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PubMed2005

Urological manifestations of chronic schistosomal myeloradiculopathy.

OBJECTIVE: To describe the clinical and urodynamic features of patients with chronic voiding dysfunction secondary to schistosomal myeloradiculopathy (SM), as the clinical involvement of the spinal cord is a well recognized complication of Schistosomiasis mansoni infection. PATIENTS AND METHODS: We reviewed the records and urodynamic studies of 26 consecutive patients (17 males and nine females, aged 8-58 years) with chronic neurological and urinary symptoms secondary to SM. The voiding function history, radiological and urodynamic findings and therapeutic approaches were reviewed. Patients with and without upper urinary tract complications were compared in terms of age, duration of voiding dysfunction and urodynamic pattern. RESULTS: The most common urinary symptoms were difficulty in emptying the bladder (17 patients, 65%), urinary incontinence (14, 54%), and urgency and frequency (13, 50%). Laboratory and radiographic evaluation showed urinary tract infection in eight (30%) patients, bilateral hydronephrosis in five (19%) and bladder calculi in five (19%). Urodynamics showed detrusor overactivity with detrusor-external sphincter dyssynergia (DESD) in 14 patients (54%), detrusor arreflexia in six (23%), detrusor overactivity with no dyssynergia in four (15%), and detrusor underactivity in two (8%). Comparing patients with and without upper tract complications showed no differences in age and duration of urinary symptoms, but there was a significant association of detrusor overactivity with DESD and upper urinary tract complications (P = 0.04). Urological management consisted of antibiotics, clean intermittent catheterization, anticholinergic medication and stone removal, as appropriate. Conservative treatment failed in three patients and they required an injection with botulinum-A toxin into the detrusor (two) or ileocystoplasty (one). CONCLUSION: Patients with chronic SM behave clinically like those with other causes of spinal cord disease and neurogenic bladder dysfunction requiring lifelong surveillance. The severity of illness in these patients should re-emphasize the need for early recognition and treatment of this condition, to prevent or reverse the neurological deficits.

Adolescent↗

PubMed1995

[The use of intravesical oxybutynin hydrochloride in patients with neurogenic bladder managed by intermittent catheterization].

Nine patients with persistent urinary incontinence due to neurogenic bladder and intolerable systemic side effects on oral anticholinergic agents were treated with intravesical instillation of oxybutynin hydrochloride. Two tablets (6 mg) dissolved in 10 ml of physiological saline or sterile water were instilled into the bladder two times daily via self intermittent catheterization. The mean bladder capacity increased from 128 to 212 ml 1 month after intravesical instillation of oxybutynin hydrochloride, although this difference was not significant. The bladder was augmented more efficaciously in patients with overactive detrusor than patients with an underactive detrusor. Subjective improvement was recognized in 4 patients. Among 5 patients who discontinued therapy due to ineffective results, maximum urethral closure pressure below 50 cmH2O was seen in 4. Intravesical instillation of oxybutynin hydrochloride was considered to be ineffective clinically in patients with underactive detrusor and low urethral closure pressure. Although no systemic side effects were observed, a decrease of bladder capacity was recognized in 2 patients.

Administration, Intravesical↗

PubMed2003

A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders.

PURPOSE: We compared the expression level of alpha 1-adrenoceptor (AR) subtype mRNA to that of beta-AR subtype mRNA in control and obstructed human bladders, and examined whether alpha 1-AR mediated contraction and beta-AR mediated relaxation of human detrusor muscle are altered by bladder outlet obstruction. MATERIALS AND METHODS: A real-time quantitative reverse transcriptase-polymerase chain reaction based method was used to quantify alpha1 and beta-AR subtype mRNA expression. The contractile response to alpha-AR agonists and the relaxant effect of beta-AR agonists were examined using an isometric contraction technique. RESULTS: The mRNA of alpha 1a, alpha 1b, alpha 1d, beta 1 and beta 2-AR mRNAs was expressed at low levels, while beta 3-AR was the most highly expressed subtype at the mRNA level in control and obstructed bladders. The expression level of alpha 1 and beta-AR subtype mRNA was not significantly different between the 2 groups. The mean contractile response to 10(-4) M phenylephrine +/- SEM was only 4.4% +/- 1.4% and 5.2% +/- 1.4% of the 10(-7) M carbachol induced contraction in the control and obstructed groups, respectively. Contractile responses to phenylephrine were not significantly increased in obstructed bladder. Isoproterenol and the beta 3-AR selective agonist L755,507 relaxed human detrusor muscle in a concentration dependent manner (10(-9) to 10(-4) M). However, the beta 1/beta 2-AR agonist dobutamine and the beta 2-AR selective agonist clenbuterol did not produce relaxation at a concentration of 10(-9) to 10(-5) M in the 2 groups. CONCLUSIONS: These findings indicate that neither up-regulation of alpha1-ARs nor down-regulation of beta-ARs occurs and relaxation mediating beta 3-ARs are by far predominant in the human obstructed bladder. Therefore, it is not likely that bladder alpha1-ARs are responsible for detrusor overactivity and storage symptoms in patients with benign prostatic obstruction.

Adrenergic Agonists↗

PubMed2006

Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?

OBJECTIVE: To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. PATIENTS AND METHODS: Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. RESULTS: Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. CONCLUSION: Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.

Administration, Oral↗

PubMed1991

The bladder cooling test for urodynamic assessment: analysis of 400 examinations.

The clinical significance of the bladder cooling test as one part of a standard urodynamic examination was studied in 375 consecutive patients and 25 controls. Inability to perceive cold sensation in the bladder was common in cases of neurogenic lesions and present in nearly half of the patients with outlet obstruction, some with no urodynamic abnormalities and some of the normal subjects. The bladder contractions provoked by the test were clearly associated with detrusor overactivity, as in those patients with upper motor neuron lesions of motor urgency, but 27% of such patients showed no response. In 7 cases the iced water provoked detrusor contractions when cystometry showed no overactivity. This clinical series confirms that the cold receptors found recently in animal experiments are also present in the human urinary bladder. The bladder cooling test is not an alternative to cystometry, but its inclusion as an integral part of the urodynamic examination seems to be useful, especially in cases where there is also a need to study the sensibility of the bladder at the same time.

Adolescent↗

PubMed2004

The effect of intravesical sodium nitroprusside on idiopathic detrusor overactivity.

Although nitric oxide (NO) plays an important role in the urethra and outlet region of the bladder, the role of this inhibitory neurotransmitter in the human detrusor remains unclear. We conducted a prospective, randomised, open study on 31 patients with urodynamically proven idiopathic detrusor overactivity in order to examine the effects of intravesical administration of the NO donor sodium nitroprusside (SNP) on detrusor overactivity. Thirty-one consecutive patients (14 male, 17 female; mean age 53.0+/-2.7 years) with idiopathic detrusor overactivity diagnosed by pressure-flow analysis were included in this study. The patients were randomised into two groups. Cystometries were performed with normal saline in the control group ( n=10) and with 7.2 mM SNP solution (2.16 mg/ml) in the study group ( n=21). We urodynamically investigated sensation, maximal cystometric capacity, compliance, instability index, amplitude and frequency of involuntary contractions. No statistically significant differences was found between the first (pressure-flow) and second (saline or SNP cystometry) urodynamic values in the control and study groups (P>0.05). We have demonstrated that SNP does not have any effect on uninhibited bladder contractions. These results suggest that the intravesical administration of SNP is not an effective treatment for detrusor overactivity.

Blood Pressure↗

PubMed2002

Non-neurogenic female voiding dysfunction.

PURPOSE OF REVIEW: The pathophysiological mechanisms of female voiding phase dysfunction are poorly understood, and there are neither standard definitions nor guidelines for diagnosis and treatment. The aim of this review is to present up-to-date data and controversies associated with non-neurogenic female voiding dysfunction. RECENT FINDINGS: Conceptually, voiding phase dysfunction may have bladder or urethral causes. Bladder causes include detrusor contraction of inadequate magnitude or duration to effect bladder emptying (detrusor underactivity), or the absence of detrusor contraction (detrusor arreflexia). Urethral causes consist of bladder outlet obstruction as a result of urethral overactivity (functional obstruction), or anatomical (mechanical obstruction) pathologies. The specific prevalence and contribution of each of the above mechanisms is unknown. Furthermore, a correct and timely diagnosis may be difficult, because clinical features are very similar to those of other lower urinary tract symptoms, and diagnostic modalities are often inconclusive or even misleading. A full urodynamic evaluation is essential in making the diagnosis; however, standard urodynamic definitions are still lacking. In the following review, we will present recent findings associated with the prevalence, etiology and diagnosis of each of the different categories of female voiding phase dysfunction, and highlight new advances presented during the past year. SUMMARY: Further epidemiological and pathophysiological investigations are needed to evaluate the causes and main risk factors of voiding dysfunction in women. A better understanding of the pathophysiological mechanisms associated with this challenging condition may provide the possibility to use appropriate diagnostic and treatment modalities, thus avoiding unnecessary interventions.

Female↗

PubMed2001

Myosin isoforms in female human detrusor.

The aim of this study was to document the relative proportions of two isoforms of myosin heavy chain in detrusor smooth muscle of women with detrusor overactivity and in asymptomatic controls. Women aged 35-65 with documented detrusor overactivity and without a history of neurologic disease, prior incontinence surgery, elevated post-void residual urine volume, or indwelling urinary catheter were eligible for the study. Full-thickness biopsies of extraperitoneal bladder dome were obtained at the time of laparotomy in six patients with documented detrusor overactivity and in a control group of eight continent patients. Biopsies were frozen in liquid nitrogen, crushed with a frozen mortar and pestle at -80 degrees C, and homogenized in buffer, and the extracts were electrophoresed on 6% polyacrylamide sodium dodecyl sulfate gels and stained with Coomassie blue. The gels were de-stained and then the protein bands were scanned with a densitometer. The mean patient age was 48 years (range, 36-59). Seven patients were Caucasian and seven patients were African American. Detrusor smooth muscle contains a mean of 34% (range, 27-43%) SM1 and 66% (range, 57-73%) SM2 isoforms. There was no difference in isoform composition when patients were compared according to urogynecologic diagnosis or according to race. In detrusor biopsies from women, approximately 34% of myosin is of the SM1 isoform and approximately 66% is of the SM2 isoform. This ratio is relatively constant in the two races studied and unchanged in women with detrusor overactivity. Animal models utilizing outlet obstruction of the bladder to provoke detrusor instability and detrusor hypertrophy are known to alter myosin isoform distribution and may not be appropriate models of detrusor instability in human females.

Adult↗

PubMed1993

Effects of terflavoxate on stimulated contractions of urinary bladder in vitro.

The antispasmodic activity of terflavoxate (CAS 86433-39-8), a flavone derivative with spasmolytic properties on the urinary tract, has been studied in vitro, in comparison to the most common drugs utilized in the therapy of overactive detrusor, namely flavoxate, oxybutynin, and terodiline. Terflavoxate showed affinity for bladder (and brain) muscarinic receptors at micromolar level, however, its activity on carbachol-induced contractions of rat bladder was clearly non competitive, indicating that the compound is devoid of functional antimuscarinic property. Moreover, the observation that unlike antimuscarinic drugs, terflavoxate inhibited by more than 50% field stimulation-induced contractions of rabbit bladder strips, indicates that mechanisms other than the anticholinergic one should be responsible for its smooth muscle relaxant properties. Terflavoxate, flavoxate, oxybutynin, and terodiline were equally effective in inhibiting the two components of K(+)-induced contractions, while nifedipine and nicardipine were more potent than the other compounds, and more effective in inhibiting tonic than phasic contractions. In addition, while nifedipine and nicardipine antagonized in a competitive manner calcium-induced contractions of potassium-depolarized bladder strips, the other spasmolytics behaved as mixed antagonists. Differences in calcium antagonistic properties between nifedipine and nicardipine on one side, and terflavoxate on the other, are further demonstrated by the data on binding experiments. Nevertheless, present results suggest that Ca(++)-antagonistic effects are mainly responsible for terflavoxate smooth muscle relaxant properties.

Animals↗

PubMed2004

Increased expression of connexin 43 in the overactive neurogenic detrusor.

PURPOSE: The cellular mechanisms involved in unstable uncontrolled detrusor contractions in the human bladder remain unknown. One hypothesis, based on electron microscopical observations and animal studies, is that gap junctions are present in the human detrusor and are increased in patients with detrusor overactivity. Thus intercellular electrical coupling between adjacent detrusor cells would be increased allowing electrical activity to spead more easily within the detrusor muscle mass and more readily generate significant contractions. The aim of this study was to prove this hypothesis. MATERIAL AND METHODS: Detrusor biopsies have been obtained from videourodynamically evaluated patients with neurogenic detrusor overactivity (NDO) (n = 19) [group I] and from patients with stress urinary incontinence (SUI) with stable, non-obstructed detrusors (n = 5) [group II] serving as controls. Specimens were fixed, paraffin embedded, sectioned, stained with a monoclonal connexin 43 antibody and evaluated by two blinded examiners using a semiquantitative scale. Connexin 43 mRNA levels were evaluated using quantitative RT-PCR with primers for connexin 43 and for 18S rRNA. The results were correlated with the patients' groups. RESULTS: Connexin 43 could be identified in cross sections of every detrusor biopsy. In all biopsies from patients with NDO a widespread presence of connexin 43 staining was observed, whereas only a limited presence of connexin 43 staining was observed in the specimen from patients with SUI. Connexin 43 mRNA levels within the detrusor were 3.7 fold higher in the NDO group than in the SUI group (p = 0.017). CONCLUSIONS: A limited amount of gap junctions seems to be present in every detrusor independently from its urodynamic stability or instability. But there is a significant increase in connexin 43 protein and RNA levels in patients with neurogenic detrusor overactivity underlining their role in intercellular electrical coupling.

Adolescent↗

PubMed1996

Physiological principles for surgical correction of detrusor dysfunction.

Urinary incontinence may be the result of various forms of detrusor overactivity. Several surgical therapies have been devised, but with the exception of procedures to relieve urethral obstruction, none abolishes the overactivity or restores normal micturition. In general, ablative neurosurgery is considered only in patients with chronic neurologic disease. Bladder augmentation is useful in selected patients. The indications for urinary diversion in patients with detrusor overactivity and urge incontinence are quite limited.

Animals↗

PubMed2002

Quest for a detrusor overactivity index.

PURPOSE: Urge incontinence, which is the predominant type of geriatric incontinence, is generally attributed to detrusor overactivity. However, detrusor overactivity is present in up to half of continent elderly individuals. We postulated that detrusor overactivity associated with urge incontinence would be more severe but there are no established criteria for judging severity. Using urge incontinence frequency as a yardstick and controlling for nonurodynamic contributing factors we sought intrinsic lower urinary tract parameters that reflect detrusor overactivity severity. We postulated that parameters in 1 or more of 5 domains would be important, namely characteristics of uninhibited contraction, bladder capacity, bladder proprioception, detrusor contractility and sphincter adequacy. MATERIALS AND METHODS: We analyzed data on 79 community dwelling incontinent individuals older than 60 years old. All subjects had urge incontinence on a 4-day voiding record and underwent multichannel videourodynamics. We examined the associations of urge incontinence frequency with the postulated key factors. RESULTS: Multivariable analysis revealed that 24-hour urine output and functional bladder capacity consistently predicted urge incontinence frequency. Bladder proprioception was significant in some models. Uninhibited contraction pressure was another predictor. Surprisingly higher uninhibited contraction pressure was associated with lower urge incontinence frequency. This negative correlation was more pronounced in a subgroup with a less adequate sphincter but absent in those with good sphincter function, implying that low uninhibited contraction pressure does not necessarily indicate less severe detrusor overactivity but rather reflects sphincter inadequacy in many patients. Age was not independently associated with urge incontinence frequency. CONCLUSIONS: We identified functional bladder capacity as a measure of detrusor overactivity severity. The measure commonly used, namely uninhibited contraction pressure, is inappropriate because it is severely confounded by sphincter function, especially in older individuals. Furthermore, we confirmed that urine output, and possibly bladder sensation and sphincter strength modify the clinical manifestation of detrusor overactivity.

Aged↗

PubMed2003

Bladder wall thickness on ultrasonographic cystourethrography: affecting factors and their implications.

OBJECTIVE: To explore factors affecting bladder wall thickness on ultrasonographic cystourethrography in female patients with lower urinary tract symptoms. METHODS: The records of 492 female patients with lower urinary tract symptoms who had undergone a urodynamic study and ultrasonography of the lower urinary tract and who had normal urinalysis findings, negative urine culture results, or both were identified from our urogynecologic database. These included 248 patients with urodynamic stress incontinence, 38 with detrusor overactivity, 39 with mixed incontinence, 35 with a hypersensitive bladder, 42 with voiding difficulty, and 90 with normal urodynamic findings. RESULTS: Age, resting bladder neck angle, urethral mobility, and maximum urethral closure pressure were significantly associated with bladder wall thickness at the trigone and dome. Bladder wall thickness at the trigone was correlated with that at the dome (P < .0001). Bladder wall thickness at the trigone was positively correlated with pressure transmission ratios in the first and second quarters of the urethra (P < .0001; P = .002, respectively), whereas that at the dome was positively correlated with intravesical pressure at maximum flow and with detrusor opening pressure (P = .027; P = .046, respectively). Age and intravesical pressure at maximum flow were independently associated with bladder wall thickness at the trigone and dome (P = .007; P = .028), respectively. A thickened bladder wall was a common finding in female lower urinary tract symptoms, except in the patients with a hypersensitive bladder. CONCLUSIONS: Demographic, anatomic, and urodynamic factors may affect the bladder wall thickness at the trigone, dome, or both.

Female↗

PubMed2004

Role of C afferent fibers and monitoring of intravesical resiniferatoxin therapy for patients with idiopathic detrusor overactivity.

PURPOSE: Resiniferatoxin (RTX) is a specific C fiber neurotoxin which produces desensitization. In this study we performed intravesical RTX therapy in patients with idiopathic detrusor overactivity. In addition we measured the current perception threshold of C and A delta fibers before and after treatment to evaluate clinical significance. MATERIALS AND METHODS: The protocol involved an RTX solution (100 ml of 50 nM) instilled in the bladder for 30 minutes. Four men and 6 women 59 to 75 years old were treated. Effects on bladder function were evaluated before and 30 days after treatment by cystometry and Neurometer (Neurotron, Inc., Baltimore, Maryland). Subjective and objective measures included bladder diaries and quality of life before treatment, and 7, 30 and 90 days subsequently. RESULTS: Of the 10 patients 5 noted improvement and 2 of them became dry. The other 5 patients were considered to have stationary symptoms. Mean maximal cystometric capacity +/- SD increased from 229 +/- 108 ml at baseline to 271 +/- 99.5 ml at 30 days (p = 0.04). The mean number of daily episodes of urinary incontinence decreased from 3.5 +/- 2.2 to 2.0 +/- 1.6 (p = 0.008) at 7 days, to 1.9 +/- 1.6 (p = 0.018) at 30 days and to 2.5 +/- 1.7 (p = 0.018) at 90 days. Mean current perception threshold values of C and A delta fibers did not change significantly, from 46.9 +/- 35.2 to 56.4 +/- 32.1 (p = 0.161) and from 66.9 +/- 31.7 to 66.4 +/- 25.2 (p = 0.952), respectively. However, values of C fibers increased in all patients who showed improvement from 46.2 +/- 33.2 to 64.0 +/- 36.8 (p = 0.043). CONCLUSIONS: Intravesical RTX improved bladder capacity and leak episodes in patients with idiopathic detrusor overactivity. Intravesical RTX is a promising treatment for this condition.

Administration, Intravesical↗

PubMed2004

Videourodynamic findings in young infants with severe primary reflux.

PURPOSE: We investigated bladder function on videourodynamic studies in infants with severe primary vesicoureteral reflux (VUR) and analyzed the relationship between VUR and intravesical detrusor pressure during the micturition cycle. MATERIALS AND METHODS: From 1999 to 2001, 3 female and 9 male infants with a median age of 9 months with VUR underwent conventional filling videourodynamics at our institution. Four cases were diagnosed by prenatal detection and 8 were diagnosed after symptomatic urinary tract infections. Reflux was bilateral in 5 cases and unilateral in 7 (grades III to V in 7, 7 and 3, respectively). Controls included 10 age matched infants (median age 4 months) studied with the same urodynamic methodology. RESULTS: Median cystometric bladder capacity expected for age +/- SD was 50% +/- 58% (range 20% to 240%). Bladder capacity was low (less than 80%) in 10 patients. Detrusor overactivity during filling was found in only 1 patient. In all except 1 case voiding alternated with peaks of high detrusor pressure (median 87 +/- 25 cm water), associated with intermittent external sphincter contractions with normal coordinated micturition (median 36 +/- 7 cm water). Cystometric residual urine (30% or greater) was noted in 3 cases. In 5 patients VUR occurred with an increase in bladder pressure, while in 7 it occurred during stable filling. No significant cystometric differences were found between patients with reflux and controls. CONCLUSIONS: Most infants with VUR had decreased cystometric bladder capacity and normal detrusor activity during filling. High voiding pressure with concomitant sphincteric overactivity coexisted with normal micturition. This voiding pattern might represent a developmental stage of normal urine control and it may have a role in the etiology of reflux in some infants.

Child, Preschool↗

PubMed2001

Is the irritable bladder associated with anterior compartment relaxation? A critical look at the 'integral theory of pelvic floor dysfunction'.

The 'integral theory of pelvic floor dysfunction', first proposed by Petros and Ulmsten in 1990, claims that anterior vaginal wall relaxation is associated with symptoms of urgency, frequency, nocturia and urge incontinence. A retrospective study was designed to test this hypothesis. Imaging data and urodynamic reports from 272 women suffering from symptoms of lower urinary tract dysfunction were evaluated. Opening of the retrovesical angle, bladder neck descent, urethral rotation and descent of a cystocele during Valsalva were used to quantify anterior vaginal wall laxity. None of the tested parameters were associated with symptoms and signs of detrusor overactivity On the contrary, patients with higher grades of urethral and bladder descent were less likely to suffer from nocturia and urge incontinence and were less likely to have sensory urgency and detrusor instability diagnosed on urodynamic testing. The findings of this study therefore do not support this hypothesis of the 'integral theory'.

Adult↗

PubMed2006

Urodynamic effects of intravesical administration of the new small/intermediate conductance calcium activated potassium channel activator NS309 in freely moving, conscious rats.

PURPOSE: We investigated the effects of the new K+ channel activator NS309, which acts on small and intermediate conductance Ca2+ activated K+ channels, on detrusor activity in normal rats. MATERIALS AND METHODS: NS309 was given intravesically at different concentrations to conscious female Sprague-Dawley rats undergoing continuous cystometry. The effects of the drug on oxyhemoglobin induced detrusor overactivity were also tested. RESULTS: Intravesical NS309 (100, 300 and 1,000 ng ml(-1)) increased bladder capacity, micturition volume and intercontraction intervals in a concentration dependent way. NS309 (1,000 ng ml(-1)) given intravesically for 1 hour before instillation of intravesical oxyhemoglobin (250 microM) decreased or completely prevented the detrusor overactivity induced by oxyhemoglobin. CONCLUSIONS: Opening small and intermediate conductance Ca2+ activated K+ channels with NS309 given intravesically increased bladder capacity, micturition volume and intercontraction intervals in a concentration dependent way and prevented oxyhemoglobin induced detrusor overactivity. Results suggest that these channels can be interesting targets for drugs aiming to control micturition.

Administration, Intravesical↗

PubMed2006

A gap junction blocker inhibits isolated whole bladder activity in normal rats and rats with partial bladder outlet obstruction.

We examined the effect of 18alpha-glycyrrhetinic acid (18alpha-GA), a gap junction blocker, or propiverine hydrochloride on the activity of isolated whole bladders obtained from intact rats and rats with partial bladder outlet obstruction (BOO). Thirty-two female Sprague-Dawley rats were divided into an intact group and a BOO group. The whole bladder was harvested from each rat and isovolumetric cystometry was performed in Krebs solution. Changes of bladder activity were recorded after addition of 18alpha-GA or propiverine hydrochloride to the perfusate. Propiverine hydrochloride inhibited the amplitude and duration of contraction in both intact and BOO groups. Propiverine hydrochloride also reduced the baseline bladder pressure in the BOO group, but not in the intact group. In contrast, 18alpha-GA inhibited the amplitude and duration of bladder contraction, and also reduced the baseline pressure, in both intact and BOO groups. BOO bladders showed inhibition of the amplitude and duration of bladder contraction at lower concentrations of 18alpha-GA than intact bladders. A gap junction blocker suppressed the in vitro activity of BOO bladders more effectively than that of intact bladders. Therefore, inhibition of intercellular communication in the bladder via gap junctions may be useful for treating detrusor overactivity, as well as propiverine hydrochloride.

Animals↗