Medical Specialties Commons^™

Elongation Factor 1 Alpha Interacts With Phospho-Akt In Breast Cancer Cells And Regulates Their Proliferation, Survival And Motility., Luisa Pecorari, Oriano Marin, Chiara Silvestri, Olivia Candini, Elena Rossi, Clara Guerzoni, Sara Cattelani, Samanta A Mariani, Francesca Corradini, Giovanna Ferrari-Amorotti, Laura Cortesi, Rita Bussolari, Giuseppe Raschellà, Massimo R Federico, Bruno Calabretta

Kimmel Cancer Center Faculty Papers

BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …

The Efficacy Of Surgical Decompression Before 24 Hours Versus 24 To 72 Hours In Patients With Spinal Cord Injury From T1 To L1--With Specific Consideration On Ethics: A Randomized Controlled Trial., Vafa Rahimi-Movaghar, Soheil Saadat, Alexander R Vaccaro, Seyed Mohammad Ghodsi, Mohammad Samadian, Arya Sheykhmozaffari, Seyed Mohammad Safdari, Bahram Keshmirian

Department of Neurosurgery Faculty Papers

BACKGROUND: There is no clear evidence that early decompression following spinal cord injury (SCI) improves neurologic outcome. Such information must be obtained from randomized controlled trials (RCTs). To date no large scale RCT has been performed evaluating the timing of surgical decompression in the setting of thoracolumbar spinal cord injury. A concern for many is the ethical dilemma that a delay in surgery may adversely effect neurologic recovery although this has never been conclusively proven. The purpose of this study is to compare the efficacy of early (before 24 hours) verse late (24-72 hours) surgical decompression in terms of neurological …

Hematologic Effects Of Placental Pathology On Very Low Birthweight Infants Born To Mothers With Preeclampsia., Kelly J. Zook, Md, Amy B. Mackley, Rnc, Jennifer Kern, David A. Paul. Md

Department of Pediatrics Faculty Papers

OBJECTIVE: To investigate the effect of placental pathology on neonatal neutrophils, platelets, hematocrit and nucleated red blood cells in very low birthweight (VLBW) infants born to mothers with preeclampsia. STUDY DESIGN: Retrospective cohort study of infants with birthweight < 1500 g born to mothers with preeclampsia from july, 2002 to july, 2006 at a single level III neonatal intensive care unit. Placental pathology was reviewed for the presence of placental infarction and vasculopathy. Hematologic parameters from day of life 0, 1 and 2 were obtained. Statistical analysis included repeated-measures analysis of variance and multivariable analysis using logistic regression. RESULT: The study sample included 203 infants with estimated gestational age of 28+/-3 weeks; 45% had placental infarctions and 26% placental vasculopathy. Infants with neutropenia and thrombocytopenia did not have an increased occurrence of placental infarction or maternal vasculopathy but were more likely to be of small gestational age (SGA) and of lower gestational age compared with infants without neutropenia or thrombocytopenia. After multivariable analysis, gestational age and SGA remained associated with both neutropenia and thrombocytopenia whereas placental infarction and vasculopathy did not remain in the models. CONCLUSION: In our population of VLBW infants born to mothers with preeclampsia, placental pathology was common. There was no association of placental infarction or vasculopathy with neonatal neutropenia and thrombocytopenia. The data suggest that neonatal hematologic effects of maternal preeclampsia, if related to the placenta, are associated with factors other than placental histology.

Increased Susceptibility Of Spinal Muscular Atrophy Fibroblasts To Camptothecin Is P53-Independent., Chia-Yen Wu, Ilsa Gómez-Curet, Vicky L Funanage, Mena Scavina, Wenlan Wang

Department of Pediatrics Faculty Papers

BACKGROUND: Deletion or mutation(s) of the survival motor neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA). The SMN protein is known to play a role in RNA metabolism, neurite outgrowth, and cell survival. Yet, it remains unclear how SMN deficiency causes selective motor neuron death and muscle atrophy seen in SMA. Previously, we have shown that skin fibroblasts from SMA patients are more sensitive to the DNA topoisomerase I inhibitor camptothecin, supporting a role for SMN in cell survival. Here, we examine the potential mechanism of camptothecin sensitivity in SMA fibroblasts.

RESULTS: Camptothecin treatment reduced the DNA relaxation activity …

Autistic Disorder Associated With A Paternally Derived Unbalanced Translocation Leading To Duplication Of Chromosome 15pter-Q13.2: A Case Report., David J Wu, Nicholas J Wang, Jennette Driscoll, Naghmeh Dorrani, Dahai Liu, Marian Sigman, N Carolyn Schanen

Department of Pediatrics Faculty Papers

Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15. Here we describe a boy with a chromosome 15 duplication arising from a 3:1 segregation error of a paternally derived translocation between chromosome 15q13.2 and chromosome 9q34.12, which led to trisomy of chromosome 15pter-q13.2 and 9q34.12-qter. Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15. The child manifests many characteristics of the maternally-derived duplication …

Functional Interleukin-17 Receptor A Is Expressed In Central Nervous System Glia And Upregulated In Experimental Autoimmune Encephalomyelitis., Jayasri Das Sarma, Bogoljub Ciric, Ryan Marek, Sanjoy Sadhukhan, Michael L. Caruso, Jasmine Shafagh, Denise C. Fitzgerald, Kenneth S. Shindler, Am Rostami

Department of Neurology Faculty Papers

BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ …

Repression Of E-Cadherin By The Polycomb Group Protein Ezh2 In Pancreatic Cancer, A. D. Toll, A. Dasgupta, M. Potoczek, C. G. Kleer, J. R. Brody, A. K. Witkiewicz

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Our study suggest that E-cadherin downregulation may lead to EZH20-mediated invasion and metastasis. While strong diffuse EZH2 expression is seen in PDA, overexpression may be present in IPMN.

Identification Of Gastrointestinal Contamination In Pancreatic Fna, A. D. Toll, M. Bibbo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In contrast to previous work, our preliminary results indicate B72.3 expression cannot be reliably used to identify GIC. A lack of CEA expression, however, may be used to identify both gastric and duodenal contamination. This represents an important diagnostic aid in the evaluation of suspected low-grade mucinous lesions.

Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation. RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed …

Isolated Polyethylene Exchange Versus Acetabular Revision For Polyethylene Wear, Camilo Restrepo, Elie Ghanem, Carrie Houssock, Mathew Austin, Javad Parvizi, William J. Hozack

Department of Orthopaedic Surgery Faculty Papers

Polyethylene wear and osteolysis are not uncommon in THA mid- and long-term. In asymptomatic patients the dilemma faced by the orthopaedic surgeon is whether to revise the cup and risk damage to the supporting columns and even pelvic discontinuity or to perform isolated polyethylene exchange and risk a high rate of postoperative recurrent instability and dislocation that will necessitate further surgery. We retrospectively reviewed 62 patients (67 hips) who underwent revision arthroplasty for polywear and osteolysis. Thirty-six hips had isolated polyethylene exchange, while 31 had full acetabular revision. The minimum followup was 2 years (mean, 2.8 years; range, 2-5 years). …

High-Resolution Analysis Of Dna Copy Number Alterations In Patients With Primary Open-Angle Glaucoma., Khaled K Abu-Amero, Ali Hellani, Patrick Bender, George L. Spaeth, Jonathan Myers, L Jay Katz, Marlene Moster, Thomas M Bosley

Wills Eye Hospital Papers

PURPOSE: To determine whether patients with isolated primary open-angle glaucoma (POAG) have evidence of chromosomal copy number alterations.

METHODS: Twenty-seven Caucasian and African-American POAG patients and 12 ethnically matched controls were carefully screened for possible glaucoma and tested for chromosomal copy number alterations using high resolution array comparative genomic hybridization.

RESULTS: No POAG patient had evidence of chromosomal copy number alterations when compared to normal ethnically matched controls. Additionally, there was no evidence of somatic mosaicism in any tested POAG patient.

CONCLUSIONS: Chromosomal deletions and/or duplications were not detected in POAG patients as compared to controls. Other chromosomal imbalances such …

Prolonged Monitoring After Decelerations On Outpatient Non-Stress Tests: How Long Is Enough?, P. Koduri, Md, M. Giraldo, Md, V. Berghella, Md, S. P. Chauhan, Md

Department of Obstetrics and Gynecology Faculty Papers

Objective: To determine the appropriate duration of prolonged monitoring following decelerations noted on outpatient non-stress test (NST).

Conclusion: Prolonged monitoring beyond 120 min is not associated with increased rate of delivery secondary to NRFS or worse neonatal outcome measured by the 5 minute Apgar score. Monitoring after a deceleration on outpatient NST may be limited to less than 120 minutes. Larger studies are needed to confirm this finding.

Does 17 Alpha-Hydroxyprogesterone Caproate Decrease The Rate Of Preterm Birth In Women With An Ultrasound-Indicated Cerclage?, T. J. Rafael, D. Mackeen, V. Berghella

Department of Obstetrics and Gynecology Faculty Papers

Objective: To estimate whether the use of 17 alpha-hydroxyprogesterone caproate (17P) in women with an ultrasound-indicated cerclage (UIC) reduces the rate of preterm birth (PTB).

Conclusions: Among women with a prior spontaneous PTB and current UIC for CL<25mm, 17P did not reduce the rate of PTB <35 weeks.

Effectiveness Of 17-Alpha-Hydroxyprogesterone Caproate On The Prevention Of Preterm Birth In Women With A History-Indicated Cerclage, D. Mackeen, Md, T. J. Rafael, Md, J. Zavodnick, Ba, V. Berghella, Md

Department of Obstetrics and Gynecology Faculty Papers

Objective: To determine whether 17-alpha-hydroxyprogesterone caproate (17P) reduces the incidence of preterm birth (PTB) in women with a history-indicated cerclage.

Conclusions: 17P does not appear to have an effect on preterm birth <35 weeks in women with a history-indicated cerclage.

Cervical Cancer Prevention In Pregnant Women: Is Biopsy Useful?, N. S. Seligman, Md, J. Zavodnick, Ba, K. Mccullen, Md

Department of Obstetrics and Gynecology Faculty Papers

Objective: To estimate if cervical biopsy at the time of colposcopy changes the management or outcome of abnormal cervical cytology during pregnancy.

Conclusion: Biopsy of suspected cervical lesions can be safely deferred until after pregnancy because there were no significant changes between antepartum and postpartum CC and no missed cases of cervical cancer were detected.

The Value Of Implantable Cardioverter-Defibrillators In Managing Atrial Fibrillation, Daniel Frisch

Division of Cardiology Faculty Papers

Atrial fibrillation (AF) is associated with an increased risk of mortality as well as significant morbidity including bothersome symptoms, exacerbation of heart failure, and thromboembolic events. Explanations for the mortality risk are variable, but the majority opinion favors AF as a marker of reduced health status, especially cardiovascular health.

Intramedullary Spinal Cord Metastases And Radiation Therapy: A Case Report, Daniel Ikeda, James S. Harrop Md

JHN Journal

Intramedullary spinal cord metastases (ISCM) are a clinically rare, although devastating, complication of disseminated cancer. These lesions have been reported to originate from many types of solid tumors, although primary lung carcinoma, particularly small cell, is the most common etiology. These metastases, which can occur anywhere along the spinal cord, often represent the end-stage of the disease process with limited survival outcomes.

Patients with ISCM may develop a variety of neurological deficits with treatment goals aimed at palliation. Different modalities of treatment have been found to preserve or restore ambulation and neurological function. The options for therapeutic intervention include surgical, …

Cervical Intramedullary Ganglioma, Harminder Singh Md, Ashwini Sharan Md, John K. Ratliff Md

JHN Journal

A 48 year male presented to the ER with severe headaches which were episodic in nature and which had been present for several weeks. Patient had a history of traumatic head injury (TBI) several years prior. Otherwise, he was in good health with no significant past medical or surgical history.

On physical exam, patient was oriented x 3 with an intact cranial nerve exam. He had significant upper and lower extremity spasticity with mild hand intrinsic weakness. His motor exam was otherwise unremarkable. His gait was very spastic. He had sustained lower extremity clonus, upgoing toes, and increased tone in …

Surgeon Opinions On Use Of Epidural Steroids In Treatment Of Lumbar Disk Disease: Results Of An Online Survey, John K. Ratliff Md, Mitchell Maltenfort Phd, Bryan Lebude

JHN Journal

“Standard of care” can vary along regional and specialty lines; it is common to discover that a local “standard” can be different somewhere else. Opinions may differ between pain management specialists, primary care physicians, and spine surgeons with regard to use of conservative treatment modalities.

Opinion within a given group of practitioners, however, should converge. Local differences between hospitals may exist, but conferences, professional journals, and national boards for certification are mechanisms that should act to maintain homogeneity within a professional group. It could be expected that commonly utilized treatment approaches within a well defined group of sub-specialists should converge. …

Case Report: Intramedullary Cervical Spinal Cord Hemangioblastoma With An Evaluation Of Von Hippel-Lindau Disease, Steven Falowski Md, Ashwini Sharan Md, James S. Harrop Md, John K. Ratliff Md

JHN Journal

History of Present Illness

MO is a 49 year old male with a history of multiple sclerosis who presents with a one year history of progressive numbness in his shoulders bilateral and upper back. The patient describes occasional sharp pains that radiate to his first three fingers on his right hand. He denies weakness, clumsiness, difficulty walking, or bladder/bowel dysfunction. He describes no problems with handwriting, or fine motor skills.

Jhn Journal (Download The Full Pdf Of This Issue), Robert H. Rosenwasser Md

JHN Journal

Complete December 2008 issue of JHN Journal

Spinal Cord Stimulators: An Introduction, Steven Falowski Md

JHN Journal

Pain can be divided into two broad categories, nociceptive pain and neuropathic pain. Nociceptive pain is a dull, throbbing pain which results from irritated nerves after physical tissue injury. This is seen commonly in cancer or after a fracture. Nociceptive pain is amenable to treatment with pain medications such as opioids and/or anti-inflammatories. Neuropathic pain is described as burning, shooting, or shocking pain. This type of pain results from nerve damage or abnormal nerve conduction such as pain exhibited with failed back syndrome, post surgical pain, neuromas, shingles, and complex regional pain syndrome (previously called RSD or causalgia). Neuropathic pain …

Minimally Invasive Surgery For Skull Base Tumors, James J. Evans Md, Marc R. Rosen Md

JHN Journal

The Jefferson Center for Minimally Invasive Cranial Base Surgery and Endoscopic Neurosurgery reflects three of the current evolutions in neurological surgery. The first of these is reflected in the name of the Center itself. Surgical Procedures, Minimally Invasive, a Medline Subject Heading since 1998, is defined as:

Procedures that avoid use of open invasive surgery in favor of closed or local surgery. These generally involve use of laparoscopic devices and remote-control manipulation of instruments with indirect observation of the surgical field through an endoscope or similar device. With the reduced trauma associated with minimally invasive surgery, long hospital stays may …

Clinical Guidelines Written By Residents, David W. Andrews Md

JHN Journal

“Variation” is an innocent word that that can represent many levels of frustration to the clinician. Variation among patients is the least of these; the physician expects patients and their individual problems to be as diverse as the human race itself. Variation within a practice should be due to matching the specific needs of the specific patient. Other variations can mean trouble if they represent differences in understanding of the problem among clinicians and other allied health practitioners. These differences could be between institutions or even between shifts within one institution.

Intracerebral Hemorrhage For The Palliative Care Provider: What You Need To Know., B Brent Simmons, Susan M Parks

Department of Family & Community Medicine Faculty Papers

Intracerebral hemorrhage (ICH) makes up 10%-30% of all strokes. Palliative care providers are often asked to get involved with ICH cases to aid with development of short-term and long-term goals. Prognosis can be calculated using the ICH score (based on Glasgow Coma Score score, ICH volume, presence of intraventricular hemorrhage, age, and location of origin) or the Essen score (based on age, NIH Stroke Scale [NIHSS], and level of consciousness). Do-not-resuscitate (DNR) status is important to discuss with families. Expert consensus states DNR is appropriate if the patient has two of the following: severe stroke, life-threatening brain damage, or significant …

Angioedema After Local Trauma In A Patient On Angiotensin-Converting Enzyme Inhibitor Therapy, B. B. Simmons, Michelle A. Folsom, L.Eslie A. Bryden, James Studdiford

Department of Family & Community Medicine Faculty Papers

Angioedema is a side effect that is often associated with use of angiotensin converting enzyme inhibitor medications. These medications result in increased levels of circulating bradykinins. This case illustrates the result of a local traumatic event to the upper lip, presumably causing marked bradykinin release in a patient who was taking an ACE-inhibitor. The local release of bradykinin from trauma, in addition to decreased bradykinin catabolism secondary to ACE-inhibitor therapy resulted in angioedema predominantly in the upper lip. The angioedema resolved with discontinuation of the ACE-inhibitor.

Young Woman With Chronic Conversion Disorder With Dramatic Improvement In Upper Motor Neuron Type Syndromes Through The Use Of Electromyography (Emg) Triggered Biofeedback, Bruce H. Hsu, Md, Nethra S. Ankam, Md, Ralph J. Marino

Department of Rehabilitation Medicine Faculty Papers

Patient: 31 year old woman chronic flexion contracture of hand, prior history seizure disorder, chronic conversion disorder.

Program Description: Patient presented initially to neurology service with chronic right hand flexion contracture in the context of 3 days of weakness and numbness in lower extremities after exertion. MRI/MRA Brain, Head CT, CT of entire spine were all unrevealing. Patient was transferred to the rehabilitation unit 8 days after initial admission. On rehabilitation admission patient exam was noted to have right hand markedly flexed with pain to passive ranging out of extreme flexion, chronic in nature. Patient initially had her hand ranged …

Increasing Appropriateness Of Hospital Admissions In The Emilia-Romagna Region Of Italy., Daniel Louis, Francesco Taroni, Rita Melotti, Carol Rabinowitz, Maria Vizioli, Monica Fiorini, Joseph Gonnella

Department of Family & Community Medicine Faculty Papers

OBJECTIVES: The Emilia-Romagna region of Italy has reduced the number of available hospital beds and introduced financial incentives to curb hospital use. The goal of this study was to assess the impact of these policies on changes over time in the number of acute hospital admissions classified in diagnosis related groups (DRGs) that could be treated safely and effectively in alternative, less costly settings.

METHODS: The assessment of the appropriate site of care was based on analysis of hospital discharge data for all hospitals for the selected diagnosis related groups in the Emilia-Romagna region for 2001 to 2005. The necessity …

Deletion Of Gsk-3beta In Mice Leads To Hypertrophic Cardiomyopathy Secondary To Cardiomyoblast Hyperproliferation., Risto Kerkela, Lisa Kockeritz, Katrina Macaulay, Jibin Zhou, Bradley W. Doble, Cara Beahm, Sarah Greytak, Kathleen Woulfe, Chinmay M. Trivedi, James R. Woodgett, Jonathan A. Epstein, Thomas Force, Gordon S. Huggins

Center for Translational Medicine Faculty Papers

Based on extensive preclinical data, glycogen synthase kinase-3 (GSK-3) has been proposed to be a viable drug target for a wide variety of disease states, ranging from diabetes to bipolar disorder. Since these new drugs, which will be more powerful GSK-3 inhibitors than lithium, may potentially be given to women of childbearing potential, and since it has controversially been suggested that lithium therapy might be linked to congenital cardiac defects, we asked whether GSK-3 family members are required for normal heart development in mice. We report that terminal cardiomyocyte differentiation was substantially blunted in Gsk3b(-/-) embryoid bodies. While GSK-3alpha-deficient mice …