Medicine and Health Sciences Commons^™

Ibuprofen Ameliorates Fatigue- And Depressive-Like Behavior In Tumor-Bearing Mice, Diana M. Norden, Donna O. Mccarthy, Sabahattin Bicer, Raymond Devine, Peter J. Reiser, Jonathan P. Godbout, Loren E. Wold

College of Nursing Faculty Research and Publications

Aims: Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF.

Main methods: Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10 mg/kg) in the …

Dna-Repair Defects And Olaparib In Metastatic Prostate Cancer., Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula Mcgovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A'Hern, Amanda Swain, Lakshmi P Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J Lord, Alan Ashworth, Mark A Rubin, Karen E Knudsen, Felix Y Feng, Arul M Chinnaiyan, Emma Hall, Johann S De Bono

Department of Medicine Faculty Papers

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the …

A Randomized Controlled Trial Of Exercise In Spinal And Bulbar Muscular Atrophy., Joseph A Shrader, Ilona Kats, Angela Kokkinis, Cris Zampieri, Ellen Levy, Galen O Joe, Joshua G. Woolstenhulme, Bart E Drinkard, Michaele R Smith, Willie Ching, Laboni Ghosh, Derrick Fox, Sungyoung Auh, Alice B Schindler, Kenneth H Fischbeck, Christopher Grunseich

Physical Therapy and Health Care Sciences Faculty Publications

OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA).

METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up …

A Teaching Tool To Visually Illustrate How Manipulating The Physiology Of The Ventilatory Muscle Pump Alters Functional Performance, Dennis Sobush

Physical Therapy Faculty Research and Publications

This clinical perspective article describes an inexpensive pedagogical tool intended for use in a laboratory setting as part of a cardiovascular and pulmonary physical therapy course. It uses a dual balance scale schematic/model. As a teaching resource, physical therapy students can use it to visually reinforce their understanding of the complex cause-and-effect interplay between physiological factors that affect ventilatory muscle pump (VMP) performance for sustained breathing or contribute to VMP fatigue/failure.

Fluoxetine Prevents The Development Of Depressive-Like Behavior In A Mouse Model Of Cancer Related Fatigue, Diana M. Norden, Raymond Devine, Sabahattin Bicer, Runfeng Jing, Peter J. Reiser, Loren E. Wold, Jonathan P. Godbout, Donna O. Mccarthy

College of Nursing Faculty Research and Publications

Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue-like behaviors in a mouse model of CRF. Inflammatory cytokines increase the activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin …

Recurrent Nocturnal Hypoglycaemia As A Cause Of Morning Fatigue In Treated Addison’S Disease – Favourable Response To Dietary Management: A Case Report, Kristina S. Petersen, R Louise Rushworth, Peter M. Clifton, David J. Torphy

Medical Papers and Journal Articles

Background: Addison’s disease, or primary adrenal insufficiency, is often associated with reduced well-being and fatigue despite use of currently recommended adrenal hormone replacement. Hypoglycaemia is a known manifestation of glucocorticoid deficiency, but is generally considered rare in adults and not relevant to troubling ongoing symptoms in patients with Addison’s disease.

Case presentation: A 43 year old woman with a three year history of Addison’s disease complained of severe morning fatigue and headaches, despite standard glucocorticoid replacement therapy in the form of thrice daily hydrocortisone and mineralocorticoid replacement with fludrocortisone. Alternative glucocorticoid replacement regimens and the addition of dehydroepiandrosterone replacement therapy …

Tumor Growth Increases Neuroinflammation, Fatigue And Depressive-Like Behavior Prior To Alterations In Muscle Function, Diana M. Norden, Sabahattin Bicer, Yvonne Clark, Runfeng Jing, Christopher J. Henry, Loren E. Wold, Peter J. Reiser, Jonathan P. Godbout, Donna O. Mccarthy

College of Nursing Faculty Research and Publications

Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that …

Eccentric Fatigue Modulates Stretch-Shortening Cycle Effectiveness - A Possible Role In Lower Limb Overuse Injuries, James R. Debenham, M Travers, William Gibson, A Campbell, G Allison

Physiotherapy Papers and Journal Articles

The role of fatigue in injury development is an important consideration for clinicians. In particular, the role of eccentric fatigue in stretch shortening cycle (SSC) activities may be linked to lower limb overuse conditions. The purpose of this study was to explore the influence of ankle plantarflexor eccentric fatigue on SSC effectiveness during a hopping task in healthy volunteers. 11 healthy volunteers (23.2 ± 6.7 years) performed a sub-maximal hopping task on a custom- built sledge system. 3D motion capture and surface EMG were utilised to measure lower limb stiffness, temporal kinematic measures and muscle timing measures at baseline and …