recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH 2 O detrusor pressure (C dp40 ) and a systolic BP of >140 mmHg or diastolic BP of >90 mmHg (C HT ). RESULTSThere was an increase in BP and a decrease in heart rate in all patients during bladder filling before capsaicin treatment. Instillation of capsaicin produced a significant increase in both systolic and diastolic BP and a significant decrease in heart rate. The maximum cardiovascular effects were at 5-10 min after instillation and gradually returned to baseline within 40 min. The vehicle had negligible effects on either BP or heart rate. After capsaicin treatment, the responses of BP and heart rate to bladder distension were significantly reduced. Both serum catecholamine values and the blood ethanol concentration remained within normal limits. The mean (range) follow-up after the first treatment was 15 (6-30) months. One month after treatment all seven patients became continent and their episodes of AD became negligible and well tolerable between catheterizations (for 3-4 h); the effects lasted for ≥ 3 months in all. MCC was significantly increased at 4 weeks and 3 months, and UICmax significantly decreased at 4 weeks after treatment. Both mean C dp40 and C HT increased 1 week, 1 and 3 months after treatment. Two patients received a second instillation, and have been continent with no symptomatic AD for 6 and 24 months. The remaining five patients have been continent with no symptomatic AD for 6-12 months. CONCLUSIONThese results indicate that intravesical capsaicin, but not the vehicle, acutely triggers AD in patients with SCI, suggesting involvement of bladder capsaicin-sensitive afferents in AD in these patients. The results also suggest that intravesical capsaicin may be a promising therapy for both AD and DH in such patients. Further long-term follow-up studies are needed to evaluate the duration of its effect. KEYWORDS autonomic dysreflexia, capsaicin, detrusor hyper-reflexia, spinal cord injury OBJECTIVESTo determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). PATIENTS AND METHODSSeven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyperreflexia (DH) were enrolled. Under general anaesthesia, capsaicin solution (100 mL of 2 mmol/L in 10% ethanol) was instilled in the bladder and retained for 30 min. The patients were assessed by medium-fill cystometry (CMG) just before and 50 min after the capsaicin treatment. Intra-arterial blood pressure (BP) and heart rate were monitored continuously throughout the procedure; 10% ethanol was instilled before capsaicin treatment in four patients as a control. Serum catecholamines were measured during bladder filling and capsaicin treatment, and the blood ethanol concentration also measured after instillation in all patients. The CMG with concomitant...

Abbreviations & AcronymsObjectives: To investigate whether the anticholinergic agent, propiverine hydrochloride, is clinically effective for stress urinary incontinence. Methods: The participants were adult female patients with the chief complaint of stress incontinence. Propiverine (20 mg once daily) was given for 8 weeks. If the response was inadequate after 4 weeks of treatment, the dose was increased to 40 mg/day. Before and after 4 and 8 weeks of treatment, lower urinary tract symptoms were assessed. The urethral pressure and blood catecholamine levels were also measured. Results: A total of 37 patients (mean age 69 ± 11 years) were enrolled, including 15 patients with stress incontinence and 22 with mixed incontinence. The number of episodes of stress incontinence decreased significantly from 2.6 ± 2.3 times per day to 1.3 ± 2.2 times per day after 4 weeks, and 0.4 ± 0.6 times per day after 8 weeks. The daytime and night-time frequency of urination, and quality of life score showed significant improvement. The maximum urethral closing pressure and the functional urethral length increased significantly after treatment, but blood catecholamine levels, blood pressure and pulse rate at 8 weeks were not significantly different from those at baseline. Conclusions: Propiverine could be an effective drug for stress urinary incontinence by increasing urethral closing pressure without increasing blood catecholamine levels.

TZT-1027 is a novel anticancer agent that inhibits microtubule polymerisation and manifests potent antitumour activity in preclinical models. We have examined the effect of TZT-1027 on cell cycle progression as well as the anticancer activity of this drug both in vitro and in vivo. With the use of tsFT210 cells, which express a temperature-sensitive mutant of Cdc2, we found that TZT-1027 arrests cell cycle progression in mitosis, the phase of the cell cycle most sensitive to radiation. A clonogenic assay indeed revealed that TZT-1027 increased the sensitivity of H460 cells to g-radiation, with a dose enhancement factor of 1.2. Furthermore, TZT-1027 increased the radiosensitivity of H460 and A549 cells in nude mice, as revealed by a marked delay in tumour growth and an enhancement factor of 3.0 and 2.2, respectively. TZT-1027 also potentiated the induction of apoptosis in H460 cells by radiation both in vitro and in vivo. Histological evaluation of H460 tumours revealed that TZT-1027 induced morphological damage to the vascular endothelium followed by extensive central tumour necrosis. Our results thus suggest that TZT-1027 enhances the antitumour effect of ionising radiation, and that this action is attributable in part to potentiation of apoptosis induction and to an antivascular effect. Combined treatment with TZT-1027 and radiation therefore warrants investigation in clinical trials as a potential anticancer strategy.

ABSTRACT:This study was performed to investigate the effects of goshajinkigan, a traditional Chinese herbal mixture, in conscious rats undergoing continuous cystometry.Systemic resiniferatoxin (RTX) pretreatment can block resiniferatoxin-sensitive (C-fiber) nerve-mediated bladder overactivity, such as that induced by intravesical administration of acetic acid. The effects of pretreatment with goshajinkigan and resiniferatoxin (RTX) alone or in combination on acetic acid-induced bladder overactivity in conscious rats were also compared. Female SD rats were divided into 4 groups. Group (1), (3) received normal food for 4 weeks, while groups (2) and (4) received goshajinkigan (0.09 g/kg/day) during the same period. Two days after bladder catheterization, groups (3) and (4) received RTX (0.3 mg/kg) injection, while groups (1) and (2) received vehicle alone. Cystometric investigations were performed on all animals 24 h after RTX or vehicle injection. The effects of intravesical instillation of acetic acid (pH=4.0) were compared with those of intravesical saline. Goshajinkigan significantly increased threshold pressure, voiding interval, micturition volume, and bladder capacity. Intravesical instillation of acetic acid induced bladder overactivity in both normal rats and in those pretreated with goshajinkigan. However, the effects of acetic acid on voiding interval and micturition volume were significantly different between rats given normal diet and those pretreated with goshajinkigan. The effect of acetic acid was not different between goshajinkigan-and RTX-pretreated rats. The results of the present study indicated that goshajinkigan increases voiding interval, micturition volume, and bladder capacity, and pretreatment partially blocks the bladder overactivity induced by intravesical administration of acetic acid in rats.

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