[More quality of life again with tolterodine].
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Benzhydryl Compounds↗
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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↗
[Clinical effects of clenbuterol-HCL in urge incontinence and stress incontinence].
A total of 49 patients complaining of pollakisuria and incontinence; 20 patients with overactive neurogenic bladder and 29 patients with stress incontinence, were treated with clenbuterol, and the effects of the drug were studied. Subjective symptoms were improved markedly in 8 patients (17%), moderately in 14 patients (29%), and slightly in 10 patients (21%). The symptoms were unchanged in 15 patients (31%) and aggravated in 1 patient (2%). In objective observation, the volume at first desire to void (P less than 0.01) and the maximum urethral closure pressure (P less than 0.05) significantly increased. The objective symptoms were improved markedly in 2 patients (5%), moderately in 12 patients (27%), and slightly in 11 patients (25%). The symptoms were unchanged in 15 patients (34%) and aggravated in 4 patients (9%). Overall improvement was graded as marked in 7 patients (15%), moderate in 17 patients (35%), slight in 11 patients (23%), unchanged in 13 patients (27%) and aggravated in none. In neurogenic bladder, the overall improvement was graded as marked in 2 patients (11%), moderate in 4 patients (21%), slight in 4 patients (21%), unchanged in 9 patients (47%) and aggravated in none. In stress incontinence, the overall improvement was graded as marked in 5 patients (17%), moderate in 13 patients (45%), slight in 7 patients (24%), unchanged in 4 patients (14%) and aggravated in none. Side effects were noted in 12 patients (25%) and they were all not serious. Finger tremor was the most common side effect (5 patients).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Bladder diary volume per void measurements in detrusor overactivity.
PURPOSE: We investigated the clinical usefulness of adjusting reference volume per void values for a recently reported strong tendency for volume per void to increase with increasing 24-hour volume in asymptomatic individuals. Our approach was to 1) test whether the adjustment increases the separation between volume per void measurements in patients with detrusor overactivity and an asymptomatic reference population, and 2) compare by regression analysis volume per void vs 24-hour volume relationships in patients with detrusor overactivity and asymptomatic volunteers. MATERIALS AND METHODS: We studied 3-day bladder diaries in 29 patients with detrusor overactivity and without genuine stress incontinence, an age matched control group of 29 asymptomatic women and a reference population of 161 asymptomatic women. Minimum, maximum and average volume per void measurements were calculated. The incidence of volume per void measurements below the 10th reference percentile was used as the measure of separation between the detrusor overactivity and asymptomatic populations. RESULTS: In patients with detrusor overactivity volume per void showed a highly significant positive relationship to 24-hour volume (p <0.0005). However, patient data points tended to lie below and parallel to control data points. Adjusting for the 24-hour volume relationship significantly increased the incidence of volume per void measurements below the 10th reference percentile in patients with detrusor overactivity (p <0.01). CONCLUSIONS: Adjusting for the 24-hour volume relationship increased the separation of patients with detrusor overactivity volume per void measurements from the reference population. Adjusting volume per void percentiles for the 24-hour volume relationship decreased the incidence of false-negative volume per void percentiles above the 10th percentile in patients with detrusor overactivity and false-positive volume per void percentiles below the 10th percentile in asymptomatic volunteers.
Adult↗
Antimuscarinics and the overactive detrusor--which is the main mechanism of action?
Contraction of the bladder, voluntary or involuntary, involves stimulation of the muscarinic receptors on the detrusor by acetylcholine, released from activated cholinergic nerves. Antimuscarinics are the drugs of choice for treatment of detrusor overactivity and the overactive bladder (OAB) syndrome. However, antimuscarinics at clinically recommended doses have little effect on voiding contractions, and may act mainly during the bladder storage phase, during which there is normally no parasympathetic outflow from the spinal cord. Supporting this, antimuscarinics have been shown to reduce bladder tone during storage, and to increase cystometric bladder capacity. A basal release of acetylcholine from non-neuronal (urothelial) as well as neuronal sources has been demonstrated in isolated human detrusor muscle. It is suggested that this release, which is increased by stretching the muscle and in the aging bladder, contributes to detrusor overactivity and OAB by eventually increasing bladder afferent activity during storage.
Humans↗
Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment.
OBJECTIVE: To compare PGP9.5 and transient receptor potential vanilloid receptor (TRPV1) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, as suburothelial PGP9.5-staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin, and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder. PATIENTS AND METHODS: Patients with refractory NDO were enrolled in a prospective, randomized, parallel-group, double-blind, placebo-controlled trial using escalating doses of resiniferatoxin to a maximum of 1 micro mol/L. Flexible cystoscopic bladder biopsies obtained at baseline, 4 weeks after each instillation and at the time of maximum clinical response were compared with biopsies taken from control subjects. Frozen sections were incubated with rabbit antibodies to TRPV1 and PGP9.5, and assessed using standard immunohistochemical methods. PGP9.5 nerve density was analysed using a nerve-counting graticule by an observer unaware of sample origin. Another two independent observers unaware of each other's results used a random grading scale to evaluate TRPV1 nerve fibre density and intensity. The immunohistochemistry results were compared with histology findings (haematoxylin-eosin), and the Mann-Whitney test used to assess any differences (P < 0.05 significant) and the Pearson test for correlation. RESULTS: There were eight controls and 20 patients with spinal NDO, 14 (five clinical responders and nine not) who received the maximum dose of resiniferatoxin. There were more PGP9.5 and TRPV1 nerve fibres in patients with NDO than in controls (P = 0.007 and 0.002, respectively). Immunoreactivity before resiniferatoxin was similar in both groups for both PGP9.5 and TRPV1. In responders there were fewer PGP9.5 and TRPV1-positive fibres after treatment (P = 0.008 for each) but no change in those not responding. Changes after treatment for TRPV1 correlated well with those for PGP9.5 (r = 0.88, P < 0.001). CONCLUSIONS: The decrease of PGP9.5 and TRPV1 immunoreactive nerve fibres in responders to resiniferatoxin (to levels in control tissues) suggests that the increased numbers of nerve fibres in patients with NDO are mainly of sensory origin and express TRPV1. As baseline nerve fibre values were similar in responders and nonresponders, an additional factor may account for the difference in treatment outcome.
Administration, Intravesical↗
The case for bladder botulinum toxin application.
Botulinum toxin (BoNT) has been shown to be and effective agent in suppressing detrusor overactivity due to neurogenic causes. Recently, BoNT has been extended to patients who have idiopathic detrusor overactivity. This article reviews the use of BoNT to treat disorders of neurogenic detrusor overactivity and establishes BoNT as a therapeutic modality to treat idiopathic bladder overactivity. It is important to remember that the application of BoNT in the lower urinary tract is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.
Administration, Intravesical↗
Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy.
BACKGROUND: Surgery performed to improve or replace the function of the diseased urinary bladder has been carried out for over a century. Main reasons for improving or replacing the function of the urinary bladder are bladder cancer, neurogenic bladder dysfunction, detrusor overactivity and chronic inflammatory diseases of the bladder (such as interstitial cystitis, tuberculosis and schistosomiasis). There is still much uncertainty about the best surgical approach. Options available at the present time include: (1) conduit diversion (the creation of various intestinal conduits to the skin) or continent diversion (which includes either a rectal reservoir or continent cutaneous diversion), (2) bladder reconstruction and (3) replacement of the bladder with various intestinal segments. OBJECTIVES: To determine the best way of improving or replacing the function of the lower urinary tract using intestinal segments when the bladder has to be removed or when it has been rendered useless or dangerous by disease. SEARCH STRATEGY: We searched the Cochrane Incontinence Group's specialised register (3 May 2001), The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2001), MEDLINE (1966 to May 2001), PREMEDLINE (4 June 2001), Dissertation Abstracts (18.6.2001) and the reference lists of relevant articles. Date of most recent search: June 2001. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of surgery involving transposition of an intestinal segment into the urinary tract. DATA COLLECTION AND ANALYSIS: Trials were evaluated for appropriateness for inclusion and for methodological quality by the reviewers. Three reviewers were involved in the data extraction. The data collected was then analysed for statistical significance. MAIN RESULTS: Two trials met the inclusion criteria with a total of 164 participants. These trials addressed only four of the 14 comparisons pre-specified in the protocol. There were no statistically significant differences found in the incidence of upper urinary tract infection, ureterointestinal stenosis and renal deterioration in the comparison of continent diversion with conduit diversion. There was no evidence of a difference in incidence of upper urinary tract infection and uretero-intestinal stenosis when conduit diversions were fashioned from either ileum or colon. No statistically significant difference was found in the incidence of renal scarring between anti-refluxing versus freely refluxing uretero-intestinal anastomotic techniques in conduit diversions. The confidence intervals were all wide, however, and did not rule out important differences. There was some limited evidence that use of the more complex nipple valve at the ureteroileal anastomosis was more likely to lead to upper tract deterioration than implantation into a non-detubularised, isoperistaltic ileal afferent limb. REVIEWER'S CONCLUSIONS: The evidence from the included trials was very limited. Only two studies met the inclusion criteria; these were small, of moderate or poor methodological quality, and reported few of the pre-selected outcome measures. This review did not find any evidence that bladder replacement (orthotopic or continent diversion) was better than conduit diversion following cystectomy for cancer. There was no evidence to suggest that bladder reconstruction was better than conduit diversion for benign disease. The small amount of usable evidence for this review suggests that collaborative multicentre studies should be organised, using random allocation where possible.
Cystectomy↗
Assessment of bladder and urethral sphincter function before and after radical retropubic prostatectomy.
PURPOSE: In a prospective study we analyzed the effects of radical retropubic prostatectomy (RRP) on detrusor and urethral sphincter function by comparing urodynamic status preoperatively with that during longitudinal followup. MATERIALS AND METHODS: A total of 49 consecutive patients underwent urodynamics with pressure flow studies and Valsalva leak point pressure measurements 3 to 7 days before RRP (baseline), and then 1 and 8 months after surgery. We assessed bladder compliance, detrusor overactivity, detrusor contractility and intrinsic sphincter deficiency (ISD). RESULTS: There was no significant change in detrusor overactivity at 1 and 8 months of followup. Decreased bladder compliance was observed in 20.4% of patients at baseline, and in 38.7% and 30.6% at 1 and 8 months, respectively. De novo decreased compliance was detected in 18.4% and 10.2% of patients at the same points. Impaired bladder compliance was comparable to that before surgery in 20% of cases. Impaired detrusor contractility was detected in 42.8% of patients at baseline, and in 61.2% (p <0.05) and 42.8% at 1 and 8 months, respectively. De novo hypocontractility was observed in 28.6% and 10.2% of patients at 1 and 8 months, respectively. A strong association between detrusor overactivity and ISD was observed at 1 and 8 months (p <0.01). CONCLUSIONS: Following RRP detrusor hypocontractility and decreased bladder compliance represent de novo transient dysfunction probably due to bladder denervation and an established condition not influenced by the operation. The strong association between overactivity and ISD suggests that stress urinary incontinence increases urethral afferent nerve activity and induces involuntary detrusor contractions.
Aged↗
Current trends in the evaluation and management of female urinary incontinence.
Despite its common occurrence and often seemingly obvious causes, female urinary incontinence requires a thorough and thoughtful evaluation for its proper diagnosis and treatment. With rare exceptions, urinary incontinence is the result of failure of the sphincter mechanism to resist bladder pressures encountered during daily activities. This may be the result of sphincter failure, overactivity of the bladder detrusor muscle or both. In uncomplicated cases, the diagnosis is usually based on an evaluation in the office. Urodynamic and cystoscopic study may be helpful in complex, resistant and recurring cases of urinary incontinence of any cause. Most cases of incontinence may be classified as stress, urge or mixed urinary incontinence. Treatment of stress urinary incontinence focuses on supplementing the urethral continence mechanisms, particularly the urethral supports and periurethral striated muscle function. The current paradigm for the treatment of urge incontinence centres on pharmacologic therapy, primarily by correcting detrusor overactivity with antimuscarinic drugs. Other therapies aimed at altering sensorimotor function may be used in resistant cases. The treatment of mixed urinary incontinence requires consideration of the contribution of each of its components. With proper diagnosis, effective treatment is possible for most patients.
Female↗
The evolution of detrusor overactivity after watchful waiting, medical therapy and surgery in patients with bladder outlet obstruction.
PURPOSE: We analyzed the evolution of detrusor overactivity in patients with bladder outlet obstruction treated with either medical or surgical therapy or watchful waiting. MATERIALS AND METHODS: Of 255 patients with symptomatic benign prostatic enlargement who completed the International Prostate Symptom Score and underwent full urodynamic investigation 161 presented with bladder outlet obstruction. Of the 161 men 101 were reevaluated with a second clinical evaluation and urodynamics 1 to 5 years (mean 2) after watchful waiting in 20, medical treatment (alfuzosin 20 and finasteride 16) in 36 and surgery (transurethral incision of the prostate 13 and prostatectomy 32) in 45. For statistical analysis Wilcoxon matched paired data and Kruskal Wallis tests were used as appropriate. RESULTS: Overall detrusor overactivity was present in 53 patients (52%) at baseline and 41 (40%) at followup. Detrusor overactivity was present in 9 patients (45%) at baseline and 11 (55%) at followup in the watchful waiting group (p = 0.17); 7 (35%) at baseline and 6 (30%) at followup in the alfuzosin group (p = 0.37); 10 (62.5%) at baseline and 10 at followup in the finasteride group (p = 1); 6 (46%) at baseline and 4 (30%) at followup in the transurethral prostate incision group (p = 0.48); and 21 (68%) at baseline and 10 (31%) at followup in the prostatectomy group (p = 0.02). CONCLUSIONS: Detrusor overactivity is highly prevalent (52%) in patients with bladder outlet obstruction, and appears to persist for long periods when obstruction is left untreated or treated only with medical therapy. However, surgical treatment of bladder outlet obstruction, prostatectomy in particular, significantly reduces the incidence of detrusor overactivity and lessens the chance of its de novo appearance for up to 5 years.
Humans↗
Response of bladder smooth muscle cells to obstruction: signal transduction and the role of mechanosensors.
Bladder hypertrophy and detrusor overactivity are well-known bladder responses to outlet obstruction. Mechanical stretch stress is considered the trigger inducing these responses in the urodynamically overloaded bladder. Several studies using an in vitro model of mechanical stress demonstrate that repetitive stretch stimulation of bladder smooth muscle cells results in increased expression of a variety of growth factors and other specific proteins. In the bladder smooth muscle cell, stretch-activated ion channels (SACs) and protein kinase C (PKC) sarcolemmal proteins may function as sensors for external mechanical forces. In particular, SACs couple mechanical stress to activation of c-jun NH2-terminal kinase, which leads to a rapid induction of nuclear transcription factors. PKC also may involve an indirect or direct regulation of nuclear events. In addition, mechanical stress may induce the release of angiotensin II in an autocrine fashion. These factors in turn stimulate expression of specific gene-encoding proteins, such as heparin-binding epidermal growth factor-like growth factor, nerve growth factor, and an isomer of cyclooxygenase-2, all of which have the potential to contribute to structural and functional alterations in the bladder after obstruction.
Animals↗
Longitudinal changes in post-void residual and voided volume among community dwelling men.
PURPOSE: We describe the natural history of post-void residual (PVR) and voided volume (VV) in men. MATERIALS AND METHODS: A random sample of community dwelling men (529 men 40 to 79 years old) were followed with a sonographic PVR and VV every 2 years for up to 12 years (median 5 examinations). Men were censored at the time of treatment for a prostate condition. RESULTS: The median annual change (slope) for PVR was 2.2% (p=0.03) and for VV was -2.1% (p <0.0001). There was considerable variability in PVR slopes (25th percentile -11%, 75th percentile 18%). A rapid increase in PVR slope (greater than 80th percentile) was more likely in men with a baseline American Urological Association Symptom Index greater than 7 (age adjusted odds ratio [OR]1.6, 95% CI 1.0 to 2.5). There was less variability in VV slopes (25th percentile -8.0%, 75th percentile 3.1%). A rapid decrease in VV slope (less than 20th percentile) was more likely in men with baseline age 70 to 79 years than 40 to 49 years (OR 3.9, 95% CI 2.1 to 7.2) and in men with a baseline PVR greater than 50 ml (age adjusted OR 2.1, 95% CI 1.2 to 3.6). CONCLUSIONS: Although it is highly variable, there is progressive bladder dysfunction in community dwelling men as they age. In addition, signs and symptoms attributed to benign prostatic hyperplasia were modest predictors of the development of bladder dysfunction. A baseline increased PVR predicted a rapid decrease in VV, consistent with a bladder outlet obstruction contributing to the development of detrusor overactivity and decreased bladder compliance.
Adult↗
Botulinum-A toxin injections into the detrusor muscle decrease nerve growth factor bladder tissue levels in patients with neurogenic detrusor overactivity.
PURPOSE: We investigated the effects of BTX-A on visceral afferent nerve transmission by measuring bladder tissue NGF levels in patients with neurogenic detrusor overactivity before and after intravesical treatment with BTX-A. We also compared the bladder tissue NGF content with clinical and urodynamic data. MATERIALS AND METHODS: A total of 23 patients underwent clinical evaluation and urodynamics with detection of the UDC threshold, maximum pressure and maximum cystometric capacity before, and at the 1 and 3-month followups. Endoscopic bladder wall biopsies were also obtained at the same time points. NGF levels were measured in tissue homogenate by enzyme-linked immunosorbent assay (Promega, Madison, Wisconsin). RESULTS: At 1 and 3 months mean catheterization and incontinent episodes were significantly decreased (p <0.05 and <0.001, respectively). On urodynamics we detected a significant increase in the UDC threshold and maximum cystometric capacity, and a significant decrease in UDC maximum pressure at the 1 and 3-month follow-ups compared to baseline (each p <0.001). At the same time points we detected a significant decrease in NGF bladder tissue content (each p <0.02). CONCLUSIONS: BTX-A intravesical treatment induces a state of NGF deprivation in bladder tissue that persists at least up to 3 months. As caused by BTX-A, the decrease in acetylcholine release at the presynaptic level may induce a decrease in detrusor contractility and in NGF production by the detrusor muscle. Alternatively BTX-A can decrease the bladder level of neurotransmitters that normally modulate NGF production and release.
Administration, Intravesical↗
Changes in urethral resistance in the presence of detrusor activity.
This was a prospective study performed at two tertiary referral teaching hospitals. The aim of our study was to investigate changes in urethral resistance with the bladder full compared to empty in women with different urodynamic diagnoses. Consecutive women attending the urodynamic clinics were asked to undergo urethral retro-resistance pressure (URP) measurement with the bladder empty and then full. 106 women were recruited - 25 had normal urodynamic studies, 17 had detrusor overactivity, 57 had urodynamic stress incontinence and 7 had mixed incontinence. Women with urodynamic stress incontinence have lower URP values than women with normal urodynamic studies or those with detrusor overactivity with the bladder empty (p = 0.01). Women with normal urodynamic studies and urodynamic stress incontinence showed a statistically significant rise in URP with the bladder full (p = 0.013 and p = 0.003, respectively). In women with detrusor overactivity, the converse was seen - URP was significantly lower with the bladder full compared to empty (p = 0.004). Our study has shown that bladder filling alters URP measurement and bladder volume should be standardised for reporting URP.
Adult↗
Intercellular communication and bladder function.
There is now considerable experimental and clinical evidence supporting the supposition that overactivity of the bladder is associated with detectable alterations in the electrical properties of the detrusor smooth muscle cells. The preliminary data described in this report indicates that intercellular communication through gap junctions might play an important role in this process. Moreover, alterations in Cx43 mRNA expression may represent a tissue response to a physiologic insult (i.e., increased after load) in an attempt to further increase the syncytial nature and force of detrusor contractility to compensate for an increased pressure load. Finally, this report elucidates the rationale for suspecting that intercellular communication through gap junctions may play a role in normal bladder physiology and the pathophysiology of urinary incontinence caused by partial outlet obstruction.
Animals↗
Adherens junctions of the human detrusor.
OBJECTIVE: To immunohistochemically identify the protein composition of adherens junctions, which couple smooth muscle cells mechanically, and to confirm their decrease in different bladder dysfunctions, as studies in geriatric bladder dysfunction show fewer such junctions in patients with detrusor overactivity (DO) and bladder outlet obstruction (BOO). MATERIAL AND METHODS: Detrusor biopsies were obtained from video-urodynamically evaluated patients with neurogenic DO (NDO, 31 patients), BOO (six patients) and from six patients with stress urinary incontinence (SUI) with stable, unobstructed detrusors (serving as controls). Specimens were fixed, paraffin-embedded, sectioned, stained with a polyclonal pan-cadherin antibody, monoclonal alpha-, beta- and gamma-catenin antibodies, and a monoclonal integrin-beta1 antibody. All antibodies were known to react with proteins of adherens junctions. Two examiners unaware of sample origin evaluated the sections qualitatively and using a semiquantitative scale. The results were correlated with the patient groups. RESULTS: Specific immunohistochemical staining of pan-cadherin, alpha-, beta- and gamma-catenin could not be detected in any detrusor smooth muscle compartment, but was present in the urothelium. There was integrin-beta1 reactivity in the basement membranes of bladder smooth muscle cells in 38 of 43 detrusor biopsies. There were no differences among the three groups. CONCLUSION: The known proteins of cell-cell adherens junctions are not part of the cell-cell junctions of detrusor smooth muscle. The specific staining of integrin-beta1 indicates either the presence of cell-matrix junctions or of cell-cell junctions within the human detrusor. Further studies are needed to identify the complete protein composition of adherens junctions within smooth muscle cells.
Adherens Junctions↗
Botulinum toxin in the management of lower urinary tract dysfunction: contemporary update.
PURPOSE OF REVIEW: To review the most recent experience concerning the application of botulinum toxin in the human lower urinary tract. RECENT FINDINGS: Botulinum toxin was initially applied in the bladder of patients with spinal neurogenic detrusor overactivity and urinary incontinence, or in the urethra in cases of detrusor external sphincter dyssynergia. A large multicentric European study fully confirmed the initial expectancy in the former condition. In addition, the application of botulinum toxin was extended to the treatment of other urological disorders including non-neurogenic detrusor overactivity, non-relaxing urethral sphincter and detrusor underactivity. Interesting reports on the injection of botulinum toxin into the prostate of patients with benign prostatic hyperplasia are also reviewed. SUMMARY: Bladder injection of botulinum toxin is not yet an approved treatment for lower urinary tract dysfunction. Nevertheless, available data suggest that in the near future the toxin will become a standard therapeutic option in incontinent patients with neurogenic and non-neurogenic forms of overactive bladder, who do not respond to or do not tolerate anticholinergic medication. In addition, it might be expected that urethral botulinum toxin injections improve bladder emptying in patients with dysfunctional voiding problems besides detrusor external sphincter dyssynergia.
Adult↗