Medicine and Health Sciences Commons^™

Right Ventricular Outflow Tract Obstruction Caused By Double-Chambered Right Ventricle Presenting In Adulthood, John Kokotsakis, Efthymia G Rouska, Leanne Harling, Hutan Ashrafian, Vania Anagnostakou, Christos Charitos, Thanos Athanasiou

The Texas Heart Institute Journal

Congenital heart diseases that cause obstruction of the right ventricular outflow tract are often difficult to diagnose. We report the case of a 49-year-old man who presented with long-standing shortness of breath on exertion. Imaging revealed right ventricular outflow tract obstruction caused by a double-chambered right ventricle, and he was referred for surgical correction. This case emphasizes both the detailed perioperative evaluation that is needed when diagnosing adults who present with manifestations of congenital heart disease and a method of successful surgical correction that resulted in symptom resolution.

Use Of Oversized Injectable Valves In Growing Children For Total Repair Of Right Ventricular Outflow Tract Anomalies (Preliminary Results), Luca Deorsola, Pietro Angelo Abbruzzese

The Texas Heart Institute Journal

Right ventricular outflow tract surgery was originally confined to transannular patching, in the belief that pulmonary regurgitation was well tolerated. Because follow-up evaluations revealed the deleterious effects of pulmonary regurgitation, surgery today aims to spare or replace the valve. Available replacement devices have short lifetimes, considering growth mismatch in children. We hypothesize that oversizing the right infundibulum anticipates growth and that a squeezed prosthesis can complete the expansion process.

The No-React® Injectable BioPulmonic Valve is designed for right infundibular surgery in adults, and hundreds of implants have shown promising results. We used this device for surgery in babies, with the …

Nontyphoidal Cardiac Salmonellosis: Two Case Reports And A Review Of The Literature, Daniel Ortiz, Eric M Siegal, Christopher Kramer, Bijoy K Khandheria, Ernesto Brauer

The Texas Heart Institute Journal

Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary …

Abdominal Fat Suspension Device For Maintaining Normal Cardiorespiratory Function In Patients Undergoing Conscious Sedation During Surgery: A Feasibility Study, Norman F Truong, Joanna C Nathan, Daeun Yoon, Gabriel Ochoa, Marisa Prevost, Sehyun Yun, Z Maria Oden, Mehdi Razavi

The Texas Heart Institute Journal

Obese patients undergoing conscious-sedation surgery have increased perioperative morbidity because their excess abdominal tissue limits diaphragmatic excursion. We describe a simple device that might help attenuate this risk. We created a noninvasive suction device for abdominal suspension. By lifting the burden of excess weight, this device should decrease respiratory effort. To test the feasibility of excess weight removal in relieving cardiac stress, we tested 22 supine, healthy, normal-weight subjects by measuring their heart rates with and without a 13-kg tissue model on their abdomen to simulate excess weight. There was no significant difference in blood oxygen saturation before and after …

The In-Hospital Consultation Today: Whom Does It Best Serve?, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Intravitreal Triamcinolone Acetonide Injection For Macular Edema Due To Central Retinal Vein Occlusion Persisting Despite Multiple Intravitreal Bevacizumab Injections., Rayan A Alshareef, Sunir Garg, Jason Hsu, James Vander, Carl Park, Marc J Spirn

Wills Eye Hospital Papers

PURPOSE: To evaluate the response to intravitreal triamcinolone acetonide for macular edema persisting or recurring despite multiple intravitreal bevacizumab (IVB) treatments for central retinal vein occlusion (CRVO).

METHODS: Retrospective interventional case series of 21 eyes with CRVO from 21 patients who were diagnosed with persistent or recurrent macular edema secondary to CRVO and treated with 0.1mL (4mg) intravitreal triamcinolone acetonide (IVTA) after initial treatment with 3 or more IVB injections. Anatomic and visual responses were the study primary outcomes.

RESULTS: Mean logarithm of the minimum angle of resolution visual acuity was 1.19 (20/316) immediately before IVTA injection, and improved to …

Sleep Environment Risks For Younger And Older Infants., Jeffrey D. Colvin, Vicki Collie-Akers, Christy Schunn, Rachel Y. Moon

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Sudden infant death syndrome and other sleep-related causes of infant mortality have several known risk factors. Less is known about the association of those risk factors at different times during infancy. Our objective was to determine any associations between risk factors for sleep-related deaths at different ages.

METHODS: A cross-sectional study of sleep-related infant deaths from 24 states during 2004-2012 contained in the National Center for the Review and Prevention of Child Deaths Case Reporting System, a database of death reports from state child death review teams. The main exposure was age, divided into younger (0-3 months) and older …

Making A Decision About Trial Participation: The Feasibility Of Measuring Deliberation During The Informed Consent Process For Clinical Trials, Katie Gillies, Glyn Elwyn, Jonathan Cook

Dartmouth Scholarship

Background:

Informed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of ‘informed-ness’ is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making.

Methods:

Potential trial participants who were approached regarding participation in …

Novel Role Of Pancreatic Differentiation 2 In Facilitating Self-Renewal And Drug Resistance Of Pancreatic Cancer Stem Cells., Arokia P. Vaz, Moorthy P. Ponnusamy, Satyanarayana Rachagani, P Dey, Apar Kishor Ganti, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.

METHODS: Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.

RESULTS: A …

Three-Dimensional Carotid Ultrasound Plaque Texture Predicts Vascular Events, Arna Van Engelen, Thapat Wannarong, Grace Parraga, Wiro J Niessen, Aaron Fenster, J David Spence, Marleen De Bruijne

Medical Biophysics Publications

BACKGROUND AND PURPOSE: Carotid ultrasound atherosclerosis measurements, including those of the arterial wall and plaque, provide a way to monitor patients at risk of vascular events. Our objective was to examine carotid ultrasound plaque texture measurements and the change in carotid plaque texture during 1 year in patients at risk of events and to compare these with measurements of plaque volume and other risk factors as predictors of vascular events.

METHODS: We evaluated 298 patients with carotid atherosclerosis using 3-dimensional (3D) ultrasound at baseline and after 1 year and measured carotid plaque volume and 376 measures of plaque texture. Patients …

Methylseleninic Acid Sensitizes Notch3-Activated Ovca429 Ovarian Cancer Cells To Carboplatin., Tiffany J. Tzeng, Lei Cao, Yangxin Fu, Huawei Zeng, Wen-Hsing Cheng

CALS Publications

Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein …

Stag2 Promotes Error Correction In Mitosis By Regulating Kinetochore–Microtubule Attachments, Marianna Kleyman, Lilian Kabeche, Duane A. Compton

Dartmouth Scholarship

Mutations in the STAG2 gene are present in ∼20% of tumors from different tissues of origin. STAG2 encodes a subunit of the cohesin complex, and tumors with loss-of-function mutations are usually aneuploid and display elevated frequencies of lagging chromosomes during anaphase. Lagging chromosomes are a hallmark of chromosomal instability (CIN) arising from persistent errors in kinetochore-microtubule (kMT) attachment. To determine whether the loss of STAG2 increases the rate of formation of kMT attachment errors or decreases the rate of their correction, we examined mitosis in STAG2-deficient cells. STAG2 depletion does not impair bipolar spindle formation or delay mitotic progression. Instead, …

The Relationship Of Cpe To Hiv Dementia: Slain By An Ugly Fact?, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

No abstract provided.

Evaluation Of An Emergency Department Lean Process Improvement Program To Reduce Length Of Stay, Marian J. Vermeulen, Therese A. Stukel, Astrid Guttmann, Brian H. Rowe

Dartmouth Scholarship

In recent years, lean principles have been applied to improve wait times in the emergency department (ED). In 2009, an ED process improvement program based on lean methods was introduced in Ontario as part of a broad strategy to reduce ED length of stay and improve patient flow. This study seeks to determine the effect of this program on ED wait times and quality of care. We conducted a retrospective cohort study of all ED visits at program and control sites during 3 program waves from April 1, 2007, to June 30, 2011, in Ontario, Canada. Time series analyses of …

Dual-Channel Red/Blue Fluorescence Dosimetry With Broadband Reflectance Spectroscopic Correction Measures Protoporphyrin Ix Production During Photodynamic Therapy Of Actinic Keratosis, Stephen Chad Kanick, Scott C. Davis, Yan Zhao, Tayyaba Hasan, Edward V. Maytin, Brian W. Pogue, M Shane Chapman

Dartmouth Scholarship

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for …

Self-Injurious Behaviours Are Associated With Alterations In The Somatosensory System In Children With Autism Spectrum Disorder., Emma G Duerden, Dallas Card, S Wendy Roberts, Kathleen M Mak-Fan, M Mallar Chakravarty, Jason P Lerch, Margot J Taylor

Brain and Mind Institute Researchers' Publications

Children with autism spectrum disorder (ASD) frequently engage in self-injurious behaviours, often in the absence of reporting pain. Previous research suggests that altered pain sensitivity and repeated exposure to noxious stimuli are associated with morphological changes in somatosensory and limbic cortices. Further evidence from postmortem studies with self-injurious adults has indicated alterations in the structure and organization of the temporal lobes; however, the effect of self-injurious behaviour on cortical development in children with ASD has not yet been determined. Thirty children and adolescents (mean age = 10.6 ± 2.5 years; range 7-15 years; 29 males) with a clinical diagnosis of …

Continuous Executive Function Disruption Interferes With Application Of An Information Integration Categorization Strategy., Sarah J Miles, Kazunaga Matsuki, John Paul Minda

Brain and Mind Institute Researchers' Publications

Category learning is often characterized as being supported by two separate learning systems. A verbal system learns rule-defined (RD) categories that can be described using a verbal rule and relies on executive functions (EFs) to learn via hypothesis testing. A nonverbal system learns non-rule-defined (NRD) categories that cannot be described by a verbal rule and uses automatic, procedural learning. The verbal system is dominant in that adults tend to use it during initial learning but may switch to the nonverbal system when the verbal system is unsuccessful. The nonverbal system has traditionally been thought to operate independently of EFs, but …

Profiling Thiol Metabolites And Quantification Of Cellular Glutathione Using Ft-Icr-Ms Spectrometry, Sadakatali S. Gori, Pawel Lorkiewicz, Daniel S. Ehringer, Alex C. Belshoff, Richard M. Higashi, Teresa W-M Fan, Michael H. Nantz

Toxicology and Cancer Biology Faculty Publications

We describe preparation and use of the quaternary ammonium-based α-iodoacetamide QDE and its isotopologue *QDE as reagents for chemoselective derivatization of cellular thiols. Direct addition of the reagents to live cells followed by adduct extraction into n-butanol and analysis by FT-ICR-MS provided a registry of matched isotope peaks from which molecular formulae of thiol metabolites were derived. Acidification to pH 4 during cell lysis and adduct formation further improves the chemoselectivity for thiol derivatization. Examination of A549 human lung adenocarcinoma cells using this approach revealed cysteine, cysteinylglycine, glutathione, and homocysteine as principal thiol metabolites as well as the sulfinic acid …

Death Of A Child In The Emergency Department., Patricia O'Malley, Isabel Barata, Sally Snow, American Academy Of Pediatrics Committee On Pediatric Emergency Medicine, American College Of Emergency Physicians Pediatric Emergency Medicine Committee, Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

The death of a child in the emergency department (ED) is one of the most challenging problems facing ED clinicians. This revised technical report and accompanying policy statement reaffirm principles of patient- and family-centered care. Recent literature is examined regarding family presence, termination of resuscitation, bereavement responsibilities of ED clinicians, support of child fatality review efforts, and other issues inherent in caring for the patient, family, and staff when a child dies in the ED. Appendices are provided that offer an approach to bereavement activities in the ED, carrying out forensic responsibilities while providing compassionate care, communicating the news of …

Death Of A Child In The Emergency Department., American Academy Of Pediatrics Committee On Pediatric Emergency Medicine, American College Of Emergency Physicians Pediatric Emergency Medicine Committee, Emergency Nurses Association Pediatric Committee, Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

The American Academy of Pediatrics, American College of Emergency Physicians, and Emergency Nurses Association have collaborated to identify practices and principles to guide the care of children, families, and staff in the challenging and uncommon event of the death of a child in the emergency department in this policy statement and in an accompanying technical report.

Sex Hormones Regulate Tenofovir-Diphosphate In Female Reproductive Tract Cells In Culture, Zheng Shen, John V. Fahey, Jack E. Bodwell, Marta Rodriguez-Garcia, Angela D.M Kashuba, Charles R. Wira

Dartmouth Scholarship

The conflicting results of recent pre-exposure prophylaxis (PrEP) trials utilizing tenofovir (TFV) to prevent HIV infection in women led us to evaluate the accumulation of intracellular TFV-diphosphate (TFV-DP) in cells from the female reproductive tract (FRT) and whether sex hormones influence the presence of TFV-DP in these cells. Following incubation with TFV, isolated epithelial cells, fibroblasts, CD4⁺ T cells and CD14⁺ cells from the FRT as well as blood CD4⁺ T cells and monocyte-derived macrophages convert TFV to TFV-DP. Unexpectedly, we found that TFV-DP concentrations (fmol/million cells) vary significantly with the cell type analyzed and the site …

Family-Specific, Novel, Deleterious Germline Variants Provide A Rich Resource To Identify Genetic Predispositions For Brcax Familial Breast Cancer., Hongxiu Wen, Yeong C. Kim, Carrie Snyder, Fengxia Xiao, Elizabeth A. Fleissner, Dina Becirovic, Jiangtao Luo, Bradley Downs, Simon Sherman, Kenneth Cowan, Henry T. Lynch, San Ming Wang

Journal Articles: Eppley Institute

BACKGROUND: Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide …

Overt Responses During Covert Orienting., Brian D Corneil, Douglas P Munoz

Brain and Mind Institute Researchers' Publications

A distributed network of cortical and subcortical brain areas controls our oculomotor behavior. This network includes the superior colliculus (SC), which coordinates an ancient visual grasp reflex via outputs that ramify widely within the brainstem and spinal cord, accessing saccadic and other premotor and autonomic circuits. In this Review, we discuss recent results correlating subliminal SC activity in the absence of saccades with diverse components of the visual grasp reflex, including neck and limb muscle recruitment, pupil dilation, and microsaccade propensity. Such subtle manifestations of covert orienting are accessible in the motor periphery and may provide the next generation of …

Non Melanoma Skin Cancer And Subsequent Cancer Risk, Judy R. Rees, M. Scot Zens, Jiang Gui, Maria O. Celaya, Bruce L. Riddle, Margaret R. Karagas

Dartmouth Scholarship

Introduction:

Several studies have shown an increased risk of cancer after non melanoma skin cancers (NMSC) but the individual risk factors underlying this risk have not been elucidated, especially in relation to sun exposure and skin sensitivity to sunlight.

Purpose:

Methods:

Heuristic Modeling Of Carcinogenesis For The Population With Dichotomous Susceptibility To Cancer: A Pancreatic Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool) of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i) determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate) from the observed hazard rate in the …

Obesity And Diabetes Cause Cognitive Dysfunction In The Absence Of Accelerated Β-Amyloid Deposition In A Novel Murine Model Of Mixed Or Vascular Dementia, Dana M. Niedowicz, Valerie L. Reeves, Thomas L. Platt, Katharina Kohler, Tina L. Beckett, David K. Powell, Tiffany L. Lee, Travis R. Sexton, Eun Suk Song, Lawrence D. Brewer, Caitlin S. Latimer, Susan D. Kraner, Kara L. Larson, Sabire Özcan, Christopher M. Norris, Louis B. Hersh, Nada M. Porter, Donna M. Wilcock, Michael Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APP^ΔNL/ΔNLx PS1^P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small …

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

Treatment Preferences Among Problem Drinkers In Primary Care., Daniel Z Lieberman, Anne Cioletti, Suena H Massey, Rochelle S Collantes, Brad B Moore

Psychiatry and Behavioral Sciences Faculty Publications

OBJECTIVE: Alcohol misuse is common among primary care patients, yet many do not receive treatment because doctors believe problem drinkers are "in denial," or are unwilling to change their drinking habits. The real problem, however, may be that patients are being offered treatment modalities that do not meet their needs. This study was designed to measure the acceptability of various treatment options among drinkers who were currently not receiving treatment.

METHOD: Patients in a primary care clinic were given a self-report questionnaire that included: (1) the Alcohol Use Disorders Questionnaire, (2) a measure of readiness to change drinking behavior, and …

Francis F. Maury, M.D. (1840 To 1879): An Often Forgotten Pioneer In Early American Surgery., Guillaume S. Chevrollier, B.S., Scott W. Cowan, Md, Charles J. Yeo, Md, John C. Kairys, Md

Department of Surgery Gibbon Society Historical Profiles

Francis F. Maury (Fig. 1) was born on August 9, 1840, in Danville, Kentucky, where he was raised on a farm by his mother and father. His father was an Episcopal clergyman of Huguenot descent, whose forefathers had fled from France to escape religious persecution. After receiving a Bachelor of Arts degree from Center College in the summer of 1860, he entered medical school at the University of Virginia. After one full term, he matriculated to Philadelphia’s Jefferson Medical College and completed his medical education as a private student under the direction of Dr. Samuel D. Gross.1, 2 He obtained …

Ambroise Paré (1510 To 1590): A Surgeon Centuries Ahead Of His Time., James T. Shen, B.S., Michael Weinstein, Md, Alec C. Beekley, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

In their extensive writings, Hippocrates and Celsus counseled physicians to be knowledgeable in both the medical and surgical management of patient recovery. However, their words fell by the wayside because cutting of the body was forbidden by the Roman Catholic Church. Furthermore, the contemporaneous Arabic medical teachings emphasized tradition and authority over observation and personal experience. This created an ever-growing rift between the schools of surgical and pharmacologic medicine with both groups denying their involvement in the other domain. Surgeons had been plagued by postoperative complications including infection, malnutrition, and muscular wasting for centuries. Surgeons were forced to re-examine how …