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Background The renal function of the remaining kidney in living donors recovers up to 60~70% of pre-donation estimated-glomerular filtration rate (eGFR) by compensatory hypertrophy. However, the degree of this hypertrophy varies from donor to donor and the factors related to it are scarcely known. Methods We analyzed 103 living renal transplantations in our institution and divided them into two groups: compensatory hypertrophy group [optimal group, 1-year eGFR ≥60% of pre-donation, n = 63] and suboptimal compensatory hypertrophy group (suboptimal group, 1-year eGFR n = 40). We retrospectively analyzed the factors related to suboptimal compensatory hypertrophy. Results Baseline eGFRs were the same in the two groups (optimal versus suboptimal: 82.0 ± 13.1 ml/min/1.73m2 versus 83.5 ± 14.8 ml/min/1.73m2, p = 0.588). Donor age (optimal versus suboptimal: 56.0 ± 10.4 years old versus 60.7 ± 8.7 years old, p = 0.018) and uric acid (optimal versus suboptimal: 4.8 ± 1.2 mg/dl versus 5.5 ± 1.3 mg/dl, p = 0.007) were significantly higher in the suboptimal group. The rate of pathological chronicity finding on 1-h biopsy (ah≧1 ∩ ct + ci≧1) was much higher in the suboptimal group (optimal versus suboptimal: 6.4% versus 25.0%, p = 0.007). After the multivariate analysis, the pathological chronicity finding [odds ratio (OR): 4.8, 95% confidence interval (CI): 1.3–17.8, p = 0.021] and uric acid (per 1.0 mg/dl, OR: 1.5, 95% CI: 1.1–2.2, p = 0.022) were found to be independent risk factors for suboptimal compensatory hypertrophy. Conclusion Chronicity findings on baseline biopsy and higher uric acid were associated with insufficient recovery of the post-donated renal function.

Background Compensation of contralateral kidney function after living-donor kidney donation is well known, and many predictive factors have been proposed. However, no prediction model has been proposed. This study was performed to establish a tool with which to estimate the degree of compensation of the contralateral kidney after living-donor kidney donation. Methods We retrospectively analyzed 133 living donors for renal transplantation in our institution. We defined a favorable compensation as a post-donation estimated glomerular filtration rate (eGFR) at 1 year (calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) of > 60% of the pre-donation eGFR. We analyzed the living donors’ clinical characteristics and outcomes. Results The median (range) donor age was 59 (24–79) years, median (range) body mass index was 22.9 (16.8–32.7) kg/m2, and median (range) body surface area was 1.6 (1.3–2.0) m2. All donors were Japanese, and 73% of the donors were biologically related. The median (range) donor pre-donation eGFR was 108.7 (82–144) ml/min/1.73 m2, and the median (range) post-donation eGFR at 1 year was 86.9 (43–143) ml/min/1.73 m2. Eighty-six percent of donors had compensatory hypertrophy. In the univariate analysis, age, female sex, history of hypertension, body surface area, and pre-donation eGFR were significantly associated with hypertrophy (p

T cell-mediated rejection (TCMR) became controllable, and the long-term renal graft survival came to be obtained by the recent progress and innovation of the immuno-suppressants. Whereas the prophylaxis and control of antibody-mediated rejection (ABMR) caused by donor-specific anti-HLA antibody (DSA) are still insufficient and affect the long-term renal graft survival. DSA was classified roughly as follows: preexisting DSA existed in the patients before renal transplantation (RTx), and de novo DSA produced in the patients after RTx. There are many reports about the effect that preexisting DSA gives to a renal graft, and the treatment for ABMR with preexisting DSA is established to some degree. In contrast to preexisting DSA, it cannot be said that de novo DSA are considered enough at present. In this study, we examined the impact that de novo DSA gave to a renal graft in 40 RTx patients under treatment in our hospital. Although there was no significant difference as to the renal graft function in DSA positive and negative group, the renal graft survival showed the tendency that was better in a DSA negative group than a positive group (85% vs. 55%, P=0.0553). We perform monitoring of the de novo DSA positively and should contribute to the prognosis improvement of the renal graft in future.

(Case 1) A 63-year-old man was diagnosed as retroperitoneal fibrosis by the exploratory laparotomy for the pelvic mass with high IgG4 levels. (Case 2) A 64-year-old man had past medical history of autoimmune pancreatitis which was treated by steroid use. Three years later, he was diagnosed as IgG4-related gallbladder tumor by the cholecystectomy. And, then he was diagnosed as right hydronephrosis with high IgG4 levels. (Case 3) A 71-year-old man was diagnosed as left hydronephrosis and pelvic mass by computerized tomography with high IgG4 levels. We reported three cases of IgG4-related focal retroperitoneal fibrosis. All cases had pelvic mass with high IgG4 levels and were also treated effectively with steroid use. Those symptoms of the patients occurred in close association with IgG4 levels. It is necessary to acknowledge that retroperitoneal fibrosis may have aspects of IgG4-related systemic disease and that the measurement of serum IgG4 should be considered for diagnosing and treating the conditions.

Objectives: We evaluated the effects of age on the prevalence and bothersomeness of overactive bladder (OAB) in female patients with chronic diseases visiting primary care doctors. Methods: We used the pooled data of the SURPRISE survey in which 121 doctors and 1388 female patients aged 40 years or older responded to questionnaires. Results: The OAB prevalence rate in patients was estimated by doctors to be 9.5%. However, the OAB prevalence rate according to patients, as defined by the OAB symptom score, was 22.3%. The rate was increased with age. The number of patients with OAB was much higher than estimated by doctors. Approximately 25% of patients were dissatisfied with their present urinary condition. The rate was increased with age. Dissatisfaction with present urinary condition was strongly correlated with severe urgency score in all age groups. In elderly patients, contribution of urgency incontinence and nocturia to dissatisfaction was also increased. Thirteen percent of patients were receiving treatment for their OAB. However, 15.8% were untreated, regardless of having OAB, suggesting that treated patients comprise less than half of all OAB patients. This tendency was observed in all age groups. In the correlation between satisfaction with pharmacological treatment and each OAB symptom, contribution of urgency to satisfaction with pharmacological treatment was the highest. Conclusion: Urgency is the most bothersome symptom and shows the highest contribution to treatment satisfaction. In elderly patients, urgency incontinence and nocturia are proportionally greater problems. Management of urgency is essential for improving quality of life and satisfaction with treatment in OAB patients.

Calcifying fibrous (pseudo) tumour (CFP) is an uncommon and distinct pathological entity, which is usually occurring in the soft tissue of the extremities, trunk, axilla, pleura, mediastinum and peritoneum. We report a case of CFP of the adrenal gland. A 29-years-old previously healthy woman complained the left lumbago. A solid mass was found on computed tomography on the left adrenal gland. There were no abnormalities in physical examination and laboratory studies. Only urinary noradrenalines and dopamines levels were slightly high. Laparoscopic left adrenalectomy was performed. Pathological findings of the left adrenal tumor showed dense hyalinized fibrous tissue containing bland spindle-shaped cells, calcifications, and lymphoplasmacytic infiltrate. Our case seems to be the first case of CFP to be published in the Japanese literature.

Objective: To investigate the effects of M-1, a major active metabolite of propiverine on the bladder. Methods: We have evaluated the effects of M-1 on the contractions induced by carbachol, KCl, CaCl2, and electrical field stimulation (EFS) in human detrusor smooth muscles, and pelvic nerve stimulation-induced bladder contractions in rats. The effects of M-1 were also compared with the effects of propiverine and tolterodine. Results: Pretreatment with propiverine and tolterodine caused parallel shifts to the right of the concentration-response curves to carbachol. M-1 caused concentration-dependent reduction in the maximum contractile responses induced by carbachol. Although tolterodine did not inhibit the KCl- and CaCl2-induced contractions, M-1 and propiverine significantly inhibited these contractions. In the presence of atropine, M-1 and propiverine significantly inhibited the atropine resistant part of the contraction induced by EFS. On the other hand, tolterodine did not have significant inhibitory effects on atropine resistant contractions. Pelvic nerve stimulation induced bimodal phasic and tonic contractions in the rat bladder. M-1 mainly inhibited the phasic contraction. Tolterodine caused a significant inhibition in the tonic contraction, and propiverine had inhibitory effects on both contractions. Conclusions: The present results suggest that M-1 has inhibitory effects on the bladder smooth muscles through calcium antagonistic action. It is possible that the clinical effects of propiverine on the human bladder are based not only on the action of propiverine itself but also on one of its active metabolites, M-1.

A case of bilateral pheochromocytomas with von Hippel Lindau disease (VHL) is reported. A 32-year-old man visited Kumamoto Red Cross Hospital for further examination of hypertension. Computed tomography revealed bilateral adrenal tumors and noradrenalin levels in serum and urine were elevated. Suspecting bilateral pheochromocytoma, he was reffered to our hospital for further examination and treatment. 131I-MIBG scintigraphy showed accumulation in bilateral adrenal glands. Moreover, he had cerebellar and spinal hemangioblastomas. Bilateral adrenalectomies and left nephrectomy were performed because tumor thrombus extended into the left renal vein, and pathological diagnosis was pheochromocytoma. His sister had been diagnosed as VHL disease. We diagnosed the patient as VHL disease because of the existence of cerebellar and spinal hemangioblastomas, bilateral pheochromocytomas, missense mutation and his family history. This is the eleventh case of bilateral pheochromocytomas with VHL disease reported in Japanese literatures.

Aim: Recent studies have shown that various factors contribute to the increased excitability into the bladder afferent nerves in spinal cord injury (SCI) rats. It has been reported that prostaglandins (PG) act as local modulators of reflex micturition in pathological conditions. In the present study, we measured the amount of PGE2 release from the bladder of chronic SCI rats. Methods: Spinal cord was transected at the level of T8–9 in adult female Sprague-Dawley rats. After 10 weeks, specimens of the urinary bladder were obtained from SCI rats and sham-injured control rats, and bladder strips were dissected from the bladder. Using an muscle-bath technique and a microdialysis procedure, the dialysate, containing substance released from bladder strips, was collected. Then the amount of PGE2 in the dialysate was measured by radioimmunoassay. Results: Excretion of urinary PGE2 was significantly higher in SCI rats than in control rats. PGE2 release from bladder strips was significantly higher in SCI rats than in control rats. Removal of urothelium caused significant decreases in PGE2 release in both control and SCI rats. Stretches of the bladder strips caused significant resting tension-dependent increases in PGE2 release from the strips with urothelium. Conclusions: The present data suggest that bladder urothelium partly contributes to the increase in PGE2 release from the bladder, and that bladder distension may cause increases in PGE2 release in SCI rats.

Objectives To evaluate the non-neuronal cholinergic system in the isolated human bladder. Recently, several reports have demonstrated that non-nerve-evoked acetylcholine (ACh) release may contribute to various pathophysiologic conditions. Methods Human bladders were obtained from 15 patients. Bladder strips with or without urothelium were suspended in an organ bath filled with Krebs-Henseleit solution. ACh release was measured using microdialysis and high-performance liquid chromatography. The contribution of urothelium to non-nerve-evoked ACh release was tested, and the effects of age and elevation of the resting tension (0 to 40 mN) on ACh release were also evaluated. Furthermore, choline acetyltransferase (ChAT) immunohistochemical staining of bladder was performed. Results Immunohistochemistry showed marked ChAT-positive staining in the urothelium and suburothelial region. Tetrodotoxin-insensitive non-nerve-evoked ACh release occurred and was significantly greater in strips with than without urothelium. The non-nerve-evoked ACh release from strips with urothelium increased with age, and the positive correlation between age and release was significant. Stretching of the strips caused increases in non-nerve-evoked ACh release that was significantly greater in strips with than without urothelium. The stretch-induced release of non-nerve-evoked ACh increased with age. Conclusions These data have demonstrated that a non-neuronal cholinergic system is present in the human bladder and that the urothelium/suburothelium partially releases ACh. We found a significant age-related and stretch-induced increase in non-nerve-evoked ACh release. This suggests that the non-neuronal cholinergic system may contribute to the physiology and pathophysiology of human bladder function.

Background: Muscarinic M3 (M3) receptor has been recognized as a major muscarinic receptor for smooth muscle contractions of the urinary bladder. Under the hypothesis that overexpression of M3 receptor in the urinary bladder would enhance urinary bladder contractions, we have transferred the M3 receptor gene into rat bladders using electroporation (EP) and evaluated the functional expression of the transferred gene. Methods: Plasmids expressing luciferase, a green fluorescence protein and M3 receptor were injected into the rat bladder and square-wave electric pulses were immediately applied. Two days after gene transfer, we analyzed gene expression. Immunohistochemical staining was performed and the contractile responses from isolated bladder strips, which were induced KCl, carbachol and electrical field stimulation (EFS), were evaluated. Results: The optimal conditions of electroporation were 8 pulses, 45 voltages, 50 milliseconds/pulses and 1 Hz. Under these conditions, luciferase gene expression was enhanced approximately 300-fold, compared to an injection of DNA only. Regarding immunohistochemistry with an anti-M3 receptor, an increase in immunoactivity was observed in the M3 receptor gene transferred rat bladder, compared to the bladder of the control rat. In rats with the transferred M3 receptor gene, carbachol- and EFS-induced maximum contractile responses of bladder smooth muscle strips significantly increased. Conclusions: These findings suggest that an in vivo EP procedure is an useful method for gene transfer into the bladder and that an overexpression of M3 receptor in the rat bladder enhances bladder contractility. This technique may become a new treatment modality for detrusor underactivity.

Numerous studies have detailed age-related changes in the structure and function of the bladder that may contribute to the high prevalence of overactive bladder (OAB) in the elderly population, but the relation of these changes to OAB symptoms remains unclear. Physiologic and neurochemical studies have been conducted in human detrusor strips obtained from people of different ages, focusing on potential changes in cholinergic and purinergic neurotransmission, as well as the release and actions of acetylcholine (ACh) from nonneuronal bladder cells. Results from physiologic and microdialysis experiments indicate that purinergic transmission increases with age, whereas cholinergic transmission decreases. These effects are most likely because of decreased release of ACh and increased release of adenosine triphosphate (ATP) from postganglionic parasympathetic axons innervating the bladder. Immunohistochemical experiments showed that choline acetyltransferase in the human detrusor is contained not only in parasympathetic axons, but also in cells of the urothelium. The release of nonneuronal ACh increases with age and detrusor stretch. The age-related increase in purinergic transmission in the detrusor and other data indicating that responses to ATP are increased in detrusor overactivity suggest that purinergic receptor antagonists may provide a useful complement to muscarinic receptor antagonists in the treatment of older patients with OAB. Nonneuronal ACh release may play a key role in the storage phase of the micturition reflex, and this may explain, at least in part, the effectiveness of antimuscarinic agents for the treatment of OAB.

Introduction: To investigate the mechanism of voiding dysfunction in non-insulin-dependent diabetes mellitus, we attempted to measure the acetylcholine (ACh) release using an in vivo microdialysis technique and measuring the detrusor pressure after electrical field stimulation (EFS) of the pelvic nerve. Materials and Methods: Eight- and 32-week-old female Goto-Kakizaki (GK) rats (non-insulin-dependent diabetes mellitus model) and age-matched female Wistar rats (controls) were used in this study. The pelvic nerve was exposed on a bipolar platinum electrode to EFS, and a cannula was inserted into the bladder to measure the detrusor pressure. The microdialysis probe was inserted into the bladder wall and was connected to a microinfusion syringe pump. Dialysate was constantly perfused, collected in a microtube, and then injected into the ACh assay system. Histological examinations were performed by staining with hematoxylin and eosin and S-100 immunohistochemical staining in bladder preparations of both GK and control rats. Results: In 8-week-old rats, both detrusor pressures and amounts of ACh release of GK rats were not significantly different from those of control rats. In 32-week-old rats, both detrusor pressures and ACh releases were only significantly increased at 5 and 10 Hz of EFS. In the histological study, the number of nerve fibers or bundles of 32-week-old GK rats was significantly decreased as compared with control rats. Conclusion: The present data suggest that the decrease in EFS-induced ACh release in GK rats, which may be caused by the decreased number of nerve fibers, may contribute to the decrease in bladder contractions.

KRP-197, 4-(2-methylimidazol-l-yl)-2,2-diphenylbutyramide, is a newly synthesized antimuscarinic drug, developed for the treatment for overactive bladder. For evaluation of pharmacological characteristics of KRP-197, we investigated whether it influenced both prejunctional and postjunctional muscarinic receptors on the isolated human detrusor smooth muscles as compared with the effects of atropine, oxybutynin, and propiverine. Using the muscle bath technique, we investigated the effects of various antimuscarinic drugs on the contractions induced by carbachol, KCl, CaCl2, and electrical field stimulation. Furthermore, using high-performance liquid chromatography with a microdialysis technique, we measured the acetylcholine release from the muscle strips during electrical field stimulation. The effects of various antimuscarinic drugs on acetylcholine releases were also evaluated. Pretreatment with various antimuscarinic drugs caused parallel shifts to the right in carbachol-induced concentration-response curves. The rank order of pA2 values was KRP-197 ≧ atropine > oxybutynin > propiverine. Atropine and KRP-197 did not cause significant inhibition of KCl- and CaCl2-induced contractions. All drugs caused concentration-dependent inhibitions in electrical field stimulation-induced contractions. Pretreatment with atropine and propiverine did not cause significant changes in electrical field stimulation-induced acetylcholine release. However, KRP-197, and oxybutynin caused significant decreases in acetylcholine release. The present study demonstrates that KRP-197 has an inhibitory effect on postjunctional muscarinic receptors as well as on prejunctional muscarinic receptors to modulate acetylcholine release in human detrusor smooth muscles. The findings suggest the usefulness of KRP-197 as a therapeutic drug for an overactive bladder with symptoms of frequency, urgency, and urge incontinence.

Objective To evaluate the effects of tolterodine, vamicamide and temiverine, novel antimuscarinic drugs developed for the treatment of frequency and urinary incontinence, on human detrusor smooth muscle. Materials and methods Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy for malignant bladder tumour. Using an organ-bath technique, the effects of various drugs on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in the detrusor strips were investigated. Results Carbachol (0.001–10000 µmol/L) caused concentration-dependent contractions in human detrusor smooth muscles. Tolterodine (0.01–10 µmol/L), vamicamide (0.01–10 µmol/L), temiverine (0.01–1 µmol/L) and atropine (0.001–1 µmol/L) caused parallel shifts to the right of the concentration-response curves to carbachol. All slopes for the regression line of Schild plots were close to unity, and the rank order of pA2 values was atro-pine = tolterodine > vamicamide > temiverine. Tolterodine, vamicamide and atropine did not inhibit the maximum contractile responses to carbachol, while temiverine (10 µmol/L) significantly inhibited the maximum contractions. Tolterodine (0.001–1 µmol/L) and vamicamide (0.01–10 µmol/L) did not inhibit the KCl- (80 mmol/L) and CaCl2-induced (5 mmol/L) contractions, while temiverine (0.01–10 µmol/L) significantly inhibited the contractions. Electrical field stimulation (2–60 Hz) caused frequency-dependent contractions in human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 1 µmol/L atropine, tolterodine and vamicamide did not inhibit the contractions induced by electrical field stimulation at all frequencies, while temiverine (10 µmol/L) significantly inhibited the contractions. Conclusion Tolterodine and vamicamide inhibited contractions of human detrusor smooth muscles only through their antimuscarinic action, while temiverine had both antimuscarinic and calcium-antagonist actions. Furthermore, these novel drugs have different efficacies and potencies for inhibiting human detrusor smooth muscle.

The effects of ovarian hormones on beta-adrenergic receptor-mediated responses in female rabbit detrusor smooth muscles were investigated. Ovariectomized mature female New Zealand white rabbits were untreated or treated with estrogen and/or progesterone for 2 weeks. The contractile responses to carbachol and KCl in the detrusor strips were not significantly different in all groups. As compared with dobutamine and GS-332, isoproterenol and procaterol significantly relaxed the detrusor strips derived from all groups on KCl-induced tonic contractions. Combined with estrogen treatment, isoproterenol, procaterol and GS-332 caused a significant increase in this muscle relaxation. Furthermore, estrogen treatment caused a significant increase in relaxation as a result of forskolin and the cyclic AMP (cAMP) production that was induced by isoproterenol, procaterol and GS-332. However, estrogen treatment did not affect the relaxant response to dibutyryl cyclic AMP. Progesterone treatment did not affect beta-adrenergic receptor-mediated responses. These results suggest that estrogen treatment causes the increased relaxant responses mediated by beta2- and beta3-adrenergic receptor subtypes, which may be related to the increased cAMP content in female rabbit detrusor smooth muscles.

We investigated the presence and subtypes of functionally prejunctional receptors in cholinergic nerve endings of rabbit detrusor smooth muscle strips using high-performance liquid chromatography coupled with a microdialysis procedure. The effects of pretreatment with various drugs on acetylcholine (ACh) release and contractile responses induced by electrical field stimulation were evaluated. Although atropine (a muscarinic nonselective antagonist) and 4-DAMP (a muscarinic M3 antagonist) did not influence the ACh release, they markedly reduced the contractile responses. Pirenzepine (M1 antagonist) decreased ACh release and contractile responses. Methoctramine (M2 antagonist) increased the ACh release, but did not influence to the contractile responses. These results suggest that the muscarinic receptors in the rabbit detrusor smooth muscle are heterogeneous, prejunctional facilitatory (M1 receptors), and inhibitory (M2 receptors) for ACh release and postjunctional M3 receptors mediating contractile responses.

Aims To evaluate the action mechanism of α1-receptor blockers in improving nocturia, we have studied effectiveness of tamsulosin hydrochloride (TAM) in the patients with nocturia associated with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Methods LUTS/BPH patients with nocturia (nocturnal frequency ≥2 times per day) were administered TAM (0.2 mg/day) for 8 weeks. A frequency volume chart (FVC), the International Prostate Symptom Score (I-PSS), quality of life (QOL) index, post-void residual, and uroflowmetry were recorded before and after TAM administration for the patients. The parameters affected by TAM were examined. Results The FVC and I-PSS of the 160 patients analyzed revealed significant clinical improvements in the nocturnal frequency. On the basis of the FVC, the patients were divided into two groups: the responder group comprising 97 patients with significantly improved nocturnal frequency and the non-responder group comprising 63 patients with less improvement in the nocturnal frequency. Significant differences between groups were observed in the following parameters: the hours of undisturbed sleep (HUS), the interval between the time of sleeping and the first instance of nocturnal voiding, the volume of urine in the first nocturnal voiding episode, nocturnal urine volume, nocturnal polyuria index, daytime urine volume, maximum and average flow rates, and post-void residual. Conclusions TAM improved the QOL of LUTS/BPH patients by significantly reducing the nocturnal frequency and increasing HUS; moreover, it improved nocturia by decreasing the nocturnal urine volume. Neurourol. Urodynam. 29:1276–1281, 2010. © 2010 Wiley-Liss, Inc.

To investigate the effects of solifenacin on human detrusor smooth muscles, we evaluate the effects of solifenacin on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation (EFS), and the EFS-induced acetylcholine release from detrusor smooth muscle strips by using the muscle bath and microdialysis technique. The effects of solifenacin were also compared with effects of other antimuscarinic agents (atropine, oxybutynin and propiverine). Pretreatment with various antimuscarinic agents caused parallel shifts to the right of the concentration-response curves to carbachol. The pA2 value of the Schild plots for solifenacin was similar to that for oxybutynin. Atropine did not inhibit the KCl- and CaCl2-induced contractions, while solifenacin, oxybutynin and propiverine significantly inhibited these contractions. EFS-induced contractions were inhibited by various antimuscarinic drugs in a concentration-dependent manner. In the presence of atropine, solifenacin tended to inhibit the residual atropine-resistant contractions induced by EFS, but it was not significant. However, oxybutynin and propiverine inhibited them under the same conditions. Although pretreatment with atropine and propiverine did not cause significant changes in EFS-induced acetylcholine release, solifenacin and oxybutynin caused significant decreases in acetylcholine release. The present results suggest that solifenacin inhibits contractions of human detrusor smooth muscles mainly by the antimuscarinic action and that the high concentration of solifenacin has Ca2+ channel antagonist action. Moreover, solifenacin may block not only postjunctional receptors, but also prejunctional receptors to modulate acetylcholine releases in cholinergic nerve endings in human detrusor smooth muscles. The findings support that muscarinic-receptor-inhibitory actions in human bladder mainly contribute to the usefulness of solifenacin as a therapeutic drug for overactive bladder.

Percutaneous needle biopsy of a transplanted kidney is indicated as a diagnostic procedure in the evaluation of unexplained deteriorated renal function after renal transplantation. This procedure is not always without complications. We report a case of a subcapsular hematoma and hypertension following a percutaneous needle biopsy of a transplanted kidney. The cause of hypertension in this patient and the management of the subcapsular hematoma are discussed.

Tolterodine, (R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine+ ++, is an antimuscarinic drug developed for the treatment of overactive bladder with symptoms of frequency, urgency and urge incontinence. We investigated the effects of tolterodine and its major active metabolite, DD 01 (PNU-200577), (R)-N,N-diisopropyl-3-(2-hydroxy-5-hydroxymethylphenyl)-3-phenylpropa namine, on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation in human isolated urinary bladder smooth muscles, using the muscle bath technique. Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy due to malignant bladder tumor. The detrusor preparations were taken from the intact part of the dome region of the bladder. Carbachol (10(-9)-10(-2) M) caused concentration-dependent contraction of human detrusor smooth muscles. Tolterodine (10(-9)-10(-6) M), DD 01 (10(-9)-10(-6) M), oxybutynin (10(-8)-10(-6) M), propiverine (10(-8)-10(-6) M), atropine (10(-9)-10(-6) M), pirenzepine (10(-8)-10(-5) M), methoctramine (10(-8)-10(-5) M) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (10(-9)-10(-6) M) caused typical shifts to the right of the concentration-response curves for carbachol, except for higher concentrations (10(-5) M) of oxybutynin and propiverine, which caused a decrease of about 30% of the maximum contractile responses to carbachol. All the slopes of the regression lines of Schild plots were close to unity, and the rank order of pA2 values was: atropine = DD 01 = tolterodine = 4-DAMP = oxybutynin > propiverine = pirenzepine > methoctramine. Tolterodine (10(-9)-10(-6) M) and DD 01 (10(-9)-10(-6) M) did not inhibit the KCl-induced (80 mM) and CaCl2-induced (5 mM) contractions, while oxybutynin (10(-8)-10(-5) M) and propiverine (10(-8)-10(-5) M) significantly inhibited the contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent contraction of human detrusor smooth muscles, which were significantly inhibited by various drugs. In the presence of 10(-6) M atropine, tolterodine and DD 01 did not inhibit the residual contractions induced by electrical field stimulation at any of the frequencies, while oxybutynin (10(-5) M) and propiverine (10(-5) M) significantly inhibited the atropine-resistant part of the contractions. The results suggest that the inhibitory effects of tolterodine and DD 01 are mediated only by their antimuscarinic action, which is equal to that of oxybutynin and significantly greater than that of propiverine, and that tolterodine and DD 01 have neither Ca2+ channel antagonist action nor inhibitory effect on the atropine-resistant part of the contractions in human detrusor smooth muscles. These findings support the usefulness of tolterodine as a therapeutic drug for overactive bladder with symptoms of frequency, urgency and urge incontinence.

In the present study, we measured acetylcholine (ACh) released from rabbit detrusor smooth muscle strips induced by electrical field stimulation (EFS) using high-performance liquid chromatography coupled with microdialysis procedure. There were frequency- and duration-dependent increases in contractile response and ACh release. There was a significant, but not simple correlation between EFS-induced contraction and ACh release. Atropine caused a decrease and increase in the contractile response and ACh release, respectively. Pretreatment with propranolol increased ACh release, but pretreatment with phentolamine had no significant effect. These results demonstrate that this method is applicable to direct measurement of ACh release by EFS, and that neurotransmitters other than ACh may relate to EFS-induced contraction. In addition, it is suggested that there are prejunctional inhibitory muscarinic receptors and beta-adrenoceptors, which contribute to ACh release induced by EFS in the rabbit detrusor smooth muscles.