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Changes in urethral function with bladder filling in the presence of urodynamic stress incontinence and detrusor overactivity.

OBJECTIVE: The purpose of this study was to assess the effect of detrusor overactivity and bladder filling on urethral function with the use of urethral profilometry. STUDY DESIGN: Women with symptoms of urinary incontinence were recruited from our urodynamic clinic. All of the women underwent videocystourethrography and urethral pressure profilometry with the bladder empty and then full. The maximum urethral closure pressure, mean urethral pressure, functional urethral length, and pressure transmission ratios for each quartile were analyzed. RESULTS: Thirty-five women were recruited: 17 women had urodynamic stress incontinence, and 18 women had detrusor overactivity. In women with urodynamic stress incontinence, there was a significant increase in maximum urethral closure pressure and pressure transmission ratios over all quartiles when the bladder was full compared with empty. In women with detrusor overactivity, there was a significant decrease in functional urethral length and pressure transmission ratios in the second and third quartile of the urethral pressure profiles when the bladder was full compared with empty. CONCLUSION: Decreases in functional urethral length and pressure transmission ratios with bladder filling in those women with detrusor overactivity are at variance with the normal physiologic response to bladder filling, which suggests that urethral function is affected by the presence of abnormal detrusor activity and that the valid assessment of urethral function may not be possible if the detrusor overactivity is not treated.

Adult↗

Muscarinic stimulation of the rat isolated whole bladder: pathophysiological models of detrusor overactivity.

1 Hypotheses as to the pathophysiological basis of bladder detrusor muscle overactivity (DO) have identified both central nervous and peripheral mechanisms as likely contributory factors. In this paper, we describe peripheral autonomous bladder activity in two animal models of DO and discuss how the differences observed between the two models support the likelihood that clinical DO has a multifactorial basis. 2 A total of 12 adult female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Six adult female spontaneously hypertensive rats (SHR) were compared with normal Wistar controls. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure in response to the muscarinic receptor agonist arecaidine were performed under standardized conditions. 3 In the partially obstructed rat bladder, the amplitude of pressure fluctuations elicited by the muscarinic agonist arecaidine was significantly increased compared with sham-operated animals. The tonic component of the response was no different for the two groups. No difference from controls was apparent in the SHR. 4 We conclude that alterations in autonomous bladder activity in the obstructed rat model suggest that peripheral functional changes contribute to the pathophysiological abnormality. In contrast, the fundamental abnormality in the SHR appears to be at a more central level. The observations support the supposition that lesions at widely separate sites can give rise to apparently similar abnormalities of lower urinary tract function.

Animals↗

Structural basis of geriatric voiding dysfunction. VI. Validation and update of diagnostic criteria in 71 detrusor biopsies.

PURPOSE: Refined criteria of distinctive patterns of detrusor ultrastructure in geriatric voiding dysfunctions have been developed as standard protocols for pathological evaluation of detrusor biopsies. This study was performed to test completeness and routine applicability of these protocols, corroborate our original ultrastructural/urodynamic correlations in larger material and identify subtle correlations that may have been elusive in our original study of 35 cases. MATERIALS AND METHODS: A total of 71 endoscopic detrusor biopsies was obtained from 44 elderly subjects grouped following comprehensive clinical and urodynamic evaluation into those with normal aging bladder, detrusor overactivity, impaired detrusor contractility, bladder outlet obstruction or a combination. Biopsies were evaluated ultrastructurally and randomly, and blinded to clinical information. Using standard protocols the primary ultrastructural pattern(s) was identified, additional auxiliary features were recorded and pathological diagnoses were made. Biopsies were grouped accordingly, still blindly, and correlated with urodynamic groups determined independently prior to biopsy. RESULTS: Our observations confirmed that the standard protocols are complete and readily applicable to routine ultrastructural evaluation of detrusor biopsies. They corroborated our previously reported ultrastructural/urodynamic matching of the biopsies in every case and revealed new constant features of the normally aging detrusor. We identified ultrastructural correlates distinguishing moderate and severe from mild or borderline (but not moderate from severe) impairment of detrusor contractility. CONCLUSIONS: The proposed protocols are consistently applicable to the routine pathological diagnosis of geriatric voiding dysfunction in detrusor biopsies. A diagnostic algorithm was developed to serve as a practical guide for making such diagnoses, and gaining insights into the pathophysiology of geriatric and possibly other voiding dysfunctions.

Aged↗

[Staghorn calculi of the kidney and ureter as a urologic complication ina child with cerebral palsy].

UNLABELLED: We present a child with cerebral palsy, treated for renal and ureteral staghorn calculi. Calculosis was associated with neurogenic voiding dysfunction. CASE REPORT: A 10 year boy was admitted to Pediatric Surgery Clinic in Poznań because of urolithiasis. In neurologic examination four-extremities spastic paresis and convergent strabismus was found. Intellectual contact with this child was very poor. Constant urine leakage from urethra was observed. In urine analysis pH < 7, leucocytes and erythrocytes, in urine culture Proteus vulgaris > 10(5). Ultrasonography revealed three staghorn calculi in right kidney. On the plain x-ray film three calculi in right kidney and two staghorn calculi in right ureter. In urodynamic evaluation in cystometry: low bladder compliance, no detrusor overactivity, no bladder sensation, "leak point" pressure 25-27 cm H2O. In profilometry incompetent urethral closure mechanism. All stones were evacuated during one operation. Postoperative course was uneventful. Risk factors in the treatment of patients with cerebral palsy are stressed. CONCLUSIONS: 1. Dysfunction of lower urinary tract is an important clinical problem in children with cerebral palsy. 2. Voiding dysfunction could be a risk factor in the development of urinary stones. 3. In the treatment of children with cerebral palsy multispecialistic team is needed.

Cerebral Palsy↗

Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations.

BACKGROUND: The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1), provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. METHODS: Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16), idiopathic detrusor overactivity (IDO, n = 14), and asymptomatic microscopic hematuria (controls, n = 17), were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. RESULTS: TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated) fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249) and PBS (P < 0.0001) specimens, compared with controls. A significantly higher number of TRPM8-immunoreactive axons were also seen in the IDO (P = 0.0246) and PBS (P < 0.0001) groups. Urothelial TRPM8 and TRPM8-immunoreactive thick myelinated fibres appeared unchanged in IDO and PBS. The relative density of TRPM8-immunoreactive nerve fibres significantly correlated with the Frequency (r = 0.5487, P = 0.0004) and Pain (r = 0.6582, P < 0.0001) scores, but not Urgency score. CONCLUSION: This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

Adult↗

Detrusor responses to prostaglandin E2 and bladder outlet obstruction in wild-type and Ep1 receptor knockout mice.

PURPOSE: Prostaglandins (PGs) are suggested to be involved in the pathophysiology of different bladder disorders and it has been demonstrated that cyclooxygenase-2 expression is increased as a consequence of bladder outflow obstruction. We investigated whether the PGE2 receptor EP1 is involved in the regulation of normal micturition, the response to intravesical PGE2 administration, and the development of bladder hypertrophy and overactivity due to bladder outlet obstruction (BOO). MATERIALS AND METHODS: Moderate BOO was created in EP1 receptor knockout (EP1KO) mice and their WT counterparts. After 1 week cystometry was performed in conscious animals before and after PGE2 instillation. Findings were compared to those in unobstructed control animals. Bladder wet weight was measured to document the degree of hypertrophy after BOO. RESULTS: There was no difference between unobstructed EP1KO and WT mice in urodynamic parameters but EP1KO mice did not respond to intravesical PGE2 instillation, while WT mice showed detrusor overactivity. The lack of EP1 receptor did not prevent bladder hypertrophy due to BOO. After BOO WT mice had pronounced detrusor overactivity, while this was negligible in EP1KO mice. CONCLUSIONS: The EP1 receptor appears not to be essential for normal micturition or the mediation of bladder hypertrophy due to BOO but it seems to have a role in the development of detrusor overactivity caused by PGE2 and outlet obstruction.

Animals↗

Detrusor overactivity in spina bifida: how long does it need to be treated?

AIMS: To determine whether a lasting therapeutic effect can be expected from long-term antimuscarinic therapy for neurogenic detrusor overactivity in spina bifida and to answer the question whether detrusor overactivity in spina bifida children with detrusor/sphincter dyssynergia is primarily based on the neuropathy or, in part, can be a secondary detrusor reaction to the functional urethral obstruction. METHODS: Fifteen spina bifida patients, aged between 1 and 12 years, all on a regime of clean intermittent catheterisation (CIC) and oxybutynin since shortly after birth, underwent three consecutive urodynamic studies (UDS). One prestudy UDS for treatment control, one UDS after withdrawal of oxybutynin for 3-5 days and one UDS after reinstallment of oxybutynin treatment. Urodynamic results were compared concerning detrusor overactivity, cystometric bladder capacity, and compliance. RESULTS: Detrusor overactivity was seen in two patients on the prestudy UDS. After several days of withdrawal of oxybutynin overactivity was seen in 11 patients. After oxybutynin withdrawal, bladder compliance was within safe margins for two patients only, after reinstallment, safe vesical pressures were seen in 11 patients. CONCLUSION: The functional obstruction due to detrusor/sphincter dyssynergia has been by-passed chronically in all these children by CIC and oxybutynin. Due to the fact that detrusor overactivity recurs immediately after withdrawal of medication after long-term treatment with oxybutynin, one can conclude that there is no long-lasting therapeutic effect of pharmacological suppression. This suggests that in children with detrusor/sphincter dyssynergia, detrusor overactivity is primarily of neuropathic origin.

Child↗

Human bladder as a novel target for vitamin D receptor ligands.

Human prostate is now considered a target for vitamin D receptor (VDR) ligands, such as BXL-628. Because BXL-628 inhibited prostate growth without interfering with androgen signaling, it represents a new option for benign prostate hyperplasia (BPH) therapy. However, BPH symptoms are related not only to prostate size, but also to compensatory bladder hypertrophy and eventual overactivity. We now report that human bladder expresses VDR (determined by real-time PCR immunohistochemistry and Western blot) and responds to VDR agonists, such as the natural ligand, calcitriol, and its synthetic and less hypercalcemic derivative, BXL-628. Experiments were conducted with stromal cells derived from human bladder neck obtained at surgery from BPH patients. BXL-628 counteracted keratinocyte growth factor (KGF) and androgen-induced cell proliferation and stimulated apoptosis with a parallel reduced expression of the survival oncoprotein Bcl-2. Prolonged serum starvation time-dependently pushed bladder stromal cells to express activated myofibroblast markers, such as desmin and smoothelin, without changing other contractile-related proteins and intermediate filaments, such as vimentin. Chronic exposure to BXL-628 prevented starvation-induced cell phenotype modification. Because hypertrophy and starvation-induced bladder remodeling are supposed to underlie bladder overactivity, it is possible that BXL-628 might be helpful in reducing not only cumbersome symptoms related to prostate overgrowth, but also those related to bladder irritation.

Bone and Bones↗

[Neurogenic bladder in patients with cervical cord compression disorders].

Bladder and urethral functions were evaluated urodynamically in 62 patients with cervical cord compression disorder caused by either ossification of the posterior longitudinal ligament of the cervical spine (32 patients), cervical spondylosis (14 patients), prolapsed cervical intervertebral disc (14 patients) or cervical spinal canal stenosis (2 patients). The patients included 46 males and 16 females with average age of 57 years (range 39 to 73 years). Symptomatic organic infravesical obstruction was excluded by physical and radiographic examination. Cystometry revealed preoperative neurogenic bladder in 22 patients (35%) including overactive detrusor in 10 patients (45%) and underactive in 6 (27%). Twenty-one of them underwent electromyographic examination of external sphincter and 14 (67%) had overactive sphincter. Bladder and urethral functions appeared to be impaired in association with myelopathy of the pyramidal and spinothalamic tract of the cervical cord, because of high incidence of neurogenic bladder associated with positive Babinski's reflex and sensory disturbance at the perineal and lower extremity area. Furthermore, since many patients with deep sensory disturbance in the lower extremities had underactive detrusor, it appears likely that underactive detrusor was accompanied with myelopathy in the posterior funiculus of the cervical cord which mediates bladder proprioceptive sensation. Of twenty-two neurogenic bladder patients, seventeen underwent a cervical bone operation and eleven received postoperative urodynamic evaluation. The average interval from the operation to urodynamic evaluation was 1.6 months (range 1.1 to 2.3 months). Over half of the patients were found to be improved urodynamically as well as neurologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biofeedback training for detrusor overactivity in children.

PURPOSE: We evaluated biofeedback training for incontinence due to detrusor overactivity in children. MATERIALS AND METHODS: Included in our study were 22 boys and 17 girls with a mean age of 11.2 years. We noted nighttime incontinence in 3 patients, nighttime incontinence and daytime urinary symptoms in 26, and daytime incontinence in 10. All patients had detrusor overactivity and incontinence refractory to conventional treatment, including bladder training, tricyclic antidepressants, anticholinergics, desmopressin and/or conditioning therapy. Urodynamic study was performed using an 8Fr double lumen transurethral catheter for cystometry, a double balloon transrectal catheter for rectal pressure and external anal sphincter pressure measurement, and surface electrodes for sphincter electromyography. During biofeedback training patients were instructed to contract the anal sphincter without raising abdominal pressure to inhibit overactive bladder contractions. Biofeedback training was repeated monthly until cystometry revealed a stable bladder or lower urinary tract symptoms improved considerably. RESULTS: Four patients were lost to followup. Of the remaining 35 children urinary symptoms were cured in 23 and improved in 4. Urodynamic studies after 6 months of biofeedback training in 33 cases showed that bladder overactivity disappeared in 10 and improved in 18. Bladder capacity at the initial desire to void and maximum cystometric capacity increased significantly (p = 0.0115 and <0.0001, respectively). Detrusor-sphincter dyssynergia in 2 patients before biofeedback training resolved in each after therapy. CONCLUSIONS: Biofeedback training for detrusor overactivity is effective even in pediatric cases refractory to conventional treatment.

Biofeedback, Psychology↗

Efficacy of botulinum-A toxin bladder injections for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients: an objective and subjective analysis.

AIMS: We studied the use of botulinum-a toxin (BTX-A) injections into the bladder as an alternative approach in patients with neurogenic detrusor overactivity due to multiple sclerosis (MS) with drug-refractory overactive bladder (OAB) symptoms. METHODS: Sixteen MS patients--11 women, 5 men; mean age 48.6 years--with refractory OAB symptoms were included in a one-center prospective study. For outcome analysis, we used a bladder diary, a complete urodynamic study, and validated questionnaires for subjective assessment. We injected 300 U of BTX-A (Botox) into the bladder and into the external sphincter muscle to reduce the probability of posttreatment urine retention. RESULTS: There was an increase in residual volume from 81.3 +/- 23.8 to 126.3 +/- 32.9 ml after 4 weeks. In one woman, transient self-catheterization was unavoidable. Four weeks and 3 and 6 months after BTX-A injection, the significant results were as follows: daytime frequency was reduced by 29%, 44%, and 30%, respectively. Nocturia diminished by 33%, 72%, and 40%. Use of pads was be reduced by 38% after 4 weeks and by 64% after 3 months. Urodynamically, reflex volume and maximal cystometric bladder capacity increased by 73%, 77%, and 58% (at 6 months, the increase was not significant) and by 36%, 27%, and 36% (not significant). Maximal detrusor pressure decreased by 35%, 22%, and 57%. Subjective outcome indicated significant improvement of symptoms at 4 weeks and 3 months, but not at 6 months. Patient satisfaction with the therapy was very high. CONCLUSIONS: BTX-A detrusor injections are very effective in the treatment of drug-resistant OAB symptoms in MS patients as reflected in urodynamic measurements and in patient satisfaction. Build up of residual urine remains a problem of which patients must be informed.

Adult↗

Botulinum toxin for the management of bladder dysfunction.

This review highlights a recent innovation in the medical treatment of detrusor overactivity (DO). Anticholinergics are usually the gold standard to treat bladder overactivity. Adverse effects and lack of efficacy are the two main causes for considering alternative treatments. Until recently, invasive surgery (mainly bladder augmentation) was the only available treatment option for patients with intractable DO. This article considers botulinum toxin type A (BTX-A) injection as an alternative treatment to surgery in patients with DO who do not respond to anticholinergic therapy. To identify papers for inclusion in this review, we searched PubMed with the keywords 'botulinum toxin', 'overactive bladder', 'urinary incontinence' and 'neurogenic bladder' for the years 2000-5. Review articles were not included. Abstracts were cited only if they contained important new information. Experimental animal studies and articles or book chapters related to the use of botulinum toxin for other indications (such as achalasia and cervical dystonia) were analysed with regard to the mechanisms of action of botulinum toxin. From this review, it appears that BTX-A injection into the detrusor muscle is a very effective method for treating urinary incontinence secondary to neurogenic detrusor overactivity (NDO), as well as urinary incontinence due to idiopathic overactive bladder (IDO). In both conditions, the duration of effect seems to be at least 6 months. Overall success rates seem to be similar in both patient populations. For NDO, only one evidence-based medicine level 1 study is available, whereas for IDO, only evidence-based medicine level 3 or 4 studies have been published. Particularly in this latter indication, injection technique and outcome parameters vary from study to study and need to be standardised. Without randomised controlled studies aimed at comparing different techniques and dosages, it remains difficult to decide what technique is optimal for treating patients with IDO who are not willing to perform clean intermittent self-catheterisation (CISC). Therefore, studies that compare different dosages and techniques with the risk of needing CISC in regard to the duration of the effect are mandatory. As more studies of repeated injections have been published, it appears that, at least at medium follow-up, the toxin remains as effective as after the first injection, and there is no evidence of change in bladder compliance or detrusor fibrosis. However, long-term observational studies are necessary to assess these last points. Finally, the commonly reported dose appears to be well tolerated, since few adverse effects have been reported.

Animals↗

Electrostimulation: a future treatment option for patients with neurogenic urodynamic disorders?

This paper provides an overview of electrical stimulation of the nervous system as a treatment option for urodynamic dysfunction and of some of the recent results in this field. The set-up used in our studies for improved bladder filling in spinal cord injured patients by conditional stimulation of the dorsal penile/clitoral nerve is a highly efficient way to limit neurogenic detrusor overactivity and increase bladder capacity. Ongoing studies suggest that recording of bladder nerve activity is stable over time and may be a technique for chronic monitoring of bladder activity. Bladder emptying exploiting an anodal blocking technique permits bladder emptying without simultaneous urethral-perineal contraction, thus enabling a physiological voiding pattern in one continuous sequence. In patients with supraspinal lesions, deep brain electrical stimulation is established only as treatment for a subgroup of patients suffering from Parkinson's disease. Yet, with improved electrode designs and increased clinical experience and experimental results, probably other groups of patients may be candidates for deep brain stimulation. In our study in pigs there was a trend towards increased bladder capacity and compliance in response to stimulation, which is encouraging as several neurological diseases are accompanied by overactive bladder with reduced capacity.

Animals↗

[Intravesical instillation of atropine in treatment of detrusor overactivity in children].

UNLABELLED: We present our own experiences with intravesical Atropine instillation in patients with voiding dysfunction. We used concentration of 10(-6) Atropine in 14 patients with detrusor overactivity. In 12 patients neurogenic voiding dysfunction was caused by a meningomyelocoele. In 2 dysfunction was non-neurogenic. Patients were selected on the base of urodynamic investigation in which low bladder cystometric capacity was caused by detrusor overactivity and poor bladder compliance. This type of therapy was started in patients who had not responded to oral oxybutynin therapy, had major side-effects, or oral therapy had not been possible. All were on clean intermittent catheterisation. The effects on the functional parameters were estimated in urodynamic investigations. With the aim of estimating systemic side-effects blood pressure and heart rate was monitored during Atropine infusion. RESULTS: 6 patients responded to intravesical instillation of Atropine. The increase in bladder cystometric capacity was caused by the decrease in bladder overactivity. No effect on bladder wall compliance was noted. No systemic side-effects were observed. CONCLUSIONS: 1. Intravesical Atropine instillation was useful method of treatment in some patients with detrusor overactivity. 2. No systemic side effects were noted. 3. Because of limited effectiveness and low cost, this method should be considered as an alternative way of decreasing bladder overactivity.

Administration, Intravesical↗