Takehisa Yoneyama

Functional and molecular biological evidence for a possible β3-adrenoceptor in the human detrusor muscle

The possible existence of a β3‐adrenergic receptor (β3‐AR) in the human detrusor muscle was investigated by in vitro functional studies and analysis of mRNA expression. Isoprenaline, noradrenaline and adrenaline each produced a concentration‐dependent relaxation of the human detrusor. The rank order for their relaxing potencies was isoprenaline (pD2 6.37±0.07) noradrenaline (pD2 6.07±0.12) adrenaline (pD2 5.88±0.11). Neither dobutamine (β1‐ and β2‐AR agonist) nor procaterol (β2‐AR agonist) produced any significant relaxation at concentrations up to 10−5 M. BRL37344A, CL316243 and CGP‐12177A (β3‐AR agonists), relaxed the preparations significantly at concentrations higher than 10−6 M. The pD2 values for BRL37344A, CL316243 and CGP‐12177A were 6.42±0.25, 5.53±0.09 and 5.74±0.14, respectively. CGP‐20712A (10−7–10−5 M), a β1‐AR antagonist, did not affect the isoprenaline‐induced relaxation. On the other hand, ICI‐118,551, a β2‐AR antagonist, produced a rightward parallel shift of the concentration‐relaxation curve for isoprenaline only at the highest concentration used (10−5 M) and its pKB value was 5.71±0.19. Moreover, SR58894A (10−7–10−5 M), a β3‐AR antagonist, caused a rightward shift of the concentration‐relaxation curve for isoprenaline in a concentration‐dependent manner. The pA2 value and slope obtained from Schild plots were 6.24±0.20 and 0.68±0.31. The β1‐, β2‐ and β3‐AR mRNAs were all positively expressed in detrusor smooth muscle preparations in a reverse transcription polymerase chain reaction assay. In conclusion, the present results provide the first evidence for the existence of the β3‐AR subtype in the human detrusor. They also suggest that the relaxation induced by adrenergic stimulation of the human detrusor is mediated mainly through β3‐AR activation.

Relaxant effects of isoproterenol and selective β3 : Adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders

PURPOSE We compared the relaxant effects of the stimulation of beta-adrenoceptors with isoproterenol and of drugs selective for beta-adrenoceptor subtypes in detrusor preparations from patients with normal and neurogenic bladder, respectively. MATERIALS AND METHODS We studied in vitro preparations of a cystometrically normal, low compliant and hyperreflexic bladder from 45, 26 and 7 patients, respectively. RESULTS Isoproterenol relaxed concentration dependently and with the same potency as detrusor preparations obtained from normal and neurogenic bladders. In 37 normal detrusor, 25 low compliant and 7 hyperreflexic cases pD2 values were 6.36, 6. 25 and 6.38, respectively. Maximal relaxation did not differ significantly among the 3 groups (about 80% of 10-5 M. forskolin induced relaxation). Neither the beta1-/beta2-adrenoceptor agonist dobutamine nor the beta2-adrenoceptor agonist procaterol produced any significant relaxation of preparations from the 3 groups at a concentration of up to 10-5 M. At a concentration of 10-4 M. the preparations were relaxed but neither of these effects reached a maximum. BRL37344A and CL316243, selective beta3-adrenoceptor agonists and CGP-12177A (a selective beta3-adrenoceptor partial agonist and beta1-/beta2-adrenoceptor antagonist) relaxed detrusor preparations from the normal, low compliant and hyperreflexic groups when applied at concentrations greater than 10-6 M. For each agonist the pD2 value did not differ significantly among the 3 groups. CONCLUSIONS beta-adrenoceptor stimulation is an effective way of relaxing the human detrusor and the effect is similar in normal and neurogenic bladders. A major portion of the relaxant effect of isoproterenol is mediated via beta3-adrenoceptor stimulation. Clinical trials may reveal whether this method is useful for treating bladder overactivity.

Urinary Tract Dysfunctions in Tethered Spinal Cord Syndrome: Improvement After Surgical Untethering

We reviewed 55 patients with urinary tract dysfunction owing to the tethered spinal cord syndrome, a form of spina bifida occulta with or without mild myelodysplasia, to evaluate the effects of neurosurgical treatment. Of the patients 24 underwent laminectomy with release of a tethered spinal cord and 31 were followed without the operation. Median followup was approximately 5 years. Urological findings at the most recent examination were compared between the 2 groups. In the operated group 5 patients, including 2 with myelodysplasia, apparently were cured of urinary tract dysfunction and 6, including 2 with myelodysplasia, had somewhat satisfactory results, whereas in the unoperated group only 4 patients had satisfactory results and the remainder were unaffected. Urinary tract dysfunction in some patients with spina bifida occulta may be relieved by surgical release of a tethered spinal cord.

Single Vaginal Ectopic Ureter via Gartner’s Duct Cyst Spontaneously Perforating into the Bladder

We report on a girl with a rare variant of single vaginal ectopic ureter via Gartners duct cyst, which ruptured spontaneously into the bladder leading to aggravation of urinary incontinence. The patient also had a megalovagina, and a fistula between the distal urethra and vagina. She became continent after removal of a dysplastic kidney, unroofing of the cyst and closure of the fistulas.

Granular cell tumor of the urethra.

Abstract:  A 38‐year‐old woman was referred for urethral tumor treatment. Needle biopsy of the tumor was performed. Histologically, the tumor was composed of large polygonal cells with eosinophilic and periodic acid‐Schiff (PAS)‐positive granular cytoplasm, indistinct cell margins and small round central nuclei. Immunohistochemical staining for S100 protein, vimentin, and neuron‐specific enolase (NSE) was positive, indicating that it was a granular cell tumor. Excision of the tumor including the urethra and appendicovesicostomy using the Mitrofanoff principle were performed. There has been no tumor recurrence in the 8 months after the operation.

Adenocarcinoma in an Ileal Conduit: Recurrence of Bladder Adenocarcinoma

Recurrent adenocarcinoma developed in an ileal conduit in a 75-year-old man who had undergone cystectomy and ileal conduit diversion for adenocarcinoma of the bladder 16 months before. The excised tumor was histologically identical to the original bladder tumor, and the mucosa of the ileal conduit was not involved by the tumor. Multiple lung metastases preceded the development of the recurrent tumor. The recurrent adenocarcinoma in the ileal conduit seemed to be a manifestation of a generalized spread of the tumor.

Chemical Pericystitis: A Rare Complication of Intravesical Doxorubicin

We report a rare instance of chemical pericystitis in a 60-year-old man who had undergone transurethral resection of a bladder tumor and subsequent intravesical instillation of doxorubicin. The patient had a high fever lasting for 18 days, lower abdominal pain and mild hydronephrosis. Extravasation of doxorubicin through the resected and thinned region of the bladder wall seemed to be responsible for this complication. The lesion improved spontaneously without any sequela.

A clinical and pathological study of radical prostatectomy for prostate cancer

BACKGROUND Thirty-one patients with prostate cancer underwent radical prostatectomy and simultaneous pelvic lymphadenectomy at Matsumoto National Hospital between 1988 and 1994. Prognostic factors are discussed from their clincopathological findings. METHODS The patients ranged from 54 to 80-year-old, with an average age of 69.9 years. The median follow-up period was 44 months. The diagnosis was confirmed by needle biopsy or transurethral resection of the prostate. All the patients received short-term endocrine therapy preoperatively, and only noncuratively resected patients underwent adjuvant therapy postoperatively. At initial diagnosis, the tumor grades were well, moderately, and poorly differentiated adenocarcinoma in 9, 12, and 10 patients, respectively. The clinical stage was defined as A2, B, C, D1, and D2 in 12, 4, 6, 3, and 6 patients, respectively. RESULTS A difference of tumor grade was found between the initial diagnosis and the final diagnosis based on the resected prostate in 8 patients (26%), with 7 of them (88%) showing an increase in grade in the final diagnosis. Also revealed was that 11 of the 25 patients (44%) in stage A2, B, C, or D1 had been understaged preoperatively. The five-year actuarial survival rates were 100%, 92%, and 51% for patients with well, moderately, and poorly differentiated adenocarcinoma, respectively, with a significant difference noted between well and poorly differentiated adenocarcinoma (p = 0.03). Recurrence only developed in patients with pathological stage D tumors. However, the presence or absence of lymph node metastasis did not affect the crude 5-year survival rate. Several stage D patients were successfully treated by radical prostatectomy and adjuvant therapy, achieving long survival. CONCLUSION These results indicate that patients in clinical stage C have tumors which exhibit differing biological behavior. These patients should be analyzed and classified more precisely so that the most appropriate therapy can be chosen.