Medicine and Health Sciences Commons^™

Preliminary Investigations Into Triazole Derived Androgen Receptor Antagonists, Jarrad Altimari, Birunthi Niranjan, Gail Risbridger, Stephanie Schweiker, Anna Lohning, Luke Henderson

Anna Lohning

A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated as non-steroidal androgen receptor (AR) antagonists. The motivation for this study was to replace the N-phenyl amide portion of small molecule antiandrogens with a 1,2,3-triazole and determine effects, if any, on biological activity. The synthetic methodology presented herein is robust, high yielding and extremely rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized from commercially available starting materials in less than 3 h. After preliminary biological screening at 20 and 40 lM, the most promising three compounds were found to display IC50 values of 40–50 lM against androgen dependent …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Betsy Donahoe-Fillmore

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

The Effect Of Yoga Postures On Balance, Flexibility, And Strength In Healthy High School Females, Betsy Donahoe-Fillmore, C. Brahler, Mary Fisher, Kelly Beasley

Betsy Donahoe-Fillmore

Objective: The purpose of this study was to document the effects of yoga interventions on balance, flexibility, and strength in adolescent girls 14 to 18 years. Study Design: Quasi-experimental, nonrandomized. Background: Research on the effects of yoga on balance, flexibility, and strength has focused on adults, although yoga is being marketed to all ages. Methods and Measures: A convenience sample of 33 female adolescents participated in yoga training 2 times per week and a walking program 3 times per week, for 7 weeks. The instructor-led group received instruction from a registered yoga therapist in person, while the video-led group watched …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold Merriman

Harold L. Merriman

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

The Importance Of Managing Psychosocial Health: A Case Study, Mary Insana Fisher, Harold L. Merriman

Harold L. Merriman

Managing the physical aspects of lymphedema requires an individual to be committed to daily treatment of this chronic condition. Performing manual lymph drainage, using compression bandaging or compression garments, exercising, and caring for the skin all take time and a high level of dedication. This commitment to self-care can be emotionally and psychologically exhausting. When coupled with other emotional stressors in a patient’s life, successful treatment of lymphedema is challenging. We present a case demonstrating how the physical and psychological aspects of care interplay, and, when well-managed, can positively affect the outcome.

Contributions Of Body Fat And Effort In The 5k Run: Age And Body Weight Handicap, Anne R. Crecelius, Paul M. Vanderburgh, Lloyd L. Laubach

Paul M. Vanderburgh

The 5K handicap (5KH), designed to eliminate the body weight (BW) and age biases inherent in the 5K run time (RT), yields an adjusted RT (RTadj) that can be compared between runners of different BW and age. As hypothesized in a validation study, however, not all BW bias may be removed, because of the influences of body fatness (BF) and effort (run speed; essentially the inverse as measured by rating of perceived exertion (RPE)). This study's purpose was to determine the effects of BF and RPE on BW bias in the 5KH. For 99 male runners in a regional 5K …

Political Drive To Screen For Pre-Dementia: Not Evidence Based And Ignores The Harms Of Diagnosis, David Le Couteur, Jenny A. Doust, Helen Creasey, Carol Brayne

Jenny Doust

Current policy in many countries is aimed at increasing the rates of diagnosis of dementia and cognitive impairment.1 2 3 This policy drive has been accompanied by research into early detection of dementia, including preclinical identification of underlying neurobiology that might later be associated with dementia.4 Although the clinical features of people with established dementia are unmistakable,5 6 the ability of these preclinical features to predict future disease is less clear. Nevertheless, the belief that there is value in screening for “pre-dementia” or mild cognitive impairment is creeping into clinical practice, with the resulting overdiagnosis having potential adverse consequences for …

Development Of A Novel Screening Strategy Designed To Discover A New Class Of Hiv Drugs, Nancy Cheng, Sook-Kyung Lee, P. Donover, Mel Reichman, Celia Schiffer, Emily Hull-Ryde, Ronald Swanstrom, William Janzen

Celia A. Schiffer

Current antiretroviral treatments target multiple pathways important for human immunodeficiency virus (HIV) multiplication, including viral entry, synthesis and integration of the DNA provirus, and the processing of viral polyprotein precursors. However, HIV is becoming increasingly resistant to these "combination therapies." Recent findings show that inhibition of HIV Gag protein cleavage into its two structural proteins, matrix (MA) and capsid (CA), has a devastating effect on viral production, revealing a potential new target class for HIV treatment. Unlike the widely used HIV protease inhibitors, this new class of inhibitor would target the substrate, not the protease enzyme itself. This approach offers …

Interview With Celia Schiffer, Celia Schiffer

Celia A. Schiffer

Celia Schiffer, a Professor in Biochemistry and Molecular Pharmacology; a former Director of UMass Center for AIDS Research; and a Founder and Co-Director for the Institute for Drug Resistance (University of Massachusetts Medical School, MA, USA). Schiffer has an undergraduate degree in physics from the University of Chicago, with a PhD in biophysics from University of California, San Francisco (CA, USA). She was a postdoctoral associate first at the ETH in Zurich and then at Genentech in San Francisco. Schiffer has published more than 100 peer reviewed journal articles. Her laboratory primarily uses structural biology, biophysical and chemistry techniques to …

Prototypical Recombinant Multi-Protease Inhibitor Resistant Infectious Molecular Clones Of Human Immunodeficiency Virus Type-1, Vici Varghese, Yumi Mitsuya, W. Jeffrey Fessel, Tommy F. Liu, George Melikian, David Katzenstein, Celia Schiffer, Susan Holmes, Robert Shafer

Celia A. Schiffer

The many genetic manifestations of HIV-1 protease inhibitor (PI) resistance present challenges to research into the mechanisms of PI-resistance and the assessment of new PIs. To address these challenges, we created a panel of recombinant multi-PI resistant infectious molecular clones designed to represent the spectrum of clinically relevant multi-PI resistant viruses. To assess the representativeness of this panel, we examined the sequences of the panel's viruses in the context of a correlation network of PI-resistance amino acid substitutions in sequences from more than 10,000 patients. The panel of recombinant infectious molecular clones comprised 29 of 41 study-defined PI-resistance amino acid …

Understanding Atp-Mediated Vasodilatation In Humans, Anne R. Crecelius, Frank A. Dinenno

Anne R. Crecelius

Negative results, cynicism, the piecing together of puzzles and integrating physiology with experimental approaches are all part of the inspiring and meandering journey on the path to understand ATP-mediated vasodilatation. While it is satisfying to be "right" as scientists, we know sometimes the most important progress occurs when data are surprising or contrary to our original hypothesis. The pursuit of explanations for unexpected findings often leads to the best advancements. The story of how our laboratory came to investigate the underlying vasodilatator pathways of adenosine triphosphate (ATP) is an example of such a path to our current understanding.

Impaired Skeletal Muscle Blood Flow Control With Advancing Age In Humans: Attenuated Atp Release And Local Vasodilation During Erythrocyte Deoxygenation, Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno

Anne R. Crecelius

Rationale: Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown. Objective: To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation. Methods and Results: We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, …

Contributions Of Body Fat And Effort In The 5k Run: Age And Body Weight Handicap, Anne R. Crecelius, Paul M. Vanderburgh, Lloyd L. Laubach

Anne R. Crecelius

The 5K handicap (5KH), designed to eliminate the body weight (BW) and age biases inherent in the 5K run time (RT), yields an adjusted RT (RTadj) that can be compared between runners of different BW and age. As hypothesized in a validation study, however, not all BW bias may be removed, because of the influences of body fatness (BF) and effort (run speed; essentially the inverse as measured by rating of perceived exertion (RPE)). This study's purpose was to determine the effects of BF and RPE on BW bias in the 5KH. For 99 male runners in a regional 5K …

Muscle Contraction Duration And Fibre Recruitment Influence Blood Flow And Vo2 Independent Of Contractile Work During Steady-State Exercise In Humans, Jennifer C. Richards, Anne R. Crecelius, Brett S. Kirby, Dennis G. Larson, Frank A. Dinenno

Anne R. Crecelius

We tested the hypothesis that, among conditions of matched contractile work, shorter contraction durations and greater muscle fibre recruitment result in augmented skeletal muscle blood flow and oxygen consumption (O2) during steady-state exercise in humans. To do so, we measured forearm blood flow (FBF; Doppler ultrasound) during 4 minutes of rhythmic handgrip exercise in 24 healthy young adults and calculated forearm O2 via blood samples obtained from a catheter placed in retrograde fashion into a deep vein draining the forearm muscle. In Protocol 1 (n = 11), subjects performed rhythmic isometric handgrip exercise at mild and moderate intensities under conditions …

Reactive Hyperemia Occurs Via Activation Of Inwardly-Rectifying Potassium Channels And Na+/K+-Atpase In Humans, Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno

Anne R. Crecelius

Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear. Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (KIR) channels and Na+/K+-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans. Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, we studied 2 groups of 8 …

Isoniazid Completion Rates For Latent Tuberculosis Infection Among College Students Managed By A Community Pharmacist, Karl Hess, Jeffery Goad, Joanne Wu, Kathleen Johnson

Jeff Goad

Objective: The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy oil a college Campus. and to describe patient characteristics. Participants: Participants were university Students diagnosed with LTBI. Methods: The authors conducted a retrospective review, of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken. characteristics of completers versus noncompleters. average time to treatment completion, and reported adverse drug events. Results: The 9-month completion rate was 59%, and the …

Accuracy Of Electrocardiogram Reading By Family Practice Residents, Denise Sur, Lily Kaye, Michael Mikus, Jeffery Goad, Anthony Morena

Jeff Goad

Objectives: This study evaluated the electrocardiogram (EKG) reading skills of family practice residents. Methods: A multicenter study was carried out to evaluate the accuracy of EKG reading in the family practice setting. Based on the frequency and potential for clinical significance, we chose 18 common findings on 10 EKGs for evaluation. The EKGs were then distributed to residents at six family practice residencies. Residents were given one point for the identification of each correct EKG finding and scored based on the number correct over a total of 18. Results: Sixty-one residents (20 first year 23 second year; and 18 third …

A Comparison Of Pharmacist Travel-Health Specialists' Versus Primary Care Providers' Recommendations For Travel-Related Medications, Vaccinations, And Patient Compliance In A College Health Setting, Melissa J. Durham, Jeffery A. Goad, Lawrence S. Neinstein, Mimi Lou

Jeff Goad

Background. Pretravel medication and vaccination recommendations and receipt were compared between primary care providers (PCPs) without special training and clinical pharmacists specializing in pretravel health. Methods. A retrospective chart review of patients seen for pretravel health services in a pharmacist-run travel clinic (PTC) compared to PCPs at a University Student Health Center. Vaccine/medication recommendations were assessed for consistency with national/international guidelines. Medical/pharmacy records were queried to determine the receipt of medications/vaccinations. Results. The PTC recommended antibiotics for travelers' diarrhea were given more often when indicated (96% vs 50%, p < 0.0001), and patients seen in the PTC received their medications more …

Vaccine-Preventable Diseases In Travelers, Edith Mirzaian, Jeffery Goad, Ani Amloian, Fady Makar

Jeff Goad

Travel to the developing world is increasing among those from developed countries, placing them at risk for vaccine preventable and non-vaccine preventable diseases. From 2007-2011, the GeoSentinel Network reported 737 returned travelers with a vaccine preventable disease. While it is essential that clinicians use vaccines when available for a disease of risk, they should also be aware that the vast majority of diseases acquired by travelers are non-vaccine preventable. The vaccine preventable diseases can be divided into routine travel vaccines, special travel vaccines and routine vaccines used for travel. The routine travel vaccines include Hepatitis A and B, typhoid; special …

Intravenous Artesunate For Severe Malaria, Karl M. Hess, Jeffery A. Goad, Paul M. Arguin

Jeff Goad

OBJECTIVE: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria.

DATA SOURCES: Literature was retrieved through PubMed (1999 March 2010), MEDLINE (1996 March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles in English that were identified from the data sources were reviewed. Focus was placed on post-marketing trials examining the safety and efficacy of artesunate in comparison with other regimens.

DATA SYNTHESIS …

Real-Time Mri-Guided Catheter Tracking Using Hyperpolarized Silicon Particles, Nicholas Whiting, Jingzhe Hu, Jay V. Shah, Maja C. Cassidy, Erik Cressman, Niki Zacharias Millward, David G. Menter, Charles M. Marcus, Pratip K. Bhattacharya

Nicholas Whiting

The Effect Of Foam Rolling Duration On Hamstring Range Of Motion, Grace Couture, Dustin Karlic, Stephen Glass, Brian Hatzel

Stephen C Glass

Abstract: Musculoskeletal health benefits from flexibility training and maintaining a functional, or sport specific, range of motion is important to one’s overall fitness. Commercial foam rollers are commonly used in gyms, therapy clinics and homes, yet data are lacking on the optimal rolling duration and effect on range of motion. Purpose: The purpose of this study was to examine the effect of varied durations of a commercial foam roller treatment on hamstring range of motion. Methods: The knee extension range of motion of 33 college aged men and women (age= 20±1.5y, mass= 72.2±10.8 kg) was assessed after a short (2 …

Spin-Exchange Optical Pumping At High Xenon Densities And Laser Fluxes: Principles And Practice, Boyd M. Goodson, Nicholas Whiting, Hayley Newton, Jason G. Skinner, Kaili Ranta, Panayiotis Nikolaou, Michael J. Barlow, Eduard Y. Chekmenev

Nicholas Whiting

Hyperpolarization Methods For Mrs, Boyd M. Goodson, Nicholas Whiting, Aaron M. Coffey, Panayiotis Nikolaou, Fan Shi, Brogan M. Gust, Maxwell E. Gemeinhardt, Roman Shchepin, Jason G. Skinner, Jonathan R. Birchall, Michael J. Barlow, Eduard Y. Chekmenev

Nicholas Whiting