Intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity incontinence: do we need urodynamic investigation for outcome assessment?

OBJECTIVE: To evaluate if urinary continence in patients with refractory neurogenic detrusor overactivity (NDO) incontinence after intradetrusor onabotulinumtoxinA injections is sufficient for appropriate outcome assessment or if urodynamic investigation (UDI) is needed. PATIENTS AND METHODS: A consecutive series of 148 patients undergoing intradetrusor onabotulinumtoxinA injections for refractory NDO incontinence were prospectively evaluated. Patients underwent UDI before and at 6 weeks after onabotulinumtoxinA injections. The primary outcome was the prevalence of maximum storage detrusor pressure (Pdetmax storage) of >40 cmH2 O in continent patients at 6 weeks after treatment. The secondary outcomes were treatment effects on other clinical and video-urodynamic variables. RESULTS: At 6 weeks after intradetrusor onabotulinumtoxinA injections, 98 of the 148 patients (66%) with NDO incontinence were continent. Of these patients, 18 (18%, confidence interval 12-27%) had a Pdetmax storage of >40 cmH2 O. Gender, underlying neurological disorder, and high Pdetmax storage before treatment appear to increase the risk of poor urodynamic outcomes. CONCLUSIONS: Urinary continence is not sufficient for outcome assessment after intradetrusor onabotulinumtoxinA injections, as high intravesical pressures threatening the upper urinary tract may be missed in a relevant proportion of continent patients. Therefore, we strongly recommend UDI as a routine part of the follow-up.

Comprehensive Assessment of Compliance with Antimuscarinic Drug Treatment in the Case of Urge Urinary Incontinence of Older Patients.

AIM: To investigate the heterogeneous factors affecting the stability of patients older than 60 years in the UI treatment with Antimuscarinics. BACKGROUND: The prevalence of Urge Incontinence (UI) in older persons reaches 29.3%. The symptoms of urinary incontinence in older people reduce the health related life quality. MATERIALS AND METHODS: In 1257 patients over 60 years (857 (68.2%) women - average age 67.8, 400 (31.8%) men - 71.4), who received AM for one year, demographic, socio-economic and health parameters were studied. OABq-SF questionnaires, MOS SF-36, urination diaries, uroflowmetry, income information from the tax offices and outpatient records were used. RESULT: The compliance to AM treatment within 6 months was retained in 44.2%, and within the year - 26.8% of older patients. At least 40% of the total number of patients refused to continue the treatment for medical reasons. The persons taking Solifenacin (p≤ 0.01), Trospium (p≤ 0.05), or Darifenacin (p≤ 0.05), suffering from severe UI symptoms (p≤ 0.01), and experiencing minor side effects (p≤ 0.01), well-informed about UI treatment methods (p≤ 0.01) prevailed among the treatment compliant patients. At least 20.4% of the patients discontinued their treatment due to economic reasons. The persons with significantly larger annual income (p≤ 0.05) and annual medical cost (p≤ 0.01) prevailed among the treatment compliant patients. About 12.2% of the patients stopped their treatment for reasons related to the social background and psychological status. CONCLUSION: In this experiment, we found that AM treatment compliance in older patients, in addition to medical parameters and health conditions, is largely affected by the economic as well as social, demographic and psychological factors. The study results can be claimed by practitioners involved in correcting UI symptoms in older people.

What is the role of combination drug therapy in the treatment of overactive bladder? ICI-RS 2014.

AIMS AND METHODS: The role of combination therapy using oral antimuscarinic medications for the treatment of overactive bladder was proposed at the 2014 International Consultation on Incontinence-Research Society in Bristol, UK to identify key factors to consider when making clinical decisions and to guide future research design. RESULTS: Combination therapy is justified if monotherapy is associated with suboptimal efficacy or bothersome side effects. Combination therapy has the potential to improve efficacy with fewer side effects than monotherapy. Two Phase 2 studies comparing combination therapy that included an antimuscarinic demonstrated improvement in mean voided volume, the primary outcome chosen, with some combinations showing improved micturition frequency and quality of life. The two studies found no evidence of an increased safety risk with combination therapy compared to monotherapy. Future studies should use clinically meaningful or patient reported outcomes such as incontinence episodes when comparing efficacy. If surrogate measures are used, a clear justification should be provided. Cost analyses should be planned for clinical research trials evaluating combination drug therapy. CONCLUSIONS: Combination therapy is reasonable when monotherapy has suboptimal efficacy or bothersome side effects. Future research studies evaluating combination therapy for urgency urinary incontinence should ideally(1) be performed as part of a randomized clinical trial,(2) evaluate non-responders to monotherapy,(3) evaluate combination therapy using medications with different mechanisms of action,(4) include clinically meaningful and patient reported outcomes when evaluating efficacy, and(5) include cost-effectiveness analyses to justify any increased cost by showing improvement in efficacy or reduction in side effects.

Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis.

CONTEXT: There is a lack of evidence about the efficacy and safety of anticholinergic drugs and about the optimal anticholinergic drug, if any, for the treatment of adult neurogenic detrusor overactivity (NDO). OBJECTIVE: Review the current evidence on the efficacy, safety, and tolerability of anticholinergic drugs in the treatment of adult NDO. EVIDENCE ACQUISITION: A literature search was conducted from 1966 to May 2011. Meta-analysis of all published randomised controlled trials (RCTs) comparing anticholinergic drugs with placebo and comparing different types, doses, and routes of administration of anticholinergic drugs, in adults with NDO, was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The primary outcome was patient-reported cure/improvement of overactive bladder symptoms. Secondary outcomes were quality of life (QoL) changes, bladder diary events, urodynamic outcomes, adverse events, and costs to health services. EVIDENCE SYNTHESIS: A total of 960 patients from 16 RCTs with mean follow-up of 3.8 wk were included. Anticholinergic drugs were associated with statistically significantly better patient-reported cure/improvement (risk ratio: 2.80; 95% confidence interval [CI], 1.64 to 4.77), higher maximum cystometric capacity (weighted mean difference [WMD]: 49.49; 95% CI, 15.38 to 84.20), higher volume at first contraction (WMD: 49.92; 95% CI, 20.06 to 79.78), and lower maximum detrusor pressure (WMD: -38.30; 95% CI, -53.17 to -23.43) when compared with placebo. The dry-mouth rates were statistically significantly higher with anticholinergics, with no difference in withdrawals because of adverse events. There was no statistically significant difference in any of the outcomes between oxybutynin and other anticholinergics or among different doses and preparations of anticholinergic drugs. No study reported QoL changes or costs to health services. CONCLUSIONS: Compared with placebo, anticholinergic treatment in patients with NDO is associated with better patient-reported cure/improvement and significant reduction of maximum detrusor pressure; however, there is a higher incidence of adverse events. None of the anticholinergic drugs or different dosages assessed in this review was superior to another.

Urodynamic assessment of children treated with botulinum toxin A injections for urge incontinence: a pilot study.

OBJECTIVE: This study aimed to investigate changes in urodynamic findings and symptoms after detrusor injections of botulinum toxin A (BTX-A) in children with idiopathic detrusor overactivity (IDO) and urge incontinence. MATERIAL AND METHODS: Eight girls and five boys, aged 7-19 years, who had urge incontinence refractory to scheduled voiding and anticholinergics, were included this prospective study. Urodynamic studies showed postoperative IDO in 12 patients. A dose of 50-100 IU (1.3 -- 4.8 IU/kg) BTX-A was primarily administered at 15-20 detrusor sites. A control urodynamic study was performed within 3 months after the injections. Seven patients had a repeated procedure 16 (range 6-24) months on the average after the first one. RESULTS: Eleven of the 13 patients had daily incontinence and two had incontinence a couple of times a week in association with urge symptoms. Postoperatively, no patient had urinary retention, but one girl had a urinary tract infection 4 months after the therapy. Five patients had a full response, seven partial responses and one no response 1-3 months after the first treatment. After 1 year, three of nine patients still have full response. Maximum cystometric capacity increased after the first treatment from a median of 227 ml to 379 ml (p = 0.005) and the number of patients with uninhibited detrusor contractions more than 30 cmH2O during the filling phase decreased from eight to two out of 13 (p = 0.041). CONCLUSIONS: Intradetrusor BTX-A injections effectively reduce day-time wetting, significantly increase bladder volume and decrease detrusor overactivity in children with urge incontinence refractory to scheduled voidings and anticholinergics.

Uroflowmetric assessment of acute effects of sildenafil on the voiding of men with erectile dysfunction and symptomatic benign prostatic hyperplasia.

PURPOSE: To evaluate the acute effects of sildenafil (50 mg) on the micturation of men with erectile dysfunction (ED) and concomitant benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) using uroflowmetric parameters. MATERIALS AND METHODS: A total of 68 male patients randomized into two groups (36 treatment, 32 control groups) with International Prostate Symptom Score (IPSS) greater than 7 and International Index of Erectile Dysfunction-erectile function domain score lower than 26 were enrolled in the study. Patients in the treatment group received a single dose of 50 mg of oral sildenafil. Patients in the control group received no treatment. Prevoiding urine volumes determined ultrasonographically and voided urine volumes were also recorded. Statistical comparisons were made with the use of analysis of variance (ANOVA). RESULTS: Mean ages were similar between treatment and control groups (60.4 +/- 9.8 and 58.6 +/- 8.3 years, respectively, P = 0.430). In the treatment group the maximum and average flow rates increased significantly (Q (max) from 15.6 +/- 6.8 cc/s to 19.3 +/- 7.2 cc/s, P < 0.0001; Q (avg) from 7.3 +/- 3.0 cc/s to 9.1 +/- 3.0 cc/s, P < 0.0001) with sildenafil administration, while other parameters studied remained unchanged. CONCLUSION: Despite the limitations of variations of uroflowmetry, this study showed that sildenafil improves Q (max) and Q (avg) in patients suffering from ED with concomitant BPH-LUTS. Long-term studies are needed to evaluate the effects on IPSS, side effects, and drug interactions.

Effects of milnacipran and paroxetine on overactive bladder due to neurologic diseases: a urodynamic assessment.

AIMS: To determine the effects of milnacipran hydrochloride, a serotonin-norepinephrine reuptake inhibitor (SNRI), or paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on overactive bladder (OAB) in neurologic diseases, given by objective measures of urodynamic studies. METHODS: This is a prospective open trial, and we enrolled 24 patients (16 men, 8 women; mean age, 63.9 years) with OAB in a neurology clinic. They were randomly allocated into two groups: the milnacipran group (11 patients), and paroxetine group (13 patients). We started with 100 mg/day of milnacipran or 40 mg/day of paroxetine. Before and 3 months after the treatment, we performed a urinary questionnaire and urodynamic studies. RESULTS: Milnacipran reduced daytime urinary frequency (average, from 9.4 to 7.1 times, p < 0.001), improved the quality of life index (p = 0.023), and increased bladder capacity (average, from 289 to 377 ml, p = 0.009) as shown in urodynamic studies. No such changes were noted in the other categories of the lower urinary tract symptoms questionnaire or urodynamic studies, or in the paroxetine group. One male patient complained of mild voiding difficulty. Other adverse effects were not seen during the observation period. CONCLUSION: Milnacipran, an SNRI, increased bladder capacity as shown in urodynamic studies, and thereby ameliorated OAB in patients with neurologic diseases without serious adverse effects.

Comparison of darifenacin and oxybutynin in patients with overactive bladder: assessment of ambulatory urodynamics and impact on salivary flow.

OBJECTIVES: To evaluate the effects of darifenacin, an M3 selective receptor antagonist, compared with oxybutynin, on ambulatory urodynamics, salivary flow, heart rate and visual nearpoint in patients with overactive bladder (OAB). METHODS: A double-blind, randomized, crossover study (n=65) with three treatment cohorts: darifenacin immediate release (IR) 2.5 mg three times a day (t.i.d.) or oxybutynin 2.5 mg t.i.d.; darifenacin controlled release (CR) 15 mg once daily (q.d.) or oxybutynin 5 mg t.i.d.; darifenacin CR 30 mg q.d. or oxybutynin 5 mg t.i.d. Within cohorts, patients received 7 days' treatment with each agent separated by 14 days' washout. RESULTS: All active treatments improved urodynamic parameters. Both darifenacin CR doses had significantly less effect on salivary flow than oxybutynin. Effects on urodynamic parameters, heart rate and visual nearpoint were comparable. CONCLUSION: Ambulatory urodynamics appears to be an innovative and potentially useful investigative tool in the evaluation of the efficacy of new therapeutic agents. Darifenacin CR is an efficacious therapy for OAB with comparable effects on urodynamic parameters but producing significantly less dry mouth than oxybutynin.

Preliminary communication: urodynamic assessment of donepezil hydrochloride in patients with Alzheimer's disease.

BACKGROUND AND AIMS: Donepezil hydrochloride, a central cholinergic drug, is widely used for improving cognitive decline in Alzheimer's disease (AD). We investigated whether donepezil might affect the lower urinary tract (LUT) function in AD. METHODS: Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) (0-70, increase as impairment), urinary questionnaire, and electromyography (EMG)-cystometry were performed in eight patients with AD before and after treatment with 5 mg/day of donepezil. RESULTS: The first assessment (before donepezil) showed moderate cognitive decline in the patients as a mean ADAS-cog score of 27.0 (range: 17-35) (normal < 15). Seven patients had urinary symptoms including urinary urgency incontinence in five. EMG-cystometry revealed neurogenic detrusor overactivity in seven with a mean detrusor pressure of 44.9 cm H(2)O (20-101), mean bladder capacity of 202 ml (20-412), and post-void residuals in none. The second assessment (3 months after donepezil) showed a decrease in the ADAS-cog score to 23.3 (11-35) though without statistical significance. Urinary incontinence disappeared in one and none had a new onset of incontinence. EMG-cystometry revealed an increase in the detrusor pressure on overactivity to 54.1 cm H(2)O (20-122), but also an increase in the bladder capacity to 234 ml (80-400), and post-void residuals in one (40 ml). CONCLUSION: Although the number of our patients was small, it seems possibly that donepezil could ameliorate cognitive function without serious adverse effects on the LUT function in patients with AD.

Renal adenosine A3 receptors in the rat: assessment of functional role.

The functional roles of adenosine A3 receptors in the rat kidney were assessed for the first time with respect to A1 receptor-mediated responses. Utilizing a chronically instrumented conscious rat preparation, we tested renal excretory responses to acute administration of the A3 receptor antagonists 3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1 ,4-(+)-dihydropridine-3,5-dicarboxylate (MRS-1191) and 9-chloro-2-(2-furyl)-5-phenylacetylamino-[1,2,4]-triazolo[1,5-c]qu inazoline (MRS-1220) with reference to the effects of the A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The intravenous administration of DPCPX resulted in significant increases in fluid and sodium excretions without affecting glomerular filtration rate (GFR). This suggests that DPCPX-induced diuretic and natriuretic responses are related to decreased tubular reabsorption. However, neither MRS-1191 nor MRS-1220 alone affected fluid or sodium excretions, or GFR, indicating lack of an effect of either compound on renal function. On the other hand, the co-administration of MRS-1220 with DPCPX abolished both the diuretic and natriuretic responses to DPCPX, being suggestive of antagonism between these two compounds. MRS-1191, however, did not affect the DPCPX-induced fluid and sodium excretions. Neither the A1 nor the A3 receptor antagonists altered potassium excretion individually or in combination. The data suggest that while adenosine A1 receptors are involved in the regulation of renal fluid and sodium transport, A3 receptors do not appear to have a major role in regulation of renal excretory function under baseline physiological conditions.

Urodynamic assessment during intravesical infusion of capsaicin for the treatment of refractory detrusor hyperreflexia.

PURPOSE: Parameters to predict outcome and the urodynamic effects during infusion of capsaicin, seem not to have been assessed in patients with chronic cord injury. We monitored bladder activity urodynamically during infusion of high dosage of capsaicin. MATERIAL AND METHODS: Thirty patients, 18 women and 12 men (average age 29 years, range 20-59 years), suffering from chronic spinal myelopathy, who presented a refractory detrusor hyperreflexia, were studied. They received saline solution containing 10(-3) M capsaicin at a flow rate of 2 ml min(-1) for 15 min (total volume 30 c.c.). The detrusor activity was monitored by a real-time cystometrogram during infusion and 15 min after the end of the infusion itself. New filling cystometrograms were recorded after 30 days and after 6 months. RESULTS: We obtained a clinical and significant urodynamic improvement in 15 of the 30 patients (50%), confirming that intravesical capsaicin may represent a therapeutic option for a selected group of patients suffering from refractory detrusor hyperreflexia due to chronic spinal upper motor neuron lesion. Best results were observed in patients who showed, during the infusion of capsaicin, early uninhibited bladder contractions which disappeared within 10-12 min from the beginning of the infusion (desensitisation). The patients of this group presented a significant increase of mean cystomanometric capacity after 6 months (from 190.7 to 396.7 ml). No significant clinical or urodynamic improvement was observed in the group of patients in whom uninhibited activity of detrusor was recorded for all the time of infusion. CONCLUSION: Our results support the idea of a major complexity of spinal reflex in paraplegic patients and may offer a clue to explain the failure of therapy with capsaicin. The present results support a new approach in the treatment of detrusor hyperreflexia. The ideal dosage and treatment interval are not at present established and further studies are needed to explain substantial differences in the outcome according to different urodynamic responses.

Effects of doxazosin in men with benign prostatic hyperplasia: urodynamic assessment.

OBJECTIVE: In this study, a randomized and placebo controlled trial, we aimed to study the effectiveness and safety of doxazosin based upon urodynamic parameters, especially pressure/flow studies, in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 57 men (29 doxazosin, 28 placebo) 48-82 years of age with BPH were enrolled. Yet, 8 of 29 in the doxazosin group and 10 of 28 in the placebo group were excluded due to side effects of doxazosin and intolerability of urodynamic assessment of free uroflow, postvoiding residual urine volume (PVR) and pressure/flow studies. RESULTS: There were improvements in all urodynamic parameters (Free Qmax: 30.4% and 28%, PVR: 14 ml and 12 ml, invasive Qmax: 29.3% and 26.2%, Pdet at Qmax: -32.7% and -30%, Pdet-max: -29% and -27.7% at end of the 1st and 6th months whereas placebo effects were worsening in all urodynamic parameters. CONCLUSIONS: We suggest that doxazosin is an important treatment option for patients with BPH, and efficacy of doxazosin should be evaluated with objective, quantitative urodynamic studies not with subjective symptom scores. But additional costs and invasiveness of urodynamic studies restrict their common usefulness.

The Hytrin Community Assessment Trial study: a one-year study of terazosin versus placebo in the treatment of men with symptomatic benign prostatic hyperplasia. HYCAT Investigator Group.

OBJECTIVES: To determine the clinical effectiveness and safety of alpha(1)-blockade therapy versus placebo in the treatment of men with moderate to severe symptoms of prostatism in a community-based population under usual care conditions. METHODS: The Hytrin Community Assessment Trial is a prospective, placebo-controlled, randomized, double-blinded, 1-year clinical trial, conducted at 15 academic medical centers (regional sites) and 141 private urology practices (satellite sites). A total of 2084 men at least 55 years old with moderate to severe symptoms of benign prostatic hyperplasia (BPH) as determined by an American Urological Association (AUA) Symptom Score (AUA-SS) of 13 or more points and a bother score (AUA-BS) of 8 or more were enrolled. Randomized patients at regional sites were required to have a peak urinary flow rate less that 15 mL/s with voided volume of at least 150 mL. Treatment with terazosin was initiated with 1 mg daily for 3 days, followed by 2 mg daily for 25 days. Thereafter, patients were titrated stepwise to 5 or 10 mg if they failed to achieve a 35% or greater improvement in the AUA-SS. Primary outcome measures were AUA-SS, AUA-BS, BPH Impact Index (BII), disease-specific quality of life (QQL) score, and treatment failure as defined as discontinuation due to persistent or worsening symptoms or need for surgical intervention for BPH. Secondary outcome measures were peak urinary flow rate and postvoid residual urine volume. RESULTS: AUA-SS (0 to 35 point scale) improved from a baseline mean of 20.1 points by 37.8% during terazosin (n=976) and by 18.4% during placebo (n=973) treatment (P<0.001). Similarly, statistically superior improvements were observed in regard to the AUA-BS, BII, and the QQL score in the terazosin-treated patients. Peak urinary flow rate improved from a baseline of 9.6 mL/s (both regional treatment groups) by 2.2 mL/s in the terazosin group (n=137) and by 0.7 mL/s in the placebo group (n=140) (P< or = 0.05). Treatment failure occurred in 11.2% of terazosin- and 25.4% of placebo-treated patients (P<0.001; Kaplan-Meier adjusted withdrawal rates of 365 days). Withdrawal from study drug treatment due to adverse events occurred in 19.7% of terazosin- and 15.2% of placebo-treated patients (P<0.001). CONCLUSIONS: Terazosin given once daily in a dose ranging from 2 to 10 mg in community-based urology practices under conditions simulating usual care is effective in reducing the symptoms, perception of bother, and the impairment of QQL due to urinary symptoms in men with moderate to severe symptoms of prostatism. This effect is superior to placebo and maintained over 12 months of follow-up. Clinical research outcome studies in BPH can be conducted in community-based practices, thus simulating as closely as possible "usual care" conditions.

Preclinical assessment of a new transdermal delivery system for clonidine (M-5041T).

The effects of a new transdermal delivery system for clonidine (M-5041T) on hypotensive effect, urine volume, plasma renin activity (PRA) and antidiuretic hormone (ADH) in spontaneously hypertensive rats (SHRs) were compared to the effects of the continuous infusion of clonidine. Both M-5041T (1.5 and 4.5 mg/kg) and the continuous infusion of clonidine (250 micrograms/kg/24 h) elicited hypotensive effects persisting for 12 hours or more. These effects were based on consistent plasma concentrations of clonidine. These two treatments produced diuresis followed by antidiuresis, which was remarkably observed by continuous infusion of clonidine. Single subcutaneous injection of clonidine (50 micrograms/kg) produced diuresis accompanied by increases in electrolytes corresponding to plasma levels of clonidine. M-5041T at 1.5 mg/kg did not affect PRA until 12 h, and produced an increase in PRA at 24 h. M-5041T at 4.5 mg/kg and the continuous infusion of clonidine resulted in a decrease in PRA at 2 and 1 h followed by an increase at 12 and 24 h, respectively. M-5041T at 1.5 mg/kg did not affect plasma levels of ADH. Plasma ADH did increase at 2 and 4 h accompanied by diuresis following M-5041T at 4.5 mg/kg or the continuous infusion of clonidine, respectively. Clonidine-induced diuresis was not at least due to the inhibition of ADH release. The decrease in urine volume observed by continuous infusion of clonidine may be due to decrease in renal blood flow based on stimulation of peripheral adorenoceptors of clonidine. These findings suggest that the increases in ADH and PRA are due to the compensatory effects related to both diuresis and the long-lasting hypotensive effect induced by high plasma concentrations of clonidine. Thus, it can be expected that M-5041T at 1.5 mg/kg showing the minimum effective plasma concentration of clonidine will not result in tolerance to the hypotensive effect of clonidine associated with the retention of sodium in SHRs.

Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia: assessment by urodynamic studies.

Thirty-two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an alpha 1-blocker, at doses of 25-75 mg/day for 4-6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001). Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance. A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.

[The information value of rheography and loading tests in the functional assessment of the ureter (experimental research)]. / Informativnost' reografii i nagruzochnykh testov v otsenke funktsii mochetochnika (éksperimental'noe issledovanie).

Functional tests, using electro-ureterography, ureteral rheography, electromanometry and electromagnetic flowmetry in the presence of diuretic and perfusion load tests, were performed at surgery in dogs. Ureteral rheography is shown to be a valuable method for the assessment of ureteral motility (as evidenced by ureteral volume changes), and have certain advantages over other techniques so that it can be used clinically for preoperative functional assessment of ectatic ureters. Load tests are necessary at functional tests of the upper urinary system in order to assess the pattern of ureteral wall contractility and reserves.

Renal toxicity of propyleneimine: assessment by non-invasive techniques in the rat.

The nephrotoxicity of three different dose levels of propyleneimine (10, 20 and 30 microliter/kg body wt) administered intraperitoneally to rats was studied and 20 microliters/kg body weight was found to be the most appropriate sublethal dose. Injection of propyleneimine (10 microliters/kg body wt) produced a small rise in N-acetyl-beta-D-glucosaminidase (NAG) activity, minor histological damage but no change in urine volume. Six rats were injected with 20 microliters/kg body weight, and urine was collected over the following 16 days. An immediate increase in urine volume, osmolality together with a concomitant decrease in specific gravity, was accompanied by a small increase in creatinine excretion and a more marked increase in the sodium and potassium content of urine after the administration of the nephrotoxin. NAG activity increased immediately and peaked on day 3, the activity remained elevated until day 12 when it fell to near normal levels. The activity of both beta-D-galactosidase and beta-D-glucosidase increased 9 days after administration of the nephrotoxin. In contrast, no consistent change was found in the excretion of the brush border marker enzymes, leucine aminopeptidase (LAP), alanine aminopeptidase (AAP) or alkaline phosphatase (ALP). Proteinuria increased sharply the day after injection and remained abnormal. Increased urinary albumin excretion and the predominance of low molecular weight proteins was demonstrated by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. Evidence is presented that propyleneimine exerts its early toxic effect on the renal papilla.

Assessment of the antihypercholesterolemic drug, Probucol, in benign prostatic hyperplasia.

Seventy patients were administered either Probucol, an anti-cholesterol agent or a placebo in a double blind manner for a period of 1 year in an effort to assess the effectiveness of this agent in treating benign prostatic hyperplasia. Sensation of incomplete voiding and peak and mean voiding flow rates showed a trend which indicated a therapeutic effect, however, this effect was comparable for both placebo and the drug group. This is interpreted as indicating the effectiveness of standard urologic therapy, and double blind trials are therefore needed in assessing different agents for the medical management of benign prostatic hyperplasia.