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After Avandia: The Use Of Antidiabetic Drugs In Patients With Heart Failure, Khaled I Khalaf, Heinrich Taegtmeyer

The Texas Heart Institute Journal

Managing diabetes mellitus is an ongoing concern, especially in the presence of heart failure. Recent reports have drawn attention to adverse cardiovascular events associated with the use of thiazolidinediones, including rosiglitazone (Avandia). In 2011, the U.S. Food and Drug Administration implemented a stringent “restricted access program” for the prescription of Avandia. Other studies, which have revealed increased mortality rates in association with tight glycemic control, raise serious concerns about managing diabetes in heart-failure patients.

Herein, we provide a perspective on the management of noninsulin-dependent diabetes in patients with heart failure. We point out that thiazolidinediones exert their major effects through …

Hypoplastic Right-Heart Syndrome Presenting As Multiple Miscarriages, Chadi Dib, Philip A Araoz, Norman P Davies, Joseph A Dearani, Naser M Ammash

The Texas Heart Institute Journal

Reversible causes of miscarriage are many, but they affect only 1% of women who are trying to conceive. Herein, we describe the case of a 23-year-old woman who presented for evaluation of repeated miscarriages and was found to have hypoxemia and erythrocytosis. Further evaluation revealed hypoplastic right-heart syndrome with an intracardiac shunt. She underwent hybrid repair with pulmonary valve balloon valvuloplasty, followed by surgery to perform atrial septal defect closure and a Glenn anastomosis. The erythrocytosis and hypoxemia resolved, and she was able to conceive and deliver a healthy baby at term 2 years later.

This is a unique case …

Transcatheter Retrieval And Repositioning Of Embolized Stent From The Right Ventricle In An Infant, Daisuke Kobayashi, Harinder R Singh, Daniel R Turner, Thomas J Forbes, Srinath T Gowda

The Texas Heart Institute Journal

Intracardiac stent embolization is a challenging complication in a small infant. A Palmaz stent was placed across the atrial septum in a 3-month-old boy to relieve symptoms of right-side heart failure. On routine chest radiography one week later, the stent was found to have embolized into the right ventricle. The stent was retrieved and repositioned by means of transcatheter technique, without subsequent complications. We found this method to be a viable alternative to surgery in a high-risk infant. To our knowledge, this is the first report of the successful transcatheter retrieval and repositioning of an expandable intravascular stent from an …

Medical Education On The Brink: 62 Years Of Front-Line Observations And Opinions, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Pulmonary Resection In The 21st Century: The Role Of Robotics, Robert J Cerfolio

The Texas Heart Institute Journal

No abstract provided.

Coronary Arteriovenous Fistulae: The Complexity Of Coronary Artery-To-Coronary Sinus Connections, Todd L Kiefer, Anna Lisa Crowley, James Jaggers, J Kevin Harrison

The Texas Heart Institute Journal

Coronary artery fistulae are a rare cardiovascular anomaly. Even less common are multiple fistulae involving more than 1 coronary artery. Herein we report the case of a 47-year-old woman who had fistulae from both the right coronary and left circumflex coronary arteries draining into the coronary sinus. These lesions we attempted to close percutaneously but subsequently closed surgically. We discuss diagnostic imaging approaches, along with closure indications, closure options, and outcomes.

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments …

Changes In Spirituality Partly Explain Health-Related Quality Of Life Outcomes After Mindfulness-Based Stress Reduction., Jeffrey M Greeson, Daniel M Webber, Moria J Smoski, Jeffrey G Brantley, Andrew G Ekblad, Edward C Suarez, Ruth Quillian Wolever

College of Science & Mathematics Departmental Research

Mindfulness-Based Stress Reduction is a secular behavioral medicine program that has roots in meditative spiritual practices. Thus, spirituality may partly explain Mindfulness-Based Stress Reduction outcomes. Participants (N = 279; M (SD) age = 45(12); 75% women) completed an online survey before and after an 8-week Mindfulness-Based Stress Reduction program. Structural equation modeling was used to test the hypothesis that, following Mindfulness-Based Stress Reduction, the relationship between enhanced mindfulness and improved health-related quality of life is mediated by increased daily spiritual experiences. Changes in both spirituality and mindfulness were significantly related to improvement in mental health. Although the initial mediation hypothesis …

An Automated Internet Application To Help Patients With Bipolar Disorder Track Social Rhythm Stabilization., Daniel Z Lieberman, Susan Swayze, Frederick K Goodwin

Psychiatry and Behavioral Sciences Faculty Publications

This column describes a pilot study of a fully automated, Internet-based program that provides a key element of interpersonal and social rhythm therapy, a form of psychotherapy shown to be effective in the treatment of bipolar disorder when combined with mood-stabilizing medication. Participants (N=64) recorded the time they completed activities of daily living and their mood at the time of each entry. After 90 days they demonstrated a 31% increase in social rhythm stability and a small, though statistically significant, decrease in symptoms of abnormal mood. Internet-based programs can enhance access to a best practice in the management of bipolar …

Margaret Mitchell's Lost Letter To A Kansas Horse Buggy Doctor., Jane F. Knapp, Robert Schremmer

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Erect Wing Facilitates Context-Dependent Wnt/Wingless Signaling By Recruiting The Cell-Specific Armadillo-Tcf Adaptor Earthbound To Chromatin, Nan Xin, Hassina Benchabane, Ai Tian, Kerrie Nguyen, Lindsay Klofas, Yashi Ahmed

Dartmouth Scholarship

During metazoan development, the Wnt/Wingless signal transduction pathway is activated repetitively to direct cell proliferation, fate specification, differentiation and apoptosis. Distinct outcomes are elicited by Wnt stimulation in different cellular contexts; however, mechanisms that confer context specificity to Wnt signaling responses remain largely unknown. Starting with an unbiased forward genetic screen in Drosophila, we recently uncovered a novel mechanism by which the cell-specific co-factor Earthbound 1 (Ebd1), and its human homolog jerky, promote interaction between the Wnt pathway transcriptional co-activators B-catenin/Armadillo and TCF to facilitate context-dependent Wnt signaling responses. Here, through the same genetic screen, we find an unanticipated requirement …

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Regional Gray Matter Correlates Of Perceived Emotional Intelligence, Nancy S. Koven, Robert M. Roth, Matthew A. Garlinghouse, Laura A. Flashman, Andrew J. Saykin

Dartmouth Scholarship

Coping with stressful life events requires a degree of skill in the ability to attend to, comprehend, label, communicate and regulate emotions. Individuals vary in the extent to which these skills are developed, with the term ‘alexithymia’ often applied in the clinical and personality literature to those individuals most compromised in these skills. Although a frontal lobe model of alexithymia is emerging, it is unclear whether such a model satisfactorily reflects brain-related patterns associated with perceived emotional intelligence at the facet level. To determine whether these trait meta-mood facets (ability to attend to, have clarity of and repair emotions) have …

The Meaning Of Breast Cancer Risk For African American Women., Janice Phillips, Marlene Z. Cohen

Journal Articles: College of Nursing

PURPOSE: To describe African American women's experience of being at high risk for breast cancer.

DESIGN: A hermeneutic phenomenological approach was used to guide in-depth interviews and analysis. Methods to ensure trustworthiness and rigor were included.

METHODS: Open interviews were conducted with 20 African American women who were at high risk for breast cancer (family history, personal history, genetic mutation). They were recruited from a cancer risk clinic and community-based settings. Data were transcribed verbatim, and themes were labeled among and between all interviews.

FINDINGS: Five themes were identified: (a) life-changing experience; (b) relationships: fears, support, and concerns; (c) the …

Assessing Medicare Beneficiaries’ Strength‐Of‐Preference Scores For Health Care Options: How Engaging Does The Elicitation Technique Need To Be?, Trafford Crump, Hilary A. Llewellyn-Thomas

Dartmouth Scholarship

The objective was to determine if participants’ strength‐of‐preference scores for elective health care interventions at the end‐of‐life (EOL) elicited using a non‐engaging technique are affected by their prior use of an engaging elicitation technique.

Decision Quality Instrument For Treatment Of Hip And Knee Osteoarthritis: A Psychometric Evaluation, Karen R. Sepucha, Dawn Stacey, Catharine F. Clay, Yuchiao Chang

Dartmouth Scholarship

A high quality decision requires that patients who meet clinical criteria for surgery are informed about the options (including non-surgical alternatives) and receive treatments that match their goals. The aim of this study was to evaluate the psychometric properties and clinical sensibility of a patient self report instrument, to measure the quality of decisions about total joint replacement for knee or hip osteoarthritis.

Recruitment And Retention Of Diverse Populations In Antiretroviral Clinical Trials: Practical Applications From The Gender, Race And Clinical Experience Study., Ron Falcon, Dawn Averitt Bridge, Judith Currier, Kathleen Squires, Debbie Hagins, Deborah Schaible, Robert Ryan, Joseph Mrus

Division of Infectious Diseases and Environmental Medicine Faculty Papers

BACKGROUND: Women, particularly women of color, remain underrepresented in antiretroviral (ARV) clinical trials. To evaluate sex-based differences in darunavir/ritonavir-based therapy, the Gender, Race And Clinical Experience (GRACE) study was designed to enroll and retain a high proportion of women representative of the racial/ethnic demographics of women with HIV/AIDS in the United States. The recruitment and retention strategies used in GRACE are described in this article.

METHODS: Recruitment and retention strategies targeting women included selecting study sites that focused on women, involving community consultants, site-specific enrollment plans, access to other ARV drugs, study branding, site and patient toolkits, targeted public relations, …

Tnfα Enhances The Motility And Invasiveness Of Prostatic Cancer Cells By Stimulating The Expression Of Selective Glycosyl- And Sulfotransferase Genes Involved In The Synthesis Of Selectin Ligands., Prakash Radhakrishnan, Vishwanath Chachadi, Ming-Fong Lin, Rakesh Singh, Reiji Kannagi, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Sialyl Lewis x (sLe(x)) plays an important role in cancer metastasis. But, the mechanism for its production in metastatic cancers remains unclear. The objective of current study was to examine the effects of a proinflammatory cytokine on the expression of glycosyltransferase and sulfotransferase genes involved in the synthesis of selectin ligands in a prostate cancer cell line. Androgen-independent human lymph node-derived metastatic prostate cancer cells (C-81 LNCaP), which express functional androgen receptor and mimic the castration-resistant advanced prostate cancer, were used. TNFα treatment of these cells increased their binding to P-, E- and L-selectins, anti-sLe(x) antibody, and anti-6-sulfo-sialyl Lewis x …

Outcomes Of Treatment For Hepatitis C Virus Infection By Primary Care Providers, Sanjeev Arora, Karla Thornton, Glen Murata, Paulina Deming, Summers Kalishman, Denise Dion, Brooke Parish, Thomas Burke, Wesley Pak, Jeffrey Dunkelberg, Martin Kistin, John Brown, Steven Jenkusky, Miriam Komaromy, Clifford Qualls

Project ECHO Bibliography

BACKGROUND: The Extension for Community Healthcare Outcomes (ECHO) model was developed to improve access to care for underserved populations with complex health problems such as hepatitis C virus (HCV) infection. With the use of video-conferencing technology, the ECHO program trains primary care providers to treat complex diseases.

METHODS: We conducted a prospective cohort study comparing treatment for HCV infection at the University of New Mexico (UNM) HCV clinic with treatment by primary care clinicians at 21 ECHO sites in rural areas and prisons in New Mexico. A total of 407 patients with chronic HCV infection who had received no previous …

Partnering Urban Academic Medical Centers And Rural Primary Care Clinicians To Provide Complex Chronic Disease Care, Sanjeev Arora, Summers Kalishman, Denise Dion, Dara Som, Karla Thornton, Arthur Bankhurst, Jeanne Boyle, Michelle Harkins, Kathleen Moseley, Glen Murata, Miriam Komaramy, Joanna Katzman, Kathleen Colleran, Paulina Deming, Sean Yutzy

Project ECHO Bibliography

Many of the estimated thirty-two million Americans expected to gain coverage under the Affordable Care Act are likely to have high levels of unmet need because of various chronic illnesses and to live in areas that are already underserved. In New Mexico an innovative new model of health care education and delivery known as Project ECHO (Extension for Community Healthcare Outcomes) provides high-quality primary and specialty care to a comparable population. Using state-of-the-art telehealth technology and case-based learning, Project ECHO enables specialists at the University of New Mexico Health Sciences Center to partner with primary care clinicians in underserved areas …

Phase 1 Pilot Study Of E-Mail Support For People With Long Term Conditions Using The Internet., Bryony Sheaves, Ray B. Jones, Graham R. Williamson, Rohan Chauhan

School of Nursing and Midwifery

BACKGROUND: Use of the Internet for people with Long Term Conditions (LTCs) can have a positive effect on knowledge, social support, behavioural and clinical outcomes, yet there is concern that a 'digital divide' prevents some patients from benefitting. While some patients do not have access to the Internet, others that do may still lack expertise or the confidence to make full use of it. The aim of this pilot study was to develop an intervention and test methods for a definitive randomised controlled trial (RCT) of anonymous personal online email support for patients in this latter group. METHODS: Recruitment success …

Response To An Abnormal Ovarian Cancer-Screening Test Result: Test Of The Social Cognitive Processing And Cognitive Social Health Information Processing Models, Michael A. Andrykowski, Edward J. Pavlik

Behavioral Science Faculty Publications

All cancer screening tests produce a proportion of abnormal results requiring follow up. Consequently, the cancer-screening setting is a natural laboratory for examining psychological and behavioural response to a threatening health-related event. This study tested hypotheses derived from the social cognitive processing and cognitive-social health information processing models in trying to understand response to an abnormal ovarian cancer (OC) screening test result. Women (n = 278) receiving an abnormal screening test result a mean of 7 weeks earlier were assessed prior to a repeat screening test intended to clarify their previous abnormal result. Measures of disposition (optimism, informational coping style), …

An Evaluation Of Hospital Breastfeeding Policies In The Philadelphia Metropolitan Area 1994-2009: A Comparison With The Baby-Friendly Hospital Initiative Ten Steps., Andrea Crivelli-Kovach, Esther K Chung

Department of Pediatrics Faculty Papers

OBJECTIVE: The purpose of this study was to describe current breastfeeding policies and practices among Philadelphia, PA metropolitan hospitals and changes in their policies and practices over time.

METHODS: In-person group interviews were conducted to obtain a composite picture of actual breastfeeding policies and practices. One questionnaire per hospital was completed based on responses from group consensus. Twenty-five hospitals providing maternity care were contacted. Information was obtained from personnel representing different areas of maternity services. Hospitals were classified according to the degree to which they were implementing the Ten Steps to Successful Breastfeeding.

RESULTS: Mean breastfeeding rates at suburban hospitals …

Regulation Of The Androgen Receptor By Set9-Mediated Methylation., Luke Gaughan, Jacqueline Stockley, Nan Wang, Stuart R C Mccracken, Achim Treumann, Kelly Armstrong, Fadhel Shaheen, Kate Watt, Iain J Mcewan, Chenguang Wang, Richard Pestell, Craig N Robson

Kimmel Cancer Center Faculty Papers

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain …

Targeted Drug-Resistance Testing Strategy For Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008, Gustavo E. Velásquez, Martin Yagui, J Peter Cegielski, Luis Asencios, Jaime Bayona, Cesar Bonilla, Hector O. Jave, Gloria Yale, Carmen Suárez, Sidney Atwood, Carmen C. Contreras, Sonya S. Shin

Dartmouth Scholarship

The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005–November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household …

Nonuniform High-Gamma (60-500 Hz) Power Changes Dissociate Cognitive Task And Anatomy In Human Cortex, Charles M. Gaona, Mohit Sharma, Zachary V. Freudenburg, Jonathan D. Breshears, David T. Bundy, Jarod Roland, Dennis L. Barbour, Gerwin Schalk, Eric C. Leuthardt

Open Access Publications

High-gamma-band (>60 Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. Despite discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma-band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60 Hz. Based on nonuniformities in time-frequency analyses of electrocorticographic (ECoG) signals, we hypothesized that …

Does Treatment Of Premature Labor With Terbutaline Increase The Risk Of Autism Spectrum Disorders?, Patricia Rodier, Richard K Miller, Robert L Brent

Department of Pediatrics Faculty Papers

Beta-adrenergic agents have been used in pregnant women for the treatment of premature labor and for the treatment of asthma. Concerns have been expressed that exposure to terbutaline, a beta-2 adrenergic agonist, may increase the risk of autism spectrum disorders (ASDs) in the offspring. This hypothesis deserves critical review, given the number of patients exposed to the drug in the last two decades. The results are important to both the obstetricians and patients who weigh the risks and benefits of interventions and to the pediatricians who counsel the families of affected children.

Steroids Up-Regulate P66shc Longevity Protein In Growth Regulation By Inhibiting Its Ubiquitination., Santosh Kumar, Satyendra Kumar, Mythilypriya Rajendran, Syed Mahfuzul Alam, Fen-Fen Lin, Pi-Wan Cheng, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: p66Shc, an isoform of Shc adaptor proteins, mediates diverse signals, including cellular stress and mouse longevity. p66Shc protein level is elevated in several carcinomas and steroid-treated human cancer cells. Several lines of evidence indicate that p66Shc plays a critical role in steroid-related carcinogenesis, and steroids play a role in its elevated levels in those cells without known mechanism.

METHODS AND FINDINGS: In this study, we investigated the molecular mechanism by which steroid hormones up-regulate p66Shc protein level. In steroid-treated human prostate and ovarian cancer cells, p66Shc protein levels were elevated, correlating with increased cell proliferation. These steroid effects on …

Neuroinflammation Leads To Region-Dependent Alterations In Astrocyte Gap Junction Communication And Hemichannel Activity., Nikolay Karpuk, Maria Burkovetskaya, Teresa Fritz, Amanda Angle, Tammy Kielian

Journal Articles: Pathology and Microbiology

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, …

Efficacy And Safety Of Once-Daily Aclidinium In Chronic Obstructive Pulmonary Disease, Paul W. Jones, Stephen I. Rennard, Alvar Agusti, Pascal Chanez, Helgo Magnussen, Leonardo Fabbri, James F. Donohue, Eric D. Bateman, Nicholas J. Gross, Rosa Lamarca, Cynthia Caracta, Esther Garcia Gil

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

METHODS: In two double-blind, 52-week studies, ACCLAIM/COPD I (n=843) and II (n=804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1< 80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.

RESULTS: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p< 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p< 0.001). More patients had a SGRQ improvement≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p=0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p=0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p=0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p=0.9). Adverse events were minor in both studies.

CONCLUSION: Aclidinium is effective and well tolerated …