Medicine and Health Sciences Commons^™

The Devil Is In The Third Year: A Longitudinal Study Of Erosion Of Empathy In Medical School., Mohammadreza Hojat, Michael J. Vergare, Kaye Maxwell, George Brainard, Steven K. Herrine, Gerald A. Isenberg, John Veloski, Joseph S. Gonnella

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: This longitudinal study was designed to examine changes in medical students' empathy during medical school and to determine when the most significant changes occur.

METHOD: Four hundred fifty-six students who entered Jefferson Medical College in 2002 (n = 227) and 2004 (n = 229) completed the Jefferson Scale of Physician Empathy at five different times: at entry into medical school on orientation day and subsequently at the end of each academic year. Statistical analyses were performed for the entire cohort, as well as for the "matched" cohort (participants who identified themselves at all five test administrations) and the "unmatched" …

Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Although embryonic stem (ES) cells can generate dopamine (DA) neurons that are potentially useful as a cell replacement therapy in Parkinson's disease (PD), associated ethical and practical concerns remain major stumbling blocks to their eventual use in humans. In this study, we examined human amniotic fluid stem (hAFS) cells derived from routine amniocenteses for their potential to give rise to DA neurons in vitro and following transplantation into the 6-hydroxydopamine-lesioned rat brain. We show that undifferentiated hAFS cells constitutively expressed mRNAs and proteins typical of stem cells but also cell derivatives of all three germ layers, including neural progenitors/neurons (nestin, …

Jnk1 Activation Predicts The Prognostic Outcome Of The Human Hepatocellular Carcinoma, Qingshan Chang, Jianguo Chen, Kevin J. Beezhold, Vince Castranova, Xianglin Shi, Fei Chen

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC based on the molecular signature is not well-established.

RESULTS: In the present study, we reported HCC signature genes based on the JNK1 activation status in 31 HCC specimens relative to the matched distal noncancerous liver tissue from 31 patients. The HCCs with high JNK1 (H-JNK1) and low JNK1 (L-JNK1) were sub-grouped. Two different signature gene sets for both H-JNK1 and L-JNK1 HCC were identified through gene expression profiling. A striking overlap of signature genes was observed between the H-JNK1 …

Aging And Environmental Exposures Alter Tissue-Specific Dna Methylation Dependent Upon Cpg Island Context, Brock C. Christensen, E Andres Houseman, Carmen J. Marsit, Shichun Zheng, Margaret R. Wrensch, Joseph L. Wiemels, Heather H. Nelson, Margaret R. Karagas

Dartmouth Scholarship

Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are related to epigenomic states that vary across individuals. Thus, population-based investigations are needed to further our understanding of the fundamental dynamics of normal individual epigenomes. We analyzed 217 non-pathologic human tissues from 10 anatomic sites at 1,413 autosomal CpG loci …

Cd19 Signaling Is Impaired In Murine Peritoneal And Splenic B-1 B Lymphocytes, Trivikram Dasu, Vishal Sindhava, Stephen H. Clarke, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells reside predominantly within the coelomic cavities, tonsils, Peyer's patches, spleen (a minor fraction – ∼5%) and are absent in the lymph nodes. They are the primary sources of natural IgM in the body. B-1 cells express polyreactive B cell receptors (BCRs) that cross react with self-antigens and are thus implicated in auto-immune disorders. Previously, we reported that peritoneal B-1 cells are deficient in CD19-mediated intracellular signals leading to Ca²⁺ mobilization. Here, we find that splenic B-1 cells, like peritoneal B-1 cells, are defective in Ca²⁺ release upon B cell activation by co-cross-linking BCR and CD19. In …

Functional State Following The Fontan Procedure., Ismee A. Williams, Lynn A. Sleeper, Steven D. Colan, Minmin Lu, Elizabeth A. Stephenson, Jane W. Newburger, Welton M. Gersony, Meryl S. Cohen, James F. Cnota, Andrew M. Atz, Richard V. Williams, Renee Margossian, Andrew J. Powell, Mario P. Stylianou, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function.

METHODS AND RESULTS: We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by …

Dynamic Mechanical (Brush) Allodynia In Cluster Headache: A Prevalence Study In A Tertiary Headache Clinic., Michael J Marmura, Muhammad Abbas, Avi Ashkenazi

Department of Jefferson Headache Center papers and presentations

Cutaneous allodynia (CA) has been described in migraine and has been related to treatment failure. There are little data about the incidence of CA in other primary headache syndromes such as cluster headache (CH). The objectives of this study are to evaluate the prevalence of dynamic mechanical (brush) allodynia (BA) in CH patients attending a tertiary headache clinic, and to assess its relation to disease characteristics. Adult patients with episodic or chronic CH were recruited. We obtained demographic data and data on disease characteristics through a structured questionnaire, and tested the patients for brush allodynia BA by applying a 4 …

Depressive Symptoms And Marital Satisfaction In The Context Of Chronic Disease: A Longitudinal Dyadic Analysis, Rachel Pruchno, Maureen Wilson-Genderson, Francine P Cartwright

Rowan-Virtua School of Osteopathic Medicine Departmental Research

These analyses examined the longitudinal relationships between depressive symptoms and marital satisfaction over a 2-year period as experienced by 315 patients with end-stage renal disease and their spouses. Using multilevel modeling, the authors examined both individual and cross-partner effects of depressive symptoms and marital satisfaction on patients and spouses, testing bidirectional causality. Results indicate that mean and time-varying depressive symptoms of both patients and spouses were associated with their own marital satisfaction. Although mean marital satisfaction was associated with own depressive symptoms for both patients and spouses, time-varying marital satisfaction did not affect depressive symptoms for either patients or spouses. …

Comparison Of Echocardiographic And Cardiac Magnetic Resonance Imaging Measurements Of Functional Single Ventricular Volumes, Mass, And Ejection Fraction (From The Pediatric Heart Network Fontan Cross-Sectional Study)., Renee Margossian, Marcy L. Schwartz, Ashwin Prakash, Lisa Wruck, Steven D. Colan, Andrew M. Atz, Timothy J. Bradley, Mark A. Fogel, Lynne M. Hurwitz, Edward Marcus, Andrew J. Powell, Beth F. Printz, Michael D. Puchalski, Jack Rychik, Girish S. Shirali, Richard Williams, Shi-Joon Yoo, Tal Geva, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement …

Intra-Tumor Heterogeneity Of Mlh1 Promoter Methylation Revealed By Deep Single Molecule Bisulfite Sequencing., Katherine E Varley, David G Mutch, Tina B Edmonston, Paul J Goodfellow, Robi D Mitra

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A single tumor may contain cells with different somatic mutations. By characterizing this genetic heterogeneity within tumors, advances have been made in the prognosis, treatment and understanding of tumorigenesis. In contrast, the extent of epigenetic intra-tumor heterogeneity and how it influences tumor biology is under-explored. We have characterized epigenetic heterogeneity within individual tumors using next-generation sequencing. We used deep single molecule bisulfite sequencing and sample-specific DNA barcodes to determine the spectrum of MLH1 promoter methylation across an average of 1000 molecules in each of 33 individual samples in parallel, including endometrial cancer, matched blood and normal endometrium. This first glimpse, …

Food Insecurity Among Homeless And Marginally Housed Individuals Living With Hiv/Aids In San Francisco, Sheri D. Weiser, David R. Bangsberg, Susan Kegeles, Kathleen Ragland, Margot B. Kushel, Edward A. Frongillo Jr.

Faculty Publications

Food insecurity is a risk factor for both HIV transmission and worse HIV clinical outcomes. We examined the prevalence of and factors associated with food insecurity among homeless and marginally housed HIV-infected individuals in San Francisco recruited from the Research on Access to Care in the Homeless Cohort. We used multiple logistic regression to determine socio-demographic and behavioral factors associated with food insecurity, which was measured using the Household Food Insecurity Access Scale. Among 250 participants, over half (53.6%) were food insecure. Higher odds of food insecurity was associated with being white, low CD4 counts, recent crack use, lack of …

A Functional Difficulty And Functional Pain Instrument For Hip And Knee Osteoarthritis, Alan M. Jette, Christine M. Mcdonough, Pengsheng Ni, Stephen M. Haley

Dartmouth Scholarship

The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field.

Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity And Reduces Messenger Ribonucleic Acid Translation Initiation And Nutrient Sensing In Fetal Liver And Skeletal Muscle., Stephanie R Thorn, Timothy Regnault, Laura D Brown, Paul J Rozance, Jane Keng, Michael Roper, Randall B Wilkening, William W Hay, Jacob E Friedman

Paediatrics Publications

Expression of key metabolic genes and proteins involved in mRNA translation, energy sensing, and glucose metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR). PI-IUGR fetuses weighed 55% less; had reduced oxygen, glucose, isoleucine, insulin, and IGF-I levels; and had 40% reduction in net branched chain amino acid uptake. In PI-IUGR skeletal muscle, levels of insulin receptor were increased 80%, whereas phosphoinositide-3 kinase (p85) and protein kinase B (AKT2) were reduced by 40%. Expression of eukaryotic initiation factor-4e was reduced 45% in liver, suggesting a unique mechanism limiting …

Dicer Is Required For Female Reproductive Tract Development And Fertility In The Mouse, Gabriel Gonzalez, Richard R Behringer

Student and Faculty Publications

Dicer encodes a riboendonuclease required for microRNA biosynthesis. Dicer was inactivated in Müllerian duct mesenchyme-derived tissues of the reproductive tract of the mouse, using an Amhr2-Cre allele. Although Amhr2-Cre; Dicer conditional mutant males appeared normal and were fertile, mutant females were infertile. In adult mutant females, there was a reduction in the size of the oviducts and uterine horns. The oviducts were less coiled compared to controls and cysts formed at the isthmus near the uterotubal junction. Unfertilized, degenerate oocytes were commonly found within these cysts, indicating a defect in embryo transit. Beads transferred into the mutant oviduct failed to …

Perirhinal Cortex Contributes To Accuracy In Recognition Memory And Perceptual Discriminations., Edward B O'Neil, Anthony D Cate, Stefan Köhler

Brain and Mind Institute Researchers' Publications

The prevailing view of the medial temporal lobe (MTL) holds that its structures are dedicated to long-term declarative memory. Recent evidence challenges this position, suggesting that perirhinal cortex (PRc) in the MTL may also play a role in perceptual discriminations of stimuli with substantial visual feature overlap. Relevant neuropsychological findings in humans have been inconclusive, likely because studies have relied on patients with large and variable MTL lesions. Here, we conducted a functional magnetic resonance imaging study in healthy individuals to determine whether PRc shows a performance-related involvement in perceptual oddball judgments that is comparable to its established role in …

Il-9 As A Mediator Of Th17-Driven Inflammatory Disease, Elizabeth C. Nowak, Casey T. Weaver, Henrietta Turner, Sakhina Begum-Haque, Burkhard Becher, Bettina Schreiner, Anthony J. Coyle, Lloyd H. Kasper, Randolph J. Noelle

Dartmouth Scholarship

We report that like other T cells cultured in the presence of transforming growth factor (TGF) beta, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-beta as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6-producing macrophages in …

Epidemiology And Outcomes Of Candidemia In 2019 Patients: Data From The Prospective Antifungal Therapy Alliance Registry., David L Horn, Dionissios Neofytos, Elias J Anaissie, Jay A Fishman, William J Steinbach, Ali J Olyaei, Kieren A Marr, Michael A Pfaller, Chi-Hsing Chang, Karen M Webster

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing.

METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis.

RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher …

A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple

Dartmouth Scholarship

Tre-2, BUB2, CDC16, 1 domain family member 4 (TBC1D4) (AS160) is a Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes. To determine whether loss-of-function mutations in TBC1D4 might impair GLUT4 translocation and cause insulin resistance in humans, we screened the coding regions of this gene in 156 severely insulin-resistant patients. A female presenting at age 11 years with acanthosis nigricans and extreme postprandial hyperinsulinemia was heterozygous for a premature stop mutation (R363X) in TBC1D4. After demonstrating reduced expression of wild-type TBC1D4 protein and expression of the truncated protein in lymphocytes from the proband, …

A Retrospective Claims Analysis Of Combination Therapy In The Treatment Of Adult Attention-Deficit/Hyperactivity Disorder (Adhd), Gerhardt M. Pohl, David L. Van Brunt, Wenyu Ye, William W. Stoops, Joseph A. Johnston

Behavioral Science Faculty Publications

BACKGROUND: Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy.

METHODS: Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for …

Development And Validation Of An Index Of Musculoskeletal Functional Limitations, Jeffrey N. Katz, Elizabeth A. Wright, John A. Baron, Elena Losina

Dartmouth Scholarship

While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index.

Mitogen-Activated Protein Kinase (Mapk) Pathways Mediate Embryonic Responses To Culture Medium Osmolarity By Regulating Aquaporin 3 And 9 Expression And Localization, As Well As Embryonic Apoptosis., Christine E Bell, Nathalie M K Larivière, Patricia H Watson, Andrew J Watson

Obstetrics & Gynaecology Publications

BACKGROUND: In order to advance the development of culture conditions and increase the potential for supporting normal preimplantation embryo development in vitro, it is critical to define the mechanisms that early embryos utilize to survive in culture. We investigated the mechanisms that embryos employ in response to culture medium osmolarity. We hypothesized that mitogen-activated protein kinase (MAPK) pathways mediate responses to hyperosmotic stress by regulating Aquaporin (AQP) 3 and 9 expression as well as embryonic apoptosis.

METHODS: Real-time reverse transcription and polymerase chain reaction and whole-mount immunofluorescence were used to determine the relative mRNA levels and protein localization patterns of …

It Is More Than Just A Reproductive Healthcare Visit: Experiences From An Adolescent Medicine Clinic, Marlene B. Huff, Kimberly K. Mcclanahan, Heather A. Brown, Hatim A. Omar

Pediatrics Faculty Publications

The gynecologist may be the only physician that an adolescent depends on for primary and reproductive healthcare services. Because adolescent females often make personal healthcare decisions without the benefit of supportive parents/caregivers, it is imperative that the gynecologist understands the developmental issues encountered during this phase of life. The objective of this study is to identify cited complaints of adolescent females seeking reproductive care and, thus, provide gynecologists with needed information about the medical/mental health issues that may be encountered during routine reproductive care exams. The study group was adolescent females between the ages of 12 and 20 years old. …

Therapeutic Targeting Of Atp7b In Ovarian Carcinoma, Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin, Alpa M Nick, Christopher G Danes, Jeong-Won Lee, Nicholas B Jennings, Pablo E Vivas-Mejia, Judith K Wolf, Robert L Coleman, Zahid H Siddik, Gabriel Lopez-Berestein, Svetlana Lutsenko, Anil K Sood

Student and Faculty Publications

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models.

EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).

RESULTS: ATP7A …

Cancer Information-Seeking Experiences: The Implications Of Hispanic Ethnicity And Spanish Language, Robin C. Vanderpool, Julie Kornfeld, Lila Finney Rutten, Linda Squiers

Health, Behavior & Society Faculty Publications

BACKGROUND: Strategies to support cancer information-seeking among Hispanics are needed.

METHODS: We analyzed data from the 2005 Health Information National Trends Survey (HINTS) to explore cancer information-seeking experiences among respondents according to ethnicity and language of interview.

RESULTS: Over 80% of Spanish-speaking Hispanics had never looked for cancer information. Compared to English-speaking respondents, Spanish-speaking Hispanics who sought cancer information indicated their search took a lot of effort (67%), was hard to understand (54%), and frustrating (42%). Spanish-speaking Hispanics noted minimal confidence in obtaining cancer information.

CONCLUSIONS: Language and cultural differences must be considered in the design, implementation, and dissemination of …

Genome Based Cell Population Heterogeneity Promotes Tumorigenicity: The Evolutionary Mechanism Of Cancer., Christine J. Ye, Joshua B. Stevens, Guo Liu, Steven W. Bremer, Aruna S. Jaiswal, Karen J. Ye, Ming-Fong Lin, Lesley Lawrenson, Wayne D. Lancaster, Markku Kurkinen, Joshua D. Liao, C. Gary Gairola, Malathy P. V. Shekhar, Satya Narayan, Fred R. Miller, Henry H. Q. Heng

Journal Articles: Biochemistry & Molecular Biology

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis. The tumorigenicity of each model has been linked to different molecular pathways, and there is no common molecular mechanism shared among them. According to our hypothesis that genome level heterogeneity is a key to cancer evolution, we expect to reveal …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

State Infant Mortality: An Ecologic Study To Determine Modifiable Risks And Adjusted Infant Mortality Rates., David A. Paul. Md, Amy Mackley, Rnc, Robert G. Locke, Do, John L. Stefano, Md, Charlan Kroelinger, Phd

Department of Pediatrics Faculty Papers

OBJECTIVE: To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. DESIGN/METHODS: Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization …

Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam E. Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias J. Schnell, Laurence C. Eisenlohr, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Cancer mucosa antigens are emerging as a new category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors. These antigens leverage the established immunologic partitioning of systemic and mucosal compartments, limiting tolerance opposing systemic antitumor efficacy. An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization. In the context of cancer mucosa antigens, immune effectors to self-antigens risk amplifying mucosal inflammatory disease promoting carcinogenesis. Here, we examined the relationship between immunotherapy for systemic colon cancer metastases targeting the intestinal cancer mucosa antigen guanylyl cyclase C (GCC) and its effect on inflammatory …

Long-Term Survival After Multidisciplinary Management Of Resected Pancreatic Adenocarcinoma, Matthew H G Katz, Huamin Wang, Jason B Fleming, Charlotte C Sun, Rosa F Hwang, Robert A Wolff, Gauri Varadhachary, James L Abbruzzese, Christopher H Crane, Sunil Krishnan, Jean-Nicolas Vauthey, Eddie K Abdalla, Jeffrey E Lee, Peter W T Pisters, Douglas B Evans

Student and Faculty Publications

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.

RESULTS: …

Comorbidities, Patient Knowledge, And Disease Management In A National Sample Of Patients With Copd, R Graham Barr, Bartolome R Celli, David M Mannino, Thomas Petty, Stephen I Rennard, Frank C Sciurba, James K Stoller, Byron M Thomashow, Gerard M Turino

Faculty and Staff Publications

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States but is often undertreated. COPD often overlaps with other conditions such as hypertension and osteoporosis, which are less morbid but may be treated more aggressively. We evaluated the prevalence of these comorbid conditions and compared testing, patient knowledge, and management in a national sample of patients with COPD.

METHODS: A survey was administered by telephone in 2006 to 1003 patients with COPD to evaluate the prevalence of comorbid conditions, diagnostic testing, knowledge, and management using standardized instruments. The completion rate was 87%.

RESULTS: …