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PubMed2006

Treatment-resistant detrusor overactivity--underlying pharmacology and potential mechanisms.

Bladder function during filling and micturition is regulated by peripheral and central nervous and hormonal control systems. Micturition occurs in response to afferent signals from the lower urinary tract, and distention of the bladder wall is the primary stimulus. In the animal and human bladder, efferent adrenergic, cholinergic and nonadrenergic, noncholinergic (NANC) neurotransmission has been demonstrated. The most important receptors for activation of contraction are muscarinic (M3) and purinergic receptors (P2X1), however, the contribution of these receptors to contraction may differ between species, and may be changed in bladder dysfunction associated with detrusor overactivity (DO) and/or the overactive bladder (OAB) syndrome, such as outflow obstruction, neurogenic bladders, idiopathic DO and diabetes. The NANC component of the nerve-induced response in such disorders may be responsible for up to 40-50% of the total bladder contraction. Whether this in vitro'atropine-resistance' corresponds to DO/OAB seen in patients not responding to antimuscarinic treatment is not known. Afferent signalling from the urothelium may be involved in both normal bladder function and in DO/OAB, but its role in antimuscarinic-refractory patients remains to be established. Several central nervous system (CNS) transmitters/transmitter systems, including gamma aminobutyric acid (GABA), opioid, serotonin, noradrenaline, dopamine or glutamatergic receptors and mechanisms are known to be involved in micturition control. The contribution of these receptors and mechanisms in DO/OAB resistant to treatment with antimuscarinics is not known, but drugs acting at these sites may offer future treatment possibilities.

Animals↗
PubMed2005

Detrusor overactivity and urge urinary incontinence [corrected] following midurethral versus bladder sling procedures.

OBJECTIVE: The objective of the study was to compare detrusor overactivity and urge urinary incontinence rates after midurethral slings versus bladder neck slings. STUDY DESIGN: Three hundred forty subjects underwent midurethral slings or bladder neck slings. Comparisons were made using Student's t test and chi2 test. Multivariate analysis was performed to detect confounding factors. RESULTS: More patients in the midurethral sling group resolved detrusor overactivity than in the bladder neck sling group (38% versus 15%, P < .001). In addition, subjects in the midurethral sling group had significantly lower rates of de novo detrusor overactivity than subjects in the bladder neck sling group (29% versus 62%, P = .002). The only significant predictors of postoperative detrusor overactivity were preoperative detrusor overactivity (P < .001) and sling type (P < .001). After adjusting for preoperative detrusor overactivity, bladder neck slings significantly increased the risk for persistent detrusor overactivity (odds ratio 3.9). CONCLUSION: Midurethral slings have increased rates of resolution of detrusor overactivity and lower rates of de novo detrusor overactivity than transvaginal bladder neck sling procedures.

Aged↗
PubMed2003

Overactive bladder symptoms: do we need urodynamics?

AIMS: The aim of our study was to determine whether the urodynamic diagnosis is useful in the management of women with symptoms of an overactive bladder (OAB). METHODS: Women with lower urinary tract symptoms, attending a tertiary referral urogynaecology clinic were studied. All women were fully evaluated, with history, urinary symptoms questionnaire, frequency-volume chart, vaginal examination, and videocystourethrography. Women with symptoms consistent with an overactive bladder (urinary frequency, urgency, and/or urge incontinence) were selected. Women with neurological disorders were excluded. Finally, urinary symptoms and urodynamic diagnosis were correlated. All terms and definitions are in accordance with the International Continence Society [Abrams et al., 1988, Scand J Urol Nephrol 114(Suppl):5-19.]. RESULTS: A total of 4,500 women 22-73 years of age were studied. Only 843 women (18.7%) could be classified as having an OAB. Of these, 457 women (54.2%) had urodynamically proven detrusor instability, whereas 386 women (45.8%) had a stable urodynamic trace. Sixty-eight (8.1%) of the women studied had postvoid residual greater than 100 mL. Of the 4,500 women studied, 1,641 (36.5%) had detrusor instability on laboratory urodynamics. Only 27.5% of these women (457 of 1,641) had OAB symptoms. CONCLUSIONS: Symptomatic diagnosis of OAB does not correlate with a urodynamic diagnosis of detrusor instability. The diagnosis of overactive bladder based on urinary symptoms underdiagnoses the condition of detrusor instability in a population of women suffering from lower urinary tract symptoms. Therefore, symptomatic diagnosis of OAB alone is not recommended. Our study suggested that urodynamic evaluation is mandatory in the management of the women with symptoms of an overactive bladder.

Adult↗
PubMed2006

Refractory neurogenic detrusor overactivity.

Refractory neurogenic detrusor overactivity refers to the clinical condition that is no longer manageable by anticholinergic therapy. This condition represents a formidable task to caregivers because the treatment of urinary incontinence and adequate protection of the upper urinary tract become extremely difficult. Treatment options for refractory neurogenic detrusor overactivity include detrusor injections of botulinum toxin and intravesical instillation of vanilloid compounds, mainly resiniferatoxin, or anticholinergic drugs. If these options fail, bladder augmentation or sacral anterior root stimulation offers excellent outcomes, although at much higher costs and risks to the patients.

Botulinum Toxins, Type A↗
PubMed2006

Mild brain ischemia produces bladder hyperactivity without brain damage in rats.

INTRODUCTION: The influence of brain ischemia without cerebral infarction on voiding function is unknown. To investigate the effects of a reduction in cerebral blood flow on voiding function, the influence of chronic cerebral hypoperfusion (CH) on bladder activity was examined in rats. MATERIALS AND METHODS: CH was induced in each of 11 female Sprague-Dawley rats by anastomosis between the right external jugular vein and the right common carotid artery with partial obstruction of the left common carotid artery. Twelve intact animals comprised a control group. Voided volume per micturition was assessed in a metabolic cage for 24 h on weeks 2, 4, and 8. Eight weeks after the operation, the rats were tested in a hippocampus-related learning paradigm, the Morris water maze. Bladder activity was monitored in 13 rats with continuous infusion cystometrography (CMG) at 2 weeks. After evaluation, the rats' brains were stained by perfusion with 2% 2,3,5-triphenyltetrazolium chloride (TTC). RESULTS: Voided volume per micturition was significantly reduced and voiding frequency was significantly increased in CH rats 2 weeks after CH as compared to the control group (p < 0.05). Bladder capacity on CMG of CH rats was significantly reduced 14 days after CH as compared to the controls (p < 0.05). Although TTC staining of the CH rat brain did not show cerebral infarction, CH induced impairment of water maze learning. CONCLUSIONS: These results indicate that mild forebrain ischemia without infarction results in the development of bladder hyperactivity and impairment of memory. Mild brain ischemia with aging may induce bladder overactivity in humans. Further studies of the nervous system related to bladder hyperactivity using this animal model may lead to pharmacological therapy or prevention of bladder overactivity in the aging individual with an unidentified origin of voiding dysfunction.

Animals↗
PubMed2006

Epidemiology, prescribing patterns and resource use associated with overactive bladder in UK primary care.

This study aimed to estimate the incidence and prevalence of overactive bladder (OAB) symptoms in the UK and analyse the use of anticholinergic/antispasmodic medications and other healthcare resources within UK general practice. Patients with a record of urinary frequency, urgency, nocturia, urge incontinence or irritable/unstable bladder between 1987 and 2004 were identified from the General Practice Research Database. Demographic characteristics, referrals, consultations, investigations and prescriptions for medications licensed for use in OAB were identified. Regression analyses were used to identify the factors determining switches between medications, referrals and use of healthcare resources. The overall prevalence of OAB-related symptoms was 3.87 per 1000 persons, with an incidence of 2.79 per 1000 person-years. Among 68,910 patients with OAB symptoms, 19,444 (28.2%) received anticholinergic medication, of whom 14,454 (74.3%) received one drug and 4055 (20.9%) received two medications sequentially. Overall, 59.1% of patients were referred to relevant secondary care specialities, 2.8% underwent urinary tests/investigations in primary care and 0.2% were seen by a continence nurse. Resource use was higher among patients who tried several different medications. In conclusion, this study suggests that OAB may be under-diagnosed in the UK and that current guidelines recommending use of anticholinergic medication, continence nurse consultations and urinary tests/investigations are inadequately followed.

Cholinergic Antagonists↗
PubMed2006

Overactive bladder: prevalence and implications in Brazil.

OBJECTIVES: To assess overactive bladder (OAB) prevalence, associated factors and implications in a young population. METHODS: An independent population-based study was carried out. A self-applicative questionnaire covering urinary symptoms, coping strategies, quality of life and treatment seeking behavior was developed. RESULTS: A total of 848 subjects between 15 and 55 years completed the questionnaire. The overall prevalence of OAB was 18.9%. Women were significantly more affected than men (p = 0.001). All age groups were equally affected (p = 0.152). Subjects with OAB reported significant impairment on household chores (p = 0.009), physical activities (p = 0.016), sleep (p < 0.001), work (p < 0.001), social life (p < 0.001) and sexual life (p < 0.001). In addition, OAB individuals present higher prevalence of depression (p = 0.036), anxiety (p < 0.001), shame (p < 0.001) and tiredness (p < 0.001) OAB was independently associated to sexual life impairment (OR = 3.36, 95% CI=1.20-9.39). Only 27.5% of OAB subjects sought for medical counseling. CONCLUSIONS: OAB is a highly prevalent condition, even in such a young population. It affects both genders, yet it is more frequently observed in women. OAB is an important health condition, with serious impact on quality of life and sexual function. A large percentual of individuals remain unrecognized, under treated and consequently suffer for long periods of time.

Adult↗
PubMed2005

Pelvic floor symptoms and lifestyle factors in older women.

OBJECTIVES: To measure the prevalence of pelvic floor symptoms in noncare-seeking older women and the association between symptoms and lifestyle factors. METHODS: Women enrolled at one site of the Women's Health Initiative Hormone Therapy clinical trial completed a questionnaire, modified from the Pelvic Floor Distress Inventory, on bladder, bowel, and prolapse symptoms. Individual symptoms and symptom groups were examined in a cross-sectional analysis. RESULTS: In the 297 women who participated, mean age was 68.2 years, mean body mass index (BMI) was 30.2 kg/m(2), and median vaginal parity was 3. The median number of symptoms endorsed was 3 (range 0-18). The most prevalent symptoms were stress urinary incontinence (51.2%), urge urinary incontinence (49.2%), urinary frequency (29.0%), straining for bowel movements (25.0%), a sense of incomplete bowel movements (34.8%), and involuntary loss of gas (33.0%). The symptom groups most frequently endorsed were stress urinary incontinence, overactive bladder, obstructive voiding, and obstructive colorectal groups (>/=1 symptom per group in 51.2%, 61.3%, 40.8%, and 48.3%, respectively). In analyses adjusted for age, BMI, caffeine ingesting, smoking, and exercise, older women more frequently reported incomplete bladder emptying (adjusted OR 3.4, 95% CI 1.3, 9.2), weak urinary stream (adjusted OR 6.4, 95% CI 2.0, 20.0), intermittent urinary stream (adjusted OR 4.0, 95% CI 1.6, 10.4), and a feeling of incomplete bowel movements (adjusted OR 2.7, 95% CI 1.2, 5.9). Women who exercised weekly had less fecal urgency (adjusted OR 0.3, 95% CI 0.2, 0.8). Coffee drinking was associated with difficulty emptying the bladder (adjusted OR 8.6, 95% CI 1.4, 55.0) and weak stream (adjusted OR 5.3, 95% CI 1.5, 19.0). CONCLUSIONS: Pelvic floor symptoms, especially urinary incontinence and irritative and obstructive urinary and bowel symptoms, are common in older women. Some symptoms are associated with potentially modifiable lifestyle factors.

Age Factors↗
PubMed2007

Obstructive urodynamic findings in idiopathic detrusor overactivity.

PURPOSE: To investigate the obstructive findings urodynamically in idiopathic detrusor overactivity and compare them (maximum flow rate 'Q max' detrusor pressure at maximum flow 'PQ max') with control group. MATERIALS AND METHODS: Cystometric evaluation and pressure flow studies were performed in 25 women with symptoms of idiopathic detrusor overactivity and control group comprised 40 women with anatomic incontinence without cystocele. Patients with pelvic floor prolapse, motor urgency and poor compliance were excluded from the study. Q max less than 15 ml/s and PQ max more than 40 cm water were accepted as obstruction. RESULTS: After cystometric evaluation, obstruction was found in 36% of patients with idiopathic detrusor overactivity and 15% in control group. The range of maximum flow rate and PQ max values were 2-43.7 ml/s (mean 14.47 +/- 10.22) and 10-143 cm water (mean 58.97 +/- 35.13) in idiopathic urge syndrome group. These values were 6.6-51.8 ml/s (mean 23.24 +/- 12.43) and 9.7-61 cm water (mean 25.56 +/- 12.43) respectively in control group. Q max and PQ max parameters were compared statistically between the two groups. Idiopathic detrusor overactivity group had lower mean Q max and higher mean PQ max values than control group (P < 0.001) Table 1. CONCLUSION: Obstruction percentage was found to be more in idiopathic detrusor overactivity group than the control group.

Adult↗
PubMed2007

The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder.

AIM: Treatments targeting vanilloid receptor TRPV1 are effective in some bladder disorders. Our aim was to determine the expression profiles of TRPV1 in regions of human bladder and test the hypothesis that there would be an upregulation of TRPV1 in mucosa of patients with bladder hypersensitivity but not idiopathic detrusor overactivity (IDO). MATERIALS AND METHODS: Women with sensory urgency (SU), interstitial cystitis (IC), and IDO were investigated by videourodynamics and cystoscopy. Control biopsies were used for comparison. Biopsies were dissected into mucosa and muscle, and evaluated for TRPV1 mRNA expression using quantitative competitive RT-PCR (QC-RT-PCR). RESULTS: TRPV1 mRNA from SU trigonal mucosa was significantly higher than control trigonal mucosa or SU bladder body mucosa. In contrast, in IDO patients, there was no difference between trigonal mucosa and body mucosa. In IC biopsies, RNA quality was substandard and unable to be used for analysis. The most striking finding was that TRPV1 mRNA expressed in SU trigonal mucosa was significantly inversely correlated with the bladder volume at first sensation of filling during cystometry. No such relationship was seen for IDO trigonal mucosa. No difference was seen in bladder body mucosa from any disease groups compared with age-matched control. CONCLUSIONS: The symptoms of SU were associated with the increased expression of TRPV1 mRNA in the trigonal mucosa. No upregulation or regional differences of TRPV1 mRNA were seen in IDO patients. TRPV1 may play a role in SU and premature first bladder sensation on filling.

Adult↗
PubMed2006

[Comparative study of overactive bladder prevalence in patients younger than 50 years with and without hyperprolactinemia].

OBJECTIVE: To determine if the hyperprolactinemia is associated with idiopathic overactive bladder. PATIENTS AND METHODS: We performed a transversal and analytic two groups study. We included all the patients whom plasma levels of prolactin were measured in the National Institute of Perinatology from March 1st to May 31, 2005 and fulfilled the selection criteria. To all these patients we applied a questionnaire of eight questions for the overactive bladder diagnostic. We used chi square statistical technique to establish if hyperprolactinemia is associated with the overactive bladder. RESULTS: One hundred sixty years patients were studied, establishing a relative prevalence of 2.82 (IC 95%: 1.45-3.17), determining association between the variables. CONCLUSIONS: hyperprolactinemia is associated with overactive bladder.

Adult↗
PubMed2006

Prevalence and risk factors of overactive bladder syndrome in Fuzhou Chinese women.

AIMS: We randomly sampled a community-based, healthy population to evaluate the prevalence and associated risk factors of overactive bladder (OAB) syndrome by using the International Continence Society (ICS) definition. METHODS: We randomly sampled 6,066 women (3.0% of registered female residents aged 20 years and older in Fuzhou) and mailed Bristol Female Lower Urinary Tract Symptoms questionnaire for women self-completion. Women (4,684; 77.2%) with evaluable data were included in this study. RESULTS: The prevalence of OAB was 8.0% (n = 377), OAB(dry) 2.4% (n = 114), and OAB(wet) 5.6% (n = 263), hence 30% had OAB(dry) and 70% OAB(wet.) The prevalence of OAB and OAB(wet) demonstrated an significant increasing with advancing age (P < 0.01). A multiple logistic regression analysis showed menopause, parity >2, constipation, episiotomy, and higher BMI were potential risk factors for OAB, constipation increased the occurrence of OAB(dry). OAB(wet) was associated with menopause, parity >2, higher fetal birthweight, episiotomy, while cesarean delivery protected against the development of OAB(wet). CONCLUSIONS: The prevalence of OAB in chinese women is lower than that of most reports in Occidental women, and increases with advancing age. Many potential risk factors increase the occurrence of OAB.

Adult↗
PubMed2006

Effect of antimuscarinic drugs used for overactive bladder on learning in a rat passive avoidance response test.

Antimuscarinic drugs are used for the treatment of overactive bladder. One adverse effect associated with their use, however, is cognitive impairment arising from their anticholinergic action. Here, we examined the effects of antimuscarinic drugs on learning using a passive avoidance task in rats. Drugs were intravenously administered 10 min before an acquisition trial, followed 24 h later by measurement of latency time in the passive avoidance task in a retention trial. Oxybutynin (0.1-1 mg/kg i.v.), propiverine (1-10 mg/kg i.v.) and scopolamine (0.1-1 mg/kg i.v.) impaired learning at doses of 0.3 mg/kg i.v. or more, 10 mg/kg i.v., and 0.3 mg/kg i.v. or more, respectively. Tolterodine (0.1-1 mg/kg i.v.) tended to impair these functions at a dose of 1 mg/kg i.v. In contrast, darifenacin (0.1-1 mg/kg i.v.) and solifenacin (0.3-3 mg/kg i.v.) showed no impairment of these functions. We also examined the effects of antimuscarinic drugs on learning enhanced by the cholinesterase inhibitor donepezil at a dose of 0.1 mg/kg i.v. in scopolamine-treated rats. Oxybutynin (0.1-1 mg/kg i.v.) impaired these donepezil-enhanced functions, whereas solifenacin (0.3-3 mg/kg i.v.) produced no significant impairment. These results suggest that antimuscarinic drugs such as darifenacin, solifenacin and tolterodine may have less effect on cognitive function in the treatment of patients with overactive bladder.

Animals↗
PubMed2006

Symptom-specific efficacy of tolterodine extended release in patients with overactive bladder: the IMPACT trial.

We evaluated the efficacy of tolterodine extended release (ER) for patients' most bothersome overactive bladder (OAB) symptom in a primary care setting. Patients with OAB symptoms for >or=3 months received tolterodine ER (4 mg q.d.) for 12 weeks. Among incontinent patients (n = 772), the most bothersome OAB symptoms were daytime frequency (28%), urgency urinary incontinence (UUI; 27%), nocturnal frequency (26%) and urgency (19%); among continent patients (n = 91), they were daytime frequency (47%), nocturnal frequency (42%) and urgency (10%). Sixty-nine per cent of patients had one or more comorbid conditions. By week 12, there were significant reductions in patients' most bothersome symptom: -80% for UUI, -78% for urgency episodes, -40% for nocturnal frequency and -30% for daytime frequency (p < 0.0001). The most common adverse events were dry mouth (10%) and constipation (4%). In primary care practice, bothersome OAB symptoms can be effectively and safely treated with tolterodine ER, even in patients with comorbid conditions.

Adult↗