Small Functional Bladder Capacity Research Articles

Sex and Gender Differences in the Pharmacology of the Overactive Urinary Bladder.

Dysfunction of the lower urinary tract in general and the overactive bladder syndrome (OAB) in particular are prevalent and have major impact on the quality of life of the afflicted patients and their partners. We concisely review sex and gender differences in patients and animal models in physiological bladder function, its alterations in disease (mostly OAB), and its responses to treatment. Women appear to have a smaller functional bladder capacity and, therefore, must void more often than men. On the other hand, men have a greater bladder outlet resistance, which is partly attributed to a longer urethra and partly to the presence of the prostate. Sex and gender differences in bladder contractility appear small and were not found consistently. The ability of bladder smooth muscle to relax may be somewhat smaller in females. However, females are heavily underrepresented in experimental studies on bladder function. Stress urinary incontinence is found predominantly in women (particularly those after childbirth). OAB is similarly prevalent in men and women.Females seek treatment much more often and are overrepresented in clinical trials. Treatment responses in OAB patients are similar in both genders for oral medications, but improvements upon injections of onabotulinum toxin type A appear smaller in men. We conclude that there is no evidence for major sex and gender differences in bladder dysfunction as related to OAB and its treatment responses, but female animals are heavily underrepresented in experimental studies.

Features of Various Bladder Lesions and Their Impact on Clinical Symptoms and Recurrence in Interstitial Cystitis

We aimed to investigate the impact of various bladder lesions on the clinical symptoms and recurrence of interstitial cystitis (IC). Patients with IC who underwent transurethral resection and cauterization for Hunner lesions (HLs) were enrolled. Features of HLs-noninflamed, inflamed, and gradually inflamed-and associated cystoscopic findings, including waterfall bleeding (none, focal or extensive), submucosal hemorrhage, and mucosal streak, were analyzed to investigate their association with preoperative symptoms and recurrence. We included 272 procedures from 141 patients (male:female ratio 37:104) with a mean±SD age of 61.4±10.5 years. Recurrence was observed in 160 procedures after a mean of 15.6 months (range 0.7-91.7); repeat transurethral resection and cauterization was performed in 131 cases. The number of HLs observed at each procedure was variable, and sufficient bladder filling revealed hidden lesions in 10.7% of cases. Waterfall bleeding was frequently accompanied with inflamed/gradually inflamed HLs. Inflammatory HLs were associated with smaller functional bladder capacity and preoperative urgency (p=0.007). Extensive waterfall bleeding was associated with smaller functional bladder capacity (p=0.006). On multivariate analysis, initially inflamed HLs (HR: 1.675, 95% CI: 1.022-2.746, p=0.041) and gradual inflammatory changes in HLs (HR: 1.893, 95% CI: 1.050-3.410, p=0.034) were found to be risk factors for recurrence. Sufficient bladder filling revealed hidden HLs. The features of HLs were not associated with subjective symptoms; inflamed changes were a predictive factor for IC recurrence, and associated with frequent urgency episodes and smaller bladder capacity.

Associations between nighttime and daytime maximum voided volumes: Relevance for nocturia?

The relationship between maximum voided volumes (MVV) during the night and day is poorly understood. Such measurements are important because they are often used to indicate functional bladder capacity (FBC), a relevant parameter for nocturia. This study examined the association of such nighttime and daytime measurements in men with nocturia. We retrospectively analyzed 356 24-hour voiding diaries showing ≥2 nocturnal voids from 220 men at an outpatient urology clinic. We defined small FBC as MVV ≤ 200 mL. A total of 131 entries demonstrated a nocturnal MVV ≤ 200 mL, of which a majority (98 [74.8%]) also showed a 24-hour MVV ≤ 200 mL (ie, global small FBC), and 33 (25.2%) exceeded the 200 mL threshold during the day (ie, nocturnal-specific small FBC). Correspondingly, among voiding diaries without global small FBC (n = 258), most (225/258 [87.2%]) showed a nocturnal MVV > 200 mL. Data were similar when analyzing only the first complete voiding diary per case, when limiting analyses to those without benign prostatic obstruction, and when limiting analyses to cases with nocturnal polyuria. Nocturia may be attributable to nocturnal-specific small FBC or global small FBC. Although the etiology of nocturnal-specific small FBC remains unclear, it was present in a significant minority of patients with small FBC, thus necessitating more directed research. Conversely, diminished nocturnal MVV was nevertheless relatively uncommon in the absence of global small FBC, such that nocturnal-only voiding diaries may provide a rational alternative for follow-up evaluation in patients with nocturia due to global small bladder capacity.

Cardiovascular risk independently predicts small functional bladder storage capacity.

We aimed to determine the potential relationship between atherosclerotic cardiovascular disease (ASCVD) score, which equates to 10-year risk of atherosclerotic cardiovascular events, and functional bladder capacity (FBC) among men in the outpatient urology setting. We secondarily analyzed voiding diaries from men aged 40 to 79years with nocturia. Patients with a history of cardiovascular disease or who had nocturnal polyuria were excluded. Patients were stratified by whether they met the high-risk ASCVD threshold (≥ 20%) following current cardiology consensus guidelines and assessed for the presence of small FBC (24-h maximum voided volume ≤ 200ml). Logistic regression analyses were employed to explore associations between small FBC and ASCVD. Eighty-four men (median ASCVD score 18.4 [IQR 12.8-26.9] %, age 66 [61-71] years, body mass index [BMI] 29.4 [26.4-32.7] kg/m2) were included, of whom 36 (42.9%) were high-risk and 48 (57.1%) fell below the high-risk threshold. High-risk patients were more likely to have small FBC (23 [63.9%] vs. 14 [29.2%], p = 0.002). ASCVD risk predicted small FBC on univariate analysis (p = 0.002). No such effect was observed with age (p = 0.116), BMI (p = 0.523), or benign prostatic obstruction (p = 0.180). The association between ASCVD risk and small FBC persisted on multivariate analysis after controlling for BMI and benign prostatic obstruction (p = 0.002). No significant predictors of small FBC were observed when age, a major determinant of ASCVD risk and independent correlate of small FBC, was substituted for ASCVD score (p = 0.108). Small FBC is related to a higher predicted cardiovascular event rate in men with nocturia.

Clam augmentation enterocystoplasty as management of urge urinary incontinence and reduced bladder capacity

Objectives: Third line treatment of urge urinary incontinence (UUI) and/or reduced bladder capacity is bladder augmentation. The aim of this study was to investigate whether clam enterocystoplasty (CECP) was an efficient treatment for patients who were refractory to conservative treatments of UUI and small functional bladder capacity and secondly if there was a difference in outcome in patients with neurogenic and non-neurogenic bladders.Methods: We evaluated 118 patients retrospectively treated in the period 2006–2018 at a single university hospital. Data were collected retrospectively. Patient groups were compared with Wilcoxon signed-rank test and Fisher’s exact test.Results: Overall, 76% became continent with 92% using clean intermittent self-catherization (CISC) of patients with neurogenic bladder, 82% became continent and 100% were using CISC, whereas of patients with non-neurogenic bladder 64% became continence and 77% were using CISC. The median overall improvement of capacity was 296.5 mL (IQR: 142–440), 310 mL (186–467) in the neurogenic group and 214 mL (IQR: 126.8–361.5) in non-neurogenic (p = 0.01).Conclusion: CECP is an efficient treatment in UUI and reduced bladder capacity. Difference in outcome was seen with neurogenic patients having a bigger functional capacity and a higher rate of continence compared to the non-neurogenic.

Commentary on Ronen T, Hamama L and Rosenbaum M (2012) Enuresis--children's predictions of their treatment's progress and outcomes. Journal of Clinical Nursing 22, 222-232.

Ronen et al. (2012) discuss children’s ability in predicting their enuresis treatment’s progress and outcomes. There are numerous studies on childhood enuresis; however, few explore the predictability of determining outcomes. The study focuses on children being active participants in their treatment and acknowledges Bandura’s (1977) concept of self-efficacy in recognising that individuals are capable of achieving the behaviours they are asked to perform. This is linked with motivation and positive reinforcement and is used in the management of enuresis and other behaviour change interventions (Thiedke 2003). Ronen et al. (2012) diagnose enuresis using the Manual of Mental Disorders (DSM-IV; American Psychiatric Association 1994); however, this gives little information about the cause of enuresis. The three-system approach by Butler and Holland (2000) is often used in practice to diagnose the cause of enuresis and appropriate treatment. Butler and Holland (2000) suggest that nocturnal enuresis can be due to a lack of antidiuretic hormone (vasopressin), small functional bladder capacity or lack of arousal. It is not clear within the study whether these data have been collected and this may be a reason why some of the participants did not improve. Furthermore, group therapy may not have been the most appropriate form of treatment. Ronen et al. (2012) sampled 101 children aged 8–14 randomly assigned to three groups. One predicted baseline outcomes, one predicted weekly outcomes and one did not predict at all. The children had training completing a practice prediction curve, by predicting how many hours of television they will watch over the next few weeks; however, this seems a rather limited measure – there appears to be no evidence to support accuracy in terms of prediction, given the variances in age and cognitive ability of 8to 14-year-olds. Indeed, the authors of the study have identified that conclusions cannot be easily drawn as most children progressed, regardless of which group they were in. Similarly, the questions asked prior to treatment may be beyond the cognitive ability of some of the sample, the questions are similar with only subtle differences, and there is no account of the children’s responses that would support or refute this. Given the age range of the sample, it is worth noting that levels of self-efficacy can be difficult to determine as this is linked to cognitive ability; however, positive reinforcement and belief of success can be a strong motivator. This effect may be more evident in the weekly predictive group as they are being prompted to reinforce their own self-belief which may be the causative factor. The intervention lasted 16 weeks, and it is unclear how many children would have stopped bed-wetting naturally (Thiedke 2003). Maintenance of the behaviour is also worthy of further study as 35 participants had received previous treatment. Ronen et al. (2012) provide useful information about self-efficacy and motivation in treating enuresis; the ability of children to predict treatment outcomes is less convincing, and further study on the development of reliable tools is warranted.

Down Regulation of Vascular Endothelial Growth Factor Is Associated With Decreased Inflammation After Intravesical OnabotulinumtoxinA Injections Combined With Hydrodistention for Patients With Interstitial Cystitis—Clinical Results and Immunohistochemistry Analysis

To measure the expression of vascular endothelial growth factor (VEGF) in bladder tissue and improvement of clinical symptoms and inflammatory biomarkers after repeated onabotulinumtoxinA injections in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Twenty-one patients with IC/BPS received 4 sets of intravesical 100-U onabotulinumtoxinA injections combined with hydrodistention. Assessments at baseline and 6 months after each treatment included O'Leary-Sant Symptom Score, bladder pain visual analog scale, functional bladder capacity (FBC), grade of glomerulations under cystoscopic hydrodistention, and urodynamic parameters. The bladder specimens at baseline and at the fourth treatment were investigated by western blotting for the expression of VEGF, Bcl-2-associated X protein (Bax), and phospho-p38 (p-p38), and immunohistochemistry staining for apoptotic and mast cell activity. Six women with genuine stress urinary incontinence served as controls for comparison. The measured immunohistochemical parameters were significantly higher in patients with IC/BPS than the controls. Statistically significant decrease in the expression of VEGF was noted in patients treated with repeated onabotulinumtoxinA injections compared with baseline (0.83 ± 0.28 vs 1.00; P = .016). The apoptotic cell count (0.86 ± 1.00 vs 1.76 ± 1.69; P = .026) and mast cell activity (1.81 ± 2.29 vs 5.82 ± 4.97; P = .009) were also reduced. Significant increases in FBC and global response assessment score were also observed after onabotulinumtoxinA treatment; however, except for mast cell activity, VEGF expression and apoptotic cell count were still significantly higher than the controls. Increased VEGF was associated with bladder inflammation and smaller FBC in patients with IC/BPS and decreased after repeated onabotulinumtoxinA injections and hydrodistention, suggesting VEGF plays an important role in the pathogenesis of IC/BPS.

Intravesical Botulinum Toxin A Injections Do Not Benefit Patients with Ulcer Type Interstitial Cystitis

Background: Ulcer type and non-ulcer type interstitial cystitis/bladder pain syndromes (IC/BPS) are considered different disease entities. Thus, intravesical botulinum toxin A (BoNT-A) treatment outcomes could differ for each entity. Objectives: To evaluate and compare the treatment outcomes of BoNT-A injections for treatment of each IC/BPS type. Study Design: Prospective interventional study. Setting: Tertiary medical center affiliated with Buddhist Tzu Chi General Hospital and Tzu Chi University, Taiwan. Methods: Forty-four consecutive patients with IC/BPS for whom conventional treatments failed were prospectively enrolled in this study. Patients were classified as having ulcer (n = 10) or non-ulcer (n = 30) IC/BPS based on their previous cystoscopic findings. Intervention: All patients received 4 sets of intravesical BoNT-A injections (100 U in 40 suburothelial injections) every 6 months. The primary end-point was the global response assessment (GRA) 6 months after the fourth set of BoNT-A injections. Secondary end-points included the O’Leary-Sant score (OSS) including symptom indexes (ICSI) and problem indexes (ICPI), visual analog scale (VAS) pain score, voiding diary, and urodynamics variables. Results: After 4 sets of BoNT-A injections, 15 patients with non-ulcer IC/BPS had GRA scores ≥ 2, while the other 15 had GRA scores < 2. All 10 patients with ulcer IC/BPS had GRA scores < 2 at the study end-point (treatment failure). At baseline, patients with ulcer IC/BPS had significantly higher daytime frequency, nocturia, smaller functional bladder capacity, smaller voided volume, greater VAS, smaller maximal bladder capacity, and greater glomerulation grade than did patients with non-ulcer IC/BPS. After 4 sets of BoNT-A injections, patients with non-ulcer IC/BPS and GRA scores ≥ 2 or < 2 all had significantly decreased ICSI, ICPI, OSS, VAS pain scores, frequency episodes, and increased functional bladder capacity. However, patients with ulcer IC/BPS showed no significant change in any clinical or urodynamic variable. After failure of repeated BoNT-A injections, all 10 patients with ulcer IC/ BPS underwent transurethral electrocauterization of their ulcers, which resulted in immediate pain relief. Limitations: Lack of a control arm in this study. Conclusion: Repeated intravesical BoNT-A injections provided effective treatment outcomes at the end-point in half of the patients with non-ulcer IC/BPS, but did not benefit any patient with ulcer type IC/BPS. Ulcer type IC/BPS should be treated as a different disease than non-ulcer IC/BPS. Institutional Review: This study was approved by the Institutional Review Board of the Tzu-chi General Hospital (TCGH 100-06). Key words: Botulinum toxin, interstitial cystitis, bladder pain syndrome, intravesical treatment, Hunner’s ulcer

Is there a difference between women with or without detrusor overactivity complaining of symptoms of overactive bladder?

What's known on the subject? and what does the study add?: Overactive bladder syndrome (OAB) is a highly prevalent medical condition, which is linked to the urodynamic observation of detrusor overactivity (DO). Urodynamics detect DO in about half of female patients with OAB. Our study detects significant differences between female patients with OAB with and without DO. DO could be considered as a more severe form in the wide OAB spectrum and the two terms should not be used interchangeably. The detected differences should be taken into account in the design of studies for the assessment of new selective or combination treatments of OAB and in the provision of treatment in everyday clinical practice. To determine if there are differences between female patients complaining of symptoms of overactive bladder (OAB) with and without detrusor overactivity (DO). The present study was a cross-sectional study of consecutive women attending a one-stop urodynamic assessment clinic with OAB symptoms. The King's Health Questionnaire (KHQ) and a 3-day bladder diary incorporating the Patient's Perception of Intensity of Urgency Scale (PPIUS) were used to assess symptoms and health-related quality of life (HRQoL). The participants underwent multichannel urodynamics (UDS) according to the International Continence Society (ICS) recommendations. Patients whose symptom of urgency was not reproduced during the laboratory test underwent a 4-h ambulatory UDS test. Of the 556 patients who were included in the study, 43% were diagnosed with DO by either laboratory (227/556) or ambulatory UDS (11/39). There was no difference between the groups in age, body mass index (BMI), menopausal status or the presence of prolapse. Patients with DO had a smaller functional bladder capacity (P < 0.001), higher urgency episode frequency (P < 0.001) and larger maximum and mean urge ratings (P < 0.001). No significant differences were found in daytime or nocturnal micturitions between the groups. The presence of DO had a more negative impact on the quality of life, with a statistically significant difference between the groups in six of the domains of the KHQ. The present study detects objective and subjective differences between female patients with OAB with and without DO. Women with DO experience more significant impairment to their quality of life and have a greater degree of bladder dysfunction.

Role of Posterior Tibial Nerve Stimulation in the Treatment of Refractory Monosymptomatic Nocturnal Enuresis: A Pilot Study

We evaluated the early clinical and urodynamic results of posterior tibial nerve stimulation in patients with refractory monosymptomatic nocturnal enuresis. We randomly assigned 28 patients with refractory monosymptomatic nocturnal enuresis to 2 equal groups. Group 1 received a weekly session of posterior tibial nerve stimulation for 12 weeks and group 2 was the placebo group. Evaluation was performed in each group at baseline and after posterior tibial nerve stimulation to compare clinical and urodynamic findings. Another clinical assessment was done 3 months after the first followup. The 2 groups were comparable in baseline clinical and urodynamic data. Overall, 13 patients (46.4%) had detrusor overactivity and 14 (50%) had decreased bladder capacity. After treatment 11 group 1 patients (78.6%) had a partial or full response to posterior tibial nerve stimulation but only 2 (14.3%) in group 2 had a partial response (p = 0.002). Also, the average number of wet nights in group 1 was significantly lower than at baseline (p = 0.002). All urodynamic parameters significantly improved in group 1. In contrast, the number of wet nights and urodynamic parameters did not change significantly in group 2. At 3-month followup the number of patients with a partial or full response in group 1 had decreased from 11 (78.6%) to 6 (42.9%). No change was evident in group 2. Posterior tibial nerve stimulation can be a viable treatment option in some patients with refractory monosymptomatic nocturnal enuresis. However, deterioration in some responders with time suggests the need for maintenance protocols.

Diagnostic Value of Functional Bladder Capacity, Urine Osmolality, and Daytime Storage Symptoms for Severity of Nocturnal Enuresis

PurposeTo investigate the correlation between functional bladder capacity, first morning urine osmolality, daytime voiding symptoms, and severity of nocturnal enuresis.Materials and MethodsWe assessed a total of 101 children with nocturnal enuresis (mean age, 7.7±2.3 years). Patients were divided into three groups according to the severity of enuresis: (1) one to six episodes per week (46 cases, 45.5%), (2) one episode every day (29 cases, 28.7%), and (3) multiple episodes every day (26 cases, 25.8%). Baseline parameters were obtained from frequency volume charts for 2 days, first morning urine osmolality, and a questionnaire for the presence of frequency, urgency, and daytime incontinence.ResultsThe severity of enuresis increased with younger age (p=0.037) and reduced functional bladder capacity (p=0.007) and daytime symptoms of frequency and daytime incontinence (p=0.012, p=0.036). No statistical difference in urine osmolality or urgency was found among the three groups. Both reduced functional bladder capacity and low urine osmolality increased according to the severity of enuresis (p=0.012).ConclusionsIn children with nocturnal enuresis, severity was increased by younger age, reduced functional bladder capacity, and the presence of daytime voiding symptoms of frequency and daytime incontinence. The incidence of small functional bladder capacity was increased in children with everyday wetting, and the incidences of both small functional bladder capacity and low urine osmolality were increased in children with everyday multiple wetting.

Bladder Reduction Surgery Accelerates the Appearance of Spontaneous Voiding in Neonatal Rats

Patients with nocturnal enuresis may have small functional bladder capacity or altered bladder fullness sensation. We determined whether reducing bladder volume would affect the central inhibition of voiding that is normally present between birth and 2 weeks of life in neonatal rats. One and 3-week-old Sprague-Dawley rats underwent 50% bladder volume reduction by suture closure of the bladder dome. T8-T10 spinal cord injury was done in select animals. Latency of the perigenital-bladder reflex, spontaneous voiding onset and body weight were measured. Cystometry using urethane anesthesia, and measurements of in vitro spontaneous and KCl evoked contractions were done. Bladder reduction surgery led to the immediate appearance of spontaneous voiding in 1-week-old rats. Cystometry at 2 weeks showed voiding contractions in rats with bladder reduction, which was abolished by acute T8-T10 spinalization. Voiding contractions were not seen in animals with sham surgery or concurrent T8-T10 spinalization and bladder reduction. The perigenital-bladder reflex, somatic growth, spontaneous bladder contractions and bladder contractility were not affected by bladder reduction. Bladder capacity at 9 weeks was significantly larger in animals that underwent bladder reduction at 1 week than in sham treated animals (540 vs 256 microl, p = 0.04) but not in animals that underwent bladder reduction at 3 weeks. Bladder reduction removes the central inhibition of spontaneous voiding in neonatal rats. This suggests that decreased neonatal bladder capacity may alter how the brain regulates the bladder.

Smooth Muscle Remodeling following surgical reduction of Bladder Capacity: An Animal Model

PURPOSE Studies have shown that a small functional bladder capacity and detrusor overactivity may play an important role in the pathophysiology of nocturnal enuresis. We propose to use an animal model to evaluate bladder functional changes as well as the expression level of smooth muscle myosin in detrusor in response to surgically induced bladder disorders. MATERIAL AND METHODS Adult male Wistar rats underwent either surgical reduction of bladder volume or sham operation ((RBV, n = 6, and SHAM, n = 6, respectively. Animals were kept in metabolic cages at 5th week postoperatively and urine output and voiding frequency were continuously monitored. Animals were then anesthetized and the bladder harvested. For measuring the area of detrusor smooth muscle (DSM) cross-sections of bladder obtained through the mid-portion and stained using Masson's Trichrom stain. Semithin sections of bladder were prepared and immunostained with anti-smooth muscle myosin antibody. RESULTS Our RESULTS demonstrated an increase in smooth muscle bundle size in rats with RBV compared to that of SHAM. Metabolic cage monitoring revealed decreased void volume and increased voiding frequency in RBV group compared to SHAM (Mean: 0.85 ± 0.186 vs 1.75 ± 0.299 ml, 2.53 ± 0.30 vs 0.53 ± 0.05/hr respectively,p < 0.005). Immunostaining with anti-Myosin antibody revealed DSM samples from SHAM and RBV bladders reacted with anti-Myosin antibody. Furthermore, the intensity of the staining is higher for the DSM sample from SHAM compared to that of RBV. CONCLUSIONS Our RESULTS demonstrate bladder dysfunction elicited by surgical reduction of bladder capacity can induce detrusor smooth muscle proliferation in rats. Alteration in expression of myosin in DSM from RBV group implicates the alteration of myosin isoform composition in response to bladder disorders. Our current research is focusing the expression levels of myosin heavy chain isoforms SM - A and SM-B at protein level in detrusor under normal and pathological conditions.

Reduction of bladder capacity alters expression of cholecystokinin B (Cck-B) receptor of the brainstem in rats

Purpose Nocturnal enuresis patients often have a smaller functional bladder capacity. Meanwhile, enuretic children with nocturnal bladder instability have frequent cortical arousal episodes and impaired startle responses. The mechanisms underlying these disorders have not been elucidated. CCK-B receptor is a novel factor which is involved in the modulation of anxiety, pain perception, and sleep-wake rhythm. We therefore studied the CCK-B receptor expression in the brainstem in response to the reduction of bladder capacity in rats. Material and methods Male adult Wistar rats underwent either surgical reduction of bladder capacity (RBC, n = 6) or SHAM operation (n = 6). The voided volume and voiding frequency were observed. After 8 weeks, the brainstem was sampled. Total RNA was digested and reverse transcribed. cDNA was analyzed by using DNA array technique. The values with relative differences from both groups in gene expression of greater than 3 times were considered as significant. Results Postoperatively, RBC rats voided with smaller volumes and higher frequency. Water intake and body weight in RBC rats did not change significantly. In RBC rats, a significant up-regulation of the CCK-B receptor (7.281 times higher vs. SHAM group) in brainstem was observed, suggesting an alteration related to the sleep-wake rhythm may be involved in the pathophysiological changes following the reduction of bladder capacity. Conclusions An alteration of the gene expression of the CCK-B receptor in the brainstem occurred in response to the surgical reduction of bladder capacity in rats, which probably indicate that the sleep related changes are involved in the pathophysiology of the bladder dysfunction.

Characteristics of a Tertiary Center Enuresis Population, With Special Emphasis on the Relation Among Nocturnal Diuresis, Functional Bladder Capacity and Desmopressin Response

We evaluated pretreatment values of circadian rhythm of urine production and urine osmolality in children with different subtypes of monosymptomatic nocturnal enuresis, and investigated their predictive value for desmopressin response. We assessed 125 consecutive patients with monosymptomatic nocturnal enuresis, nocturnal polyuria and normal functional bladder capacity who were treated with desmopressin for a median of 17 months (range 3 to 100). Patients were characterized according to the desmopressin response as full responders or nonfull responders. Baseline parameters were obtained from a 2-week home recording diary. Results were compared with 125 consecutive children with monosymptomatic nocturnal enuresis and reduced functional bladder capacity. No differences in pretreatment values of functional bladder capacity, circadian rhythm of urine production or urine osmolality were found between desmopressin full responders and nonfull responders. Patients with nocturnal polyuria had a significantly higher 24-hour diuresis volume compared to children with reduced functional bladder capacity. Some children with reduced functional bladder capacity also had nocturnal polyuria. Our findings show that the characteristics of nocturnal polyuria in patients with monosymptomatic nocturnal enuresis and normal functional bladder capacity do not predict desmopressin response. The wide overlap among the different subgroups suggests that dividing patients with monosymptomatic nocturnal enuresis into those with reduced functional bladder capacity and those with desmopressin responsive nocturnal polyuria might be insufficient. Patients with nocturnal polyuria and normal functional bladder capacity have a significantly higher daytime and nighttime diuresis volume compared to children with reduced functional bladder capacity, suggesting a direct correlation between daytime fluid intake and nocturnal diuresis rate. Some children with reduced functional bladder capacity also have nocturnal polyuria.

The Role of Bladder Capacity in Antidiuretic and Anticholinergic Treatment for Nocturnal Enuresis

We evaluated combination treatment with desmopressin and oxybutynin in patients with enuresis who did not respond to desmopressin monotherapy. Furthermore, we compared 2 methods of estimating bladder capacity and evaluated the ability of these methods to predict the response to desmopressin and oxybutynin. A total of 60 children with a mean age +/- SD of 10.6 +/- 3.0 years who had monosymptomatic nocturnal enuresis completed the study. After a 2-week observation period maximal voided volume during free access to fluid intake was determined by a 2-day frequency-volume chart and maximal voided volume after water load was determined on a separate day. Patients then received 20 mug desmopressin intranasally at bedtime during 2 weeks. In nonresponders to desmopressin with less than a 50% decrease in wet nights 5 mg oxybutynin twice daily was added for another 2 weeks. Of the patients 41 (68%) showed more than 50% decrease in wet nights during the 2-week desmopressin treatment period (4.6 +/- 1.6 to 0.7 +/- 0.8, p <0.001). In desmopressin nonresponders combined treatment with desmopressin and oxybutynin resulted in a further decrease in wet nights (4.0 +/- 1.2 to 1.7 +/- 1.4, p <0.001). Maximal voided volume during free access to fluid intake was significantly higher in desmopressin responders than in nonresponders (244 +/- 111 vs 160 +/- 65 ml, p <0.001). In contrast, maximal voided volume after water load was not significantly different between desmopressin responders and nonresponders. The study indicates a role for oxybutynin in combination with desmopressin in children who are not responding to desmopressin monotherapy. Maximal voided volume during free access to fluid intake is a clinically useful predictor of the response to desmopressin but not to oxybutynin.

Bladder Reservoir Function in Children With Monosymptomatic Nocturnal Enuresis and Healthy Controls

We investigated bladder reservoir function in children with monosymptomatic nocturnal enuresis and in healthy controls. A total of 18 children with monosymptomatic nocturnal enuresis and 119 controls who were 7 to 13 years old were recruited. Children completed frequency volume charts and measurements of nocturnal urine production. Mean diuresis in the period preceding each voiding was calculated. Those with enuresis were grouped according to bladder capacity and hospitalized for 4 nights, including a baseline night and 3 with an oral water load. Enuresis volumes and post-void residual volume were estimated, allowing the calculation of bladder volume at the time of enuresis. Nine children with monosymptomatic nocturnal enuresis were characterized as having normal bladder capacity and 9 had decreased bladder capacity. We found large intra-individual variability in daytime voided volume in all 3 groups of participants. Children with enuresis and small bladder capacity generally voided with volumes close to maximal voided volume. A total of 93 enuresis episodes were recorded. Large intra-individual variability was seen in bladder volume at enuresis and it was lower than maximal voided volume in more than 50% of episodes. Variability in bladder volume at enuresis was greatest in the patient group with decreased bladder capacity. We found a significant correlation between diuresis and bladder capacity in all groups during the day and night. There is a great intra-individual diurnal variability in voided volume in children with enuresis and in healthy children. Enuresis seems to occur at bladder volumes that are smaller and larger than the maximal voided volume obtained from voiding charts.

FACTORS THAT DISTINGUISH CONTINENT FROM INCONTINENT OLDER ADULTS WITH DETRUSOR OVERACTIVITY

In older adults detrusor overactivity (DO) is almost as common in continent individuals as in those with urge incontinence (UUI). Thus, UUI likely reflects the contribution of additional factors. We postulated that of functionally independent individuals in whom transient causes were excluded those in whom DO was accompanied by UUI would be more likely to have smaller functional bladder capacity, less warning and less ability to avert urine loss in the face of DO. While blinded to continence status, we reviewed the records of all 52 cognitively intact and nonobstructed volunteers older than 65 years who had DO associated with urgency during urodynamic testing and had been asked to try to prevent leakage for 2 minutes. Of these individuals 31 were continent at home. In patients with UI mean functional bladder capacity +/- SD was smaller (313 +/- 153 vs 390 +/- 178 ml, p = 0.06) and warning was briefer (87 +/- 81 vs 120 +/- 116 ml), although the association with warning was less impressive (p = 0.14). The ability to forestall leakage for at least 2 minutes correlated strongly with being continent at home (p < 0.002). For continence detrusor suppression at the onset of DO was more important than sphincter contraction. Urge incontinence in older adults involves more than simply the presence of DO. Physical function, cognitive function and medications are already known to be important for continence. Our data suggest that functional bladder capacity and the ability to suppress involuntary contraction (and possibly warning) are also potentially important covariates. These factors may represent additional potential targets for behavioral and pharmacological therapy.

Home Uroflowmetry for the Evaluation of Boys with Urinary Incontinence

We recorded uroflowmetry at home in boys with urinary incontinence and correlated the results with videourodynamics. Thirty-nine boys (mean age 8.4 +/- 2.0 years) with urinary incontinence underwent home uroflowmetry for 1 weekend. Artifactual spikes in 1 or more uroflow curves were present in 16 home uroflowmetry recordings. One patient, in whom none of the uroflow curves was interpretable, was excluded from the study. Of the remaining 38 boys 18 had monosymptomatic nocturnal enuresis, and 20 had nocturnal enuresis and diurnal voiding symptoms. Percentage expected bladder capacity is defined as functional/expected bladder capacity x 100%. Normal and obstructive home uroflowmetry levels are defined as functional bladder capacity at least 50% expected bladder capacity associated with multiple bell-shaped and obstructive uroflow curves, respectively. Small functional bladder capacity is defined as capacity less than 50% expected bladder capacity, regardless of uroflow patterns. Videourodynamics and cystoscopy were performed in 17 patients. Normal home uroflowmetry was noted in 5 patients (13%), obstructive uropathy in 8 (21%) and small functional bladder capacity in 25 (66%). Urodynamically 3 boys with normal home uroflowmetry had normal voiding, and 6 with obstructive home uroflowmetry had bladder outlet obstruction (of whom 1 also had detrusor overactivity). In addition, of 8 boys with small functional bladder capacity 4 had detrusor overactivity, 3 had bladder outlet obstruction and 1 had both findings. Normal home uroflowmetry predicted normal voiding, and abnormal recordings implied abnormal voiding function in boys with incontinence. Bladder outlet obstruction and detrusor overactivity were frequently disclosed by obstructive home uroflowmetry and small functional bladder capacity.

Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion.

To assess urinary nitrite excretion, a stable end product of nitric oxide (NO), in patients with enuresis and in normal controls, and to evaluate the effects of indomethacin (a potent prostaglandin synthesis inhibitor) on urinary nitrite excretion, other urinary variables and bladder capacity. The study comprised 10 patients with primary enuresis and 10 normal comparable controls (age range 6-14 years). Nitrite was assayed in 'spot' morning urine samples in both the enuretics and normal controls. Enuretics were then given 50 mg indomethacin suppositories each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes and urinary nitrite were assayed before indomethacin treatment and after 15 days of treatment. The mean (sd) urinary nitrite excretion was 24.4 (19.6) micromol/L in normal children and 275.9 (111.2) micromol/L in enuretics (P<0.05). With indomethacin, the urinary nitrite concentration was significantly decreased to 141 (45.1) micromol/L (P<0.05) and associated with a significant reduction in bed-wetting episodes and voiding frequency. The functional bladder capacity was <70% of the predicted value for age in six of the patients; they had significant improvements on indomethacin, to values similar to those in patients with a nearly normal functional bladder capacity. Indomethacin decreased the 24-h urinary volume by 41%, the night volume by 40%, clearance of free water by 46% and increased the day : night urinary volume ratio by 55%. The absolute amounts of urinary calcium, magnesium, phosphorus, urea, creatinine, and glucose were lower on indomethacin, although not statistically significantly so. Indomethacin decreased the 24-h urinary and 'spot' morning osmolality and osmotic clearance. There were no significant changes in serum osmolality and electrolyte concentrations. Indomethacin also decreased the absolute amount of urinary sodium, chloride and potassium, fractional sodium and potassium excretion, and filtered sodium. Creatinine clearance was decreased by 20% (P>0.05) and normal 24-h urinary protein was significantly lower, by 47%, after indomethacin treatment (P<0.05). Urinary nitrite excretion increased significantly in patients with primary nocturnal enuresis; indomethacin markedly reduced bed-wetting episodes and decreased the frequency of voiding in enuretics with small or normal functional bladder capacity, which was associated with a significant decrease in urinary nitrite excretion. Indomethacin reduced bed-wetting by decreasing the urine volume, clearance of free water and urinary electrolytes, and through possible effects on bladder and urethral contraction, by inhibiting NO and prostaglandin synthesis. NO and prostaglandins might be important in the pathogenesis of primary enuresis.