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Longitudinal Changes In Vascular Risk Markers And Mortality Rates Among A Latino Population With Hypertension, Matthew C Pflederer, Carlin S Long, Brenda Beaty, Edward P Havranek, Philip S Mehler, Angela Keniston, Mori J Krantz

The Texas Heart Institute Journal

Vascular markers such as pulse-wave velocity and carotid intima-media thickness (CIMT) might improve the prediction of incident cardiovascular disease beyond traditional risk factors. These vascular markers have not been well characterized in minority populations and might be more useful than inflammatory biomarkers. We conducted a prospective, longitudinal cohort study among hypertensive patients in an urban safety-net hospital. We evaluated inflammatory biomarkers, arterial pulse-wave velocity, and carotid intima-media thickness at baseline, 1 year, and 2 years. The primary outcome variable was CIMT. Generalized linear mixed-effects models were used to evaluate associations between CIMT and predictive variables accounting for the correlation of …

Medical Therapy For Inappropriate Sexual Behaviors In A Teen With Autism Spectrum Disorder., Loyal Coshway, Julia Broussard, Kruti Acharya, Karen Fried, Michael E. Msall, John Lantos, Leena Nahata

Manuscripts, Articles, Book Chapters and Other Papers

Teens with autism spectrum disorder often exhibit sexual behaviors in public that are disturbing to parents, teachers, and peers. Some have proposed that such behaviors can be curtailed with hormonal suppression. There is information on the Internet suggesting that such medications work, and some reports in the peer-reviewed medical literature support these claims. Such medications can have serious side effects. In this paper, we present a case in which parents requested such treatment of their teenage son with autism spectrum disorder.

Rebound Growth Of Infantile Hemangiomas After Propranolol Therapy., Sonal D. Shah, Eulalia Baselga, Catherine Mccuaig, Elena Pope, Julien Coulie, Laurence M. Boon, Maria C. Garzon, Anita N. Haggstrom, Denise Adams, Beth A. Drolet, Brandon D. Newell, Julie Powell, Maria Teresa García-Romero, Carol Chute, Esther Roe, Dawn H. Siegel, Barbara Grimes, Ilona J. Frieden

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Propranolol is first-line therapy for problematic infantile hemangiomas (IHs). Rebound growth after propranolol discontinuation is noted in 19% to 25% of patients. Predictive factors for rebound are not completely understood and may alter the management approach. The goal of the study was to describe a cohort of patients with IHs treated with propranolol and to identify predictors for rebound growth.

METHODS: A multicenter retrospective cohort study was conducted in patients with IHs treated with propranolol. Patient demographic characteristics, IH characteristics, and specifics of propranolol therapy were obtained. Episodes of rebound growth were recorded. Patients' responses to propranolol …

Evidence That A Lipolytic Enzyme—Hematopoietic-Specific Phospholipase C-Β2—Promotes Mobilization Of Hematopoietic Stem Cells By Decreasing Their Lipid Raft-Mediated Bone Marrow Retention And Increasing The Promobilizing Effects Of Granulocytes, M. Adamiak, A. Poniewierska-Baran, S. Borkowska, G. Schneider, A. Abdelbaset-Ismail, M. Suszynska, Ahmed Abdel-Latif, M. Kucia, J. Ratajczak, M. Z. Ratajczak

Internal Medicine Faculty Publications

Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α₄β₁-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an …

An In Vivo Model For Postinflammatory Hyperpigmentation: An Analysis Of Histological, Spectroscopic, Colorimetric And Clinical Traits, P. Isedeh, Indermeet Kohli, Mohammed Al-Jamal, O. N. Agbai, M. Chaffins, Suneetha Devpura, Meredith Mahan, G. Vanderover, Henry W. Lim, M. S. Matsui, Iltefat H. Hamzavi

Dermatology Articles

BACKGROUND: Acne vulgaris is a common condition that occurs in all skin types. Postinflammatory hyperpigmentation (PIH) is often associated with acne in patients of darker skin types, making it a common complaint in dermatology offices. Despite this, there is limited understanding of and effective treatment options for PIH.

OBJECTIVES: The study objective was to validate an in vivo model for PIH and to compare the clinical, histological and spectroscopic characteristics of artificially induced PIH and acne-induced PIH.

METHODS: A nonblinded, nonrandomized pilot study was performed. Thirty subjects served as their own control in which four sites treated with 35% trichloroacetic …

The Liberty Study: Design Of A Prospective, Observational, Multicenter Trial To Evaluate The Acute And Long-Term Clinical And Economic Outcomes Of Real-World Endovascular Device Interventions In Treating Peripheral Artery Disease., George L Adams, Jihad Mustapha, William Gray, Nick J Hargus, Brad J Martinsen, Gary Ansel, Michael R Jaff

Heart and Vascular Articles

Background: Most peripheral artery disease (PAD) clinical device trials are supported by commercial manufacturers and designed for regulatory device approval, with extensive inclusion/exclusion criteria to support homogeneous patient populations. High-risk patients with advanced disease, including critical limb ischemia (CLI), are often excluded leading to difficulty in translating trial results into real-world clinical practice. As a result, physicians have no direct guidance regarding the use of endovascular devices. There is a need for objectively assessed studies to evaluate clinical, functional, and economic outcomes in PAD patient populations.

Study design: LIBERTY is a prospective, observational, multicenter study sponsored by Cardiovascular Systems Inc …

Urgent Care And Emergency Department Visits In The Pediatric Medicaid Population., Amanda Montalbano, Jonathan Rodean, Juhi Kangas, Brian R. Lee, Matt Hall

Manuscripts, Articles, Book Chapters and Other Papers

Background: Urgent care (UC) is one of the fastest growing venues of health care delivery. We compared clinical and cost attributes of pediatric UC and emergency department (ED) visits that did not result in admission.

Methods: Our study examined 5 925 568 ED and UC visits of children under 19 years old in the 2010 through 2012 Marketscan Medicaid Multi-State Database. Basic demographics, diagnoses, severity, and payments were compared. Between ED and UC visits, χ(2) tests were used for proportions and Wilcoxon rank-sum tests were used for continuous variables.

Results: The UC and ED had the same most common diagnoses. …

Reliability And Validity Of An Observational Measure Of Client Decision-Making: The Client Language Assessment - Proximal/Distal (Cla-Pd)., Molly Magill, Timothy R. Apodaca, Mitchell Karno, Jacques Gaume, Ayla Durst, Justin Walthers, Robert L. Stout, Carlo Diclemente

Manuscripts, Articles, Book Chapters and Other Papers

OVERVIEW: The Client Language Assessment - Proximal/Distal (CLA-PD) is a language rating system for measuring client decision-making in interventions that target a specified behavior change (e.g., alcohol or other drug use). In the CLA-PD, there are five dimensions of change language (Reason, Ability, Commitment, Taking Steps, Other) adapted from the client portion of the Motivational Interviewing Skill Code (MISC). For the CLA-PD, language codes are sub-divided to discriminate statements regarding the primary, or target behavior change (distal change) from the intermediate coping activities (proximal change) that are prescribed to facilitate that target behavior change. The goal of the CLA-PD is …

Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.

STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.

RESULTS: Annualized GFR change in subjects …

The Genomic Cds Sandbox: An Assessment Among Domain Experts., Ayesha Aziz, Kensaku Kawamoto, Karen Eilbeck, Marc S Williams, Robert R Freimuth, Mark A Hoffman, Luke V Rasmussen, Casey L Overby, Brian H Shirts, James M Hoffman, Brandon M Welch

Manuscripts, Articles, Book Chapters and Other Papers

Genomics is a promising tool that is becoming more widely available to improve the care and treatment of individuals. While there is much assertion, genomics will most certainly require the use of clinical decision support (CDS) to be fully realized in the routine clinical setting. The National Human Genome Research Institute (NHGRI) of the National Institutes of Health recently convened an in-person, multi-day meeting on this topic. It was widely recognized that there is a need to promote the innovation and development of resources for genomic CDS such as a CDS sandbox. The purpose of this study was to evaluate …

Alcohol Toxicity In Diabetes And Its Complications: A Double Trouble?, Srikar Munukutla, Guodong Pan, Mandar Deshpande, Rajarajan A. Thandavarayan, Prasanna Krishnamurthy, Suresh S. Palaniyandi

Hypertension and Vascular Research Articles

BACKGROUND: Eight percent of the U.S. population has been diagnosed with diabetes mellitus (DM), while another large percentage has gone undiagnosed. As the epidemiology of this disease constitutes a larger percentage of the American population, another factor presents a dangerous dilemma that can exacerbate the hazardous effects imposed by DM. Excessive alcohol consumption concerns the health of more than 50% of all adults. When this heavy-alcohol-drinking population overlaps with DM and its complications, the effects can be dangerous. In this review, we term it as "double trouble."

METHODS: We provide evidence of alcohol-induced exacerbation of organ damage in diabetic conditions. …

Peripheral (Deep) But Not Periventricular Mri White Matter Hyperintensities Are Increased In Clinical Vascular Dementia Compared To Alzheimer's Disease, Charles D. Smith, Eleanor S. Johnson, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Richard J. Kryscio, Richard R. Murphy, Clinton V. Wellnitz

Neurology Faculty Publications

Background and purpose: Vascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer's disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum. In this study, we sought to show whether the amount of WMH in deep white matter (dWMH), versus periventricular white matter (PVH), would aid in the distinction between VAD and AD, independent of age. Methods: Blinded semiquantitative ratings of WMH validated by objective quantitation of WMH volume from standardized MRI image acquisitions. …

Protease-Activated Receptor 4 Induces Bladder Pain Through High Mobility Group Box-1, Dimitrios E. Kouzoukas, Fei Ma, Katherine L. Meyer-Siegler, Karin N. Westlund, David E. Hunt, Pedro L. Vera

Physiology Faculty Publications

Pain is the significant presenting symptom in Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS). Activation of urothelial protease activated receptor 4 (PAR4) causes pain through release of urothelial macrophage migration inhibitory factor (MIF). High Mobility Group Box-1 (HMGB1), a chromatin-binding protein, mediates bladder pain (but not inflammation) in an experimental model (cyclophosphamide) of cystitis. To determine if PAR4-induced bladder hypersensitivity depends on HMGB1 downstream, we tested whether: 1) bladder PAR4 stimulation affected urothelial HMGB1 release; 2) blocking MIF inhibited urothelial HMGB1 release; and 3) blocking HMGB1 prevented PAR4-induced bladder hypersensitivity. HMGB1 release was examined in immortalized human urothelial cultures (UROtsa) exposed to …

Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan

Internal Medicine Faculty Publications

Background: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes.

Methods: …

Variants In Cxcr4 Associate With Juvenile Idiopathic Arthritis Susceptibility., Terri H. Finkel, Jin Li, Zhi Wei, Wei Wang, Haitao Zhang, Edward M. Behrens, Emma L. Reuschel, Sophie Limou, Carol Wise, Marilynn Punaro, Mara L. Becker, Jane E. Munro, Berit Flatø, Øystein Førre, Susan D. Thompson, Carl D. Langefeld, David N. Glass, Joseph T. Glessner, Cecilia E. Kim, Edward Frackelton, Debra K. Shivers, Kelly A. Thomas, Rosetta M. Chiavacci, Cuiping Hou, Kexiang Xu, James Snyder, Haijun Qiu, Frank Mentch, Kai Wang, Cheryl A. Winkler, Benedicte A. Lie, Justine A. Ellis, Hakon Hakonarson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, the etiology of which involves a strong genetic component, but much of the underlying genetic determinants still remain unknown. Our aim was to identify novel genetic variants that predispose to JIA.

METHODS: We performed a genome-wide association study (GWAS) and replication in a total of 1166 JIA cases and 9500 unrelated controls of European ancestry. Correlation of SNP genotype and gene expression was investigated. Then we conducted targeted resequencing of a candidate locus, among a subset of 480 cases and 480 controls. SUM test was performed …

Arf6 Controls Platelet Spreading And Clot Retraction Via Integrin ΑIibΒ3 Trafficking, Yunjie Huang, Smita Joshi, Binggang Xiang, Yasunori Kanaho, Zhenyu Li, Beth A. Bouchard, Carole L. Moncman, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

Platelet and megakaryocyte endocytosis is important for loading certain granule cargo (ie, fibrinogen [Fg] and vascular endothelial growth factor); however, the mechanisms of platelet endocytosis and its functional acute effects are understudied. Adenosine 5'-diphosphate–ribosylation factor 6 (Arf6) is a small guanosine triphosphate–binding protein that regulates endocytic trafficking, especially of integrins. To study platelet endocytosis, we generated platelet-specific Arf6 knockout (KO) mice. Arf6 KO platelets had less associated Fg suggesting that Arf6 affects α_IIbβ₃-mediated Fg uptake and/or storage. Other cargo was unaffected. To measure Fg uptake, mice were injected with biotinylated- or fluorescein isothiocyanate (FITC)–labeled Fg. Platelets …

Toward Earlier Inclusion Of Pregnant And Postpartum Women In Tuberculosis Drug Trials: Consensus Statements From An International Expert Panel., Amita Gupta, Jyoti S. Mathad, Susan M. Abdel-Rahman, Jessica D. Albano, Radu Botgros, Vikki Brown, Renee S. Browning, Liza Dawson, Kelly E. Dooley, Devasena Gnanashanmugam, Beatriz Grinsztejn, Sonia Hernandez-Diaz, Patrick Jean-Philippe, Peter Kim, Anne D. Lyerly, Mark Mirochnick, Lynne M. Mofenson, Grace Montepiedra, Jeanna Piper, Leyla Sahin, Radojka Savic, Betsy Smith, Hans Spiegel, Soumya Swaminathan, D Heather Watts, Amina White

Manuscripts, Articles, Book Chapters and Other Papers

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human …

Heart Rhythm Monitoring Strategies For Cryptogenic Stroke: 2015 Diagnostics And Monitoring Stroke Focus Group Report., Gregory W. Albers, Richard A. Bernstein, Johannes Brachmann, John Camm, J. Donald Easton, Peter Fromm, Shinya Goto, Christopher B. Granger, Stefan H. Hohnloser, Elaine Hylek, Amir K. Jaffer, Derk W. Krieger, Rod Passman, Jesse M. Pines, Shelby D. Reed, Peter M. Rothwell, Peter R. Kowey

Department of Medicine Faculty Papers

No abstract provided.

Ubiquitin-Specific Peptidase 10 (Usp10) Deubiquitinates And Stabilizes Muts Homolog 2 (Msh2) To Regulate Cellular Sensitivity To Dna Damage, Mu Zhang, Chen Hu, Dan Tong, Shengyan Xiang, Kendra Williams, Wenlong Bai, Guo-Min Li, Gerold Bepler, Xiaohong Zhang

Toxicology and Cancer Biology Faculty Publications

MSH2 is a key DNA mismatch repair protein, which plays an important role in genomic stability. In addition to its DNA repair function, MSH2 serves as a sensor for DNA base analogs-provoked DNA replication errors and binds to various DNA damage-induced adducts to trigger cell cycle arrest or apoptosis. Loss or depletion of MSH2 from cells renders resistance to certain DNA-damaging agents. Therefore, the level of MSH2 determines DNA damage response. Previous studies showed that the level of MSH2 protein is modulated by the ubiquitin-proteasome pathway, and histone deacetylase 6 (HDAC6) serves as an ubiquitin E3 ligase. However, the deubiquitinating …

Smn Protein Can Be Reliably Measured In Whole Blood With An Electrochemiluminescence (Ecl) Immunoassay: Implications For Clinical Trials, Phillip Zaworski, Katharine M. Von Herrmann, Shannon Taylor, Sara S. Sunshine, Kathleen Mccarthy, Nicole Risher, Tara Newcomb, Marla Weetall, Thomas W. Prior, Kathryn J. Swoboda, Karen S. Chen, Sergey Paushkin

Dartmouth Scholarship

Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5μL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, …

Restricted Mobility Of Specific Functional Groups Reduces Anti-Cancer Drug Activity In Healthy Cells, Murillo L. Martins, Rosanna Ignazzi, Juergen Eckert, Benjamin Watts, Ramon Kaneno, Willian F Zambuzzi, Luke Daemen, Margarida J Saeki, Heloisa N Bordallo

Chemistry Faculty Publications

The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the …

Managing Agitation Associated With Schizophrenia And Bipolar Disorder In The Emergency Setting, Scott Zeller, Leslie Citrome

NYMC Faculty Publications

INTRODUCTION: Patient agitation represents a significant challenge in the emergency department (ED), a setting in which medical staff are working under pressure dealing with a diverse range of medical emergencies. The potential for escalation into aggressive behavior, putting patients, staff, and others at risk, makes it imperative to address agitated behavior rapidly and efficiently. Time constraints and limited access to specialist psychiatric support have in the past led to the strategy of "restrain and sedate," which was believed to represent the optimal approach; however, it is increasingly recognized that more patient-centered approaches result in improved outcomes. The objective of this …

Depressive And Anxiety Symptoms Predict Sustained Quality Of Life Deficits In Hiv-Positive Ugandan Adults Despite Antiretroviral Therapy: A Prospective Cohort Study., Amara E. Ezeamama, Makhabele N. Woolfork, David Guwatudde, Danstan Bagenda, Yukari C. Manabe, Wafaie W. Fawzi, Mary C. Smith Fawzi

Journal Articles: Epidemiology

The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period.Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in …

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

Fear Conditioning And Extinction In Youth With Obsessive-Compulsive Disorder, Joseph F. Mcguire, Scott P. Orr, Monica S. Wu, Adam B. Lewin, Brent J. Small, Vicky Phares, Tanya K. Murphy, Sabine Wilhelm, Daniel S. Pine, Daniel Geller, Eric A. Storch

Psychology Faculty Publications

BACKGROUND: Fear acquisition and extinction are central constructs in the cognitive-behavioral model of obsessive-compulsive disorder (OCD), which underlies exposure-based cognitive-behavioral therapy (CBT). Youth with OCD may have impairments in fear acquisition and extinction that carry treatment implications. We examined these processes using a differential conditioning procedure.

METHODS: Forty-one youth (19 OCD, 22 community comparisons) completed a battery of clinical interviews, rating scales, and a differential conditioning task that included habituation, acquisition, and extinction phases. Skin conductance response (SCR) served as the primary dependent measure.

RESULTS: During habituation, no difference between groups was observed. During acquisition, differential fear conditioning was observed …

Antimicrobial Stewardship Barriers And Goals In Pediatric Oncology And Bone Marrow Transplantation: A Survey Of Antimicrobial Stewardship Practitioners., Joshua Wolf, Yilun Sun, Li Tang, Jason G. Newland, Jeffrey S. Gerber, Christie J. Van Dyke, Saul R. Hymes, Diana Yu, Delia C. Carias, Penelope A. Bryant, Pediatric Hematology/Oncology Antimicrobial Stewardship Interest Group

Manuscripts, Articles, Book Chapters and Other Papers

We undertook a cross-sectional survey of antimicrobial stewardship clinicians in North America and Australasia regarding practices, goals, and barriers to implementation of stewardship for pediatric oncology patients. Goals and barriers were similar regardless of clinician or institutional characteristics and geographic location. Strategies addressing these factors could help optimize antimicrobial use.

Pharmacokinetics And Bioequivalence Of A Liquid Formulation Of Hydroxyurea In Children With Sickle Cell Anemia., Jeremie H. Estepp, Chiara Melloni, Courtney D. Thornburg, Paweł Wiczling, Zora Rogers, Jennifer A. Rothman, Nancy S. Green, Robert Liem, Amanda M. Brandow, Shelley E. Crary, Thomas H. Howard, Maurine H. Morris, Andrew Lewandowski, Uttam Garg, William J. Jusko, Kathleen A. Neville, Best Pharmaceuticals For Children Act-Pediatric Trials Network Administrative Core Committee

Manuscripts, Articles, Book Chapters and Other Papers

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability …

Big Data Transforms Discovery-Utilization Therapeutics Continuum., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems-level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical-, and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across …

Retigabine Holds Kv7 Channels Open And Stabilizes The Resting Potential, Aaron Corbin-Leftwich, Sayeed M. Mossadeq, Junghoon Ha, Iwona Ruchala, Audrey Han Ngoc Le, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 …

When A Surgical Colleague Makes An Error., Ryan M. Antiel, Thane A. Blinman, Rebecca M. Rentea, Katherine W. Gonzalez, E Marty Marty Knott, David Juang, Tolulope A. Oyetunji, G W. Holcomb Iii, Peter Angelos, John D. Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Professionalism requires that doctors acknowledge their errors and figure out how to avoid making similar ones in the future. Over the last few decades, doctors have gotten better at acknowledging mistakes and apologizing to patients when a mistake happens. Such disclosure is especially complicated when one becomes aware of an error made by a colleague. We present a case in which consultant surgeons became aware that a colleague seemed to have made a serious error. Experts in surgery and bioethics comment on appropriate responses to this situation.