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PubMed2003

Storage and voiding symptoms: pathophysiologic aspects.

Lower urinary tract symptoms (LUTS) can be categorized as storage, voiding, and postmicturition symptoms. Although often associated with benign prostatic hyperplasia (BPH), they may also occur in women. This observation, the beneficial effects of alpha-adrenoceptor (AR) antagonists in men with BPH and LUTS, and the frail correlation between LUTS, and prostatic enlargement and/or outflow obstruction have focused interest on the role of extraprostatic alpha-ARs in the pathogenesis of LUTS. It has been suggested that an upregulation of contraction-mediating alpha-ARs and a downregulation of relaxation-mediating beta-ARs can contribute to LUTS generation. However, recent investigations on human bladder tissue could not confirm such a change. Antimuscarinic agents are effective for treatment of the overactive bladder, which is characterized by urge, frequency, urge incontinence, and nocturia (ie, LUTS). This suggests that muscarinic receptors are involved in the pathogenesis of LUTS, and there is recent evidence implicating purinergic receptors. Structural changes in the bladder, such as smooth muscle hypertrophy and connective tissue infiltration, are associated with detrusor overactivity in about 50% to 66% of patients with BPH. However, it is unclear whether this is caused by bladder outlet obstruction because the symptoms may remain in up to 33% of the patients after surgical removal of the obstruction. When outflow obstruction is reversed in rats, there is a subset (20%) that continues to have overactive voiding, despite a reversal of the bladder hypertrophy, suggesting that changes within the central nervous system may be a contributing factor. LUTS can be caused by many, often overlapping, pathophysiologic mechanisms, which may contribute to individual variation in response to treatment.

Adrenergic alpha-Antagonists↗

PubMed1981

Voiding disorders in young male adult.

Two hundred four male patients (aged twenty to forty-five years) with symptoms of lower urinary tract dysfunction have been investigated by urodynamic studies. Patients with symptoms of bladder overactivity (53 per cent) had a low incidence of bladder outflow obstruction but a high incidence of bladder hypersensitivity and bladder instability. Their symptomatic complaints accurately reflected their cystometric findings and, therefore, a urine flow rate estimation was the only necessary urodynamic investigation in most cases. Urine flow studies are an essential first investigation in all patients with possible bladder outflow obstruction (26 per cent), and full studies were necessary in many patients to discriminate the low flow rates produced both by outflow obstruction and by bladder underactivity which were diagnosed in a high proportion of patients. Similarly, in the neurologically abnormal patients (12 per cent), full urodynamic studies were necessary with the studies described in this article the minimum required.

Adult↗

PubMed2005

A role for muscarinic receptors or rho-kinase in hypertension associated rat bladder dysfunction?

PURPOSE: Essential arterial hypertension is a frequent condition. Spontaneously hypertensive rats (SHRs) show bladder dysfunction similar to that seen in patients with overactive bladder. Since muscarinic receptors and rho-kinase have a key role in the regulation of bladder contractility, we determined whether alterations of either one might contribute to hypertension associated bladder dysfunction. MATERIALS AND METHODS: The bladders of SHRs and normotensive Wistar Kyoto rats (WKYs) were compared in in vitro radioligand binding and contractility studies. RESULTS: The mean total number of muscarinic receptors +/- SEM (181 +/- 14 vs 191 +/- 22 fmol/mg protein) and the relative roles of their subtypes were similar in SHRs and WKYs. Contractile responses to the muscarinic agonist carbachol (maximum effect 2.04 +/- 0.24 vs 2.05 +/- 0.14 mN/mm strip length and -log EC50 5.61 +/- 0.07 vs 5.64 +/- 0.04) and to KCl in a receptor independent manner were similar in the 2 strains. The M3 selective antagonist darifenacin inhibited carbachol responses much more potently than the M2 selective antagonist methoctramine but the potency of the 2 drugs was similar in each strain. The rho-kinase inhibitor Y27,632 attenuated carbachol induced contraction in a quantitatively similar manner in SHRs and WKYs. CONCLUSIONS: An altered function of muscarinic receptor subtypes or rho-kinase does not appear to contribute to bladder dysfunction in SHRs.

Animals↗

PubMed2004

Food does not affect the pharmacokinetics of solifenacin, a new muscarinic receptor antagonist: results of a randomized crossover trial.

AIM: To determine the effect of food ingestion on the pharmacokinetic profile of solifenacin succinate (YM905; Vesicare, a new bladder selective muscarinic receptor antagonist for the treatment of overactive bladder, a chronic disease usually caused by involuntary detrusor muscle contractions during bladder filling. METHODS: A randomized, two-period, crossover study in two groups of 12 healthy men (aged 18-45 years, body weight 60-100 kg, body mass index < or =30). A single 10-mg dose of solifenacin was administered to the first group in the fasting state during period 1 and in the fed state during period 2, and to the second group in the fed state during period 1 and in the fasting state during period 2 (10 mg is two times the suggested starting dose). There was a 14-day washout between treatment periods. Parameters obtained included C(max), AUC(last), and AUC(0-inf), as well as t(1/2), t(max), and t(lag). RESULTS: One subject withdrew during the first period for personal reasons. No statistically or clinically significant pharmacokinetic differences occurred between subjects in the fed and fasting states. All geometric mean ratios were close to 1 (C(max), 1.033; AUC(last), 1.068; AUC(0-inf), 1.040). The 90% confidence intervals (CIs) fell in the predefined no-food-effect boundaries of 0.8-1.25 (C(max), 0.953-1.120; AUC(last), 0.990-1.153; AUC(0-inf), 0.976-1.109). The mean difference in t(1/2) was -3.8 h (90% CI 7.6-0.0). There were no significant differences between the fed and fasting states with regard to t(max) and t(lag) (P > 0.05). CONCLUSIONS: The pharmacokinetics of oral solifenacin was not affected by food ingestion, suggesting that this drug may be administered with or without food. The results observed in this investigation are consistent with those of previous studies of solifenacin.

Adolescent↗

PubMed2005

Bladder-health diaries: an assessment of 3-day vs 7-day entries.

OBJECTIVES: To assess the reliability of symptom reports in 3-day vs 7-day bladder diaries used in clinical trials of patients with overactive bladder (OAB) and to compare those results and related issues with previous reports. MATERIALS AND METHODS: We analysed two large-scale, randomized, phase 3 clinical trials of the use of transdermal oxybutynin for treating patients with OAB. The first trial (Trial A, 520 patients) compared three doses of transdermal oxybutynin (1.3, 2.6 and 3.9 mg/day) with placebo. Patients documented their OAB symptoms in a 7-day diary. The second clinical study (Trial B, 361 patients) compared the efficacy of 3.9 mg/day transdermal oxybutynin with 4 mg/day extended-release tolterodine and with placebo; this trial required symptom recording for only 3 days. The internal consistency of the data from the 7-day trial was determined and then compared with the 3-day trial results. RESULTS: Patients on transdermal oxybutynin or long-acting tolterodine for their OAB symptoms showed a clinically and statistically significant improvement, results that were documented in both 3-day and 7-day bladder diaries. However, compared with 7-day symptom records, 3-day diaries were associated with significantly better compliance with record-keeping (P < 0.001). CONCLUSIONS: Seven-day diaries used in clinical trials supply accurate and reproducible data on clinical manifestations of OAB, but 3-day diaries are equally effective and have the potential for better accuracy through increased patient convenience. Three-day diaries may also reduce the tendency for patients to complete gaps in record-keeping from memory.

Benzhydryl Compounds↗

PubMed2005

Effect of age on the pharmacokinetics of solifenacin in men and women.

OBJECTIVE: The pharmacokinetics of solifenacin succinate (YM905; Vesicare), a new, bladder-selective, muscarinic receptor antagonist for the treatment of overactive bladder in young/middle-aged and elderly subjects were compared. MATERIAL: Solifenacin. METHODS: 47 healthy adults (24 young/middle-aged: mean age 35; and 23 elderly: mean age 68; 12 males in each age group) were enrolled in a single-center, multi-dose, open-label, crossover trial. Solifenacin, 5 or 10 mg, was administered once daily during two 14-day study periods separated by a washout period. Subjects were randomized to one dose in the first period and the other dose in the second period. Primary outcome variables were maximum plasma concentration (C(max)) and area under the curve from time 0 - 24 hours (AUC(0-24)). Secondary parameters included terminal elimination half-life (t1/2), time to C(max) (t(max)), fraction unbound, renal clearance, amount/percent of dose excreted in urine as solifenacin and its metabolites, and trough plasma metabolite concentrations. Adverse events and other safety parameters were also evaluated. RESULTS: Mean C(max) and AUC(0-24) were 16% (90% confidence interval 0.973 - 1.373) and 20% (1.003 - 1.435) higher, respectively, in elderly subjects. Mean t(max) and t1/2 were higher in elderly subjects. In both elderly and younger subjects, increasing the dose from 5 to 10 mg dose proportionally increased C(max), AUC(0- 24), and the amount excreted in urine. As expected, t(max) and t1/2 were not affected. Plasma concentrations and amounts of metabolites excreted in urine also increased dose proportionally. Solifenacin was highly bound to plasma proteins (fraction of the drug unbound in plasma was approximately 0.02), but there was no clear effect of gender or age. Solifenacin 5 or 10 mg once daily for 14 days was well tolerated by all subjects. CONCLUSION: Although C(max) and AUC(0-24) were higher in elderly subjects than in younger subjects and there was a tendency toward longer t(max) and t1/2, these differences were small and not considered clinically relevant. In this study, no consistent safety/tolerability issues were associated with these pharmacokinetic differences and the administration of solifenacin 5 or 10 mg once daily was well tolerated. The number of adverse events in elderly subjects was similar to that in younger subjects, indicating that no age-related dose adjustments are needed with this agent.

Adult↗

PubMed2004

Report of a mail survey of women with bladder control disorders.

INTRODUCTION: Very little is known about a patients perception of the severity of incontinence, absorbent product use, and interaction with health care professionals despite the growing prevalence of bladder control disorders such as urinary incontinence (UI) and overactive bladder. PURPOSE: Using a simple mail-in questionnaire, this survey was meant to evaluate the limitations in intervention for UI in women due to communication shorffalls. It cites common resources utilized once a woman finds significance to her bladder control problem. The survey explores the adequacy of intervention relative to the effective availability of information, materials, and treatment. The objective was to understand the current patient-professional relationship in order to evaluate different vehicles that might effectively increase communication regarding incontinence issues. METHODS: In partnership with a mail order medical product company, the author formulated a questionnaire that was mailed by the company to 1,500 women. Half of the sample was derived from randomly selected "leads" from advertising sources and personal referrals who had identified themselves as incontinent but had never purchased incontinence supplies from them. The other half were randomly selected customers who had purchased the company's incontinence products. The 33-item multiple-choice questionnaire had 422 responses; of these, 405 women, aged 56 and older were evaluated. A research firm that conducts and analyzes consumer surveys using standard consumer research protocol tabulated results. FINDINGS: Of those suffering from UI, two groups emerged. The first felt that incontinence was related to aging, and were not embarrassed to discuss it with their physician. They had mixed feelings regarding impact on quality of life. The second group was reluctant to seek professional advice and was uncomfortable speaking about it. They felt strongly about its negative impact on daily life. Respondents from both groups who seek professional assistance still desired more information about the causes, treatments, and coping mechanisms. Most wanted more provider interaction and wanted their doctor or health care provider to proactively initiate discussion on incontinence and provide information, educational materials, and product samples. CONCLUSION: Respondents indicated that they want more information regarding incontinence. While they may not be equipped to fully understand the problem, they expect doctors, nurses, medical professionals, retail outlets, medical supply companies, and mail order houses to provide the information. Since respondents are receiving information through consumer advertising, which is usually commercially funded, a partnership between the health care community and these sources to produce this information would be ideal.

Activities of Daily Living↗

PubMed2002

Mechanical stretch regulates cell survival in human bladder smooth muscle cells in vitro.

Our understanding of the pathophysiology of the overactive bladder is poor. It has been proposed that localized contractions result in the abnormal stretching of bladder smooth muscle. We hypothesize that stretch regulates the cellular processes that determine tissue size. The purpose of this study was to investigate the effect of stretch on apoptosis, proliferation, cell hypertrophy, and growth factor production in human bladder smooth muscle cells in vitro. Normal human detrusor muscle was obtained from patients undergoing radical cystectomy for invasive bladder cancer, and primary cultures were established. Cells were mechanically stretched on flexible plates at a range of pressures and times. Apoptosis was assessed by propidium iodide incorporation and flow cytometry. Radiolabeled thymidine and amino acid incorporation were used to assess proliferation and cell hypertrophy. ELISA and RT-PCR were used to assess growth factor production. Mechanical stretch inhibits apoptosis in a time- and dose-dependent manner and was associated with increases in the antiapoptotic proteins heat shock protein-70 and cIAP-1. Stretch also increases smooth muscle cell proliferation and hypertrophy, but hypertrophy is the more dominant response. These changes were associated with increases in IGF-1 and basic FGF and a decrease in transforming growth factor-beta1. Mechanical stretch regulates apoptosis, proliferation, and cell hypertrophy in human bladder smooth muscle cells.

Cell Division↗

PubMed2005

Cost-consequence analysis evaluating the use of botulinum neurotoxin-A in patients with detrusor overactivity based on clinical outcomes observed at a single UK centre.

OBJECTIVE(S): This study aimed to assess the resource utilisation, health benefits and cost-effectiveness of intra-detrusor injections of botulinum neurotoxin-A (BoNT/A) in patients with overactive bladder (OAB). METHODS: 101 patients with urodynamically-proven detrusor overactivity of either neurogenic (NDO; n = 63) or idiopathic (IDO; n = 38) origin received intra-detrusor injections of 200-300 units of BoNT/A in 20-30 ml saline as part of a research protocol. Twenty-nine patients received repeat injections after 7-26 months. Symptom severity and urodynamic parameters were assessed at 0, 4 and 16 weeks. The cost of therapy was quantified based on the NHS resources used by typical patients and was used to calculate the cost-effectiveness of BoNT/A compared with standard care from the perspective of the UK NHS. RESULTS: In an intent-to-treat analysis, 82% of patients showed a 25% or greater improvement in at least two out of five parameters (urinary frequency, urgency, urgency incontinence episodes, maximum cystometric capacity and maximum detrusor pressure) four weeks after treatment, reducing to 65% after 16 weeks. A 50% or greater improvement in the frequency of micturition, urgency or urgency incontinence was seen in 73% of patients at four weeks and 54% at 16 weeks. There were no significant differences between IDO and NDO patients in the proportion meeting these endpoints. Therapy cost pounds 826 per patient, with a cost-effectiveness ratio of pounds 617 per patient-year with > or = 25% clinical improvement. CONCLUSION(S): This study demonstrates that intra-detrusor BoNT/A is an effective treatment for OAB that is highly likely to be cost-effective in both idiopathic and neurogenic disease.

Adult↗

PubMed1999

Mechanisms underlying the pathogenesis of urinary bladder instability - new perspectives for the treatment of reflex incontinence.

The urine storage ability of the urinary bladder is markedly impaired following inflammation of the urinary bladder and spinal cord injury because of a hyperexcitability of micturition reflexes. Using two rat models of inflammation-induced bladder overactivity and detrusor hyper-reflexia following spinal cord injury we investigated changes in the neuronal pathways to the urinary bladder which may underlie the development of this instability. Our results suggest that among the factors involved in inflammation-induced bladder instability are significant changes in the expression of the neuropeptides substance P, calcitonin gene-related peptide and galanin at the primary afferent level, as well as of the enzyme neuronal nitric oxide synthase (nNOS) at the afferent and postganglionic efferent level. In the lumbar and sacral spinal cord nNOS-immunoreactivity was depleted from dorsal horn neurones in both cystitis and spinal cord injured rats and from preganglionic parasympathetic neurones after spinal cord injury. Distension of the bladder in chronically spinalized rats elicited c-Fos expression in a significantly greater number of neurones throughout the lumbar and sacral segments than in rats with an intact neuraxis. Thus, under pathological conditions rather complicated changes in the synthesis of neuropeptides and nNOS occur at the primary afferent, spinal cord and postganglionic efferent level that together control the activity of the urinary bladder. Further mechanisms like unmasking of silent synapses and axonal sprouting in the spinal cord might further contribute to an increase in activity in micturition reflex pathways. Local cooling of the dorsal spinal cord at the level L6/S1 with temperatures between 14 and 20 degrees C proved a simple technique to control the unstable bladder and restore continence in both inflammation-induced detrusor overactivity and detrusor hyperreflexia following spinal cord injury. The effects of cooling are probably the result of a blockade of synaptic transmission within the dorsal cord which eliminates neuronal overactivity. Thus, local spinal cord cooling could offer a new method to treat bladder instability and reflex incontinence.

Journal Article↗

PubMed1993

[Long-term results and indications of intraurethral stents in elderly patients with prostatic hypertrophy complaining of urinary retention].

Thirty-two elderly male patients with benign prostatic hypertrophy complaining of urinary retention were treated by polyurethane intraurethral stents. All of them were unfit for prostatic surgery due to the presence of several complications, and had been indwelt with a urethral balloon catheter. Cystometry before stent insertion was performed in 23 of the 32 patients. Eleven patients showed overactive bladder, 5 patients normal bladder, and 7 patients underactive bladder. Duration of stent indwelling ranged from 2 days to 22 months (mean 6.7 months), and stent could successfully function for more than 6 months in 20 of the 32 patients (62.5%). Nine of these 20 patients (45%) could keep continence of urine, and urinary tract infections improved in 7 of these 20 patients (35%). The stent failed in 4 of the 5 patients who had had previous operations for prostatic hypertrophy. In a comparison of the findings of urodynamic study prior to insertion of stent with the results of the stent, the results were significantly better in the patients with overactive or normal bladder than in those with underactive bladder (p < 0.05, chi-square test). Bladder stone formation was found in one patient and was the only complication among the 32 patients. In conclusion, stent placement without incontinence or urinary tract infection can be successful for more than 6 months in patients who do not have an underactive bladder and who had not had a previous prostatic operation.

Aged↗

PubMed2006

A randomized comparative study of the effects of oral and topical estrogen therapy on the lower urinary tract of hysterectomized postmenopausal women.

OBJECTIVE: To compare the effects of oral and vaginal estrogen therapy (ET) on the lower urinary tract in postmenopausal women with prior hysterectomy. DESIGN: Randomized, prospective study. SETTING: Tertiary teaching hospital. PATIENT(S): Fifty-seven hysterectomized, postmenopausal women. INTERVENTION(S): Patients were randomized to receive either oral (0.625 mg of conjugated equine E per tablet; n = 27) or topical (0.625 mg conjugated equine E per 1 g vaginal cream; n = 30) E, administered once daily. MAIN OUTCOME MEASURE(S): All subjects had E2 measurements, urinalysis, pelvic examination, introital color Doppler ultrasonographies, and personal interviews with the Bristol Female Lower Urinary Tract Symptoms Questionnaires before and 3 months after ET. RESULT(S): A higher serum level of E2 was noted in the oral group compared with the topical group after ET. The post-ET pulsatility index of periurethral vessels and bladder neck revealed statistically significant decreases in both groups. The incidences of urinary frequency and nocturia were significantly decreased after 3 months of ET in both groups. Changes in the incidence of other symptoms, including stress incontinence and urge incontinence, were not statistically significant. However, subjective improvement of stress incontinence was found in 72.7% of the oral group and 60% of the topical group. CONCLUSION(S): The results suggest that ET alone, by an oral or vaginal route, could increase the blood flow around the bladder neck and mid-urethra and relieve the symptoms of overactive bladder and stress incontinence in postmenopausal women with prior hysterectomy. In addition, vaginal preparations are as effective as systemic therapy at the lower serum level of E2.

Administration, Intravaginal↗

PubMed2005

In vivo effects of botulinum toxin A on visceral sensory function in chronic spinal cord-injured rats.

OBJECTIVES: To analyze the in vivo effects of botulinum toxin type A (BTX-A) on visceral sensory function in chronic spinal cord-injured (SCI) rats. METHODS: One group of rats underwent spinal cord transection at the T8-T9 level (SCI) and the other group was left untreated. In 21 days, baseline open cystometrography (CMG) was performed. The rats were then treated intravesically with either 1 mL of 1% protamine sulfate (PS) to increase urothelial permeability or saline, followed by either 1 mL of BTX-A (20 U) or saline. CMG was repeated 48 hours after instillation, and any changes in the bladder contraction frequency and amplitude were evaluated. RESULTS: After the instillation of PS and BTX-A or BTX-A alone, the bladder contraction frequency was significantly decreased in the SCI rats compared with the control rats (P < 0.05); no change was seen in the contraction amplitude. When normal rats were given intravesical PS and/or BTX-A, or SCI animals were treated with PS alone, neither the frequency nor the amplitude of the contractions was affected. Also, no significant differences were found in the bladder contraction frequency or amplitude of contractions in any animal treated with instillation of saline alone. CONCLUSIONS: Intravesical BTX-A inhibits bladder sensory mechanisms by reducing the frequency of bladder contractions in an SCI rat model. Furthermore, our results suggest that intravesically applied BTX-A does not penetrate to the smooth muscle layer even after PS disruption of the bladder urothelium. These findings may have important clinical applications in treating overactive bladders after SCI.

Animals↗

PubMed2004

Solifenacin demonstrates high absolute bioavailability in healthy men.

OBJECTIVE: Solifenacin succinate (YM905; Vesicare) is a promising new bladder selective muscarinic receptor antagonist under investigation for the treatment of overactive bladder. This study was designed to assess the absolute bioavailability of a single oral dose of solifenacin 10 mg, which is twice the suggested starting dose. STUDY DESIGN: Single-centre, open-label, randomised, two-period, crossover, single-dose study. METHODS: Solifenacin was administered orally as a 10 mg dose and intravenously as a 5 mg dose. Oral and intravenous (IV) doses were divided by a washout period of > or =14 days. STUDY PARTICIPANTS: The study group consisted of 12 healthy young men, aged 20-45 years, nine of whom completed the study. RESULTS: The pharmacokinetic analysis comprised nine subjects. A single oral dose of solifenacin 10 mg had a high absolute bioavailability of 88.0% (95% confidence interval 75.8, 102.1), low clearance (9.39 L/h [SD 2.68]), and an extensive mean volume of distribution at steady state (599L [SD 86]). Only 7% of solifenacin was excreted intact in the urine. Single oral and IV administration of solifenacin was well tolerated in this study. The most common adverse events related to drug treatment were headache and somnolence. CONCLUSIONS: Pharmacokinetic analyses of single oral and IV doses of solifenacin demonstrated that the drug has a high absolute oral availability of 88%. This finding suggests that solifenacin may have a higher and less variable bioavailability than other antimuscarinic agents.

Adult↗

PubMed2004

[Dynamic bladder neck stenosis as a cause of psychogenic mictrition discomforts and mictrition disorders].

Symptoms of an "overactive bladder" can be psychological and in many cases are considered to be the result of psychogenic muscular tension of the pelvic floor causing a "dynamic stenosis" of the bladder neck. Psychogenic muscular tension can have its origin in psychic trauma during bladder training at the age of 1-3 years, leading to an obsessive-compulsive personality structure. A tendency to muscular tension, especially in the pelvic region, as well as to disorders of the lower bowl can be found in afflicted persons. Psychological defence and avoidance reactions, problems with contact and security, sexual abuse in childhood, as well as stress, anxiety, disappointment and anger can be the result of psychic trauma. Typical triggers involve psychological actualisation or compression. Because of the tendency to muscular tension with many psychogenic symptoms of voiding dysfunction, dispensing of medication, physical muscle relaxant measures show good therapeutic results.

Humans↗

PubMed2005

Localization of the urge to void in patients with painful bladder syndrome.

AIMS: Our aim was to describe the location of urinary urgency or bladder discomfort in patients with painful bladder syndrome (PBS) and controls. METHODS: Patients with symptomatic diagnoses of PBS, overactive bladder (OAB) syndrome, stress urinary incontinence (SUI), and asymptomatic controls were asked to indicate the location of their urinary urge/urgency/discomfort on a body map. RESULTS: We present results for 30 PBS patients, 25 OAB patients, 15 SUI patients, and 15 asymptomatic controls. In asymptomatic subjects and those with SUI, the urge to void was localized to the suprapubic region only. More than half (53%) of patients with PBS and a minority (20%) of those with OAB localized their urinary urgency/discomfort to both suprapubic and vulvar/urethral locations. Some patients with PBS also localized their urinary discomfort to other body sites including low back, upper and lateral buttocks, lower abdomen, and upper thighs. CONCLUSIONS: In most patients with PBS and some with OAB, complaints of bladder discomfort or urgency may refer to sensations that are localized at sites other than suprapubic. The etiology of widespread sensation may include an expansion of dermatomes of referral of bladder sensation, and/or the presence of associated somatic abnormalities.

Adult↗

PubMed2005

Increased spinal cord phosphorylation of extracellular signal-regulated kinases mediates micturition overactivity in rats with chronic bladder inflammation.

Spinal processing of somatosensory and viscerosensory information is greatly facilitated in some persistent pain states. Growing evidence suggests that the so-called central sensitization depends in part on intracellular activation and signalling via specific MAP kinases. Here we studied the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (phosphoERK), the active form of these kinases, in spinal neurons following innocuous and noxious distension of non-inflamed and cyclophosphamide (CYP)-inflamed rat urinary bladders. Additionally, we investigated the nature of bladder primary afferents responsible for spinal ERK activation. Finally, we used a specific inhibitor of ERK phosphorylation to study the influence of these kinases on the bladder reflex activity of normal and inflamed bladders. Results indicated that, in non-inflamed rats, noxious but not innocuous bladder distension significantly increased spinal phosphoERK immunoreactivity from its normal very low level. However, in CYP-inflamed rats, innocuous and noxious bladder distension significantly increased the number of spinal neurons immunoreactive to phosphoERK. ERK activation was rapid (within minutes) and transient. Desensitization of vanilloid-sensitive afferents by intravesical resiniferatoxin, a capsaicin analogue, did not decrease phosphoERK immunoreactivity in normal or CYP-inflamed rats. ERK inhibition by intrathecal PD 98059 had no effect on bladder reflex contractions of non-inflamed bladders but significantly decreased its frequency in inflamed animals. Our results suggest that spinal ERK intervene in acute and chronic inflammatory pain perception and mediate bladder reflex overactivity accompanying chronic bladder inflammation. In addition, bladder noxious input conveyed in vanilloid-resistant primary afferents is important to spinal ERK phosphorylation in both noninflamed and CYP-inflamed animals.

Animals↗

PubMed2006

Needle suspension of the bladder neck for stress urinary incontinence: objective results at 11 to 16 years.

We analyzed the objective and subjective long-term outcomes of women who underwent needle suspension of the bladder neck 11 to 16 years previously. A total of 132 women underwent a needle suspension procedure at our institution between 1986 and 1991. In a retrospective cohort study, 63 of these women were evaluated by clinical examination, urodynamic testing, cough stress test, and standardized personal interview. Objective continence was defined as no loss of urine either during cystometry or during coughing with the bladder filled to 300 ml. The objective continence rate was 56% (25/45) and the subjective continence rate was 41% (26/63). With regard to patient satisfaction, only 38% (24/63) of the studied patients considered themselves completely cured, and an additional 30% (19/63) improved. The objective and subjective long-term results of needle suspension of the bladder neck are modest. Long-term complications such as urinary retention and overactive bladder syndrome are rare.

Adult↗