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PubMed2005

Urinary stress incontinence treatment with Remeex in a patient with epispadias: a case report.

Epispadias is a rare condition in women. A postmenopausal 53-year-old woman with a known problem of epispadias came to our outpatient clinic complaining of persistent severe urinary stress incontinence without overactive bladder symptoms. She had previously undergone an inefficacious tension-free vaginal tape (TVT) procedure in another institution. We implanted a Remeex (Mechanic External Regulation) device without applying any tension to the sling. Two tape regulations were performed the day after surgery and 2 months later to gain continence. At 13 months of follow up, this woman was asymptomatic and satisfied. As documented by this case here, the Remeex procedure is particularly suitable in selected high-risk patients where TVT and TVT live slings are less effective.

Epispadias↗

PubMed2005

Obstruction after Burch colposuspension: a return to retropubic urethrolysis.

We compare our postoperative outcomes of a vaginal vs abdominal urethrolysis after an obstructed Burch colposuspension. We performed a retrospective review of all women who had undergone a Burch urethrolysis from 1997 through 2003. Data collected included pelvic examination, cystoscopic and urodynamic findings, surgical morbidity, and pre- and postoperative urogynecologic symptomatology. Sixteen women underwent Burch urethrolysis. Preoperative symptoms were obstructive in 6, overactive in 2, and both (obstructive/overactive) in 8. All had an acute retropubic angulation of the urethral axis as well as a retropexed urethra that prohibited sagittal rotation of a rigid cystoscope. Seventy-eight percent of the women with urodynamic information met urodynamic criteria for urethral obstruction. Average follow-up was 7 months, and of those undergoing a vaginal urethrolysis, three out of seven (43%) had resolution of their obstructive or overactive symptoms postoperatively. In contrast, seven out of nine women (78%) who underwent a retropubic urethrolysis had relief of their obstructive or overactive bladder symptoms. In our cohort study, an abdominal retropubic urethrolysis was more successful in relieving urethral obstruction than a vaginal urethrolysis.

Abdomen↗

PubMed2005

Epidemiology of prolapse and incontinence questionnaire: validation of a new epidemiologic survey.

The epidemiology of prolapse and incontinence questionnaire (EPIQ) was developed to screen for female pelvic floor disorders (PFD). Content and face validity, reliability, internal consistency and criterion validity of the EPIQ to detect the presence of pelvic organ prolapse (POP), stress urinary incontinence (SUI), overactive bladder (OAB) and anal incontinence (AI) is presented. Cronbach's alpha; Spearman's, kappa, intraclass correlations, factor analysis and Chi-Squared tests were used for analysis. Questions related to PFD proved internally consistent (alpha = 0.91) and reproducible (correlations >0.70) for all but three items on the EPIQ. Positive and negative predictive values of the EPIQ to detect PFD were: POP = 76% and 97%, SUI = 88% and 87%, OAB = 77% and 90% and AI = 61% and 91% respectively. EPIQ is a psychometrically validated screening instrument that may identify women at high risk of having pelvic floor disorders in large undiagnosed populations.

Adult↗

PubMed2006

Has the true prevalence of voiding difficulty in urogynecology patients been underestimated?

Voiding difficulty has been relatively overlooked as a diagnosis. Previous estimates of its prevalence have generally been no more than 14% with one exception at 24%. The aim of this study is to determine the true prevalence and associations of voiding difficulty using a validated definition [urine flow rate under 10th centile of the Liverpool Nomograms and/or residual urine volume (by transvaginal ultrasound) more than 30 ml]. This study involved 592 women referred for an initial urogynecological assessment including urodynamics. Data were separated according to the presence or absence of voiding difficulty. The prevalence of voiding difficulty was 39%, far higher than previous estimates. It is the third most common urodynamic diagnosis behind urodynamic stress incontinence (USI-72%) and uterine/vaginal prolapse (61%) and ahead of the overactive bladder (13%). Voiding difficulty significantly increased in prevalence with age and increasing grades of all types of uterine/vaginal prolapse. Prolapse appeared to be the main factor in the age deterioration. Other significant positive relationships with voiding difficulty were prior hysterectomy and prior continence surgery, whilst USI and the symptom and sign of stress incontinence had significant inverse relationships.

Adolescent↗

PubMed2006

Propiverine and metabolites: differences in binding to muscarinic receptors and in functional models of detrusor contraction.

Propiverine is a commonly used antimuscarinic drug used as therapy for symptoms of an overactive bladder. Propiverine is extensively biotransformed into several metabolites that could contribute to its spasmolytic action. In fact, three propiverine metabolites (M-5, M-6 and M-14) have been shown to affect various detrusor functions, including contractile responses and L-type calcium-currents, in humans, pigs and mice, albeit with different potency. The aim of our study was to provide experimental evidence for the relationship between the binding of propiverine and its metabolites to human muscarinic receptor subtypes (hM(1)-hM(5)) expressed in chinese hamster ovary cells, and to examine the effects of these compounds on muscarinic receptor-mediated detrusor function. Propiverine, M-5, M-6 and M-14 bound to hM(1)-hM(5) receptors with the same order of affinity for all five subtypes: M-6 > propiverine > M-14 > M-5. In HEK-293 cells expressing hM(3), carbachol-induced release of intracellular Ca(2+) ([Ca(2+)](i)) was suppressed by propiverine and its metabolites; the respective concentration-response curves for carbachol-induced Ca(2+)-responses were shifted to the right. At higher concentrations, propiverine and M-14, but not M-5 and M-6, directly elevated [Ca(2+)](i). These results were confirmed for propiverine in human detrusor smooth muscle cells (hDSMC). Propiverine and the three metabolites decreased detrusor contractions evoked by electric field stimulation in a concentration-dependent manner, the order of potency being the same as the order of binding affinity. We conclude that, in comparison with the parent compound, loss of the aliphatic side chain in propiverine metabolites is associated with higher binding affinity to hM(1)-hM(5) receptors and higher functional potency. Change from a tertiary to a secondary amine (M-14) results in lower binding affinity and reduced potency. Oxidation of the nitrogen (M-5) further lowers binding affinity as well as functional potency.

Animals↗

PubMed2005

Phosphodiesterase inhibitors in female sexual dysfunction.

Based on the increasing knowledge on both the physiology of penile erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have been successfully introduced in the oral treatment of male erectile dysfunction. Because of their central role in smooth muscle tone regulation, PDEs remain an attractive target for drug development in urology. Since the distribution and functional significance of PDE isoenzymes vary in different tissues, selective inhibitors of the isoenzymes have the potential to exert at least partially specific effects on the target tissue. Currently, PDE inhibitors are under investigation with potential uses in urinary stone disease, overactive bladder and the so-called benign prostatic syndrome. The convincing clinical data on the use of the orally active PDE5 inhibitors sildenafil (VIAGRA), vardenafil (LEVITRA) and tadalafil (CIALIS) in the treatment of erectile dysfunction are accompanied by boosting research activities on intracellular signal transduction and PDE characterisation in female genital tissues with the aid of immunohistochemistry and immunocytochemistry and molecular biology. The expression of various PDE isoforms in the human clitoris, vagina and labia minora was shown by means of immunohistochemistry and RT-PCR analyses and it was concluded from functional studies that an increase in cGMP or cAMP might be involved in the regulation of female genital blood flow and the control of genital non-vascular smooth muscle. As a consequence, the efficacy and safety of the PDE5 inhibitor sildenafil in the treatment of symptoms of female sexual dysfunction (FSD), including female sexual arousal disorders (FSAD), have been evaluated. Although the experiences from these early clinical studies have so far not been conclusive, they suggest that, after appropriate evaluation of patients, inhibition of PDE5 might be of benefit for selected individuals with FSAD. Such research efforts will possibly allow the identification of efficacious and diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.

Female↗

PubMed2004

Confusion about measuring central nervous system effects.

Anticholinergic therapy together with behavioral treatment are the main stays of treatment for the overactive bladder. Successful therapy and patient compliance depend very much on side effects. In the past, little attention has been paid to anticholinergic side effects in the central nervous system (CNS), which can be critical, especially for elderly patients. Incidence and intensity of CNS effects depend on the pharmacokinetic and pharmacodynamic properties that are decisive whether anticholinergics pass the blood-brain barrier as a result of passive and active transport mechanisms. To measure potential CNS side effects of anticholinergic drugs, rapid eye movement sleep analysis, quantitative-topographic electroencephalogram studies, and psychometric tests were performed. Structural changes in brain morphology resulting from anticholinergics also were analyzed in a post-mortem study.

Brain↗

PubMed2004

Determinants of patient satisfaction after the tension-free vaginal tape procedure.

OBJECTIVE: This study was undertaken to compare patient satisfaction with subjective and objective measures of success. STUDY DESIGN: Satisfaction at 1-year was measured by using a self-administered written questionnaire. Success was assessed both subjectively and objectively by using the short form Urogenital Distress Inventory, stress testing, and multichannel urodynamics. Outcomes were compared to determine the relationship between satisfaction and success. Satisfied and dissatisfied patients were compared with respect to pre-, intra-, peri-, and postoperative characteristics. Student t and chi(2) tests were used for continuous and ordinal data, respectively. RESULTS: Of 66 (80%) patients, 53 were satisfied. These patients were more likely to achieve subjective cure (91% vs 62%, P=.009) but not statistically more likely to be objectively cured (92% vs 75%, P=.08). Dissatisfied patients tended to have overactive bladder symptoms, voiding difficulty, and required sling release. Other patient characteristics did not influence satisfaction rates. CONCLUSION: Satisfaction after tension-free vaginal tape procedure is highly dependent on normal bladder function. Dissatisfied patients deserve comprehensive evaluation, although objective measures may not reflect patient satisfaction.

Adult↗

PubMed2006

Management of incontinence for family practice physicians.

Family practice physicians are likely to encounter urinary incontinence and overactive bladder (OAB) in their patients. An informed family practice physician can generally accurately diagnose the cause and type of incontinence in patients with a properly focused physical examination and, if necessary, auxiliary testing. Accurate diagnosis can lead to effective treatment when physicians are familiar with available treatment options, including pharmacologic, surgical, behavioral therapies, and catheterization.

Family Practice↗

PubMed2005

Pharmacokinetic interaction of solifenacin with an oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women: a double-blind, placebo-controlled study.

BACKGROUND: Solifenacin succinate (YM905; Vesicare, Astellas Pharma Inc., Tokyo, Japan) is a new once-daily, orally administered muscarinic receptor antagonist under investigation for the treatment of overactive bladder. OBJECTIVE: The aim of this study was to evaluate the effect of solifenacin on the pharmacokinetic (PK) parameters of an oral contraceptive (OC) containing ethinyl estradiol (EE) and levonorgestrel (LNG). METHODS: In a double-blind, placebo-controlled, 2-period, crossover study, 24 healthy, young, white women received a combined OC (EE 30 microg + LNG 150 microg) daily for two 21-day cycles, separated by a 7-day washout. On day 12 of each cycle, subjects began a 10-day regimen of solifenacin 10 mg QD, which is 2 times the suggested starting dose, or placebo. Subjects crossed over to the other treatment arm for the second cycle. Primary PK end points were C(max) and AUC from time 0 to 24 hours (AUC(0-24 h)) for EE and LNG. Women ranged in age from 20 to 37 years and had a mean body weight of 64 kg, mean height of 167.4 cm, and mean body mass index of 23 kg/m2. Seven women had never smoked, while 5 were former smokers and 12 were regular smokers. Safety assessments included the nature, frequency, and severity of spontaneously reported or observed adverse events, vital signs, electrocardiogram, laboratory values, and physical examination. RESULTS: Statistical analysis of AUC(0-24 h)/product of baseline concentration and total blood sampling time, and C(max)/baseline concentration ratios of solifenacin versus placebo for EE and LNG found the 90% CI to be within the predefined range of 0.8 to 1.25 (EE: 0.854-1.164 and 0.822-1.167; LNG: 0.920-1.125 and 0.910-1.139). The number of samples with non-quantifiable luteinizing hormone (LH) and folliclestimulating hormone (FSH) levels were comparable after administration of the OC with either solifenacin or placebo. The adverse event most frequently reported was dry mouth (solifenacin, n = 25 [9 mild, 13 moderate, and 3 severe] vs placebo, n = 1 [moderate]). There were no clinically relevant effects on vital signs, electrocardiogram, or laboratory parameters. CONCLUSIONS: A PK interaction between solifenacin and the OC containing EE and LNG was not found in this study. Solifenacin was not found to have altered suppression of LH or FSH. The drug was well tolerated in these healthy, young, white, adult female volunteers.

Adult↗

PubMed2005

Solifenacin is effective for the treatment of OAB dry patients: a pooled analysis.

OBJECTIVE: The aim of this analysis was to determine the effects of solifenacin in patients considered overactive bladder (OAB) dry at baseline. METHODS: This was a pooled analysis of 4 randomized, placebo-controlled 12-week, phase 3 studies. Patients received placebo or solifenacin 10 mg once daily (2 studies), or placebo or solifenacin 5 mg or 10 mg once daily (2 studies). A subgroup of patients without incontinence at baseline was identified from a 3-day diary. Mean changes from baseline to endpoint for urgency episodes, micturition, frequency and nocturia episodes per 24 hours, and volume voided/micturition were evaluated. The proportion of patients with normalization of micturition frequency (<8 micturitions), resolution of urgency, or resolution of nocturia at endpoint was also determined. RESULTS: Of 2848 evaluable patients treated with placebo or solifenacin, 975 (34%) were OAB dry at baseline. Solifenacin 5 mg and 10 mg were significantly (p < 0.001) more effective than placebo for improving urgency, micturition frequency, and volume voided. In addition, solifenacin 10mg was significantly (p < 0.01) more effective than placebo for improving nocturia. Resolution of urgency occurred significantly (p < 0.05) more often with solifenacin 5 mg (37%) and 10 mg (33%) than with placebo (25%). Significantly (p < 0.01) more OAB dry patients had normalization of micturition frequency with solifenacin 5 mg (29%) and 10 mg (35%) compared with placebo (19%). Resolution of nocturia occurred in 14%, 21%, and 13% of patients treated with solifenacin 5mg, solifenacin 10 mg, and placebo, respectively (p < 0.01 for solifenacin 10 mg versus placebo). CONCLUSION: Solifenacin significantly improved urgency, frequency, and nocturia symptoms and increased volume voided in OAB dry patients.

Adult↗

PubMed2005

Prognostic factors for successful percutaneous tibial nerve stimulation.

OBJECTIVE: In sacral as well as tibial nerve stimulation test stimulation is the main prognostic factor for success. In our study we tried to identify prognostic patient characteristics to improve patient selection for neuromodulation therapy. METHODS: PTNS was applied to 132 patients in 8 study centers (51 men, 81 women, mean age of 53 years (range: 21-82)). 83 patients were treated for overactive bladder, 16 for non-obstructive urinary retention and 33 for chronic pelvic pain. All patients had to fill out micturition or pain diaries, as well as quality of life questionnaires before and after treatment. Patient characteristics were evaluated for their prognostic value for successful outcome of neuromodulation therapy with use of logistic regression. RESULTS: Objective success was seen in 32.6% of patients, subjective success in 51.5%. Most evaluated clinical parameters proved not to be of prognostic value. A history of sexual and/or physical abuse was found in 12 of 103 interviewed patients, but did not alter PTNS treatment outcome. However, a low total score at baseline in the SF-36 questionnaire proved to be predictive for not obtaining objective (OR 0.444 [95% CI: 0.198-0.996], p = 0.04) or subjective success (OR 0.424 [CI: 0.203-0.887], p = 0.02). Especially patients with a low SF-36 Mental Component Summary were prone to fail neuromodulation therapy: OR 0.123 (95% CI: 0.273-0.552), p = 0.006 for objective success. These patients also scored worse on disease-specific quality of life questionnaires, although they had no different disease severity compared to patients with good mental health. CONCLUSION: Bad mental health as measured with the SF-36 Mental Component Summary does not depend on symptom severity and is a negative predictive factor for success of percutaneous tibial nerve stimulation. It therefore might be used as a tool for better patient selection in neuromodulation therapy.

Adult↗

PubMed2006

Transdermal oxybutynin: sticking to the facts.

OBJECTIVES: This article critically reviews all the available published and presented data about transdermal oxybutynin to provide a summary of its efficacy, tolerability, and acceptability. RESULTS: For patients with urge incontinence or mixed incontinence, transdermal oxybutynin offers equivalent efficacy to variable dose oral oxybutynin IR and tolterodine LA 4 mg/d. At present no data are available for patients with frequency and urgency but without incontinence (overactive bladder [OAB] dry). Transdermal oxybutynin offers marked improvements compared with placebo in incontinence episodes, daily urinary frequency, and nocturia. These objective improvements are matched by improvements in quality of life. The rate of anticholinergic side-effects is lower than that for oral anticholinergic preparations. This benefit is offset by a rate of local skin reactions. CONCLUSIONS: The balance of efficacy and tolerability suggests that transdermal oxybutynin should be considered as a potential first-line therapy in OAB or mixed incontinence.

Administration, Cutaneous↗

PubMed2006

New transdermal bioadhesive film containing oxybutynin: In vitro permeation across rabbit ear skin.

Oxybutynin is used extensively in the treatment of patients with overactive bladder. The aim of this work was to realize and test in vitro a new transdermal bioadhesive film containing oxybutynin. Transdermal films were prepared by dissolving in water an adhesive (Plastoid), a film-forming polymer (polyvinyl alcohol), a plasticizer (sorbitol) and the drug. The mixture was then spread on siliconized paper and oven-dried. Permeation experiments were conducted in Franz-type diffusion cells using rabbit ear skin as barrier. The donor compartment contained a water solution, the prepared film (with or without backing) or the commercial patch (Oxytrol). The experiments were performed for 24h. Oxybutynin showed good permeation characteristics across the skin. When the film was applied in occlusive conditions the release profiles were much higher than in non-occlusive conditions, reaching 50% of drug permeated after 24h. Compared to the commercial patch Oxytrol, the film was more efficient suggesting that a smaller area or a lower drug loading could be employed. The results obtained show that the bioadhesive film can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.

Administration, Cutaneous↗

PubMedDate not supplied

Common problems of urination in nonpregnant women: causes, current management, and prevention strategies.

This article uses a case-based approach to review common problems of urination in nonpregnant women, including overactive bladder; stress, urge, and mixed incontinence; and retention and prolapse. Up-to-date clinical issues related to assessment, diagnosis, treatment, and follow-up are reviewed, with a discussion of underlying pathophysiology and prevention strategies. Suggestions are made for relevant curriculum content at both the basic and advanced levels of advanced practice education.

Adolescent↗

PubMed2005

What affects the occurrence of nocturia more: menopause or age?

OBJECTIVES: Prevalence studies show that nocturia is a very common condition, affecting older age groups in particular. In this study, we evaluate (1) the community-based prevalence of nocturia and its associated overactive bladder according to the patient's perception and disturbance to sleep and (2) whether age or menopausal (MP) transition has a greater effect on the occurrence of nocturia. METHODS: The questions regarding nocturia were part of the Bristol female lower urinary tract symptoms questionnaire (translated into Mandarin, the correlation coefficient r = 0.91). A total of 1253 (79.1% response rate) women were randomly sampled from a community-based female population, aged 20 years or older. Samples were subdivided into reproductive age, perimenopausal stage and elderly. If the participants reported having nocturia, they were further questioned with, "Does it interfere with your sleep or bother your daily life?" The chi-square test and the Cochran-Armitage trend test were used to analyze the data. RESULTS: Nocturia in older age groups was significantly higher than that of the younger age groups. The occurrence of nocturia was significantly associated with the elderly (compared with the reproductive age, P < 0.05). There were no significant differences in the prevalence of nocturia between the perimenopausal stage and the reproductive age (P > 0.05). CONCLUSIONS: Our data implies that the increasing occurrence of nocturia is age-related and is not affected by the transition from pre- to postmenopause. Large-scale prospective longitudinal studies need to be conducted to clarify the effects of the aging process and estrogen deficiency.

Adult↗

PubMed2006

Effects of electrical stimulation of the raphe area on the micturition reflex in cats.

The raphe nucleus has a variety of physiological functions, including emotion, regulation of skeletal muscle motoneurons, spinal transmission of nociceptive signals, sleep, respiration, gastric motility, and cardiovascular function. Recent evidence has shown that centrally administered serotonin has modulatory effects on micturition function, and that decreased brain serotonin might underlie depression and an overactive bladder. We applied high-frequency stimulation (HFS; 0.2-ms duration, 100 Hz) in the raphe nucleus and the adjacent midline area in 20 supracollicular decerebrate cats, which mostly elicited inhibition of the micturition reflex. The effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 muA. We also examined single neuronal activities in the raphe nucleus in response to isovolumetric spontaneous micturition reflexes. In total, 79 neurons were recorded in the raphe nucleus that were related to urinary storage/micturition cycles. Of the neurons recorded, the most common were tonic storage neurons (48%), followed by tonic micturition neurons (28%), phasic storage neurons (18%), and phasic micturition neurons (6%). In addition to the tonic/phasic as well as storage/micturition classification, the neurons showed diverse discharge patterns: augmenting, constant and decrementing, with the constant discharge pattern being most common. Among neurons in the raphe nucleus, the neurons with a decrementing discharge pattern were concentrated in the rostral portion, whereas the augmenting and constant neurons existed diffusely. The storage and micturition neurons were intermingled in the rostral portion, whereas they were separate in the caudal portion. In conclusion, the results of the present study indicate that HFS of the raphe area inhibits the micturition reflex and that there are micturition-related neuronal firings in the raphe area in cats, suggesting that the raphe nucleus is involved in neural control of micturition.

Action Potentials↗

PubMed2004

The patient's perspective: redefining end points.

Overactive bladder (OAB) is a common symptom syndrome that has a considerable effect on quality of life (QOL) and that may contribute to the development of other disabling conditions. Whereas all symptoms of OAB are associated with reductions in QOL, urge incontinence appears to have the greatest negative consequences. Goals of OAB therapy should be to improve symptoms, with a subsequent improvement in QOL. The best tools for evaluating the effects of OAB therapies on QOL remain to be determined. In the past, objective end points, including the reduction of urge incontinence episodes and number of micturitions per 24 hours, have been used to assess the efficacy of pharmacologic agents in the treatment of OAB. However, the subjective nature of OAB demands novel tools to assess patient perception of treatment outcome. In 2 recent studies with the antimuscarinic agent tolterodine, it is suggested that the King's Health Questionnaire is sensitive to therapy-related changes in QOL in patients with OAB, but additional methods to measure patient benefit are still needed.

Humans↗