Medicine and Health Sciences Commons^™

Mitochondrial Genome Sequence Analysis: A Custom Bioinformatics Pipeline Substantially Improves Affymetrix Mitochip V2.0 Call Rate And Accuracy., Hongbo M Xie, Juan C Perin, Theodore G Schurr, Matthew C Dulik, Sergey I Zhadanov, Joseph A Baur, Michael P King, Emily Place, Colleen Clarke, Michael Grauer, Jonathan Schug, Avni Santani, Anthony Albano, Cecilia Kim, Vincent Procaccio, Hakon Hakonarson, Xiaowu Gai, Marni J Falk

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate …

Basal Internal Anal Sphincter Tone, Inhibitory Neurotransmission, And Other Factors Contributing To The Maintenance Of High Pressures In The Anal Canal, S. Rattan, J. Singh

Division of Gastroenterology and Hepatology Faculty Papers

Maintenance of the basal tone in the internal anal sphincter (IAS) is critical for rectoanal continence. Effective evacuation requires a fully functional rectoanal inhibitory reflex (RAIR)-mediated relaxation of the IAS via inhibitory neurotransmission (INT). Systematic studies examining the nature of the INT in different species have identified nitric oxide (NO) as the major inhibitory neurotransmitter. However, other mediators such as vasoactive intestinal polypeptide (VIP), ATP, and carbon monoxide (CO) may also play species-specific role under certain experimental conditions. Measurements of the intraluminal pressures in the IAS along with the force of the isolated IAS tissues are the mainstay in the …

Patient Empowerment And Multimodal Hand Hygiene Promotion: A Win-Win Strategy., Maryanne Mcguckin, Julie Storr, Yves Longtin, Benedetta Allegranzi, Didier Pittet

College of Population Health Faculty Papers

Patient empowerment is a new concept in health care that has now been extended to the domain of patient safety. Within the framework of the development of the new World Health Organization (WHO) Guidelines on Hand Hygiene in Health Care, the authors conducted a review of the literature from 1997 to 2008 to identify the evidence supporting programs aimed at encouraging patients to take an active role in their care. Patient empowerment is an integral part of the WHO hand hygiene multimodal strategy. Hand hygiene promotion strategies that have demonstrated evidence of successfully empowering patients include one or all of …

Adrenal Beta-Arrestin 1 Inhibition In Vivo Attenuates Post-Myocardial Infarction Progression To Heart Failure And Adverse Remodeling Via Reduction Of Circulating Aldosterone Levels, Anastasios Lymperopoulos, Phd, Giuseppe Rengo, Md, Carmela Zincarelli, Md, Jihee Kim, Phd, Walter J. Koch, Phd

Center for Translational Medicine Faculty Papers

ABSTRACT

OBJECTIVES: We investigated whether adrenal betaarrestin 1 (betaarr1)-mediated aldosterone production plays any role in post-MI HF progression.

BACKGROUND: Heart failure (HF) represents one of the most significant health problems worldwide and new and innovative treatments are needed. Aldosterone contributes significantly to HF progression after myocardial infarction (MI) by accelerating adverse cardiac remodeling and ventricular dysfunction. It is produced by the adrenal cortex after angiotensin II (AngII) activation of AngII type 1 receptors (AT1Rs), G protein-coupled receptors (GPCRs) that also signal independently of G proteins. G protein-independent signaling is mediated by betaarrestin (betaarr) -1 and -2. We recently reported that …

The Infected Hip: A Treatment Algorithm, Bahar Adeli, Javad Parvizi Md

Department of Orthopaedic Surgery Faculty Papers

The management of periprosthetic joint infection following total joint arthroplasty is presently a major challenge to orthopedic surgeons. Despite various treatment options available, the two-stage revision procedure is most often chosen in North America because of a high success rate, especially in cases involving resistant organisms. Sometimes the use of antibiotics alone, irrigation with debridement, or a one-stage exchange may be a more appropriate treatment option. Various factors such as the status of a patient’s immune system, time of onset of the infection, as well as susceptibility of causative microorganism should be considered as they play an important role in …

Jefferson Alumni Bulletin – Volume 60, Number 1, Winter 2011

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Features:

• Women in Medicine: Bridging the Gaps
• Time & Place
• Jefferson Women: Leaders Through the Decades
• Personal Stories

Ventral Hernia Repairs: 10 Year Single Institution Review At Thomas Jefferson University Hospital, Frederick C. Sailes, Md, Jason Walls, Md, Daria Guelig, Md, Mike Mirzabeigi, Ma, William D. Long, Ms, Albert Crawford, Phd, John H. Moore Jr, Md, Facs, Steven E. Copit, Md, Gary A. Tuma, M.D, James Fox, Md

Department of Surgery Faculty Papers

Abstract

Background Definitive repair of recurrent ventral hernias using abdominal wall reconstruction techniques is an essential tool in the armentarium for general and plastic surgeons. Ramirez 1 et al describes the “component separation” technique to mobilize the rectus-abdominus internal oblique and external oblique flap to correct the defect. The recurrence rate of incisional hernias increases to 20% after gastric bypass or extensive weight loss.2 The incidence of ventral hernias after failed recurrent hernia repair increases to 40%.3 It has been reported that utilizing the sliding myofascial flap repair technique, the recurrence rate was reduced to 8.5%.4

Materials and Methods This …

Serum Monocyte Chemoattractant Protein-1 In Pancreatic Cancer., Jennifer Sullivan, Qiaoke Gong, Terry Hyslop, Harish Lavu, Galina Chipitsyna, Charles Yeo, Hwyda A Arafat

Department of Surgery Faculty Papers

Background/Aims. Pancreatic ductal adenocarcinoma (PDA) has etiological association with chronic inflammation. Elevated circulating levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), are found in obese individuals. We hypothesized that serum MCP-1 levels are elevated in obese PDA patients. Methods. ELISA was used to analyze MCP-1 serum levels in PDA (n = 62) and intraductal papillary mucinous neoplasms (IPMN) (n = 27). Recursive partitioning statistical analysis investigated the relationship between log MCP-1 and clinicopathological parameters. Results. Log MCP-1 values were significantly (P < 0.05) elevated in patients with BMI ≥ 37.5. In patients with BMI < 37.5, average log MCP-1 values were significantly elevated in PDA patients when compared to IPMN patients. Within the IPMN group, higher log MCP-1 levels correlated with increased age. Recursive partitioning analysis of IPMN versus PDA revealed a strategy of predicting characteristics of patients who are more likely to have cancer. This strategy utilizes log MCP-1 as the primary factor and also utilizes smoking status, gender, and age. Conclusion. MCP-1 is a promising biomarker in pancreatic cancer. The potential of using MCP-1 to distinguish PDA from IPMN patients must be studied in larger populations to validate and demonstrate its eventual clinical utility.

Neurologic Improvement After Thoracic, Thoracolumbar, And Lumbar Spinal Cord (Conus Medullaris) Injuries, James S. Harrop, Md, Swetha Naroji, Mitchell G. Maltenfort, Phd, John K. Ratliff, Md, Stavropoula L. Tjoumakaris, Brian Frank, D. Greg Anderson, M.D., Todd Albert, Md, Alexander R. Vaccaro, Md, Phd

Department of Orthopaedic Surgery Faculty Papers

Study Design. Retrospective. Objective. With approximately 10,000 new spinal cord injury (SCI) patients in the United States each year, predicting public health outcomes is an important public health concern. Combining all regions of the spine in SCI trials may be misleading if the lumbar and sacral regions (conus) have a neurologic improvement at different rates than the thoracic or thoracolumbar spinal cord.

Summary of Background Data. Over a 10-year period between January 1995 to 2005, 1746 consecutive spinal injured patients were seen, evaluated, and treated through a level 1 trauma referral center. A retrospective analysis was performed on 150 patients …

Amyloid-Beta/Fyn–Induced Synaptic, Network, And Cognitive Impairments Depend On Tau Levels In Multiple Mouse Models Of Alzheimer’S Disease, Erik D. Roberson, Brian Halabisky, Jong W. Yoo, Jinghua Yao, Jeannie Chin, Fengrong Yan, Tiffany Wu, Patricia Hamto, Nino Devidze, Gui-Qiu Yu, Jorge J. Palop, Jeffrey L. Noebels, Lennart Mucke

Farber Institute for Neuroscience Faculty Papers

Alzheimer's disease (AD), the most common neurodegenerative disorder, is a growing public health problem and still lacks effective treatments. Recent evidence suggests that microtubule-associated protein tau may mediate amyloid-β peptide (Aβ) toxicity by modulating the tyrosine kinase Fyn.Weshowed previously that tau reduction prevents, and Fyn overexpression exacerbates, cognitive deficits in human amyloid precursor protein (hAPP) transgenic mice overexpressing Aβ. However, the mechanisms by which Aβ, tau, and Fyn cooperate in AD-related pathogenesis remain to be fully elucidated. Here we examined the synaptic and network effects of this pathogenic triad. Tau reduction prevented cognitive decline induced by synergistic effects of Aβ …

Potential For Interdependent Development Of Trna Determinants For Aminoacylation And Ribosome Decoding., Cuiping Liu, Howard Gamper, Hanqing Liu, Barry S Cooperman, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Although the nucleotides in tRNA required for aminoacylation are conserved in evolution, bacterial aminoacyl-transfer RNA synthetases are unable to acylate eukaryotic tRNA. The cross-species barrier may be due to the absence of eukaryote-specific domains from bacterial aminoacyl-transfer RNA synthetases. Here we show that whereas Escherichia coli CysRS cannot acylate human tRNA(Cys), the fusion of a eukaryote-specific domain of human CysRS overcomes the cross-species barrier in human tRNA(Cys). In addition to enabling recognition of the sequence differences in the tertiary core of tRNA(Cys), the fused eukaryotic domain redirects the specificity of E. coli CysRS from the A37 present in bacterial tRNA(Cys) …

Defining The Phenotypes Of Sickle Cell Disease., Samir K. Ballas

Department of Medicine Faculty Papers

The sickle cell gene is pleiotropic in nature. Although it is a single gene mutation, it has multiple phenotypic expressions that constitute the complications of sickle cell disease. The frequency and severity of these complications vary considerably both latitudinally in patients and longitudinally in the same patient over time. Thus, complications that occur in childhood may disappear, persist or get worse with age. Dactylitis and stroke, for example, occur mostly in childhood, whereas leg ulcers and renal failure typically occur in adults. It is essential that the phenotypic manifestations of sickle cell disease be defined accurately so that communication among …

Update On Pain Management In Sickle Cell Disease., Samir K Ballas

Department of Medicine Faculty Papers

Acute pain is the hallmark of sickle cell disease and is the most common cause of hospital admissions. Tissue damage due to vaso-occlusion releases numerous inflammatory mediators that initiate the transmission of painful stimuli that culminate in the perception of pain. The acute sickle cell painful crisis evolves along four phases. Each phase is coupled with changes in certain markers of the disease. Hospital readmission occurs within 1 week in about 16% of discharged patients and within 1 month in about 50% of discharged patients. Failure to treat acute pain aggressively may lead to chronic pain syndrome which, in turn, …

Dyssynchrony In Obese Subjects Without A History Of Cardiac Disease Using Velocity Vector Imaging, Bhaskar Purushottam Md, Anoop C. Parameswaran Md, Mph, Vincent M. Figueredo Md

Division of Cardiology Faculty Papers

Abstract

Aim: To examine the occurrence of intra-left ventricular (LV) dyssynchrony in obese versus non-obese subjects without known cardiac disease using velocity vector imaging (VVI).

Methods: One hundred ninety consecutive subjects with no known cardiac disease had their echocardiograms analyzed using VVI after excluding subjects with QRS duration >120ms or LV ejection fraction (LVEF) <55%. Study subjects were divided into two groups based on body mass index (BMI): obese (BMI >30 kg/m2) and non-obese (BMI <30 kg>/m2).

Results: The final cohort included 136 subjects (74 were obese), 32% female and mean age 55 + 16 years. Occurrence of intra LV dyssynchrony was higher in the obese compared to non-obese group.

Conclusions: There was an increased prevalence of …