Medical Specialties Commons^™

Autoimmune Enteropathy With A Cd8+ Cd7- T-Cell Small Bowel Intraepithelial Lymphocytosis: Case Report And Literature Review, Shrinivas Bishu, Violeta Arsenescu, Eun Y. Lee, H. David Vargas, Willem J. S. De Villiers, Razvan Arsenescu

Surgery Faculty Publications

Background

Adult onset autoimmune enteropathy (AIE) is a rare condition characterized by diarrhea refractory to dietary therapy diagnosed in patients with evidence of autoimmune conditions. Auto-antibodies to gut epithelial cells and other tissues are commonly demonstrated. Despite increasing awareness, the pathogenesis, histologic, immunologic and clinical features of AIE remain uncertain. There remains controversy regarding the diagnostic criteria, the frequency and types of auto-antibodies and associated autoimmune conditions, and the extent and types of histologic and immunologic abnormalities. CD4+ T-cells are thought to at least responsible for this condition; whether other cell types, including B- and other T-cell subsets are involved, …

A Brief Overview Of Adolescent Developmental Problems In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

Several adolescent developmental problems in Hong Kong are briefly reviewed in this paper. First, rising adolescent substance abuse trends are described. Second, Internet use problems and Internet addiction among young people are examined. Third, worrying trends in adolescent sexuality are identified. Fourth, phenomena on bullying among young people are reviewed. Finally, phenomena related to adolescent materialistic orientation are focused upon. With reference to these adolescent developmental problems, possible solutions are briefly discussed particularly with reference to the ecological perspective. It is argued that the related scientific literature provides useful pointers for designing the curriculum in the extension phase of the …

Percutaneous Implantation Of The Edwards Sapien Transcatheter Heart Valve For Conduit Failure In The Pulmonary Position: Early Phase 1 Results From An International Multicenter Clinical Trial., Damien Kenny, Ziyad M. Hijazi, Saibal Kar, John Rhodes, Michael Mullen, Raj Makkar, Girish S. Shirali, Mark Fogel, John Fahey, Mary G. Heitschmidt, Christopher Cain

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: The purpose of this study was to evaluate the safety and effectiveness of the Edwards SAPIEN transcatheter heart valve (Edwards Lifesciences LLC, Irvine, California) in the pulmonary position in patients with moderate to severe pulmonary regurgitation with or without stenosis.

BACKGROUND: Transcatheter pulmonary valve replacement is evolving, but to date, experience has been limited to the Melody valve (Medtronic Inc., Minneapolis, Minnesota).

METHODS: Eligible patients with dysfunctional right ventricle-to-pulmonary artery conduits were screened if body weight was ≥35 kg and the in situ conduit diameter was ≥16 mm and ≤24 mm. Standardized implantation and follow-up protocols were used.

RESULTS: …

Development Of A New Curriculum In A Positive Youth Development Program: The Project P.A.T.H.S. In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

The design of a new curriculum in a positive youth development program (Project P.A.T.H.S.) in Hong Kong is outlined. The Tier 1 Program of the original phase of the Project P.A.T.H.S. is a universal positive youth development program for students in Secondary 1 to Secondary 3 with the curricula developed by a research team comprising scholars in different disciplines (e.g., social work, psychology, and education). The 120 teaching units are designed with reference to 15 positive youth development constructs identified in the successful positive youth development programs. In the extension phase of the project, a new curriculum with 60 teaching …

An Automated Internet Application To Help Patients With Bipolar Disorder Track Social Rhythm Stabilization., Daniel Z Lieberman, Susan Swayze, Frederick K Goodwin

Psychiatry and Behavioral Sciences Faculty Publications

This column describes a pilot study of a fully automated, Internet-based program that provides a key element of interpersonal and social rhythm therapy, a form of psychotherapy shown to be effective in the treatment of bipolar disorder when combined with mood-stabilizing medication. Participants (N=64) recorded the time they completed activities of daily living and their mood at the time of each entry. After 90 days they demonstrated a 31% increase in social rhythm stability and a small, though statistically significant, decrease in symptoms of abnormal mood. Internet-based programs can enhance access to a best practice in the management of bipolar …

The Gross Clinic, The Agnew Clinic, And The Listerian Revolution., Caitlyn M. Johnson, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Thomas Eakins was an American artist whose unique and prolific style set him apart from other artists of the late 19th century.1 He chose to portray his subjects with intense objectivity, never deviating from reality. Even during his era when art was expected to be always beautiful, demonstrating Victorian morals of decency and decorum, Eakins chose to paint the naked truth.1 Walt Whitman was noted to have said, ‘‘I never knew of but one artist, and that’s Tom Eakins, who would resist the temptation to see what they ought to be rather than what it is.’’2 It was Eakins’ rigid …

Robert Milton Zollinger, M.D., Teacher, Surgeon, Soldier, And Farmer., Fiona M. Chory, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

From Humble roots, Dr. Robert Milton Zollinger worked his way to a position in history among the giants of American surgery. He was born on September 4, 1903, in the central Ohio town of Millersport, the son of Elmira and William Zollinger. Neither of his parents had a high school education, but they supported education and always expressed a confidence that young Robert would be successful at anything he attempted.1 He had aspirations of attending West Point, a dream that was never fulfilled when he decided to be a surgeon. On being informed of his son’s intentions, Zollinger’s father bestowed …

Functional Recovery Of Untreated Human Immunodeficiency Virus-Associated Guillain-Barré Syndrome: A Case Report, Adam L. Schreiber, John W. Norbury Iii, Eduardo A. De Sousa

Department of Rehabilitation Medicine Faculty Papers

HIV-associated Guillain-Barré Syndrome is a well-documented phenomenon, typically occurring at seroconversion. GBS may result in functional impairment treated with a combination of medications, plasmapheresis, and rehabilitation. The quantified functional recovery of HIV-associated GBS with or without HIV treatment is not well-described. Utilizing serial FIM scoring, we describe a patient’s recovery from HIV-associated GBS after treatment with IVIg and acute inpatient rehabilitation without HIV treatment.

Postenucleation Adjuvant Chemotherapy With Vincristine, Etoposide, And Carboplatin For The Treatment Of High-Risk Retinoblastoma., Swathi Kaliki, Carol L Shields, Sanket U Shah, Ralph C Eagle, Jerry A Shields, Ann Leahey

Wills Eye Hospital Papers

BACKGROUND: Analysis of 52 eyes with high-risk retinoblastoma managed with postenucleation adjuvant chemotherapy using vincristine sulfate, etoposide phosphate, and carboplatin showed no evidence of systemic metastasis in any case during a mean (range) follow-up of 66 (12-202) months.

PURPOSE: To determine the efficacy of postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin in the prevention of metastasis for patients with high-risk retinoblastoma.

METHODS: Retrospective, nonrandomized, interventional case series of 52 eyes in 51 patients with high-risk retinoblastoma consisting of tumor invasion into the anterior segment, posterior uvea 3 mm or greater, postlaminar optic nerve, or any combination of posterior uvea …

Childhood Obesity And Blood Pressure: Back To The Future?, Bonita Falkner, Samuel Gidding

Department of Pediatrics Faculty Papers

The prevalence of childhood hypertension is increasing.^{1, 2} Studies that apply the 95^th percentile definition and repeat measurements on three separate visits, report a pediatric hypertension prevalence of approximately 3.5%^{3, 4}, and among obese children and adolescents the prevalence of both hypertension and prehypertension is even greater. The recently documented increase in hypertension among the young is due largely to the childhood obesity epidemic and possibly other secular changes in lifestyles. These publications and others confirm that hypertension is a prevalent child health condition, especially among overweight and obese children. A consistent positive association between body …

Abca12-Mediated Lipid Transport And Snap29-Dependent Trafficking Of Lamellar Granules Are Crucial For Epidermal Morphogenesis In A Zebrafish Model Of Ichthyosis., Qiaoli Li, Michael Frank, Masashi Akiyama, Shiu-Ying Ho, Hiroshi Shimizu, Christine Thisse, Bernard Thisse, Eli Sprecher, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Zebrafish (Danio rerio) can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5-6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM) of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM) reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and …

Non-Geometric Echocardiographic Indices Of Ventricular Function In Patients With A Fontan Circulation., Jonathan Rhodes, Renee Margossian, Lynn A. Sleeper, Piers Barker, Timothy J. Bradley, Minmin Lu, Mark Fogel, Matthew A. Harris, Wyman W. Lai, Andrew J. Powell, Michael D. Puchalski, Girish S. Shirali, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Complex anatomy and limited windows complicate echocardiographic assessments of ventricular function in Fontan patients. For the Pediatric Heart Network Fontan Cross-Sectional Study, data were acquired from which mean ventricular pressure change during isovolumetric contraction (dP/dt(ic)), Tei index, and maximal systolic annular velocity (S') could be measured. The purpose of this study was to compare these nongeometric indices of ventricular function to cardiac magnetic resonance (CMR) measurements of ventricular ejection fraction (EF).

METHODS: Echocardiographic and CMR studies were performed prospectively using standardized protocols; measurements were completed by core laboratories. Data from both modalities were available from 137 patients.

RESULTS: A …

Margaret Mitchell's Lost Letter To A Kansas Horse Buggy Doctor., Jane F. Knapp, Robert Schremmer

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Elevated Stearoyl-Coa Desaturase In Brains Of Patients With Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Vitaly Vasilevko, Nicholas V. Dipatrizio, Sarah K. Martin, David H. Cribbs, Elizabeth Head, Carl W. Cotman, Daniele Piomelli

Sanders-Brown Center on Aging Faculty Publications

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong …

Cardiovascular Magnetic Resonance Myocardial Feature Tracking Detects Quantitative Wall Motion During Dobutamine Stress., Andreas Schuster, Shelby Kutty, Asif Padiyath, Victoria Parish, Paul Gribben, David A. Danford, Marcus R. Makowski, Boris Bigalke, Philipp Beerbaum, Eike Nagel

Journal Articles: Pediatrics

BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) is an established tool to assess hibernating myocardium and ischemia. Analysis is typically based on visual assessment with considerable operator dependency. CMR myocardial feature tracking (CMR-FT) is a recently introduced technique for tissue voxel motion tracking on standard steady-state free precession (SSFP) images to derive circumferential and radial myocardial mechanics.We sought to determine the feasibility and reproducibility of CMR-FT for quantitative wall motion assessment during intermediate dose DS-CMR.

METHODS: 10 healthy subjects were studied at 1.5 Tesla. Myocardial strain parameters were derived from SSFP cine images using dedicated CMR-FT software (Diogenes MRI prototype; …

Duration Of Symptoms Resulting From Lumbar Disc Herniation: Effect On Treatment Outcomes: Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Jeffrey A Rihn, Alan Hilibrand, Kristen Radcliff, Mark Kurd, Jon Lurie, Emily Blood, Todd J Albert, James N Weinstein

Rothman Institute Papers

BACKGROUND: The purpose of the present study was to determine if the duration of symptoms affects outcomes following the treatment of intervertebral lumbar disc herniation.

METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial (SPORT) for the treatment of intervertebral lumbar disc herniation. Randomized and observational cohorts were combined. A comparison was made between patients who had had symptoms for six months or less (n = 927) and those who had had symptoms for more than six months (n = 265). Primary and secondary outcomes were measured at baseline and at regular follow-up …

Duration Of Symptoms Resulting From Lumbar Disc Herniation: Effect On Treatment Outcomes: Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Jeffrey A Rihn, Alan S Hilibrand, Kristen Radcliff, Mark Kurd, Jon Lurie, Emily Blood, Todd J Albert, James N Weinstein

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The purpose of the present study was to determine if the duration of symptoms affects outcomes following the treatment of intervertebral lumbar disc herniation.

METHODS: An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial (SPORT) for the treatment of intervertebral lumbar disc herniation. Randomized and observational cohorts were combined. A comparison was made between patients who had had symptoms for six months or less (n = 927) and those who had had symptoms for more than six months (n = 265). Primary and secondary outcomes were measured at baseline and at regular follow-up …

Proliferating Cell Nuclear Antigen Is Required For Loading Of The Smcx/Kmd5c Histone Demethylase Onto Chromatin., Zhihui Liang, Marc Diamond, Johanna A Smith, Matthias Schnell, René Daniel

Department of Medicine Faculty Papers

UNLABELLED: ABSTRACT:

BACKGROUND: Histone methylation is regulated by a large number of histone methyltransferases and demethylases. The recently discovered SMCX/KMD5C demethylase has been shown to remove methyl residues from lysine 4 of histone H3 (H3K4), and constitutes an important component of the regulatory element-1-silencing transcription factor (REST) protein complex. However, little is known about the cellular mechanisms that control SMCX activity and intracellular trafficking.

RESULTS: In this study, we found that small interfering RNA-mediated knockdown of proliferating cell nuclear antigen (PCNA) resulted in the reduction of the chromatin-bound SMCX fraction. We identified a PCNA-interaction protein motif (PIP box) in the …

Burden Of Traumatic Spine Fractures In Tehran, Iran., Maziar Moradi-Lakeh, Mohammad R Rasouli, Alexander Vaccaro, Soheil Saadat, Mohammad R Zarei, Vafa Rahimi-Movaghar

Rothman Institute Papers

UNLABELLED: ABSTRACT:

BACKGROUND: The Disability-Adjusted Life Year (DALY) was designed by the World Health Organization (WHO) to measure, compare, and analyze the burden of various diseases. To the best of our knowledge, this is the first study on the assessment of burden of traumatic spinal fracture (TSF) in an Iranian community. We estimated burden of TSF includes both isolated (iTSF) and associated injuries related to traumatic spinal fractures (aTSF) in Tehran, the capital of Iran, for the year 2006-2007 using DALYs.

METHODS: Burden of TSF was estimated based on information provided by the national data on Iranian trauma, data from …

Specific Sequence Determinants Of Mir-15/107 Microrna Gene Group Targets, Peter T. Nelson, Wang-Xia Wang, Guogen Mao, Bernard R. Wilfred, Kevin Xie, Mary H. Jennings, Zhen Gao, Xiaowei Wang

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) target mRNAs in human cells via complex mechanisms that are still incompletely understood. Using anti-Argonaute (anti-AGO) antibody co-immunoprecipitation, followed by microarray analyses and downstream bioinformatics, 'RIP-Chip' experiments enable direct analyses of miRNA targets. RIP-Chip studies (and parallel assessments of total input mRNA) were performed in cultured H4 cells after transfection with miRNAs corresponding to the miR-15/107 gene group (miR-103, miR-107, miR-16 and miR-195), and five control miRNAs. Three biological replicates were run for each condition with a total of 54 separate human Affymetrix Human Gene 1.0 ST array replicates. Computational analyses queried for determinants of miRNA:mRNA binding. The …

Systemic Adiponectin Malfunction As A Risk Factor For Cardiovascular Disease., Wayne Bond Lau, Ling Tao, Yajing Wang, Rong Li, Xin L Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad's metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad's anti-inflammatory …

Executive Summary: The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: Clinical Practice Guidelines By The Pediatric Infectious Diseases Society And The Infectious Diseases Society Of America., John S. Bradley, Carrie L. Byington, Samir S. Shah, Brian Alverson, Edward R. Carter, Christopher Harrison, Sheldon L. Kaplan, Sharon E. Mace, George H. Mccracken, Matthew R. Moore, Shawn D. St Peter, Jana A. Stockwell, Jack T. Swanson, Pediatric Infectious Diseases Society And The Infectious Diseases Society Of America

Manuscripts, Articles, Book Chapters and Other Papers

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.

Strain-Dependent Variation In The Early Transcriptional Response To Cns Injury Using A Cortical Explant System, David J. Graber, Brent T. Harris, William F. Hickey

Dartmouth Scholarship

While it is clear that inbred strains of mice have variations in immunological responsiveness, the influence of genetic background following tissue damage in the central nervous system is not fully understood. A cortical explant system was employed as a model for injury to determine whether the immediate transcriptional response to tissue resection revealed differences among three mouse strains. Immunological mRNAs were measured in cerebral cortex from SJL/J, C57BL/6J, and BALB/cJ mice using real time RT-PCR. Freshly isolated cortical tissue and cortical sections incubated in explant medium were examined. Levels of mRNA, normalized to β-actin, were compared using one way analysis …

Whole-Exome Sequencing Of Dna From Peripheral Blood Mononuclear Cells (Pbmc) And Ebv-Transformed Lymphocytes From The Same Donor., Eric R Londin, Margaret A Keller, Michael R D'Andrea, Kathleen Delgrosso, Adam Ertel, Saul Surrey, Paolo Fortina

Kimmel Cancer Center Faculty Papers

BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial for cell biology research and a renewable source of DNA. While LCLs have been used extensively in cellular and genetic studies, the process of cell transformation and expansion during culturing may introduce genomic changes that may impact their use and the interpretation of subsequent genetic findings.

RESULTS: We performed whole exome sequencing on a tetrad family using DNA derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We generated over 4.7 GB of mappable sequence to …

Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain …

Pipkiγ Regulates Focal Adhesion Dynamics And Colon Cancer Cell Invasion, Zhaofei Wu, Xiang Li, Manjula Sunkara, Heather Spearman, Andrew J. Morris, Cai Huang

Markey Cancer Center Faculty Publications

Focal adhesion assembly and disassembly are essential for cell migration and cancer invasion, but the detailed molecular mechanisms regulating these processes remain to be elucidated. Phosphatidylinositol phosphate kinase type Iγ (PIPKIγ) binds talin and is required for focal adhesion formation in EGF-stimulated cells, but its role in regulating focal adhesion dynamics and cancer invasion is poorly understood. We show here that overexpression of PIPKIγ promoted focal adhesion formation, whereas cells expressing either PIPKIγ^K188,200R or PIPKIγ^D316K, two kinase-dead mutants, had much fewer focal adhesions than those expressing WT PIPKIγ in CHO-K1 cells and HCT116 colon cancer cells. Furthermore, …

Activation Of Matrix Metalloproteinases Following Anti-Aβ Immunotherapy; Implications For Microhemorrhage Occurrence, Donna M. Wilcock, Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, Carol A. Colton

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur.

METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which …

John H. Gibbon, Jr., M.D.: Surgical Innovator, Pioneer, And Inspiration., Jordan P. Bloom, B.S., Charles J. Yeo, Md, Herbert E. Cohn, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Throughout history there have been many discoveries that have changed the world, including Albert Einstein’s theory of relativity, Alexander Graham Bell’s telephone, and Jack Kilby and Robert Noyce’s microchip. There are a few analogous contributions that have been made in medicine: Sir Alexander’s discovery of penicillin, Lister’s principles of antiseptic technique, Salk and Sabin’s vaccines for polio, as well as numerous others. These innovative thinkers all had two factors in common. First, they were pioneers who faced problems that had no solutions at the time and who refused to accept the status quo in the face of great scrutiny and …

Mechanisms Of Resistance To Raf Inhibitors In Melanoma., A E Aplin, Fred M Kaplan, Yongping Shao

Department of Cancer Biology Faculty Papers

The recent RAF inhibitor trial with PLX4032/RG7204 in late-stage mutant B-RAF melanoma patients has been lauded as a success story for personalized cancer therapy since short-term clinical responses were observed in the majority of patients. However, initial responses were followed by subsequent tumor re-growth, and a subset of patients showed intrinsic resistance. Bi-directional translational efforts are now essential to determine the mechanisms underlying acquired/secondary and intrinsic resistance to RAF inhibitors.