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A contracted noncompliant bladder is an infrequent but severe complication of cutaneous ureterostomy. Recently, we effected a significant increase in bladder capacity by long-term, gentle hydraulic dilation with saline solution plus an anticholinergic drug (emepronium bromide). Based on this experience, we suggest a conservative approach like this before electing a patient for bladder augmentation or permanent diversion for any child with vesical contracture.

Cystometric changes produced by 3 parenterally administered drugs, flavoxate hydrochloride, emepronium bromide and imipramine hydrochloride, have been evaluated in 15 female patients with detrusor instability. Each patient was given 2 of the 3 drugs and cystometric recordings were done 10 and 30 minutes after the administration of each drug. Emepronium bromide was found to be the only drug to cause a significant improvement in bladder capacity and reduction in detrusor pressure.

The effect of emepronium bromide in 13 patients, most of whom had uninhibited bladders, has been studied urodynamically. Under the influence of this drug, the detrusor pressure and the urinary flow was reduced, and abdominal straining during during micturition was commonly recorded. The bladder capacity increased considerably, but all subjects developed residual urine. The effect of emepronium bromide on the bladder capacity seemed to last for a longer period than the effect on the detrusor pressure.

Emepronium bromide and flavoxate have both and separately been used with success in the treatment of detrusor instability. In this study we have combined the two drugs emepronium bromide and flavoxate and compared the results with emepronium bromide. 20 consecutive patients with an uninhibited bladder, 12 men and 8 women, were randomly allocated to treatment with either emepronium bromide/flavoxate or emepronium bromide. In this trial we found that treatment with the combination is significantly better than treatment with emepronium bromide only.

Of 41 children, aged 5-15 years, referred consecutively because of recurrent urinary tract infections (UTIs) and/or enuresis, 18 (44%) showed detrusor instability (DI) in at least 2 of 6 CO2 cystometries. One child was excluded from the study because of lack of follow-up. Four children with less pronounced DI (instability during less than or equal to 50% of the cystometries performed) and frequent UTIs were given antibiotics prophylactically for 3 months. In the remaining 13 children, DI was found during more than half the cystometries performed, and 11 of these children, who also had urge incontinence, were treated with emepronium bromide, 400-600 mg daily (10-12 mg/kg) for 3 months. In 7 of the patients this treatment was supplemented by antibiotics prophylactically because of frequent UTIs. Two children with special problems received other types of treatment. All children were free from symptoms at a clinical check-up 6 months later, 95% confidence limits 0-20%.

Urinary incontinence was treated conservatively in 100 patients. The follow-up period was 12-24 mth. For post-menopausal women, the oestrogen therapy consisted of oral oestradiol valerate or vaginal oestrone sulphate combined with emepronium bromide. In post-menopausal patients the best results were noted when incontinence had begun at the menopause and when the duration of the complaint was not more than 3 yr. For pre-menopausal patients, the treatment given was generally emepronium bromide. During the follow-up period 15 of the patients, 11 of whom were post-menopausal, became symptomless and 77 improved; that is, the incontinence was only slight and occasional. The treatment was without any effect in 8 of the patients. Oestrogen therapy was successful in most post-menopausal women. In these patients, the best results were obtained when the duration of the incontinence was not more than 3 yr.

Today neuropharmacas are a helpful part in the conservative treatment of the neurogenic bladder disorders. They are, or course, no "wonder-drugs" and usually lead to an improvement only of the troubles, but rarely to complete cure. If monotherapy does not lead to the results wanted, one should combine drugs of the same of similar effects but with different pharmacologic targets. A real progress was reached through alpha-receptor-blockers, whose use has, especially in children with myelomeningocele, changed the therapeutic concept in favour of a largely conservative treatment. We already know a number of substances that in one way or other influence the muscles of the bladder and the bladder outlet. If only part of them will reach clinical usage, it can be assumed that the pharmacotherapy will become even more meaningful in the treatment of neurogenic bladder disorders.

63 patients with multiple sclerosis underwent urodynamic evaluation. Hyperreflexia of the bladder was found in 64% and areflexia in 8%. Hypertrophy or sclerosis of the bladder neck (internal sphincter) was detected in 27% of the patients and a spastic external sphincter (dyssynergia) was encountered in 57%. 16 patients were admitted for surgery: 9 for TUR of the bladder neck, 5 for percutaneous selective sacral nerve block, 2 for ileal diversion, 2 for prolonged bladder distension and 1 for nephrectomy for staghorn calculi of the renal pelvis. Highly effective conservative therapy is available in the form of Lioresal for treatment of the hyperactive detrusor muscle and Dibenzyran - an alpha-adrenergic blocking agent - to relieve bladder neck spasticity.

To find out whether Cetiprin reduces the vesical spasms seen after cystotomias, a double-blind investigation including 22 men was carried out. Eleven of the men were given 25 mg Cetiprin i.m. twice a day for 2 days after transvesical prostatectomy, then 200 mg orally 3 times a day the following 12 days. The rest of the men, 11 patients, received placebo. In the Cetiprin group 9 patients had no vesical spasm postoperatively, whereas 1 had moderate and 1 had severe spasms. Only 4 patients were without spasms in the control group, whereas 5 had moderate and 2 severe spasms. The postoperative reduction of the bladder volume were counteracted by Cetiprin. No significant influence on liver- or kidney function was seen with the dosages mentioned.

In a placebo-controlled, randomized, double-blind, cross-over study, terodiline (50 mg/d) was compared with emepronium (600 mg/d) in 20 patients with motor urge incontinence. Evaluation of clinical efficacy was based on changes in micturition pattern, flow measurements, residual urine, cystometry and patient preferences, and safety on adverse reactions, blood chemistry, urine examinations and ECG. The number of voluntary micturitions decreased from a mean of 21.5 per 48 h on placebo by 1.6 on terodiline and 2.8 on emepronium. Involuntary micturitions decreased from 3.6 per 48 h by 1.3 on both treatments (p less than 0.05). The maximal flow rate decreased from a mean of 24.5 ml/sec to 19.6 ml/sec on emepronium and increased to 25.4 ml/sec on terodiline. Residual urine decreased from a mean of 54 ml to 49 ml on terodiline and increased to 60 ml on emepronium. Volume at first desire to void in the supine position increased on emepronium by 44 ml (p less than 0.05) and on terodiline by 3 ml, on the upright position by 11 ml and 18 ml, respectively. Bladder capacity increased in the supine position on emepronium by 32 ml and decreased on terodiline by 8 ml, in the upright position increased by 9 ml and 5 ml, respectively. The bladder pressure at first desire to void in the supine position increased on emepronium by 2 cmH2O, and decreased on terodiline by 2 cmH2O. The intravesical pressure at strong desire to void decreased on emepronium by 6 cmH2O and on terodiline by 7 cmH2O, in the upright position by 2 cmH2O and 1 cmH2O, respectively. 39% of the patients preferred terodiline, 39% emepronium and 22% placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred consecutive female patients with urinary incontinence were investigated with CO2 cystometry including detrusor reflex activation procedures such as postural change and ability to suppress self-induced detrusor contractions. Detrusor hyperreflexia was seen in 20 patients during bladder filling in the supine position, and in an additional 35 patients after detrusor reflex activation procedures. Four different types of detrusor hyperreflexia are described based on the cystometric findings. In 38 patients treated with parasympatholytics, 66% showed a good result independent of the type of detrusor hyperreflexia.

The effect of 4 weeks' treatment with emepronium bromide in 20 incontinent female patients with detrusor hyperreflexia was compared to the effect in 20 patients who did not have uninhibited detrusor contractions during filling cystometry but who were unable to suppress a voluntarily induced detrusor contraction. In both groups, 65% benefited from the drug and no statistically significant differences were seen in the decrease in frequency of voiding and incontinence episodes during treatment. There were no differences between the groups for age, type and degree of urinary incontinence, and radiological findings of bladder suspension defects. In these patients it is important to perform cystometry, including detrusor reflex activation procedures and the testing of their ability to suppress a voluntarily induced detrusor contraction.

A double-blind controlled trial was conducted of emepronium bromide against placebo in elderly mentally ill patients in hospital with urinary incontinence. No significant difference was found between 200 mg emepronium bromide 3-times daily and placebo in treating day-time or nocturnal urinary incontinence for patients suffering from chronic organic brain syndrome or from chronic functional psychiatric illness.

Six elderly volunteers (4 men and 2 women), suffering from urinary incontinence due to small capacity, hyper-reflexic bladders, were assessed cystometrically 1/2 h, 1 h and 4 h after an intramuscular injection of emepronium bromide (Cetiprin). The dose given was sufficient to raise serum levels of emepronium to approximately 10 times those that could be reached with an oral dose. Analysis of the results showed that there was no significant difference in the state of the bladder at any time. The study confirms that emepronium bromide is ineffective in increasing bladder capacity in subjects with small, hyper-reflexic bladders. It has no value, therefore, in the management of urinary incontinence in elderly patients with this condition.

Emepronium bromide, a drug used to control urinary frequency, has been reported as causing oesophageal ulceration but not stricture formation. This paper presents 3 cases in which the use of emepronium bromide preceded development of an oesophageal stricture and suggests that the drug played a causative role.

Eighteen women (median age 54 years, 36-79) with urinary motor urge (n = 13) or sensory urge (n = 5) incontinence were treated for three 2-week periods with emepronium carrageenate (EC) (Cetiprin Novum) in daily doses of 500 and 1000 mg and placebo. Subjectively the women experienced an increased ability to control micturition, i.e. less urge, during EC treatment. Only mild and mainly anticholinergic side effects were recorded, most frequently dryness of the mouth. As regards side effects, the evaluation of objective effects were complicated by a tendency towards carry-over effect to placebo. Placebo in the first treatment periods were analysed solely; no effects of placebo could be demonstrated. Compared with the reference period, decreases in the total number of micturitions (approx. 20%) and in the number of urge incontinence episodes (approx. 75%) were seen. As compared with placebo, a significant increase (approx. 25%) in the average micturition volume could be demonstrated. The percentage urinary excretion of emepronium decreased with increasing oral intake and with advancing age. Probably, an initial daily dosage of 500 mg EC will do well in younger women (less than 50 years), whereas elder patients may need 1000 mg. Further dosage recommendations are given.

In a randomised, double-blind study, 20 women with idiopathic detrusor instability and associated symptoms were treated with terodiline 25 mg bd, placebo, and emepronium bromide 200 mg tds--each drug being given for 3 weeks with placebo as wash-out period before cross-over. The results were evaluated according to drug preference, frequency charts and elimination of detrusor instability on cystometry. Serum levels of both drugs were monitored as control of tablet intake. The preference for terodiline to placebo was statistically significant: 14/3 women (P less than 0.05), and the majority of women (12/4) preferred terodiline to emepronium. Terodiline also gave a small but significant reduction in 24 h micturition frequency and eliminated detrusor instability in almost 50% of the patients (P less than 0.05). Side effects were frequent but mild in all three treatment periods. It was concluded that terodiline offers an alternative in the treatment of female detrusor instability.

75 patients were randomized to be treated with either emepronium bromide (Cetiprin) 200 mg 4 times a day or placebo after transurethral resection of the prostate. The patients were evaluated urodynamically pre- and postoperatively, and further evaluated by micturition symptom charts. No significant differences in symptoms or objective findings were found between the patients treated with emepronium bromide and those treated with placebo.

Seventy-two women with proven detrusor instability completed a novel clinical trial of the new anticholinergic emepronium carrageenate (Cetiprin novum), which allowed for dose titration. The tolerated dose has been shown to correlate with the severity of symptoms. Statistically significant improvement was achieved in symptomatic and urodynamic parameters without serious side effects.

In a randomised double-blind cross-over trial of 19 females with motor urge incontinence but without bladder suspension defect, the effects of 14 days' treatment with emepronium bromide 200 mg qid, flavoxate chloride 200 mg qid or placebo qid were compared by means of micturition charts, the patients' drug preferences and evaluation of side effects. Placebo was the only drug giving rise to a statistically significant decrease in the frequency of voidings, incontinence and nocturia. Forty-seven per cent of the patients preferred placebo and side effects were less frequent during treatment with this medication. No differences could be demonstrated between the effects of emepronium bromide and flavoxate chloride. Perhaps detrusor instability is not always the main reason for the voiding dysfunction in these patients, in whom the effect of placebo was equal or superior to the effect of "active drugs" and superior to no treatment at all.

Symptoms and objective characteristics of 86 female patients with bladder instability and uninhibited detrusor contractions suffering from urgency incontinence were analyzed. The subjective and objective response to a six week-parasympathicolytic treatment with Emepronium-Bromide (Cetiprin) was examined and the results are discussed.

Terodiline has been compared with emepronium in the treatment of 20 women suffering with frequency, urgency and incontinence in a double-blind, two-way cross-over study with fixed placebo as wash-out. A significant number of patients preferred terodiline treatment and a closer correlation between symptomatic and cystometric improvement has been seen during treatment with this drug. Regression analyses indicate that patients with high micturition frequencies (12 to 15 per 24 hours) benefit more from treatment than those with lower frequencies do.

Two female patients were treated because of pollakiuria with emeproniumbromide tablets. They developed extended ulcers of the esophageal mucosa. The tablets had been taken late in the evening with only little fluid. Ulcer formation is thought to be due to prolonged passage time and to a locally damaging effect of the hygroscopic compound. There may be lesions of the esophageal musculature as well, as demonstrated by considerable disturbance of esophageal motility. Ulcers tend to be painfull; they heel fast without formation of scars.

A detailed study and analysis of several hundred cases of motor urge incontinence in the female is presented and summarized. This includes the incidence, the history referring to a questionnaire with a new urge and stress score, the symptomatology, possible etiological factors, the cystometric manifestation and the responsiveness to several treatment modalities and medications. A comparison of flavoxate, emepronium, propantheline and a placebo for the treatment of urinary incontinence due to bladder instability is made, the results are discussed and recommendations are made.

A double-blind study of the short-term effects of intravesically administered emepronium bromide (Cetiprin) versus placebo on bladder spasms after transurethral prostatectomy was done in 40 male patients. In the Cetiprin group there was a significant decline in the need for analgesia, and significantly fewer catheter problems. The use of intravesically instilled Cetiprin is recommended only in cases of severe postoperative bladder spasms.

By use of a sensitive technique, simultaneous registration of intravesical and intra-urethral pressure changes was performed in 14 patients with urgency incontinence before and after intramuscular or oral administraiton of emeprone. The serum concentrations of the drug at different times after administration were also measured. After intramuscular injection, emeprone caused an increased bladder capacity in all the patients, and they experienced urge at larger bladder volumes. The urethral pressure was little affected. Thus, there were no significant changes of the maximum urethral pressure or of the functinal length of the urethra. Eight out of nine patients got a residual urine. After oral administration of emeprone, two out of five patients got an increased bladder capacity, and experienced urge at a larger bladder volume. They had no residual urine. In the patients receiving emeprone intramuscularly, the maximum plasma concentrations ranged from 1171 ng/ml to 378 ng/ml; they were found after 15 or 30 min. After oral intake, the maximum concentrations ranged from 36 ng/ml to 64 ng/ml and were found after 60 to 180 min. The results suggest that emeprone has actions mainly on the bladder; the effects on the urethra seem to be small.

The effect of the anticholinergic agent, emepronium bromide (Cetiprin), was studied in a double blind crossover study of a group of elderly patients with urinary incontinence and uninhibited bladder contractions during cystometry. There was no statistically significant difference between the subjective effect of emepronium bromide and that of placebo, and no change in the cystometric parameters. The overall subjective cure or improvement rate was 79%. The effect of anticholinergic drugs in the treatment of urinary incontinence in elderly patients with uninhibited bladder contractions might to some extent be due to an improvement in the patients' understanding and acceptance of the bladder disorders.

Sixty patients were randomized to treatment with either emepronium bromide (Cetiprin) 25 mg t.i.d. or placebo, both medications administered intramuscularly, after transurethral resection of the prostate. Postoperatively, the number of episodes with vesical tenesms and the need for adjuvant analgesic medication were registered. No significant differences in the number of episodes with vesical tenesms or the need for adjuvant analgesic medication were found between the patients treated with emepronium bromide and those treated with placebo.

A 4-week randomised, double-blind, cross-over study is described which compared the effects of a combination of emepronium bromide and flavoxate hydrochloride with placebo on incontinence and cystometrogram findings in 20 female patients aged 59 to 88 years. All patients initially had detrusor instability demonstrated on cystometrography: 14 patients completed the study; on placebo 10 still had unstable bladders and on active drugs seven were unstable. The number of wettings over a 48-h period before the study commenced and at the end each course of tablets showed no significant differences; also the patients' opinions about the effect on their incontinence indicated that the majority had the same opinion of each course. Active drugs significantly increased residual urine but did not significantly alter the values obtained for maximum cystometric capacity or effective cystometric capacity (the latter volume being maximum cystometric capacity minus the residual urine). No correlation was found, on either course of treatment, between the change to detrusor stability and the amount of improvement in incontinence. Some side effects are described. Despite evidence of a pharmacological effect on the bladder and patients' opinions tending to favour the active combination, nonetheless the main results of this small study do not suggest that the combination of emepronium bromide and flavoxate hydrochloride is an effective treatment of urinary incontinence associated with detrusor instability in elderly women.

Response to oral and intramuscular emepronium bromide was assessed cystometrically in nine patients with urinary incontinence caused by an uninhibited bladder. Oral therapy had no effect, whereas intramuscular administration increased bladder capacity and significantly delayed the onset of bladder spasm and the desire to void. Plasma-propranolol response was delayed and concentrations were reduced after an oral 40 mg dose of propranolol in 3 patients who had received oral emepronium bromide. These results indicate that although oral emepronium bromide had some anticholinergic effect--i.e., in reducing gastrointestinal motility--absorption of an oral dose was not sufficient for the bladder to be affected.

The possibility of a purely local action of intravesically instilled emepronium bromide (Cetiprin) was investigated. Subjective reports and simultaneous urethrocystometry were used to assess such effect. In order to ascertain the purely local nature of effect, the serum was analyzed for freely circulating emepronium ion at increasing intravesical concentrations. No adverse effects were found at the highest dosage (100 mg in 100 ml saline solution), and the concentrations in serum were very low or were not detectable. The seemingly promising influence on micturition frequency and urge prompted a double-blind study of 20 patients with chronic urgency. In ten of them 100 mg emepronium bromide in 100 ml saline solution was instilled intravesically, while the other ten received only the same volume of saline solution. The symptoms were relieved in eight of the ten patients given emepronium bromide. The observation time was one week. The therapeutic possibilities were further evaluated in 24 women with frequency and urgency with or without urge incontinence. Emepronium bromide was intravesically instilled in the mentioned concentration and, if the symptoms were not totally relieved, this was repeated at weekly intervals. The maximum number of instillations was four and the observation time after the final treatment was at least three weeks. Frequency and urgency disappeared in approximately 70% of the affected women, nocturia in 60%, but urge incontinence in only 30%. Both frequency and urgency therefore were therapeutically influenced by intravesical instillation of emepronium bromide.