Medicine and Health Sciences Commons^™

Differences In Responses Of Platelets To Fluid Shear Stress In Patients With Peripheral Artery Disease (Pad) And Coronary Artery Disease (Cad)., Vijay Nambi, Kay T Kimball, Paul Bray, Angela L Bergeron, Shawna L Johnson, Joel D Morrisett, Changyi Chen, Peter H Lin, Alan B Lumsden, Christie M Ballantyne, Jing-Fei Dong

Cardeza Foundation for Hematologic Research

Information on differences in platelet function between patients with peripheral arterial disease (PAD) and patients with coronary artery disease (CAD) is limited. We sought to examine the differences in the platelets response to shear stress in patients with PAD compared to those with CAD. Men with symptomatic PAD (ankle brachial index [ABI] < 0.9; n = 29) were compared with similarly aged men with CAD (post coronary artery bypass grafting; n = 40) but without PAD. All participants were on aspirin, and none were on clopidogrel. We measured changes in shear-induced platelet aggregation (SIPA) and shear-induced P-selectin expression (SIPE) under fluid shear rates of 5000 and 10,000 s(-1)which are typically found in arterioles and stenosed arteries, respectively. Aggregation was also induced by a combined stimulation of collagen, fluid shear stress, and adenosine diphosphate (ADP) or epinephrine using a platelet function analyzer (PFA-100) as well as optical aggregometry (arachidonic acid, collagen and epinephrine). Analyses of covariance adjusted for age, aspirin dose, and statin use were used to estimate differences between the groups. Values of SIPA at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in the PAD group, while there were no differences between the PAD and CAD groups in SIPE at both fluid shear rates. However, baseline shear-induced P-selectin expression was higher in patients with PAD than CAD (mean fluorescence intensity [MFI] = 2.93 +/- 1.37 vs.1.94 +/- 0.67; p = 0.01), while the percentage increases in SIPA and SIPE at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in patients with CAD when compared to PAD (p < 0.001 for all comparisons). Although there were several similarities in platelet function between men with PAD and men with CAD, significant differences in platelet responses to shear stress were observed in men with PAD when compared to those with CAD. Although the mechanism for these observed differences are not clear, we hypothesize that in vivo platelet activation in PAD patients may contribute to the differences and will need to be further investigated.

Us And Mr Imaging Features Of Benign Cystic Mesothelioma Of The Liver: A Diagnostic Dilemma, Sachit K. Verma, Donald G. Mitchell, Oksana H. Baltarowich, Diane Bergin, Raphael Rubin

Department of Radiology Faculty Papers

Cystic mesotheliomas are benign neoplasms, often seen in the parietal and visceral peritoneum, omentum and pelvic organs, and are exceedingly rare in the liver. It is however important to be familiar with the radiological findings of this tumour because the signal-intensity and enhancement pattern of this tumor are unusual and not typical for any of the more frequently seen mass lesions. In our patient, characteristic imaging findings on dynamic contrast-enhanced MRI and histopathological confirmation with appropriate immunohistochemical markers facilitated a correct diagnosis. We herein describe the clinical, imaging and histopathological features, pathogenesis, differential diagnosis and treatment of benign cystic mesothelioma …

Basement Membrane Proteoglycans: Modulators Par Excellence Of Cancer Growth And Angiogenesis., Renato V. Iozzo, Jason J. Zoeller, Alexander Nyström

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans located in basement membranes, the nanostructures underling epithelial and endothelial layers, are unique in several respects. They are usually large, elongated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more "active configuration" to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical …

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 …

Plant Vaccines: An Immunological Perspective., Douglas C. Hooper

Department of Cancer Biology Faculty Papers

The advent of technologies to express heterologous proteins in planta has led to the proposition that plants may be engineered to be safe, inexpensive vehicles for the production of vaccines and possibly even vectors for their delivery. The immunogenicity of a variety of antigens of relevance to vaccination expressed in different plants has been assessed. The purpose of this article is to examine the utility of plant-expression systems in vaccine development from an immunological perspective.

Sustaining A Fall Prevention Initiative- It Can Be Done!, Liz Gutwein-Guenther, Rn Bsn- Tjuh, Patricia Horner, Rn Msn-Tjuh

Jefferson Hospital Nurses Week

Prompted by an increase in falls in December of 2006, a group of nurses convened to address new approaches in fall prevention. This group quickly identified the need for a multidisciplinary approach. During the first year, the interdisciplinary committee effected policy changes in many departments and provided multi-hospital wide education. The committee also supported the development of a nursing Fall Prevention Resource Group that meets monthly and is composed of nurses and aides from each unit. The members are the “Champions for Fall Prevention”. The monthly meetings of both groups keep the fall prevention initiative alive.

Prediction Of Sublingual Bioavailability Of Buprenorphine In Newborns With Neonatal Abstinence Syndrome—A Case Study On Physiological And Developmental Changes Using Nonmem And Simcyp, Di Wu, Walter K. Kraft, Michelle E. Ehrlick, Jeffrey S. Barnett

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Poster presented at 2009 American College of Clinical Pharmacology conference in Orlando. April 24-28.

Background: About 55 to 94% of infants born to opioid dependent mothershave neonatal abstinence syndrome (NAS). Buprenorphine (BUP) is usedclinically as an analgesic and a detoxification agent and a maintenancetreatment for opioid dependence. No data, however, has been reported about the use of sublingual administration of BUP below the age of 4 year, especially for term infants with NAS.

Objectives: Characterize pharmacokinetics (PK) of BUP in newborn patients;Evaluate the developmental changes in newborns in order to assist dosingoptimization in ongoing clinical studies.

Methods: In silico prediction …

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 …

An Adrenal Beta-Arrestin 1-Mediated Signaling Pathway Underlies Angiotensin Ii-Induced Aldosterone Production In Vitro And In Vivo., Anastasios Lymperopoulos, Giuseppe Rengo, Carmela Zincarelli, Jihee Kim, Stephen Soltys, Walter J Koch

Center for Translational Medicine Faculty Papers

Aldosterone produces a multitude of effects in vivo, including promotion of postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced and secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation of AngII type 1 receptors (AT(1)Rs). Until now, the general consensus for AngII signaling to aldosterone production has been that it proceeds via activation of G(q/11)-proteins, to which the AT(1)R normally couples. Here, we describe a novel signaling pathway underlying this AT(1)R-dependent aldosterone production mediated by beta-arrestin-1 (betaarr1), a universal heptahelical receptor adapter/scaffolding protein. This pathway results in sustained ERK activation and subsequent …

Primary Cardiac Tumors., Suraj Maraj, Md, Gregg S. Pressman, Md, Vincent M. Figueredo, Md

Division of Cardiology Faculty Papers

Primary cardiac tumors are a rare entity compared to tumors that metastasize to the heart. Patients with such tumors may be asymptomatic. Many cases are found incidentally during evaluation of an unrelated medical condition. It is important for the clinician to have a high index of suspicion when evaluating a patient presenting with signs and systemic symptoms concerning possible malignancy, plus cardiac specific symptoms or complications. These can include new onset dyspnea, congestive heart failure, arrhythmias or murmurs varying with body positions. Imaging, particularly the use of echocardiography, remains the cornerstone of diagnosis, and may be combined with new imaging …

Jefferson Review - Spring 2009

Jefferson Review

Contents

Features

• 4 - University Restructures to Reflect Schools' Importance
• 8 - Extraordinary Growth at JCHP Marks Dean Erdmann's Tenure
• 12 - Pharmacy Students Learn Through Experience
• 16 - What's New in Interprofessional Education
• 18 - Jefferson Hospital Nursing Achieves MAGNET Status
• 20 - Groundbreaking Team Symposium Brings Disciplines Together
• 28 - Alumni Profile: Amanda Kingsland, MS '09

On Campus

• 22 - School of Health Professions
• 25 - School of Nursing
• 27 - School of Pharmacy
• 29 - Class Notes

A Study Of Micrornas In Silico And In Vivo: Diagnostic And Therapeutic Applications In Cancer., Scott A Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is emerging evidence of the production in human tumors of abnormal levels of microRNAs (miRNAs), which have been assigned oncogenic and/or tumor-suppressor functions. While some miRNAs commonly exhibit altered amounts across tumors, more often, different tumor types produce unique patterns of miRNAs, related to their tissue of origin. The role of miRNAs in tumorigenesis underscores their value as mechanism-based therapeutic targets in cancer. Similarly, unique patterns of altered levels of miRNA production provide fingerprints that may serve as molecular biomarkers for tumor diagnosis, classification, prognosis of disease-specific outcomes and prediction of therapeutic responses.

Jefferson Alumni Bulletin – Volume 58, Number 1, Spring 2009

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 58, Number 1, Spring 2009

JMC’s New Dean, page 2

Findings- Researchers Use Toxin Gene to “Kill Cancer Cells”, page 4

Restrictions, Hospitalists, PA s: Dramatic Changes in Education, page 6

Scholarship Dinner, page 13

Breaking Ground with Team-Based Education, page 14

On Campus, page 18

Class Notes, page 24

In Memoriam, page 28

By The Numbers, page 29

Transperitoneal Robotic-Assisted Laparoscopic Prostatectomy After Prosthetic Mesh Herniorrhaphy., Costas D. Lallas, Mark L. Pe, Jitesh V. Patel, Pranav Sharma, Leonard G. Gomella, Edouard J. Trabulsi

Department of Urology Faculty Papers

BACKGROUND AND OBJECTIVES: We report our institutional experience performing transperitoneal robotic-assisted laparoscopic prostatectomy (RALP) in patients with prior prosthetic mesh herniorrhaphy to assess the feasibility of this procedure in this patient population. METHODS: From October 2005 to January 2008, transperitoneal robotic-assisted laparoscopic prostatectomies were performed and prospectively recorded. We retrospectively reviewed 309 patients. RESULTS: Twenty-seven patients (8.7%) were found to have a history of prior hernia repair with prosthetic mesh placement. The mean age was 55.7, estimated blood loss (EBL) was 228 mL, operative (console) time was 197 minutes, and length of hospital stay (LOS) was 1.62 days. In contrast, …

Heme Oxygenase Activity And Hemoglobin Neurotoxicity Are Attenuated By Inhibitors Of The Mek/Erk Pathway., Jing Chen-Roetling, Zhi Li, Mai Chen, Olatilewa O. Awe, Raymond F. Regan

Department of Emergency Medicine Faculty Papers

Hemoglobin breakdown produces an iron-dependent neuronal injury after experimental CNS hemorrhage that may be attenuated by heme oxygenase (HO) inhibitors. The HO enzymes are phosphoproteins that are activated by phosphorylation in vitro. While testing the effect of kinase inhibitors in cortical cell cultures, we observed that HO activity was consistently decreased by the MEK inhibitor U0126. The present study tested the hypothesis that MEK/ERK pathway inhibitors reduce HO activity and neuronal vulnerability to hemoglobin. The MEK inhibitors U0126 and SL327 and the ERK inhibitor FR180204 reduced baseline culture HO activity by 35-50%, without altering the activity of recombinant HO-1 or …

Coronary Steal Syndrome After Coronary Artery Bypass For Anomalous Aortic Origin Of A Coronary Artery., Benjamin A. Youdelman, Glenn J. Pelletier, C Igor Mesia, Marshall L. Jacobs

Department of Surgery Faculty Papers

Anomalous aortic origin of a coronary artery found in a symptomatic 9-year-old boy was initially treated with coronary artery bypass grafting using a left internal mammary artery anastomoses to the left anterior descending coronary artery, but resulted in coronary ischemia, likely from a steal phenomenon. Subsequent transection of the proximal left internal mammary artery with anastomosis to the ascending aorta, and coronary ostial enlargement, resulted in a durable treatment. We recommend caution in choosing coronary artery bypass grafting using a left internal mammary artery pedicle graft for the treatment of anomalous aortic origin of a coronary artery.

The Significance Of Gata3 Expression In Breast Cancer: A 10-Year Follow-Up Study., Vincenzo Ciocca, Constantine Daskalakis, Robin M. Ciocca, Alejandra Ruiz-Orrico, Juan P. Palazzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

GATA3 is a transcription factor closely associated with estrogen receptor alpha in breast carcinoma, with a potential prognostic utility. This study investigated the immunohistochemical expression of GATA3 in estrogen receptor alpha-positive and estrogen receptor alpha-negative breast carcinomas. One hundred sixty-six cases of invasive breast carcinomas with 10-year follow-up information were analyzed. Positive GATA3 and estrogen receptor alpha cases were defined as greater than 20% of cells staining. Time to cancer recurrence and time to death were analyzed with survival methods. Of 166 patients, 40 were estrogen receptor alpha negative and 121 estrogen receptor alpha positive. Thirty-eight (23%) recurrences and 51 …

Comparison Of Side Effects With Extended Release Epidural Morphine And Other Analgesic Modalities, Kathleen M. Colfer, Msn, Rn-Bc, Kishor Gandhi, Md, Mph, Robert F. Olszewski, Bs, Deborah A. Colli, Bsn, Rn-Bc

Jefferson Hospital Nurses Week

Opioids are the mainstay of post-operative pain management and may produce side effects that impact patient recovery. Use of Extended Release Epidural Morphine (EREM) has been shown to result in significantly less average morphine usage and to have superior analgesic efficacy than other modes of postoperative pain management. The purpose of this retrospective review was to compare the incidence and onset of side effects of ERE and other post-operative Analgesic regiments.

Dosimetric Evaluation Of Heterogeneity Corrections For Rtog 0236: Stereotactic Body Radiotherapy Of Inoperable Stage I-Ii Non-Small-Cell Lung Cancer., Ying Xiao, Lech Papiez, Rebecca Paulus, Robert Timmerman, William L. Straube, Walter R. Bosch, Jeff Michalski, James M. Galvin

Department of Radiation Oncology Faculty Papers

PURPOSE: Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations.

METHOD AND MATERIALS: A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified …

Y27632, A Rho-Activated Kinase Inhibitor, Normalizes Dysregulation In Alpha1-Adrenergic Receptor-Induced Contraction Of Lyon Hypertensive Rat Artery Smooth Muscle., Maria Regina Freitas, Masumi Eto, Jason A Kirkbride, Christa Schott, Jean Sassard, Jean-Claude Stoclet

Department of Molecular Physiology and Biophysics Faculty Papers

RhoA-activated kinase (ROK) is involved in the disorders of smooth muscle contraction found in hypertension model animals and patients. We examined whether the alpha1-adrenergic receptor agonist-induced ROK signal is perturbed in resistance small mesentery artery (SMA) of Lyon genetically hypertensive (LH) rats, using a ROK antagonist, Y27632. Smooth muscle strips of SMA and aorta were isolated from LH and Lyon normotensive (LN) rats. After Ca(2+)-depletion and pre-treatment with phenylephrine (PE), smooth muscle contraction was induced by serial additions of CaCl(2). In LH SMA Ca(2+) permeated cells to a lesser extent as compared with LN SMA, while CaCl(2)-induced contraction of LH …

What Is The Cost Of Maintaining A Kidney In Upper-Tract Transitional-Cell Carcinoma? An Objective Analysis Of Cost And Survival., Raymond W Pak, Eric J Moskowitz, Demetrius H Bagley

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: For many years, the gold standard in upper urinary tract transitional-cell carcinoma (UT-TCC) management has been nephroureterectomy with excision of the bladder cuff. Advances in endourologic instrumentation have allowed urologists to manage this malignancy. The feasibility and success of conservative measures for UT-TCC have been widely published, but there has not been an objective cost analysis performed to date. Our goal was to examine the direct costs of renal-sparing conservative measures v nephroureterectomy and subsequent chronic kidney disease (CKD) or end-stage renal disease (ESRD). Secondary analysis includes a discussion of survival and quality-of-life issues for both treatment …

Recent Trends In Soft-Tissue Infection Imaging., Nicholas Petruzzi, Md, Nylla Shanthly, Mbbs, Drm, Mathew L. Thakur, Phd

Department of Radiation Oncology Faculty Papers

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, central nervous system, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection-specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory tract infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to …

Positional Information Generated By Spatially Distributed Signaling Cascades., Javier Muñoz-García, Zoltan Neufeld, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile …

Immunological Assessment Of Plant-Derived Avian Flu H5/Ha1 Variants., S Spitsin, V Andrianov, N Pogrebnyak, Y Smirnov, N Borisjuk, C Portocarrero, V Veguilla, H Koprowski, M Golovkin

Department of Cancer Biology Faculty Papers

Polypeptide variants of the HA1 antigenic domain of the H5N1 avian influenza virus hemagglutinin (HA) molecule were produced in plants using transient and stable expression systems and fused with His/c-myc tags or with mouse or human Fc antibody fragments. The resulting peptides were purified and used for intramuscular immunization of mice. While the recombinant HA1 variants induced a significant serum humoral immune response in the mice, none of the HA1 preparations induced virus-neutralizing antibodies. Fusion with the Fc fragment improved overall yield of the constructs and allowed purification requiring only a single step, but led to no detectable fusion-related enhancement …

Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients …

Download The Pdf Of The Full Issue

CenterPieces

Download the PDF of the Full Issue of CenterPieces, Fall 2007, Volume 2, Issue 1.

We Are Seeking Participants For The Following Studies

CenterPieces

All participants in our research projects receive compensation for participating in study interviews. For further information about these and other studies, please visit our website at www.jefferson.edu/jchp/carah or call 215-503-2897 to speak to a member of our staff.

Coping Tips For Caregivers

CenterPieces

Educate yourself about the disease your family member is facing and how it may affect his or her behavior, pain level or quality of life.

Find sources of help for caregiver tasks. Contact family, friends, neighbors, church/synagogue, workplace, Area Agency on Aging or other organizations.

Protect your personal time for something you enjoy or something you need to get done.

Helping Caregivers To Cope

CenterPieces

When Deb Lacktman promised her dying father that she would care for her mother, Margaret Rimato, after he passed, she wasn’t prepared for the challenges to come. Shortly after he passed, Margaret became increasingly forgetful and delusional. Deb attributed her mother’s memory loss to the stress of losing her husband. With time, however, Margaret’s condition worsened and she was diagnosed with Alzheimer’s disease.

As the primary caregiver of a parent with Alzheimer’s, Deb dealt with various complications beyond the memory loss. Her mother continually roamed the house in the middle of the night, for no apparent reason. It turned out …

Speaking With Barry Rovner, Md

CenterPieces

Q: What Alzheimer’s related studies are you involved in currently at the Farber Institute for Neurosciences?

Dr. Rovner: We are evaluating three exciting new disease-modifying drug treatments that may slow down the course of Alzheimer’s disease. I am also a Principal Investigator of Jefferson’s Center for Excellence in Neurodegenerative Diseases funded by the Pennsylvania Department of Health Tobacco Settlement grant. We are testing innovative screening methods to identify dementia in community-based agencies serving older adults, as well as testing in-home skills training services to delay nursing home placement and reduce stress for a racially diverse group of family caregivers. This …