Medicine and Health Sciences Commons^™

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model., Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J Yasha Kresh, John W.C. Entwistle, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

The Activity Of Azithromycin Against Leishmania (Viannia) Braziliensis And Leishmania (Leishmania) Amazonensis In The Golden Hamster Model., Angel Sinagra, Concepción Luna, David Abraham, Maria Del Carmen Iannella, Adelina Riarte, Alejandro J. Krolewiecki

Department of Microbiology and Immunology Faculty Papers

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, …

Rhabdomyolysis After Laparoscopic Nephrectomy., Deborah T. Glassman, William G. Merriam, Edouard J. Trabulsi, Dolores Byrne, Leonard Gomella

Department of Urology Faculty Papers

BACKGROUND AND OBJECTIVES: Laparoscopic renal surgery has become a widely applied technique in recent years. The development of postoperative rhabdomyolysis is a known but rare complication of laparoscopic renal surgery. Herein, 4 cases of rhabdomyolysis and a review of the literature are presented with respect to pathogenesis, treatment, and prevention of this dire complication. METHODS: A retrospective review of over 600 laparoscopic renal operations over the past 8 years was performed. All cases of postoperative rhabdomyolysis were identified. A Medline search was performed to find articles related to the development of postoperative rhabdomyolysis. Cases of rhabdomyolysis developing after laparoscopic renal …

Microvascular Endothelial Cells Express A Phosphatidylserine Receptor: A Functionally Active Receptor For Phosphatidylserine-Positive Erythrocytes, Yamaja Setty, Suhita Gayen Betal

Department of Pediatrics Faculty Papers

Phosphatidylserine (PS)-positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1alpha, TNF-alpha, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface-expressed PS (PSR) similar to that expressed on activated macrophages. …

Teaching Case: Headache Stigmata, Michael Marmura, Seymour Solomon

Department of Neurology Faculty Papers

A 38-year-old man with past medical history of hypertension and obesity presented to our clinic for evaluation of severe headaches and multiple episodes of discoloration of the forehead on the same side as the headache.

Human Collagen Krox Up-Regulates Type I Collagen Expression In Normal And Scleroderma Fibroblasts Through Interaction With Sp1 And Sp3 Transcription Factors., Magdalini Kypriotou, Gallic Beauchef, Christos Chadjichristos, Russell Widom, Emmanuelle Renard, Sergio A. Jimenez, Joseph Korn, François-Xavier Maquart, Thierry Oddos, Otto Von Stetten, Jean-Pierre Pujol, Philippe Galéra

Department of Medicine Faculty Papers

Despite several investigations, the transcriptional mechanisms that regulate the expression of both type I collagen genes (COL1A1 and COL1A2) in either physiological or pathological situations, such as scleroderma, are not completely known. We have investigated the role of hc-Krox transcription factor on type I collagen expression by human dermal fibroblasts. hc-Krox exerted a stimulating effect on type I collagen protein synthesis and enhanced the corresponding mRNA steady-state levels of COL1A1 and COL1A2 in foreskin fibroblasts (FF), adult normal fibroblasts (ANF), and scleroderma fibroblasts (SF). Forced hc-Krox expression was found to up-regulate COL1A1 transcription through a -112/-61-bp sequence in FF, ANF, …

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model, Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J. Yasha Kresh, John W.C. Entwhistle Iii, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Relationships Between Scores On The Jefferson Scale Of Physician Empathy, Patient Perceptions Of Physician Empathy, And Humanistic Approaches To Patient Care: A Validity Study., Karen M. Glaser, Fred W. Markham, Herbert M. Adler, Patrick R. Mcmanus, Mohammadreza Hojat

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Empathy is the backbone of a positive physician-patient relationship. Physician empathy and the patient's awareness of the physician's empathic concern can lead to a more positive clinical outcome.

MATERIAL/METHODS: The Jefferson Scale of Physician Empathy (JSPE) was completed by 36 physicians in the Family Medicine residency program at Thomas Jefferson University Hospital, and 90 patients evaluated these physicians by completing the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE), and a survey about physicians' humanistic approaches to patient care.

RESULTS: A statistically significant correlation was found between scores of the JSPE and JSPPPE (r=0.48, p

CONCLUSIONS: These findings …

The Pharmacokinetics Of Taurolidine Metabolites In Healthy Volunteers., Li Gong, Howard E Greenberg, James L Perhach, Scott A Waldman, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Taurolidine is an experimental antibacterial and antiendotoxic compound whose clinical utility as an antitumor agent is being investigated in human clinical trials. Taurolidine in aqueous solution exists in equilibrium with taurultam. Taurultam is subsequently transformed to taurinamide. The pharmacokinetic profiles of these metabolites are not well established. In this study, 18 healthy volunteers were administered 5.0 g of taurolidine in 250 mL of 5% polyvinylpyrrolidone in water over 2, 1, or 0.5 hours by intravenous infusion in a parallel-group design. All subjects noted discomfort at the infusion site, although there were no serious adverse events. t(max) generally occurred at the …

Surgical Versus Nonsurgical Treatment For Lumbar Degenerative Spondylolisthesis., James N Weinstein, Jon D Lurie, Tor D Tosteson, Brett Hanscom, Anna N A Tosteson, Emily A Blood, Nancy J O Birkmeyer, Alan Hilibrand, Harry Herkowitz, Frank P Cammisa, Todd J Albert, Sanford E Emery, Lawrence G Lenke, William A Abdu, Michael Longley, Thomas J Errico, Serena S Hu

Rothman Institute Faculty Papers

BACKGROUND: Management of degenerative spondylolisthesis with spinal stenosis is controversial. Surgery is widely used, but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials.

METHODS: Surgical candidates from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a randomized cohort or an observational cohort. Treatment was standard decompressive laminectomy (with or without fusion) or usual nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) bodily pain and physical function scores (100-point scales, …

The Modifier Of Min 2 (Mom2) Locus: Embryonic Lethality Of A Mutation In The Atp5a1 Gene Suggests A Novel Mechanism Of Polyp Suppression., Amy A Baran, Karen A Silverman, Joseph Zeskand, Revati Koratkar, Ashley Palmer, Kristen Mccullen, Walter J Curran, Tina Bocker Edmonston, Linda D Siracusa, Arthur M Buchberg

Kimmel Cancer Center Faculty Papers

Inactivation of the APC gene is considered the initiating event in human colorectal cancer. Modifier genes that influence the penetrance of mutations in tumor-suppressor genes hold great potential for preventing the development of cancer. The mechanism by which modifier genes alter adenoma incidence can be readily studied in mice that inherit mutations in the Apc gene. We identified a new modifier locus of ApcMin-induced intestinal tumorigenesis called Modifier of Min 2 (Mom2). The polyp-resistant Mom2R phenotype resulted from a spontaneous mutation and linkage analysis localized Mom2 to distal chromosome 18. To obtain recombinant chromosomes for use in refining the Mom2 …

Signaling Through Galphai2 Protein Is Required For Recruitment Of Neutrophils For Antibody-Mediated Elimination Of Larval Strongyloides Stercoralis In Mice., Udaikumar M. Padigel, Louis Stein, Kevin Redding, James J. Lee, Thomas J. Nolan, Gerhard A. Schad, Lutz Birnbaumer, David Abraham

Department of Microbiology and Immunology Faculty Papers

The heterotrimeric guanine nucleotide-binding protein Galphai2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. Galphai2-/- mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN-gamma and IL-4. The goal of the present study was to determine if a deficiency in the Galphai2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. Galphai2-/- and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses …

Management Of Morel-Lavallee Lesion Of The Knee: Twenty-Seven Cases In The National Football League, Samir G. Tejwani, Steven B. Cohen, James P. Bradley

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The Morel-Lavallee lesion is a closed degloving injury most commonly described in the region of the hip joint after blunt trauma. It also occurs in the knee as a result of shearing trauma during football and is a distinct lesion from prepatellar bursitis and quadriceps contusion.

PURPOSE: To review the authors' experience with Morel-Lavallee lesion of the knee in the elite contact athlete to construct a diagnostic and treatment algorithm.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: Twenty-seven knees in 24 players were identified from 1 National Football League team's annual injury database as having sustained a …

Lessons Learned: A Pilot Study On Occupational Therapy Effectiveness For Children With Sensory Modulation Disorder., Lucy Jane Miller, Sarah A. Schoen, Katherine James, Roseann C Schaaf

Department of Occupational Therapy Faculty Papers

OBJECTIVE: The purpose of this pilot study was to prepare for a randomized controlled study of the effectiveness of occupational therapy using a sensory integration approach (OT-SI) with children who have sensory processing disorders (SPD).

METHOD: A one-group pretest, posttest design with 30 children was completed with a subset of children with SPD, those with sensory modulation disorder.

RESULTS: Lessons learned relate to (a) identifying a homogeneous sample with quantifiable inclusion criteria, (b) developing an intervention manual for study replication and a fidelity to treatment measure, (c) determining which outcomes are sensitive to change and relate to parents' priorities, and …

Occupational Therapy Using A Sensory Integrative Approach: A Case Study Of Effectiveness., Roseann C. Schaaf, Kathleen Mckeon Nightlinger

Department of Occupational Therapy Faculty Papers

OBJECTIVE: This article presents a case report of a child with poor sensory processing and describes the disorders impact on the child's occupational behavior and the changes in occupational performance during 10 months of occupational therapy using a sensory integrative approach (OT-SI).

METHOD: Retrospective chart review of assessment data and analysis of parent interview data are reviewed. Progress toward goals and objectives is measured using goal attainment scaling. Themes from parent interview regarding past and present occupational challenges are presented.

RESULTS: Notable improvements in occupational performance are noted on goal attainment scales, and these are consistent with improvements in behavior. …

Transgenic Avian-Derived Recombinant Human Interferon-Alpha2b (Avi-005) In Healthy Subjects: An Open-Label, Single-Dose, Controlled Study., T B Patel, E Pequignot, S H Parker, M C Leavitt, H E Greenberg, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND/AIMS: This study characterized the safety and pharmacological properties of AVI-005, a novel glycosylated recombinant human interferon-alpha2b produced from the egg whites of chickens transfected with human cDNA.

METHODS: 18 healthy volunteers received single subcutaneous rising doses (0.5, 1.66 or 5 million international units, MIU) of AVI-005. A randomized parallel comparator group of 10 subjects received 5 MIU of unglycosylated IFN-alpha2b (Intron A). The pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-24h, Vd, and clearance were compared between AVI-005 and unglycosylated IFN-alpa2b.

RESULTS: At equipotent doses, AVI-005 had a larger AUC0-24h than the control interferon. Pharmacodynamic markers ofneopterin and beta2-microglobulin for the …

Rotator Cuff Contusions Of The Shoulder In Professional Football Players: Epidemiology And Magnetic Resonance Imaging Findings, Steven B. Cohen, Jeffrey D. Towers, James P. Bradley

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: No published reports have studied the epidemiology and magnetic resonance imaging findings associated with rotator cuff contusions of the shoulder in professional football players.

PURPOSE: To determine a single professional football team's incidence, treatment, and magnetic resonance imaging appearance of players sustaining rotator cuff contusions of the shoulder.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: From 1999 to 2005, a North American professional football team's injury records were retrospectively reviewed for athletes who had sustained a rotator cuff contusion of the shoulder during in-season participation. Those patients who had magnetic resonance imaging of the shoulder with a …

Hepatitis C Risk Assessment, Testing And Referral For Treatment In Urban Primary Care: Role Of Race And Ethnicity., Stacey B. Trooskin, Victor J. Navarro, Robert J. Winn, David J. Axelrod, A. Scott Mcneal, Maricruz Velez, Steven K. Herrine, Simona Rossi

Division of Gastroenterology and Hepatology Faculty Papers

AIM: To determine rates of hepatitis C (HCV) risk factor ascertainment, testing, and referral in urban primary care practices, with particular attention to the effect of race and ethnicity.

METHODS: Retrospective chart review from four primary care sites in Philadelphia; two academic primary care practices and two community clinics was performed. Demographics, HCV risk factors, and other risk exposure information were collected.

RESULTS: Four thousand four hundred and seven charts were reviewed. Providers documented histories of injection drug use (IDU) and transfusion for less than 20% and 5% of patients, respectively. Only 55% of patients who admitted IDU were tested …

Genome-Wide Analysis Of Neuroblastomas Using High-Density Single Nucleotide Polymorphism Arrays., Rani E George, Edward F Attiyeh, Shuli Li, Lisa A Moreau, Donna Neuberg, Cheng Li, Edward A Fox, Matthew Meyerson, Lisa Diller, Paolo Fortina, A Thomas Look, John M Maris

Cardeza Foundation for Hematologic Research

BACKGROUND: Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array.

FINDINGS: Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p …

Jefferson Scale Of Patient's Perceptions Of Physician Empathy: Preliminary Psychometric Data., Gregory C. Kane, Joanne L. Gotto, Salvatore Mangione, Susan West, Mohammadreza Hojat

Department of Psychiatry and Human Behavior Faculty Papers

AIM: To develop a brief scale for measuring patient's perceptions of their physician's empathic engagement and to provide preliminary evidence in support of aspects of the scale's psychometrics.

METHOD: Study comprised 225 patients, out of 436 patients (52% response rate) seen by 166 residents in the internal medicine residency program at the Jefferson Hospital Ambulatory Clinic as part of their ambulatory training at Thomas Jefferson University Hospital. A 5-item questionnaire entitled the Jefferson Scale of Patient's Perceptions of Physician Empathy was developed and administered to the study participants. Its factor structure, item-total score correlations, and correlations with several relevant criterion …

The Interplay Of Obesity And Asthma, James Plumb, Rickie Brawer, Nancy Brisbon

Department of Family & Community Medicine Faculty Papers

The relationships, interactions, and association between obesity and asthma are complex, and are active sources of hypotheses and research. An association between obesity and asthma has been reported in many studies, although considerable debate about the existence of the association and its meaning still exists. Potential associative relationships may result from genetics, immune system modifications, and mechanical mechanisms. The rising prevalence of asthma and obesity in children and adults, and the significant morbidity from both, makes it imperative that clinicians recognize the importance of weight management in patients with and without asthma.

Homocysteine Levels In Preterm Infants: Is There An Association With Intraventricular Hemorrhage? A Prospective Cohort Study., Wendy J Sturtz, Kathleen H Leef, Amy B Mackley, Shailja Sharma, Teodoro Bottiglieri, David A Paul

Department of Pediatrics Faculty Papers

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants < 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman's Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels.