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PubMed2006

Intravesical instillation of human urine after oral administration of trospium, tolterodine and oxybutynin in a rat model of detrusor overactivity.

OBJECTIVE: To study the effects of antimuscarinics excreted into human urine on normal bladder in a rat model of detrusor overactivity. MATERIALS AND METHODS: Two 'normal' adult volunteers collected voided urine after taking trospium (20 mg, twice daily), tolterodine LA (4 mg, four times daily), or oxybutynin XL (10 mg, four times daily). The drugs were taken in a random order for 5 days with a 7-day washout period between the drugs. The urine collected from the two volunteers was mixed together and then blindly labelled and used for testing. Control human urine (no oral antimuscarinics) was also used. The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats anaesthetised with urethane. Cystometric variables during continuous infusion (0.04 mL/min) for >1 h each of saline, human urine, then a mixture of carbachol (30 microm) and human urine were compared in the four groups (control and the three different antimuscarinics tested; six rats per group). RESULTS: Human urine, with or with no intake of antimuscarinic agents, had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after adding carbachol to urine containing vehicle, tolterodine or oxybutynin. However, urine collected from the humans who had taken trospium prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case. CONCLUSION: This is the first report that the urine excreted after oral ingestion of trospium (20 mg, twice daily) has a significant inhibitory effect in a rat model of detrusor overactivity. This suggests that antimuscarinic agents have a local bladder effect during the bladder-storage phase in addition to the smooth muscle-mediated voiding phase.

Administration, Intravesical↗
PubMed2004

Development of the first ultra-potent "capsaicinoid" agonist at transient receptor potential vanilloid type 1 (TRPV1) channels and its therapeutic potential.

Olvanil (N-9-Z-octadecenoyl-vanillamide) is an agonist of transient receptor potential vanilloid type 1 (TRPV1) channels that lack the pungency of capsaicin and was developed as an oral analgesic. Vanillamides are unmatched in terms of structural simplicity, straightforward synthesis, and safety compared with the more powerful TRPV1 agonists, like the structurally complex phorboid compound resiniferatoxin. We have modified the fatty acyl chain of olvanil to obtain ultra-potent analogs. The insertion of a hydroxyl group at C-12 yielded a compound named rinvanil, after ricinoleic acid, significantly less potent than olvanil (EC(50) = 6 versus 0.7 nM), but more versatile in terms of structural modifications because of the presence of an additional functional group. Acetylation and phenylacetylation of rinvanil re-established and dramatically enhanced, respectively, its potency at hTRPV1. With a two-digit picomolar EC(50) (90 pM), phenylacetylrinvanil (PhAR, IDN5890) is the most potent vanillamide ever described with potency comparable with that of resiniferatoxin (EC(50), 11 pM). Benzoyl- and phenylpropionylrinvanil were as potent and less potent than PhAR, respectively, whereas configurational inversion to ent-PhAR and cyclopropanation (but not hydrogenation or epoxidation) of the double bond were tolerated. Finally, iodination of the aromatic hydroxyl caused a dramatic switch in functional activity, generating compounds that behaved as TRPV1 antagonists rather than agonists. Since the potency of PhAR was maintained in rat dorsal root ganglion neurons and, particularly, in the rat urinary bladder, this compound was investigated in an in vivo rat model of urinary incontinence and proved as effective as resiniferatoxin at reducing bladder detrusor overactivity.

Amidohydrolases↗
PubMed2006

Tension-free vaginal tape for stress incontinence in women with detrusor overactivity.

In this case report, we discuss two cases of the successful use of the tension-free vaginal tape (TVT) to treat women with detrusor overactivity (DO) but no evidence of urodynamic stress incontinence (USI). The use of the TVT for the treatment of DO has been evaluated in a small number of studies of women with mixed incontinence. There is no data in the literature concerning its use in women with DO only. Here, we briefly review the literature including the postulated mechanism by which stress leakage due to DO is cured by the TVT.

Adult↗
PubMed2006

Acute urodynamic effects of posterior tibial nerve stimulation on neurogenic detrusor overactivity in patients with MS.

OBJECTIVES: The aim of this study was to investigate whether acute electrical stimulation of the posterior tibial nerve could suppress detrusor contractions in multiple sclerosis (MS) patients with neurogenic detrusor overactivity. METHODS: Two successive slow-fill cystometries (16 ml/min) were carried out in eight MS patients with neurogenic detrusor overactivity. The first filling served as control without stimulation. In the second filling, electrical stimulation using needle electrodes was applied automatically to the posterior tibial nerve when the detrusor pressure exceeded 10 cm H(2)O. An additional filling in which the needle electrodes were replaced by surface electrodes was carried out in three patients. RESULTS: The control filling showed detrusor overactivity in eight patients, but electrical stimulation of the posterior tibial nerve failed to suppress detrusor contractions in all tested patients. CONCLUSIONS: Although neuromodulative effects may be obtained with therapeutic electrical stimulation of the posterior tibial nerve, no acute effects were demonstrated. For this reason, electrical stimulation of pudendal afferents remains the only option if acute suppression of a detrusor contraction is required.

Adult↗
PubMed2006

Will suburothelial injection of small dose of botulinum A toxin have similar therapeutic effects and less adverse events for refractory detrusor overactivity?

OBJECTIVES: To investigate whether suburothelial injection of different doses of botulinum A toxin (BTX-A) will have a similar therapeutic effect but fewer adverse events than 200 U BTX-A in patients with refractory detrusor overactivity. METHODS: A total of 75 patients with detrusor overactivity refractory to anticholinergics were enrolled and randomized to receive 100, 150, or 200 U of BTX-A injected into the suburothelial space at 40 sites. Urinary incontinence was graded on a self-reported scale of 0 to 3, representing continence and mild, moderate and severe incontinence, respectively. The therapeutic effects, adverse events, and urodynamic parameters were assessed at 3 months. RESULTS: An excellent result at 3 months was obtained in 34.8%, 36%, and 40.7% of patients treated with 100, 150, and 200 U of BTX-A, respectively. The patients who received 100 U of BTX-A had a lower incidence of a large postvoid residual urine volume (150 mL or more) than did those who received 150 or 200 U (30.4% versus 52% and 72%, respectively, P = 0.011) after treatment. The posttreatment urodynamic parameters were similar between the patients who received 150 or 200 U of BTX-A, but the changes in bladder capacity and postvoid residual urine volume were greater than those for the patients who received 100 U. The duration of therapeutic effectiveness was significantly shorter for the patients treated with 100 U compared with that for those treated with 150 or 200 U of BTX-A. CONCLUSIONS: Suburothelial injection of 100 U of BTX-A achieved a similar rate of excellent results and had significantly fewer adverse events compared with 150 or 200 U. The dose of suburothelial BTX-A also affected the duration of therapeutic effectiveness.

Botulinum Toxins, Type A↗
PubMed2007

Correlation between motor function and lower urinary tract dysfunction in patients with infantile cerebral palsy.

AIMS: The aim of this study was to evaluate urodynamic findings in patients with infantile cerebral palsy (CP) and to correlate the findings with impaired motor function. METHODS: We conducted a videourodynamic investigation on a highly select group of 29 patients (3-53 years). Motor function was assessed in each patient by the Gross Motor Function Classification System for CP (GMFCS). With this system, motor function is divided into five levels: patients in Level I have the most independent motor function and patients in Level V the least. The patients were divided into Group 1 (23 symptomatic patients with recurrent urinary tract infection or urinary incontinence) and Group 2 (6 asymptomatic patients). RESULTS: In Group 1, 21 patients (91%) had reduced compliance (0.6-16.4 ml/cmH(2)O) and 16 patients (70%) had increased DLPP (>40 cmH(2)O). Detrusor overactivity and pelvic floor overactivity were found in all 23 patients. In Group 2, two patients (33%) had reduced compliance (0.7 and 5.8 ml/cmH(2)O) and four (67%) had increased DLPP (>40 cm H(2)O). Detrusor overactivity and pelvic floor overactivity were observed in five patients (83%). Symptomatic patients showed higher GMFCS levels than asymptomatic patients. In the group of asymptomatic patients, there was no one classified as Levels IV or V, while there were no symptomatic patients classified as Level I. CONCLUSIONS: We conclude that urinary symptoms and pathological urodynamic findings increase along with the degree of motor function impairment shown by the GMFCS. Pathologic urodynamic findings can be found in both symptomatic and in asymptomatic patients.

Adolescent↗
PubMed2006

Randomized controlled trial of foot reflexology for patients with symptomatic idiopathic detrusor overactivity.

The aim of this study was to examine whether foot reflexology has beneficial effects on patients with idiopathic detrusor overactivity. One hundred and nine women with symptomatic idiopathic detrusor overactivity were randomized into either foot reflexology treatment group or nonspecific foot massage control group. The primary outcome measure was the change in the diurnal micturition frequency. There was significant change in the number of daytime frequency in the reflexology group when compared with the massage group (-1.90 vs -0.55, p = 0.029). There was also a decrease in the 24-h micturition frequency in both groups, but the change was not statistically significant (-2.80 vs -1.04 p = 0.055). In the reflexology group, more patients believed to have received "true" reflexology (88.9 vs 67.4%, p = 0.012). This reflects the difficulty of blinding in trials of reflexology. Larger scale studies with a better-designed control group and an improved blinding are required to examine if reflexology is effective in improving patients' overall outcome.

Adult↗
PubMed2006

Botulinum toxin injections for neurogenic and idiopathic detrusor overactivity: A critical analysis of results.

OBJECTIVE: In recent years there has been an increasing use of the botulinum neurotoxins for the management of conditions characterised by detrusor overactivity. Early studies showed promising results in an area where few options previously existed between pharmacotherapy and surgery. This has led to an urgent need to assess the wide range of techniques and therapies available, as well as the efficacy and tolerability of the treatment. We performed a critical analysis of the numerous clinical studies for this novel treatment option in the management of neurogenic and idiopathic detrusor overactivity, with a view to directing further research and assisting urologists in the management of these conditions. METHODS: A systematic review of the literature, as well as a search for abstracts presented to relevant peer-reviewed meetings, was performed. All articles from 1988 onwards were included, prior to which no articles describing urologic use of botulinum neurotoxins had been published, although the majority of the articles have been published since 2000. RESULTS AND CONCLUSIONS: Although many of the studies were small, overwhelming evidence supports the efficacy, safety, and tolerability of the botulinum toxins, specifically serotype A, for the management of these conditions. Before this is accepted as a widespread treatment modality, good-quality evidence from large-scale randomised controlled trials is needed. These studies should identify not only the most appropriate patients to treat but also the best dose, administration technique, and frequency for treatment.

Adult↗
PubMed2007

Detrusor overactivity and urge urinary incontinence following trans obturator versus midurethral slings.

AIMS: To compare the rates of resolution of detrusor overactivity (DO) and subjective urge urinary incontinence (UUI) as well as de novo DO and UUI between the Monarc, TVT, and SPARC midurethral sling procedures. METHODS: Two hundred and seventy-six subjects with urodynamic stress or mixed urinary incontinence underwent retropubic midurethral slings (TVT, N = 99; SPARC, N = 52) or transobturator slings (Monarc, N = 125). All evaluable subjects had a routine office evaluation, subjective assessment of UUI, and multichannel urodynamic testing pre- and 3 months postoperatively. Comparisons were made using Student's t-test, ANOVA, McNemar's test, and Chi-Square test where appropriate. Multivariate logistic regression was performed to detect possible confounding factors such as sling type, and differences in concomitant surgical procedures. RESULTS: De novo subjective UUI differed significantly between the Monarc and the other two slings (33% TVT vs. 8% Monarc vs. 17% SPARC, P = 0.04). Fourteen to Sixteen percents of patients with preoperative UUI who underwent TVT or SPARC had worsening of their UUI symptoms while only 6% of the Monarc group did (P = 0.02). There was no difference in rates of resolution of DO among the three groups (40% vs. 48% vs. 32%, P = 0.39) or de novo DO (32% vs. 22% vs. 22%, P = 0.64) at 3 months. CONCLUSIONS: Patients who undergo transobturator procedures have significantly lower rates of de novo UUI than those who undergo midurethral sling procedures. Rates of resolution of DO, UUI, and de novo DO do not differ between groups.

Cohort Studies↗
PubMed2007

Sacral nerve stimulation for voiding dysfunction: One institution's 11-year experience.

AIM: The purpose of this study was to review our institution's 11-year experience with SNS for the treatment of refractory voiding dysfunction. Dating back to 1993, it covers a span of time which describes the evolution of SNS as it includes PNE trials, non-tined (bone-anchored or fascial-anchored) leads, percutaneous tined leads with two-staged procedures, and even percutaneous pudendal trials. METHODS: A retrospective review was performed on SNS patients who received an implantable pulse generator (IPG) in our practice from 12/1993 to 12/2004. After Institutional Review Board approval, consents for chart review were obtained from 104 patients, representing 44% of this neuromodulatory patient population. RESULTS: Of our population, 87% were female and 13% were male. Average age at implant was 50 years +/- 13.4 years. Duration of symptoms before implantation was 116 months (range 9-600 months). Eighty percent were implanted for a predominant complaint of urinary urgency and frequency (U/F). Overall, 22% had U/F only, 38% had concomitant urge incontinence (UI), and 20% had concomitant mixed incontinence (MI). Twenty percent were treated for non-obstructive urinary retention (UR), with half of these associated with a neurogenic etiology. Additionally, 46.2% had pelvic pain, 58.6% had bowel complaints, and 51% reported sexual dysfunction. In patients with U/F, mean voiding parameters as described by pre-implant voiding diaries revealed the following: 12.4 (+/-5.1) voids per 24 hr; 2.3 (+/-1.8) voids per night; 5.0 (+/-4.7) leaks per 24 hr; and 2.3 (+/-2.6) pads per 24 hr. Statistically significant improvements post-implantation were noted with mean decreases in the following: 4.3 voids per 24 hr; 1.0 void per night; 4.4 leaks per 24 hr; and 2.3 pads per 24 hr (all P < 0.05). In the UR group a statistically significant improvement post-implantation was noted only in voids per night, with a mean decrease of 0.8 (P < 0.05). With a mean follow up of 22 months (range 3-162 months), sustained subjective improvement was >50%, >80%, and >90% in 69%, 50%, and 35% of patients, respectively. By quality of life survey, 60.5% of patients were satisfied and 16.1% were dissatisfied with current urinary symptoms. Only 13% (14 patients) abandoned therapy, making up a significant portion of those dissatisfied with current urinary symptoms. Good overall lead durability was seen (mean 22 months, range 1-121 months), with the first successful lead proving to be the most durable (mean 28 months, range 1.4-120 months). Lead durability decreased progressively with subsequent trials. Overall, 53% of patients experienced at least one reportable event (RE) attributable to either lead or IPG. A total of 126 REs were noted, with 97% mild-to-moderate in severity. REs included lack of efficacy, loss of efficacy, infection, hematoma/seroma, migration, pain, undesirable change in sensation, and device malfunction. In this population, 47.1% of leads were tined while 52.9% were non-tined. Tined leads had an overall lower RE rate as compared to non-tined leads: 28% and 73%, respectively. CONCLUSIONS: SNS is an effective method for treating certain types of voiding dysfunction. Although 53% of patients experienced at least one RE, 97% were mild-to-moderate and did not appear to affect the continued use of this therapy. With improved technology, such as percutaneous tined leads, the RE rate is decreasing. Further analyses of subsets of this population are currently underway.

Adult↗
PubMed2005

Urethral syndrome: response to alpha-adrenergic blocking agents.

Urethral syndrome patients have irritative bladder symptoms in the absence of any objective urological findings. While not life threatening, it can have a severe disruptive effect on the quality of life. Attempts at symptom control are not always effective because of lack of clarity about the underlying aetiology. We describe a case of a 27-year-old patient whose irritative bladder symptoms showed response to alpha-adrenergic blocking agents on two separate occasions during the course of her treatment.

Adrenergic alpha-Antagonists↗
PubMed2006

The relationship of urethral resistance pressure and pressure flow parameters in women with lower urinary tract symptoms.

This prospective study aims to evaluate the relationship between urethral resistance pressure (URP) and pressure flow parameters in women with lower urinary tract symptoms (LUTS). Consecutive women with LUTS attending three tertiary referral urodynamic clinics were asked to undergo urodynamic evaluation, pressure flow studies and URP measurement. The pressure flow parameters such as detrusor pressures at the start of flow (ODP), detrusor pressure at peak flow rate (PdetQmax), peak flow rate (Qmax) and detrusor pressure at the end of flow (CDP) were measured. The relationship between URP and pressure flow parameters was evaluated as well as differences between each urodynamic group. Two hundred seventy-nine women attended for urodynamic investigations. Two hundred twenty-three (79.9%) women had good quality pressure flow measurements and were included in the study. The mean age was 58 years (range 21-83). Women with urodynamic stress incontinence had significantly lower URP and ODP than those with detrusor over-activity [54.8 (+/-17.9) and 12.4 (+/-4.1) cmH(2)O, respectively, vs 85.6 (+/-21.4) and 33.7 (+/-13.3) cmH(2)O, respectively) (p<0.05, Bonferroni test). Furthermore, women with urodynamic stress incontinence have significantly lower PdetQmax values as well as higher Qmax than women with competent urethral sphincters (p<0.05, Bonferroni test). There was a significant correlation between ODP, PdetQmax, Qmax and URP measurements. In urodynamic stress incontinence, both URP and pressure flow parameters are reduced. Although the trend for values of both tests were similar and there was a significant correlation between these tests, we should consider that urethral function at rest differ from that during voiding due to activation of additional mechanisms. Therefore, further study is needed to confirm our results.

Adult↗
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↗
PubMed2006

Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects.

OBJECTIVES: To investigate the effects of darifenacin controlled-release (CR) and oxybutynin extended-release (ER) on cognitive function (particularly memory) in older subjects. METHODS: Healthy subjects (n=150) >/=60 years were randomised to darifenacin, oxybutynin ER or placebo in a multicentre, double-blind, double-dummy, parallel-group, 3-week study. Doses were administered according to US labels: oxybutynin ER 10mg once daily (od), increasing to 15mg od then 20mg od by week 3; darifenacin 7.5mg od in weeks 1 and 2, then 15mg od in week 3. The primary end point was accuracy on the Name-Face Association Test (delayed recall) at week 3. RESULTS: Results of the Name-Face Association Test at week 3 showed no significant difference between darifenacin and placebo on delayed recall (mean difference, -0.06, p=0.908). In contrast, oxybutynin ER resulted in memory impairment, with significantly lower scores than placebo and darifenacin (mean differences, -1.30, p=0.011 and -1.24, p=0.022, respectively) for delayed recall on the Name-Face Association Test at week 3. Additional tests of delayed recall indicated significant memory impairment with oxybutynin ER versus placebo at certain time points, whereas darifenacin was similar to placebo. No between-treatment differences were detected in self-rated memory, demonstrating that subjects were unaware of memory deterioration. CONCLUSIONS: While darifenacin had no significant effects on memory versus placebo, oxybutynin ER caused significant memory deterioration (magnitude of effect comparable to brain aging of 10 years). The results also demonstrate that subjects may not recognise/report memory deterioration.

Aged↗