The Baylor Pelvic Floor Dysfunction Unit as part of the NICHD Clinical Trials Network will be a productive and dynamic center. Close collaboration among the Departments of Obstetrics and Gynecology, Urology, and Surgery combined with a large public and private patient population will facilitate subject enrollment. This unit treats over 1500 patients annually with pelvic floor disorders. Facilities include three private hospitals, a public hospital, and a Veteran?s Administration hospital. These have a combined bed total over 3000. The Baylor Pelvic Floor Dysfunction Unit as part of the NICHD Clinical Trials Network would provide special and unique strengths that include: (1) Ten very experienced pelvic floor surgeons willing to randomize patients (2) A large minority patient base (40%) coupled with our Spanish-speaking Principal Investigator provides the ability for substantial minority recruitment (3) This unit has expertise in outcomes research and epidemiology (4) The Baylor Department of Obstetrics and Gynecology has exceptional strength in molecular and human genetics, exemplified by multiple NIH funded investigators and physicians trained in obstetrics and gynecology as well as clinical and molecular genetics. The applicant highlights his strengths with this proposal which has as its underlying hypothesis that genetic predisposition is important to the development of pelvic floor relaxation - specifically stress urinary incontinence (SUI). There are two principal arms of this proposal, basic science and clinical. Each interacts with and is dependent on the other in order to succeed in its aims. The basic science arm takes advantage of the quantitative nature of urodynamic testing. To this end a genome wide scan will be performed to identify areas of the genome unique to those patients with SUI. Sub-analysis will be based on multiple demographic and clinical variables.
This aim will proceed with the follow-up of genomic regions of interest by searching for genes using genome databases, in addition to identifying mutations/ polymorphisms of suspect genes. Natural candidates include genes that encode collagens and those responsible for turnover of extracellular matrix glycosaminoglycans. Early analysis will include a candidate gene approach to genome wide scanning. The clinical arm takes advantage of unique strengths described above. Patients with genuine SUT (absence of detrusor instability) will undergo urodynamic and urethral mobility testing. Participating patients will be prospectively randomized to undergo either Burch urethropexy or pubovaginal sling. Outcomes analysis will address success of surgical intervention at twelve and thirty months. Genomic variation among those with a successful repair versus those that failed will be compared before and after stratification. Furthermore, genomic variation as a function of preoperative clinical presentation and diagnostic testing will be analyzed before and after stratification by demographic and clinical variables. The findings of genomic variability will offer insight into the specific genes responsible for stress urinary incontinence.
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