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PubMed2006

When to use antimuscarinics in men who have lower urinary tract symptoms.

Although alpha-blockers are commonly used and generally effective in men who have symptomatic bladder outlet obstruction (BOO), a subset of these patients who have detrusor overactivity (DOA) often complain of persistent symptoms even after alpha-blocker therapy. What are the barriers to using antimuscarinics induce additional benefit? Should these men be treated primarily with antimuscarinics? The authors review several recent publications that look at this important issue and discuss when antimuscarinics should be used. It appears that BOO with concomitant DOA can be safely and accurately treated with a combination of alpha-blockers and antimuscarinics.

Humans↗
PubMed2003

Percutaneous tibial nerve stimulation in the treatment of overactive bladder: urodynamic data.

AIM: The aim of this study was to evaluate urodynamic changes after percutaneous tibial nerve stimulation (PTNS) for the treatment of complaints related to overactive bladder syndrome and to search for urodynamic-based predictive factors. METHODS: Ninety consecutive patients with symptoms related to overactive bladder syndrome were enrolled in this study. Patients underwent 12 PTNS sessions. For evaluating objective success, the primary outcome measure was a reduction in number of urinary leakage episodes of 50% or more per 24 hours. Patients' request for continuation of therapy was considered subjective success. This study focussed on urodynamic features at baseline and on changes found after 12 PTNS treatments. RESULTS: The objective success rate was 56% (leakages/24 hours). Subjective success rate was 64%. Frequency/volume chart data and quality of life scores improved significantly (P < 0.01). Pre- and posturodynamic data were available from 46 participants. Detrusor instabilities (DI) could be abolished in a few cases only. Increments in cystometric bladder capacity and in volume at DI were significant (P = 0.043 and 0.012, respectively). Subjects without detrusor instabilities at baseline were 1.7 times more prone to respond to PTNS (odds ratio, 1.75; 95% confidence interval [CI], 0.67-4.6). The more the bladder overactivity was pronounced, the less these patients were found to respond to PTNS, the area under the receiver operating curve was 0.644 (95% CI, 0.48-0.804). CONCLUSION: PTNS could not abolish DI. PTNS increased cystometric capacity and delayed the onset of DI. Cystometry seemed useful to select good candidates: patients without DI or with late DI onset proved to be the best candidates for PTNS.

Adult↗
PubMed1998

Vesicourethral dysfunction associated with multiple sclerosis: clinical and urodynamic perspectives.

PURPOSE: We investigate the association of clinical and urodynamic findings with corresponding clinical grade and possible predictors of clinical grade of multiple sclerosis (MS). MATERIALS AND METHODS: A total of 90 patients, 28 to 62 years old (mean age 45.8 +/- 12.1), with the clinical syndrome of MS were consecutively and prospectively studied. All patients were subjected to detailed video urodynamic evaluation and electromyography of the external urethral sphincter. RESULTS: Urodynamic evaluation revealed detrusor hyperreflexia in 52 patients (57.7%), detrusor external sphincter dyssynergia in 27 (30%) and hypocontractility or areflexia of the detrusor in 15 (16.6%). Residual urine varied widely from 50 to 900 ml. Decreased compliance with areflexia was seen in 5 patients (5.5%) and nonrelaxing sphincter (but not contracting) with bladder hypercontractility was noted in 9 (10%). Statistical analysis followed comparison of 2 proportions. When patients with a less severe form (grades 1 and 2) were differentiated from those with a more severe form of MS (grade 3), we observed a significant difference only in incontinence, high post-void residual, leg spasticity, urinary stones, hydronephrosis, type 3 detrusor external sphincter dyssynergia, no electromyography activity and positive sharp waves. The variables with the highest predictive value between the groups were urinary stones, sepsis, type 3 detrusor external sphincter dyssynergia and no electromyography activity of the external urethral sphincter (100%). CONCLUSIONS: Proper identification of the bladder and external urethral sphincter status, especially exclusion of detrusor overactivity or a dyssynergic response of the external urethral sphincter, will prevent complications that may result in deterioration of quality of life.

Adult↗
PubMed2004

Urodynamic findings in adults with primary nocturnal enuresis.

PURPOSE: We evaluate bladder function in adults with primary nocturnal enuresis (PNE) since childhood. MATERIALS AND METHODS: We recruited all patients older than 16 years who presented to our PNE clinic with persistent enuretic symptoms. All patients were assessed by a detailed voiding diary, uroflowmetry and ultrasonography of the urinary tract. Urodynamic studies were performed for those with moderate or severe PNE (more than 3 wet nights a week). RESULTS: The study included 18 males and 29 females with a mean age of 20 years (range 16 to 43). Of these patients 37 (79%) had moderate or severe symptoms and 17 (38%) also had daytime urinary symptoms. Urodynamic studies were conducted in 30 patients, including 12 males and 16 females (93%) with detrusor overactivity. In addition, 73% of patients had urodynamic evidence of functional bladder outflow obstruction, including dysfunctional voiding and detrusor sphincter or detrusor pelvic discoordination. Two male patients (6.7%) had an obstructive pattern on urodynamics and subsequent cystoscopic examination confirmed the presence of congenital obstructive urethral lesions. Sixteen patients (53%) had significantly reduced bladder capacity of less than 300 ml. CONCLUSIONS: Unlike in early childhood, the majority (79%) of enuretic adults had significant symptoms, and more than a third also had daytime urinary symptoms. We believe that PNE in adults is not only a psychologically disturbing condition, but also a urological disorder with significant underlying bladder dysfunction that warrants special attention to management.

Adolescent↗
PubMed2004

Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats.

PURPOSE: We investigated the effects of endothelin (ET) receptor activation in the bladder and the spinal cord on the micturition reflex in urethane anesthetized rats. MATERIALS AND METHODS: The effects of ET receptor activation on bladder activity were examined during continuous infusion cystometrograms. ET-1 was administered intrathecally or intravesically in normal rats or rats pretreated with capsaicin. The effects of intravenous injection of the selective ETA receptor antagonist ABT-627, or selective ETB receptor antagonist A-192621 (Abbott Laboratories, Abbott Park, Illinois) intrathecal injection of the opioid receptor antagonist naloxone hydrochloride on changes in bladder activity induced by intravesical or intrathecal ET-1 administration were investigated. RESULTS: Intravesical injection of ET-1 (0.1 to 10 microM) induced detrusor overactivity, as evidenced by a decrease in intercontraction intervals, in a dose dependent manner. ET-1 induced detrusor overactivity was suppressed by intravenous application of ABT-627 (0.1 mg/kg) as well as capsaicin pretreatment but not by A-192621. In contrast, intrathecal injection of ET-1 (0.5 to 50 fmol) increased intercontraction intervals dose dependently and ET-1 at a higher dose (50 fmol) induced urinary retention. These inhibitory effects were antagonized by ABT-627 (10 mg/kg) and also by intrathecal application of naloxone but not by A-192621. CONCLUSIONS: These results indicate that the activation of ETA receptors in capsaicin sensitive C-fiber afferents in the bladder can induce detrusor overactivity, while ETA receptor activation in the spinal cord can inhibit the micturition reflex via activation of a spinal opioid mechanism. Thus, targeting peripheral ETA receptors could be an effective treatment for bladder overactivity and/or painful conditions.

Afferent Pathways↗
PubMed2000

Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice.

Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder.

Adenosine Triphosphate↗
PubMed1992

The action potential and net membrane currents in isolated human detrusor smooth muscle cells.

The basic electrophysiological properties of the human detrusor have been investigated in vitro using isolated single cells obtained by collagenase digestion of bladder biopsy specimens. Recordings were made using the 'whole-cell patch clamp' technique using either a physiological filling solution or one in which cesium was used to block any outward current. Spontaneous and stimulated action potentials have been recorded and we have performed the first voltage clamp analysis of the currents that underlie the action potential in human detrusor. The depolarising phase of the action potential occurs by an inward current of Ca2+ ions which can be shown to be of sufficient magnitude to support the rate of upstroke. Repolarisation occurs due to an outward K+ current that is partially Ca2+ dependent. The techniques described here permit the investigation of the ionic basis for the control of contractility in the human bladder and may permit the characterisation of any underlying abnormality in the overactive detrusor.

Action Potentials↗
PubMed2006

Mechanisms of disease: role of purinergic signaling in the pathophysiology of bladder dysfunction.

Although the 'purinergic nerve hypothesis' proposed by Burnstock in the early 1970s was met with considerable skepticism, it is now accepted that certain neurons use a purine nucleotide or nucleoside such as ATP or adenosine as a neurotransmitter. Likewise, early studies indicated that the human bladder is devoid of purinergic nerves mediating contraction; however, later studies demonstrated that purinergic nerve-mediated bladder contraction is increased in pathologic conditions such as interstitial cystitis. Cloning and sequencing studies have revealed four subtypes of adenosine receptors and eight subtypes of P2Y receptors, all of which are G-protein-coupled receptors. There are no reports of the cellular location of these receptors in the human bladder. P2X receptors are ligand-gated ion channels, and seven subunits have been cloned and sequenced. Immunohistochemical studies have determined that P2X(1,2,4) subunits are on detrusor-muscle cells, P2X(1-3,5) subunits are on bladder nerves and P2X(2,3,5) subunits are on bladder urothelial cells. Development of purinergic antagonist drugs with selectivity for P2X(1) receptors on detrusor muscle cells might be useful for treatment of detrusor overactivity. Antagonists with selectivity for P2X(3) receptors on bladder sensory nerves might be clinically beneficial for treatment of urinary urgency, and perhaps chronic pelvic pain.

Adenosine Diphosphate↗
PubMed2003

[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↗
PubMed2006

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↗
PubMed1997

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↗