Sophie Fletcher

Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer’s Disease?

PURPOSE In elderly patients oxybutynin (Sigma-Aldrich) is commonly used to treat overactive bladder despite increased prevalence of Alzheimers disease in this population. We determined whether oxybutynin altered plaque formation, amyloid beta peptide expression and behavior in a transgenic mouse model of Alzheimers disease expressing the mutant human presenilin 1 (deltaE9) and a chimeric mouse/human amyloid precursor protein (APPswe). MATERIALS AND METHODS Mice were treated for 30 days in an acute experiment or 5 months in a chronic experiment with oxybutynin (30 mg/kg) or vehicle. Behavioral testing was performed monthly with the elevated plus maze (Med Associates, St. Albans, Vermont) in the chronic experiment. Brains were tested for plaque burden using Hirano silver and thioflavin-S (Sigma-Aldrich) staining. Amyloid beta peptide expression was tested using enzyme-linked immunosorbent assay for amyloid beta peptides 1-40 and 1-42. RESULTS Animals treated with chronic oxybutynin had a decreased plaque burden in the hippocampus (mean +/- SEM 2.2 +/- 0.4 vs 4.1 +/- 0.9 plaques, p <0.05) and cortex (5.8 +/- 0.7 vs 11.6 +/- 2.1, p <0.05) compared to animals treated with vehicle. Oxybutynin treated animals also had decreased expression of amyloid beta 1-42 (82.8 +/- 9.0 etag/ml vs 105.6 +/- 5.5 etag/ml, p = 0.05) compared to animals treated with vehicle. Female Alzheimers disease mice treated with oxybutynin but not males showed improved behavior with a greater percent of time spent in the closed arm or elevated plus maze (95.9% +/- 1.6% vs 35.6% +/- 18.9%, p <0.05). The greatest difference was noted at 3 months of treatment compared to vehicle. CONCLUSIONS These results suggest that oxybutynin may slow the progression of Alzheimers disease in this model.

Impaired Detrusor Contractility and the Treatment of Female Stress Urinary Incontinence

Introduction and hypothesis: Little conclusive data exists regarding Urodynamic (UD) variables predictive of voiding dysfunction after synthetic Midurethral Sling (MUS) placement. This study aims to evaluate outcomes of MUS in female patients with Impaired Detrusor Contractility (IDC), Valsalva Voiding (VV), or both. We propose that there would be no direct relationship between these variables and urinary retention requiring Clean Intermittent Catheterization (CIC) or reoperation at 6 wk follow up. Methods: Retrospective chart review was performed for all MUS procedures at a single institution, 1/2010- present. Subjects with complete pre-operative UD records and 6 wk follow up were included. The primary outcome measure was urinary retention requiring CIC or re-operation at 6 wk follow up. Results: 187 women who underwent MUS from January 2010 to present had complete UD and ≥ 6 wk follow up data. Average age was 56.7 years. Pre-operative UD identified 64 (34.2%) IDC subjects. At 6-wk follow up, no new subjects in this group required CIC for obstruction or reoperation. No subjects without IDC required CIC or reoperation for urinary retention; however there were 2 reoperations in this group: persistent stress incontinence and vaginal extrusion. Pre-operative UD identified 50 (26.7%) VV subjects. One patient in this group required reoperation; however sling removal was for vaginal extrusion. In the group with both IDC and VV (n=23) no subjects required reoperation. Conclusions: Neither IDC nor VV appear to be risk factors for post-operative urinary retention or reoperation after MUS and have little predictive value for outcomes after MUS.

PD1-05 HIGHER NEURAL CORRELATES FOLLOWING INTRAVESICAL BOTULINUM TOXIN- A IN MULTIPLE SCLEROSIS (MS) PATIENTS VIA CONCURRENT FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) AND URODYNAMIC STUDIES (UDS)

Hypothesis / aims of study Neurogenic bladder dysfunction is seen in 95% of multiple sclerosis patients and has a significant impact on their quality of life. Botulinum toxin A (BTX-A) is a well-described treatment for Neurogenic Detrusor Overactivity (NDO) and while its motor effects on detrusor muscle is extensively studied, its sensory effects is not. In this preliminary study, we evaluate the impact of BTX-A on bladder afferent responses in patients with NDO using concurrent fMRI and UDS pre and post treatment.

V268 ROBOTIC UTEROSACRAL LIGAMENT SUSPENSION: PROXIMITY OF THE URETERS AND THE UTEROSACRAL LIGAMENTS ANATOMY REVIEWED

Design This video is based on a prospective IRB approved collection of our series from 6/2011-7/2012. 59 patients undergone vaginal uterosacral ligament suspension during that time either concurrent with vaginal hysterectomy or in a delayed fashion. We are presenting our technique and modifications to this procedure. A lone star (Scott) retractor is modified using two metal springs secured by four removable clips. All sutures placed in the uterosacral ligament are tagged using marked hemostats in numerical order from 1 thru 6 in colors blue for the needle side and red for the free tail.