Digital Commons Network^™

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …

Open Versus Laparoscopic Hiatal Hernia Repair., Terrence M. Fullum, Tolulope A. Oyetunji, Gezzer Ortega, Daniel D. Tran, Ian M. Woods, Olusola Obayomi-Davies, Orighomisan Pessu, Stephanie R. Downing, Edward E. Cornwell

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The literature reports the efficacy of the laparoscopic approach to paraesophageal hiatal hernia repair. However, its adoption as the preferred surgical approach and the risks associated with paraesophageal hiatal hernia repair have not been reviewed in a large database.

METHOD: The Nationwide Inpatient Sample dataset was queried from 1998 to 2005 for patients who underwent repair of a complicated (the entire stomach moves into the chest cavity) versus uncomplicated (only the upper part of the stomach protrudes into the chest) paraesophageal hiatal hernia via the laparoscopic, open abdominal, or open thoracic approach. A multivariate analysis was performed controlling for …

Incomplete Polyp Resection During Colonoscopy—Results Of The Complete Adenoma Resection (Care) Study, Heiko Pohl, Amitabh Srivastava, Steve P. Bensen, Peter Anderson, Richard I. Rothstein, Stuart R. Gordon, L Campbell Levy, Arifa Toor, Todd A. Mackenzie, Thomas Rosch, Douglas J. Robertson

Dartmouth Scholarship

Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice.We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. …

The Ambiguity Of Panem: Capitalism, Nationalism, And Sexuality In Suzanne Collins' The Hunger Games Series, Megan Ann Peters

All Graduate Theses, Dissertations, and Other Capstone Projects

The publication of and the critical and public success of Suzanne Collins' The Hunger Games trilogy marks a significant departure from the norms of traditionally-popular young adult literature, particularly in its portrayal of a fiercely active female protagonist. This thesis argues that despite the noticeable progress these novels make in representing a strong female character, The Hunger Games series fails to adequately challenge other important aspects of oppression. I conduct a feminist literary analysis of The Hunger Games, Catching Fire, and Mockingjay, focusing specifically on representations of capitalism and commodification, national and district pride, and sexual objectification and sexual harassment …

Nitric Oxide Affects Short-Term Olfactory Memory In The Antennal Lobe Of Manduca Sexta, S. L. Gage, K. C. Daly, A. Nighorn

Faculty & Staff Scholarship

No abstract provided.

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …

Toward A Female Clown Practice: Transgression, Archetype And Myth, Margaret J Irving

Other Faculty of Arts, Humanities and Business Theses

Women who learn to clown within Western contemporary theatre and performance training lack recognizably female exemplars of this popular art form. This practice-as-research thesis analyses my past and present clowning experiences in order to create an understanding of a woman-centered clown practice which allows for the expression of material bodies and lived experiences. It offers a feminist perspective on Jacques Lecoq’s pedagogy, which revolves around a notion of an ‘inner clown’ and is prevalent in contemporary UK clown training and practice. The thesis draws on both the avant-garde and numerous clown types and archetypes, in order to understand clowning as …

The Ecology Of Medical Care In Beijing, Shuang Shao, Feifei Zhao, Jing Wang, Lei Feng, Xiaoqin Lu, Juan Du, Yuxiang Yan, Chao Wang, Yinghong Fu, Jingjing Wu, Xinwei Yu, Kaykeng Khoo, Youxin Wang, Wei Wang

Research outputs 2013

Background: We presented the pattern of health care consumption, and the utilization of available resources by describing the ecology of medical care in Beijing on a monthly basis and by describing the socio-demographic characteristics associated with receipt care in different settings. Methods: A cohort of 6,592 adults, 15 years of age and older were sampled to estimate the number of urbanresident adults per 1,000 who visited a medical facility at least once in a month, by the method of three-stage stratified and cluster random sampling. Separate logistic regression analyses assessed the association between those receiving care in different types of …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

Immune Response To Snake Envenoming And Treatment With Antivenom; Complement Activation, Cytokine Production And Mast Cell Degranulation, Shelley Stone, Geoffrey K. Isbister, Seyed Shahmy, Fahim Mohamed, Chandana Abeysinghe, Harendra Karunathilake, Ariaranee Ariaratnam, Tamara E. Jacoby-Alner, Claire L. Cotterell, Simon G A Brown

Research outputs 2013

Background:Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.Methodology/Principal Findings:Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and …

Neither Heavy Nor Light Load Resistance Exercise Acutely Exacerbates Lymphedema In Breast Cancer Survivor, Prue Cormie, Daniel A. Galvao, Nigel A. Spry, Robert Newton

Research outputs 2013

Resistance exercise has great potential to aid in the management of breast cancer-related lymphedema (BCRL), but little is known regarding the acute response of performing resistance exercises with the affected limb. Purpose. To examine the acute impact of upper body resistance exercise on the amount of swelling and severity of symptoms in women with BCRL and to compare these effects between resistance exercise involving high and low loads (heavier vs lighter weights). Methods. Seventeen women aged 61 ± 9 years with mild to severe BCRL participated in this study. Participants completed a high load (6-8 repetition maximum) and low load …

The Genetic Contribution Of Cidea Polymorphisms, Haplotypes And Loci Interaction To Obesity In A Han Chinese Population, Jingjing Wu, Ling Zhang, Jie Zhang, Ying Dai, Lili Bian, Manshu Song, Alyce C. Russell, Wei Wang

Research outputs 2013

To investigate the association of tag-SNPs and haplotype structures of the CIDEA gene with obesity in a Han Chinese population. Five single nucleotide polymorphisms (SNPs) (rs1154588/V115F, rs4796955/SNP1, rs8092502/SNP2, rs12962340/SNP3 and rs7230480/SNP4) in the CIDEA gene were genotyped in a case-control study. Genotyping was performed using the sequenom matrixassisted laser desorption/ionization time-of-flight mass spectrometry iPLEX platform. There were significant differences between the obese and control groups in genotype distributions of V115F (P>0.001), SNP1 (P = 0.006) and SNP2 (P = 0.005). Carriers of V115F-TT, SNP1-GG and SNP2-CC genotypes had a 2.84-fold (95 % CI 1.73-4.66), 2.19-fold (95 % CI 1.09-4.38) …

Learning Medical Alarms Whilst Performing Other Tasks., Judy Edworthy, Christina Meredith, Elizabeth Hellier, David Rose

School of Psychology

UNLABELLED: Two studies are reported which first observe, and then attempt to replicate, the cognitive demands of intensive care unit (ICU) activity whilst concurrently learning audible alarms. The first study, an observational study in an ICU ward, showed that the alarms are very frequent and co-occur with some activities more than others. The three most frequently observed activities observed in the ICU were drugs (calculation, preparation and administration), patient observation and talking. The cognitive demands of these activities were simulated in a second, laboratory-based experiment in which alarms were learned. The results showed that performance in the alarm task generally …

Cervical Assessment By Ultrasound For Preventing Preterm Delivery., Vincenzo Berghella, Jason K. Baxter Md, Mscp, Nancy W Hendrix

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Measurement of cervical length (CL) by transvaginal ultrasound (TVU) is predictive of preterm birth (PTB). It is unclear if this screening test is effective for prevention of PTB.

OBJECTIVES: To assess the effectiveness of antenatal management based on transvaginal ultrasound of cervical length (TVU CL) screening for preventing PTB.

SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2012), reviewed the reference lists of all articles and contacted experts in the field for additional and ongoing trials.

SELECTION CRITERIA: Published and unpublished randomized controlled trials including pregnant women between the gestational ages of 14 …

Barriers And Facilitators That Influence The Delivery Of Prevention Guidance In Health Service Dental Practice: A Questionnaire Study Of Practising Dentists In Southwest England., Rv Witton, Dr Moles

Peninsula Dental School

UNLABELLED: Objective: OBJECTIVE: To investigate the barriers and facilitators influencing the delivery of prevention in accordance with a national guideline (Delivering Better Oral Health, Department of Health England) in health service dental practice. DESIGN: Self-completion questionnaire. SETTING: Health service general dental practices. SUBJECTS AND METHODS: Questionnaires were sent via two mailings to all 508 dentists registered to work in health service general dental practice in Devon, South West England. RESULTS: In total 266 questionnaires were returned (52% response rate). Examples of barriers and facilitators were evident at various organisational levels of dentistry. These were principally the healthcare system, practice (dental …

Inverted Takotsubo Cardiomyopathy And The Fundamental Diagnostic Role Of Echocardiography, Arantza Manzanal, Lara Ruiz, Jose Madrazo, Majesh Makan, Julio Perez

The Texas Heart Institute Journal

Takotsubo cardiomyopathy is characterized by the development of transient focal wall-motion abnormalities that involve the apical and midventricular segments, in the absence of obstructive coronary artery disease. A variant, inverted takotsubo cardiomyopathy, was described in 2010. We report 3 cases in which each patient's transthoracic echocardiogram revealed the characteristic basal and midventricular segmental akinesis of this variant. This pattern is not associated with coronary artery distribution, and it therefore can be differentiated from coronary artery disease with the use of echocardiography, by evaluating the distribution and temporal changes of akinetic areas.

Preventing Sudden Cardiac Death In Athletes: In Search Of Evidence-Based, Cost-Effective Screening, Paolo Angelini, Mladen I Vidovich, Christine E Lawless, Macarthur A Elayda, J Alberto Lopez, Dwayne Wolf, James T Willerson

The Texas Heart Institute Journal

Sudden cardiac death in athletes is a recurrent phenomenon at sporting events and during training. Recent studies have associated sudden cardiac death with such cardiovascular conditions as coronary artery anomalies, cardiomyopathies, and electrocardiographic abnormalities, most of which are screenable with modern imaging techniques. We recently inaugurated the Center for Coronary Artery Anomalies at the Texas Heart Institute, which is dedicated to preventing sudden cardiac death in the young and investigating coronary artery anomalies. There, we are conducting 2 cross-sectional studies intended to firmly establish and quantify, in a large group of individuals from a general population, risk factors for sudden …

Emerging Modifiable Risk Factors For Cardiovascular Disease In Women: Obesity, Physical Activity, And Sedentary Behavior, Ann Smith Barnes

The Texas Heart Institute Journal

No abstract provided.

The Diagnosis Of Exclusion: An Ongoing Uncertainty, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Cardiovascular Disease In Late Survivors Of Tetralogy Of Fallot: A Tertiary Care Center Experience, Elisa Bradley, Jeff Parker, Eric Novak, Philip Ludbrook, Joseph Billadello, Ari Cedars

The Texas Heart Institute Journal

Patients with tetralogy of Fallot can survive to late adulthood; however, there are few data on cardiovascular outcomes in this population. We conducted a single-center retrospective analysis of cardiovascular outcomes and risk factors in 208 patients with tetralogy of Fallot to better evaluate the burden of cardiovascular disease in this group. Descriptive statistics were used to determine the prevalence of relevant cardiovascular risk factors and outcomes, including a composite analysis of cardiovascular disease. Rates and mean values from the American Heart Association 2011 Heart Disease and Stroke Statistics Update were used as population estimates for comparison.

In tetralogy of Fallot …

Perventricular Device Closure Of Residual Muscular Ventricular Septal Defects After Repair Of Complex Congenital Heart Defects In Pediatric Patients, Da Zhu, Kaiyu Tao, Qi An, Shuhua Luo, Changping Gan, Ke Lin

The Texas Heart Institute Journal

Residual muscular ventricular septal defects are surgical challenges, especially after the repair of complex congenital heart defects. We investigated perventricular device closure as a salvage technique in pediatric patients who had postoperative residual muscular ventricular septal defects.

From February 2009 through June 2011, 14 pediatric patients at our hospital had residual muscular ventricular septal defects after undergoing surgical repair of complex congenital heart defects. Ten patients met our criteria for perventricular device closure of the residual defects: significant left-to-right shunting (Qp/Qs >1.5) or substantial hemodynamic instability (a defect ≥2 mm in size). The patients' mean age was 20.4 ± 13.5 …

Coronary Artery Diameter Related To Calcium Scores And Coronary Risk Factors As Measured With Multidetector Computed Tomography: A Substudy Of The Accuracy Trial, Yasmin S Hamirani, Khurram Nasir, Emil Avanes, Jigar Kadakia, Matthew J Budoff

The Texas Heart Institute Journal

Arterial remodeling, an early change of atherosclerosis, can cause dilated arterial diameter. We measured coronary artery diameter with use of noncontrast 64-slice multidetector computed tomography (MDCT), and studied its association with coronary artery calcium levels and traditional coronary risk factors.

We included 140 patients from the ACCURACY trial whose noncontrast MDCT images showed measurable coronary arteries. Using 3 measurements of left main coronary artery (LMCA) and right coronary artery (RCA) diameters within 3 mm of the ostium, we associated the results with traditional coronary risk factors and calcium scores.

The prevalence of LMCA and RCA calcium was 22% and 51%, …

Low Serum Triglyceride Levels As Predictors Of Cardiac Death In Heart Failure Patients, Guliz Kozdag, Gokhan Ertas, Ender Emre, Yasar Akay, Umut Celikyurt, Tayfun Sahin, Gozde Gorur, Kurtulus Karauzum, Irem Yilmaz, Dilek Ural, Mira Sarsekeyeva

The Texas Heart Institute Journal

Understanding the influence of sex differences on predictors of cardiac mortality rates in chronic heart failure might enable us to lengthen lifetimes and to improve lives. This study describes the influence of sex on cardiovascular mortality rates among chronic heart failure patients.

From January 2003 through December 2009, we evaluated 637 consecutive patients (409 men and 228 women) with chronic heart failure, who ranged in age from 18 through 94 years (mean age, 64 ± 13 yr) and ranged in New York Heart Association (NYHA) functional class from II through IV. The mean follow-up period was 38 ± 15 months, …

Feasibility Of Temporary Biventricular Pacing After Off-Pump Coronary Artery Bypass Grafting In Patients With Reduced Left Ventricular Function, Daniel Y Wang, Lauren A Kelly, Marc E Richmond, T Alexander Quinn, Bin Cheng, Michelle D Spotnitz, Santos E Cabreriza, Yoshifumi Naka, Allan S Stewart, Craig R Smith, Henry M Spotnitz

The Texas Heart Institute Journal

In selected patients undergoing cardiac surgery, our research group previously showed that optimized temporary biventricular pacing can increase cardiac output one hour after weaning from cardiopulmonary bypass. Whether pacing is effective after beating-heart surgery is unknown. Accordingly, in this study we examined the feasibility of temporary biventricular pacing after off-pump coronary artery bypass grafting.

The effects of optimized pacing on cardiac output were measured with an electromagnetic aortic flow probe at the conclusion of surgery in 5 patients with a preoperative mean left ventricular ejection fraction of 0.26 (range, 0.15–0.35). Atrioventricular (7) and interventricular (9) delay settings were optimized in …

Surgical Pulmonary Embolectomy: The Resurrection Of An Almost Discarded Operation, Samuel Z Goldhaber

The Texas Heart Institute Journal

No abstract provided.

Preoperative Statin Therapy In Cardiac Surgery Is More Effective In Patients Who Display Preoperative Activation Of The Inflammatory System, José Martínez-Comendador, José Rubio Alvarez, Juan Sierra, Elvis Teijeira, Belén Adrio

The Texas Heart Institute Journal

We sought to determine whether preoperative statin treatment is more effective in reducing, after cardiac surgery with cardiopulmonary bypass, systemic inflammatory response and myocardial damage markers in patients who have elevated preoperative interleukin-6 levels than in patients who have normal preoperative interleukin-6 levels.

The study involved a prospective cohort of 164 patients who underwent coronary and valvular surgery with cardiopulmonary bypass. There were 2 study groups: group A (n = 60), patients with elevated preoperative interleukin-6 levels; and group B (n = 104), patients with normal preoperative interleukin-6 levels. Each group was subdivided according to whether patients were (group 1) …

Stab Wound Of The Heart With Unusual Sequelae, Peter I Praeger, Jonathan Praeger, Ahmed M Abdel-Razek, Elie M Elmann

The Texas Heart Institute Journal

A 31-year-old woman was admitted to the emergency department with a stab wound to the heart. She was initially stable but rapidly developed hypotension. While the operating room and staff were in preparation, she underwent pericardiocentesis. She was then rushed to the operating room by the general surgical trauma team, who performed a bilateral anterior thoracotomy to control the bleeding. In the recovery room, the patient was still hypotensive, so cardiothoracic surgery was consulted.

An echocardiogram revealed severe hypokinesis of both ventricles. The cardiothoracic surgeons returned her to the operating room and discovered that the anterior pericardium had been completely …

Osteosarcoma Tumor Thrombus: A Case Report With A Review Of The Literature, Pournima Navalkele, Sarah M Jones, Jason K Jones, Jorge D Salazar, Patrick C Toy, Rathi V Iyer, Betty Herrington

The Texas Heart Institute Journal

Tumor thrombus arising from osteosarcoma is rare. We report the case of a 20-year-old man with proximal humerus osteosarcoma, accompanied by an extensive intravascular tumor thrombus extending into the heart. Our review of the literature found 14 previous reports on osteosarcoma with tumor thrombus. The combination of positron emission tomography and computed tomography is very useful in differentiating tumor thrombus from vascular thrombus, thereby avoiding unnecessary anticoagulation therapy. This same imaging combination can also be used to evaluate the response to treatment. Surgical resection of the tumor thrombus is highly recommended. The effect of tumor thrombus on survival is still …

A Fimh Inhibitor Prevents Acute Bladder Infection And Treats Chronic Cystitis Caused By Multidrug-Resistant Uropathogenic Escherichia Coli St131., Makrina Totsika, Maria Kostakioti, Thomas J. Hannan, Mathew Upton, Scott A. Beatson, James W. Janetka, Scott J. Hultgren, Mark A. Schembri

School of Biomedical Sciences

BACKGROUND: Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent. METHODS: Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958. RESULTS: We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration …

On The Interplay Of Telomeres, Nevi And The Risk Of Melanoma, Clara Bodelon, Ruth M. Pfeiffer, Valentina Bollati, Julien Debbache, Donato Calista, Paola Ghiorzo, Maria Concetta Fargnoli, Giovanna Bianchi-Scarra, Ketty Peris, Mirjam Hoxha, Amy Hutchinson, Laura Burke, Shenying Fang, Margaret A. Tucker, Alisa M. Goldstein, Jeffrey E. Lee, Qingyi Wei, Sharon A. Savage, Xiaohong R. Yang, Christopher Amos, Maria Teresa Landi

Dartmouth Scholarship

The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or …