Search

Aim To evaluate efficacy and safety of combination of tadalafil + mirabegron for overactive bladder/benign prostatic hyperplasia (OAB/BPH). Methods Male patients with lower urinary tract symptoms (50 to 89 years), with remaining OAB symptoms even after administering tadalafil for more than 8 weeks were randomly assigned to either tadalafil monotherapy group (5 mg/day) or tadalafil/mirabegron combination therapy group (5 mg/50 mg/day). The primary endpoint was change from baseline in total OAB symptom score (OABSS) at week 12. The secondary endpoints were changes in International Prostate Symptom Score (IPSS), NIH‐chronic prostatitis symptom index (NIH‐CPSI), and micturition chart parameters at weeks 4 and 12. Results A total of 176 patients were randomized to either monotherapy (87 patients) or combination therapy (89 patients). The baseline characteristics of patients in the two groups were similar. The total OABSS (95% confidence interval) of combination therapy was significantly decreased by 1.78 (1.05‐2.50) points compared with that of monotherapy (P

Objective To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. Methods Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. Results For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. Conclusions This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

Introduction Phosphodiesterase type 5 inhibitors (PDE5i) are first-line therapy for most men with erectile dysfunction (ED). If ineffective, vacuum erection devices, intracavernous injections, and penile prosthesis implantation are suitable as second- or third-line therapies. However, very few patients select these therapies. It is critically important to improve erectile function with oral administration of effective agents. Administration of L-citrulline or transresveratrol in animal experiments has been reported to improve erectile function, but few such experiments have been performed on humans with ED. Aim We aimed to investigate the efficacy of combination therapy of L-citrulline and transresveratrol in patients with ED despite their use of PDE5i. Methods In this randomized, double-blind, placebo-controlled crossover pilot study, men with ED (Sexual Health Inventory for Men [SHIM] score below 16) despite on-demand use of PDE5i received a placebo for 1 month or the active treatment (L-citrulline 800 mg/day and transresveratrol 300 mg/day) for another month. Patients continued on-demand use of PDE5i. Main Outcome Measure The SHIM score, Erection Hardness Score (EHS), Aging Male Symptoms Scale-sexual domain (AMS-SD), and adverse events were examined. Results 20 patients ages 29–78 years were enrolled, and after 6 men withdrew, 13 concluded the study without adverse events. Mean SHIM score for the active treatment increased significantly (10.96 ± 1.21) compared with baseline (8.32 ± 1.21) and placebo (8.31 ± 1.23) (both P < .05). Mean EHS score for the active treatment (2.56 ± 0.26) also increased from baseline (2.31 ± 0.26), but not significantly (P = .79). Mean AMS-SD score was not significantly different in either group. Conclusion To our knowledge, this is the first study to show that combination therapy of L-citrulline and transresveratrol is effective for ED treatment in men with added on-demand use of PDE5i. This combination supplement may be added if PDE5i is insufficient.

Objectives To evaluate changes over time in subjective symptom scores and urination parameters before and after oral administration of formulated food containing a combination of Peucedanum japonicum (P. japonicum) extract and saw palmetto extract (SPE) in male patients with lower urinary tract symptoms (LUTS). Methods This study was conducted in an open label manner on male patients with untreated LUTS. The urination state of patients was evaluated before and after administration of food formulated with P. japonicum extract and SPE for 4 weeks, based on urodynamic parameters and subjective symptom scores (International Prostate Symptom Score [IPSS and IPSS-QOL], Overactive Bladder Symptom Score [OABSS], Overactive Bladder Questionnaire [OAB-q], and International Index of Erectile Function [IIEF]). Results After the administration of food formulated with these extracts, the following results were obtained: (i) Subjective findings: The IPSS-QOL score improved significantly; both parameters related to nocturia, i.e., frequency of nighttime urination and OABSS-2, improved significantly; other ratings for subjective symptoms slightly improved. (ii) Objective findings: Residual urine volume decreased significantly, and blood prostate specific antigen (PSA) and urinary 8-OHdG levels decreased slightly after the treatment. (iii) Other findings: Blood pressure decreased slightly. No adverse drug reactions were reported. (iv) Patient impressions: 75% of patients gave a rating of “Good” or higher, with 15 out of 20 patients wanting to continue treatment after the end of 4-week administration period. Conclusions Food formulated with P. japonicum extract and SPE may be useful to decrease frequency of nighttime urination and residual urine volume in male patients with LUTS.

症例は68歳，男性．透析歴は6年であり，約1年は腹膜透析．既往症として，狭心症に対する冠血管インターベンション，副甲状腺全摘除・前腕自家移植術がある．透析導入直後から皮膚そう痒症が顕著であり，副甲状腺全摘・自家移植術の術直後と腹膜透析への移行期間を除いて常に強い掻痒感が持続していた．皮膚外用剤や各種のスキンケア製剤および抗ヒスタミン剤などいろいろ使用したが掻痒感の改善は得られなかった．当院受診時は副甲状腺機能の再亢進に対して静注ビタミンD注入を行っており，血清のカルシウムは高値であった．副甲状腺機能亢進症に対する静注ビタミンD療法を，シナカルセト内服に切り替えたところ，PTHは低下傾向を示した．また血清カルシウム，リン値は至適レベルに低下した．PTHが低下し，血清カルシウム×リン積が著明に低下することにより，皮膚そう痒症が劇的に改善することは，副甲状腺摘除後に多く経験されている．シナカルセト内服により，PTHが低下し，カルシウム・リン値のコントロールが良好となり，結果的に副甲状腺機能亢進症の治療がより強力となり，難治性の皮膚そう痒症に効果的であったと考えられる症例を経験したので，若干の考察を加えて報告する．

Objectives To evaluate the efficacy and safety of mirabegron compared with imidafenacin for the treatment of female patients with overactive bladder. Methods Patients (n = 89) were randomized to receive 0.1 mg imidafenacin twice daily (n = 47) or 50 mg mirabegron once daily (n = 42) for 12 weeks. The primary efficacy end-point was change in total Overactive Bladder Symptom Score. Secondary efficacy end-points included change in Overactive Bladder Symptom Score, 3-day micturition diary, International Prostate Symptom Score and Overactive Bladder Questionnaire. Safety assessments included adverse events, vital signs, post-void residual volume and patient-reported incidence, and severity of distinctive symptoms related to adverse events. Results The mirabegron group showed a significantly reduced mean total Overactive Bladder Symptom Score from baseline, but no significant differences were noted in change of total Overactive Bladder Symptom Score compared with the imidafenacin group. Significant improvements in secondary efficacy end-points were observed regarding the mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of incontinence episodes/24 h, mean volume voided/micturition, total International Prostate Symptom Score and quality of life in both groups, with no significant differences between the groups. The overall incidence of adverse events and the incidence of dry mouth were significantly higher in the imidafenacin group than in the mirabegron group. Patient-reported incidence and the severity of dry mouth were significantly exacerbated in the imidafenacin group. Conclusions Treatment with 50 mg mirabegron once daily effectively relieves overactive bladder symptoms in women with fewer adverse events than treatment with antimuscarinics.

Thymidine phosphorylase (TdR-Pase) is an essential enzyme in the metabolism of fluorouracil-related drugs and is also a potent angiogenic factor. We measured the TdR-Pase activity in human renal cell carcinomas (RCCs) to assess the relationship between TdR-Pase activity and the degree of tumor malignancy. We also investigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil-related drugs. A total of 61 RCC tissue specimens and 39 normal kidney tissue specimens were obtained. TdR-Pase activity was measured by enzyme-linked immunosorbent assay. The in vitro histoculture drug response assay was also performed to examine tumor sensitivity to 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR). The TdR-Pase activity of RCCs was 13-fold that of the normal tissues. Activity increased with histological grade, and,was significantly higher in high-stage tumors (T3 or higher). TdR-Pase activity exhibited a significant positive correlation with sensitivity to 5-FU and 5'-DFUR. High TdR-Pase activity in human RCC was confirmed to predict high tumor grade and stage. RCCs with high TdR-Pase activity were also sensitive to FU-related drugs.

Bikunin is a Kunitz-type protease inhibitor found in serum and urine. It has been implicated in urinary stone formation. This study was designed to investigate the role of urinary bikunin in stone formation.Urinary concentrations of bikunin were measured in 18 male formers of urinary stones 28 to 74 years old and in 77 healthy controls, including 39 males and 38 females, without urological abnormality. A sensitive competitive solid phase enzyme immunoassay was established for urinary bikunin. Bikunin was also qualitatively assessed by Western blot analysis.The mean urinary bikunin-to-creatinine ratio plus or minus standard deviation in stone formers was significantly elevated compared with that in healthy male and female controls (52.9 +/- 46.0 microg./mg. creatinine versus 28.0 +/- 30.4 and 26.5 +/- 21.7, p = 0.005 and 0.006, respectively). By Western blot analysis all urine samples contained authentic 40 kDa. bikunin species. However, a significantly higher proportion of patients was found to have aberrant 25 kDa. bikunin species compared with controls (10 of 18 or 55.6% versus 15 of 77 or 19.5%, p = 0.002). Experiments on de-glycosylation with chondroitinase ABC, amino acid sequencing of the aberrant bikunin species and calcium oxalate crystal growth inhibition assay demonstrated that the 25 kDa. bikunin fragment was identical to de-glycosylated bikunin and less inhibitory on calcium oxalate crystal growth.If urinary bikunin is important in the pathogenesis of urolithiasis, its effect is probably attributable to the concentration and degree of glycosylation.

Laparoscopic surgery for urological conditions has now become popular worldwide. The case is reported of a 56-year-old woman who underwent simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia (AIMAH), followed by autotransplantation of resected adrenal gland fragments. Simultaneous laparoscopic adrenalectomies seem feasible for a patient with AIMAH because of its minimally invasive nature. However, autotransplantation of adrenal fragments failed in this patient with AIMAH.

The details are reported of bladder dysfunction in a Japanese boy with adrenoleukodystrophy. He developed gait disturbance at the age of 15 years. Spastic paraparesis progressed from the legs to the hands and brain magnetic resonance imaging showed characteristic degenerative change. Detrusor hyperreflexia was found by a urodynamic study and detrusor-sphincter dyssynergia was also suspected.

Purpose: We propose a criterion to clarify the underlying etiologies of nocturia. Materials and Methods: Frequency-volume charts were recorded for 24 hours by 35 men and 32 women who were subjectively free of lower urinary tract symptoms and had no evidence of voiding disorders. At least 5 subjects were included in each of 5 age groups of 20 to 49, 50 to 59, 60 to 69, 70 to 79, 80 to 89 years for both genders. The charts were used to make a tentative criterion, which was validated in 39 elderly individuals with nocturnal frequency. Results: Correlation and regression analyses indicated that the quotients of nocturnal urine output divided by body weight (U N /BW) and largest voided volume divided by body weight (V L /BW) were useful classification factors. Cutoffs, which were set close to worst quartiles, were 10 ml./kg. for U N /BW and 4 ml./kg. for V L /BW, respectively. Correction by body weight made the same criterion applicable irrespective of weight. Symptomatic elderly patients were classified into 3 mutually exclusive groups of nocturnal polyuria (U N /BW greater than 10 ml./kg.), low bladder capacity (V L /BW less than 4 ml./kg.) and combined nocturia. Of 20 subjects who voided 2 times a night 11 (55%) were classified as having nocturnal polyuria and 15 of 19 who voided 3 or 4 times (79%) were classified as having low bladder capacity or combined nocturia. Conclusions: The criterion provides a reasonable distinction of etiologies of nocturia, and may be usefulness in examination and treatment.

SummaryWe describe the performance of retroperitoneoscopy-assisted total nephroureterectomy, combined with transurethral extraction of the ureter, in a patient with renal pelvic cancer. There were no significant complications during or after the operation. After follow-up for 14 months, there has been no local recurrence of the tumour. Our technique may be advantageous for patients with early renal pelvic and upper ureteral cancer because it is minimally invasive.

We successfully performed a laparoscopic nephrectomy on 2 young girls in March 1994 and August 1994. The first patient was a 9-year-old girl with a hypoplastic kidney associated with an ectopic ureterocele, and the other was a 3-year-old girl with a nonfunctioning hydronephrotic kidney caused by stricture of the pyeloureteral junction. The operating times were 153 and 183 minutes, respectively. No complications occurred intraoperatively or postoperatively in either patient. The 9-year-old girl resumed normal daily activities by postoperative day 2, and the 3-year-old girl by postoperative day 3. Both girls were discharged on day 4.

We performed laparoscopy-assisted partial nephrectomy for a calcified cystic lesion of the kidney. This new technique combines the merits of laparoscopic and conventional open surgery. Although our method leaves a slightly larger scar than laparoscopic surgery, suturing of the cut renal parenchymal margin is easy, and CO2 pneumoperitoneum is not needed. In addition, if the frozen section reveals malignancy, it is easy to change the procedure to radical nephrectomy without making another incision. This new method may be useful for various renal lesions, as well as for surgery on the abdominal organs.

Cell culture models of calcium phosphate renal stone formation were established using the MDCK cell line. Renal microliths were detected within pseudocysts in three-dimensional soft agar cultures, and were also observed in the basal region of cells lining the cell sheet, and immediately beneath domes or blisters in monolayers and collagen gel cultures. Light and scanning electron microscopy indicated that these microliths had a similar lamellated and spherical appearance to those in humans. These microliths were first detected microscopically after 21 days of culture, and were found to be composed of calcium phosphate by X-ray and micro-infrared spectroscopic analyses. These culture models may provide a powerful new tool to study the pathogenesis of renal stone diseases and/or calcium phosphate stone formation in humans and animals.

SummarySince March 1993, we have performed gasless laparoscopy-assisted nephrectomy (GLAN) for patients with renal tumours and have found that it is a useful minimally invasive procedure. We have recently also performed GLAN for living kidney donors. The objectives of the present study were to evaluate the efficacy of GLAN for living kidney transplantation and to compare the results of GLAN and open donor nephrectomy. Since March 1995, we have performed GLAN for five living kidney donors. The surgical outcome and the post-operative graft function were compared with the results for donors operated on by open nephrectomy. The mean operating time and mean blood loss were 292.8 min and 185.2 ml in the five GLAN procedures. There were no operative or post-operative complications apart from blood loss of 500 ml in one obese donor whose right kidney was removed. Although the operating time was longer, the post-operative recovery of the donors was significantly more rapid than with open donor nephrectomy. GLAN co...

In order to evaluate the utility of laparoscopic adrenalectomy for Cushing's syndrome, the results of 6 laparoscopic adrenalectomies for Cushing's syndrome were compared with those of 34 other laparoscopic adrenalectomies, consisting of 7 pre-Cushing's syndromes, 13 primary aldosteronisms, and 14 non-functioning adrenal tumors. The results were also compared with 5 open adrenalectomies for Cushing's syndrome. The results of the laparoscopic adrenalectomies for Cushing's syndrome were as follows: the mean operating time was 216 +/- 46 min, and the mean estimated blood loss was 180 +/- 194 ml. From the third patient, an ultrasonic surgical system was used and the estimated blood loss decreased significantly. The ultrasonic surgical system, together with a more experienced surgical technique, also cut down the operating times. During surgical intervention, 2 complications occurred; a hemorrhage of more than 500 ml in one patient, and splenic injury in another, which was treated by compression. Postoperative complications occurred in 2 patients; paralytic ileus in one, and abdominal pain due to the pneumoperitoneum in the other. All patients except 2 patients with vertebral fracture began oral intake and ambulation 1 to 4 days postoperatively, and resumed normal daily activity on postoperative day 5 to 7. Compared with the laparoscopic adrenalectomies for the other adrenal tumors, the operating time and estimated blood loss in the Cushing's syndrome patients was not substantially different, though postoperative recovery was slightly longer. When compared with the open adrenalectomies, the operating time was longer, but the postoperative recovery period was significantly shorter. We conclude that with careful surgical intervention, experience of technique, and the introduction of proper equipment, a laparoscopic adrenalectomy for Cushing's syndrome can be performed as less-invasively as a laparoscopic adrenalectomy is for the other adrenal tumors. Furthermore, our findings suggest that laparoscopic adrenalectomy for Cushing's syndrome is likelier to have better postoperative results than conventional procedures, including a more rapid recovery to normal daily activity.

(PURPOSE). To determine the efficacy of extraperitoneal laparoscopic adrenalectomy for patients with adrenal tumor, the clinical results of 9 patients treated with this procedure were analysed. (PATIENT AND METHOD). Between July 1994 and March 1995, we have performed extraperitoneal laparoscopic adrenalectomy using the modified Gaur technique of balloon dilatation of the retroperitoneum in 4 men and 5 women with unilaterla small adrenal tumor who were 30 to 79 years old (mean age 56 years). Preoperative diagnosis was primary aldosteronism in 2, 18-hydroxycorticosterone producing adnoma in 1, pre-Cushing syndrome in 5, and nonfunctioning adrenal tumor in 1 patient. The operations were performed with the patients on lateral position and 4 torocars were positioned. The retroperitoneal space was first dissected bluntly by the index finger and a balloon dissector through a small skin incision, and the retroperitoneal space was insufflated with carbon dioxide at the pressure of 10 to 12 mmHg. After the dissection of the adrenal gland, adrenal vein was clipped and transected. The completely freed adrenal gland was enclosed in an entrapment sack and removed en bloc through the open laparoscopy wound. (RESULTS). All 9 procedures were successfully performed. The mean estimated blood loss and the mean operating time were 53 ml and 168 min respectively. There was no intraoperative complication. A postoperative retroperitoneal hematoma was observed in one patient, however it spontaneously resolved without surgical management. (CONCLUSION). In open adrenalectomy, the benefit of the extraperitoneal approach (excluding patients with pheochromocytoma or bilateral lesions) have already been established elsewhere. Although the working space is smaller than that of peritoneal approach, and the surgical techniques are slightly more difficult, extraperitoneal laparoscopic adrenalectomy promises to be safe and a minimally invasive treatment for patients with unilateral small adrenal tumors except for pheochromocytoma.

A 39-year-old male presented with gross hematuria and left lower abdominal discomfort. Excretory urography showed a left ureteral stone and hydronephrosis. CT scans and magnetic resonance imaging showed a solid mass at the upper pole of the left kidney. Angiography revealed a hypervascular lesion at this area. The laboratory data showed a slightly decreased serum potassium level. In the endocrinological study, the serum deoxycorticosterone (DOC) level was markedly elevated. There was, however, no evidence of hypertension. The operation was performed on November 13, 1992. The tumor was almost separated from the left kidney, but an aberrant artery which divided from the renal artery and penetrated the renal parenchyma was found. Therefore, we had to carry out en bloc removal of the tumor together with the left kidney and the ureter which contained the ureteral stone. Pathological diagnosis was adrenocortical carcinoma. After the operation, hypokalemia and the serum concentration of DOC returned to normal range. Therefore, the tumor was diagnosed as DOC producing adrenocortical carcinoma. The patient was discharged 30 days after the operation with uneventful postoperative course. He received 2.5 g of op'-DDD a day. There was no evidence of distant metastasis or local recurrence 12 months after the operation. Nineteen cases of DOC producing adrenocortical tumor have been reported in the world literature. A case and a review of the literature are herein reported.

BACKGROUND The objective of this study is to evaluate the diagnostic utility of digital rectal examination (DRE), prostate specific antigen (PSA) and transrectal ultrasonography (TRUS) for prostate cancer. METHODS On 266 patients ultrasonography guided transrectal biopsies were performed using the automatic biopsy gun fitted with an 18 gauge biopsy needle. RESULTS There was no major complication. Cancers were found in 52 patients (19.5%), and 16 of them were not identified by echography. Among 67 hypoechoic areas detected by echography, 36 (53.7%) were found to be cancer. The positive predictive value of DRE was 52.1% and that of PSA and TRUS were 24.4% and 53.7%, especially the rate increased to 93.7% by combining of these three techniques. CONCLUSION These results suggest that the use of DRE, PSA in conjunction with TRUS enhances early detection of prostate cancer.

Laparoscopic adrenalectomy is a new procedure for the treatment of adrenal tumors. The clinical experience with this operation in 12 patients is reported. While adrenal tumors are relatively small and seem to be good candidates for laparoscopic surgery, this procedure is difficult because of the anatomical location. In our study laparoscopic adrenalectomy appeared to be successful, although massive bleeding occurred in 3 patients. These problems should be overcome as the technique is improved and new laparoscopic instruments are introduced.

Primary tumor in the ureteral stump is rare. A 66-year-old woman visited our hospital because of microscopic hematuria. She had undergone right nephrectomy for the contracted kidney 36 years ago. Intravenous pyelography and cystoscopy showed no positive findings for hematuria. But urine cytology indicated class V. The flexible ureterorenoscopy disclosed a nonpapillary sessile tumor in the ureteral stump. We also did the biopsy of the tumor under the direct vision before open surgery. The specimen showed transitional cell carcinoma, grade 3. The ureteral stump was successfully removed. The flexible ureterorenoscopy was most useful for the diagnosis in this case.

The Randomized Aldactone Evaluation Study showed that low-dose spironolactone treatment dramatically reduced mortality in patients with heart failure. However, the clinical use of this drug may be limited due to its tendency to cause life-threatening hyperkalemia in hemodialysis (HD) patients. We assessed whether low-dose spironolactone could be safely administered to HD patients for a long period. The study design comprised 2-month baseline and 6-month treatment periods. Sixty-one oligoanuric HD patients were administered a spironolactone dose of 25 mg/day. Serum potassium levels at baseline were compared with those during the treatment. Eleven patients discontinued the treatment because of adverse events other than hyperkalemia or for other reasons. The remaining 50 patients completed the trial, and none of them showed a potassium level of >6.8 mEq/l or required additional ion exchange resin therapy throughout the study period. The mean potassium levels during the treatment were higher than those at baseline; the differences were statistically significant, but only marginally. The safety of spironolactone should be examined in larger trials. However, from this study, we conclude that long-term low-dose spironolactone treatment is clinically safe for many HD patients. A more extensive treatment may help in determining whether spironolactone can reduce cardiovascular mortality in HD patients.

To determine whether subjective or objective seasonal changes occur in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH).A total of 31 patients with LUTS were observed for5 years. Their International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum flow rate (Qmax), voided volume (VV) a nd post-void residual (PVR) we re measured every month.Total IPSS, QOL, VV or PVR did not show any seasonal changes between the three seasons: summer (hot season: June to September); winter (cold season: December to March); and spring and fall (comfortable season: April, May, October and November). Furthermore, when the IPSS was examined by dividing it into storage symptoms (frequency, urgency and nocturia) and voiding symptoms (incomplete emptying, intermittency, weak stream and straining), no significant seasonal changes were detected. Only Qmax showed a significant seasonal change, being higher in both the cold season (median 10.4 ml/s) and the comfortable season (median 10.1 ml/s) than in the hot season (median 9.4 ml/s).It has generally been thought that LUTS worsen in winter. Our results indicate that the IPSS and the QOL score remain nearly constant if they are determined regularly over an extended period of time. Qmax may however be influenced by seasonal changes in temperature.

Economical elements including surgical fee and hosipital stay become larger in the selection of surgical methods for the treatment of urinary stones. Then, urologists need to explain to patients the treatment cost to obtain informed consent. By comparing the data from participants' answer to Debate 1 at the 82th annual meeting of the Japanese Urological Association (April 2002, Tokyo) and questionnaire responses from the members of the annual meeting of central division of Japanese Urological Association (November 2002, Nagoya), we surveyed the trends of surgical methods on the treatments of staghorn caliculi and lower ureter stones. Furthermore, we clarified the cost of these methods. Based on the status of world countries, we demonstrate the ideal selection including economical aspects on the selection of endourological method.

Purpose: We determine the value of an ultrasonic surgical system for laparoscopic adrenalectomy.Materials and Methods: We analyzed 16 patients who underwent laparoscopic adrenalectomy using the ultrasonic surgical system and compared the results with those of patients undergoing laparoscopic adrenalectomy without the system.Results: The system simplified exposure of the renal pedicles and inferior vena cava, and facilitated adrenal separation from the perinephric fat as well as dissection and identification of the adrenal vessels. Operating time was shorter and blood loss was also less with use of the ultrasonic surgical system.Conclusions: The ultrasonic surgical system simplified laparoscopic adrenalectomy and made the operation much safer.

We report on our experience in telementoring during laparoscopic adrenalectomy. An experienced laparoscopic surgeon supervised a less experienced surgeon from a control room about 100 meter away. Mentoring was accomplished over a fiber optic cable employing real-time video imaging, two-way audio communication, OES ImageTrac Video System used to control the laparoscopic image, and a telestrator. The patient was a 52-year-old male with primary aldosteronism due to a left adrenal adenoma 2 cm in diameter. The procedure was successfully performed in 195 minutes with minimal blood loss. The patient recovered without complications and returned home on postoperative day 7. As broadband telecommunication expands, telementoring will become an important method for the training and supporting of laparoscopic surgery.

Objectives: Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine dehydrogenase (DPD) are thought to be key enzymes in the metabolic pathway of 5-fluorouracil (5-FU). Theoretically, cancer cells which have high TdR-Pase activity and/or low DPD activity should be sensitive to 5-FU. TdR-Pase is also known to have angiogenic activity which helps tumor progression and metastasis. On the other hand, little is known concerning the relationship of DPD activity with clinical malignant potential in renal cell carcinoma (RCC). In this study, we measured both TdR-Pase and DPD activities in surgically obtained RCC tissues and examined the relationship between these enzymatic activities and histological parameters. In addition, the results of in vitro chemosensitivity testing were also analyzed to determine whether TdR-Pase and/or DPD activity in carcinoma cells can predict the efficacy of 5-FU. Methods: RCC tissues from 53 patients were obtained. TdR-Pase and DPD activities were measured by ELISA and radioenzyme assay, respectively. Sensitivity to 5-FU was assessed by histoculture drug response assay (HDRA), an in vitro chemosensitivity test, for 20 of the 53 specimens. Results: Both TdR-Pase and DPD activities of RCC increased with histological grade. There was a significant positive correlation between the TdR-Pase activity and 5-FU sensitivity. In addition, a stronger positive correlation was found between TdR-Pase / DPD ratio and 5-FU sensitivity. DPD exhibited no correlation with 5-FU sensitivity. Conclusions: The activity of both enzymes increased with malignant potential of RCC. TdR-Pase appeared to be the enzyme regulating activation of 5-FU in RCC.

Adrenalectomy was performed on a 37-year-old woman with right adrenal pheochromocytoma. Although the histological diagnosis was benign, telomerase repeat amplification protocol (TRAP) demonstrated positive telomerase activity. Thirty-five months after adrenalectomy, a recurrent tumor was found. Forty-seven months after adrenalectomy, bone metastases also appeared. Malignant pheochromocytoma was clinically diagnosed. Our experience suggests that telomerase-positive tumor cells are highly likely to repeat cell proliferation when they are left in the patient's body, and lead to recurrence. Therefore, telomerase-positive tumors should be clinically treated as malignant even if they have been histologically diagnosed as benign.

BACKGROUND The response of symptoms caused by benign prostate hypertrophy (BPH) to alpha blockade is related to the area density of the smooth muscle of the prostate. If this density could be determined by ultrasound examination, ultrasound might be useful in predicting the efficacy of alpha-blocker therapy. In this study, various ultrasonographic parameters obtained by transrectal method (TRUS) were compared with histologically measured components. METHODS Before surgery, ultrasonic power Doppler imaging (PDI) of the prostate was performed using a transrectal probe. The volume of total prostate, transition zone (TZ), and the presumed circle area ratio (PCAR) [1,2] were calculated. Pulsatile blood flow was recorded, and the resistive index (RI) was calculated. Based on the serum concentration of total prostate specific antigen (PSA), ratio of PSA to prostate volume (PSAD), and ratio of PSA to TZ (PSAT) were calculated. Prostate tissues were obtained from 26 patients undergoing transurethral resection, suprapubic prostatectomy, or radical cystectomy, and were analyzed by quantitative morphometry. Computer image analysis was used to determine the mean area densities of the smooth muscle (SM), connective tissue (CT), glandular epithelium (GE) and lumen (GL), and vascular lumen (V). Correlations between ultrasonographic parameters and morphometric data were studied. RESULTS On microscopic examination, the specimens showed a wide variety, ranging from normal prostate to typical glandular hyperplasia. There was a correlation between RI and the ratios of the four components (SM: r = −0.42 P = 0.034; CT: r = −0.42 P = 0.030; GE: r = 0.42 P = 0.032; GL: r = 0.46 P = 0.018). However, correlations between the other five transrectal parameters and the composition of the prostate were not so clear. This may have been because the blood vessels are compressed within the surgical capsule together with the urethra. CONCLUSIONS The present study demonstrates that when RI is calculated by PDI, it can be quite useful for predicting component ratios, thereby making it possible to predict the therapeutic efficacy of alpha-blockers in individual patients. Prostate 53: 168–174, 2002. © 2002 Wiley-Liss, Inc.

Frequencies of voiding and urinary incontinence are commonly measured by a patient's recall or a diary. The recommended diary length varies from 1 to 14 days, with 7 days apparently being most common. To examine the statistical precision of these different modalities, we analyzed recall data and diary data of 74 patients with urinary frequency, incontinence, or both. Recall data on voiding and incontinence frequency were systematically higher and more variable than diary data. Longer diary length provided less variable diary data. The confidence interval of diary data was calculated by applying the normal distribution to daytime voiding frequency and the Poisson distribution to daytime incontinence frequency. For daytime voiding frequency, the 95% confidence interval was estimated to be (x - 2.65, x + 2.65) (x - 1.53, x + 1.53) (x - 1, x + 1), where x is the 1-day, 3-day, and 7-day diary mean, respectively. For daytime incontinence frequency, the confidence interval depended on both the diary length and the diary mean. It was estimated to be (0, 6.39), (1.72, 4.28), (2.36, 3.64), by using a diary mean of 3 or 1-day, 7-day, and 28-day diaries, respectively. Also, it was estimated to be (0, 1.02), (1.72, 4.28), (7.66, 12.34), when the 7-day diary mean was 0.5, 3, and 10, respectively. Studies with different samples of genuine stress incontinence (n = 37) and urge incontinence (n = 25) confirmed these results. In conclusion, we believe the 7-day diary is highly reliable for estimating voiding frequency and is a reasonable option for predicting incontinence episodes. However, the diary length should be extended in a patient with rarer events of incontinence, and it should be shortened for those who are incontinent more often or who are diagnosed with voiding frequency only.

We report a case and surgical technique of successful sling suspension of insufficient efferent limb of continent urinary reservoir, which has occurred urinary incontinence. A 64-year-old male, who received radical cystectomy with continent urinary reservoir, had been suffered urinary incontinence from the reservoir about one year after surgery. Various procedures, such as the repair of the efferent limb of the reservoir, addition of the ileal patch, instillation of scopolamine, oxybutynin into the reservoir and an injection of GAX collagen in the efferent limb, were not effective for his urinary incontinence. Finally, anti-incontinence procedure of sling at an efferent limb using abdominal rectus muscle fascia was employed and obtained a continence for 2 years after operation. The principle of this surgery is same with that of sling suspension for female stress incontinence. It is advisable for the incontinent urinary reservoir when it has an enough length of efferent limb.

To clarify the characteristics of surgical approaches to laparoscopic adrenalectomy we performed background matched analysis of clinical outcomes of the 3 approaches.From February 1992 to July 2000 we performed 118 laparoscopic adrenalectomies in 115 patients with adrenal tumors. For these operations we used the anterior transperitoneal approach in 46 patients, the lateral transperitoneal approach in 32 and the lateral retroperitoneal approach in 40.To exclude the learning curve effect we eliminated our initial 20 patients treated with the anterior transperitoneal approach. To allow background matching of the 3 groups we also excluded 14 patients with tumors more than 5 cm., 6 who underwent conversion to open surgery and 1 patient who required 5 days of bed rest for retroperitoneal hematoma caused by bleeding from a trocar port. The final analysis included 16, 25 and 36 cases managed via the anterior transperitoneal, lateral transperitoneal and lateral retroperitoneal approach, respectively. Average operative time was significantly shorter for the lateral transperitoneal approach. Postoperative recovery was not significantly different in the lateral transperitoneal and lateral retroperitoneal groups. Postoperative complications included mild paralytic ileus in 2 patients and shoulder tip pain, probably peritoneal irritation due to carbon dioxide insufflation and bowel preparation, in 4 in the transperitoneal groups. Our results imply that the easiest procedure is the lateral transperitoneal approach but the lateral retroperitoneal approach is slightly less invasive.Although it is important to remember that this study was not a prospective randomized trial and, thus, had from certain biases, we believe that if a tumor is more than 5 cm. and/or the surgeon is not yet skilled in laparoscopic adrenalectomy, the lateral transperitoneal approach is the most suitable method. If the surgeon has performed at least 20 operations, the adrenal tumor is unilateral and the lesion is less than 5 cm., the lateral retroperitoneal approach seems to be more suitable because of its minimally invasive nature. The lateral retroperitoneal approach is also preferred in patients with a history of upper abdominal surgery. With improvements in technique and new instruments the time required for the lateral retroperitoneal approach has been significantly decreased.

A 19-year-old woman with von Recklinghausen's disease was referred to our hospital because of right adrenal pheochromocytoma. The tumor was detected incidentally with the abdominal ultrasonography when she complained epigastralgia to the home doctor who treated her hypertension. Plasma and urinary catecholamines level were elevated. The tumor was removed by laparoscopy assisted adrenalectomy without pneumoperitoneum. The resected specimen was 35 x 60 x 75 mm in size and weighed 70 g. Pathological diagnosis was adrenomedullary pheochromocytoma. Postoperative course was uneventful. She has been well with no signs of recurrence after 7.5 years. We reviewed 67 Japanese patients previously reported as von Recklinghusen's disease with pheochromocytoma. Of the 60 patients whose details were described, 16.7% had metastases and pathological malignancy from pheochromocytoma.

Detrusor hyperreflexia (DH) is frequently found in patients with benign prostatic hypertrophy (BPH) and persists in 30–50% of patients after successful removal of bladder neck obstruction by transurethral prostatectomy (TUR-P) or surgical enucleation of the prostate. It would be beneficial for surgeons to be able to identify patients who are at risk of persistent post-operative urinary irritation symptoms and DH. Twenty-three patients who showed DH pre-operatively were included in this study. Of these 23 patients, four had neurogenic bladder because of previous cerebrovascular disease. The other 19 patients were considered to have DH because of BPH. These 19 patients were classified according to their cystometry chart patterns. Pattern 1 was the continual sporadic onset and offset of DH, pattern 2 was a single episode of DH at a bladder volume of 160 mL. Preoperative single-photon emission computed tomography (SPECT) was performed on 14 patients. Cystometric findings at 3 to 6 months after surgery were compared with the pre-operative findings. Four of the six patients with pattern 2 (67%) and all patients with pattern 3 (100%) showed an absence of DH after surgery. In contrast, all five patients with pattern 1 and all four patients with neurogenic bladder showed persistent DH. Compared with pattern 3 patients, pattern 1 patients more frequently complained of urgency before surgery, and their symptoms and uroflowmetry parameters did not improve afterward. Among 14 patients who had pre-operative SPECT, all eight patients with low cerebral blood flow in the frontal region showed persisting DH. Conversely, all six patients with normal SPECT results showed no DH after surgery. When DH occurs repeatedly (pattern 1) or occurs at a bladder volume of

We analyzed the complications of endoscopic adrenalectomy.We retrospectively reviewed the operative and postoperative complications among 75 patients with adrenal tumors who underwent endoscopic adrenalectomy by the same surgeon.Five patients (6.7%) were converted to open surgery. Of these, there were 2 with metastatic adrenal carcinoma, and 1 with adrenal tuberculosis. A total of 21 patients (28%) had 24 complications (32%). There was no mortality. As for access and pneumoperitoneum-related complications, 5 cases of subcutaneous emphysema and 3 of radiating shoulder pain occurred. Intraoperative complications included 2 cases of vascular injury, 2 of organ injury, and 4 of massive bleeding (500 ml). Postoperative complications included 2 cases of mild paralytic ileus, 2 asthma, and 1 each of angina, wound infection, retroperitoneal hematoma, and contralateral atelectasis. Except for the patients with adrenal malignancy and adrenal tuberculosis, 71% of the complications occurred among the initial 25 patients with laparoscopic adrenalectomy and 80% occurred in the initial 10 retroperitoneoscopic patients.Although endoscopic adrenalectomy is a valuable alternative to open surgery, it should be done by a skilled laparoscopist in patients with adrenal inflammatory lesions or malignancy. Careful patient selection and correct choice of surgical approach according to the tumor size and the patient's condition are the most important points for avoiding the complications of laparoscopic adrenalectomy.

We successfully performed a laparoscopy-assisted radical nephrectomy for renal cell carcinoma in 2 patients on long-term hemodialysis. Both tumors were incidentally discovered on screening by abdominal CT scanning. There were no complications during the operation or in the postoperative period, and both patients resumed normal activities by the fifth postoperative day. A laparoscopic-assisted radical nephrectomy may be useful for the treatment of renal cell carcinoma in hemodialysis patients.

We report the clinical outcomes of 2 patients undergoing laparoscopic adrenalectomy for adrenal malignancy. CASE REPORTS Case 1. A 50-year-old woman had Cushing's syndrome due to left adrenal adenoma. Computerized tomography showed a 5 x 4.5 cm. tumor in the left adrenal gland that was slightly irregular (part A of figure). The tumor was removed en bloc without any damage by laparoscopic adrenalectomy. However, local recurrence and abdominal dissemination of the tumor occurred about 19 months after laparoscopic surgery. When the previously resected adrenal specimen was carefully reexamined, the diagnosis was changed to adrenocortical carcinoma. Although combination chemotherapy was administered, the patient died about 3 years aRer the first laparoscopic procedure. 1 Case 2. A 62-year-old man had left adrenal metastasis from poorly differentiated adenocarcinoma of the lung. Magnetic resonance imaging showed a 5.5 X 4.0 cm. tumor in the leR adrenal gland (part B of figure). We attempted to perform retroperitoneal adrenalectomy but the procedure had to be changed to open surgery (en bloc removal with an upper part of the kidney) because of severe adhesions between the kidney and adrenal tumor. The patient died of multiple metastases from lung cancer about 8 months after the surgery.

A 30-year-old man presented at our hospital with microscopic hematuria. Ultrasonography and computed tomography scanning revealed a right adrenal mass measuring 20 × 20mm. The tumor was asymptomatic, but there was obvious accumulation on the right side when scintigraphy was performed with radioactive iodine (131I)-labeled adosterol. Endocrinology studies showed elevation of the plasma cortisol and renin concentrations, while the plasma aldosterone level was low. Right laparoscopic adrenalectomy was done on July 4, 1994. Histologic examination showed an adrenocortical adenoma. Serum levels of adrenocortical hormones were measured before and after surgery, and the tissue content for the same hormones was determined in the resected tumor. The hormonal studies showed that the tumor produced 1 8-hydroxycorticosterone.

PURPOSE Laparoscopic nephrectomy has become widely performed because of its minimally invasive nature. We have performed laparoscopic nephrectomies for non-functioning kidneys and laparoscopy-assisted radical nephrectomies for renal carcinomas. Recently, we have successfully performed laparoscopy-assisted transperitoneal living related donor nephrectomy for kidney transplantation. To determine the efficacy of laparoscopy-assisted live donor nephrectomy, we investigated the clinical results of 2 patients operated upon with this new operation. PATIENTS Case 1 was a 64-year-old healthy male and the left kidney was removed for his son who had a history of 4 months hemodialysis. Case 2 was 67-year-old healthy female who decided to donate her left kidney for her son with the history of 3 years and 2 months hemodialysis. METHODS An upper abdominal midline incision of approximately 10 cm in length was made. Two retractors were attached to either side of the midline incision. The abdominal wall was raised by suspending these retractors from a special hanger. Then three trocars were introduced. The Gerota's fascia was incised and the kidney was suspended by grasping the perirenal fatty tissues. The renal artery and vein were carefully isolated without any manipulations of the kidney (non-touch method). After the transection of the ureter, the renal artery was ligated with a free tie of 1-0 silk and a suture ligature of 3-0 silk and the renal vain was clamped with a Satinski forceps. Immediately after the transection of the renal pedicle, the kidney was irrigated and transplanted to the right iliac fossa of the recipient in the usual fashion. A pen-rose drain was placed in the retroperitoneal space and the posterior peritoneal membrane was completely closed with 3-0 silk interrupted sutures. RESULTS The mean operating time was 298 minutes and the mean blood loss was minimal. The average time of warm ischemia and cold ischemia of the graft were 4.5 minute and 37 minutes, respectively. There were no complications during either the operation or the postoperative period in both patients. The donors began oral intake and ambulation within 48 hours and resumed their normal daily activities by postoperative day 6.5 on average. Postoperative recovery of the patients were far faster than that of the patients receiving open donor nephrectomy. The graft functions were also excellent. The serum creatinine concentration of the recipients fell down to 0.82 mg/dl and 1.02 mg/dl at the third postoperative day. CONCLUSION Laparoscopy-assisted live donor nephrectomy might be advantageous for kidney transplantation because of its minimally invasive procedure.

Background: Glutaraldehyde cross-linked (GAX) collagen has recently become available ds injection material for treatment of urinary incontinence and should be evaluated for its long-term efficacy. Methods: The subjects included 78 females with genuine stress incontinence (GSI) and 19 male or female patients with intrinsic sphincter deficiency (ISD: urinary incontinence due to urethrdl sphincter damage). GAX collagen was injected transperineally or trdnsurethrally through an injection needle under direct endoscopic observation. The efficacy was evaluated by the patients' overall assessment at two years post-treatment. Results: Under local or regional anesthesia, CAX collagen was injected 1.9 times on average (total injection volume: 23.5 mL) in GSJ patients and 2.2 times (40.1 mL) in ISD patients. Improvement at two years post-treatment by patients' assessment was observed in 71.7% of GSI patients and 53.3% in ISD patients. Side effects were urinary retention and difficulty in voiding after 48 of the total of 188 injections (15.5%). a large amount of residual urine in four (2.1%) and miscellaneous in 19 (10.1%), for a short period after injection and were not serious. Conclusion: Our study indicates that GAX collagen injection is an effective, safe and easy non-medical treatment for urinary incontinent patients.

Background: The mechanism of renal stone genesis as well as the location of stone crystal formation in the kidney remains unclear. Possible sites of stone generation are either in the tubular lumen or tubular cell. Methods: We cultured Madin Darby canine kidney (MDCK), LLC-PK1 and Magen Krebs Niigata-28 (MKN-28) cells in DMEM + 10% FBS medium in a well without passage for 30 days. Results: MDCK cells produced microliths at the basolateral side but not on the lumen side of these cells. The other two cell lines did not form microliths. Conclusion: Our data show that microlith formation is a characteristic of MDCK cells and that biological mineralization of MDCK cells may serve as a human urolithiasis model in vitro. The findings support a significant role of the renal distal convoluted tubule and collecting ducts in the in vitro generation of urinary stones.

Purpose To determine the influence of pneumoperitoneum on respiratory function during urological laparoscopic surgery. Materials and methods We performed laparoscopic surgery on 82 patients, 45 of these patients were examined in detail of the effect of pneumoperitoneum on the respiratory function. Of these 45 patients, 14 patients received lymphadenectomy and 31 patients received adrenalectomy. For comparative analysis, 4 patients with laparoscopic cholecystectomies were also examined. Under general anesthesia, carbon dioxide tension (PaCO2) was analyzed before, during, and after the pneumoperitoneum. The data were analysed along with 4 factors; the patient's spirographic parameters, alveolar-arterial gas difference (AaDO2), insufflation pressure for the pneumoperitoneum, and operating time. Result After starting the pneumoperitoneum, PaCO2 levels rose significantly. The PaCO2 levels of patients underwent laparoscopic adrenalectomy were higher than that of patients underwent laparoscopic cholecystectomy. The preoperative vital capacity and forced expiratory volume in one second (FEV1.0) did not show a significant difference of increase in the degree of PaCO2 increase. In contrast, the important factors that were closely related to the elevation of PaCO2 were preoperative AaDO2 and intraoperative insufflation pressure. Patients with high preoperative AaDO2 (> 10 torr) showed a significant increase in PaCO2 levels after pneumoperitoneum. When insufflation pressure was high (> = 10 mmHg), there was a significant rise of PaCO2 after pneumoperitoneum. In all patients whose operating time was 300 minutes or more, high levels of PaCO2 continued on the next day after surgery. Conclusion We should still carefully observe the insufflation pressure, operating time, and other ventilation conditions during laparoscopic surgery.

Ten patients with post-prostatectomy urinary incontinence underwent collagen implantation via the transrectal ultrasonographic guided method. Mean followup was 14 months (range 9 to 18 months). The procedure was performed through the perineum with the patient under local or epidural block anesthesia. The mean amount of collagen implantation was 20.0 ml. (range 10 to 37.5) and the mean number of treatments was 1.5 sessions (range 1 to 3). Results were successful in 6 patients, 1 of whom was completely cured (became dry). There were no marked complications associated with this procedure. We previously performed collagen implantation under cystoscopic observation. However, the ultrasonography guided method allows for the bladder neck to be identified and the needle to be positioned with real-time monitoring. After insertion of a urethral balloon catheter, the bladder neck and needle can be visualized clearly by transrectal ultrasonography. In our series the average amount of collagen injected was less than in the conventional method but the results were superior. In conclusion, transrectal ultrasonographically guided collagen implantation via the transperineal approach may be superior for the treatment of urinary incontinence.

From November 1991 through January 1993, we performed laparoscopic lymphadenectomy on 10 patients. These patients were aged 54 to 77 years. All laparoscopic procedures were performed under general anesthesia. We dissected obturator lymph nodes on bilateral side. Total operation time ranged from 127 to 325 minutes. We could excise 3 to 9 lymph nodes on right side and 0 to 10 lymph nodes on left side. Blood loss was 180 ml in one patient, but minimal in the remaining 9 patients. Ureteral injury occurred during laparoscopic procedure in one patient. This injury could be managed with laparoscopic and cystoscopic procedure. Postoperatively complications were observed in 5 procedures, which consisted of subcutaneous emphysema in 2 procedures, fever (over 38 degrees C) in 2, shoulder and arm pain in 1, ileus in 1. The patient with ileus complained of abdominal fullness but he was able to ingest. All patients resumed their preoperative activity by postoperative day 3 to 5. We believe that this procedure was safe and useful for decision making in the management of our patients. We need further study on indications and techniques for this procedure.

An atrophic right kidney located in the pelvic cavity associated with an ectopic ureter was completely removed from a 4-year-old girl by laparoscopic surgery. There were no serious complications during the operation or the postoperative period. The light shining from the tip of a fine fiberscope inserted into the ureter was used to delineate this structure during laparoscopic surgery.

We characterized the binding affinities of several antimuscarinic agents in human muscarinic receptors.Competitive inhibitory effects of antimuscarinic agents on specific NMS [H] (PerkinElmer Life Sciences, Boston, Massachusetts) binding were examined in human tissue homogenates and in CHO-K1 cell membranes expressing human muscarinic receptor subtypes.Oxybutynin, propiverine, tolterodine, the respective metabolites DEOB, DPr-P-4(N--O) and 5-HM, and darifenacin inhibited in concentration dependent fashion specific [(3)H]NMS binding in homogenates of the human bladder and parotid gland as well as in membranes of CHO-K1 cell lines expressing human muscarinic M(1) to M(5) receptor subtypes. Based on inhibition constant values the inhibitory effects of tolterodine, 5-HM and DPr-P-4(N--O) were 1.4 to 1.7 times greater in the bladder than in the parotid gland, whereas the inhibitory effects of oxybutynin, DEOB, propiverine and darifenacin were 2 to 10 times greater in the parotid gland. Consequently tolterodine, 5-HM and DPr-P-4(N--O) compared with oxybutynin, DEOB, propiverine and darifenacin were found to show 3 to 4 times greater affinity to muscarinic receptors in the human bladder than in the parotid gland. Tolterodine and 5-HM were 2-fold more potent for inhibiting specific [(3)H]NMS binding at cell membranes expressing the M(2) vs the M(3) subtype. Conversely oxybutynin, DEOB, propiverine, DPr-P-4(N--O) and darifenacin showed 2 to 22 times higher affinity to the M(3) than to the M(2) subtype.Compared with oxybutynin, tolterodine, 5-HM and DPr-P-4(N--O) may bind more selectively to muscarinic receptors in the human bladder than in the parotid gland.