients showed no clear findings. The site of the findings was in the superior calyces in 8 cases, middle calyces in 4 cases, inferior calyces in 4 cases, and renal pelvic wall in 1 case. In addition, the findings were located at multiple sites in 6 cases, including all renal calyces in 2 cases. Ten patients with findings underwent hemostatic interventions (electrocoagulation and laser treatment). The median postoperative follow-up period was 32.4 months (range, 6.4-65.4 months). In all the cases, the hematuria disappeared after treatment. One of the 2 patients with findings in all renal calyces showed recurrence of macroscopic hematuria at 1 year and 6 months, which disappeared after conservative treatment. (Conclusions) In this study, observation using digital flexible ureteroscope was useful in the treatment of chronic unilateral hematuria, and the hemostatic interventions performed on the bleeding sites in the renal pelvis were effective.

[Case of brain infarction during cisplatin-based combined chemotherapy with bleomycin, etoposide and cisplatin for testicular cancer].

A 31-year-oldman presented with a 6-month history of right testicular enlargement. The patient underwent a right inguinal orchiectomy. Histopathological examination showed nonseminomatous germ cell tumor (choriocarcinoma>seminoma) which was confined to the tunica albuginea. The postoperative serum level of alpha-fetoprotein (AFP) and lactate dehydrogenase were normal. Serum level of human chorionic gonadotrophin(HCG), however, was 23,000 mIU/ml (normal, < 0.7 mIU/ml). A thoracic computed tomography (CT) at that time showed bilateral and multiple metastases to the lungs but the abdominal CT was normal. After the surgery, the patient was treated with conventional doses of cisplatin, etoposide, and bleomycin. On day 11 of the second chemotherapy course, the patient developed confusion and right sided weakness. Brain magnetic resonance imaging (MRI) showed an ischemic lesion in the left middle cerebral artery area. An echocardiogram showed normal left ventricular function and no valvular vegetations. Finally, the patient completed one additional course of chemotherapy with considerable measures to prevent side effects. A thoracic CT at the end of the third cycle showed no evidence of tumor. At 3 months followup after chemotherapy, he suffered from partial paralysis of right-sided upper and lower limbs but due to intensive rehabilitation he overcame the paralysis and is able to walk by himself. There was no evidence of tumor recurrence.

The long-term voiding function and sexual function after pelvic nerve-sparing radical surgery for rectal cancer.

BACKGROUND: The aim of the present study is to symptomatically analyze the extent to which pelvic nerve-sparing radical surgery for rectal cancer impacts on long-term voiding and male sexual function. METHODS: A self-administered questionnaire was mailed to 68 patients who underwent pelvic nerve-sparing radical surgery for invasive rectal cancer with 52 responses (28 men and 24 women; 27 complete and 25 incomplete preservation; response rate 76.5%). Each patient was asked to record if there had been any changes in lower urinary tract symptoms after surgery. Sexual function was also investigated in men. RESULTS: Of the 52 patients, 48 (92%) maintained voluntary voiding without catheterization in the long term. Clean intermittent self-catheterization was performed in only four patients with incomplete preservation because of persistent voiding dysfunction. Subjectively, approximately 60% of the patients remained unchanged in lower urinary tract symptoms after surgery. The satisfaction rate regarding the current voiding status was significantly higher in women than in men (83% versus 61%, P = 0.0294), but was not significantly different between those with complete (76%) and incomplete preservation (64%). Despite the acceptable urinary status, 88% of men had some deterioration in the erectile function, regardless of the types of surgical procedures. Overall, 64% of men were unsatisfied with the current sexual function. CONCLUSIONS: Pelvic nerve-sparing radical surgery for rectal cancer preserved the long-term voiding function in the majority of patients. In completely preserved patients and in women, symptomatic outcomes were more satisfactory. Postoperative erectile dysfunction was found to be a serious problem, even in complete nerve-sparing procedure.

The estimated prevalence of hypospadias in Hokkaido, Japan.

BACKGROUND: Hypospadias is one of the most common congenital anomalies in the world. Recently, increases in the prevalence of hypospadias have been reported in various countries including Japan. In this study, we examined whether the prevalence of hypospadias in Hokkaido, Japan, increased or not, using standardized diagnostic criteria. We also investigated the degree of its severity. METHODS: We calculated prevalence of hypospadias using hospital records of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by dividing the number of patients obtained from hospital records by the number of births. RESULTS: The average prevalence of hypospadias in Hokkaido was 3.9 per 10,000 births, and did not significantly change (p=0.7). The average proportions of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively. The decrease in the proportion of the proximal type was statistically significant (p=0.05) for the entire time period, whereas the proportion of the distal type did not have a significant upward trend for the observed 13 years (p=0.1). CONCLUSION: No significant changes in the prevalence of hypospadias existed in Hokkaido.

Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer.

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer. METHODS: Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph node-positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node-positive disease was conducted to evaluate disease-free survival and overall survival rates. RESULTS: In this series, the median follow-up period was 39 months (range, 4-163) after surgery. Disease-free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease-free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node-positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease-free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376). CONCLUSION: These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node-positive disease.

Medical management of recurrent aggressive angiomyxoma with gonadotropin-releasing hormone agonist.

Patients with aggressive angiomyxoma may experience local recurrences. We report a case of recurrent aggressive angiomyxoma medically treated successfully with a gonadotropin-releasing hormone agonist. A 34-year-old woman with a huge perineal tumor underwent an extensive resection of the abdominoperineal tumor combined with total pelvic exenteration. Histology showed aggressive angiomyxoma and the tumor cells were immunoreactive for estrogen and progesterone receptors. Although the patient had experienced no local recurrence for 12 months under adjuvant therapy with a gonadotropin-releasing hormone agonist, a recurrence occurred 3 months after the completion of adjuvant therapy. The patient underwent medical treatment with a gonadotropin-releasing hormone agonist and had a complete resolution of the recurrent tumor again. Hormonal treatment with a gonadotropin-releasing hormone agonist can be applied for small primary aggressive angiomyxomas in addition to adjuvant therapy for residual tumors.

Multiple primary malignancies in Japanese patients with renal cell carcinoma.

AIM: To evaluate the incidence, nature and prognosis of multiple primary malignancies involving renal cell carcinoma (RCC) in Japan. METHODS: Between 1975 and 1998, 319 patients underwent an operation for RCC at Hokkaido University, Sapporo, Japan. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. Follow-up was obtained by thorough chart review or telephone interview, and ranged from 0 to 276 months (median 49.0 months). To analyze the influence of other primary malignancies on prognosis, overall and cause-specific survival rates of the patients with an antecedent or synchronous malignancy were compared to the remaining patients. RESULTS: Of the 319 patients there was at least one other malignancy in 38 patients (12%). Four patients had two other malignancies. The other malignancies were antecedent in 13, synchronous in 19 and subsequent in 10 patients. Twenty-two patients had gastrointestinal cancer. In cases of antecedent or synchronous diagnosis of other primary malignancies, RCC was commonly incidental, small or low-stage. Multivariate analysis using Cox's proportional hazards model showed that, for overall survival, the presence of other antecedent or synchronous malignancies was the second most significant prognostic factor, following the pathological stage of RCC. CONCLUSIONS: In Japanese patients with RCC, the incidence of other primary malignancies was not uncommon and these malignancies contributed to the prognosis of these patients. Therefore, the malignant potential of individual tumors should be paid careful attention in the management of these patients.

Expression of vascular endothelial growth factor and its receptors Flk-1 and Flt-1 during the regeneration of autotransplanted adrenal cortex in the adrenalectomized rat.

PURPOSE: Autotransplantation of the adrenal cortex may be a therapeutic alternative in the future. For successful adrenal transplantation revascularization is necessary. It is possible that vascular endothelial growth factor (VEGF), which is a potent angiogenic peptide, may have some roles in adrenal transplantation through 2 its receptors, kinase insert domain-containing region (Flk-1) and fms-like tyrosine kinase (Flt-1). Therefore, we studied sequential changes in expression of VEGF, Flk-1 and Flt-1 in regenerated adrenal. MATERIALS AND METHODS: Eight to 9-week-old male Wistar rats underwent bilateral adrenalectomy and immediate adrenal capsular autotransplantation. The expression of VEGF, Flk-1 and Flt-1 was analyzed by immunohistochemistry and reverse-transcriptase-polymerase chain reaction. RESULTS: Angiogenesis was observed in the remodeling of adrenal sinusoidal endothelium during adrenal regeneration. Reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that VEGF expression increased in grafted tissue with time after transplantation and its Flk-1 receptor, which localized to endothelial cells, increased transiently during the regeneration process. Immunostaining for Flt-1 receptor was identified in adrenocortical cells and its intensity gradually increased during adrenal regeneration. CONCLUSIONS: During adrenal gland regeneration VEGF and its receptors Flk-1 and Flt-1 are thought to be involved in neovascularization.

[Paclitaxel, ifosfamide, nedaplatin (TIN) for patients with metastatic urothelial cancer].

TIN (ifosfamide 1.5 g/m2 daily for 3 days, paclitaxel 175 mg/m2, and nedaplatin 70 mg/m2 on day 1) was administered to patients with metastatic urothelial cancer previously treated by platinum-based chemotherapy and repeated every 4 weeks. Four patients received maintenance therapy, which consisted of 5'-DFUR 800 mg/day orally for 12 weeks and 1 subsequent course of TIN. This therapy regimen was repeated for 2 years from initiation of TIN. Eleven of 12 patients (91.6%) demonstrated a major response (3 complete responses, 8 partial responses), with durations of response ranging from 3 to 20 months. Progression-free survival time was from 0 to 20 months (median 8 months). One-year progression-free survival rate was 45.8%. Overall survival time was from 2 to 20 months (median 10.5 months). One-year overall survival rate was 53.5%. Grade 3/4 hematologic toxicity involved neutropenia in 100% and thrombocytopenia in 33.3%. Febrile neutropenia was observed in 5 patients (41.6%). Grade 3 nonhematologic toxicity involved malaise in 15.3%. No patient discontinued this therapy because of complications. TIN is a potent, well-tolerated regimen for previously treated patients with urothelial cancer.

Peritoneal carcinomatosis in refractory seminoma.

Intraperitoneal metastasis from a testicular germ cell tumor is very rare. We report a case in a 33-year-old man who was referred to Hokkaido University Hospital, Hokkaido, Japan, for further therapy for refractory seminoma. Physical examination revealed abdominal distension as a result of ascites, and cytology of the ascites showed seminoma cells. Although the ascites completely disappeared after treatment with a novel regimen of irinotecan-based chemotherapy, the patient had a recurrence of ascites and died of progressive disease 5 months after the start of the therapy.

Significance of COX-2 expression in human renal cell carcinoma cell lines.

Accumulating evidences indicate that cyclooxygenase (COX)-2 plays an important role in tumorigenesis in many human cancers. Yet the relationship between COX-2 and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to evaluate COX-2 expression in human RCC cell lines and its role in tumorigenesis of human RCC. Among the human RCC cell lines (SMKT-R4, OS-RC-2, ACHN) and normal renal cell line RPTEC, COX-2 overexpression was found in OS-RC-2 cells both at mRNA and protein levels. COX-2 sense- and antisense-orientated vectors were constructed and transferred into RCC cells. Significant suppression of cellular proliferation was demonstrated in OS-RC-2 antisense transfectants, whereas promotion was found in SMKT-R4 sense transfectants by colony-forming assay despite the observation that COX-2 specific inhibitor NS398 exhibited similar IC50 among RCC cell lines by MTT assay. In comparison with parent cells and sense transfectants, significant suppression of COX-2 expression and PGE2 production and increase in butyrate-induced apoptosis were observed in OS-RC-2 antisense transfectants by Western blot, ELISA assay and FACS analysis, respectively. Furthermore, tumor growth and angiogenesis of OS-RC-2 antisense transfectants in nude mice was significantly suppressed and the survival time of these mice was significantly prolonged. Our study demonstrates that COX-2 is overexpressed in OS-RC-2 RCC cell line and plays an important role in tumorigenesis of the cells in vivo, which implies that COX-2 may be a therapeutic target for COX-2-expressing RCC, and that suppression of COX-2 expression by antisense-based strategy may have potential utility in treatment of COX-2-expressing RCC.

Management of renal angiomyolipomas associated with tuberous sclerosis complex.

PURPOSE: Intensive management is generally recommended for angiomyolipomas associated with tuberous sclerosis complex (TSC), which are known to have a more aggressive nature than sporadic tumors. In this study we evaluated the management of these tumors. MATERIALS AND METHODS: The records of 6 men and 6 women with TSC and a mean age of 28.8 years) with angiomyolipomas treated from 1984 to 2000 were retrospectively analyzed. All patients had bilateral multiple tumors (mean size 6.6 cm). There were 10 lesions classified as small (less than 4 cm), 6 medium (4 to 10 cm) and 8 large lesions (10 cm or greater). Computerized tomography was repeated annually for followup observation and semiannually after embolization. RESULTS: Excluding from study 3 tumors treated prophylactically intervention was required in 20%, 50% and 100% of small, medium and large tumors, respectively. Among 14 tumors followed by observation, 8 grew and 4 required intervention. Uncontrollable hemorrhage did not develop in any patient. While some tumors showed remarkable growth in decade 3, growth did not exceed 1.5 cm per year. Embolization was performed in 11 tumors and tumors shrank in 10. Although 1 patient experienced renal atrophy, all patients but 1 are alive without renal failure with a mean followup of 60 months. CONCLUSIONS: Although asymptomatic angiomyolipomas associated with TSC grow gradually, severe hemorrhage is rare and most tumors can be managed conservatively with annual computerized tomography. Embolization is the first choice of intervention but should be reserved until symptoms develop.

Difference of cancer core distribution between first and repeat biopsy: In patients diagnosed by extensive transperineal ultrasound guided template prostate biopsy.

BACKGROUND: We performed extensive transperineal ultrasound guided template prostate biopsy and evaluated cancer core distribution. METHODS: From August 2000 to May 2002, 113 men with prostate specific antigen levels between 4.0 and 10.0 ng/ml underwent template biopsy. Eighty-six had no previous biopsy (first group) and 27 had previous transrectal sextant biopsies (repeat group). A mean of 18.4 biopsy cores were taken. We defined the region over 2 cm from the rectal face of the prostate as the anterior region and the other as the posterior. RESULTS: Cancer was detected in 49 of 113 (43%) men. Forty-two were in the first group and seven in the repeat group. In the first group, the cancer core rate (cancer core number/biopsy core number) in the anterior region (7.0%) had no difference from that in the posterior region (8.6%) (P = 0.7111). But in the repeat group, the cancer core rate in the anterior region (4.6%) was higher than in the posterior (1.5%) (P < 0.0001). CONCLUSIONS: These results suggest that transrectal sextant biopsies miss more cancers in the anterior region than in the posterior. We believe template technique has an advantage to be able to detect cancer equally in the anterior and posterior.

[Ureteral and bladder metastases of renal cell carcinoma following synchronous renal cell carcinoma and bladder cancer; a case report].

A 73-year-old man presented with gross hematuria. Ultrasonography and computerized tomography showed small bladder tumors and a left renal mass protruding to renal pelvis. Transurethral resection of bladder tumor and ureteroscopic tumor biopsy were performed, and pathological examinations revealed transitional cell carcinoma in the bladder and renal cell carcinoma in the kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy revealed a solitaly non-papillary tumor in the bladder. Transurethral resection was performed and pathological diagnosis was metastasis from renal cell carcinoma. At that time, multiple metastases to ureteral stump and lung were found. He had undergone palliative treatment because of his poor general condition until he died 26 months postoperatively. Care should be taken for management of ureteral stump when diagnostic ureteroscopy was done for renal cell carcinoma invading the renal pelvis.

Creation of luminal tissue covered with urothelium by implantation of cultured urothelial cells into the peritoneal cavity.

PURPOSE: We established the culture condition of seeding urothelial cells onto a scaffold for implantation into the peritoneal cavity and evaluated the histology of implanted urothelial cells. MATERIALS AND METHODS: In part 1 of the study cultured porcine bladder urothelial cells were seeded onto 3 types of collagen gel made on microporous membrane, including collagen gel with or without cultured porcine bladder fibroblasts, or a feeder layer. The macroscopic and microscopic appearance of the gel with urothelial cells were examined in vitro. As an in vivo study, cultured porcine bladder urothelial cells were seeded onto a collagen gel/sponge matrix with or without cultured fibroblasts, or a feeder layer. Urothelial cell survival on each matrix was evaluated 28 days after implantation onto the omentum or mesentery of nude rats. In part 2 of the study rat urothelial cells were cultured and seeded onto fibrin gel/atelocollagen sponge matrix as an autologous implantation model. After 7 days of cultivation the matrix was folded with urothelial cells inside, implanted onto the mesentery and serially evaluated. RESULTS: Gel containing cultured fibroblasts was shrunken and basement membrane formation was observed on the gel with cultured fibroblasts or the feeder layer in vitro. Urothelial cells cultured with the feeder layer better survived on the collagen based matrix and formed a hollow-like lumen when implanted into the peritoneal cavity. The regenerated urothelium in an autologous implantation showed the same histological features as normal bladder urothelium. CONCLUSIONS: Selection of less degradable matrix and formation of basement membrane are critical for survival of implanted urothelial cells. The regenerated urothelium in an autologous implantation model seems to have the similar properties to the normal urothelium.

Urodynamic effects of alpha1-blocker tamsulosin on voiding dysfunction in patients with neurogenic bladder.

BACKGROUND: The therapeutic role of alpha-blockers in the treatment of voiding disorders due to benign prostatic hyperplasia has been extensively examined. To investigate a possible effect of alpha1-blocker on urodynamic voiding parameters in patients with neurogenic bladder, we conducted a clinical trial using tamsulosin. METHODS: Twenty-four patients (14 men and 10 women) ranging from 24 to 82 years of age (mean age 61 years) with neurogenic bladder were analyzed. Urodynamic studies were performed before and after treatment with 0.4 mg tamsulosin daily for 4 weeks. RESULTS: On uroflowmetry, the average flow rate (from 4.6 +/- 3.3 to 6.7 +/- 3.0 mL/s, P = 0.04), maximum flow rate (from 9.4 +/- 6.8 to 14.1 +/- 7.0 mL/s, P = 0.016) and residual urine rate (from 46 +/- 29 to 32 +/- 21%, P = 0.02) improved significantly. In patients with detrusor contraction during voiding, detrusor opening pressure and detrusor pressure at maximum flow decreased significantly from 69.0 +/- 36.2 to 49.2 +/- 26.4 cmH2O (P = 0.046) and from 66.7 +/- 34.6 to 53.6 +/- 26.5 cmH2O (P = 0.007), respectively. On the other hand, in patients with detrusor areflexia, vesical opening pressure (from 78.2 +/- 23.4 to 61.6 +/- 25.2 cmH2O), or vesical pressure at maximum flow (from 68.6 +/- 23.2 to 62.9 +/- 25.2 cmH2O) did not change significantly after treatment. CONCLUSION: Tamsulosin reduces functional urethral resistance during voiding and improves flow rate in patients with neurogenic bladder. It has more beneficial urodynamic effects in patients with detrusor contraction during voiding than in patients with detrusor areflexia.

Immortalized neural stem cells transplanted into the injured spinal cord promote recovery of voiding function in the rat.

PURPOSE: Bladder dysfunction is a serious consequence of spinal cord injury. Cellular transplantation into the injured spinal cord can promote axonal growth and functional recovery. We investigated whether EG6 immortalized neural stem cells transplanted into the injured spinal cord of the rat contribute to a recovery of lower urinary tract function. MATERIALS AND METHODS: The spinal cord of 14 female Wistar rats was injured by compression. In 7 rats 9 days after spinal cord injury BrdU (5-bromo-2'-deoxyuridine) labeled EG6 cells were transplanted into the injured spinal cord. Seven operated (OP) control rats received intraspinal injections of culture medium alone. Voided volume per micturition was assessed in a metabolic cage for 24 hours on days 14 and 28 after transplantation. On day 28 saline was infused via a catheter inserted into the bladder and intravesical pressure was measured in OP control and EG6 transplant rats. RESULTS: EG6 cells identified by BrdU immunocytochemistry survived in the injured spinal cord. Voided volume per micturition significantly increased in EG6 transplant rats by day 28 after transplantation. Micturition pressure significantly decreased in EG6 transplant rats compared with OP controls. Although voided volume did not differ, post-void residual urine was significantly less in EG6 transplant than in OP control rats. Thus, voiding efficiency was significantly greater in EG6 transplant rats compared with OP controls. There was no difference in the incidence of detrusor hyperreflexia. CONCLUSIONS: Transplanted EG6 cells survived in the injured spinal cord and had beneficial effects on the recovery of voiding function after spinal cord injury in the rat.

Effects of chronic blockade of N-methyl-D-aspartate receptors by MK-801 on neuroplasticity of the micturition reflex pathway after partial urethral obstruction in the rat.

PURPOSE: To determine the role of N-methyl-D-aspartate (NMDA) glutamatergic receptors in the development of functional bladder changes after partial urethral obstruction we investigated the effects of repeat injection of MK-801, a noncompetitive NMDA receptor antagonist, on the micturition reflex in conscious obstructed rats. MATERIALS AND METHODS: In 9 female Wistar rats 1.0 mg/kg MK-801 was injected intramuscularly once weekly just prior to the creation of partial urethral obstruction until 5 weeks after obstruction. Five to 7 days after the last injection of MK-801 conscious filling cystometry was performed and compared with that in 9 obstructed rats treated with vehicle (saline). Conscious filling cystometry was also compared in 9 and 7 sham operated rats treated with repeat injection of MK-801 and vehicle, respectively. RESULTS: Partial urethral obstruction caused a significant increase in bladder weight. However, chronic MK-801 treatment did not affect bladder weight in obstructed or sham operated rats. In the obstructed/MK-801 vs the obstructed/vehicle group chronic treatment with MK-801 significantly increased bladder capacity (2.29 +/- 0.12 vs 1.73 +/- 0.16 ml, p <0.01) and voided volume (2.00 +/- 0.10 vs 1.56 +/- 0.17 ml, p <0.05) without changes in voiding efficiency (87.5% +/- 1.6% vs 87.8% +/- 1.7%) or micturition pressure (55.8 +/- 2.3 vs 56.4 +/- 3.0 cm water). Interestingly neither the frequency nor amplitude of premicturition contractions during filling was different in the groups. In sham operated rats chronic MK-801 treatment did not change bladder capacity, voided volume, voiding efficiency or micturition pressure significantly. CONCLUSIONS: The results in the current study suggest that bladder outlet obstruction causes NMDA receptor mediated alterations in bladder afferent pathways in the rat.