Browsing by Author "Whitehead, William E"
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Item Open Access A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.(Pain, 2020-07-10) van Tilburg, Miranda AL; Parisien, Marc; Boles, Richard G; Drury, Gillian L; Smith-Voudouris, Julian; Verma, Vivek; Khoury, Samar; Chabot-Doré, Anne-Julie; Nackley, Andrea G; Smith, Shad B; Whitehead, William E; Zolnoun, Denniz A; Slade, Gary D; Tchivileva, Inna; Maixner, William; Diatchenko, LudaAlterations in cellular energy metabolism have been implicated in chronic pain, suggesting a role for mitochondrial DNA. Previous studies reported associations of a limited number of mitochondrial DNA polymorphisms with specific pain conditions. In this study, we examined the full mitochondrial genomes of people with a variety of chronic pain conditions. A discovery cohort consisting of 609 participants either with or without a complex persistent pain conditions (CPPCs) was examined. Mitochondrial DNA was subjected to deep sequencing for identification of rare mutations, common variants, haplogroups, and heteroplasmy associated with 5 CPPCs: episodic migraine, irritable bowel syndrome, fibromyalgia, vulvar vestibulitis, or temporomandibular disorders. The strongest association found was the presence of the C allele at the single nucleotide polymorphism m.2352T>C (rs28358579) that significantly increased the risk for fibromyalgia (odds ratio [OR] = 4.6, P = 4.3 × 10). This relationship was even stronger in women (OR = 5.1, P = 2.8 × 10), and m.2352T>C was associated with all other CPPCs in a consistent risk-increasing fashion. This finding was replicated in another cohort (OR = 4.3, P = 2.6 × 10) of the Orofacial Pain: Prospective Evaluation and Risk Assessment study consisting of 1754 female participants. To gain insight into the cellular consequences of the associated genetic variability, we conducted an assay testing metabolic reprogramming in human cell lines with defined genotypes. The minor allele C was associated with decreased mitochondrial membrane potential under conditions where oxidative phosphorylation is required, indicating a role of oxidative phosphorylation in pathophysiology of chronic pain. Our results suggest that cellular energy metabolism, modulated by m.2352T>C, contributes to fibromyalgia and possibly other chronic pain conditions.Item Open Access Controlling anal incontinence in women by performing anal exercises with biofeedback or loperamide (CAPABLe) trial: Design and methods.(Contemp Clin Trials, 2015-09) Eric Jelovsek, J; Markland, Alayne D; Whitehead, William E; Barber, Matthew D; Newman, Diane K; Rogers, Rebecca G; Dyer, Keisha; Visco, Anthony; Sung, Vivian W; Sutkin, Gary; Meikle, Susan F; Gantz, Marie G; Pelvic Floor Disorders NetworkThe goals of this trial are to determine the efficacy and safety of two treatments for women experiencing fecal incontinence. First, we aim to compare the use of loperamide to placebo and second, to compare the use of anal sphincter exercises with biofeedback to usual care. The primary outcome is the change from baseline in the St. Mark's (Vaizey) Score 24weeks after treatment initiation. As a Pelvic Floor Disorders Network (PFDN) trial, subjects are enrolling from eight PFDN clinical centers across the United States. A centralized data coordinating center supervises data collection and analysis. These two first-line treatments for fecal incontinence are being investigated simultaneously using a two-by-two randomized factorial design: a medication intervention (loperamide versus placebo) and a pelvic floor strength and sensory training intervention (anal sphincter exercises with manometry-assisted biofeedback versus usual care using an educational pamphlet). Interventionists providing the anal sphincter exercise training with biofeedback have received standardized training and assessment. Symptom severity, diary, standardized anorectal manometry and health-related quality of life outcomes are assessed using validated instruments administered by researchers masked to randomized interventions. Cost effectiveness analyses will be performed using prospectively collected data on care costs and resource utilization. This article describes the rationale and design of this randomized trial, focusing on specific research concepts of interest to researchers in the field of female pelvic floor disorders and all other providers who care for patients with fecal incontinence.Item Open Access Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomised clinical trial(The Lancet Gastroenterology & Hepatology, 2019-07) Jelovsek, J Eric; Markland, Alayne D; Whitehead, William E; Barber, Matthew D; Newman, Diane K; Rogers, Rebecca G; Dyer, Keisha; Visco, Anthony G; Sutkin, Gary; Zyczynski, Halina M; Carper, Benjamin; Meikle, Susan F; Sung, Vivian W; Gantz, Marie G; National Institute of Child Health and Human Development Pelvic Floor Disorders Network