Takahide Sugiyama

Randomized, double‐blind, placebo‐ and propiverine‐controlled trial of the once‐daily antimuscarinic agent solifenacin in Japanese patients with overactive bladder

To compare solifenacin succinate (5 and 10 mg once‐daily) to placebo and propiverine hydrochloride (20 mg once‐daily), respectively, in Japanese patients with overactive bladder syndrome (OAB).

EXISTENCE OF A β3-ADRENOCEPTOR AND ITS FUNCTIONAL ROLE IN THE HUMAN URETER

Purpose: We tried to determine the β-adrenoceptor (AR) subtypes distributed in the human ureter and to clarify their functional role in ureteral relaxation.Materials and Methods: 1) Effects of β-AR agonists on either spontaneous or KCl-induced contractions of the human ureter and the antagonism by β-AR antagonists on isoprenaline (a non-selective β-AR agonist)-induced effects were evaluated in vitro. 2) Displacement by β-AR antagonists of [3H]-dihydroalprenolol binding to a membrane preparation derived from human ureteral smooth muscle was evaluated. 3) A reverse transcription polymerase chain reaction assay was performed to determine the expression of the mRNA for β1-, β2- and β3-ARs in human ureteral smooth muscle.Results: 1) Isoprenaline and procaterol (a β2-AR agonist) concentration-dependently suppressed both spontaneous and KCl-induced contractions of the human ureter. The β3-AR agonists, CGP-12177A and CL-316243, also suppressed these ureteral contractions, but dobutamine (a β1-AR agonist) had litt...

Efficacy of Solifenacin on Nocturia in Japanese Patients With Overactive Bladder: Impact on Sleep Evaluated by Bladder Diary

PURPOSE We compared changes in nocturia and sleep related parameters between the anticholinergic solifenacin and placebo in patients with overactive bladder associated with nocturia. MATERIALS AND METHODS We performed subgroup analysis of data from a randomized, controlled trial of solifenacin (5 or 10 mg) in Japan. Men and women 20 years old or older with overactive bladder were eligible for study participation. Patients who voided at least once during the night at baseline and who completed efficacy and quality of life assessment at baseline and 12 weeks (treatment end) were included in analysis. We compared placebo with the posttreatment change in nocturia and daytime frequency, volume voided per micturition, sleeping time, hours of undisturbed sleep and sleep related quality of life. RESULTS Subgroup analysis included 962 patients. Solifenacin 10 mg significantly decreased nocturia episodes by 0.46 episodes (p = 0.0449). Solifenacin 5 and 10 mg significantly increased nighttime volume voided per micturition by 30 and 41 ml (p = 0.0033 and <0.0001, respectively). Compared with placebo (33 minutes) the hours of undisturbed sleep significantly increased by 59 and 60 minutes (p = 0.0196 and 0.0195) in patients with solifenacin 5 and 10 mg, respectively. Significant improvement was observed in sleep related quality of life for solifenacin 5 and 10 mg (each p <0.001). Results must be interpreted with caution due to the exploratory nature of this analysis. CONCLUSIONS Solifenacin 10 mg decreases nocturia episodes. Solifenacin 5 and 10 mg increases nighttime volume voided per micturition and may improve quality of sleep and sleep related quality of life in patients with overactive bladder.

URINARY INCONTINENCE IN SENILE DEMENTIA OF THE ALZHEIMER TYPE (SDAT)

Twenty patients (1 male and 19 females) with senile dementia of the Alzheimer type were studied using cystometry in combination with sphincter electromyography, brain computed tomography (CT) and evaluating the activities of daily life (ADL), with special reference to urinary incontinence. Seven of the patients were continent and the remainder were incontinent. Cystometry revealed uninhibited detrusor contraction in 8 out of the 13 incontinent patients, while no uninhibited contraction was found in 7 continent patients. There was a significant correlation between uninhibited detrusor contraction and urinary incontinence (p 0.05). Brain CT showed that the degree of brain atrophy was more severe in those with uninhibited contraction than those without (p 0.05). There was no clear relationship between sphincter coordination and the occurrence of incontinence. The ADL score tended to be lower in incontinent patients, although no significant difference was apparent (0.05 p 0.1). Uninhibited detrusor contraction and poor ADL functioning caused by brain atrophy are thought to be major causes of urinary incontinence in patients with senile dementia of Alzheimer type.

Clinical Efficacy of Oxybutynin on Sensory Urgency as Compared with That on Motor Urgency

Objective: Anticholinergic drug is widely accepted as an effective medication for frequency, urgency and urge incontinence related to detrusor overactivity (motor urgency). In order to elucidate whether anticholinergic drug is also effective for these symptoms related to bladder hypersensitivity (sensory urgency), clinical efficacy of oxybutynin on sensory urgency was compared with that on motor urgency. Method: Twenty-four patients with sensory urgency, and 53 patients with motor urgency were treated with oxybutynin (6 mg/day) for 4 weeks and subjective and objective efficacies were evaluated. Subjective parameters were quantified with urge score (grade 0–3) and daily numbers of voiding and incontinence. Objective efficacies were evaluated with pre-/ postcomparison of cystometric parameters. Results: Excellent or good overall efficacy was obtained in 62.5% (15/24) of the sensory urgency group and 60.4% (32/53) of the motor urgency group. There was no statistical difference between these two groups. Objective cystometric parameters, bladder volume at first sensation and maximum cystometric capacity, statistically improved after the treatment in both groups. Conclucion: The results suggest that oxybutynin works as well on sensory urgency as it does on motor urgency.

Long-term outcome of the endoscopic correction of vesico-ureteric reflux: a comparison of injected substances.

To summarize the long‐term outcome of endoscopic surgery to correct vesico‐ureteric reflux (VUR) using different injected substances, i.e. autologous blood, hyaluronan/dextranomer copolymer (HDC), PTFE and glutaraldehyde cross‐linked bovine dermal (GAX) collagen.

Sympathetic Skin Response: A New Test to Diagnose Ejaculatory Dysfunction

Sympathetic skin responses were elicited from the palm and sole (plantar) with electrical stimulation on the dorsal nerve of the penis in 24 individuals. The palmar and plantar sympathetic skin responses were obtained in 12 subjects with normal ejaculatory function. On the other hand, the plantar sympathetic skin response was absent in 11 of 12 patients who lacked ejaculation. Since the plantar sympathetic skin response is correlated closely to the mechanism of ejaculation, this test is expected to be helpful to diagnose sexual dysfunction and to monitor the effects of treatment.

Oxybutynin disrupts learning and memory in the rat passive avoidance response

Background: oxybutynin, a drug for pollakisuria and urinary incontinence, has a potent antimuscarinic activity. This study was aimed to determine whether this drug disrupts learning and memory in rats, because antimuscarinic activity in the central nervous system is considered to cause amnesia in humans. Methods: male Wistar rats were given oxybutynin or scopolamine as a reference drug, and subjected to the acquisition trial of step-through passive avoidance response (PAR). Twenty-four hours later the retention test for each rat was performed and the latency time in the PAR was measured. Results: oral administration of oxybutynin at 30 mg/kg or higher and intraperitonial injection of scoplamine at 0.5 mg/kg caused a significant decrease in the latency time in the retention test. Conclusions: oxubutynin caused a decrease in the retention time of the PAR in a manner similar to scopolamine, indicating that oxybutynin may cause disruption of learning and memory.

Endoscopic correction of vesicoureteral reflux in patients with neurogenic bladder dysfunction

Transurethral injection of Teflon paste (TUI) was carried out in 24 ureters of 16 patients with vesicoureteral reflux (VUR) secondary to neurogenic bladder dysfunction at an age ranging from 4 to 77 years, and the results were compared with those of conventional open surgery. During the mean follow-up period of 20.1 months, reflux disappeared in 19 ureters (79%), so that the success rate of endoscopic operation was considered to be satisfactory as compared with that of conventional open surgery, in which reflux disappeared in 16 (80%) of 20 ureters in 16 patients with neurogenic bladder dysfunction at our department. No exacerbation of hydronephrosis was observed postoperatively, and no complication was noted. This procedure, which is minimally invasive and technically simple, may be regarded as the first choice for VUR secondary to neurogenic bladder dysfunction.

Functional electrical stimulation in the management of incontinence: Studies of urodynamics

Intermittent functional electrical stimulation (FES) was employed for the control of incontinence. One FES session lasted for 30 minutes. It was repeated at intervals of 3 days to 1 week via an anal plug electrode.The success rate was 64% in 41 patients with pollakiuria, urgency and/or urge incontinence, and 43% in 7 patients with stress incontinence. Detrusor activity measured by cystometry did not correlate significantly with the effect on subjective symptoms and the urethral pressure did not increase. The remarkable clinical effect was observed in patients with overactive detrusor function.It seems that FES indirectly inhibits detrusor contraction by suppressing the intrasacral pathway for detrusor activity.