Where have All the Female MD, PhD Applicants Gone?

Letter to the Editor: In Reply to Factors Influencing Graduate Program Choice Among Undergraduate Women, Cooper Rowan Medical Journal: Vol. 1 : Iss. 1 , Article 5

Graft-versus-Host Disease-Like Pattern in Mycophenolate Mofetil Related Colon Mucosal Injury: Role of FISH in Establishing the Diagnosis

Mycophenolate mofetil (CellCept®), a commonly used immunosuppressive drug in solid organ transplantation, has recently been shown to cause graft-versus-host disease (GVHD)-like changes in the gastrointestinal tract. On rare occasions, true GVHD has also been documented in the gastrointestinal tract of solid organ transplant patients. Because the treatment for these two entities is different, i.e. removal of the offending agent versus the administration of steroids, proper identification of the cause is imperative. We present a case of mycophenolate mofetil colitis mimicking grade I GVHD of the gut. In our study, we used fluorescence in situ hybridization for the Y chromosome to document the lack of male donor lymphocytes in the female recipient colon biopsy. We suggest that molecular techniques including fluorescence in situ hybridization could be used to discriminate between MMF-related colitis and true GVHD in order to help guide therapy

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Rhabdomyosarcoma and Wilms Tumors Contain a Subpopulation of Noggin Producing, Myogenic Cells Immunoreactive for Lens Beaded Filament Proteins

Myo/Nog cells are identified by their expression of the skeletal muscle specific transcription factor MyoD and the bone morphogenetic protein inhibitor noggin, and binding of the G8 monoclonal antibody. Their release of noggin is critical for morphogenesis and skeletal myogenesis. In the adult, Myo/Nog cells are present in normal tissues, wounds and skin tumors. Myo/Nog cells in the lens give rise to myofibroblasts that synthesize skeletal muscle proteins. The purpose of this study was to screen human lens tissue, rhabdomyosarcoma cell lines, and tissue sections from rhabdomyosarcoma, Wilms and tumors lacking features of skeletal muscle for co-localization of antibodies to Myo/Nog cell markers and the lens beaded filament proteins filensin and CP49. Immunofluorescence localization experiments revealed that Myo/Nog cells of the lens bind antibodies to beaded filament proteins. Co-localization of antibodies to G8, noggin, filensin and CP49 was observed in most RC13 and a subpopulation of RD human rhabdomyosarcoma cell lines. Western blotting with beaded filament antibodies revealed bands of similar molecular weights in RC13 and murine lens cells. Human alveolar, embryonal, pleomorphic and spindle cell rhabdomyosarcomas and Wilms tumors contained a subpopulation of cells immunoreactive for G8, noggin, MyoD and beaded filaments. G8 was also co-localized with filensin mRNA. Staining for beaded filament proteins was not detected in G8 positive cells in leiomyosarcomas, squamous and basal cell carcinomas, syringocarciomas and malignant melanomas. Lens beaded filament proteins were thought to be present only in the lens. Myo/Nog-like cells immunoreactive for beaded filaments may be diagnostic of tumors related to the skeletal muscle lineage

Prolonged hemophagocytic lymphohistiocytosis syndrome as an initial presentation of Hodgkin lymphoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hemophagocytic lymphohistiocytosis is an immune-mediated syndrome that typically has a rapidly progressive course that can result in pancytopenia, coagulopathy, multi-system organ failure and death.</p> <p>Case presentation</p> <p>A 57-year-old Caucasian woman was referred in fulminant hemophagocytic lymphohistiocytosis, with fever, pancytopenia, splenomegaly, mental status changes and respiratory failure. She was found to have stage IV classical Hodgkin lymphoma, in addition to Epstein-Barr virus and cytomegalovirus viremia. Her presentation was preceded by a 3-year prodrome consisting of cytopenia and fever that were partially controlled by steroids and azathioprine.</p> <p>Conclusion</p> <p>Fulminant hemophagocytic lymphohistiocytosis may follow a prodromal phase that possesses features suggestive of a chronic form of hemophagocytic lymphohistiocytosis, but which may also resemble immune cytopenias of other causes. A diagnosis of hemophagocytic lymphohistiocytosis should be considered in the setting of chronic pancytopenia.</p

Characterizing the role of endogenous antiangiogenic factors in neovascular pathology and normal vascular development in the retina

Pigment epithelium-derived factor (PEDF) and tissue inhibitor of metalloproteinase-3 (TIMP-3) are thought to be involved in normal and aberrant ocular angiogenesis. The goal of this project is to examine the role that each plays in these processes. In human developing retinas, polyclonal antibody (pAb) anti-PEDF labeled the retinal pigment epithelium (RPE), cones, some neuroblasts and cells in the ganglion cell layer (GCL). In adult human retinas, pAb anti-PEDF labeled rods, cones, cells of the inner nuclear and GC layers, choroid, corneal epithelium and endothelium, and ciliary body. In situ hybridization revealed PEDF mRNA in the RPE, photoreceptors, INL and GCL. In developing and adult retinas, monoclonal antibody (mAb) anti-PEDF labeled the interphotoreceptor matrix (IPM). In the mouse retina, immunohistochemical and in situ hybridization showed PEDF expression in the ciliary body and choroid during mid-gestation. Near term, protein levels increased in the GCL and remained high through the first two weeks postnatal. Levels decreased after this point but persisted through adulthood. Expression levels in the inner retina were much higher at all timepoints than in the outer retina. Because PEDF protein levels have been found to be responsive to ambient oxygen tension, we also attempted to isolate the PEDF promoter and examine its activity under normoxic and hypoxic conditions. However, the portion of promoter isolated was weakly functional in luciferase assays, and further study was not pursued. We also demonstrated inhibition of ischemia-induced ocular neovascularization via adeno-assoicated viral-induced overexpression of PEDF, TIMP-3, and endostatin using fluorescein angiography and histologic techniques. The effects of mutations in TIMP-3 known to cause inherited choroidal neovascularization on angiogenesis in vivo were also examined. Mice injected subretinally with AAV.CMV.TIMP-3 172 2/5, AAV.CMV.TIMP-3 167 2/5, or AAV.CMV.TIMP-3 wild type 2/5 demonstrated more RPE changes and white spots when observed by indirect ophtalmoscopy than control virus-injected eye. Changes were most severe in eyes injected with AAV.CMV.TlMP-3 172 2/5. However, no choroidal neovascularization or retinal degeneration was seen histologically. Transduction efficiency of AAV.CMV.EGFP 2/1, 2/2, and 2/5 in human umbilical vein endothelial cells (HUVEC) as well as COS-7 cells was also determined using microscopy and flow cytometry

Characterizing the role of endogenous antiangiogenic factors in neovascular pathology and normal vascular development in the retina

Pigment epithelium-derived factor (PEDF) and tissue inhibitor of metalloproteinase-3 (TIMP-3) are thought to be involved in normal and aberrant ocular angiogenesis. The goal of this project is to examine the role that each plays in these processes. In human developing retinas, polyclonal antibody (pAb) anti-PEDF labeled the retinal pigment epithelium (RPE), cones, some neuroblasts and cells in the ganglion cell layer (GCL). In adult human retinas, pAb anti-PEDF labeled rods, cones, cells of the inner nuclear and GC layers, choroid, corneal epithelium and endothelium, and ciliary body. In situ hybridization revealed PEDF mRNA in the RPE, photoreceptors, INL and GCL. In developing and adult retinas, monoclonal antibody (mAb) anti-PEDF labeled the interphotoreceptor matrix (IPM). In the mouse retina, immunohistochemical and in situ hybridization showed PEDF expression in the ciliary body and choroid during mid-gestation. Near term, protein levels increased in the GCL and remained high through the first two weeks postnatal. Levels decreased after this point but persisted through adulthood. Expression levels in the inner retina were much higher at all timepoints than in the outer retina. Because PEDF protein levels have been found to be responsive to ambient oxygen tension, we also attempted to isolate the PEDF promoter and examine its activity under normoxic and hypoxic conditions. However, the portion of promoter isolated was weakly functional in luciferase assays, and further study was not pursued. We also demonstrated inhibition of ischemia-induced ocular neovascularization via adeno-assoicated viral-induced overexpression of PEDF, TIMP-3, and endostatin using fluorescein angiography and histologic techniques. The effects of mutations in TIMP-3 known to cause inherited choroidal neovascularization on angiogenesis in vivo were also examined. Mice injected subretinally with AAV.CMV.TIMP-3 172 2/5, AAV.CMV.TIMP-3 167 2/5, or AAV.CMV.TIMP-3 wild type 2/5 demonstrated more RPE changes and white spots when observed by indirect ophtalmoscopy than control virus-injected eye. Changes were most severe in eyes injected with AAV.CMV.TlMP-3 172 2/5. However, no choroidal neovascularization or retinal degeneration was seen histologically. Transduction efficiency of AAV.CMV.EGFP 2/1, 2/2, and 2/5 in human umbilical vein endothelial cells (HUVEC) as well as COS-7 cells was also determined using microscopy and flow cytometry

Partnering for the Success of Online Learning

This presentation will report on a national study conducted on the current institutional practices, structures, resources, and policies that are needed to ensure that online courses are accessible for all students in higher education. Specifically, it will focus on the need to better articulate who is responsible for online accessibility; the need for institutional investment; and the sense of overwhelm of where to begin. Finally, this presentation will close with a review of best practices for ensuring accessible online courses. At the conclusion of the session, participants will receive A Guide to Increased Collaboration for Online Accessibility Initiatives

Colorectal cancer

© Springer International Publishing Switzerland 2016. All rights reserved. Molecular testing of colorectal cancer (CRC) has become the standard practice in the management of patients who are candidates for chemotherapy and geneor pathway-targeted therapies, providing critical information for precision therapy. Current and emerging testing approaches and guidelines used to select EGFR pathway-targeted therapies for CRC are reviewed, as well as the use of DNA mismatch repair deficiency testing in CRC for identification of patients who might not benefit from conventional therapies containing 5-fluorouracil (5FU). Recent recommendations for extended RAS mutation testing encompassing exons 2, 3, and 4 of KRAS and NRAS in CRC are highlighted. An overview of laboratory considerations includes the critical role of tumor tissue evaluation by pathologists, in order to select the best areas of tumor for testing. In addition to a number of conventional testing platforms, given the increasing number of gene mutations that may be critical to achieve targeted therapy efficacy in CRC, advances in the use of gene panels for mutation analysis with platforms that permit detection of hundreds of mutations in a single sample, such as next-generation sequencing (NGS) gene panels, are described

Fatal Gastrointestinal Hemorrhage in a Patient with Brunner’s Gland Hyperplasia

Brunner’s gland hyperplasia is a rare cause of duodenal mass and gastrointestinal hemorrhage. Imaging and esophagoduodenoscopic evaluation of this condition are frequently consistent with a duodenal malignancy often resulting in surgical resection. However, the malignant potential of these lesions is still unknown, and most are benign. We report the case of a 74-year-old man who presented with fatal gastrointestinal bleeding and esophagoduodenoscopy findings consistent with a duodenal mass and mucosal ulceration. At autopsy, histologic examination of the mass revealed Brunner’s gland hyperplasia with associated ulcer formation. In this report, we review the findings associated with this case as well the literature regarding presentation, clinical associations, and treatment of Brunner’s gland hyperplasia