High Bladder Pressure Research Articles

Botulinum toxin in the failure of high urinary diversion closure

IntroductionThe closure of urinary diversions performed on newly born infants has a notable failure percentage in patients with bladder disease. We present the use of botulinum toxin as a useful and minimally invasive alternative to treat these patients. Materials and methodsWe present two patients with a single kidney and with posterior urethral valves (PUV), in whom it was necessary to perform a ureterostomy due to chronic kidney disease. In both patients, the subsequent attempt to close the diversion failed. Aged 4 and 10years respectively, they presented bladders commonly known as “dry bladders”, with a low capacity (20 and 110ml), bad adaptation (1.5 and 3.1ml/cm H2O) and high opening detrusor pressure. A 10UI/kg botulinum toxin A puncture was applied in the detrusor on one and two occasions respectively, prior to the closure of the diversion. ResultsNeither of the patients suffered clinical or ecographic worsening after the closure of the diversion and their kidney function continued without change with respect to the first diversion after 1 and 4years of follow-up respectively. One year after the surgical procedure, video urodynamics showed a significant improvement in bladder capacity (451 and 250ml), in adaptation (20.4 and 81.9ml/cm H2O) and in the opening detrusor pressure. ConclusionsThe closure of high urinary diversions has a high failure percentage in infants with pathological high-pressure bladders. Botulinum toxin may be useful as bladder treatment prior to closure of the diversion, especially in patients with a single kidney.

Toxina botulínica en el fracaso del cierre de derivaciones urinarias altas

Introduction The closure of urinary diversions performed on newly born infants has a notable failure percentage in patients with bladder disease. We present the use of botulinum toxin as a useful and minimally invasive alternative to treat these patients. Material and methods We present two patients with a single kidney and with posterior urethral valves (PUV), in whom it was necessary to perform a ureterostomy due to chronic kidney disease. In both patients, the subsequent attempt to close the diversion failed. Aged 4 and 10 years respectively, they presented bladders commonly known as “dry bladders”, with a low capacity (20 and 110 ml), bad adaptation (1.5 and 3.1 ml/ cm H 2O) and high opening detrusor pressure. A 10 UI/Kg botulinum toxin A puncture was applied in the detrusor on one and two occasions respectively, prior to the closure of the diversion. Results Neither of the patients suffered clinical or ecographic worsening after the closure of the diversion and their kidney function continued without change with respect to the first diversion after one and four years of follow-up respectively. One year after the surgical procedure, video urodynamics showed a significant improvement in bladder capacity (451 and 250 ml), in adaptation (20.4 and 81.9 ml/cmH 2O) and in the opening detrusor pressure. Conclusions The closure of high urinary diversions has a high failure percentage in infants with pathological high-pressure bladders. Botulinum toxin may be useful as bladder treatment prior to closure of the diversion, especially in patients with a single kidney.

Es la inyección de Toxina botulínica-A en el detrusor una alternativa a la ampliación vesical en niños

Introductionbladder dysfunction causes urinary incontinence and kidney damage in children. When treatment with anticholinergics and intermittent bladder catheterization fails, the alternative therapy is bladder augmentation. Patients and methodsbetween 2005 and 2009, a prospective study was carried out with Botox® injected into the detrusor of children suffering from high-pressure bladder despite anticholinergic treatment. We assessed their urodynamic, clinical and radiological evolution prior to and at 4 weeks, 6 months and 1 year after the injection (10 u/kg of weight up to 300 u). Reinjection was indicated in the event of clinical or urodynamic worsening. We employed the Wilcoxom test to statistically analyze the urodynamic parameters. Results12 patients were treated, 11 with neurogenic bladder (91.7%) and 1 with posterior urethral valves (8.4%). The mean age was 12.6 (4.3-17.8) years and follow-up took place after 40.8 (16.9-45-7) months. Bladder capacity, detrusor accommodation and pressure improved after 4 weeks in all the patients except in 2 (16.7%). This improvement decreased after 6 months, although successive injections produced similar changes. One patient (8.3%) received 1 dose, six (50%) two doses and five (41.7%) received three. Clinical and urodynamic improvement in 8 patients (66.7%) prevented bladder augmentation. Conclusionsrepeated botulinum toxin injection in the detrusor is a therapeutic instrument for high pressure and low accommodation bladders in children. It could replace bladder augmentation in some cases, however further studies with long-term follow-up care are required to appropriately evaluate its safety and effectiveness.

Injection of botulinum toxin (BTX-A) in children with bladder dysfunction due to detrusor overactivity

IntroductionBladder dysfunction causes urinary incontinence and kidney damage in children. When treatment with anticholinergics and intermittent bladder catheterization fails, the alternative therapy is bladder augmentation. Patients and methodsBetween 2005 and 2009, a prospective study was carried out with Botox® injected into the detrusor of children suffering from high-pressure bladder despite anticholinergic treatment. We assessed their urodynamic, clinical and radiological evolution prior to and at 4 weeks, 6 months and 1 year after the injection (10u/kg of weight up to 300u). Reinjection was indicated in the event of clinical or urodynamic worsening. We employed the Wilcoxon test to statistically analyze the urodynamic parameters. Results12 patients were treated, 11 with neurogenic bladder (91.7%) and 1 with posterior urethral valves (8.4%). The mean age was 12.6 (4.3–17.8) years and follow-up took place after 40.8 (16.9–45–7) months. Bladder capacity, detrusor compliance and pressure improved after 4 weeks in all the patients except in 2 (16.7%). This improvement decreased after 6 months, although successive injections produced similar changes. One patient (8.3%) received 1 dose, six (50%) two doses and five (41.7%) received three. Clinical and urodynamic improvement in 8 patients (66.7%) prevented bladder augmentation. ConclusionsRepeated botulinum toxin injection in the detrusor is a therapeutic instrument for high pressure and hypocompliant bladders in children. It could replace bladder augmentation in some cases, however further studies with long-term follow-up care are required to appropriately evaluate its safety and effectiveness.

Management of neurogenic bladder in myelodysplasia patients: experience at our center

Background Myelodysplasia is the term used for lesions include Spina bifida occulta, lipomeningocoele, meningocoele and meningomyelocele. meningomyelocoele is by far the most common disease of this group. These patients are commonly having neurogenic bladder. The treatment of neurogenic bladder is not so easy.[1] we are presenting our experience of 68 cases with neurogenic bladders. The aim of our study is to achieve continence and preserve upper urinary tract from further damage. There are a battery of investigations to assess these patients for eg. renal biochemistry, ultrasonography of the urinary tract, Micturating cysto-urethrogram,isotope renal scans, Clinical and bedside assessment, and Urodynamics.Tratment options available for these patients are drug therapy in the form of prophylactic antibiotics and anticholinergic drugs. Clean intermittent catheterization advocated by Lapides plays major role in the treatment of these patients [2]. Operative procedure perform in these patients are bladder neck reconstructions like, Young Dees Leadbetter and rectus sling.[3] High pressure bladder can be converted to low pressure bladder by using bladder augmentation procedures. Bladder augmentation procedures are increasing bladder capacity also thus improving dry intervals. Continent urinary diversion can be done by using appendix [4] and segment of ileum [5]. Once these patients achieve social or urinary continence follow up is very important.

Bladder outlet obstruction: progression from inflammation to fibrosis

To investigate the progression of urodynamic changes, as well as histological and biochemical outcomes over a prolonged period of partial bladder outlet obstruction (pBOO) in an animal model with physiologically relevant pBOO. Healthy, adult, female Fischer rats underwent surgical creation of a pBOO for either 2, 4, 8, or 13 weeks and were compared with sham-operated rats. Urodynamic measurements were used to compare bladder volumes and pressure. Tissue was grossly analysed with light microscopy and bladder weights and thicknesses were compared. Reverse transcription-polymerase chain reaction for collagen, transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), hypoxia inducible factor 1α (HIF-1α), and platelet-derived growth factor (PDGF-A) was performed on all samples, as well as immunohistochemistry (IHC) for α-smooth muscle actin (α-SMA). Finally, mass spectrometry was used to quantify the collagen content of the bladders as a measure of fibrosis. After induction of pBOO, all rats remained healthy. Initial urodynamics showed an increase in capacity while maintaining normal pressures, but then deteriorated into small capacity, high-pressure bladders. Haematoxylin and eosin (H&E) staining showed an initial inflammatory response, and this was confirmed with significantly increased mRNA levels of TGF-β, CTGF, HIF-1α, and PDGF. The progression to smooth muscle hypertrophy was evident on H&E and confirmed with increased bladder mass and thickness. IHC for α-SMA showed a progressive increase associated with the elevated bladder pressures. Masson's trichrome and mass spectrometry showed a progressive increase in collagen to 13 weeks. With this model, we have effectively replicated the clinical scenario, with significant pathophysiological changes occurring insidiously in otherwise healthy rats. We believe that our observed changes represent distinct phases of bladder decompensation; with an initial inflammatory response to the stress of the pBOO, smooth muscle hypertrophy to overcome the increased urethral resistance, and eventual decompensation to fibrosis. The time course of the inflammatory markers implies the need for early intervention to prevent this cascade. Novel strategies targeting these observed physiological responses could lead to improved preventative strategies, with respect to biochemical pathways and the time course of their initiation.

A new extra-abdominal channel alternative to the mitrofanoff principle: experimental and preliminary clinical experience

The appendix is the gold-standard channel for the Mitrofanoff principle in pediatric urology, but the search for alternatives is justified considering it may not be available or preferably used for colonic stomas (Malone antegrade continence enema). The aim of this study is to report on technical feasibility of a new approach for creating catheterizable channels in a rabbit model and to present our preliminary clinical experience. We configured a tube from two rectangular skin flaps 1x4 cm opposite each other in the middle line of the lower inferior abdomen. The channel was anastomosed to the bladder dome with embedding sutures to create a valvular mechanism. The experimental study consisted of 12 rabbits, divided in 4 groups according to the sacrifice schedule at 2, 4, 8 and 12 weeks. At 30th postoperative day, an urodynamic evaluation was performed to record continence of the stoma. A histological analysis of the specimens stained with hematoxylin-eosin, Masson trichrome and Picrosirius red was also done in group 2 (sacrifice at 4 weeks postoperatively). We used this method in 3 patients with congenital non-neurogenic bladder disease presenting with massive residual volumes without compliance deficits. The technique proved feasible in all animals, 9 of 12 could be easily catheterized and underwent urodynamic study. No stoma leakage was observed in 7 animals at high bladder pressures (> 50 cm H20) and only 2 animals had some leakage at 40 cm H20. Urodynamics performed through the stoma showed urethral leakage at 20 cm H20, therefore demonstrating the efficacy of the valvular mechanism. Histological analysis confirmed good integration between the tube and the bladder. Mean follow-up of the clinical series (3 patients) was 7.2 months. Two patients remained continent up to 4 hours, whereas 1 patient had some leakage after 2 hours. We were able to confirm feasibility of a new extra-abdominal channel based on the Mitrofanoff principle and successfully reproduced the method in a clinical setting. Follow-up was short and long term results are required before any conclusive judgment can be made.

Nephrogenic diabetes insipidus with dilatation of bilateral renal pelvis, ureter and bladder

Nephrogenic diabetes insipidus (NDI) with dilatation of upper urinary tract and bladder is rarely reported. This study evaluated the urological manifestations and treatment results of this rare condition. According to a fluid deprivation test, seven men and two women were diagnosed as NDI, and underwent ultrasonography, magnetic resonance urography, cystography, and urodynamic and laboratory examination. A micturition diary and symptoms were recorded before and during treatment. All patients were given hydrochlorothiazide and followed up with ultrasonography, the postvoiding residual volume (PVR), urinalysis and kidney function tests. All patients presented with polydipsia and polyuria with severe dilatation of upper urinary tract and bladder. Urodynamics showed that the mean values of the bladder capacity, bladder pressure at the end of filling, maximum flow rate (Q(max)), detrusor pressure and PVR were 1056.3 ml, 40.5 cmH(2)O, 30.8 ml/s, 51.3 cmH(2)O, 436.3 ml, respectively. The total urine volume in all patients decreased by more than 50% after administration of hydrochlorothiazide, which improved the symptoms and hydronephrosis in seven cases. The symptoms of other two cases were relieved after treatment with an electric transurethral incision of the bladder neck and a cystostomy. NDI should be considered in patients with dilatation of the urinary tract and polyuria. Higher bladder pressure at the end of filling may contribute to the dilatation of urinary tract. Normal detrusor contractility with large PVR is a unique manifestation of this condition. Controlling the urine volume and reducing the PVR are of key importance in the treatment of this condition.

Influence of High Bladder Pressure on Vesicoureteral Reflux and Its Resolution

Objectives: Voiding dysfunction may result in lower urinary tract symptoms in children and is associated with urinary tract infection, renal damage and vesicoureteral reflux (VUR). The aim of this study was to assess the relationship between detrusor pressure, VUR and abnormal renal scintigraphy findings in children with dysfunctional voiding. Patients and Methods: Between 2004 and 2007, 30 children with VUR and voiding dysfunction, 22 girls and 8 boys, median age 8.2 years, were evaluated. Urodynamic study, renal scan and voiding cystourethrography were performed in all patients. Results: The degree of the renal scarring was found to be associated with the detrusor pressures (p = 0.018). The highest detrusor pressure was shown in the group of urge syndrome. The degree of the VUR was found to be correlated with the detrusor pressures (p = 0.038). In our study group, VUR had resolved in 11 (37%) patients, had improved in grade in 10 (33%) patients and remained unchanged in 9 (30%) patients after anticholinergic therapy. No significant relationship was found between the duration of therapy and the voiding patterns (p = 0.389). Conclusion: Every child with VUR should undergo a careful evaluation of its bladder function. The patients who have high detrusor pressures should be evaluated carefully for the presence of VUR and renal damage.

Eficacia del tratamiento endoscópico del reflujo vesicoureteral secundario: Análisis de una serie de 142 casos

To evaluate the rate of secondary or complicated vesicoureteral reflux (VUR) among the total number of VUR cases treated in our institution. To determine the efficacy of the endoscopic treatment in secondary or complicated VUR depending on etiology and grade. We review our experience with endoscopic treatment for VUR from 1992 to 2006. We have used three different materials: polytetrafluoroethylen (Teflon), polydimethyls iloxane (Macroplastique) and dextranomer/hyaluronic acid copolymer (Deflux). 479 ureters with VUR were treated in 402 patients; 124 patients and 142 ureters of them were secondary or complicated VUR cases. All patients were followed up with urinary tract ultrasound and radiological or isotopic voiding cystogram. Success is defined as VUR disappearance or improvement to grade I VUR without urinary infection after removing antibiotic prophylaxis. The success rate has been 71.13% after the first injection, 85.92% after the second injection and 90.14% after the third injection. Mean subureteral dose has been 0.65 ml. The complications rate has been 0%. The endoscopic treatment in secondary or complicated VUR is a minimally invasive procedure. It seems to be more difficult than in primary VUR cases, but its low morbidity and efficacy indicate this may be a proper first option in selected patients. In cases of VUR secondary to neurogenic bladder dysfunction it seems to be less successful, probably because of a worse control of the high bladder pressure.

Strategies to promote intermittent self-catheterisation in adults with neurogenic bladders: A systematic review.

Review Objective The purpose of this systematic review is to establish the best available evidence on strategies to promote intermittent urethral self-catheterisation in adults with neurogenic / neuropathic bladders. More specifically, the review questions are: What are the extrinsic and/or intrinsic factors that influence the suitability of individuals to perform self intermittent [urethral] catheterisation (SIMC)? What strategies promote long term compliance with SIMC? What are the advantages and disadvantages of using SIMC? Does SIMC improve the quality of life for people using this bladder management strategy? Criteria for considering studies for this review Types of Studies This review will incorporate the best available evidence for each of the sub-topics identified by the objectives and specific questions asked in this systematic review. Quantitative This component of the review will consider any randomised controlled trials (RCT) that examine the effectiveness of strategies to promote long term compliance with self-intermittent catheterisation. In the absence of RCT other quantitative research designs such as non-randomised experimental and quasi experimental, before and after studies, cohort studies and case series/case reports will be considered for inclusion in a narrative summary. For the remaining three sub-topics, i.e. quality of life, advantages and disadvantages of SIMC, and factors influencing suitability of individuals to perform SIMC, all quantitative research designs will be considered for inclusion. Qualitative This component of the review will consider any interpretive studies that draw on the experiences of intermittent self-catheterisation by adults for each of the sub-topics. This will include, but not be limited to, designs such as phenomenology, grounded theory and ethnography. Studies excluded from this review include: Those involving children and adolescents, i.e. > 18 years of age, Catheterisation performed by a carer or health professional, Catheterisation of a surgically created stoma, Indwelling catheters, Comparison of catheter types, Strategies to specifically reduce infection. Types of participants The review will include adults who are 18 years or older, who undertake urethral self-catheterisation for management of their neurogenic bladder dysfunction. Types of interventions/phenomena of interest The interventions, programs and strategies of primary interest are those TRUNCATED AT 350 WORDS

Does the type of bladder augmentation influence the resolution of pre‐existing vesicoureteral reflux? Urodynamic studies

The type of bladder augmentation on pre-existing vesicoureteral reflux (VUR) was assessed. The effects of urodynamic changes on the resolution of VUR following augmentation cystoplasty performed with various gastrointestinal segments were examined. It was queried whether elimination of high-pressure bladder is sufficient to resolve pre-existing reflux. A retrospective record review of patients who underwent bladder augmentation between 1987 and 2004. Patients were divided into two groups. Group I included patients who had a simultaneous augmentation and ureteral reimplantation. Group II included patients with reflux in whom only a bladder augmentation was performed. Pre-and post-augmentation urodynamic results were compared in both groups. The outcome of VUR and the role of various gastrointestinal (GI) segments on the resolution of VUR were studied. Sixty-three patients underwent bladder augmentation during the study period. Twenty-six of them had VUR before augmentation. There were 10 patients in Group I and 16 patients in Group II. In Group I, VUR ceased in all patients, while in group II, VUR resolved in 14 patients and persisted in two patients. Small and large bowel segments used for augmentation had no effect on the resolution of VUR but the results of gastrocystoplasties were less favorable. Urodynamically there was no significant difference between the various augmentation cystoplasties. Bladder augmentation alone without simultaneous antireflux repair is usually sufficient for the resolution of pre-existing reflux. The various GI segments used for augmentation have no effect on urodynamic results and the resolution of VUR.

MP-15.15 (Podium): Kidney transplantation before or after augmentation cystoplasty in children with high-pressure neurogenic bladder

MP-15.15 (Podium): Kidney transplantation before or after augmentation cystoplasty in children with high-pressure neurogenic bladder

Renal Cortical Deterioration in Children With Spinal Dysraphism: Analysis of Risk Factors

Background/Objective: Because hydronephrosis and reflux are reversible, we believe cortical loss represents true renal deterioration in children with spinal dysraphism. Our goal was to better define risk factors for cortical loss.Methods: After institutional review board approval, we reviewed the medical records of 272 children with spinal dysraphism. The following factors were evaluated: age, sex, renal and bladder imaging, urodynamic parameters, medications, catheterization program, continence, infections, and surgical history. Renal cortical loss was defined by scarring or a differential function greater than 15% using a nuclear scan. Univariate and multivariate logistic regression models were fitted to test the associations of specific variables with cortical loss.Results: Renal cortical loss was found in 41% of children with high-grade reflux vs 2% of children without reflux. Univariate analysis showed only high-grade reflux and female sex to be independent risk factors. Controlling for age and sex, reflux and initiation of catheterization after 1 year of age are significant risk factors. High bladder pressure and hydronephrosis in the absence of reflux were not associated with cortical loss. Multivariate analysis showed that girls with reflux have a 55-fold increased risk of cortical loss.Conclusion: By limiting the definition of renal deterioration to cortical loss, we identified relevant risk factors: reflux, female sex, and delayed initiation of clean intermittent catheterization. We have also discounted other suspected risk factors: hydronephrosis and elevated bladder pressure. Rather than continuing our focus on hydronephrosis and urodynamics, we believe more research and management debate should be afforded to females with reflux.

Role of Barrington's nucleus in micturition

Barrington's nucleus is a central component of the micturition circuit. This nucleus projects axons to the sacral parasympathetic nucleus, where preganglionic neurons innervating the urinary bladder are located. To clarify the functional role of this nucleus, the firing properties of Barrington's neurons that project axons to the spinal cord were examined. Based on these studies, a model begins to emerge that places Barrington's nucleus in the micturition pathway that is involved in increasing bladder pressure rapidly and strongly, while also maintaining high bladder pressure. In addition, Barrington's neurons are suggested to have another role, that is, increasing the probability of micturition contraction by activating a spinal excitatory pathway or disinhibiting a spinal inhibitory mechanism. In contrast to the excitatory role of Barrington's nucleus, this nucleus does not seem to trigger bladder relaxation.

Is Bladder Cycling Useful in the Urodynamic Evaluation previous to Renal Transplantation?

Objectives: To evaluate the usefulness of bladder cycling (BC) in differentiating between urodynamic abnormalities due to reversible bladder dysfunction and those due to preexisting lower urinary tract (LUT) abnormalities, and to determine if BC increases the diagnostic yield of urodynamic investigations (UIs) in these patients. Methods: Eleven patients with oligoanuria (<300 ml/day) were evaluated with complete UIs. All cases showed low compliance (mean 6 ml/cm H₂O) and low cystometric capacity (mean 146 ml) and were placed in a BC program. The indications for UIs were LUT symptoms in 2 patients, LUT abnormalities (myelodysplasia or urethral valves) in 3 patients, or the appearance of an extremely small bladder on cystogram (6 patients). BC was performed through a hypogastric catheter in an outpatient setting. UIs were repeated afterwards. Results: After BC, 5 patients (45%) continued to have low compliance (<8 ml/cm H₂O) and 4 patients (36%) had normal UIs. In 2 cases (18%), a previously unrecognized obstruction was diagnosed. No patient with LUT symptoms or abnormalities had a normal UI after BC. Conversely, 4 of 6 patients in whom BC was indicated due to a small bladder on cystogram had normal UIs after BC. Conclusions: BC is useful in explaining whether high bladder pressure is due to dysfunction or to preexisting disorders, and thus indicating the proper surgery for correction. Suprapubic BC significantly increases bladder capacity thus increasing the diagnostic yield of the UI.

Intractable high-pressure bladder in female infants with spina bifida: Clinical characteristics and use of vesicostomy

Objectives To characterize the clinical characteristics of a group of children with neurogenic bladder, high leak point pressures (LPPs), bladder wall changes, and hydronephrosis in whom medical management failed, who then underwent vesicostomy. Medical management can, rarely, fail in children with neurogenic bladder, high LPPs, bladder wall changes, and hydronephrosis. When it does, surgical intervention is necessary. Methods Between 1988 and 2001, 8 girls with spina bifida (4 with thoracic and 4 with lumbosacral) underwent vesicostomy after medical management. All had undergone neonatal back closure and five had ventriculoperitoneal shunts. The mean follow-up after vesicostomy was 6 years. Results High-grade reflux was present at birth in 3 patients and developed later in 3 patients at 1 year. Two had undergone ureteral reimplantation before vesicostomy. Four girls had trabeculation at birth and it developed in three at 1 year and one at 3 years. Hydronephrosis was present at birth in 2 patients and developed later in 6. High LPPs were noted at younger than 10 months of age in 6 patients. Oral oxybutynin was begun in 7 patients before 1 year of age and 5 were later given intravesical oxybutynin. Six patients began clean intermittent catheterization in infancy. The indications for vesicostomy were persistently elevated LPPs and hydronephrosis. Six had recurrent urinary tract infections. The mean age at vesicostomy was 3 years. Hydronephrosis resolved in 7 patients, and only 1 had additional febrile urinary tract infections. Two underwent reversal along with bladder augmentation and were continent at last follow-up. Conclusions A small subset of girls with spina bifida are unresponsive to early and intensive medical therapy. Most have high LPPs and bladder wall and upper tract changes early in infancy. Vesicostomy reverses the clinical course. At an appropriate age, these children can undergo reconstruction with a high likelihood of continence.

Feed-forward and feedback regulation of bladder contractility by Barrington's nucleus in cats.

The purpose of the present study was to clarify how Barrington's nucleus regulates bladder contractility. Single neurones that discharge at higher rates during micturition contraction were recorded from Barrington's nucleus. Spinal-projecting neurones were identified by antidromic stimulation of the spinal cord. Seventy-six spinal-projecting neurones were classified into four types based on the firing patterns displayed during the relaxation phase of the micturition contraction-relaxation rhythm: (1) ramp-tonic neurones displayed a ramp increase in firing throughout the relaxation phase, (2) ramp-silent neurones were silent initially during the relaxation phase and displayed a ramp increase later, (3) flat-tonic neurones fired constantly, and (4) flat-silent neurones displayed little firing, being virtually silent throughout relaxation. During the relaxation phase, discharge volleys from Barrington's nucleus to sacral neurones were estimated to increase exponentially as micturition contraction approached. Twenty-two neurones increased firing even further within 3 s of micturition contraction, suggesting that they are involved in the final stages of initiation of micturition contraction. During micturition contraction, 18 neurones (of which 14 belonged to the ramp-silent class) displayed maximal firing rates before maximal bladder pressures were reached; firing gradually decreased during micturition contraction. Thirty-nine neurones (of which 25 belonged to the ramp-tonic class) displayed constant firing during micturition contraction. This suggests that ramp-silent neurones might be involved in increasing bladder pressure rapidly and strongly via feed-forward regulation, while ramp-tonic neurones might be involved in maintaining high bladder pressure via positive feedback from the bladder afferents. Sixty neurones continued to fire for 1-8 s after the onset of bladder relaxation, suggesting that Barrington's nucleus does not trigger bladder relaxation.

Dynamic graciloplasty for urinary incontinence: the potential for sequential closed-loop stimulation

Muscle tissue transplantation applied to regain or dynamically assist contractile functions is known as ‘dynamic myoplasty’. Success rates of clinical applications are unpredictable, because of lack of endurance, ischemic lesions, abundant scar formation and inadequate performance of tasks due to lack of refined control. Electrical stimulation is used to control dynamic myoplasties and should be improved to reduce some of these drawbacks. Sequential segmental neuromuscular stimulation improves the endurance and closed-loop control offers refinement in rate of contraction of the muscle, while function-controlling stimulator algorithms present the possibility of performing more complex tasks. An acute feasibility study was performed in anaesthetised dogs combining these techniques. Electrically stimulated gracilis-based neo-sphincters were compared to native sphincters with regard to their ability to maintain continence. Measurements were made during fast bladder pressure changes, static high bladder pressure and slow filling of the bladder, mimicking among others posture changes, lifting heavy objects and diuresis. In general, neo-sphincter and native sphincter performance showed no significant difference during these measurements. However, during high bladder pressures reaching 40 cm H 2O the neo-sphincters maintained positive pressure gradients, whereas most native sphincters relaxed. During slow filling of the bladder the neo-sphincters maintained a controlled positive pressure gradient for a prolonged time without any form of training. Furthermore, the accuracy of these maintained pressure gradients proved to be within the limits set up by the native sphincters. Refinements using more complicated self-learning function-controlling algorithms proved to be effective also and are briefly discussed. In conclusion, a combination of sequential stimulation, closed-loop control and function-controlling algorithms proved feasible in this dynamic graciloplasty-model. Neo-sphincters were created, which would probably provide an acceptable performance, when the stimulation system could be implanted and further tested. Sizing this technique down to implantable proportions seems to be justified and will enable exploration of the possible benefits.

Adrenomedullin and nitric oxide in children with detrusor instability.

Detrusor instability (DI) and detrusor-external sphincter dyssynergia lead to poor bladder emptying and high bladder pressure. Recent results indicate that nitric oxide (NO) is an important transmitter or messenger molecule in autonomic neurotransmission. Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide, originally purified from human pheochromocytoma. Since NO and AM have vasodilatory effects on smooth muscles, we considered them to be of interest in children with DI. We determined the tissue levels of NO and AM in 14 children with DI, and compared these with 6 children with normal bladder activity. Bladder biopsy total nitrite levels (nmol/g tissue) were decreased in children with DI (10.69+/-0.91 vs. 12.83+/-0.98, P<0.01). However, AM levels (pmol/g tissue) were increased in the same patients (48.84+/-3.52 vs. 28.79+/-1.53, P<0.001). According to our results, decreased NO production probably has a role in the pathophysiology of DI, although increased AM appears to be compensatory. NO may provide a therapeutic target in clinical situations related to DI. However, the functional significance of AM and NO in bladder smooth muscle remains to be determined by further detailed studies.