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PubMed2006

Prognostic factors affecting urologic outcome after untethering surgery for lumbosacral lipoma.

OBJECTS: The authors report results of preoperative and postoperative urodynamic studies (UDS) and prognostic factors of urologic outcome in cases of lumbosacral lipomas for which prolonged follow-up data were available. MATERIALS AND METHODS: The present series includes 42 consecutive cases of lumbosacral lipoma in patients aged 2 months to 15 years who underwent untethering operation during the period from 1986 to 1997. All of them underwent preoperative and postoperative UDS. At the last follow-up (mean duration of follow-up 108 months, range 44 to 176 months), 26 cases maintained social continence with or without intermittent catheterization. Young age (< or =12 months) at operation, preoperative absence of urologic symptoms, and absence of neurologic abnormalities were significantly correlated with favorable urologic outcome. CONCLUSION: UDS in cases with lumbosacral lipomas is a valuable tool for detecting neurourologic abnormalities as well as for monitoring the postoperative course and guiding management. History taking and neurologic examination are also proved to be important aspects in the evaluation of children with lumbosacral lipomas, predictive of urologic outcome. Better urologic results are anticipated if surgery is performed when the child is 12 months old or younger.

Adolescent↗
PubMed2002

Effect of muscarinic antagonists on micturition pressure measured by cystometry in normal, conscious rats.

OBJECTIVES: To establish an in vivo model to screen new muscarinic antagonists for the treatment of overactive urinary bladder and to calculate the respective ID(50) values. METHODS: The conscious rat cystometry model was modified to determine a complete dose-response curve in each animal. Spontaneous micturition was induced by infusion of room-temperature saline into rat bladders at a constant rate of 12 mL/hr. Cumulative doses of muscarinic antagonists administered in the femoral vein caused dose-dependent inhibition of the urinary bladder contraction measured as the micturition pressure. In addition, the in vitro pK(B) values for atropine, PNU-200577 (DD01), tolterodine, oxybutynin, and terodiline were determined in carbachol-contracted rat bladder strips. RESULTS: The rank order of the in vivo ID(50) values were atropine (14 +/- 4 nmol/kg), PNU-200577 (22 +/- 12 nmol/kg), tolterodine (94 +/- 20 nmol/kg), oxybutynin (175 +/- 89 nmol/kg), darifenacin (236 +/- 144 nmol/kg), desethyloxybutynin (313 +/- 209 nmol/kg), propiverine (4561 +/- 2079 nmol/kg), and terodiline (18,339 +/- 5348 nmol/kg). Tolterodine and PNU-200577 caused a parallel shift of the in vitro concentration-response curve to the right and did not alter the maximal contraction. The ID(50) values correlated significantly with the in vitro rat pK(B) and human bladder pA(2) values. CONCLUSIONS: The present results suggest that the rat cystometry model can be used in in vivo screening for new muscarinic antagonists.

Animals↗
PubMed2006

Lower urinary tract disease: what are we trying to treat and in whom?

The diseases of the lower urinary tract are traditionally divided into abnormalities of storage and abnormalities of emptying. The targets for therapy were the organs most responsible for influencing storage and emptying. Modern understanding places the symptomatic status of the patient as the overriding criterion for treatment. It also accommodates a broader understanding of multiple and overlapping systems. Symptoms of voiding dysfunction have been clearly shown to be associated with symptoms of other genitourinary disease, for example, erectile dysfunction (ED). Treatment of voiding dysfunction has also been shown to have effects (adverse or beneficial) in these other domains. Thus, the symptoms of lower urinary tract disease (LUTD) that have to be considered now as targets relevant to these therapies include ED, ejaculatory dysfunction, sexual desire, sexual pain disorders and female sexual dysfunction. The anatomic, neural and endocrine systems that support these symptomatic functions and dysfunctions span the range from the urogenital smooth muscle to the hypothalamus, the bladder sensory output to the micturition centre and growth factors to androgens. Potentially important targets also include vascular and spinal structures, sex hormones and nitric oxide as well as the obvious genes, enzymes and receptors. The epidemiological studies prove the convergence of LUTD when viewed through the lens of the current patient-related outcomes and problem constructs. This convergence serves as a clear guidance to include wide ranging outcome instruments in all future studies with compounds being investigated for the treatment of LUTD. Out of these will come evidence of expected and unexpected collateral effects. The convergence should open the possibility to a different business model for developing therapeutic concepts. The blockbuster drug for a monolithic indication may be supplemented by agents with single or multiple pathway activity with smaller parallel targets. Using an approach based on patient reported outcomes to therapeutic targets not only widens the range of conditions, but also the patient types who can be considered as having LUTD.

Depression↗
PubMed2006

Integrated control of lower urinary tract--clinical perspective.

The neural mechanisms that determine social bladder control are reviewed, with a particular emphasis on the role played by sensation in the process. Much has been learnt about the neural control of the bladder from studying patients with neurological disease and those disorders that are known to disrupt bladder storage are described. Possible approaches to treatment of the resulting incontinence are reviewed and it is acknowledged that in the future, the optimal treatment for incontinence may be determined by its precise underlying pathophysiology in each instance, for example, suprapontine causes requiring different medication to spinal causes. Although the main emphasis of urological research and development so far has been the treatment of incontinence, effective therapy for other bladder disorders such an impaired emptying or bladder pain could have an important impact on the bladder symptoms of many patients.

Animals↗
PubMed2006

Diagnosis and management of dysfunctional voiding.

PURPOSE OF REVIEW: This review will focus on the diagnosis and management of voiding dysfunction in neurologically and anatomically normal children. The discussion will highlight recent developments and research in the clinical approach as well as the etiology and classification of these disorders. RECENT FINDINGS: Voiding dysfunction in children encompasses a wide spectrum of clinical entities, recently classified collectively as dysfunctional elimination syndromes. Voiding dysfunction typically presents after toilet training and may originate from behavioral issues that arise around this time in childhood development. The spectrum of disorders includes urge syndrome, dysfunctional voiding with an uncoordination between the detrusor and urinary sphincter, and enuresis. Clinical symptoms may vary from mild incontinence to severe disorders with endpoints of irreversible bladder dysfunction with vesicoureteral reflux, urinary tract infection and resulting nephropathy. Diagnosis relies heavily on a good history and physical examination, but also includes radiologic and urodynamic evaluation. Treatment generally consists of medical therapy, primarily with anticholinergics as well as behavioral therapy to modify learned voiding patterns that contribute to the voiding dysfunction. SUMMARY: This overview of voiding dysfunction in children outlines the established approaches to its diagnosis and treatment and highlights the most recent developments in the field.

Biofeedback, Psychology↗
PubMed2006

Characterization and restoration of altered inhibitory and excitatory control of micturition reflex in experimental autoimmune encephalomyelitis in rats.

Multiple sclerosis (MS) is characterized by inflammatory lesions throughout the central nervous system. Spinal cord inflammation correlates with many neurological defecits. Most MS patients suffer from micturition dysfunction with urinary incontinence and difficulty in emptying the bladder. In experimental autoimmune encephalomyelitis (EAE) induced in female Lewis rats, a model of MS, we investigated at distinct clinical severity scores the micturition reflex by cystometrograms. All rats presenting symptomatic EAE suffered from micturition reflex alterations with either detrusor areflexia or hyperactivity. During pre-symptomatic EAE, a majority of rats presented with detrusor areflexia, whereas at onset of clinical EAE, detrusor hyperactivity was predominant. During progression of EAE, detrusor areflexia and hyperactivity were equally expressed. Bladder hyperactivity was suppressed by activation of glycine and GABA receptors in the lumbosacral spinal cord with an order of potency: glycine > GABA(B) > GABA(A). Detrusor areflexia was transformed into detrusor hyperactivity by blocking glycine and GABA receptors. Spinalization abolished bladder activity in rats presenting detrusor hyperactivity and failed to induce activity in detrusor areflexia. Altogether, the results reveal an exaggerated descending excitatory control in both detrusor reflex alterations. In detrusor areflexia, a strong segmental inhibition dominates this excitatory control. As in treatment of MS, electrical stimulation of sacral roots reduced detrusor hyperactivity in EAE. Blockade of glycine receptors in the lumbosacral spinal cord suppressed the stimulation-induced inhibitory effect. Our data help to better understand bladder dysfunction and treatment mechanisms to suppress detrusor hyperactivity in MS.

Animals↗
PubMed2006

A retrospective claims database analysis to assess patterns of interstitial cystitis diagnosis.

OBJECTIVE: Interstitial cystitis (IC) is often misdiagnosed as one of several other conditions manifesting similar symptoms. This analysis assesses the potential extent of IC misdiagnosis while considering concomitant conditions in a managed care population and identifies predictors of IC diagnosis. RESEARCH DESIGN AND METHODS: Administrative insurance claims data covering 1.7 million lives (1999-2003) were analyzed. Insurance enrollees with >or= 1 IC diagnosis (ICD-9-CM of 595.1x) were identified as IC patients. A random sample of non-IC controls was selected using a 10:1 matching ratio. Six-month incidence rates of 'commonly misdiagnosed conditions', (overactive bladder, urinary tract infection, chronic pelvic pain, endometriosis, prostatitis) were compared before and after patients' initial IC diagnosis and the reduction in incidence rate of commonly misdiagnosed conditions was used as a suggestive measure of the extent of IC misdiagnosis. The Kaplan-Meier method was used to assess the extent that commonly misdiagnosed conditions were predictors of subsequent IC. A Cox Proportional Hazards regression model (that adjusts for patient demographics, concomitant and misdiagnosed conditions) was used to estimate the hazard ratio (HR) of these conditions. Similar analyses were performed for the 'commonly concomitant conditions' (fibromyalgia, irritable bowel syndrome, vulvodynia). RESULTS: There were 992 IC patients and 9920 controls identified. The reduced incidence of commonly misdiagnosed conditions after initial IC diagnosis suggests that the misdiagnosis rate could be as high as 38% within the 6-month period before initial IC diagnosis. CONCLUSIONS: Diagnoses of commonly misdiagnosed conditions are significant predictors of future IC diagnosis. When overlooked, potential misdiagnosis of IC can lead to underestimation of the true prevalence of IC. Similarly, diagnoses of commonly concomitant conditions are significant predictors of future IC diagnosis. These initial findings based on claims data suggest hypotheses for further investigation with clinical data. These results suggest more consideration of IC as a diagnosis is warranted, especially when certain diagnoses are repeatedly made and the resulting treatments do not alleviate the patient's symptoms.

Adolescent↗
PubMed2004

Chronic pain syndromes of gynecologic origin.

Women seek gynecologic medical attention for 2 main reasons--abnormal bleeding and pelvic pain. Gynecologists are often more comfortable with the diagnosis and management of abnormal bleeding than with the diagnosis and management of pelvic pain. One reason is that chronic pelvic pain can result from a variety of abdominal and pelvic causes, including endometriosis, pelvic inflammatory disease, adhesions and urogenital causes, such as vulvodynia, and from bladder complaints, including overactive bladder, urinary tract infection and interstitial cystitis (IC). The symptoms of IC--chronic pelvic pain with urinary urgency, frequency and nocturia--are all too frequently attributed to these other causes of chronic pelvic pain, in large part because gynecologists rarely consider the bladder as a source of pelvic pain. In addition, IC can masquerade as, and coexist with, other causes of pelvic pain, particularly endometriosis. Early diagnosis and treatment of IC can reduce the occurrence of unnecessary procedures and treatments and can improve the patient's prognosis and quality of life. Bladder-origin pelvic pain should be considered in all women who present with these symptoms.

Chronic Disease↗
PubMedDate not supplied

[Detrusor pseudohyperactivity syndrome in children with constipation].

THE AIM OF THE STUDY: was the evaluation of dependencies occurring between constipation and observed nocturia, pressing tenesmus and daytime urinary incontinence. MATERIAL AND METHODS: the studies were conducted in 51 children aged between 3 and 17 years including 25 girls and 26 boys hospitalized in the Clinical Department because of nocturia, pressing tenesmus and daytime urinary incontinence. In all children a complex diagnostic work up of the urinary system and the lower segment of alimentary tract was performed. Results of the examinations were compared to the control group. RESULTS: analysis of the results of the conducted examinations indicates that the overblown rectal ampulla, through the pressure exerted on the urinary bladder, seemingly decreases its volume causing the occurrence of pressing tenesmus, nocturia and daytime urinary incontinence. This process leads to the formation of detrusor hyperactivity syndrome characterized by: chronic constipation, increase of miction frequency and simultaneous decrease of volume of each portion of urine, nocturia and/or daytime urinary incontinence. CONCLUSIONS: chronic constipation disturbs the functional-morphological equilibrium between the end segment of alimentary tract and the urinary bladder. By influencing the process of filling and accumulation of urine in the bladder they lead to the formation of detrusor hyperactivity syndrome.

Adolescent↗
PubMed2006

Effectiveness of tolterodine in nonneurogenic voiding dysfunction.

The efficacy of tolterodine was analysed in children with non-neurogenic voiding dysfunction, using dysfunctional voiding symptom score (DVSS). Of 44 patients (mean age 9.3 yrs; M:F = 25:19), 36 received long acting tolterodine tartrate at a dose of 2mg OD and 8 at a dose of 4mg OD. The mean (SD) DVSS before and after the treatment was 17.1 (2.8) and 12.0 (2.4). There was a significant improvement in the mean DVSS score at the end of the treatment (Students t test P < 0.01). The dysfunctional symptoms were cured in 28(63.6 %), improved in 14(31.8 %) and failed to show improvement in 2 (4.6 %). Over all 95 % were compliant with the single daily medication. Our results demonstrate that long acting tolterodine is effective in children with voiding dysfunction. The single daily dose has good compliance and minimal side effect profile.

Benzhydryl Compounds↗
PubMed2006

Newer agents for the management of overactive bladder.

The anticholinergics tolterodine and oxybutynin are well established in the management of overactive bladder. However, their activity at muscarinic receptors distant from the target site (i.e., bladder) produces anticholinergic side effects leading to poor tolerability. In 2004, trospium, solifenacin, and darifenacin were approved by the U.S. Food and Drug Administration for the treatment of overactive bladder. Trospium is water soluble and therefore is less likely to enter the central nervous system, and solifenacin and darifenacin are more selective for the bladder than older agents. Although these attributes could improve tolerability, clinical trials comparing relevant agents to validate this are lacking. Trials have shown that these newer agents decrease the frequency of incontinence episodes, the number of voids per day, and the number and severity of urgency episodes compared with placebo. These agents also have been shown to improve quality of life in women with overactive bladder and urinary incontinence. Head-to-head studies of the newer agents and immediate-release oxybutynin and tolterodine have suggested similar effectiveness across the class, although the newer agents are better tolerated. Trospium and darifenacin have not been compared with extended-release formulations of tolterodine or oxybutynin, which are better tolerated than the immediate-release versions. In one study, solifenacin produced a somewhat greater decrease in the number of incontinence episodes than extended-release tolterodine, with no difference in tolerability. In general, the newer agents appear to be at least as effective as their predecessors, although it is unclear whether they are better tolerated. Important pharmacokinetic differences among the agents (e.g., route of elimination) allow for selection of an appropriate agent based on individual factors such as cost and tolerability.

Humans↗
PubMed2006

Efficacy and tolerability of tolterodine extended-release in men with overactive bladder and urgency urinary incontinence.

UNLABELLED: A group of authors from the USA evaluated the efficacy and tolerability of tolterodine extended-release on objective and subjective endpoints in men with an overactive bladder. They found that it significantly reduced incontinent episodes and improved patient perception of treatment benefit in men with an overactive bladder OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine extended-release (ER) on objective and subjective endpoints in men with overactive bladder (OAB) and urgency urinary incontinence (UI). PATIENTS AND METHODS This was a post hoc analysis of data collected from men with OAB enrolled in a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily; tolterodine ER registration trial) and included men with urinary frequency (> or =8 micturitions/24 h) and urgency UI (> or =5 episodes/week). UI episodes were assessed using 7-day bladder diaries. Patient perception of treatment benefit was evaluated after 12 weeks. Adverse events (AEs) were recorded throughout the study. RESULTS: In all, 163 men with OAB (placebo, 86; tolterodine ER, 77; mean age 65 years) were evaluated. Baseline demographics and clinical characteristics were similar for the two treatment groups. Compared with placebo, tolterodine ER significantly reduced weekly UI episodes (median % change, -71% vs - 40%, P < 0.05; mean numeric change, - 11.9 vs -5.9, P = 0.02). Men receiving tolterodine ER had fewer micturitions/24 h, but this was not a significant difference from placebo (median % change, -12% vs - 4%, P = 0.22). Significantly more men treated with tolterodine-ER (63%) than placebo-treated men (46%) reported a benefit of treatment after 12 weeks (P = 0.04). The most commonly reported AEs associated with tolterodine-ER vs placebo were dry mouth (16% vs 7%), constipation (4% vs 9%), dyspepsia (4% vs 1%), dizziness (5% vs 1%), and somnolence (3% vs 1%). One of the men receiving tolterodine ER had symptoms suggestive of urinary retention that led to his withdrawal from the study. None of the men had acute urinary retention requiring catheterization. CONCLUSION: In men with OAB and urgency UI, tolterodine ER was well tolerated and significantly reduced episodes of urgency UI, and improved patient perception of treatment benefit.

Adolescent↗
PubMed2000

Findings of a three-year retrospective study to investigate prevalence and incidence of urinary incontinence and overactive bladder in a typical managed care setting.

This study was conducted in a large, integrated HMO to determine the prevalence and incidence of urinary incontinence, identify a demographic profile of patients having the UI subgroup condition of overactive bladder, and collect data to create an economic cost of illness description regarding current diagnosis and treatment practices. Using ICD-9 and CPT codes and prescription drug claims data as markers for the disease, subjects were selected for inclusion in the study. Resource use cost data was collected from this cohort over a three-year period and analyzed for total and mean monthly costs.

Adolescent↗
PubMed2003

Risk factors for stress, urge or mixed urinary incontinence in Italy.

OBJECTIVE: To assess risk factors for different type of urinary incontinence-stress, urge or mixed-and overactive bladder without urinary incontinence. DESIGN: Case-control study. SETTING: Gynaecology clinics. POPULATION: Women attending first level gynaecological centres. METHODS: Cases were 1062 women with urinary incontinence or overactive bladder aged 40 years or more (mean age 62.3 years, range 40-88) consecutively observed in first level gynaecological centres. Controls were 1143 women (mean age 58 years, range 40-86) observed in the same centre after the identification of the cases, without any symptoms related to urinary incontinence or overactive bladder. MAIN OUTCOME MEASURES: Determinants of different types of urinary incontinence and overactive bladder. RESULTS: The risk of urinary incontinence was lower in more educated patients and increased with body mass index (BMI). The number of vaginal births was associated with the risk of stress and mixed urinary incontinence, but not urge urinary incontinence and overactive bladder. In comparison with nulliparae, the odds ratios (OR) for stress and mixed urinary incontinence were 5.4 (95% confidence interval [CI] 1.9-15.0) and 1.6 (95% CI 1.0-2.6), respectively, for women reporting one or two vaginal birth and 5.1 (95% CI 1.8-14.5) and 2.2 (95% CI 1.3-3.7), respectively, for three or more. A history of operative vaginal delivery was directly associated with the risk of stress and mixed urinary incontinence and increased the risk of urge urinary incontinence and of overactive bladder, but the latter ORs were not statistically significant. When compared with women with no birth, a history of caesarean section increased the risk of stress urinary incontinence. A history of hysterectomy, recurrent urinary infection and perineal trauma increased the risk of all types of urinary incontinence. CONCLUSIONS: Vaginal births increased the risk of stress and mixed urinary incontinence, but not of urge urinary incontinence and overactive bladder. The risk of all types of urinary incontinence was increased in women with higher BMI, with a history of hysterectomy, urinary infection and perineal traumas. These factors were not related to the risk of overactive bladder.

Adult↗
PubMed2006

The impact of detrusor overactivity on the management of stress urinary incontinence in women.

The presence of overactive bladder symptoms, urodynamic detrusor overactivity, and urge incontinence can complicate the diagnosis and management of stress urinary incontinence in women. The exact pathophysiology of mixed incontinence is not well characterized; in some patients, the stress and urge etiology may be pathologically linked. The role of urodynamics in evaluating patients with mixed incontinence remains controversial. Conservative therapies, such as bladder training, pelvic floor exercise, biofeedback, and electrical stimulation, offer moderate success in women with mixed incontinence. Surgery (colposuspension, bladder neck pubovaginal slings, and midurethral slings) offers excellent subjective and objective cure rates in patients with mixed incontinence. Preoperative detrusor overactivity is cured consistently 50%of the time with colposuspension and slings. Overall, the presence of preoperative detrusor overactivity does not appear to significantly worsen the outcome of conservative and surgical treatments for stress urinary incontinence in women.

Female↗
PubMed2006

Childhood urinary symptoms predict adult overactive bladder symptoms.

PURPOSE: A relationship between childhood urinary symptoms and adult lower urinary tract symptoms in women is often clinically suspected. In this analysis we investigated the relationship between childhood and adult urinary symptoms in middle-aged women. MATERIALS AND METHODS: A population based cohort of 2,109 women 40 to 69 years old who were members of a large health maintenance organization was randomly selected from age and race strata. Through self-reported questionnaires, women recalled a childhood history of and current urinary lower urinary tract symptoms, including frequent daytime urination, nocturia, urinary incontinence, nocturnal enuresis and UTIs. Current incontinence was also classified as urge or stress incontinence. Multivariate analysis was used to evaluate the association between childhood and current lower urinary tract symptoms controlling for age, race, hysterectomy status, parity, oral estrogen use, body mass index and diabetes. RESULTS: Women who reported childhood daytime frequency were more likely to report adult urgency (OR 1.9, 95% CI 1.3-2.6, p < 0.001). Frequent nocturia in childhood was strongly associated with adult nocturia (OR 2.3, 95% CI 1.5-3.5, p < 0.001). Childhood daytime incontinence was associated with adult urge incontinence (OR 2.6, 95% CI 1.1-5.9, p < 0.05), as was childhood nocturnal enuresis (OR 2.7, CI 1.3-5.5, p < 0.01). A history of more than 1 childhood UTI was associated with adult UTIs (OR 2.6, 95% CI 1.5-4.5, p < 0.001). CONCLUSIONS: Childhood urinary symptoms and UTIs were significantly associated with adult overactive bladder symptoms. There is a need to investigate the significance of childhood symptoms as predictors of eventual adult disorders to determine whether treatment of childhood symptoms will alter the prevalence of eventual adult disorders, and if such a history should alter clinical care of the older adult with OAB symptoms.

Adult↗