Medicine and Health Sciences Commons^™

Jefferson Digital Commons Quarterly Report: October-December 2013, Daniel G. Kipnis, Msi

Jefferson Digital Commons Reports

Year end quarterly report for the Jefferson Digital Commons. Includes statistics, pie chart breaking down types of resources indexed in the JDC, comments from users, highlighted new assets in the collection.

The Influence Of Obesity On The Outcome Of Treatment Of Lumbar Disc Herniation: Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Jeffrey A Rihn, Mark Kurd, Alan S Hilibrand, Jon Lurie, Wenyan Zhao, Todd Albert, James Weinstein

Rothman Institute Papers

BACKGROUND: Questions remain as to the effect that obesity has on patients managed for symptomatic lumbar disc herniation. The purpose of this study was to determine if obesity affects outcomes following the treatment of symptomatic lumbar disc herniation.

METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial for the treatment of lumbar disc herniation. A comparison was made between patients with a body mass index of/m² (nonobese) (n = 854) and those with a body mass index of ≥30 kg/m² (obese) (n = 336). Baseline patient demographic and clinical characteristics were documented. Primary …

Synchronous And Asynchronous Theta And Gamma Activity During Episodic Memory Formation., John F Burke, Kareem A Zaghloul, Joshua Jacobs, Ryan B Williams, Michael R Sperling, Ashwini D Sharan, Michael J Kahana

Department of Neuroscience Faculty Papers

To test the hypothesis that neural oscillations synchronize to mediate memory encoding, we analyzed electrocorticographic recordings taken as 68 human neurosurgical patients studied and subsequently recalled lists of common words. To the extent that changes in spectral power reflect synchronous oscillations, we would expect those power changes to be accompanied by increases in phase synchrony between the region of interest and neighboring brain areas. Contrary to the hypothesized role of synchronous gamma oscillations in memory formation, we found that many key regions that showed power increases during successful memory encoding also exhibited decreases in global synchrony. Similarly, cortical theta activity …

Castleman Disease In The Pediatric Neck: Case Report And Literature Review, Mindy R. Rabinowitz, Md, Jessica R. Levi, Md, Katrina Conard, Md, Udayan Shah, Md

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Objective: To investigate the common features of cervical pediatric Castleman disease (CD).

Study Design: Case report and literature review of pediatric patients with cervical CD.

Methods: Online medical journal databases were searched for patients aged 18 years or younger. Eighteen published papers were found, comprising 29 cases. One case from our institution was also included for a total of 30 patients.

Results: An asymptomatic mass in level V was the most common presentation. No gender differences were noted. Multiple forms of imaging were pursued, and no particular modality showed signs specific for CD. All cases were treated with complete surgical …

What’S Your Line? Defining Pharmacists' Role In Jejunostomy Tube Medication Administration, Jamie M. Gomes, Pharmd, Gloria M. Espinosa, Pharmd, Brian P. Roslund, Pharmd, Bcps, Joanne Heil, Pharmd, Bcps

Pharmacy Presentations, Posters, and Grand Rounds

Enteral nutrition is preferred over parenteral nutrition in patients with inadequate oral intake for an extended period of time. Enteral feeding helps preserve the functioning of the gastrointestinal (GI) tract. 1 Feeding tubes provide access to the GI tract allowing administration of medication while unable to swallow. Drug therapy is complicated by drug formulation, absorption site, first-pass elimination, as well as the size and placement of the tube.1-3 Medication errors revolving around administration via enteral feeding tubes represent a need for education and implementation of hospital guidelines.

Increased Serum And Musculotendinous Fibrogenic Proteins Following Persistent Low-Grade Inflammation In A Rat Model Of Long-Term Upper Extremity Overuse., Helen G L Gao, Paul W Fisher, Alex G Lambi, Christine K Wade, Ann E Barr-Gillespie, Steven N Popoff, Mary F Barbe

Department of Physical Therapy Faculty Papers

We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater …

Diet And Nutrition In Cancer Survivorship And Palliative Care., Anthony J Bazzan, Andrew B Newberg, William C Cho, Daniel A Monti

Marcus Institute of Integrative Health Faculty Papers

The primary goal of palliative cancer care is typically to relieve suffering and improve quality of life. Most approaches to diet in this setting have focused only on eating as many calories as possible to avoid cachexia. However, as the concept of palliative care has evolved to include all aspects of cancer survivorship and not just end of life care, there is an increasing need to thoughtfully consider diet and nutrition approaches that can impact not only quality of life but overall health outcomes and perhaps even positively affect cancer recurrence and progression. In this regard, there has been a …

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …

Implementation Of Three Times Daily Small Volume Parenteral (Svp) Processing Using Lean Methodology, Phuoc Lynsey Le, Pharmd, Dominick Bulone, Pharmd, Akta S. Patel, Pharmd, Bcps, Glenn Oettinger, Pharmd, Bcps, Dennis Delisle, Mhsa, Pmp

Pharmacy Presentations, Posters, and Grand Rounds

Clinical Importance

• Small volume parenteral (SVP) medications are batch-processed once daily at a 900+ bed academic medical center
• Labels are printed 36 hours before medications are due and prepared and delivered for a 24-hour period
• Therapy changes, discontinuations or patient transfers lead to increased rework, missing doses, and ultimately waste
• Lean methodology was originally developed as a production philosophy and quality
• system with an emphasis on problem solving, partnership, and process improvement1-3
• The Lean philosophy emphasizes the continual identification and elimination of waste in order to maximize value1
• Lean has been used in healthcare with great success4-5

Rituximab Treatment For Antibody-Mediated Rejection (Amr) Following Heart And Kidney Transplant, Laura Falconieri, Ba, Pharmd, Cheryl A. Abbas, Pharmd

Pharmacy Presentations, Posters, and Grand Rounds

Background

Antibody Mediated Rejection (AMR)1,2

• Rejection that occurs due to antibodies against donor-specific antigen (DSA)

– Antibodies activate complement system

– Leads to cell death and tissue necrosis

• Risk Factors

– Pregnancy

– Blood transfusions

– Prior transplantation

• Types of AMR

– Hyperacute

• Occurs within minutes of graft transplantation causing death of the graft

• Due to pre-formed antibodies present in high titers

• Rarely occurs now due to universal cross-matching

– Acute

• Occurs within a few days of transplantation causing graft dysfunction

• Due to pre-formed antibodies or antibodies that develop de novo after …

Use Of Apheresis And Insulin For Hypertriglyceridemia-Induced Pancreatitis And Diabetic Ketoacidosis, Drew Kirk, Pharmd, Cara Mcdaniel, Pharmd, Bcps, Rohit A. Moghe, Pharmd, Msph, Cde

Pharmacy Presentations, Posters, and Grand Rounds

CLINICAL RELEVANCE

• Acute pancreatitis (AP) is a common gastrointestinal disease that may result in multiple organ failure and death¹

– Gallstones & alcohol are the most common causes of AP¹

– Hypertriglyceridemia (HTG) causes 1-4% of cases, and should be suspected if triglycerides (TG) are > 1,000 mg/dL in the absence of gallstones or history of significant alcohol use¹

– Clinical management of hypertriglyceridemia-induced pancreatitis (HTGP) is based primarily on anecdotal evidence and case reports

• Concurrent diabetic ketoacidosis (DKA) and AP have been described in the literature

– DKA may be a risk factor for AP, but it …

Multi-Nutrient Supplement Improves Hormone Ratio Associated With Cancer Risk., Anthony J. Bazzan, Md, George P Zabrecky, Andrew B. Newberg, Md

Marcus Institute of Integrative Health Faculty Papers

BACKGROUND: Gynecological cancers are among the most common in women and are directly related to a variety of hormonal factors. One potential risk factor associated with developing a gynecological malignancy is the ratio of two hormone metabolites, 2-Hydroxyestrone (2-HE) and 16alpha-Hydroxyestrone (16alpha-HE). A number of botanical constituents such as indoles, flavonoids, and resveratrol have been shown to have a favorable effect on the metabolic pathways that affect this ratio. The present study was designed to evaluate if a multi-nutrient supplement containing targeted botanical constituents would affect the 2-HE/16 alpha-HE ratio in middle-aged women.

METHODS: A retrospective analysis was performed on …

William Edwards Ladd, M.D. (1880-1967): The Description Of His Bands., Pei-Wen Lim, Md, Niels D. Martin, Md, Barry A. Hicks, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

In the early 20th century, an established surgical specialty catering to pediatric surgery did not exist, and pediatric surgical ailments were operated on by general surgeons. With his devotion to childhood diseases and his unique thinking in surgical development, William E. Ladd would become a leading figure in America by pioneering the field of pediatric surgery.

Dynamic Recruitment Of Micrornas To Their Mrna Targets In The Regenerating Liver., Jonathan Schug, Lindsay B Mckenna, Gabriel Walton, Nicholas Hand, Sarmistha Mukherjee, Kow Essuman, Zhongjie Shi, Yan Gao, Karen Markley, Momo Nakagawa, Vasumathi Kameswaran, Anastassios Vourekas, Joshua R Friedman, Klaus H Kaestner, Linda E Greenbaum

Department of Cancer Biology Faculty Papers

BACKGROUND: Validation of physiologic miRNA targets has been met with significant challenges. We employed HITS-CLIP to identify which miRNAs participate in liver regeneration, and to identify their target mRNAs.

RESULTS: miRNA recruitment to the RISC is highly dynamic, changing more than five-fold for several miRNAs. miRNA recruitment to the RISC did not correlate with changes in overall miRNA expression for these dynamically recruited miRNAs, emphasizing the necessity to determine miRNA recruitment to the RISC in order to fully assess the impact of miRNA regulation. We incorporated RNA-seq quantification of total mRNA to identify expression-weighted Ago footprints, and developed a microRNA …

Dual Fluorescent Molecular Substrates Selectively Report The Activation, Sustainability And Reversibility Of Cellular Pkb/Akt Activity., Duanwen Shen, Mingfeng Bai, Rui Tang, Baogang Xu, Xiaoming Ju, Richard Pestell, Samuel Achilefu

Department of Cancer Biology Faculty Papers

Using a newly developed near-infrared (NIR) dye that fluoresces at two different wavelengths (dichromic fluorescence, DCF), we discovered a new fluorescent substrate for Akt, also known as protein kinase B, and a method to quantitatively report this enzyme's activity in real time. Upon insulin activation of cellular Akt, the enzyme multi-phosphorylated a single serine residue of a diserine DCF substrate in a time-dependent manner, culminating in monophospho- to triphospho-serine products. The NIR DCF probe was highly selective for the Akt1 isoform, which was demonstrated using Akt1 knockout cells derived from MMTV-ErbB2 transgenic mice. The DCF mechanism provides unparalleled potential to …

Increased Levels Of Plasma Soluble Sema4d In Patients With Heart Failure., Qiongyu Lu, Ningzheng Dong, Qi Wang, Wenxiu Yi, Yuxin Wang, Shengjie Zhang, Haibo Gu, Xin Zhao, Xiaorong Tang, Boquan Jin, Qingyu Wu, Lawrence F Brass, Li Zhu

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Semaphorin 4D (Sema4D/CD100) is a 150-kDa transmembrane glycoprotein expressed by platelets and T-cells. When these cells are activated, Sema4D is cleaved proteolytically, generating a biologically active 120-kDa fragment (soluble Sema4D) capable of targeting receptors on platelets, B-cells, endothelial cells and tumor cells. However, its plasma levels and significance in heart failure (HF) have not been reported. In this study, we established an ELISA and detected soluble Sema4D in human plasma. In healthy controls, plasma Sema4D levels were higher in men than women (5.15±3.30 ng/mL, n = 63, vs. 4.19±2.39 ng/mL, n = 63, P

Jefferson Alumni Bulletin – Volume 62, Number 1, Winter 2013

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Features:

• Jefferson and Nemours: Partnering for Pediatric Patients
• Residency Program Limits: Can We Break the Training Bottleneck?
• Whooping Cough’s Comeback and Consequences

Departments:

• Dean's Column
• Findings: Targeting Dual Roles of PARP-1 May Slow Cancer Growth
• Faculty Profile: Robert L. Brent, MD, PhD: An International Authority on Congenital Disorders
• On Campus
• Alumna Profile: Cynthia L. Sears, MD ’77: A Life’s Work Inspired by Service Overseas
• Class Notes
• In Memoriam
• By the Numbers

Acute Activation, Desensitization And Smoldering Activation Of Human Acetylcholine Receptors., Barbara Campling, M.D., Frcpc, Alexander Kuryatov, Jon Lindstrom

Department of Neuroscience Faculty Papers

The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, …

Retro-Aortic Left Renal Vein, Joann Aichroth, Rdms, Traci B. Fox, Ms, Rt(R), Rdms, Rvt

Department of Radiologic Sciences Faculty Papers

The term retro-aortic left renal vein (RLRV) is defined as the left renal vein coursing posterior to the abdominal aorta. RLRV is an uncommon condition in which the left renal vein passes posterior to the abdominal aorta and anterior to the vertebrae. RLRV may lead to left renal vein hypertension (LRVH) syndrome, which is also known as Nutcracker syndrome. Nutcracker syndrome (NCS) is a condition in which the left renal vein is compressed causing hypertension of the vessel. RLRV and Nutcracker syndrome are vascular anomalies considered to be of clinical importance especially during surgical procedures of the renal vasculature.

Tracking Transplanted Bone Marrow Stem Cells And Their Effects In The Rat Mcao Stroke Model., Gregory V Goldmacher, Rena Nasser, Daniel Y Lee, Sargon Yigit, Robert Rosenwasser, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

In this study, rat bone marrow stromal stem cells (BMSCs) were tracked after IV administration to rats with experimental stroke caused by middle cerebral artery occlusion (MCAO). In addition, the effects of BMSC treatment on blood cell composition, brain glia and sensorimotor behavior was studied and compared to that which occurred spontaneously during the normal recovery process after stroke. We found that the vast majority of radiolabeled or fluorescently labeled BMSCs traveled to and remained in peripheral organs (lungs, spleen, liver) 3 days after IV injection in the MCAO rat. Once in the circulation, BMSCs also produced rapid alterations in …

Nuclear Translocation Of Cardiac G Protein-Coupled Receptor Kinase 5 Downstream Of Select Gq-Activating Hypertrophic Ligands Is A Calmodulin-Dependent Process., Jessica I Gold, Jeffrey S Martini, Jonathan Hullmann, Erhe Gao, J Kurt Chuprun, Linda Lee, Douglas G Tilley, Joseph E Rabinowitz, Julie Bossuyt, Donald M Bers, Walter J. Koch

Department of Medicine Faculty Papers

G protein-Coupled Receptors (GPCRs) kinases (GRKs) play a crucial role in regulating cardiac hypertrophy. Recent data from our lab has shown that, following ventricular pressure overload, GRK5, a primary cardiac GRK, facilitates maladaptive myocyte growth via novel nuclear localization. In the nucleus, GRK5's newly discovered kinase activity on histone deacetylase 5 induces hypertrophic gene transcription. The mechanisms governing the nuclear targeting of GRK5 are unknown. We report here that GRK5 nuclear accumulation is dependent on Ca(2+)/calmodulin (CaM) binding to a specific site within the amino terminus of GRK5 and this interaction occurs after selective activation of hypertrophic Gq-coupled receptors. Stimulation …

Secondary Membranous Nephropathy Associated With Guillain-Barré Syndrome., Edward J Filippone, Mitul Kanzaria, Rodney Bell, Eric Newman, John L Farber

Department of Medicine Faculty Papers

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome (NS) in adults. It may be primary, usually mediated by IgG4 anti-phospholipase A2 autoantibodies or secondary to various other conditions. Guillain- Barré syndrome (GBS) has been associated with MN, but a cause and effect relation has not been proven. We present a case of concurrent development of GBS and severe NS, with renal biopsy demonstrating MN. IgG4 stain was negative, indicating that most likely, the MN was secondary and probably caused by the underlying GBS.

Advancing Maternal Survival In The Global Context: Are Our Strategies Working?, Omar A Khan, Richard Derman, Nancy L Sloan

Department of Family & Community Medicine Faculty Papers

There have been significant gains in improving maternal mortality over the last two decades. Researchers have suggested a variety of interventions and mechanisms to explain these improvements. While it is likely that much of what has been done in research and programs has contributed to this decline, the evidence regarding what works in the settings in which women deliver continues to face many challenges. We review the evidence for these improvements and suggest that there remain areas to focus on, particularly the births which currently take place in an unsupervised or substandard environments. We highlight the main areas where more …

Molecular Staging Of Node Negative Patients With Colorectal Cancer., Terry Hyslop, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Metastatic disease is the principle cause of death from colorectal cancer. In that context, the most significant indicator of overall survival and therapeutic response to adjuvant chemotherapy is the presence of metastatic tumor cells in regional lymph nodes. Although histopathologic analysis of lymph nodes is central to all colorectal cancer staging paradigms, its prognostic and predictive value is limited. Indeed, about 30% of patients with histopathology-negative lymph nodes (pN0) die from metastatic disease, reflected by microscopic lymph node metastases that are overlooked by standard techniques. These unrecognized tumor cells are especially important when considering racial disparities in outcomes in colorectal …

Two Coiled-Coil Domains Of Chlamydia Trachomatis Inca Affect Membrane Fusion Events During Infection., Erik Ronzone, Fabienne Paumet

Department of Microbiology and Immunology Faculty Papers

Chlamydia trachomatis replicates in a parasitophorous membrane-bound compartment called an inclusion. The inclusions corrupt host vesicle trafficking networks to avoid the degradative endolysosomal pathway but promote fusion with each other in order to sustain higher bacterial loads in a process known as homotypic fusion. The Chlamydia protein IncA (Inclusion protein A) appears to play central roles in both these processes as it participates to homotypic fusion and inhibits endocytic SNARE-mediated membrane fusion. How IncA selectively inhibits or activates membrane fusion remains poorly understood. In this study, we analyzed the spatial and molecular determinants of IncA's fusogenic and inhibitory functions. Using …

Toward A Network Model Of Mhc Class Ii-Restricted Antigen Processing., Michael A Miller, Asha Purnima V Ganesan, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

The standard model of Major Histocompatibility Complex class II (MHCII)-restricted antigen processing depicts a straightforward, linear pathway: internalized antigens are converted into peptides that load in a chaperone dependent manner onto nascent MHCII in the late endosome, the complexes subsequently trafficking to the cell surface for recognition by CD4(+) T cells (TCD4+). Several variations on this theme, both moderate and radical, have come to light but these alternatives have remained peripheral, the conventional pathway generally presumed to be the primary driver of TCD4+ responses. Here we continue to press for the conceptual repositioning of these alternatives toward the center while …

College Within The College: Population Health, James D. Plumb, Md, Mph, Rickie Brawer, Mph, Phd, Mches, Abbie Santana, Msph, Rob Simmons, Drph, Mph, Mches, Cph, Nancy L. Chernett, Ma, Mph

College of Population Health Lectures, Presentations, Workshops

College within the College (CwiC) – Population Health Skills for Physicians

• Incorporate culturally relevant information into a treatment plan for a patient

• Counsel individuals about healthy lifestyles

• Identify community support and resources to serve patients

• Coordinate health care services as a member of multidisciplinary teams

• Promote primary and secondary prevention

• Advocate for the needs of patients and the community

• Conduct population health research/evaluation

• Promote healthy lifestyles in communities

• Work in partnership with community based agencies and organizations

Infections In Anterior Cruciate Ligament Reconstruction, C. Stucken, D.N. Garras, J.L. Shaner, Steven B. Cohen

Rothman Institute Papers

Context: Anterior cruciate ligament (ACL) reconstruction is a safe, common, and effective method of restoring stability to the knee after injury, but evolving techniques of reconstruction carry inherent risk. Infection after ACL reconstruction, while rare, carries a high morbidity potentially resulting in poor clinical outcome.

Evidence Acquisition: Data were obtained from previously published peer-reviewed literature through a search of the entire PubMed database (up to December 2012) as well as from textbook chapters.

Results: Treatment with culture-specific antibiotics and debridement with graft retention is generally more effective than graft removal, but with persistent infection consideration should be given to graft …

Periodontal Disease Is An Independent Predictor Of Intracardiac Calcification., Gregg S Pressman, Atif Qasim, Nitin Verma, Masami Miyamae, Kumiko Arishiro, Yasuhiro Notohara, Vitalie Crudu, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND: Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease.

HYPOTHESIS: We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis.

METHODS: Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification.

RESULTS: Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In …

Value-Based Analysis Of Routine Pathologic Septal And Inferior Turbinate Specimens., James J Daniero, Jaemi S Chu, Brian J O'Hara, Edmund A. Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

This article was presented at the 2012 AAO-HNSF Annual Meeting & OTO EXPO; September 9-12, 2012; Washington, DC.

Objective To determine the frequency and clinical relevance of unanticipated histopathologic results in routine sinonasal surgery and evaluate the necessity for histologic processing of nasal septal cartilage, bone, and inferior turbinate specimens. Study Design Case series with chart review. Setting Tertiary care academic medical center. Subjects and Methods A retrospective review of surgical pathology reports on adult patients undergoing sinonasal surgery during a 5-year period from 2005 to 2010 was performed. All cases with the preoperative diagnosis of sinonasal neoplasia, autoimmune disease, …