Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.

The Role of the Supine Empty Stress Test in the Evaluation of Women with Stress Urinary Incontinence: A Retrospective Cohort Study.

The International Continence Society recommends the supine empty stress test (SEST) as an accessory test in the evaluation of women with urinary incontinence, especially for the presence of intrinsic sphincter deficiency (ISD). The aim of this study was to investigate the relationship between the SEST and clinical findings in women diagnosed with stress urinary incontinence with single voiding cycle ambulatory urodynamics (AUM). AUM tracings of patients with lower urinary tract symptoms (LUTS = Lower urinary tract symptoms) (n = 513) were retrospectively reviewed, and 364 charts with urodynamic SUI were analyzed. Demographics, examination findings, scores of the Sandvik Incontinence Severity Index and validated questionnaires, and AUM findings were compared between SEST-positive and -negative groups. Additionally, the diagnostic accuracy of the SEST in the diagnosis of low abdominal leak point pressure (ALPP ≤ 60 cm H2O) in women with pure urodynamic SUI was calculated. The SEST was positive in 41.8% (n = 152) of the cohort. Women with a positive SEST had higher scores on the Sandvik severity index (9.2 ± 3.6 vs. 7.5 ± 3.8, p = 0.003) and lower ALPP (79.6 ± 29.3 vs. 98.4 ± 31.3, p < 0.001). The negative predictive value of the SEST for ISD was found to be 92.4%. Thus, the SEST seems to be an objective clinical test reflecting urinary incontinence severity while excluding the presence of ISD.

The effect of pelvic floor muscle training on urodynamic parameters in women with stress urinary incontinence.

Introduction: Pelvic floor muscle training (PFMT) is suggested for women with stress urinary incontinence (SUI). The aim of our study is to examine the effectiveness of PFMT on urodynamic (UDS) parameters. Material and methods: This is a prospective observational study enrolling women with SUI. Pelvic surgery, prolapse, body mass index >30, and cognitive disability were exclusion criteria. Patients had baseline UDS, then PFMT only (Group A) or PFMT plus biofeedback (BFD) (Group B) for 6 months and UDS 3 months after treatment. The primary investigated parameters were the number of pads used per day and Valsalva leak point pressure (VLPP). Results: Forty-six women completed the study, 22 in Group A and 24 in Group B. At baseline, all patients documented SUI with 3 median pads used per day. Urodynamic SUI was documented with a median Valsalva leak point pressure (mVLPP) of 45 cmH2O. At the re-evaluation, 12 women (26.1%) had SUI in BDs with median number pads per day of 1, which was statistically different to baseline (p = 0.02). Urodynamic SUI was reported in 8 (17.4%) women with a mVLPP of 88 cmH2O.Six patients were from Group A and 6 from Group B. In Group A, the median number of pads per day was 1, and urodynamic SUI was found in 3 women. In Group B, the median number of pads per day was 1, and urodynamic SUI was found in 5 women. Thirty-four women (73.9%) were dry - 16 (47.1%) from Group A and 18 (52.9%) from Group B. Conclusions: PFMT improves urodynamic parameters among women with SUI.

Brain-Derived Neurotrophic Factor Is an Important Therapeutic Factor in Mesenchymal Stem Cell Secretions for Treatment of Traumatic Peripheral Pelvic Injuries.

Traumatic neuromuscular injury to the pudendal nerve and urethra during childbirth does not regenerate well and contributes to stress urinary incontinence in women. Mesenchymal stem cells (MSCs) can improve neuroregeneration via their secretions, or secretome, which includes brain-derived neurotrophic factor (BDNF). In this study, we investigated whether BDNF is a key factor in the secretome of MSCs for the facilitation of functional recovery following a dual simulated childbirth injury. BDNF knockdown (KD) MSCs were created using an anti-BDNF shRNA lentivirus vector. A scrambled sequence was used as a transduction control (scrambled). Cells were cultured for 24 h before media was concentrated 50x to create concentrated conditioned media (CCM) containing MSC secretome. CCM of unmanipulated MSCs was screened for high BDNF expression (high BDNF CCM). Concentrated control media (CM) was created by concentrating media not conditioned by cells. Female Sprague-Dawley rats underwent bilateral pudendal nerve crush and vaginal distension (Injury) or sham injury. One hour and 1 week after injury, sham injured rats received CM, and injured rats received CM, high BDNF CCM, KD CCM, or scrambled CCM (300 µl intraperitoneally). Three weeks after injury, rats underwent leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings. The urethra and pudendal nerve were harvested for anatomical assessment. ANOVA followed by the Student-Newman-Keuls test determined significant differences between groups (p < 0.05). BDNF KD CCM had significantly decreased BDNF concentration compared to scrambled CCM, while the concentration in high BDNF CCM was significantly increased. LPP was significantly decreased in CM and KD CCM treated animals compared to sham injury, but not with scrambled or high BDNF CCM. PNSBP firing rate showed a significant decrease with CM treatment compared to sham injury. Neuromuscular junctions in the urethral sphincter in KD CCM, scrambled CCM, and high BDNF CCM were healthier than CM treated rats. While anatomical and nerve function tests demonstrate regeneration of the pudendal nerve with any CCM treatment, LPP results suggest it takes longer to recover continence with reduced BDNF in CCM. BDNF in MSC CCM is an important factor for the acceleration of recovery from a dual nerve and muscle injury.

Valsalva leak point pressure (VLPP) greater than 70 cm H2O is an indicator for sling success: a success prediction model for the male transobturator sling.

INTRODUCTION AND OBJECTIVES: Urodynamic studies are often performed in the evaluation of post-prostatectomy urinary incontinence (PPUI). The male transobturator sling (TOS) is a minimally invasive treatment for PPUI. Others have reported their results with a specific Valsalva leak point pressure (VLPP) that predicts a good outcome with the male TOS. Our objective was to determine the relationship of the pre-operative VLPP on the success rate of the male TOS in a high-volume, single center. We hypothesized that a higher pre-operative VLPP better predicts successful outcomes. METHODS: We reviewed patients undergoing a male TOS placement from 2006 to 2012 at our institution. Patients who underwent TOS placement were identified using our patient data portal (DEDUCE). Demographic, urodynamic, and follow-up data were extracted by chart review. Post-operative success was defined by the use of 0 or 1 security pad, a negative stress test on exam, or pad weight of less than 8 g per 24 h. Cox and linear regression models were performed. RESULTS: 290 patients were included. All patients underwent a radical prostatectomy for prostate cancer and presented with PPUI. Mean age at surgery was 66.3 (± 7.4) years and 84% were Caucasian. Median time to follow-up was 5 months (IQR 1-15). A linear regression model shows an inverse prediction curve for sling failure versus VLPP (p = 0.02). The hazard ratio for failure with a VLPP of ≤ 70 cm H2O compared with a VLPP of > 70 cm H2O, adjusted for pelvic radiation and 24-h pad weight was 0.5 (95% CI 0.2-0.98). CONCLUSION: Patient selection is imperative in the success of the male TOS for patients with PPUI. In our cohort of patients with PPUI, those with a pre-procedural VLPP of > 70 cm H2O were 50% less likely to fail after TOS placement versus those with a VLPP ≤ 70 cm H2O. In our practice, we use these data to support the use of VLPP cut off of 70 cm H2O as an indicator for success to help in the evaluation and counseling of patients.

A Study of Urodynamic Parameters at Different Bladder Filling Stages for Predicting Upper Urinary Tract Dilatation.

PURPOSE: To identify more accurate predictors of upper urinary tract dilatation (UUTD) in neurogenic bladder (NB) children, we studied the relationship among urodynamic parameters at different bladder filling stages, detrusor leak point pressure (DLPP) and UUTD. METHODS: A total of 158 children (3-16 years) with NB were included and then divided into 2 groups according to whether their NB diagnosis was complicated with UUTD: the UUTD group (39 patients) and those without UUTD group (control group, 119 patients). The bladder filling phase was divided into 3 equal parts: the early, middle, and end filling stages. The bladder compliance (BC) and detrusor pressure (△Pdet) at each phase and DLPP at the end filling stage were recorded. RESULTS: A BC<8 mL/cm H2O both in the middle and end stages is more specific than a BC<9 mL/cm H2O in the end stage (72%, 73%, vs. 66%), and △Pdet >8 cm H2O in the early stage, 20 cm H2O in the middle stage and 25 cm H2O in the end stage are more sensitive than △Pdet >40 cm H2O in the end stage (82%, 85%, 85%, vs. 49%). A DLPP cutoff value of 20 cm H2O showed higher sensitivity for predicting UUTD than 40 cm H2O. CONCLUSION: Low BC and a high △Pdet in the middle and end filling stages are more accurate factors than classic indicators for predicting UUTD. In addition, a DLPP value of >20 cm H2O in the end bladder filling stage shows high sensitivity.

Microenergy acoustic pulse therapy restores urethral wall integrity and continence in a rat model of female stress incontinence.

OBJECTIVE: To determine the outcomes and mechanisms of microenergy acoustic pulse (MAP) therapy in an irreversible rat model of female stress urinary incontinence. MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats were randomly assigned into four groups: sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + ß-aminopropionitrile (BAPN), and VBDO + ß-aminopropionitrile treated with MAP (MAP). MAP therapy was administered twice per week for 4 weeks. After a 1-week washout period, all 24 rats were evaluated with functional and histological studies. The urethral vascular plexus was examined by immunofluorescence staining with antibodies against collagen IV and von Willebrand factor (vWF). The urethral smooth muscle stem/progenitor cells (uSMPCs) were isolated and functionally studied in vivo and in vitro. RESULTS: Functional study with leak point pressure (LPP) measurement showed that the MAP group had significantly higher LPPs compared to VBDO and BAPN groups. MAP ameliorated the decline in urethral wall thickness and increased the amount of extracellular matrix within the urethral wall, especially in the urethral and vaginal elastic fibers. MAP also improved the disruption of the urethral vascular plexus in the treated animals. In addition, MAP enhanced the regeneration of urethral and vaginal smooth muscle, and uSMPCs could be induced by MAP to differentiate into smooth muscle and neuron-like cells in vitro. CONCLUSION: MAP appears to restore urethral wall integrity by increasing muscle content in the urethra and the vagina and by improving the urethral vascular plexus and the extracellular matrix.

A pilot study assessing average detrusor pressure garnered from area under a urodynamic curve: Evaluation of clinical outcomes.

INTRODUCTION: The management of neurogenic bladder mostly relies on urodynamic studies; however, several studies have shown low interobserver reproducibility. The aim of this study was to evaluate if a new objective cystometric parameter was superior to other cystometric measures. PATIENTS AND METHODS: A new parameter (pressure adjusted area under curve ratio, PAUC) was formulated from the ratio of area under the cystometry curve to a DLPP-adjusted total area (AT). AT was figured from a rectangle designed on the cystometrogram curve with a fixed height of 200 cmH2O and a width defined by the filling phase (figure). Two different estimated pressure measures derived from this (upper mean static pressure, UMSP and theoretical end filling pressure TEFP) were then calculated. Medical records of myelomeningocele patients with ultrasonography and renal scintigraphy performed at the time of urodynamics (with an interval of >5 years) were reviewed. Hydronephrosis and new scars in scintigraphy were used as the outcome measures. RESULTS: The study group consisted of 115 subjects with a median age of 4 (0-23) years at the time of the first urodynamic study. The median follow-up was 6 (5-14) years. PAUC and its derivatives (UMSP and TEFP) had the best discriminative power in predicting high grade hydronephrosis (0.830, 95% CI:0.732-0.927, p < 0.001), worsening in hydronephrosis (0.827, 95% CI:0.723-0.931, p < 0.001), and new scar formation (0.704, 95% CI: 0.576-0.832, p = 0.002). PAUC>0.1 significantly correlated with urinary tract dilatation (p < 0.001) and new scar formation (p = 0.002). In the multivariate analysis, our three parameters and having scars at admission were the only independent risk factors for new scars (p = 0.001 and p = 0.002, respectively) and worsening in hydronephrosis (p < 0.001 and p = 0.001, respectively). DISCUSSION: Our results show that our three parameters derived from area under the urodynamic curve are more reliable than other urodynamic measures. Their major theoretical advantage is to incorporate all the pressure during filling phase giving a more accurate picture of what the intravesical pressure milleu is. Using these measures, we demonstrated their superiority in predicting clinical outcomes. Major limitations of this study are the retrospectively collected data and lack of longitudinal follow-up starting from infancy in each patient. CONCLUSION: Our new parameters (PAUC, UMSP and TEFP) which incorporate the impact of entire filling phase pressure changes in the analysis, may be useful tools to identify those patients who are under the risk of kidney damage with neurogenic lower urinary tract dysfunction.

Abdominal pressure and pelvic organ prolapse: is there an association?

INTRODUCTION AND HYPOTHESIS: The primary aim of this study was to assess for an association between maximal intra-abdominal pressure reached on Valsalva (MAP) and pelvic organ prolapse (POP) on subjective, clinical and sonographic evaluation. Another objective was to test for association between MAP and body mass index (BMI). METHODS: A retrospective cross-sectional study was carried out on 504 archived datasets of women seen for pelvic floor dysfunction symptoms between January 2017 to September 2019 at a tertiary urogynaecology clinic. Patients underwent a standardized interview including use of visual analogue scores (VAS) to evaluate bother of pelvic floor symptoms, examination using the International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q), dual-channel filling and voiding cystometry, test for MAP as well as four-dimensional (4D) transperineal ultrasound. Analysis of ultrasound volumes for pelvic organ descent was performed blinded against all other data. RESULTS: There was a weak but significant association between MAP and sonographic rectal ampulla descent (p = 0.0275). There was also a significant association between MAP and bother of obstructed defecation symptoms (p = 0.0065). Symptomatic, clinical and sonographic POP in the anterior or the apical compartments was not significantly associated with MAP. On multivariate analysis, the association between MAP and rectal descent remained significant (p = 0.01). There was no significant association between BMI and MAP. CONCLUSIONS: This cross-sectional study showed an association between MAP and posterior compartment prolapse on imaging as well as between MAP and the bother score of obstructed defecation symptoms. There was no association between BMI and MAP.

Validation of a new rat model of urethral sphincter injury and leak point pressure measurements.

AIMS: In vivo experiments were performed to establish and validate a rat model of urethral sphincter injury and to develop a method for leak point pressure (LPP) measurements performed repeatedly in the same animal. METHODS: Twenty-four Sprague-Dawley female rats underwent bladder and epidural catheter implantation. Five days later, cystometry was performed using continuous infusion. Anesthesia with isoflurane, ketamine-xylazine (KX) or fentanyl-fluanisone-midazolam (FFM) was used. After three micturition cycles, intrathecal bupivacaine was administered leading to the suppression of reflex bladder contractions. LPP measurements were performed using vertical tilt. After the initial LPP measurement, animals underwent partial resection of the striated urethral sphincter. The effect was evaluated 6 weeks after surgery, by repeating the LPP measurement in the same animal. RESULTS: Ten out of 19 animals showed full micturition cycles under isoflurane, and all 9 animals under KX anesthesia. No significant difference in micturition pressures (Mean ± SEM; 30.1 ± 2.3 vs. 26.8 ± 1.6 mmHg) and LPP (31.0 ± 2.4 vs. 28.0 ± 0.9 mmHg) was observed between isoflurane and KX groups, respectively. Reflex micturition was suppressed with FFM. Bupivacaine led to overflow incontinence in all cases. Sphincter injury caused fibrotic changes and a significant increase in LPP (26.4 ± 2.3 before vs. 46.9 ± 4.6 mmHg after injury, p < 0.05). CONCLUSIONS: KX anesthesia preserves bladder contractions. Intrathecal bupivacaine eliminates reflex micturition, allowing for repeated LPP measurements in the same animal. Resection of striated sphincter resulted in increased LPP 6 weeks post injury. The site of urethral sphincter resection healed with fibrosis.

Brain derived neurotrophic factor mediates accelerated recovery of regenerative electrical stimulation in an animal model of stress urinary incontinence.

OBJECTIVE: Stress urinary incontinence (SUI) is prevalent among older women and can result from insufficient regeneration of the pudendal nerve (PN). Electrical stimulation (ES) of the PN upregulates brain derived neurotrophic factor (BDNF) and accelerates regeneration. Using tyrosine kinase B (TrkB) to reduce the availability of free BDNF, the aim of this study was to determine if BDNF is necessary for accelerated recovery via ES in a model of SUI. METHODS: Our SUI model consists of Female Sprague-Dawley rats, whose PNs were crushed bilaterally twice for 30 s, followed by insertion of a modified Foley catheter into the vagina with balloon inflation for 4 h. These rats were divided into 4 groups: 1) Sham PN crush and sham vaginal distension without electrode implantation and with saline treatment (sham injury); 2) SUI with sham stimulation and saline treatment (SUI); 3) SUI and ES with saline treatment (SUI&ES); and 4) SUI and ES with TrkB treatment (SUI&ES&TrkB). Animals underwent ES or sham stimulation four times a week for two weeks. Four weeks after injury, animals underwent functional testing consisting of leak point pressure (LPP) with simultaneous external urethral sphincter (EUS) electromyography (EMG) and pudendal nerve recordings. Data was analyzed using ANOVA with Holm-Sidak posthoc test (p < 0.05). EUS and PN specimen were sectioned and stained to semi-quantitatively evaluate morphology, regeneration, and reinnervation. RESULTS: LPP and EUS EMG firing rate were significantly increased in the sham injury and SUI&ES groups compared to the SUI and SUI&ES&TrkB groups. EUS of SUI rats showed few innervated neuromuscular junctions compared to sham injured rats, while both treatment groups showed an increase in reinnervated neuromuscular junctions. CONCLUSION: ES accelerates functional recovery via a BDNF-mediated pathway in a model of SUI. These findings suggest ES could be used as a potential regenerative therapy for women with SUI.

Therapeutic potential of muscle growth promoters in a stress urinary incontinence model.

Weakness of urinary sphincter and pelvic floor muscles can cause insufficient urethral closure and lead to stress urinary incontinence. Bimagrumab is a novel myostatin inhibitor that blocks activin type II receptors, inducing skeletal muscle hypertrophy and attenuating muscle weakness. ß2-Adrenergic agonists, such as 5-hydroxybenzothiazolone derivative (5-HOB) and clenbuterol, can enhance muscle growth. We hypothesized that promoting muscle growth would increase leak point pressure (LPP) by facilitating muscle recovery in a dual-injury (DI) stress urinary incontinence model. Rats underwent pudendal nerve crush (PNC) followed by vaginal distension (VD). One week after injury, each rat began subcutaneous (0.3 mL/rat) treatment daily in a blinded fashion with either bimagrumab (DI + Bim), clenbuterol (DI + Clen), 5-HOB (DI + 5-HOB), or PBS (DI + PBS). Sham-injured rats underwent sham PNC + VD and received PBS (sham + PBS). After 2 wk of treatment, rats were anesthetized for LPP and external urethral sphincter electromyography recordings. Hindlimb skeletal muscles and pelvic floor muscles were dissected and stained. At the end of 2 wk of treatment, all three treatment groups had a significant increase in body weight and individual muscle weight compared with both sham-treated and sham-injured rats. LPP in DI + Bim rats was significantly higher than LPP of DI + PBS and DI + Clen rats. There were more consistent urethral striated muscle fibers, elastin fibers in the urethra, and pelvic muscle recovery in DI + Bim rats compared with DI + PBS rats. In conclusion, bimagrumab was the most effective for increasing urethral pressure and continence by promoting injured external urethral sphincter and pelvic floor muscle recovery.

Pitfalls in Urodynamics.

Although urodynamics (UDS) is essential for the diagnosis and treatment of neurogenic lower urinary tract dysfunction, several possible pitfalls can be identified. In this paper we identify pitfalls in UDS and highlight limiting factors. UDS pitfalls that depend on the patient, on the physician, or on the test itself are described and analyzed. PATIENT SUMMARY: In this report we looked into pitfalls of urodynamics. Urodynamics is an essential tool in the diagnosis and treatment of neurogenic lower urinary tract dysfunction and always requires standardization and quality control to limit possible pitfalls.

Influence of the urethral pressure transducer in measuring Valsalva leak point pressure in women undergoing multichannel urodynamic testing.

AIMS: To determine if the air-charged urethral sensor balloon currently used in urodynamic testing (UDS) significantly impacts Valsalva leak point pressure (VLPP) measurements. METHODS: This is a prospective cohort study of women undergoing UDS at an academic institution. VLPPs were obtained at 150 mL and urodynamic capacity with and without the urethral pressure sensor in the urethra. VLPP measurements were analyzed using a Wilcoxon signed-rank test. Median and interquartile range are presented. RESULTS: Sixty-three patients were enrolled in the study, 53 were included in the primary analysis. The mean age of the subjects was 56.2 ± 12.1 years. Nine patients (16%) solely leaked when the balloon was not present in the urethra either with cough or during VLPP measurement. At both 150 mL and urodynamic capacity, when VLPP testing was performed, there was a significant difference (cmH2 O) between the control and intervention values, (76.2 [55.0, 97.0] vs 68.8 [46.3, 93.3], P = .0012; 79.3 [53, 96.5] vs 72.5 [50.8, 92.3], P = .04). There was also a statistically significant difference between the control and intervention values for the lowest leak value at 150 mL and capacity (70.5 [51, 94.5] vs 60.0 [40, 88] P = .002; 73.5 [49.5, 91.5] vs 61 [45, 88], P = .017). CONCLUSIONS: The higher VLPPs obtained with the urethral balloon in place indicate that the balloon may be the cause of falsely elevated VLPPs during urodynamic testing. Additionally, the balloon may mask a diagnosis of stress urinary incontinence in some patients.

Urodynamic and imaging findings in infants with myelomeningocele may predict need for future augmentation cystoplasty.

INTRODUCTION: Urologic issues are persistent and important causes of morbidity and mortality in patients with myelomeningocele. Classically, patients with elevated bladder pressures despite adherence to clean intermittent catheterization (CIC) and pharmacotherapy undergo augmentation cystoplasty (AC). Currently, there is little understanding of which infants are more likely to require AC later. OBJECTIVE: In this context, the authors studied whether unfavorable urodynamic or imaging findings in patients with myelomeningocele during infancy could predict future AC. The authors hypothesized that infants born with elevated bladder pressures, vesicoureteral reflux (VUR), and/or hydronephrosis would be more likely to undergo AC. STUDY DESIGN: The authors retrospectively identified patients with myelomeningocele at their institution who were followed-up since infancy (<1 year of age), with a minimum of eight continuous years of follow-up. Standard care protocol included cystometrogram, voiding cystourethrogram (VCUG), and renal ultrasound during infancy. The primary outcome was AC for elevated bladder pressures despite attempts at more conservative management with medical therapy and CIC. Specifically, the authors evaluated for differences in augmentation rates based on gender, level of lesion, presence of detrusor leak point pressure (DLPP) or end-fill pressure (EFP) greater than 40 cm H2O, presence of hydronephrosis, VUR, initiation of CIC, and initiation of antimuscarinics in infancy. The authors excluded patients who underwent surgical intervention for urinary incontinence. RESULTS: A total of 97 patients met the inclusion criteria. The median follow-up time was 13.8 years. Augmentation cystoplasty was performed for 17 patients (17.5%) at a median age of 114 months (9.5 years). Detrusor leak point pressure/EFP was greater than 40 cm H2O in 34.0% (33/97) of infant cystometrogram studies, while 30.9% (30/97) had VUR on infant VCUG and 20.6% (20/97) had hydronephrosis on infant renal ultrasound. Patients with DLPP/EFP greater than 40 cm H2O or VUR during infancy were more likely to undergo AC (P = 0.02 and P = 0.03, respectively). Binomial logistic regression revealed that DLPP/EFP greater than 40 cm H2O (odds ratio [OR]: 4.28, 95% confidence interval [CI]: 1.34-13.62) and VUR (OR: 3.73, 95% CI: 1.18-11.77) were independent risk factors for future AC. DISCUSSION: Infants with myelomeningocele and elevated bladder pressures and VUR should be closely monitored by urodynamic testing and imaging studies. Parents can be counseled regarding the potentially higher risk for future AC in these patients. Nonetheless, the majority of high-risk infants will safely avoid AC with conservative management.

Multiple doses of stem cells maintain urethral function in a model of neuromuscular injury resulting in stress urinary incontinence.

Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a cesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of the present study was to determine if increasing the number of doses of MSCs improves urethral and pudendal nerve function and anatomy. We hypothesized that increasing the number of MSC doses would accelerate recovery from SUI compared with vehicle treatment. Rats underwent pudendal nerve crush and vaginal distension or a sham injury and were treated intravenously with vehicle or one, two, or three doses of 2 × 106 MSCs at 1 h, 7 days, and 14 days after injury. Urethral leak point pressure testing with simultaneous external urethral sphincter electromyography and pudendal nerve electroneurography were performed 21 days after injury, and the urethrovaginal complex and pudendal nerve were harvested for semiquantitative morphometry of the external urethral sphincter, urethral elastin, and pudendal nerve. Two and three doses of MSCs significantly improved peak pressure; however, a single dose of MSCs did not. Single, as well as repeated, MSC doses improved urethral integrity by restoring urethral connective tissue composition and neuromuscular structures. MSC treatment improved elastogenesis, prevented disruption of the external urethral sphincter, and enhanced pudendal nerve morphology. These results suggest that MSC therapy for postpartum incontinence and SUI can be enhanced with multiple doses.

Analysis of continence reflexes by dynamic urethral pressure recordings in a rat stress urinary incontinence model induced by multiple simulated birth traumas.

The present study evaluated real-time changes in urethral pressure during the storage phase using a rat model with stress urinary incontinence (SUI) induced by simulated multiple birth traumas and investigated the relationship between urethral continence function and dynamic parameters associated with the changes in urethral pressure. Sprague-Dawley rats were divided into the following two groups: the sham group, which underwent three catheterizations of the vagina without distension at 2-wk intervals, and the vaginal distension (VD) group, which underwent three VDs at 2-wk intervals. After transection of the T8-T9 spinal cord, simultaneous bladder and urethral pressure recordings were performed during intravesical pressure elevation. Urodynamic parameters such as leak point pressure (LPP), urethral baseline pressure (UBP), maximum urethral pressure (MUP), the MUP-UBP differential (dUP) during intravesical pressure elevation, the bladder pressure when urethral contraction begins (Puc), and the bladder pressure at bladder neck opening (Pno) were then measured and compared. Compared with the sham group, LPP, UBP, dUP, MUP, Puc, and Pno were significantly decreased in the VD group. Pressure differences between LPP and Pno and between LPP and UBP (LPP-UBP) were also significantly different in the two groups. However, difference values of LPP and MUP or Pno and UBP were not altered after VD. Our new methods of simultaneous recordings of dynamic changes in bladder and urethral pressures are useful to fully evaluate the functional alterations in urethral continence function in the SUI model induced by multiple VDs. Moreover, LPP-UBP values, which correspond to the difference between Valsalva LPP and maximum urethral closure pressure in clinical urodynamics, would be useful to evaluate the impaired urethral continence function after simulated birth traumas in animal models.

Daily bilateral pudendal nerve electrical stimulation improves recovery from stress urinary incontinence.

Stress urinary incontinence (SUI) in women is strongly associated with childbirth which injures the pudendal nerve (PN) and the external urethral sphincter (EUS) during delivery. Electrical stimulation (ES) can increase brain-derived neurotrophic factor (BDNF) expression in injured neurons, activate Schwann cells and promote neuroregeneration after nerve injury. The aim of this study was to determine if more frequent ES would increase recovery from SUI in a rat model. Forty female Sprague-Dawley rats underwent either sham injury or pudendal nerve crush (PNC) and vaginal distention (VD) to establish SUI. Immediately after injury, electrodes were implanted at the pudendal nerve bilaterally. Each injured animal underwent sham ES, twice per week ES (2/week), or daily ES of 1 h duration for two weeks. Urethral and nerve function were assessed with leak point pressure (LPP), EUS electromyography and pudendal nerve sensory branch potential (PNSBP) recordings two weeks after injury. LPP was significantly increased after daily ES compared to 2/week ES. EUS neuromuscular junction innervation was decreased after injury with sham ES, but improved after 2/week or daily ES. This study demonstrates that daily bilateral ES to the pudendal nerve can accelerate recovery from SUI. Daily ES improved urethral function more than 2/week ES.

Clinical score predictive of abdominal leak point pressure (ALPP) <60 cm H2O in the urodynamics study of women with stress urinary incontinence.

OBJECTIVE: The aim of this study was to perform a score predictive of ALPP <60 cm H2O from clinical factors in women with stress urinary incontinence (SUI). STUDY DESIGN: We performed a descriptive and observational study of women referred for a urodynamic study for stress urinary incontinence. Patients were divided into three groups: ALPP: >90 cm H2O, between 60 and 90 cm H2O and <60 cm H2O. A logistic regression study was performed in order to complete clinical predictors of ALPP < 60 cm H2O. Variables that were significant in the multivariate analysis were included in the score. RESULTS: We studied 158 patients: 65 presented ALPP > 90 cm H2O, 64 between 60-90 cm H2O and 29 <60 cm H2O. In the multivariate analysis, were presented as independent predictors of ALPP < 60 cm H2O, the presence of a fixed urethra (p 0.01), empty bladder test positive (p 0.02) and presence of symptoms grade III in the classification of Stamey (p 0.03). The accuracy of the test was: score 0, 42%; score 1, 58%; score 2, 81%. Receiver Operating Characteristic (ROC) analysis for the overall cutoff points revealed an area under the curve of 0,75. CONCLUSIONS: Presence of a fixed urethra, positive empty bladder test and patients with a high degree of SUI symptoms according to the Stamey score are independent clinical predictors of intrinsic sphincter deficiency. This score could represent a useful clinical tool to predict the presence of ALPP <60 cm H2O based on clinical parameters.

Effect of ASP2205 fumarate, a novel 5-HT2C receptor agonist, on urethral closure function in rats.

The pharmacological profile of ASP2205 fumarate (ASP2205), a novel 5-HT2C receptor agonist, was evaluated in vitro and in vivo. ASP2205 showed potent and selective agonistic activity for the human 5-HT2C receptor, with an EC50 of 0.85 nM in the intracellular Ca2+ mobilization assay. Rat 5-HT2C receptor was also activated by ASP2205 with an EC50 of 2.5 nM. Intraduodenal administration (i.d.) of ASP2205 (0.1-1 mg/kg) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner. This ASP2205 (0.3 mg/kg i.d.)-induced LPP elevation was inhibited by SB242084 (0.3 mg/kg i.v.), a selective 5-HT2C receptor antagonist. Urethral closure responses induced by intravesical pressure loading in rats were enhanced by ASP2205 (0.3 mg/kg i.v.), which was abolished by pretreatment with SB242084 (0.3 mg/kg i.v.) and bilateral transection of the pudendal nerve. In contrast, ASP2205 (0.3 mg/kg i.v.) did not change the resting urethral pressure in rats. These results indicate that ASP2205 can enhance the pudendal nerve-mediated urethral closure reflex via the 5-HT2C receptor, resulting in the prevention of involuntary urine loss.