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[Conservative and surgical therapy of urinary incontinence and bladder complaints in the man].

Treatment of incontinence and bladder complaints in the male should be directed to the cause whenever possible. Frequently, however, only symptomatic therapy is possible. Urge incontinence or overactive bladder due to obstruction should primarily be treated by eliminating the obstruction. Medical and surgical treatment methods are available for benign prostatic hyperplasia, bladder neck hypertrophy and prostatic cancer. In contrast, bladder neck sclerosis and uretheral strictures can only be treated surgically. Anticholinergics are primarily indicated if urge symptoms/incontinence persist after obstruction has been relieved or if urge incontinence occurs without obstruction. Seldom, in special cases injection of Botulinustoxin A or augmentation of the bladder may be indicated. Another possible cause of urge symptoms is urinary tract infection. This should be adequately treated according to resistance studies and the cause of the infection determined. In cases of overflow incontinence the infravesicle obstruction must be sought and treated. If limited detrusor contractability is the cause of overflow incontinence and the bladder cannot be emptied through pressmicturition, parasympathicometics may be of help. By insufficient effect, the procedure of intermittent self-catheterization must be taught. If this is not possible, the last resort is placement of a transuretheral or percutaneous catheter for continuous drainage. Stress incontinence is a rare complication in men, usually following prostatic surgery. It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis. Supravesicular urinary diversion is occasionally necessary after conservative and less invasive surgical measures have been exhausted and symptomatic suffering persists. Neurogenic disturbances in bladder capacity and/or emptying can be treated conservatively, medically, surgically or a combination of these depending upon the site of the lesion and the resulting urodynamic patterns.

Animals↗

Pharmacological characterization of urinary bladder smooth muscle contractility following partial bladder outlet obstruction in pigs.

Partial bladder outlet obstruction of the pig is considered as a valuable preclinical model for evaluating the profile of compounds for the treatment of bladder overactivity. In this study, we characterized the pharmacological properties of isolated bladder smooth muscle from pigs following partial outlet obstruction and its sensitivity to potassium channel openers. Bladder strips from obstructed animals showed significantly lower maximal efficacy (E(max)) and sensitivity to stimulation by ATP and carbachol, but not to those evoked by serotonin, compared to age-matched controls. Tissue strips from obstructed animals also showed a 2.5-fold increase in the potency and significantly reduced maximum response following K+ depolarization. With respect to spontaneous activity, bladder strips from control strips demonstrated little spontaneous phasic activity at all preloads examined. In contrast, bladder strips from obstructed animals showed large preload-dependent increases in spontaneous phasic activity at preload values of 16-32 g. The potencies of K(ATP) channel openers to relax carbachol-evoked contractions showed a good 1:1 correlation (r(2)=0.90) between obstructed and control bladder strips. These studies demonstrate that obstructed pig bladders show enhanced spontaneous phasic activity especially at elevated preloads, which may underlie unstable myogenic bladder contractions reported in cystometrographic measurements in vivo. The impaired responses to electrical field stimulation could be attributed to reduced efficacies and/or lower sensitivities of muscarinic and purinergic signaling pathways. K(ATP) channel sensitivities remain essentially unimpaired in the obstructed bladder and could be effectively modulated by openers with potential for the treatment of overactive bladder secondary to outlet obstruction.

Adenosine Triphosphate↗

Bladder compliance in patients with benign prostatic hyperplasia.

Factors influencing bladder compliance were examined in 116 patients with benign prostatic hyperplasia (BPH), by evaluating patients' histories, response of isolated bladder strips to acetylcholine, and the effect of prostatic urethral anesthesia. Patients' age, frequency of micturition, and duration of voiding difficulty were not correlated with bladder compliance. Bladder compliance was significantly low in patients within 30 days after urinary retention, as compared with bladder compliance in patients without an episode of retention. More than 30 days after retention, however, there was a tendency toward increased bladder compliance. Restricted to patients without an episode of retention, bladder compliance in the overactive detrusor group was found to be significantly lower than in the normal group. The responses to acetylcholine of bladder strips were compared between patients with low and normal-compliance bladders. The dose-response curve of patients with low-compliance bladders did not differ from that of those with normal compliance bladders, even when patients with an episode of retention were excluded. After prostatic urethral anesthesia, a significant increase of bladder compliance was observed in patients with an overactive detrusor, while the increase was not significant in patients with a normal detrusor. Our results strongly suggest that easy irritability of the anatomically altered prostatic urethra, as well as bladder over-distension caused by urinary retention, are important factors affecting bladder compliance in BPH patients.

Acetylcholine↗

The impact on health-related quality of life of stress, urge and mixed urinary incontinence.

OBJECTIVE: To examine the impact of each type of urinary incontinence (stress, urge, and mixed) on health-related quality of life (HRQL). SUBJECTS AND METHODS: The USA National Overactive Bladder Evaluation (NOBLE) programme of prevalence was used to identify respondents with incontinence based upon telephone survey responses. A nested case-control study was then conducted on respondents with symptoms of an overactive bladder (OAB), and on age and gender-matched controls; this consisted of the respondents completing a series of questionnaires, including the OAB-q (an HRQL scale for OAB), the Medical Outcomes Study (MOS) Short-Form-36 (SF-36), the MOS Sleep Scale, and the Center for Epidemiological Studies - Depression (CES-D) scale. Respondents were categorized into subgroups according to the primary cause of urine loss, i.e. sudden/uncomfortable urge to urinate (urge, UI), physical pressure (stress, SI), or both (mixed, MI). Descriptive analyses, t-tests and analysis of variance with post hoc comparisons were used. RESULTS: Of the 919 participants in the nested case-control study, 171 reported incontinence, i.e. UI (69), SI (62) and MI (40). Among this cohort, 82.5% were female, 85.4% were Caucasian and the population had a mean age of 55.9 years. All OAB-q subscale scores were significantly (P < 0.01) worse among those with MI than with SI. Respondents with UI reported significantly higher levels of symptom bother and lower sleep scores (both P < 0.001) than those with SI. There were no differences in HRQL between the MI and UI groups. Voiding frequency and nocturia episodes did not differ among the groups but compared with the SI group, both UI and MI groups reported significantly higher ratings of urinary urge intensity (P < 0.001) and rated their need for medical care significantly higher (P < 0.01). The MI group reported more incontinence episodes (P = 0.02) than the SI group. CONCLUSION: Compared with SI, respondents with UI and MI reported not only significantly greater ratings of urinary urge intensity and more incontinence episodes, but also significantly worse HRQL. These results are consistent with previous findings which indicated a greater impact on HRQL for the urge component of MI than for the stress component.

Case-Control Studies↗

Electrical stimulation for the treatment of bladder dysfunction: current status and future possibilities.

Electrical stimulation of peripheral nerves can be used to cause muscle contraction, to activate reflexes, and to modulate some functions of the central nervous system (neuromodulation). If applied to the spinal cord or nerves controlling the lower urinary tract, electrical stimulation can produce bladder or sphincter contraction, produce micturition, and can be applied as a medical treatment in cases of incontinence and urinary retention. This article first reviews the history of electrical stimulation applied for treatment of bladder dysfunction and then focuses on the implantable Finetech-Brindley stimulator to produce bladder emptying, and on external and implantable neuromodulation systems for treatment of incontinence. We conclude by summarizing some recent research efforts including: (a) combined sacral posterior and anterior sacral root stimulator implant (SPARSI), (b) selective stimulation of nerve fibers for selective detrusor activation by sacral ventral root stimulation, (c) microstimulation of the spinal cord, and (d) a newly proposed closed-loop bladder neuroprosthesis to treat incontinence caused by bladder overactivity.

Animals↗

(-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener efficacious in suppressing urinary bladder contractions. I. In vitro characterization.

Alterations in the myogenic activity of the bladder smooth muscle are thought to serve as a basis for the involuntary detrusor contractions associated with the overactive bladder. Activation of ATP-sensitive K(+) (K(ATP)) channels has been recognized as a potentially viable mechanism to modulate membrane excitability in bladder smooth muscle. In this study, we describe the preclinical pharmacology of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a novel 1,4-dihydropyridine K(ATP) channel opener (KCO) that demonstrates enhanced bladder selectivity for the suppression of unstable bladder contractions in vivo relative to other reference KCOs. A-278637 activated K(ATP) channels in bladder smooth muscle cells in a glyburide (glibenclamide)-sensitive manner as assessed by fluorescence membrane potential assays using bis-(1,3-dibutylbarbituric acid)trimethine oxonol (EC(50) = 102 nM) and by whole cell patch clamp. Spontaneous (myogenic) phasic activity of pig bladder strips was suppressed (IC(50) = 23 nM) in a glyburide-sensitive manner by A-278637. A-278637 also inhibited carbachol- and electrical field-stimulated contractions of bladder strips, although the respective potencies were 8- and 13-fold lower compared with inhibition of spontaneous phasic activity. As shown in the accompanying article [Brune ME, Fey TA, Brioni JD, Sullivan JP, Williams M, Carroll WA, Coghlan MJ, and Gopalakrishnan M (2002) J Pharmacol Exp Ther 303:387-394], A-278637 suppressed myogenic contractions in vivo in a model of bladder instability with superior selectivity compared with other KCOs, WAY-133537 [(R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)cyclobut-1-enylamino]-3-ethyl-benzonitrile] and ZD6169 [(S)-N-(4-benzoylphenyl)3,3,3-trifluro-2hydroxy-2-methyl-priopionamide]. A-278637 did not interact with other ion channels, including L-type calcium channels or other neurotransmitter receptor systems. The pharmacological profile of A-278637 represents an attractive basis for further investigations of selective K(ATP) channel openers for the treatment of overactive bladder via myogenic etiology.

ATP-Binding Cassette Transporters↗

Artificial urinary sphincter in patients with neurogenic bladder dysfunction.

OBJECTIVE: To assess the role of the artificial urinary sphincter (AUS) in the management of sphincter weakness incontinence in neuropathic patients. PATIENTS AND METHODS: Ninety patients (75 male and 15 female, mean age 26 years, range 13-62) with neurogenic bladder dysfunction (71 with congenital and 19 with acquired cord lesions) who underwent implantation of an AUS were reviewed. All patients were followed up for a minimum of one year after the initial implantation of the sphincter (mean 4 years, range 1-10). Pre-operative video-urodynamics demonstrated sphincter weakness incontinence in all patients, with 24 patients having an acontractile-type bladder. Of 66 patients with intermediate-type bladders, 52 underwent cystoplasty. RESULTS: Eighty-three patients (92%) were continent both night and day, three were occasionally damp and controlled by pharmacotherapy, and four had a persistent poor result. Of the 66 patients with detrusor hyper-reflexia, 52 (79%) required a cystoplasty to achieve continence and 14 (21%) were controlled with anti-cholinergic therapy. The re-operation rate was 28% (25/90) and complications included six infections, seven erosions, eight system failures, two pump failures, one sheered tube and one rectal and one bladder perforation. Seventy (78%) of the patients currently perform intermittent catheterization to treat high post-voiding residual urine volumes. CONCLUSIONS: A rate of continence > 90% was achieved in these neurogenic patients after implantation of an AUS and we recommend a simultaneous cystoplasty in patients with detrusor overactivity.

Adolescent↗

Predictive value of maximum urethral closure pressure, urethral hypermobility and urethral incompetence in the diagnosis of clinically significant female genuine stress incontinence.

PURPOSE: We determined the value of urethral hypermobility, maximum urethral closure pressure (MUCP) and urethral incompetence in the diagnosis of stress urinary incontinence (SUI). MATERIALS AND METHODS: In this study 369 women with clinical symptoms suggestive of SUI without symptoms of bladder overactivity were evaluated in regard to urethral incompetence, urethral hypermobility and mean MUCP. The cohort was divided into 2 groups according to continence/incontinence status. ROC curves were used to test the performance of the various predicting factors. These factors were combined in forward stepwise logistic regression to find the cutoff point that simultaneously optimized sensitivity and specificity. RESULTS: Continent and incontinent patients differed with regards to urethral incompetence and hypermobility (each p <0.0001). Incontinent patients had a greater probability of a higher grade of each factor. Even after adjusting for the older age of incontinent patients by ANCOVA. MUCP was significantly lower in the incontinent group (p <0.001). The best univariate optimized cutoff point for discriminating continence from incontinence was obtained with urethral incompetence greater than grade I. CONCLUSIONS: The best single predictor of clinically significant SUI is urethral incompetence, followed by urethral hypermobility and MUCP. When combining several factors, namely grade II urethral incompetence with grade III hypermobility, grade III urethral incompetence with grades I to III hypermobility and grade IV urethral incompetence with or without urethral hypermobility, all indicated more than a 90% probability of clinically significant SUI.

Adult↗

[Three cases of neurogenic bladder due to neuro-Beçhet disease].

We reported three cases of neurogenic bladder due to neuro-Beçhet disease. Case 1 (24-year-old male) and case 3 (54-year-old male) had complaint of urinary frequency and urinary incontinence. Case 2 (35-year-old male) had a complaint of urinary retention. Uro-dynamic study were performed repeatedly in each case. Two cases showed overative detrusor activity in storage phase and normal or hypo detrusor activity in voiding phase. One case (case 2) showed normal detrusor activity in storage phase and acontractile in voiding phase. All cases showed detrusor-sphincter dyssynergia (DSD). All cases were managed with clean intermittent catheterization. Six months later case 2 complained of urge incontinence. Repeated uro-dynamic study revealed that bladder function changed from normal detrusor to overactive detrusor in storage phase. These findings suggest that neurogenic bladder due to neuro-Beçhet disease is characterized uro-dynamical by overactive detrusor in storage phase and DSD in voiding phase.

Adult↗

Sexual function in women with urinary incontinence.

To date limited data exists that addresses the impact of urinary incontinence on sexual function. In the present study, we assessed sexual functions in patients with urinary incontinence and compared with healthy continent subjects by means of Female Sexual Function Index (FSFI) questionnaire. A total of 21 premenopausal incontinent women (three stress incontinence, nine overactive bladder and nine mixed incontinence) were enrolled in the study, and 18 healthy continent subjects served as controls. All subjects were asked to complete FSFI questionnaire and each FSFI domain scores including desire, arousal, lubrication, orgasm, satisfaction and pain were calculated. The mean scores in each domain were compared between the groups. Mean age of subjects with urinary incontinence and controls were 39.5+/-6.6 and 32.6+/-9.1 y, respectively. All domain scores were significantly lower in incontinent women except for pain. Among the incontinence types, no significant difference was determined in all domains of FSFI. Urinary incontinence significantly reduces sexual functions in premenopausal sexually active women.

Adult↗

Videourodynamic studies in men with lower urinary tract symptoms: a comparison of community based versus referral urological practices.

PURPOSE: We compared the clinical and urodynamic characteristics of men referred for evaluation of lower urinary tract symptoms in community based versus referral urological practices and examined the various pathophysiological mechanisms of these symptoms. MATERIALS AND METHODS: We reviewed a multicenter urodynamics database of 963 consecutive men referred for the evaluation of persistent lower urinary tract symptoms at 2 community based and 1 urological referral center. Of the 963 patients in the database 422 (44%) were excluded from study due to neurological disorder in 41%, previous urinary or pelvic surgery in 27% and the use of medications known to affect voiding in 24%. A total of 541 patients with a mean age plus or minus standard deviation of 64.4 +/- 13.8 years met study inclusion criteria and were analyzed further. We compared the clinical and urodynamic characteristics of patients at the community and referral centers. RESULTS: Lower urinary tract symptoms were equally common in men presenting to community and referral centers. The most common symptom was difficult voiding, followed by frequency, urgency and nocturia in 58%, 54%, 43% and 40% of the study population, respectively. Urodynamic diagnoses were also similar in the 2 groups. Although bladder outlet obstruction was diagnosed in 69% of patients, it was the only urodynamic finding in a third of the patients with obstruction. The main concomitant urodynamic diagnoses were detrusor overactivity, bladder hyposensitivity, impaired detrusor contractility, low bladder compliance and bladder hypersensitivity in 47%, 10%, 10%, 9% and 3% of obstructed cases, respectively. CONCLUSIONS: The pathophysiology of lower urinary tract symptoms in men is multifactorial, and similar at community practice and tertiary referral centers. The disparity in urodynamic findings and subjective symptoms emphasizes the need for a thorough and early clinical and urodynamic evaluation.

Adult↗

Altered neurogenic and mechanical responses to acetylcholine, ATP and substance P in detrusor from rat with outlet obstruction.

The well-known side effects of anticholinergic compounds used to treat urinary incontinence caused by detrusor overactivity have addressed the interest on other pharmacological intervention. The purpose of the present work was to investigate the possible changes in purinergic and cholinergic components of parasympathetic neurotransmission in obstructed rat bladders with detrusor overactivity, and to examine the effect of the association of suramin, atropine and indomethacin on nerve-mediated responses to electrical field stimulation (EFS). Mechanical responses to exogenous acetylcholine, ATP and substance P were also evaluated. Altered sensitivities to acetylcholine and to the sensory neurotransmitter substance P, but unchanged sensitivity to the stable ATP analogue alpha,beta-methyleneATP were observed in bladders from obstructed rats. Suramin and atropine inhibited purinergic and cholinergic components of the neurogenic responses evoked by EFS in detrusor strips from control and obstructed rats. Interestingly, suramin enhanced the antagonistic effect of atropine on neurogenic responses of detrusor strips at all frequencies of stimulation tested. Our results suggest that the association between an antimuscarinic drug and an antagonist of P2X purinoceptors such as suramin might be helpful to reduce the therapeutic dosage of the antimuscarinic drug, along with its side effects. This approach may be of interest in the therapy of patients with bladder incontinence caused by detrusor overactivity, which do not even respond to a maximal dosage of antimuscarinic drug.

Acetylcholine↗

Video cystometry in young infants with renal dilation or a history of urinary tract infection.

Cystometry is increasingly being used in infants to diagnose bladder dysfunction. However, infantile urodynamic patterns have not been fully established. In this study we investigated the urodynamic patterns in young infants with renal dilation or a history of urinary tract infection, but with no apparent lower urinary tract symptoms. We use video cystometry with simultaneous perineal EMG recording. Thirty-five infants (27 male and 8 female) with congenital renal dilatation or a history of urinary tract infection at age 2 days to 24 months old were involved. We found that detrusor instability occurred in 8.6% of these subjects. Bladder capacity increased with age but less than would nomally be expected. An intermittent voiding pattern was observed in 57% (20/35) of subjects and was characterized by a single or recurring increase in sphincter activity with a simultaneous rise in the voiding detrusor pressure curve. The maximum voiding detrusor pressure with pelvic floor overactivity was significantly higher than that with no pelvic floor overactivity (105+/-44 cmH2O vs 69+/-22 cmH2O, P < 0.001). The median post-voiding residual volume was 2 (range 0 to 65) ml. We conclud that in infants with no apparent lower urinary tract symptoms, bladder instability is uncommon, and the capacity is lower than the normally expected range; an intermittent voiding pattern is common and the residual urine volume showed great variation. This probably represents an immature detrusor-sphincter function.

Dilatation, Pathologic↗