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https://www.readbyqxmd.com/read/28811186/identification-and-characterization-of-small-molecule-inhibitors-of-porcine-reproductive-and-respiratory-syndrome-virus
#1
Alyssa B Evans, Pengfei Dong, Hyelee Loyd, Jianqiang Zhang, George A Kraus, Susan Carpenter
Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiological agent of PRRS, an economically significant disease of swine worldwide. PRRSV is poorly controlled by the currently available vaccines, and alternative control strategies are needed to help prevent the continual circulation of the virus. Previously, we developed a synthetic route for the natural compound atractylodinol and demonstrated anti-PRRSV activity in vitro. However, the synthetic route was inefficient and the yield was poor...
August 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28807233/overcoming-obstacles-in-the-design-of-cancer-anorexia-weight-loss-trials
#2
REVIEW
Jennifer G Le-Rademacher, Jeffrey Crawford, William J Evans, Aminah Jatoi
Most advanced cancer patients suffer loss of appetite (anorexia) and loss of weight. Despite the fact that cancer anorexia and weight loss are associated with a poor prognosis and detract from quality of life, no interventions have been demonstrated to palliate this syndrome in its entirety, particularly in patients with treatment-refractory malignancies. Recently, two registration trials - one with anamorelin and another with enobosarm - failed to reach their primary endpoints, thus raising questions. Were both these agents ineffective? Alternatively, did study design issues compromise the ability of these trials to identify effective agents? Thus, this review is timely insofar it serves as an introduction to study design, offers guidance on how to test promising agents for cancer anorexia/weight loss, and provides advice for overcoming trial design obstacles...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28793997/effect-of-intensive-versus-standard-blood-pressure-treatment-according-to-baseline-prediabetes-status-a-post-hoc-analysis-of-a-randomized-trial
#3
Adam P Bress, Jordan B King, Kathryn E Kreider, Srinivasan Beddhu, Debra L Simmons, Alfred K Cheung, Yingying Zhang, Michael Doumas, John Nord, Mary Ellen Sweeney, Addison A Taylor, Charles Herring, William J Kostis, James Powell, Anjay Rastogi, Christianne L Roumie, Alan Wiggers, Jonathan S Williams, Reem Yunis, Athena Zias, Greg W Evans, Tom Greene, Michael V Rocco, William C Cushman, David M Reboussin, Mark N Feinglos, Vasilios Papademetriou
OBJECTIVE: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). RESEARCH DESIGN AND METHODS: This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL)...
August 9, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28772291/baseline-surveillance-in-li-fraumeni-syndrome-using-whole-body-magnetic-resonance-imaging-a-meta-analysis
#4
Mandy L Ballinger, Ana Best, Phuong L Mai, Payal P Khincha, Jennifer T Loud, June A Peters, Maria Isabel Achatz, Rubens Chojniak, Alexandre Balieiro da Costa, Karina Miranda Santiago, Judy Garber, Allison F O'Neill, Rosalind A Eeles, D Gareth Evans, Eveline Bleiker, Gabe S Sonke, Marielle Ruijs, Claudette Loo, Joshua Schiffman, Anne Naumer, Wendy Kohlmann, Louise C Strong, Jasmina Bojadzieva, David Malkin, Surya P Rednam, Elena M Stoffel, Erika Koeppe, Jeffrey N Weitzel, Thomas P Slavin, Bita Nehoray, Mark Robson, Michael Walsh, Lorenzo Manelli, Anita Villani, David M Thomas, Sharon A Savage
Importance: Guidelines for clinical management in Li-Fraumeni syndrome, a multiple-organ cancer predisposition condition, are limited. Whole-body magnetic resonance imaging (WBMRI) may play a role in surveillance of this high-risk population. Objective: To assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline. Data Sources: Clinical and research surveillance cohorts were identified through the Li-Fraumeni Exploration Research Consortium...
August 3, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28772289/association-of-mismatch-repair-mutation-with-age-at-cancer-onset-in-lynch-syndrome-implications-for-stratified-surveillance-strategies
#5
Neil A J Ryan, Julie Morris, Kate Green, Fiona Lalloo, Emma R Woodward, James Hill, Emma J Crosbie, D Gareth Evans
Importance: Lynch syndrome is caused by dominantly inherited germline mutations that predispose individuals to colorectal, endometrial, ovarian, and other cancers through inactivation of the cellular mismatch repair system. Lynch syndrome-associated cancers are amenable to surveillance strategies that may improve survival. The age at which surveillance should start is disputed. Objective: To determine whether mutated gene and type of mutation influence age at onset of Lynch syndrome-associated cancers...
August 3, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28765416/the-physician-s-role-in-perioperative-management-of-older-patients-undergoing-surgery
#6
Adam L Gordon, Barry J Evans, Jugdeep Dhesi
Life-sustaining and life-improving surgical interventions are increasingly available to older, frailer patients, many of whom have multimorbidity. Physicians can help support perioperative multidisciplinary teams with assessment and preoperative optimisation of physiological reserve, comorbidities and associated geriatric syndromes. Similar structured support can be useful in the postoperative period where older patients are at increased risk of delirium, medical complications, increased functional dependency and where discharge planning can prove more difficult than in younger cohorts...
July 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/28759666/association-of-genetic-predisposition-with-solitary-schwannoma-or-meningioma-in-children-and-young-adults
#7
Omar N Pathmanaban, Katherine V Sadler, Ian D Kamaly-Asl, Andrew T King, Scott A Rutherford, Charlotte Hammerbeck-Ward, Martin G McCabe, John-Paul Kilday, Christian Beetz, Nicola K Poplawski, D Gareth Evans, Miriam J Smith
Importance: Meningiomas and schwannomas are usually sporadic, isolated tumors occurring in adults older than 60 years and are rare in children and young adults. Multiple schwannomas and/or meningiomas are more frequently associated with a tumor suppressor syndrome and, accordingly, trigger genetic testing, whereas solitary tumors do not. Nevertheless, apparently sporadic tumors in young patients may herald a genetic syndrome. Objective: To determine the frequency of the known heritable meningioma- or schwannoma-predisposing mutations in children and young adults presenting with a solitary meningioma or schwannoma...
July 31, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28757265/pathophysiology-of-eosinophilic-esophagitis
#8
Kelly M O'Shea, Seema S Aceves, Evan S Dellon, Sandeep K Gupta, Jonathan M Spergel, Glenn T Furuta, Marc E Rothenberg
Eosinophilic esophagitis (EoE) is an emerging disease that is distinguished from gastroesophageal reflux disease (GERD) by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming factor beta (TGF-β) production and signaling, to EoE pathophysiology...
July 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28755841/gene-expression-profiles-in-whole-blood-and-associations-with-metabolic-dysregulation-in-obesity
#9
Amanda J Cox, Ping Zhang, Tiffany J Evans, Rodney J Scott, Allan W Cripps, Nicholas P West
BACKGROUND: Gene expression data provides one tool to gain further insight into the complex biological interactions linking obesity and metabolic disease. This study examined associations between blood gene expression profiles and metabolic disease in obesity. METHODS: Whole blood gene expression profiles, performed using the Illumina HT-12v4 Human Expression Beadchip, were compared between (i) individuals with obesity (O) or lean (L) individuals (n=21 each), (ii) individuals with (M) or without (H) Metabolic Syndrome (n=11 each) matched on age and gender...
July 26, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28754778/cancer-risk-and-survival-in-path_mmr-carriers-by-gene-and-gender-up-to-75-years-of-age-a-report-from-the-prospective-lynch-syndrome-database
#10
Pål Møller, Toni T Seppälä, Inge Bernstein, Elke Holinski-Feder, Paulo Sala, D Gareth Evans, Annika Lindblom, Finlay Macrae, Ignacio Blanco, Rolf H Sijmons, Jacqueline Jeffries, Hans F A Vasen, John Burn, Sigve Nakken, Eivind Hovig, Einar Andreas Rødland, Kukatharmini Tharmaratnam, Wouter H de Vos Tot Nederveen Cappel, James Hill, Juul T Wijnen, Mark A Jenkins, Kate Green, Fiona Lalloo, Lone Sunde, Miriam Mints, Lucio Bertario, Marta Pineda, Matilde Navarro, Monika Morak, Laura Renkonen-Sinisalo, Mev Dominguez Valentin, Ian M Frayling, John-Paul Plazzer, Kirsi Pylvanainen, Maurizio Genuardi, Jukka-Pekka Mecklin, Gabriela Moeslein, Julian R Sampson, Gabriel Capella
BACKGROUND: Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival. OBJECTIVE AND DESIGN: This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. RESULTS: 3119 patients were followed for a total of 24 475 years...
July 28, 2017: Gut
https://www.readbyqxmd.com/read/28734575/outcomes-associated-to-serum-phosphate-levels-in-patients-with-suspected-acute-coronary-syndrome
#11
Hong Xu, Marie Evans, Alessandro Gasparini, Karolina Szummer, Jonas Spaak, Johan Ärnlöv, Bengt Lindholm, Tomas Jernberg, Juan Jesús Carrero
BACKGROUND: We investigated the association between phosphate and the risk of adverse clinical outcomes in patients with manifest cardiovascular disease (CVD). METHODS: Observational study of patients hospitalized during 2006-2011 in Stockholm, Sweden, because of suspected acute coronary syndrome (ACS). The exposure was serum phosphate during the hospitalization. We modeled the association between phosphate and in-hospital death or in-hospital events (composite of myocardial infarction, cardiogenic shock, resuscitated cardiac arrest, atrial fibrillation, or atrioventricular block) as well as the one-year post-discharge risk of death or cardiovascular event (composite of myocardial re-infarction, heart failure and stroke)...
July 17, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28730852/cannabinoid-hyperemesis-syndrome-and-topical-capsaicin-treating-smoke-with-fire-the-authors-reply
#12
Zachary Hafez, Michael E Mullins, Eike Blohm, Mark J O'Connor, Laurel Dezieck, Evan S Schwarz, Albert Conicella
No abstract text is available yet for this article.
July 21, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28698848/treatment-and-response-of-autoimmune-cytopenia-occurring-after-allogeneic-hematopoietic-cell-transplantation-in-children
#13
Seok Hwang-Bo, Seong-Koo Kim, Jae Wook Lee, Pil-Sang Jang, Nack-Gyun Chung, Dae-Chul Jeong, Bin Cho, Hack-Ki Kim
BACKGROUND: Autoimmune cytopenia (AIC) is a rare complication of allogeneic hematopoietic cell transplantation (HCT). In this study, we reviewed the diagnosis, treatment and response to therapy for pediatric patients with post-HCT AIC at our institution. METHODS: Of the 292 allogeneic HCTs performed from January, 2011 to December, 2015 at the Department of Pediatrics, The Catholic University of Korea, seven were complicated by post-HCT AIC, resulting in an incidence of 2...
June 2017: Blood Research
https://www.readbyqxmd.com/read/28691158/anticonvulsant-effect-of-cannabinoid-receptor-agonists-in-models-of-seizures-in-developing-rats
#14
Megan N Huizenga, Evan Wicker, Veronica C Beck, Patrick A Forcelli
OBJECTIVE: Although drugs targeting the cannabinoid system (e.g., CB1 receptor agonists) display anticonvulsant efficacy in adult animal models of seizures/epilepsy, they remain unexplored in developing animal models. However, cannabinoid system functions emerge early in development, providing a rationale for targeting this system in neonates. We examined the therapeutic potential of drugs targeting the cannabinoid system in three seizure models in developing rats. METHODS: Postnatal day (P) 10, Sprague-Dawley rat pups were challenged with the chemoconvulsant methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) or pentylenetetrazole (PTZ), after treatment with either CB1/2 mixed agonist (WIN 55,212-2), CB1 agonist (arachidonyl-2'-chloroethylamide [ACEA]), CB2 agonist (HU-308), CB1 antagonist (AM-251), CB2 antagonist (AM-630), fatty acid amide hydrolase inhibitor (URB-597), or G protein-coupled receptor 55 agonist (O-1602)...
July 10, 2017: Epilepsia
https://www.readbyqxmd.com/read/28680366/fatal-pulmonary-embolism-following-splenectomy-in-a-patient-with-evan-s-syndrome-case-report-and-review-of-the-literature
#15
Varun Monga, Seth M Maliske, Usha Perepu
BACKGROUND: Evans syndrome (ES) is a rare disease characterized by simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) with or without immune neutropenia. Splenectomy is one of the treatment options for disease refractory to medical therapy. Venous thromboembolism (VTE) following splenectomy for hematological diseases has an incidence of 10%. CASE PRESENTATION: Here we describe a case report of a young patient hospitalized with severe hemolytic anemia with Hgb 4...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28674119/cancer-screening-recommendations-and-clinical-management-of-inherited-gastrointestinal-cancer-syndromes-in-childhood
#16
REVIEW
Maria Isabel Achatz, Christopher C Porter, Laurence Brugières, Harriet Druker, Thierry Frebourg, William D Foulkes, Christian P Kratz, Roland P Kuiper, Jordan R Hansford, Hector Salvador Hernandez, Katherine L Nathanson, Wendy K Kohlmann, Leslie Doros, Kenan Onel, Kami Wolfe Schneider, Sarah R Scollon, Uri Tabori, Gail E Tomlinson, D Gareth R Evans, Sharon E Plon
Hereditary gastrointestinal cancer predisposition syndromes have been well characterized, but management strategies and surveillance remain a major challenge, especially in childhood. In October 2016, the American Association for Cancer Research organized the AACR Childhood Cancer Predisposition Workshop in which international experts in care of children with a hereditary risk of cancer met to define surveillance strategies and management of children with cancer predisposition syndromes. In this article, we review the current literature in polyposis syndromes that can be diagnosed in childhood and may be associated with an increased incidence of gastrointestinal neoplasms and other cancer types...
July 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28664165/clearance-of-heparan-sulfate-and-attenuation-of-cns-pathology-by-intracerebroventricular-bmn-250-in-sanfilippo-type-b-mice
#17
Mika Aoyagi-Scharber, Danielle Crippen-Harmon, Roger Lawrence, Jon Vincelette, Gouri Yogalingam, Heather Prill, Bryan K Yip, Brian Baridon, Catherine Vitelli, Amanda Lee, Olivia Gorostiza, Evan G Adintori, Wesley C Minto, Jeremy L Van Vleet, Bridget Yates, Sara Rigney, Terri M Christianson, Pascale M N Tiger, Melanie J Lo, John Holtzinger, Paul A Fitzpatrick, Jonathan H LeBowitz, Sherry Bullens, Brett E Crawford, Stuart Bunting
Sanfilippo syndrome type B (mucopolysaccharidosis IIIB), caused by inherited deficiency of α-N-acetylglucosaminidase (NAGLU), required for lysosomal degradation of heparan sulfate (HS), is a pediatric neurodegenerative disorder with no approved treatment. Intracerebroventricular (ICV) delivery of a modified recombinant NAGLU, consisting of human NAGLU fused with insulin-like growth factor 2 (IGF2) for enhanced lysosomal targeting, was previously shown to result in marked enzyme uptake and clearance of HS storage in the Naglu(-/-) mouse brain...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28660166/neuroleptic-malignant-syndrome-in-the-trauma-intensive-care-unit-diagnosis-and-management-of-a-rare-disease-in-a-challenging-population
#18
Joseph David Drews, Andrew Christopher, David Clay Evans
Neuroleptic malignant syndrome (NMS) is a life-threatening neurological disorder associated with the use of antipsychotic medications. Many of its classic signs, such as fever and altered mental status, are nonspecific in trauma intensive care unit (ICU) patients, and its rarity makes it a difficult diagnosis in this population. However, delays in treatment can be costly both in terms of hospital resources and patient outcomes. We herein report a case of a 54-year-old trauma patient with NMS precipitated by a combination of cocaine withdrawal and neuroleptic medications...
April 2017: International Journal of Critical Illness and Injury Science
https://www.readbyqxmd.com/read/28654852/adductor-canal-compression-syndrome-in-an-18-year-old-female-patient-leading-to-acute-critical-limb-ischemia-a-case-report
#19
Yi Zhou, Evan J Ryer, Robert P Garvin, Jeremy L Irvan, James R Elmore
BACKGROUND: Adductor canal compression syndrome is a rare non-atherosclerotic cause of arterial occlusion and limb ischemia. PRESENTATION OF CASE: The patient is an 18-year-old healthy female who presented to the emergency department with acute left lower extremity ischemia. Her symptoms began as sudden onset mild foot pain approximately two months ago. Over the 72h prior to presentation, she developed severe pain, pallor, paralysis, loss of pedal pulses, paresthesia, and poikilothermia...
2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28654461/natural-history-pathogenesis-and-treatment-of-evans-syndrome-in-children
#20
Elpis Mantadakis, Evangelia Farmaki
Primary Evans syndrome (ES) is defined by the concurrent or sequential occurrence of immune thrombocytopenia and autoimmune hemolytic anemia in the absence of an underlying etiology. The syndrome is characterized by a chronic, relapsing, and potentially fatal course requiring long-term immunosuppressive therapy. Treatment of ES is hardly evidence-based. Corticosteroids are the mainstay of therapy. Rituximab has emerged as the most widely used second-line treatment, as it can safely achieve high response rates and postpone splenectomy...
August 2017: Journal of Pediatric Hematology/oncology
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