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gideon hirschfield

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https://www.readbyqxmd.com/read/27880989/validation-of-the-prognostic-value-of-histologic-scoring-systems-in-primary-sclerosing-cholangitis-an-international-cohort-study
#1
Elisabeth M G De Vries, Manon de Krijger, Martti Farkkila, Johanna Arola, Peter Schirmacher, Daniel Gotthardt, Benjamin Goeppert, Palak J Trivedi, Gideon M Hirschfield, Henriette Ytting, Ben Vainer, Henk R van Buuren, Katharina Biermann, Maren H Harms, Olivier Chazouilleres, Dominique Wendum, Astrid Donald Kemgang, Roger W Chapman, Lai Mun Wang, Kate D Williamson, Annette S H Gouw, Valerie Paradis, Christine Sempoux, Ulrich Beuers, Stefan Hubscher, Joanne Verheij, Cyriel Ponsioen
: Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic utility and reproducibility, across a multicenter PSC cohort. Liver biopsies from PSC patients were collected across 7 European centers. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems...
November 23, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27806199/new-approaches-to-investigate-drug-induced-hypersensitivity
#2
Monday O Ogese, Shaheda Ahmed, Ana Alfirevic, Catherine J Betts, Anne Dickinson, Lee Faulkner, Neil S French, Andrew Gibson, Gideon M Hirschfield, Michael Ernst Kammüller, Xiaoli Meng, Stefan F Martin, Philippe Musette, Alan Norris, Munir Pirmohamed, Brian Kevin Park, Anthony Wayne Purcell, Colin F Spraggs, Jessica Whritenour, Dean John Naisbitt
The workshop on "New approaches to investigate drug-induced hypersensitivity" was held on June 5 2014 at the Foresight centre, University of Liverpool. The aims of the workshop were to (1) discuss our current understanding of the genetic, clinical and chemical basis of small molecule drug hypersensitivity (2) highlight the current status of assays that might be developed to predict potential drug immunogenicity, (3) identify the limitations, knowledge gaps and challenges that limit the use of these assays and utilise the knowledge gained from the workshop to develop a pathway to establish new and improved assays that better predict drug-induced hypersensitivity reactions during the early stages of drug development...
November 2, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27784538/phenotyping-and-auto-antibody-production-by-liver-infiltrating-b-cells-in-primary-sclerosing-cholangitis-and-primary-biliary-cholangitis
#3
Brian K Chung, Bardia T Guevel, Gary M Reynolds, D B R K Gupta Udatha, Eva Kristine Klemsdal Henriksen, Zania Stamataki, Gideon M Hirschfield, Tom Hemming Karlsen, Evaggelia Liaskou
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated biliary diseases that demonstrate prominent and restricted genetic association with human leukocyte antigen (HLA) alleles. In PBC, anti-mitochondrial antibodies (AMA) are specific and used as diagnostic biomarkers. PSC-relevant auto-antibodies remain controversial despite a distinct HLA association that mirrors archetypical auto-antigen driven disorders. Herein, we compared antibody-secreting B cells (ASCs) in PSC and PBC liver explants to determine if liver-infiltrating ASCs represent an opportune and novel source of disease-relevant auto-antibodies...
October 24, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27647428/gut-and-liver-t-cells-of-common-clonal-origin-in-primary-sclerosing-cholangitis-inflammatory-bowel-disease
#4
Eva Kristine Klemsdal Henriksen, Kristin Kaasen Jørgensen, Fatemeh Kaveh, Kristian Holm, David Hamm, Johanna Olweus, Espen Melum, Brian K Chung, Tor J Eide, Knut E A Lundin, Kirsten Muri Boberg, Tom H Karlsen, Gideon M Hirschfield, Evaggelia Liaskou
BACKGROUND & AIMS: Recruitment of gut-derived memory T cells to the liver is believed to drive hepatic inflammation in primary sclerosing cholangitis (PSC). However, whether gut-infiltrating and liver-infiltrating T cells share T-cell receptors (TCRs) and antigenic specificities is unknown. We used paired gut and liver samples from PSC patients with concurrent inflammatory bowel disease (PSC-IBD), and normal tissue samples from colon cancer controls, to assess potential T-cell clonotype overlap between the two compartments...
September 16, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27601441/mesenchymal-stromal-cells-and-liver-fibrosis-a-complicated-relationship
#5
REVIEW
Debashis Haldar, Neil C Henderson, Gideon Hirschfield, Philip N Newsome
Mesenchymal stromal cell (MSC) therapy demands the attention of clinicians and scientists because of its potential in clinical fields that are bereft of medical options, but also because of the controversies that underlie its mode of action. MSCs are potent immune modulators, yet their biologic activity may not be innate, requiring licensing by their microenvironment. This property has prompted researchers to explore unique ways in which MSCs may be able to exert distinct biologic effects in different pathologic settings...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27532829/a-placebo-controlled-trial-of-obeticholic-acid-in-primary-biliary-cholangitis
#6
RANDOMIZED CONTROLLED TRIAL
Frederik Nevens, Pietro Andreone, Giuseppe Mazzella, Simone I Strasser, Christopher Bowlus, Pietro Invernizzi, Joost P H Drenth, Paul J Pockros, Jaroslaw Regula, Ulrich Beuers, Michael Trauner, David E Jones, Annarosa Floreani, Simon Hohenester, Velimir Luketic, Mitchell Shiffman, Karel J van Erpecum, Victor Vargas, Catherine Vincent, Gideon M Hirschfield, Hemant Shah, Bettina Hansen, Keith D Lindor, Hanns-Ulrich Marschall, Kris V Kowdley, Roya Hooshmand-Rad, Tonya Marmon, Shawn Sheeron, Richard Pencek, Leigh MacConell, Mark Pruzanski, David Shapiro
BACKGROUND: Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease. METHODS: In this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5-10-mg group), or placebo...
August 18, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27431238/bat117213-ileal-bile-acid-transporter-ibat-inhibition-as-a-treatment-for-pruritus-in-primary-biliary-cirrhosis-study-protocol-for-a-randomised-controlled-trial
#7
Vinod S Hegade, Stuart F W Kendrick, Robert L Dobbins, Sam R Miller, Duncan Richards, James Storey, George Dukes, Kim Gilchrist, Susan Vallow, Graeme J Alexander, Margaret Corrigan, Gideon M Hirschfield, David E J Jones
BACKGROUND: Pruritus (itch) is a symptom commonly experienced by patients with cholestatic liver diseases such as primary biliary cholangitis (PBC, previously referred to as primary biliary cirrhosis). Bile acids (BAs) have been proposed as potential pruritogens in PBC. The ileal bile acid transporter (IBAT) protein expressed in the distal ileum plays a key role in the enterohepatic circulation of BAs. Pharmacological inhibition of IBAT with GSK2330672 may reduce BA levels in the systemic circulation and improve pruritus...
2016: BMC Gastroenterology
https://www.readbyqxmd.com/read/27325130/an-overview-of-the-diagnosis-and-management-of-immunoglobulin-g4-related-disease
#8
REVIEW
Debashis Haldar, Paul Cockwell, Alex G Richter, Keith J Roberts, Gideon M Hirschfield
No abstract text is available yet for this article.
September 20, 2016: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/27170385/the-pathogenesis-of-autoimmune-liver-disease
#9
Katherine Arndtz, Gideon M Hirschfield
BACKGROUND: Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. KEY MESSAGES: There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27166102/clinical-news
#10
Janet Fricker, Donald Sheppard, Susan Mayor, Gideon Hirschfield, Roger Williams, Dale Gerding, Sue Lyon
No abstract text is available yet for this article.
May 2, 2016: British Journal of Hospital Medicine
https://www.readbyqxmd.com/read/27109640/klinefelter-s-syndrome-47-xxy-is-in-excess-among-men-with-sj%C3%A3-gren-s-syndrome
#11
Valerie M Harris, Rohan Sharma, Joshua Cavett, Biji T Kurien, Ke Liu, Kristi A Koelsch, Astrid Rasmussen, Lida Radfar, David Lewis, Donald U Stone, C Erick Kaufman, Shibo Li, Barbara Segal, Daniel J Wallace, Michael H Weisman, Swamy Venuturupalli, Jennifer A Kelly, Marta E Alarcon-Riquelme, Bernardo Pons-Estel, Roland Jonsson, Xianglan Lu, Jacques-Eric Gottenberg, Juan-Manuel Anaya, Deborah S Cunninghame-Graham, Andrew J W Huang, Michael T Brennan, Pamela Hughes, Ilias Alevizos, Corinne Miceli-Richard, Edward C Keystone, Vivian P Bykerk, Gideon Hirschfield, Gang Xie, Wan-Fai Ng, Gunnel Nordmark, Sara Magnusson Bucher, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Marie Wahren-Herlenius, Torsten Witte, Xavier Mariette, Christopher J Lessard, John B Harley, Kathy L Sivils, R Hal Scofield
Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS)...
July 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/26873648/intestinal-ccl25-expression-is-increased-in-colitis-and-correlates-with-inflammatory-activity
#12
Palak J Trivedi, Tony Bruns, Stephen Ward, Martina Mai, Carsten Schmidt, Gideon M Hirschfield, Chris J Weston, David H Adams
CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis...
April 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/26812071/single-gene-association-between-gata-2-and-autoimmune-hepatitis-a-novel-genetic-insight-highlighting-immunologic-pathways-to-disease
#13
Gwilym Webb, Yung-Yi Chen, Ka-Kit Li, Desley Neil, Ye Htun Oo, Alex Richter, Venetia Bigley, Matthew Collin, David H Adams, Gideon M Hirschfield
Background & Aims Autoimmune hepatitis (AIH), an immune-mediated liver disease, originates as a consequence of interacting genetic and environmental risk factors. Treatment remains non-specific and prone to side effects. Deficiencies in regulatory T cell (Treg) function are hypothesized to contribute to the pathogenesis of AIH. Methods We describe an adult patient who presented with AIH in the context of monocytopenia. The patient was characterized by GATA2 gene sequencing, flow cytometry of peripheral blood for leucocyte subsets, ELISA for serum Flt-3 ligand, and immunohistochemistry of liver biopsy tissue...
May 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/26713507/x-chromosome-dose-and-sex-bias-in-autoimmune-diseases-increased-prevalence-of-47-xxx-in-systemic-lupus-erythematosus-and-sj%C3%A3-gren-s-syndrome
#14
Ke Liu, Biji T Kurien, Sarah L Zimmerman, Kenneth M Kaufman, Diana H Taft, Leah C Kottyan, Sara Lazaro, Carrie A Weaver, John A Ice, Adam J Adler, James Chodosh, Lida Radfar, Astrid Rasmussen, Donald U Stone, David M Lewis, Shibo Li, Kristi A Koelsch, Ann Igoe, Mitali Talsania, Jay Kumar, Jacen S Maier-Moore, Valerie M Harris, Rajaram Gopalakrishnan, Roland Jonsson, James A Lessard, Xianglan Lu, Jacques-Eric Gottenberg, Juan-Manuel Anaya, Deborah S Cunninghame-Graham, Andrew J W Huang, Michael T Brennan, Pamela Hughes, Gabor G Illei, Corinne Miceli-Richard, Edward C Keystone, Vivian P Bykerk, Gideon Hirschfield, Gang Xie, Wan-Fai Ng, Gunnel Nordmark, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Barbara M Segal, Timothy J Vyse, Marie Wahren-Herlenius, Torsten Witte, Bernardo Pons-Estel, Marta E Alarcón-Riquelme, Joel M Guthridge, Judith A James, Christopher J Lessard, Jennifer A Kelly, Susan D Thompson, Patrick M Gaffney, Courtney G Montgomery, Jeffrey C Edberg, Robert P Kimberly, Graciela S Alarcón, Carl L Langefeld, Gary S Gilkeson, Diane L Kamen, Betty P Tsao, W Joseph McCune, Jane E Salmon, Joan T Merrill, Michael H Weisman, Daniel J Wallace, Tammy O Utset, Erwin P Bottinger, Christopher I Amos, Katherine A Siminovitch, Xavier Mariette, Kathy L Sivils, John B Harley, R Hal Scofield
OBJECTIVE: More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls...
May 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/26641487/aspects-of-the-pathophysiology-of-primary-biliary-cirrhosis
#15
Margaret Corrigan, Gideon M Hirschfield
Primary biliary cirrhosis is a classical autoimmune liver disease and is present in around 1 in 1,000 women over the age of 40. It has a number of diagnostic characteristics consistent with autoimmune liver injury, in particular, the high specificity of circulating anti-mitochondrial antibodies. Histologically, the disease is reflected as a granulomatous lymphocytic cholangitis that consequently leads to small bile duct loss and cholestasis. Progressive disease is characterised by the development of a biliary cirrhosis, with end-stage features of liver disease ultimately impacting patient outcomes...
2015: Digestive Diseases
https://www.readbyqxmd.com/read/26597786/ustekinumab-for-patients-with-primary-biliary-cholangitis-who-have-an-inadequate-response-to-ursodeoxycholic-acid-a-proof-of-concept-study
#16
Gideon M Hirschfield, M Eric Gershwin, Richard Strauss, Marlyn J Mayo, Cynthia Levy, Bin Zou, Jewel Johanns, Ivo P Nnane, Bidisha Dasgupta, Katherine Li, Carlo Selmi, Hanns-Ulrich Marschall, David Jones, Keith Lindor
UNLABELLED: The interleukin (IL)-12 signaling cascade has been associated with primary biliary cholangitis (PBC). This multicenter, open-label, proof-of-concept study evaluated the anti-IL12/23 monoclonal antibody, ustekinumab (90 mg subcutaneous at weeks 0 and 4, then every 8 weeks through week 20), in adults with PBC and an inadequate response to ursodeoxycholic acid therapy (i.e., alkaline phosphatase [ALP] >1.67× upper limit of normal [ULN] after ≥6 months). ALP response was defined as a >40% decrease from baseline and ALP remission as ALP normalization (if baseline ALP 1...
July 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26593288/the-immunogenetics-of-autoimmune-cholestasis
#17
REVIEW
Palak J Trivedi, Gideon M Hirschfield
The immune-mediated hepatobiliary diseases, primary biliary cirrhosis and primary sclerosing cholangitis are relatively rare, albeit and account for a significant amount of liver transplant activity and liver-related mortality globally. Precise disease mechanisms are yet to be described although a contributory role of genetic predisposition is firmly established. In addition to links with the major histocompatibility complex, a number of associations outside this region harbor additional loci which underscore the fundamental role of breaks in immune tolerance and mucosal immunogenicity in the pathogenesis of autoimmune biliary disease...
February 2016: Clinics in Liver Disease
https://www.readbyqxmd.com/read/26553417/primary-biliary-cirrhosis-renaming-primary-biliary-cirrhosis-clarity-or-confusion
#18
Palak J Trivedi, Gideon M Hirschfield
No abstract text is available yet for this article.
December 2015: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/26549695/obeticholic-acid-for-the-treatment-of-primary-biliary-cirrhosis
#19
REVIEW
Palak J Trivedi, Gideon M Hirschfield, M Eric Gershwin
Primary biliary cirrhosis (PBC) is characterized by progressive nonsuppurative destruction of small bile ducts, resulting in intrahepatic cholestasis, fibrosis and ultimately end-stage liver disease. Timely intervention with ursodeoxycholic acid is associated with excellent survival, although approximately one-third of all patients fail to achieve biochemical response, signifying a critical need for additional therapeutic strategies. Obeticholic acid (OCA) is a potent ligand of the nuclear hormone receptor farnesoid X receptor (FXR)...
2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/26458216/long-term-follow-up-of-patients-with-difficult-to-treat-type-1-autoimmune-hepatitis-on-tacrolimus-therapy
#20
Nwe Ni Than, Christiane Wiegard, Christina Weiler-Normann, Katja Füssel, Jake Mann, James Hodson, Gideon M Hirschfield, Ansgar W Lohse, David H Adams, Christoph Schramm, Ye Htun Oo
INTRODUCTION: Autoimmune hepatitis (AIH) is an immune-mediated liver disease, which requires long-term immunosuppression. Ten to fifteen percent of patients experience insufficient/intolerance response to standard therapy. Although alternate immunosuppression has been applied, there is little long-term data reported on safety, efficacy, steroid-dose reduction and disease evolution in patients with difficult AIH who were on Tacrolimus therapy. MATERIALS AND METHODS: Clinical, biochemical, immunological profiles, treatment response and side effects of 17 AIH patients treated with Tacrolimus between 2003 and 2014 were analyzed from two tertiary referral liver centers...
March 2016: Scandinavian Journal of Gastroenterology
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