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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↗

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↗

PubMed2004

Muscarinic receptor subtypes of the bladder and gastrointestinal tract.

The parasympathetic nervous system is responsible for maintaining normal intestinal and bladder function, contracting the smooth muscle by releasing the neurotransmitters acetylcholine (ACh) and ATP and relaxing sphincters by releasing nitric oxide. ACh is the main transmitter released and smooth muscle contraction is mediated via a mixed M2/M3 receptor population; M3 receptors acting via phospholipase C and M2 receptors acting via inhibition of adenylate cyclase. In ileal, colonic, gastric and bladder (detrusor) smooth muscle the density of M2 receptors is far greater than the density of M3 receptors, the M2:M3 ratio being 3:1 in most species including man. Despite the predominance of M2-receptors, direct contraction of intestinal and detrusor smooth muscle is mediated via the M3-receptor subtype and only this subtype is involved in contraction in vitro. Furthermore, knocking out the M3-receptor gene can have severe consequences on intestinal and bladder responses. In some tissues however M2-receptors may mediate an indirect "re-contraction" whereby a reduction in adenylate cyclase activity reverses the relaxation induced by beta-adrenoceptor stimulation. Thus, intestinal and bladder responses to muscarinic agonists are slightly depressed in M2 receptor knockout mice. The role of receptor subtypes in disease is unclear, but an enhancement of M2 receptor mediated responses has been reported to occur in diabetes. Animal models suggest that M2 receptors may play a greater role in some situations such as in the denervated bladder and intestine. In human disease the mechanisms operating are not so clear. Detrusor sensitivity to muscarinic agonists is enhanced in the neurogenic overactive bladder, but there is controversy surrounding the role of M2 receptors and conflicting results have been reported. Thus, the main muscarinic receptor mediating contraction in normal smooth muscle is the M3 receptor, but M2 receptors are also present and possibly may have an enhanced role in disease.

Animals↗

PubMed2006

Interaction between interstitial cells and smooth muscles in the lower urinary tract and penis.

Smooth muscles in the lower urinary tract and corporal tissue exhibit spontaneous contractile activity which depends on L-type Ca(2+) channels. The mechanism underlying this activity is spontaneous electrical activity which shows varied form and property between these tissues. Recent studies revealed that interstitial cells (ICs) are widely distributed in the genitourinary system, and suggested their involvement in spontaneous muscle activity. ICs in the system are not a simple analogy of interstitial cells of Cajal (ICC) in the gut, which act as electrical pacemaker, but represent variability amongst tissues which may account for individual characteristics of each organ. In the bladder and corporal tissue, where smooth muscle cells are capable of generating spontaneous electrical activity, ICs may modulate smooth muscle activity. ICs in corporal tissue release prostaglandins via cyclooxygenase-2 (COX-2) activity and reinforce not only spontaneous but also nerve-mediated alpha-adrenergic contractions. In the bladder, their fundamental role in the integration of signals between populations of cells has been proposed, and thus changes in ICs may contribute to an overactive bladder, a pathological condition which results from increased excitability in detrusor smooth muscles. In the urethra, ICs may act as electrical pacemakers as do ICC. However, overall contractility of urethral smooth muscles does not necessarily rely on pacemaking of ICs, and thus some population of smooth muscles may also have their own excitability.

Animals↗

PubMed2005

Simplified bladder botulinum-toxin delivery technique using flexible cystoscope and 10 sites of injection.

Recently, the use of botulinum toxin A has been extended to patients with non-neurogenic urologic disorders such as refractory idiopathic overactive bladder. We describe a modification of our original injection technique that allows one to deliver botulinum toxin into the bladder quickly and efficiently in an office setting with reliable results and no local or systemic side effects.

Botulinum Toxins, Type A↗

PubMed2006

Effects of ovariectomy and oestrogen replacement on the function and expression of Rho-kinase in rat bladder smooth muscle.

OBJECTIVE: To investigate the effects of ovariectomy and oestrogen replacement on the function and expression of Rho-kinase in rat bladder smooth muscle, as the actual effects of oestrogen deprivation on bladder smooth muscle are unclear. MATERIALS AND METHODS: Female Sprague-Dawley rats were placed into one of three groups: sham-operated, bilateral ovariectomy-only, and bilateral ovariectomy plus oestrogen replacement groups. In the last group, oestrogen was replaced by weekly injection of beta-estradiol 17-cypionate (250 microg/kg subcutaneously for 6 weeks) beginning at 1 week after ovariectomy, whereas the other groups received vehicle-only injections for 6 weeks. After treatment, the bladder was removed for muscle strip studies to evaluate the effects of Y-27632, a specific inhibitor of Rho-kinase, on baseline tension and carbachol-induced tonic contractions. Also, the protein expression of RhoA and Rho-kinase isoenzymes was assessed by Western blot analysis. RESULTS: Of the three groups, incubation with 10 microm Y-27632 resulted in the largest decrease in baseline tension of strips from the bilateral ovariectomy-only group, but this was not statistically significant (P > 0.05). For carbachol-induced tonic contractions, strips from the bilateral ovariectomy-only group were attenuated the most among the three groups after adding Y-27632 (P < 0.05). However, there were no significant differences in the levels of RhoA and the two Rho-kinase isoenzymes in bladder tissues from the three groups. CONCLUSION: Our data show that oestrogen might inhibit the function of Rho-kinase in bladder smooth muscle, while having no significant effect on its expression. This finding might help to explain the greater incidence of urinary tract symptoms suggestive of overactive bladder after the menopause in women.

Animals↗

PubMed2005

Age-dependence of the spontaneous activity of the rat urinary bladder.

Abnormal mechanical function of the bladder is manifested in a number of ways including higher frequency of involuntary detrusor contractions associated with reduced compliance of the bladder that is responsible for an increase in intraluminal pressure during filling. There are basically two ways to approach experimentally these problems: (1) by studying the neural control of the lower urinary tract function, and (2) by measuring the properties of smooth muscle cells in the bladder wall. Studies on smooth muscle function often do not take the origin of smooth muscle cells into account i.e., whether they were harvested from normal or overactive bladders. Although, this simplistic view may be beneficial to understanding the generation of the spontaneous activity of the bladder, however, it does not sufficiently explain the cell-to-cell propagation of the spontaneous smooth muscle activity. The spontaneous activity of smooth muscle is an important factor that works against the bladder compliance in the filling phase, and may inversely affect the neurally evoked response during micturition. The intensity of spontaneous activity is the age-dependent; it is high in neonatal bladders it is small or almost non-existent in adults and reemerges in older bladders. This review focuses on these age-dependent alterations of spontaneous bladder contractions and describes the possible mechanisms which may have important role in regulating the spontaneous contractions using the rat as an animal model.

Age Factors↗

PubMed2001

Depression and incontinence.

The urologic literature suggests that there is an association between a variety of psychiatric disorders and incontinence. Most notably, depression is found in a significant percentage of patients with urinary incontinence. Depression also occurs in other conditions associated with urinary urge incontinence, such as aging and dementia, and in neurologic disorders such as normal pressure hydrocephalus. Correction of some neurologic disorders eliminates both depression and urge incontinence. Although chronic medical disorders such as urge incontinence may lead to depression, an alternative hypothesis is that these two conditions share a common neurochemical pathogenesis. Lowering monoamines such as serotonin and noradrenaline in the central nervous system (CNS) leads to depression and urinary frequency and a hyperactive bladder in experimental animals. Thus, depression may not only be the result of persistent urinary incontinence, but individuals with altered CNS monoamines could manifest both depression and an overactive bladder. The latter condition may lead to urge incontinence, urinary frequency, urgency, or enuresis. Uncovering further evidence for such a linkage could serve as the basis for the development of genetic markers and novel therapeutic interventions for these two conditions.

Depressive Disorder↗

PubMed2002

Prevalence and physician awareness of symptoms of urinary bladder dysfunction.

PURPOSE: To determine awareness of bladder dysfunction and attitudes towards its management among office-based physicians. MATERIALS AND METHODS: A total of 211,648 patients consulting office-based primary care physicians (PCPs), gynaecologists (OBGs) or urologists (UROs) for any reason were given a questionnaire of four questions related to symptoms of bladder dysfunction. The physicians were asked to discuss the answers with their patients and to choose from a list of suspected diagnoses. They were also asked whether medical therapy would be initiated and/or the patient referred to a specialist. RESULTS: Patients (57%) had a least one symptom of bladder dysfunction, with increased frequency being most common (41.9%), and symptoms of stress incontinence (30.6%), urgency (24.3%) and urge incontinence (20.2%) less frequent. However, patients with symptoms of overactive bladder (OAB), mixed incontinence or stress incontinence according to the questionnaire remained undiagnosed by their physician in 57.5, 47.5 and 38.1% of cases, respectively. When a diagnosis was suspected by the physician, it often did not match what would be expected based on the questionnaire, and in half of all cases did not result in medical treatment. CONCLUSIONS: Bladder dysfunction is highly prevalent among patients consulting an office-based physician for any reason, but remains undiagnosed in many cases and untreated despite diagnosis in many others. Since various effective treatment options are available for bladder dysfunction, educational programs for patients and physicians appear necessary to improve the quality of diagnosis and treatment for this wide-spread condition.

Adult↗

PubMed2002

Length-dependent regulation of basal myosin phosphorylation and force in detrusor smooth muscle.

Urinary bladder (detrusor) smooth muscle is active in the absence of an external stimulus. Tone occurs even "at rest" during the filling phase, and it is elevated in patients with overactive bladder. This study examined the role of muscle length on tone and the level of basal myosin light chain phosphorylation (MLC(20P)). MLC(20P) was 23.9 +/- 1% (n = 58) at short lengths (zero preload; L(z)). An increase in length from L(z) to the optimal length for contraction (L(o)) caused a reduction in MLC(20P) to 15.8 +/- 1% (n = 49). Whereas 10 microM staurosporine reduced MLC(20P) at L(z), 1 microM staurosporine, a Ca(2+)-free solution, and inhibitors of MLC kinase, protein kinase C (PKC) and RhoA kinase (ROK) did not. However, 1 microM staurosporine and inhibitors of ROK inhibited MLC(20P) and tone at L(o). These data support the hypothesis that a Ca(2+)-independent kinase, possibly ZIP-like kinase, regulates MLC(20P) at L(z), whereas in detrusor stretched to L(o), additional kinases, such as ROK, participate.

Animals↗

PubMed2005

Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes.

Pituitary adenylate cyclase activating polypeptide (PACAP) peptides are expressed and regulated in sensory afferents of the micturition pathway. Although these studies have implicated PACAP in bladder control, the physiological significance of these observations has not been firmly established. To clarify these issues, the roles of PACAP and PACAP signaling in micturition and cystitis were examined in receptor characterization and physiological assays. PACAP receptors were identified in various tissues of the micturition pathway, including bladder detrusor smooth muscle and urothelium. Bladder smooth muscle expressed heterogeneously PAC(1)null, PAC(1)HOP1, and VPAC(2) receptors; the urothelium was more restricted in expressing preferentially the PAC(1) receptor subtype only. Immunocytochemical studies for PAC(1) receptors were consistent with these tissue distributions. Furthermore, the addition of 50-100 nM PACAP27 or PACAP38 to isolated bladder strips elicited transient contractions and sustained increases in the amplitude of spontaneous phasic contractions. Treatment of the bladder strips with tetrodotoxin (1 muM) did not alter the spontaneous phasic contractions suggesting direct PACAP effects on bladder smooth muscle. PACAP also increased the amplitude of nerve-evoked contractions. By contrast, vasoactive intestinal polypeptide had no direct effects on bladder smooth muscle. In a rat cyclophosphamide (CYP)-induced cystitis paradigm, intrathecal or intravesical administration of PAC(1) receptor antagonist, PACAP6-38, reduced cystitis-induced bladder overactivity. In summary, these studies support roles for PACAP in micturition and suggest that inflammation-induced plasticity in PACAP expression in peripheral and central micturition pathways contribute to bladder dysfunction with cystitis.

Animals↗

PubMed2001

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↗

PubMed2002

Management of the urethral outlet in patients with severe prolapse.

PURPOSE OF REVIEW: Numbers of women seeking consultation for pelvic floor disorders, a large portion of which will involve pelvic organ prolapse (POP) and lower urinary tract dysfunction, are expected to reach epidemic proportions within the next decade. A full understanding of the complex impact of pelvic organ prolapse on lower urinary tract function is crucial to successful management. RECENT FINDINGS: Recent data lend support to the concept that women with POP, but no associated urethral dysfunction, may be best served by a surgical repair that carefully avoids dissection in the periurethral area. Conversely, preoperative evaluation will often reveal bladder outlet obstruction concomitant with 'hidden', 'potential', or 'occult' stress urinary incontinence when the prolapse is reduced. Many of these women will not have incontinence symptoms in daily life. Paradoxically, the mechanical bladder outlet obstruction may induce detrusor instability with subsequent obstructed/overactive bladder symptom complexes not dissimilar to those of men with prostatic bladder outlet obstruction. Anatomic research shows that the vessels and nerves supplying the urethra are particulary vulnerable to surgical techniques used in pelvic organ prolapse repair. SUMMARY: This mix of obstructed, overactive bladder with hidden stress incontinence increases with degree of POP, and all women with severe prolapse will fair best if evaluated for all three conditions prior to surgical repair.

Collagen↗

PubMed2005

What Americans understand and how they are affected by bladder control problems: highlights of recent nationwide consumer research.

Over the last 5 years, the National Association For Continence has sponsored epidemiologic surveys of adults across the United States in order to quantify the prevalence of bladder control problems in the community, to understand how quality of life of those people experiencing these medical disorders is affected, and what beliefs people in general hold surrounding bladder health. Collectively, these nationwide surveys offer statistically significant documentation of how widespread, how far-reaching, how misunderstood, and how real the symptoms of urinary incontinence and related symptoms of overactive bladder are, and lay a foundation to support future investment in research, education, and collaboration.

Activities of Daily Living↗

PubMed2004

The inhibitory role of melatonin on isolated guinea-pig urinary bladder: an endogenous hormone effect.

OBJECTIVE: To investigate the effects of melatonin, an endogenous hormone, on acetylcholine and KCl-induced contractions of isolated guinea-pig detrusor muscle. MATERIALS AND METHODS: Detrusor smooth muscle strips isolated from guinea-pig bladders were placed in an organ bath containing physiological saline at 37 degrees C and pH 7.4, constantly bubbled with 95% oxygen and 5% CO2. The effects of cumulatively applied melatonin on the acetylcholine- and KCl-induced contractions of isolated bladder strips were examined using isometric contraction measurements. RESULTS: Melatonin (100 and 300 micromol/L) significantly inhibited the peak amplitude of both acetylcholine (10 micromol/L) and KCl (30 mmol/L)-induced contraction of the isolated bladder strips (P < 0.05). Similarly, melatonin caused a significant reduction in the contractile frequency induced by KCl (eight strips) in a concentration-dependent manner, while having no significant effect on the frequency of contractile response to acetylcholine, even at the highest concentration (300 micromol/L) used (P = 0.58, 14 strips). CONCLUSIONS: These results suggest that melatonin inhibits acetylcholine- and KCl-induced contractions in isolated bladder strips from guinea pigs. The endogenous nature of melatonin, with its low side-effect profile, makes it a potentially useful agent to be considered in the medical management of the overactive bladder.

Animals↗

PubMed2005

Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function.

Smooth muscles from the urethra and bladder display characteristic patterns of spontaneous contractile activity in the filling phase of the micturition cycle. Tonic contractions are seen in the urethral smooth muscles, and phasic contractions occur in the detrusor. Overactivity in the detrusor is a common clinical problem. The ion channels in the smooth muscle membranes play an important role in determining the functional properties, and are obvious targets for treatment of the overactive bladder. Recent evidence suggests that interstitial cells may also play a role in determining the pattern of spontaneous activity, although their precise role is less well established in the urinary tract than in the gut. The ion channels involved in these cells are also of interest. This review discusses what is known of ion channels in these tissues, and their implications for function.

Animals↗

PubMed1997

Antimuscarinic potency and bladder selectivity of PNU-200577, a major metabolite of tolterodine.

PNU-200577 (labcode DD 01 [(R)-N, N-diisopropyl-3-(2-hydroxy-5-hydroxymethylphenyl)-3-phenylpropanamine ) is a major pharmacologically active metabolite of tolterodine, a new muscarinic receptor antagonist intended for the treatment of an overactive bladder. In vitro, PNU-200577 produced a competitive and concentration-dependent inhibition of carbachol-induced contraction of guinea-pig isolated urinary bladder strips (KB = 0.84 nM; pA2 = 9.14). In vivo, PNU-200577 was significantly more potent at inhibiting acetylcholine-induced urinary bladder contraction than electrically induced salivation in the anaesthetised cat (ID50 15 and 40 nmol.kg-1, respectively; P < 0.01). In radioligand binding studies carried out in homogenates of guinea-pig tissues and Chinese hamster ovary cell lines expressing human muscarinic m1-m5 receptors, PNU-200577 was not selective for any muscarinic receptor subtype. Thus, PNU-200577 is similar to tolterodine in terms of antimuscarinic potency, functional selectivity for the urinary bladder in vivo and absence of selectivity for muscarinic receptor subtypes in vitro. The results of this study clearly indicate that PNU-200577 contributes to the therapeutic action of tolterodine, in view of its high antimuscarinic potency, similar serum concentration and lower degree of protein binding.

Acetylcholine↗

PubMed2006

Anticholinergic drugs in patients with bladder outlet obstruction and lower urinary tract symptoms: A systematic review.

OBJECTIVES: To review the available evidence concerning the use of anticholinergic drugs, alone or in combination with alpha-blockers, in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and concomitant overactive bladder syndrome, to assess whether the currently available evidence suggests a role for antimuscarinic drugs in patients with BPH. METHODS: A systematic review of the literature was performed using Embase, MEDLINE, and Web of Science through a complex search strategy including "free text" and "MeSH" protocols. Moreover, the Cochrane database of systematic review was browsed for records regarding BPH and the abstract books of the American Urological Association, European Association of Urology, and International Continence Society annual meetings from 2000 to 2005 were hand-searched for studies concerning the topic of the review. RESULTS: From the literature search, we identified four randomised controlled trials (RCTs), two prospective case series, and a few congress abstracts. For methodologic issues, the best RCT was based on urodynamic data, but did not provide any clinical insight on the patients' symptoms. The other papers were affected by significant methodologic or clinical drawbacks. CONCLUSION: The available data may be considered promising in terms of safety and efficacy. The evidence of the limited number of RCTs available, considering their methodologic or clinical shortcomings, is not sufficient to support the clinical use of combination therapy with alpha-blockers and anticholinergic drugs in patients with associated storage and voiding symptoms. Well-designed, large, double-blind, placebo-controlled, long-term RCTs are needed to assess the long-term safety and efficacy of antimuscarinic drugs, alone or in combination with alpha-blockers, in this category of patients.

Cholinergic Antagonists↗