Tadao Niijima

A pharmacological study of alpha adrenergic receptor subtypes in smooth muscle of human urinary bladder base and prostatic urethra.

Postsynaptic alpha adrenergic receptor subtypes mediating contraction of human urinary bladder base and prostatic urethra were investigated in vitro. Alpha adrenergic receptor agonists, noradrenaline and phenylephrine, induced contraction dose-dependently in these tissues. Alpha adrenergic receptor antagonists, prazosin and yohimbine, competitively antagonized the contraction induced by these agonists in the bladder base as well as prostatic urethra. The mean pA2 values for the antagonists in the bladder base and prostatic urethra were as follows: 8.89 and 8.96 for prazosin and 6.30 and 6.45 for yohimbine, respectively. Comparison of pA2 values of prazosin and yohimbine in both the tissues with those values found in the literature for these compounds in a variety of tissues containing alpha-1 or alpha-2 adrenergic receptor indicates that the postsynaptic alpha adrenergic receptor subtype in the human urinary bladder base and prostatic urethra is the alpha-1 type, not the alpha-2 type.

Clinical evaluation of urothelial tumors of the renal pelvis and ureter based on a new classification system

Clinical evaluation of 460 cases of urothelial tumors of the renal pelvis and ureter was performed using a new clinical classification system, since no systemic clinical classification such as the TNM system for bladder tumors has been available to date. ABC, and TS and TE categories were newly adopted. The former distinguishes tumor multicentricity, and the latter indicates the clinical tumor stage. Tumors arising in one organ and homolaterally are categorized as A, while those in both organs (ureter and renal pelvis) and/or in the bladder are B, and bilateral tumors are C. TS represents the tumors of pT1 and pT2, and TE represents pT3, and pT4. Tumors belonging to pB showed a poorer prognosis than pA tumors. The TS and TE staging system clearly reflected the histopathologic stage, and produced significant differences in relative survival rates. Regarding various prognostic factors, our series gave the same results as reported by other investigators. However, it should be stressed that female patients showed a poorer prognosis than male patients.

Randomized clinical trial on chemoprophylaxis of recurrence in cases of superficial bladder cancer.

SummarySeveral postoperative adjuvant therapeutic modalities have been adopted in attempts to reduce the recurrence rate of superficial bladder cancer. However, no definite conclusions on the effectiveness of intravesical chemoprophylaxis have been reached.A randomized clinical study on intravesical chemoprophylaxis was conducted by the Japanese Urological Cancer Research Group for Adriamycin to compare the recurrence rates among 575 patients with superficial transitional cell carcinoma of the urinary bladder. Group A received 30 mg/30 ml Adriamycin; group B received 20 mg/40 ml Adriamycin; group C received 20 mg/40 ml mitomycin C, and group D, no treatment (for control). Instillation was performed twice a week for 4 weeks after surgery. The postoperative observation period was 18 months. The overall recurrence rate in group D was 61.5%, which was statistically higher than in the other groups. The Adriamycin and Mitomycin C groups showed recurrence rates of 43%–48% and 57%, respectively.Intravesical Adriamycin and Mitomycin C appeared to be effective in the prophylaxis of recurrence during this observation period. The main side-effect was cystitis syndrome, which was observed in 10%–20% of the patients. There were no life-threatening adverse effects in this series of patients.

Staging of Bladder Cancer by Ultrasonography: A New Technique by Transurethral Intravesical Scanning

A new ultrasonic scanning device has been developed for preoperative staging of bladder cancer. The device uses a transurethrally intubated probe with a head that can be angled 90 degrees against its long axis and intravesical scanning. The propagation of the ultrasound is ideal and the tomograms provide good resolution. The ultrasonic images in each stage of bladder cancer were demonstrated. Comparison of ultrasonic and pathological stages showed concordance in 19 of 20 tumors removed by total or partial cystectomy. One tumor diagnosed by ultrasonography as T3 was identified pathologically as T1. Calcification on the tumor surface obstructed ultrasonic propagation, resulting in overstaging. Transurethral intravesical scanning is valuable clinically because of its accuracy in staging bladder cancer.

Suppression of Spermatogenesis in Patients with Behçet’s Disease Treated with Cyclophosphamide and Colchicine

Reproductive function was studied in 31 adult male patients with Behçets disease during treatment with cyclophosphamide and/or colchicine for 1 to 64 months. Semen was obtained from 27 patients. Azoospermia or severe oligospermia was found in 13 of 17 patients receiving cyclophosphamide with or without colchicine, whereas the sperm count was almost normal in six patients treated with colchicine alone and in four patients receiving neither drug (control patients). Blood samples were available for 31 patients. The mean follicle-stimulating hormone level among 12 cyclophosphamide-treated patients was significantly higher than that of 6 colchicine-treated patients and 6 control patients. These results indicate that cyclophosphamide impairs spermatogenesis in adult men, whereas colchicine does not.

Use of an α1-Blocker, YM-12617, in Micturition Difficulty

The adrenergic αpblocker has been clinically used for the treatment of patients who have micturition difficulty. However, one of its remarkable adverse reactions is orthostatic hypotension, which prev

Effects of lntravesical instillation of antitumor chemotherapeutic agents on bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine

The effects of intravesical instillation of Adriamycin (doxorubicin) (ADR), and mitomycin C (MMC), as inhibitors of development of rat bladder tumors, were examined in rats treated with N‐butyl‐N‐(4‐hydroxybuty1)nitrosamine (BBN). Intravesical instillation of ADR or MMC once a week for 12 weeks into rats pretreated with BBN for 4 weeks markedly enhanced development of bladder tumors. That is, one week after the end of intravesical instillation of these compounds the incidence of papillary or nodular hyperplasias, namely preneoplastic lesions, was significantly increased, and at the end of the experiment the incidence of not only papillary or nodular hyperplasias but also of papillomas and cancers was significantly increased. These results indicate that the intravesical instillation of ADR or MMC promotes two‐stage bladder carcinogenesis in rats.

Long-term results of intravesical chemoprophylaxis of superficial bladder cancer: experience of the Japanese Urological Cancer Research Group for Adriamycin.

SummaryLong-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was <90%.

Increased sperm abnormalities due to dietary restriction

Abstract The effect of dietary restriction on sperm-head morphology in BDF 1 mice was studied. The food intake of the ice was restricted to 2.0 or 1.5 g/day during the whole experimental period, while control animals were fed ad libitum. The average food intake of control mice was 4.2 ± 0.5 g/day. The frequencies of abnormal sperm in food-restricted mice remained at the basal level for the first 2 weeks. In week 3, the frequencies of abnormal sperm increased only in mice on the severely restricted diet (1.5 g/day). In week 5, the frequencies of abnormal sperm increased significantly in both restricted groups, and a negative correlation between the food intake and the frequency of abnormal sperm was observed. These results suggest that sperm abnormalities are not always the results of exogenous mutagen-induced damage

Renal hypercalciuria and metabolic acidosis associated with medullary sponge kidney: Effect of alkali therapy

SummarySixteen patients with medullary sponge kidney (MSK) and renal stones underwent evaluation of calcium metabolism and acid base balance. Six normal subjects and eight patients with non-MSK absorptive hypercalciuria served as control. Nine (56%) were hypercalciuric and seven (44%) were normocalciuric (N-MSK). Hypercalciuria was divided into absorptive (AH-MSK, n=2) and renal leak hyerpcalciuria (RH-MSK, n=7). The mean of minimal urine pH of RH-MSK group (5.28±0.09 (SE)) was significantly higher than that of normal control (4.78±0.12) and of non-MSK AH (4.80±0.6) during acute acid challenge. The mean of the arterial blood HCO3 concentration of RH-MSK group was significantly lower than that of two control groups. The urine calcium and a frequency of stone passage were decreased significantly after alkali treatment in RH-MSK.