Medical Specialties Commons^™

Global Cns Gene Transfer For A Childhood Neurogenetic Enzyme Deficiency: Canavan Disease., Paola Leone, Christopher G Janson, Scott J Mcphee, Matthew J During

Department of Neurosurgery Faculty Papers

The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant …

Radiculopathy And Myelopathy At Segments Adjacent To The Site Of A Previous Anterior Cervical Arthrodesis., Alan S. Hilibrand, Gregory D. Carlson, M A Palumbo, P K Jones, H H Bohlman

Rothman Institute Papers

BACKGROUND: We studied the incidence, prevalence, and radiographic progression of symptomatic adjacent-segment disease, which we defined as the development of new radiculopathy or myelopathy referable to a motion segment adjacent to the site of a previous anterior arthrodesis of the cervical spine.

METHODS: A consecutive series of 374 patients who had a total of 409 anterior cervical arthrodeses for the treatment of cervical spondylosis with radiculopathy or myelopathy, or both, were followed for a maximum of twenty-one years after the operation. The annual incidence of symptomatic adjacent-segment disease was defined as the percentage of patients who had been disease-free at …

Integrin-Dependent Control Of Translation: Engagement Of Integrin Alphaiibbeta3 Regulates Synthesis Of Proteins In Activated Human Platelets., Ravinder Pabla, Andrew S. Weyrich, Dan A. Dixon, Paul F. Bray, Thomas M. Mcintyre, Stephen M. Prescott, Guy A. Zimmerman

Cardeza Foundation for Hematologic Research

Integrins are widely expressed plasma membrane adhesion molecules that tether cells to matrix proteins and to one another in cell-cell interactions. Integrins also transmit outside-in signals that regulate functional responses of cells, and are known to influence gene expression by regulating transcription. In previous studies we found that platelets, which are naturally occurring anucleate cytoplasts, translate preformed mRNA transcripts when they are activated by outside-in signals. Using strategies that interrupt engagement of integrin alphaIIbbeta3 by fibrinogen and platelets deficient in this integrin, we found that alphaIIbbeta3 regulates the synthesis of B cell lymphoma 3 (Bcl-3) when platelet aggregation is induced …

Department Of Radiology-Annual Executive Summary Report-July 1, 1998 To June 30, 1999, David C. Levin, M.D.

Department of Radiology Administrative Documents and Reports

102 page Department of Radiology Annual Executive Summary Report, July 1, 1998 to June 30, 1999, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.

Department Of Radiology-Annual Report-July 1, 1997 To June 30, 1998, David C. Levin

Department of Radiology Administrative Documents and Reports

Department of Radiology Annual Executive Summary Report, July 1, 1997 to June 30, 1998. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States. 103 pages.

Clinical Problem-Solving. Through Thick And Thin., David R. Yu, Redonda Miller, Paul F. Bray

Cardeza Foundation for Hematologic Research

No abstract provided.

The Baculovirus Anti-Apoptotic P35 Protein Promotes Transformation Of Mouse Embryo Fibroblasts., M Resnicoff, B. Valentinis, D. Herbert, D. Abraham, P D. Friesen, E. S. Alnemri, R Baserga

Department of Microbiology and Immunology Faculty Papers

The baculovirus p35 protein is a potent inhibitor of programmed cell death induced by a variety of stimuli in insects, nematodes, and mammalian cell lines. The broad ability of p35 in preventing apoptosis has led us to investigate its effect on mouse embryo fibroblasts in vitro and in vivo. For this purpose, we have used R- cells (3T3-like fibroblasts derived from mouse embryos with a targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes) and R508 cells (derived from R- and with 15 x 10(3) IGF-IRs per cell). Both cell lines grow normally in monolayer, but they do …

Identification Of Fetal Dna And Cells In Skin Lesions From Women With Systemic Sclerosis, Carol M. Artlett, J. Bruce Smith, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

BACKGROUND: Systemic sclerosis is a disease of unknown origin which often occurs in women after their childbearing years. It has many clinical and histopathological similarities to chronic graft-versus-host disease. Recent studies indicate that fetal stem cells can survive in the maternal circulation for many years post partum. This finding suggests that fetal cells persisting in the maternal circulation or tissues could be involved in the pathogenesis of systemic sclerosis by initiating a graft-versus-host reaction.

METHODS: We used the polymerase chain reaction (PCR) to identify Y-chromosome sequences in DNA extracted from peripheral-blood cells and skin lesions from women with systemic sclerosis …

Mitochondrial Myopathy With Atypical Subacute Presentation, Oren Cohen, Israel Steiner, Zohar Argov, Avi Ashkenazi, Judith Diment, Ann Saada, Yaron River

Department of Neurology Faculty Papers

Mitochondrial myopathies usually have a chronic course of progressive limb weakness, exercise induced myalgia without muscle tenderness, and normal or only mildly raised serum creatine kinase. Acute or subacute presentation or exacerbation of nervous system signs is common in Leber's hereditary optic neuropathy (LHON) and in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), but has not been reported for muscle in mitochondrial diseases. We describe a patient who presented with rapidly progressive, subacute muscle weakness due to a mitochondrial disorder.

Initial Multicenter Experience With Double Nucleoside Therapy For Human Immunodeficiency Virus Infection During Pregnancy., N S Silverman, D H Watts, J Hitti, D M Money, E Livingston, J Axelrod, J M Ernest, D Robbins, M M Divito

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications.

METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV …

Determinants Of Antepartum Human Immunodeficiency Virus Testing In A Non-Medicaid Obstetric Population., E Cardonick, S Daly, M Dooley, K Elles, N S Silverman

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To determine voluntary human immunodeficiency virus (HIV) testing rates and factors influencing testing in a private obstetric practice.

METHODS: Antepartum patients were offered HIV testing after completing a self-assessment questionnaire. Perceived risks and demographics were correlated with testing rates.

RESULTS: Overall, 348/600 (58%) women consented to HIV testing. In a univariate analysis, patients with "any" perceived risk(s) were more likely to be tested. Single women and those with an at-risk partner(s) or a history of sexually transmitted disease (STD) were more likely to desire testing. These factors remained independently associated with voluntary testing in a multivariate regression model. No …

Predicting Red Blood Cell Transfusions In Very Low Birth Weight Infants Based On Clinical Risk Factors., David A. Paul, Stephen A. Pearlman, Kathleen H. Leef, John L. Stefano

Department of Pediatrics Faculty Papers

OBJECTIVE: To describe the clinical factors most predictive of red blood cell transfusion in very low birth weight (VLBW) infants.

STUDY DESIGN: Retrospective review of VLBW infants cared for at a single level III NICU during a two year period, n = 199.

RESULTS: Overall transfusion requirement was 4.6 +/- 6.2 transfusions/infant/hospital course. Length of hospital stay, days of mechanical ventilation, requirement for dopamine support, birth weight, initial hematocrit, periventricular leukomalacia and necrotizing enterocolitis all independently correlated with number of transfusions and donors. Bronchopulmonary dysplasia and patent ductus arteriosus were associated with donor but not transfusion number.

CONCLUSIONS: Our data …

Detection And Characterization Of Sp1 Binding Activity In Human Chondrocytes And Its Alterations During Chondrocyte Dedifferentiation., Rita M. Dharmavaram, Gang Liu, Sheryl D. Mowers, Sergio A. Jimenez

Department of Medicine Faculty Papers

We have detected DNA binding activity for a synthetic oligonucleotide containing an Sp1 consensus sequence in nuclear extracts from human chondrocytes. Changes in the levels of Sp1 oligonucleotide binding activity were examined in nuclear extracts from freshly isolated human chondrocytes, from chondrocytes that had been cultured under conditions that allowed the maintenance of a chondrocyte-specific phenotype on plastic dishes coated with the hydrogel poly(2-hydroxyethyl methacrylate), and from chondrocytes induced to dedifferentiate into fibroblast-like cells by passage in monolayer culture on plastic substrata. It was observed that Sp1 binding was 2-3-fold greater in nuclear extracts from dedifferentiated chondrocytes than in nuclear …

Stent Placement Compared With Balloon Angioplasty For Obstructed Coronary Bypass Grafts. Saphenous Vein De Novo Trial Investigators., M P Savage, J S Douglas, D L Fischman, C J Pepine, S B King, J A Werner, S R Bailey, P A Overlie, S H Fenton, J A Brinker, M B Leon, S Goldberg

Department of Medicine Faculty Papers

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts.

METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later.

RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate …

Mirizzi Syndrome Type Ii: Is Laparoscopic Cholecystectomy Justified?, D C Desai, R D Smink

Department of Surgery Faculty Papers

Mirizzi syndrome type II is an uncommon cause of obstructive jaundice caused by an inflammatory response to an impacted gallstone in Hartmann's pouch or the cystic duct with a resultant cholecystocholedochal fistula. Two cases of Mirizzi syndrome type II are presented. Clinically only one patient had jaundice and endoscopic retrograde cholangiopancreatogram (ERCP) established a preoperative diagnosis of Mirizzi syndrome. The other patient's diagnosis of Mirizzi syndrome was made intraoperatively. It is important to properly identify the anatomy at the time of surgery to avoid compromising the common bile duct. Operative treatment of Mirizzi syndrome type II includes laparoscopic or open …

Department Of Radiology-Annual Report-July 1, 1996 To June 30, 1997, David C. Levin

Department of Radiology Administrative Documents and Reports

Department of Radiology Annual Report, July 1, 1996 to June 30, 1997. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States. 108 pages.

Ureteroscopic Lithotripsy., Demetrius H. Bagley

Department of Urology Faculty Papers

There is a wide array of endoscopic lithotriptors presently available. Each of these has its own advantages and disadvantages. No single lithotriptor is suitable for all applications and none can meet the goal of fragmenting all calculi while remaining harmless to tissue.

The History Of The Present Illness As Treatment: Who's Listening, And Why Does It Matter?, Herbert M. Adler, Md, Phd

Department of Family & Community Medicine Faculty Papers

BACKGROUND: The history of the present illness (HPI) is examined as a narrative communication that has the potential to be therapeutic.

METHODS: The general principles that influence the therapeutic potential of the HPI are induced from participant observation of personal experience and natural observations of conventional social interaction. These principles are corroborated by evidence from cross-cultural healing practices, clinical experience, and experimental psychology.

RESULTS: To facilitate a therapeutic HPI, the clinician should convey a sense of safety, sensitivity, affective competence, and cognitive competence. Furthermore, the effective clinician joins the patient in coprocessing the illness experience.

CONCLUSIONS: The (HPI) is not …

Glanzmann Thrombasthenia. Cooperation Between Sequence Variants In Cis During Splice Site Selection., Ying Jin, Harry C. Dietz, Robert A. Montgomery, William R. Bell, Iain Mcintosh, Barry Coller, Paul F. Bray

Cardeza Foundation for Hematologic Research

Glanzmann thrombasthenia (GT), an autosomal recessive bleeding disorder, results from abnormalities in the platelet fibrinogen receptor, GP(IIb)-IIIa (integrin alpha(IIb)beta3). A patient with GT was identified as homozygous for a G-->A mutation 6 bp upstream of the GP(IIIa) exon 9 splice donor site. Patient platelet GP(IIIa) transcripts lacked exon 9 despite normal DNA sequence in all of the cis-acting sequences known to regulate splice site selection. In vitro analysis of transcripts generated from mini-gene constructs demonstrated that exon skipping occurred only when the G-->A mutation was cis to a polymorphism 116 bp upstream, providing precedence that two sequence variations …

Department Of Radiology-Annual Report-July 1, 1995 To June 30, 1996, David C. Levin

Department of Radiology Administrative Documents and Reports

Department of Radiology Annual Report, July 1, 1995 to June 30, 1996. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States. 110 pages.

A Polymorphism Of A Platelet Glycoprotein Receptor As An Inherited Risk Factor For Coronary Thrombosis., Ethan J. Weiss, Paul F. Bray, Matthew Tayback, Steven P. Schulman, Thomas S. Kickler, Lewis C. Becker, James L. Weiss, Gary Gerstenblith, Pascal J. Goldschmidt-Clermont

Cardeza Foundation for Hematologic Research

BACKGROUND: Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PlA2, of the gene encoding glycoprotein IIIa in kindreds with a high prevalence of premature myocardial infarction.

METHODS: To investigate the relation between the PlA2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infarction or unstable angina and 68 inpatient controls without known heart disease. The …

Strategies For Prevention Of Varicella Pneumonia: A Cost-Effectiveness Analysis., G A Macones, S Ewing, N S Silverman

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: The objective of this study was to compare the cost-effectiveness of 3 strategies of serologic enzyme-linked immunosorbent assay (ELISA) testing and post-exposure varicella zoster immune globulin (VZIG) prophylaxis for the prevention of maternal varicella pneumonia during pregnancy in patients with negative or uncertain histories of varicella infection.

METHODS: A decision tree was constructed to compare the following strategies: 1) routine serologic testing for varicella immunity followed by targeted post-exposure VZIG prophylaxis, 2) post-exposure serologic testing followed by targeted VZIG prophylaxis, and 3) untargeted post-exposure VZIG administration. The probabilities for the model were obtained from the medical literature and supplemented …

Stimulation Of Alpha 1(I) Procollagen Gene Expression In Nih-3t3 Cells By The Human T Cell Leukemia Virus Type 1 (Htlv-1) Tax Gene., E. Munoz, D. Suri, S. Amini, K. Khalili, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

The mechanisms that regulate the expression of genes encoding extracellular matrix proteins in fibroblasts and other mesenchymal cells have remained elusive. Studies from several laboratories have indicated that Tax, a trans-regulatory protein from the human T cell leukemia virus type I not only augments viral gene expression but also triggers the expression of various cellular genes. Here, we examined the hypothesis that the expression of collagen genes may also be modulated by Tax. NIH-3T3 cells were simultaneously transfected with a Tax expressor plasmid and a chimeric construct containing regulatory sequences (-804 to +42 bp) of the alpha 1(I) procollagen gene …

Department Of Radiology-Annual Report-July 1, 1994 To June 30, 1995, David C. Levin

Department of Radiology Administrative Documents and Reports

Department of Radiology Annual Report, July 1, 1994 to June 30, 1995. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States. 120 pages.

Increased Alpha 1(I) Procollagen Gene Expression In Tight Skin (Tsk) Mice Myocardial Fibroblasts Is Due To A Reduced Interaction Of A Negative Regulatory Sequence With Ap-1 Transcription Factor., Neena Philips, Reza I. Bashey, Sergio A. Jimenez

Department of Medicine Faculty Papers

The TSK mouse, a model of fibrosis, displays exaggerated connective tissue accumulation in skin and visceral organs including the heart. To study the mechanisms of myocardial fibrosis in TSK mice, we established several strains of TSK mice myocardial fibroblasts in culture and examined the regulation of collagen gene expression in these cells. These strains displayed increased collagen gene expression in comparison with myocardial fibroblasts established from normal mice. On an average, the TSK myocardial fibroblast cultures showed a 4-fold increase in collagen synthesis and 4.4- and 3.6-fold increases, respectively, in alpha 1(I) and alpha 1(III) collagen mRNA steady state levels. …

Randomized Trial Of Erythromycin And Azithromycin For Treatment Of Chlamydial Infection In Pregnancy., M F Rosenn, G A Macones, N S Silverman

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: The purpose of this study was to compare erythromycin and azithromycin in the treatment of chlamydial cervicitis during pregnancy with regard to efficacy, side effects, and compliance.

METHODS: In a prospective manner, 48 pregnant patients with cervical chlamydial infections diagnosed by routine screening tests were randomly assigned to receive either erythromycin, 500 mg q.i.d. for 7 days (N = 24), or azithromycin, 1 g as a one-time dose (N = 24). All sexual partners were given prescriptions for doxycycline, 100 mg b.i.d. for 7 days. The treatment efficacy was assessed by follow-up chlamydia testing 3 weeks after the therapy …

Symptoms Six Weeks After Covid-19 Are Reduced Among Us Health Care Personnel Receiving Additional Vaccine Doses During The Omicron Period, December 2021-April 2022., Nicholas M. Mohr, Ian D. Plumb, Eliezer Santos León, Malea Pinckney, Karisa K. Harland, Anusha Krishnadasan, Karin F. Hoth, Fernand Rwamwejo, John P. Haran, Melissa Briggs-Hagen, Eric Kontowicz, David A. Talan

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: The objective of this study was to test the hypothesis that subsequent doses of the coronavirus disease 2019 (COVID-19) vaccine are associated with lower incidence of COVID-19-like symptoms at 6 weeks after infection.

METHODS: This study was a case-control analysis of health care personnel in an ongoing multicenter COVID-19 vaccine effectiveness study. We enrolled participants at the time of COVID-19-like symptoms between December 19, 2021, and April 27, 2022, which corresponded to the early Omicron-predominant period after original monovalent severe acute respiratory syndrome coronavirus 2 additional vaccination doses became available. Our outcome was self-reported symptoms completed 6 weeks after …

Epidermal Growth Factor Coordinately Regulates The Expression Of Prostaglandin G/H Synthase And Cytosolic Phospholipase A2 Genes In Embryonic Mouse Cells., Kenneth P. Chepenik, Arturo Diaz, Sergio A. Jimenez

Department of Medicine Faculty Papers

Confluent, primary cultures of mouse embryo palate mesenchyme (MEPM) cells are refractory to activation of phospholipase A2 (PLA2) by the calcium ionophore A23187. However, treatment of these cultures with epidermal growth factor (EGF) permits the cells to activate PLA2 in response to A23187. We have developed this finding by exploring molecular mechanisms by which growth factors modulate mobilization and metabolism of arachidonic acid. We found chronic treatment (> 6 h) of confluent MEPM cells with EGF (a) increases their ability to metabolize exogenous arachidonic acid to prostaglandin E2 (PGE2) and (b) stimulated constitutive expression of activities of PLA2 and cyclooxygenase …

A Randomized Comparison Of Coronary-Stent Placement And Balloon Angioplasty In The Treatment Of Coronary Artery Disease. Stent Restenosis Study Investigators., David L. Fischman, Martin B. Leon, Donald S. Baim, Richard A. Schatz, Michael P. Savage, Ian Penn, Katherine Detre, Lisa Veltri, Donald Ricci, Masakiyo Nobuyoshi, Michael Cleman, Richard Heuser, David Almond, Paul S. Teirstein, R. David Fish, Antonio Colombo, Jeffrey Brinker, Jeffrey Moses, Alex Shaknovich, John Hirshfeld, Stephen Bailey, Stephen Ellis, Randal Rake, Sheldon Goldberg

Department of Medicine Faculty Papers

BACKGROUND: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes.

METHODS: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later.

RESULTS: The patients who underwent stenting had a higher rate of procedural success than those who …

Department Of Radiology-Annual Report-July 1, 1993 To June 30, 1994, David C. Levin

Department of Radiology Administrative Documents and Reports

Department of Radiology Annual Report, July 1, 1993 to June 30, 1994. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States. 107 pages.