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PubMed2004

A case for botulinum toxin-A in idiopathic bladder overactivity.

Botulinum toxin (BTX) has been shown to be an effective agent in suppressing detrusor overactivity due to neurogenic causes. Similar to results obtained with traditional agents to treat bladder overactivity (ie, antimuscarinic medications), the use of BTX has been extended to patients with idiopathic detrusor overactivity. This article briefly reviews the use of BTX to treat disorders of detrusor overactivity and, based on early clinical and laboratory results, establishes the case for its use as a therapeutic modality to treat idiopathic detrusor overactivity.

Botulinum Toxins, Type A↗
PubMed2006

Abnormal urethral motor function is common in female stress, mixed, and urge incontinence.

AIM: To investigate the urethral motor function in incontinent women. MATERIALS AND METHODS: The intraurethral pressure was measured continuously in the high-pressure zone of the urethra at rest and during repeated short squeezes around the microtip transducer catheter in a group of 205 women with clinically manifest urinary incontinence (severe), and compared with the findings of investigations in 87 middle-aged women (53-63 years) with treatment naïve incontinence (mild-to-moderate) and healthy controls. RESULTS: Women with established incontinence significantly (P < 0.001) more often (66%) had a pressure fall during or immediately following squeeze than women with treatment naïve incontinence (35%) or asymptomatic women (25%). The acceleration of urinary flow and the maximal flow rate were significantly (P < 0.01) increased in patients with incontinence: acceleration was 13 +/- 2.2 (17.8), 20 +/- 2.8 (18.9), and 32 +/- 4.9 (24.9) degrees (mean +/- SEM; SD) for incontinence, naïve incontinence and no incontinence, respectively; maximum urinary flow rate was 23, 22, and 16 ml/sec. No statistical differences in any of these measures were seen when stress and urge incontinence were compared. CONCLUSION: Women with stress, urge, and mixed urinary incontinence seem to have a primary neuromuscular disorder in the urethra, which presents itself as an overactive opening mechanism with a urethral pressure fall instead of a pressure increase on provocation during the filling phase of the bladder, and during bladder emptying a more efficient opening of the bladder outlet than in normal women. We suggest that one and the same pathophysiological mechanism participates in female stress, urge, and mixed incontinence.

Female↗
PubMed2006

[Overactive bladder: prospects and limitations of botulinum toxin].

Botulinum toxin is the most potent poison known to man. It is produced by Clostridium botulinum and consists of a heavy chain which is responsible for the internalization of the toxin into the cytosol and a light chain that has the ability to cleave proteins within the nerve terminal. As those proteins are essential for normal vesicular transport and fusion of acetylcholine, botulinum toxins are able to prevent its release at the presynaptic membrane, resulting in a chemodenervation of the detrusor muscle after intravesical injection of the toxin and an impressive reduction of symptoms of overactive bladder. Clinical studies show success rates between 60 and 96% for neurogenic and non-neurogenic detrusor overactivity. Thus, application of botulinum toxin to the lower urinary tract appears to be an efficient, safe and minimally invasive procedure.

Administration, Intravesical↗
PubMed1980

Urinary stress incontinence.

The clinical management of urinary stress incontinence requires, firstly, careful evaluation, and then careful individualization of treatment. Much more clinical and basic research is required in order to enhance our better understanding of the causes and treatment of detrusor overactivity.

Animals↗
PubMed2006

The effect of botulinum-A toxin in incontinent children with therapy resistant overactive detrusor.

PURPOSE: We determined the effect of detrusor injection of botulinum-A toxin in a cohort of children with therapy resistant non-neurogenic detrusor overactivity. This prospective study included therapy resistant children with overactive bladder. MATERIAL AND METHODS: During the study period of 19 months 10 boys and 11 girls were included. All patients showed decreased bladder capacity for age, urge and urge incontinence. Main treatment duration before inclusion was 45 months. A dose of 100 U botulinum-A toxin (Botox) was injected in the detrusor. RESULTS: Side effects were evaluated in all 21 included patients. The side effects reported were 10-day temporary urinary retention in 1 girl and signs of vesicoureteral reflux with flank pain during voiding in 1 boy, which disappeared spontaneously after 2 weeks. No further examinations were done since the boy refused. Two girls experienced 1 episode each of symptomatic lower urinary tract infection. Eight girls and 7 boys with a minimum followup of 6 months represent the study group for long-term evaluation. In this study group after 1 injection 9 patients showed full response (no more urge and dry during the day) with a mean increase in bladder capacity from 167 to 271 ml (p <0.001). Three patients showed a partial response (50% decrease in urge and incontinence) and 3 remained unchanged. Eight of the 9 full responders were still cured after 12 months, while 1 of the initially successfully treated patients had relapse after 8 months. The 3 partial responders and the patient with relapse underwent a second injection with a full response in the former full responder and in 1 partial responder. CONCLUSIONS: Botulinum-A toxin injection in children with non-neurogenic overactive detrusor is an excellent treatment adjunct, leading to long-term results in 70% after 1 injection.

Adolescent↗
PubMed2006

Is the short-term outcome of transurethral resection of the prostate affected by preoperative degree of bladder outlet obstruction, status of detrusor contractility or detrusor overactivity?

AIM: The aim of this study was to investigate whether the preoperative degree of bladder outlet obstruction (BOO), detrusor underactivity (DUA) or detrusor overactivity (DO) affected the short-term outcome of transurethral resection of the prostate (TURP) for patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). METHODS: Ninety-two patients with LUTS/BPH aged 50 years or older who were considered to be appropriate candidates for TURP were included in this study. Pressure-flow study and filling cystometry were performed to determine BOO, DUA and DO before TURP. The efficacy of TURP was determined at 3 months after surgery using the efficacy criteria for treatment of BPH assessed by the International Prostate Symptom Score, QOL index, maximum flow rate and postvoid residual urine volume. RESULTS: On preoperative urodynamics, 60%, 40% and 48% of patients showed BOO, DUA and DO, respectively. After TURP, 76% showed 'excellent' or 'good' overall efficacy, whereas only 13% fell into the 'poor/worse' category. The efficacy was higher as the preoperative degree of BOO worsened. In contrast, neither DO nor DUA influenced the outcome of TURP. However, the surgery likely provided unfavorable efficacy for patients having DO but not BOO. Only 20% of the patients who had both DO and DUA but did not have BOO achieved efficacy. CONCLUSIONS: Transurethral resection of the prostate is an effective surgical procedure for treatment of LUTS/BPH, especially for patients with BOO. DUA may not be a contraindication for TURP. The surgical indication should be circumspect for patients who do not have BOO but have DO.

Aged↗
PubMed2004

The association between overactive bladder symptoms and objective parameters from bladder diary and filling cystometry.

AIMS: To investigate the association between overactive bladder symptoms and objective parameters from the bladder diary and conventional filling cystometry. METHODS: We reviewed the records of the 95 consecutive patients presenting at our center for urodynamic investigation. These women were asked to self-complete a questionnaire and a bladder diary for 48 hr. Urogenital symptoms and disease-specific quality of life were assessed with standardized questionnaire, namely the Dutch version of the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ). RESULTS: The frequency symptom as well as the urge incontinence symptom is significantly associated with the presence of detrusor overactivity. In univariate analysis both frequency and urgency symptoms are associated with lower micturition and bladder sensation volumes. In multivariate (ANOVA) analysis, the frequency symptom is associated with a higher 24-hr frequency, lower maximum volume voided, and mean volume voided per micturition on the bladder diary. It is also associated with lower sensation volumes on the filling cystometry. CONCLUSIONS: Of the four symptoms that are currently considered to be part of the overactive bladder syndrome, the frequency symptom is the best associated with objective parameters from the bladder diary, filling cystometry, and with the occurrence of detrusor overactivity. Therefore, we would like to suggest that reporting subjective symptoms frequency is obligatory for considering one to have an overactive bladder.

Adult↗
PubMed2004

The emerging role of solifenacin in the treatment of overactive bladder.

Although antimuscarinic drug therapy has been proven to be effective in the management of patients with symptoms of the overactive bladder syndrome, compliance with medication is often affected by the antimuscarinic adverse effects of dry mouth, constipation, somnolence and blurred vision. The development of bladder-selective M(3)-specific antagonists offers the possibility of increasing efficacy whilst minimising adverse effects. At present there are no M(3)-specific antagonists currently available although solifenacin and darifenacin are both under development and are due to be launched in 2004. The purpose of this article is to review the pharmacology and clinical trial data available for solifenacin, in addition to examining its role in the treatment of the overactive bladder syndrome.

Clinical Trials as Topic↗
PubMed1998

[Intravesical instillation of atropine in treatment of detrusor overactivity in children].

UNLABELLED: We present our own experiences with intravesical Atropine instillation in patients with voiding dysfunction. We used concentration of 10(-6) Atropine in 14 patients with detrusor overactivity. In 12 patients neurogenic voiding dysfunction was caused by a meningomyelocoele. In 2 dysfunction was non-neurogenic. Patients were selected on the base of urodynamic investigation in which low bladder cystometric capacity was caused by detrusor overactivity and poor bladder compliance. This type of therapy was started in patients who had not responded to oral oxybutynin therapy, had major side-effects, or oral therapy had not been possible. All were on clean intermittent catheterisation. The effects on the functional parameters were estimated in urodynamic investigations. With the aim of estimating systemic side-effects blood pressure and heart rate was monitored during Atropine infusion. RESULTS: 6 patients responded to intravesical instillation of Atropine. The increase in bladder cystometric capacity was caused by the decrease in bladder overactivity. No effect on bladder wall compliance was noted. No systemic side-effects were observed. CONCLUSIONS: 1. Intravesical Atropine instillation was useful method of treatment in some patients with detrusor overactivity. 2. No systemic side effects were noted. 3. Because of limited effectiveness and low cost, this method should be considered as an alternative way of decreasing bladder overactivity.

Administration, Intravesical↗
PubMed1988

Long-term follow-up of selective sacral neurectomy.

Between 1976 and 1981, 22 patients underwent selective, complete sacral root section as a treatment for severe detrusor overactivity. Eighteen were followed up for more than 4 years (mean 6.2). Thirteen of the 22 patients had significant symptomatic improvement lasting for more than 4 years post-operatively (59%), 8 of whom had stable bladders. It was concluded that this operation still has a place in the treatment of detrusor overactivity.

Adolescent↗
PubMed2002

Length-dependent regulation of basal myosin phosphorylation and force in detrusor smooth muscle.

Urinary bladder (detrusor) smooth muscle is active in the absence of an external stimulus. Tone occurs even "at rest" during the filling phase, and it is elevated in patients with overactive bladder. This study examined the role of muscle length on tone and the level of basal myosin light chain phosphorylation (MLC(20P)). MLC(20P) was 23.9 +/- 1% (n = 58) at short lengths (zero preload; L(z)). An increase in length from L(z) to the optimal length for contraction (L(o)) caused a reduction in MLC(20P) to 15.8 +/- 1% (n = 49). Whereas 10 microM staurosporine reduced MLC(20P) at L(z), 1 microM staurosporine, a Ca(2+)-free solution, and inhibitors of MLC kinase, protein kinase C (PKC) and RhoA kinase (ROK) did not. However, 1 microM staurosporine and inhibitors of ROK inhibited MLC(20P) and tone at L(o). These data support the hypothesis that a Ca(2+)-independent kinase, possibly ZIP-like kinase, regulates MLC(20P) at L(z), whereas in detrusor stretched to L(o), additional kinases, such as ROK, participate.

Animals↗
PubMed1995

Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability.

Oxybutynin possesses anticholinergic and spasmolytic properties, which together form the basis for its use as a therapeutic option in patients with overactive detrusor function--either idiopathic detrusor instability (DI) or detrusor hyperreflexia. Of the symptoms of detrusor overactivity, urge incontinence is often the most distressing to the patient. Urge incontinence and other subjective parameters (urinary frequency, urgency) improve in tandem with objective (cystometric) measures (maximum detrusor pressure during filling, volume at first desire to void, maximum bladder capacity) in ambulatory, including elderly, patients treated with oxybutynin. However, on the basis of results of limited investigations, the drug appears ineffective in elderly institutionalised individuals. Relative to other anticholinergic drugs, oxybutynin appears at least as effective as propantheline and similar in efficacy to propiverine in small trials, although these results are not definitive. Further investigation of intravesical oxybutynin may lead to this route becoming an option in patients with pre-existing catheters. Adverse effects--dry mouth, constipation, blurred vision--related to the anticholinergic activity of oxybutynin occur frequently and can be sufficiently troublesome to necessitate treatment discontinuation in up to 25% of patients, depending on the dosage. Increases in residual urine volume suggesting urinary retention (undesirable in patients with idiopathic DI), also can develop in some oxybutynin recipients. In summary, oxybutynin is one of the few drugs proven to be beneficial in some patients with overactive detrusor function. Despite the occurrence of unwanted anticholinergic effects in many patients, and apparent lack of efficacy in the elderly institutionalised population, oxybutynin should be considered for the drug of first choice in patients with detrusor overactivity, including the elderly ambulatory population, when pharmacological therapy is indicated.

Animals↗
PubMed2006

How many uncomplicated male and female overactive bladder patients reveal detrusor overactivity during urodynamic study?

OBJECTIVE: We retrospectively evaluated the incidence of detrusor overactivity (DO) in uncomplicated overactive bladder syndrome (OAB) patients. METHODS: From December 1993 to October 2003, 139 adult patients were referred to an urodynamic clinic for urodynamic evaluation of frequency and/or urinary incontinence. Of these, 50 patients (12 males and 38 females) with urgency, without any overt pathological conditions, were retrospectively evaluated in regard to patient age, storage symptoms, urodynamic parameters, and the presence or absence of DO (DO patients or no DO patients, respectively). RESULTS: The overall incidence of DO was 75% (nine of 12 patients) and 36.8% (14 of 38 patients) in male and female patients, respectively. Two of nine male DO patients and five of 14 female DO patients revealed DO after provocative maneuvers. In male patients, all DO patients were OAB wet. In female patients, 13 of 14 DO patients were OAB wet (92.9%), whereas 17 of 24 no DO patients were also OAB wet (70.8%). Compared with no DO patients, female DO patients revealed statistically significant lower maximum cystometric capacity (P = 0.0139) and lower vesical compliance (P = 0.0002). Although aged 60 years or more was associated with DO in univariate analysis in female patients, any symptoms, even incontinence, were not associated with DO in both sexes. CONCLUSION: It is supposed that, in contrast to male OAB, DO might not be a major underlying cause of uncomplicated female OAB.

Aged↗
PubMed2004

The inhibitory role of melatonin on isolated guinea-pig urinary bladder: an endogenous hormone effect.

OBJECTIVE: To investigate the effects of melatonin, an endogenous hormone, on acetylcholine and KCl-induced contractions of isolated guinea-pig detrusor muscle. MATERIALS AND METHODS: Detrusor smooth muscle strips isolated from guinea-pig bladders were placed in an organ bath containing physiological saline at 37 degrees C and pH 7.4, constantly bubbled with 95% oxygen and 5% CO2. The effects of cumulatively applied melatonin on the acetylcholine- and KCl-induced contractions of isolated bladder strips were examined using isometric contraction measurements. RESULTS: Melatonin (100 and 300 micromol/L) significantly inhibited the peak amplitude of both acetylcholine (10 micromol/L) and KCl (30 mmol/L)-induced contraction of the isolated bladder strips (P < 0.05). Similarly, melatonin caused a significant reduction in the contractile frequency induced by KCl (eight strips) in a concentration-dependent manner, while having no significant effect on the frequency of contractile response to acetylcholine, even at the highest concentration (300 micromol/L) used (P = 0.58, 14 strips). CONCLUSIONS: These results suggest that melatonin inhibits acetylcholine- and KCl-induced contractions in isolated bladder strips from guinea pigs. The endogenous nature of melatonin, with its low side-effect profile, makes it a potentially useful agent to be considered in the medical management of the overactive bladder.

Animals↗