215 results on '"Mitchell B. Cohen"'
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2. Bacterial, viral, and toxic causes of diarrhea, gastroenteritis, and anorectal infections
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Gail A. Hecht, Jerrold R. Turner, Phillip I. Tarr, and Mitchell B. Cohen
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- 2022
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Catalog
3. Good Habits Do Not Necessarily Help Childhood Constipation
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Mitchell B. Cohen and Carlo Di Lorenzo
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Pediatrics, Perinatology and Child Health - Published
- 2023
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4. IBD hurts
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Mitchell B. Cohen
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Pediatrics, Perinatology and Child Health - Published
- 2021
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5. Need for therapy to support improved neurodevelopmental outcomes in children with congenital heart disease
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Mitchell B, Cohen
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Heart Defects, Congenital ,Pediatrics, Perinatology and Child Health ,Humans ,Child - Published
- 2022
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6. Human Challenge Studies for Cholera
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Mitchell B, Cohen
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The human challenge model permits an estimate of the vaccine protection against moderate and severe cholera. It eliminates the difficulty in setting up a vaccine study in endemic area including uncertainties about the incidence of cholera and the logistic arrangements for capturing those who do/do not become ill. Valuable information from small groups of subjects can be obtained in a short period. Under proper precautions and study design, the challenge model is safe and efficient. Although the model has evolved since it was introduced over 50 years ago, it has been used extensively to test vaccine efficacy. Vaccine licensure has resulted from data obtained using the human challenge model. In addition, the model has been used to: (1) Establish and validate a standardized inoculum, (2) Identify immune markers and immune responses, (3) Determine natural immunity (in re-challenge studies), (4) Identify the role of the gastric acid barrier in preventing cholera infection, (5) Show homologous and heterologous infection-derived immunity, and (6) Test the efficacy of anti-diarrheal/anti-secretory small molecules. The aim of this chapter is to present an overview on the state of the art for human challenge models used to study cholera and new medical interventions against it. more...
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- 2022
7. Human Challenge Studies for Cholera
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Mitchell B. Cohen
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- 2022
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8. Advocacy and Community Engagement: Perspectives from Pediatric Department Chairs
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Richard J. Chung, Melanie R. Ramirez, Debra L. Best, Mitchell B. Cohen, and Lisa J. Chamberlain
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Academic Medical Centers ,Faculty, Medical ,Pediatrics, Perinatology and Child Health ,Hospital Departments ,Humans ,Child - Published
- 2021
9. Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children
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David S. Reasner, Ramesh Boinpally, Benjamin D. Gold, Stavra A. Xanthakos, Hanna Kwak, Madhuja Mallick, Christopher R. O'Dea, Mitchell B. Cohen, Wilmin Bartolini, Taryn Weissman, Pei Ge, and Nicholas CaJacob more...
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medicine.medical_specialty ,Adolescent ,Colon ,Duodenum ,Mrna expression ,Colonoscopy ,Gastroenterology ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Intestinal Mucosa ,Receptor ,Child ,Irritable bowel syndrome ,Chronic constipation ,medicine.diagnostic_test ,business.industry ,Infant ,Guanylate cyclase 2C ,medicine.disease ,Endoscopy ,medicine.anatomical_structure ,Guanylate Cyclase ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,business - Abstract
Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children.Mucosal biopsies were obtained from subjects aged 6 months to 18 years during clinically indicated upper, that is, esophago-gastro-duodenal, and/or colonic endoscopy. Tissue samples without histologic abnormalities were grouped by subject age (24 months, 24 months to6 years, 6 to12 years, and 12 to18 years) and analyzed for GC-C mRNA expression by qPCR. The relationship between GC-C mRNA levels and age was modeled using regression analyses.Ninety-nine subjects underwent upper endoscopy/colonoscopy; 93 had evaluable samples. Mean relative GC-C mRNA expression was 2.36 (range 2.21-2.46) for duodenal samples and 1.56 (range 1.22-1.91) for colonic samples. Predicted and observed normalized GC-C mRNA expression in each region were comparable among age groups. Pooled expression by region demonstrated lower expression in colonic versus duodenal samples.Uniform levels of GC-C mRNA expression were detected in children aged6 months in the duodenum and12 months in the colon. Higher expression was observed in all age groups in duodenal versus colonic samples, indicating regional variability in GC-C receptor density. These data are reassuring for further studies of GC-C agonists in children. more...
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- 2021
10. Mind the Gap
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Morissa J, Ladinsky and Mitchell B, Cohen
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Pediatrics, Perinatology and Child Health ,Humans ,Comprehensive Health Care ,Child ,Inflammatory Bowel Diseases ,Article - Abstract
OBJECTIVES: To describe patterns of primary and specialty care delivery in pediatric patients with inflammatory bowel diseases (IBD), delineate which members of the healthcare team provided services, and identify gaps in care. STUDY DESIGN: Cross-sectional survey of parents of children (2-17 years) with IBD and adolescents with IBD (13-17 years) at a free-standing, quaternary children’s hospital regarding healthcare receipt. RESULTS: 161 parents and 84 adolescents responded to the survey (75 and 60% response, respectively). Mean patient age 14 years (SD 3); 51% male; 80% Crohn’s disease, 16% ulcerative colitis, 4% IBD-unspecified. Most parents were Caucasian (94%), living in a suburban setting (57%). 69% of households had at least one parent with a bachelor’s degree or higher. Most had private insurance (43%) or private primary with public secondary insurance (34%). Most patients received annual check-ups (70%), vaccinations (78%), and care for minor illnesses (74%) from their primary care provider. Check-ups for gastrointestinal symptoms, IBD monitoring, and changes in type/dosing of IBD treatment were provided by their gastroenterology (GI) provider (77, 93, and 86% of patients, respectively). Discussions about family/peer relationships, school/extracurricular activities, and mood were not addressed in 30-40% of participants. Adolescents frequently reported that no one had talked to them about substance use (40%), sexual health (50%), or body image (60%); 75% of adolescents and 76% of their parents reported that no one had discussed transitioning to an adult provider. CONCLUSIONS: There were gaps in the psychosocial care of pediatric patients with IBD. Coordinated, comprehensive care delivery models are needed. more...
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- 2020
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11. Left Ventricular Aneurysm in a Child After Recovering From Dilated Cardiomyopathy
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Mitchell B. Cohen, Ramiro Lizano-Santamaria, Lucas Collazo, and Melany Atkins
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Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Heart Ventricles ,Magnetic Resonance Imaging, Cine ,Aneurysm ,Internal medicine ,Idiopathic dilated cardiomyopathy ,medicine ,Humans ,cardiovascular diseases ,Cardiac Surgical Procedures ,Heart Aneurysm ,business.industry ,Dilated cardiomyopathy ,General Medicine ,medicine.disease ,Left Ventricular Aneurysm ,Echocardiography ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,cardiovascular system ,Cardiology ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
Left ventricular aneurysms are extremely rare in children. A child developed an aneurysm a year after recovering from idiopathic dilated cardiomyopathy. The initial management was conservative. After several years and due to aneurysm enlargement and other complications, the patient underwent successful aneurysm surgical repair with left ventricular aneurysmorrhaphy. We describe our experience treating this child during the course of this disease. more...
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- 2020
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12. 50 Years Ago in THEJournal ofPediatrics: Diarrheagenic Escherichia coli: Enduring and Evolving
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Adam W, Cohen and Mitchell B, Cohen
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Diarrhea ,Enteropathogenic Escherichia coli ,Humans ,History, 20th Century ,Global Health ,History, 21st Century ,Escherichia coli Infections - Published
- 2021
13. Infectious Diarrhea
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David Galloway and Mitchell B. Cohen
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- 2021
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14. Contributors
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H. Hesham A-Kader, Sophia Abdulhai, Kareem Abu-Elmagd, Maisam Abu-El-Haija, Douglas G. Adler, Lindsey Albenberg, Estella M. Alonso, Ruchi Amin, Orhan Atay, Renata Auricchio, Robert D. Baker, Susan S. Baker, Katherine Baldwin, Jessica Barry, Todd H. Baron, Bradley Barth, Dorsey M. Bass, Lee M. Bass, Jaime Belkind-Gerson, Marc A. Benninga, Natalie Bhesania, Andrea Bischoff, Samuel Bitton, Samra S. Blanchard, Athos Bousvaros, Brendan Boyle, Jennifer Brewer, Jefferson N. Brownell, Steven W. Bruch, Brendan T. Campbell, Jacob Campbell, Michael Gerard Caty, Carolina S. Cerezo, Ryaz Chagpar, Beth Chatfield, Rebecca N. Cherry, Gail Cohen, Mitchell B. Cohen, Arnold G. Coran, Guilherme Costa, Gail A.M. Cresci, Eileen Crowley, Michael Cruise, Steven J. Czinn, Zev Davidovics, Luis De La Torre, Anthony L. DeRoss, David Devadason, Rajitha Devadoss Venkatesh, Carlo Di Lorenzo, Jennifer L. Dotson, Tracy R. Ediger, Bijan Eghtesad, John F. Eisses, Mounif El Yousif, Karan McBride Emerick, Steven H. Erdman, Rima Fawaz, Ariel E. Feldstein, Melissa Fernandes, Laura S. Finn, Kristin Nicole Fiorino, Douglas S. Fishman, Joel A. Friedlander, Masato Fujiki, John Fung, Ivan Fuss, David Galloway, Donald E. George, Fayez K. Ghishan, Raffaelle Girlanda, Donna Gitt, Deborah A. Goldman, Sue Goodine, Glenn R. Gourley, Nicole Green, Gabrielle Grisotti, Sandeep K. Gupta, Nedim Hadzic, Sanjiv Harpavat, Koji Hashimoto, Maheen Hassan, James E. Heubi, Sohail Z. Husain, Séamus Hussey, Jeffrey S. Hyams, Warren Hyer, Paul E. Hyman, Sabine Iben, Veronica E. Issac, Maureen M. Jonas, Marsha Kay, Mohit Kehar, Deidre Kelly, Karlo Kovacic, Shaun Michael Kunisaki, Jacob A. Kurowski, Jacob C. Langer, Frances C. Lee, Rose Lee, Neal S. LeLeiko, Chris A. Liacouras, Henry Lin, Quin Y. Liu, Kathleen M. Loomes, Peter L. Lu, Sarah Shrager Lusman, Cara Mack, Anshu Maheshwari, Petar Mamula, Michael A. Manfredi, James F. Markowitz, Jonathan E. Markowitz, Maria R. Mascarenhas, Ryann Mayer, Patrick McKiernan, Adam G. Mezoff, Ethan A. Mezoff, Giorgina Mieli-Vergani, Franziska Mohr, Jasmeet Mokha, Hayat Mousa, Lindsay Moye, Simon Murch, Karen F. Murray, Robert Naples, Jaimie D. Nathan, Vicky Lee Ng, Vi Nguyen, Samuel Nurko, Jodie Oauhed, Tina Ogholikhan, Keith T. Oldham, Mohammed Osman, Nadia Ovchinsky, Jennifer Panganiban, Alberto Pena, Robert E. Petras, Marian D. Pfefferkorn, David Piccoli, Travis Piester, Beth Pinkos, Thomas Plesec, Stephanie Polites, Todd Ponsky, Christine Rader, Kadakkal Radhakrishnan, Yannis Reissis, Leonel Rodriguez, Ricardo J. Rodriguez, Isabel Rojas, Ellen S. Rome, Joel R. Rosh, Rachel M. Ruiz, Benjamin Sahn, Atif Saleem, Kate A. Samela, Neha R. Santucci, Miguel Saps, Eleanor H. Sato, Thomas T. Sato, Erica C. Savage, Federico G. Seifarth, Praveen Kumar Conjeevaram Selvakumar, Jason Shapiro, Allan E. Siperstein, Joseph Skelton, Scott Snapper, Oliver S. Soldes, Manu R. Sood, Marisa Gallant Stahl, Shikha S. Sundaram, Francisco A. Sylvester, Jonathan E. Teitelbaum, Natalie A. Terry, Peter Townsend, Riccardo Troncone, Kate Vance, Yvan Vandenplas, Robert S. Venick, David S. Vitale, Jerry Vockley, Eugene Vortia, Mana H. Vriesman, Ghassan T. Wahbeh, R. Matthew Walsh, Suz Warner, Robert Wyllie, Jessica L. Yasuda, Donna Zeiter, and Hengqi (Betty) Zheng more...
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- 2021
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15. Guanylate cyclase C deficiency causes severe inflammation in a murine model of spontaneous colitis.
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Eleana Harmel-Laws, Elizabeth A Mann, Mitchell B Cohen, and Kris A Steinbrecher
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Medicine ,Science - Abstract
Guanylate Cyclase C (GC-C; Gucy2c) is a transmembrane receptor expressed in intestinal epithelial cells. Activation of GC-C by its secreted ligand guanylin stimulates intestinal fluid secretion. Familial mutations in GC-C cause chronic diarrheal disease or constipation and are associated with intestinal inflammation and infection. Here, we investigated the impact of GC-C activity on mucosal immune responses.We utilized intraperitoneal injection of lipopolysaccharide to elicit a systemic cytokine challenge and then measured pro-inflammatory gene expression in colonic mucosa. GC-C(+/+) and GC-C(-/-) mice were bred with interleukin (IL)-10 deficient animals and colonic inflammation were assessed. Immune cell influx and cytokine/chemokine expression was measured in the colon of wildtype, IL-10(-/-), GC-C(+/+)IL-10(-/-) and GC-C(-/-)IL-10(-/-) mice. GC-C and guanylin production were examined in the colon of these animals and in a cytokine-treated colon epithelial cell line.Relative to GC-C(+/+) animals, intraperitoneal lipopolysaccharide injection into GC-C(-/-) mice increased proinflammatory gene expression in both whole colon tissue and in partially purified colonocyte isolations. Spontaneous colitis in GC-C(-/-)IL-10(-/-) animals was significantly more severe relative to GC-C(+/+)IL-10(-/-) mice. Unlike GC-C(+/+)IL-10(-/-) controls, colon pathology in GC-C(-/-)IL-10(-/-) animals was apparent at an early age and was characterized by severely altered mucosal architecture, crypt abscesses, and hyperplastic subepithelial lesions. F4/80 and myeloperoxidase positive cells as well as proinflammatory gene expression were elevated in GC-C(-/-)IL-10(-/-) mucosa relative to control animals. Guanylin was diminished early in colitis in vivo and tumor necrosis factor α suppressed guanylin mRNA and protein in intestinal goblet cell-like HT29-18-N2 cells.The GC-C signaling pathway blunts colonic mucosal inflammation that is initiated by systemic cytokine burst or loss of mucosal immune cell immunosuppression. These data as well as the apparent intestinal inflammation in human GC-C mutant kindred underscore the importance of GC-C in regulating the response to injury and inflammation within the gut. more...
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- 2013
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16. Pediatric Chair Turnover and Demographics
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Mitchell B. Cohen, Bruce K. Rubin, Inmaculada Aban, Charlotte M. Boney, Michael Artman, Geoffrey Binney, Patricia Emmanuel, Lewis R. First, Abigail Blake, Morris Gessouroun, and Mary B. Taylor
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medicine.medical_specialty ,Demographics ,business.industry ,MEDLINE ,Personnel Turnover ,Job Satisfaction ,Pediatric chair ,Family medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Child ,business ,Demography - Published
- 2022
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17. Universal Recommendations for the Management of Acute Diarrhea in Nonmalnourished Children
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Bhupinder Sandhu, James A. Berkley, Eduardo Salazar-Lindo, Ilaria Liguoro, Sylvia Cruchet, Jorge Amil Dias, Mitchell B. Cohen, Alfredo Guarino, Andrea Lo Vecchio, Chris Boey, Philip M. Sherman, Toshiaki Shimizu, Dario Bruzzese, Guarino, Alfredo, Lo Vecchio, Andrea, Dias, Jorge Amil, Berkley, James A, Boey, Chri, Bruzzese, Dario, Cohen, Mitchell B, Cruchet, Sylvia, Liguoro, Ilaria, Salazar-Lindo, Eduardo, Sandhu, Bhupinder, Sherman, Philip M, and Shimizu, Toshiaki more...
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recommendation ,Diarrhea ,Male ,Acute diarrhea ,medicine.medical_specialty ,Adolescent ,purl.org/pe-repo/ocde/ford#3.03.04 [https] ,diarrhea ,MEDLINE ,Psychological intervention ,Guidelines ,Pediatrics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Consistency (negotiation) ,children ,Clinical Protocols ,Medical ,030225 pediatrics ,Humans ,Medicine ,guidelines ,030212 general & internal medicine ,Preschool ,Child ,Intensive care medicine ,Children ,Societies, Medical ,purl.org/pe-repo/ocde/ford#3.02.03 [https] ,purl.org/pe-repo/ocde/ford#3.02.19 [https] ,business.industry ,Infant, Newborn ,Gastroenterology ,Infant ,Recommendation ,Acute gastroenteritis ,Newborn ,Gastroenteritis ,Clinical Practice ,Child, Preschool ,Acute Disease ,Practice Guidelines as Topic ,Pediatrics, Perinatology and Child Health ,Female ,Societies ,business ,gastroenteritis - Abstract
Objective: Despite a substantial consistency in recommendations for the management of children with acute gastroenteritis (AGE), a high variability in clinical practice and a high rate of inappropriate medical interventions persist in both developing and developed countries. The aim of this study was to develop a set of clinical recommendations for the management of nonseverely malnourished children with AGE to be applied worldwide. Methods: The Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) Working Group (WG) selected care protocols on the management of acute diarrhea in infants and children aged between 1 month and 18 years. The WG used a 3-step approach consisting of: systematic review and comparison of published guidelines, agreement on draft recommendations using Delphi methodology, and external peer-review and validation of recommendations. Results: A core of recommendations including definition, diagnosis, nutritional management, and active treatment of AGE was developed with an overall agreement of 91% (range 80%–96%). A total of 28 world experts in pediatric gastroenterology and emergency medicine successively validated the set of 23 recommendations with an agreement of 87% (range 83%–95%). Recommendations on the use of antidiarrheal drugs and antiemetics received the lowest level of agreement and need to be tailored at local level. Oral rehydration and probiotics were the only treatments recommended. Conclusions: Universal recommendations to assist health care practitioners in managing children with AGE may improve practitioners’ compliance with guidelines, reduce inappropriate interventions, and significantly impact clinical outcome and health care-associated costs. more...
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- 2018
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18. Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection
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Marc Gurwith, Mitchell B. Cohen, Beth D. Kirkpatrick, Jakub K. Simon, Marcelo B. Sztein, Douglas Haney, Jason B. Harris, Glenn Ishioka, Myron M. Levine, Caroline E. Lyon, Wilbur H. Chen, and Michael Lock more...
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Adult ,Lipopolysaccharides ,0301 basic medicine ,Cholera Toxin ,Time Factors ,Administration, Oral ,Vaccines, Attenuated ,medicine.disease_cause ,Article ,03 medical and health sciences ,Cholera ,medicine ,Humans ,Seroconversion ,Memory B cell ,B-Lymphocytes ,Attenuated vaccine ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Cholera toxin ,Vibrio cholerae O1 ,Public Health, Environmental and Occupational Health ,Cholera Vaccines ,medicine.disease ,Antibodies, Bacterial ,Immunoglobulin A ,Vaccination ,030104 developmental biology ,Infectious Diseases ,Vibrio cholerae ,Immunoglobulin G ,Immunology ,Molecular Medicine ,Cholera vaccine ,business ,Immunologic Memory - Abstract
Background The single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naive adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1–2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response. Methods In a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera. Results There was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = −0.56, p Discussion Oral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection. Clinical trials registration: NCT01895855. more...
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- 2018
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19. Loss of guanylyl cyclase C (GCC) signaling leads to dysfunctional intestinal barrier.
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Xiaonan Han, Elizabeth Mann, Shila Gilbert, Yanfang Guan, Kris A Steinbrecher, Marshall H Montrose, and Mitchell B Cohen
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Medicine ,Science - Abstract
Guanylyl Cyclase C (GCC) signaling via uroguanylin (UGN) and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function.Paracellular permeability of intestinal segments was assessed in wild type (WT) and GCC deficient (GCC-/-) mice with and without lipopolysaccharide (LPS) challenge, as well as in UGN deficient (UGN-/-) mice. IFNγ and myosin light chain kinase (MLCK) levels were determined by real time PCR. Expression of tight junction proteins (TJPs), phosphorylation of myosin II regulatory light chain (MLC), and STAT1 activation were examined in intestinal epithelial cells (IECs) and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi). We found that intestinal permeability was increased in GCC-/- and UGN-/- mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC-/- mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC-/- and UGN-/- mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability.GCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury. more...
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- 2011
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20. Impact of Obesity on Left Ventricular Thickness in Children with Hypertrophic Cardiomyopathy
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Maria Ilina, Andreas Pflaumer, Margaret J. Strieper, Ilana Zeltser, George McDaniel, Andrew D. Blaufox, Michaela Horndasch, Seshadri Balaji, Michal J. Kantoch, Anne Fournier, Christopher C. Erickson, Philip Chang, Stephanie J. Nakano, Frank Zimmerman, Jeremy P. Moore, Naomi J. Kertesz, Svjetlana Tisma, Robert J. Hamilton, Ian H. Law, Hannah Katcoff, Anjan S. Batra, Mitchell B. Cohen, Michael P. DiLorenzo, Jason M. Garnreiter, Shubhayan Sanatani, Harinder R. Singh, Frank A. Fish, Mark W. Russell, Christopher M. Janson, Peter F. Aziz, Richard T. Smith, Walter Li, Maully J. Shah, Leonardo Liberman, Susan P. Etheridge, Peter Kubuš, and Narayanswami Sreeram more...
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Male ,medicine.medical_specialty ,Adolescent ,Heart Ventricles ,Cardiomyopathy ,Ventricular Septum ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,Sudden death ,Body Mass Index ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Obesity ,Young adult ,Child ,business.industry ,Hypertrophic cardiomyopathy ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Cardiac surgery ,030228 respiratory system ,Echocardiography ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Body mass index - Abstract
Obesity is associated with additional left ventricular hypertrophy (LVH) in adults with hypertrophic cardiomyopathy (HCM). It is not known whether obesity can lead to further LVH in children with HCM. Echocardiographic LV dimensions were determined in 504 children with HCM. Measurements of interventricular septal thickness (IVST) and posterior wall thickness (PWT), and patients' weight and height were recorded. Obesity was defined as a body mass index (BMI) ≥ 99th percentile for age and sex. IVST data was available for 498 and PWT data for 484 patients. Patient age ranged from 2 to 20 years (mean ± SD, 12.5 ± 3.9) and 340 (68%) were males. Overall, patient BMI ranged from 7 to 50 (22.7 ± 6.1). Obesity (BMI 18-50, mean 29.1) was present in 140 children aged 2-19.6 (11.3 ± 4.1). The overall mean IVST was 20.5 ± 9.6 mm and the overall mean PWT was 11.0 ± 8.4 mm. The mean IVST in the obese patients was 21.6 ± 10.0 mm and mean PWT was 13.3 ± 14.7 mm. The mean IVST in the non-obese patients was 20.1 ± 9.5 mm and mean PWT was 10.4 ± 4.3 mm. Obesity was not significantly associated with IVST (p = 0.12), but was associated with increased PWT (0.0011). Obesity is associated with increased PWT but not IVST in children with HCM. Whether obesity and its impact on LVH influences clinical outcomes in children with HCM needs to be studied. more...
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- 2019
21. 50 Years Ago in T J P
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Mitchell B. Cohen and Adam W Cohen
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Diarrheagenic Escherichia coli ,business.industry ,Pediatrics, Perinatology and Child Health ,Medicine ,business ,Microbiology - Published
- 2021
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22. Update on Diarrhea
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Mitchell B. Cohen and Nicholas CaJacob
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Diarrhea ,medicine.medical_specialty ,Pediatrics ,business.industry ,Antidiarrheal Agent ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Rotavirus ,Pediatrics, Perinatology and Child Health ,Epidemiology ,medicine ,Norovirus ,Humans ,030211 gastroenterology & hepatology ,medicine.symptom ,Intensive care medicine ,Adverse effect ,business ,Pediatric gastroenterology ,Cause of death - Abstract
1. Nicholas J. CaJacob, MD*,† 2. Mitchell B. Cohen, MD*,† 1. *Departments of Pediatric Gastroenterology, Hepatology, and Nutrition and 2. †Pediatrics, University of Alabama at Birmingham, Birmingham, AL. The mainstay of management of infectious diarrheal illness in children remains supportive care with oral or intravenous rehydration. In the postvaccine era, norovirus has supplanted rotavirus as the leading cause of gastroenteritis presenting to medical facilities in the United States. After reading this article, the reader should be able to: 1. Recognize the common pathogens associated with infectious diarrhea and develop a management plan. 2. Identify the key differences between infectious and noninfectious causes of diarrhea. 3. Effectively treat a child with cow milk protein intolerance. 4. Recognize that antidiarrheal and antimotility agents are not indicated or recommended in the treatment of infectious diarrhea. 5. Understand the changing epidemiology of infectious diarrhea in the postvaccine era. Diarrhea is a worldwide problem that is frequently encountered in the practice of pediatric medicine. According to the World Health Organization, diarrheal illness is the second leading cause of death in children younger than age 5 years, accounting for 760,000 deaths per year in this age group. (1) The overwhelming majority of diarrheal illnesses are due to acute infectious diarrhea, commonly referred to as acute gastroenteritis (AGE). The degree of dehydration, assessed by both history and physical examination, is the most important indicator of disease severity. However, most children who have infectious diarrhea are not dehydrated and can be successfully treated at home with replacement of ongoing fluid losses using oral rehydration solution (ORS). The routine use of antibiotics and antidiarrheal agents is not recommended for treatment of acute diarrhea and may cause harm. Restrictive diets are not necessary; the adverse effects on nutritional status during diarrheal illness can be lessened or prevented by rapid reinstitution of a regular … more...
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- 2016
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23. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection WithVibrio choleraeO1 El Tor
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Michael Lock, Wilbur H. Chen, Beth D. Kirkpatrick, Douglas Haney, Myron M. Levine, Marc Gurwith, Caroline E. Lyon, Mitchell B. Cohen, Sharon M. Tennant, Jakub K. Simon, David Galloway, Robert A. Kessler, R H Hall, Flora Szabo, Marcela F. Pasetti, and Rebecca C. Brady more...
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,Adolescent ,030106 microbiology ,Administration, Oral ,Vaccines, Attenuated ,medicine.disease_cause ,El Tor ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Cholera ,medicine ,Humans ,030212 general & internal medicine ,Seroconversion ,Articles and Commentaries ,Vibrio cholerae ,biology ,business.industry ,Vibrio cholerae O1 ,Cholera Vaccines ,Middle Aged ,biology.organism_classification ,medicine.disease ,Vaccine efficacy ,Antibodies, Bacterial ,Virology ,Vaccination ,Diarrhea ,Infectious Diseases ,Immunology ,Female ,medicine.symptom ,Cholera vaccine ,business - Abstract
Background. No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance. PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model. Methods. Consenting healthy adult volunteers, 18–45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 × 108 colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 105 CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. Results. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001). Conclusions. The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT01895855","term_id":"NCT01895855"}}NCT01895855 more...
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- 2016
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24. Required and Elective Experiences During the 4th Year: An Analysis of ACGME Accredited Psychiatry Residency Program Websites
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Richard Belitsky, Carol A. Bernstein, Lucy Hutner, Edward K. Silberman, Stephen C. Scheiber, Mitchell B. Cohen, Leah J. Dickstein, Deanna Chaukos, Donald M. Hilty, Ferda Sakman, Marika I. Wrzosek, and Heather S. Vestal more...
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medicine.medical_specialty ,Future studies ,020205 medical informatics ,02 engineering and technology ,Accreditation ,Education ,03 medical and health sciences ,0302 clinical medicine ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Humans ,Outpatient clinic ,030212 general & internal medicine ,Psychiatry ,Psychiatric Training ,Curriculum ,Medical education ,business.industry ,Internship and Residency ,General Medicine ,Residency program ,United States ,Psychiatry and Mental health ,Family medicine ,business - Abstract
The objective of this study was to assess and describe required and elective components of the 4th post-graduate year (PGY4) in psychiatry residency programs. We reviewed the websites of all 193 2014–2015 ACGME accredited psychiatry residency programs for content describing the specific components of the PGY4 year. Nearly all residency programs (99 %) had some form of required experiences during the PGY4 year. Ninety-four percent had clinical requirements for PGY4 residents, with longitudinal outpatient clinic being the most common (77 %). All programs offered some elective time during PGY4, but the amount of time ranged from 2 months to 100 %. Virtually all residency programs include some requirements in the 4th year (most commonly didactics and outpatient clinic) in addition to a broad array of elective experiences. Although 3 years may suffice for residents to complete ACGME requirements, a variety of factors may motivate programs to include required 4th year curricula. Future studies should explore the rationales for and possible benefits of programmatic requirements throughout 4 versus only 3 years of psychiatric training. more...
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- 2016
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25. Risk factors for lethal arrhythmic events in children and adolescents with hypertrophic cardiomyopathy and an implantable defibrillator: An international multicenter study
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Ilana Zeltser, Maria Ilina, Michael P. DiLorenzo, Susan P. Etheridge, Stephanie J. Nakano, Jason M. Garnreiter, Frank A. Fish, Frank Zimmerman, Svjetlana Tisma, Mark W. Russell, Seshadri Balaji, Margaret J. Strieper, Jeremy P. Moore, Ian H. Law, Mitchell B. Cohen, Andrew D. Blaufox, Michaela Horndasch, Christopher C. Erickson, Walter Li, Christopher M. Janson, Shubhayan Sanatani, Harinder R. Singh, Peter F. Aziz, Leonardo Liberman, Hannah Katcoff, Peter Kubuš, Michal J. Kantoch, Maully J. Shah, Narayanswami Sreeram, Robert J. Hamilton, Naomi J. Kertesz, Anjan S. Batra, Philip Chang, Richard T. Smith, Andreas Pflaumer, George McDaniel, and Anne Fournier more...
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Male ,medicine.medical_specialty ,Internationality ,Adolescent ,Cardiomyopathy ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Implantable defibrillator ,Risk Assessment ,Severity of Illness Index ,Cohort Studies ,03 medical and health sciences ,Electrocardiography ,Young Adult ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Prospective cohort study ,Child ,Proportional Hazards Models ,Retrospective Studies ,Univariate analysis ,business.industry ,Hazard ratio ,Hypertrophic cardiomyopathy ,Retrospective cohort study ,Arrhythmias, Cardiac ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Hospitals, Pediatric ,Defibrillators, Implantable ,Death, Sudden, Cardiac ,Treatment Outcome ,Echocardiography ,Child, Preschool ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Cohort study ,Follow-Up Studies - Abstract
Predictors of risk of lethal arrhythmic events (LAE) is poorly understood and may differ from adults in children with hypertrophic cardiomyopathy (HCM).The purpose of this study was to determine predictors of LAE in children with HCM.A retrospective data collection was performed on 446 children and teenagers 20 years and younger (290 [65%] male; mean age 10.1 ± 5.7 years) with idiopathic HCM from 35 centers. Patients were classified as group 1 (HCM with LAE) if having a secondary prevention implantable cardioverter-defibrillator (ICD) or primary prevention ICD with appropriate interventions or group 2 (HCM without LAE) if having a primary prevention ICD without appropriate interventions.There were 152 children (34%) in group 1 and 294 (66%) in group 2. Risk factors for group 1 by univariate analysis were septal thickness, posterior left ventricular (LV) wall thickness, lower LV outflow gradient, and Q wave3 mm in inferior electrocardiographic leads. Factors not associated with LAE were family history of SCD, abnormal blood pressure response to exercise, and ventricular tachycardia on ambulatory electrocardiographic monitoring. Risk factors for SCD by multivariate analysis were age at ICD placement (hazard ratio [HR] 0.9; P = .0025), LV posterior wall thickness z score (HR 1.02; P.005), and LV outflow gradient30 mm Hg (HR 2.0; P.006). LV posterior wall thickness z score ≥ 5 was associated with LAE.Risk factors for LAE appear different in children compared to adults. Conventional adult risk factors were not significant in children. Further prospective studies are needed to improve risk stratification for LAE in children with HCM. more...
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- 2019
26. Murray Davidson Award: Susan S. Baker, MD, PhD
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Mitchell B. Cohen
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business.industry ,Pediatrics, Perinatology and Child Health ,Awards and Prizes ,Gastroenterology ,Humans ,Art history ,Medicine ,business ,United States - Published
- 2020
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27. A Phase 1 dose escalating study of double mutant heat-labile toxin LTR192G/L211A (dmLT) from Enterotoxigenic Escherichia coli (ETEC) by sublingual or oral immunization
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Marcela F. Pasetti, A. Louis Bourgeois, Shahida Baqar, Amanda D. Buskirk, Michelle Dickey, Jill El-Khorazaty, Marcelo B. Sztein, Nicole Maier, Rebecca C. Brady, Holly Baughman, David I. Bernstein, Rezwanul Wahid, and Mitchell B. Cohen more...
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Adult ,Male ,Saliva ,Adolescent ,030231 tropical medicine ,Bacterial Toxins ,Administration, Sublingual ,Dose-Response Relationship, Immunologic ,Administration, Oral ,medicine.disease_cause ,Article ,03 medical and health sciences ,Enterotoxins ,Young Adult ,0302 clinical medicine ,Antigen ,Adjuvants, Immunologic ,Oral administration ,Enterotoxigenic Escherichia coli ,Medicine ,Humans ,030212 general & internal medicine ,Neutralizing antibody ,Escherichia coli Infections ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Escherichia coli Vaccines ,Immunogenicity ,Escherichia coli Proteins ,Vaccination ,Public Health, Environmental and Occupational Health ,Antibody titer ,Middle Aged ,Antibodies, Bacterial ,Antibodies, Neutralizing ,Healthy Volunteers ,Immunoglobulin A ,Diarrhea ,Infectious Diseases ,Immunoglobulin G ,Immunology ,biology.protein ,Molecular Medicine ,Female ,medicine.symptom ,business - Abstract
Background The public health burden of Enterotoxigenic Escherichia coli (ETEC) is high but no vaccine is specifically approved to prevent ETEC infections. Methods We performed a Phase 1, dose escalation study (1–50 µg) evaluating the sublingual (SL) delivery of the double mutant heat-labile toxin LTR192G/L211A (dmLT) in 80 healthy adult volunteers. The primary objective was safety and the secondary was the immunogenicity of the dmLT. Subjects received 3 doses of dmLT at days 1, 15, and 29. Subjects receiving the first dose at each dosage level were observed overnight in a research facility. The second and third doses were administered on an outpatient basis. Data from cohorts 1–4 were used to select the cohort 5 dose (25 µg), comparing SL and oral routes. Results The vaccine appeared safe and well tolerated with only rare development of vomiting or diarrhea. The serum anti-dmLT IgA and IgG and neutralizing antibody responses were modest after any of the SL immunizations. Serum IgA and IgG titers were increased at the higher antigen doses (25 or 50 µg) but the percent with 4-fold increases was at best 38% for both IgA and IgG. The 4-fold increase among subjects receiving all 3 doses was 43% for both IgA and IgG. Antibody titers following oral administration were, in general, significantly higher than after SL. The frequency of IgA- or IgG-ASCs in circulation were somewhat vaccine dose dependent and were detected at a moderate level. However, antibodies in saliva or stool were rarely detected. Post-vaccination increases in T cells or cytokine production were also infrequent. Conclusion The dmLT vaccine formulation evaluated here was safe but only moderately immunogenic at doses up to 50 µg when administered by the SL or oral route. Studies at higher doses with better formulations appear warranted. more...
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- 2018
28. Current Issues in Transitioning from Pediatric to Adult-Based Care for Youth with Chronic Health Care Needs
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Albert C. Hergenroeder, Constance M. Wiemann, and Mitchell B. Cohen
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Adult ,Health Services Needs and Demand ,Transition to Adult Care ,medicine.medical_specialty ,Adolescent ,business.industry ,digestive, oral, and skin physiology ,Pilot programs ,MEDLINE ,Pediatrics ,Health Services Accessibility ,Young Adult ,Nursing ,Family medicine ,Pediatrics, Perinatology and Child Health ,Health care ,Self care ,medicine ,Humans ,Young adult ,Child ,business ,Health policy - Abstract
For over 25 years, with medical advances increasing the lifespan of YYASHCN, we have been aware of the need to improve health care transition to adult-based care services. Barriers to health care transition have been identified and in a number of settings, recognition of the problem and preliminary success has been achieved for pilot programs. Evidence-based solutions to improve health care transition for YYASHCN are needed. There are barriers at the patient, family, pediatric, and adult provider, and insurance system levels that must be overcome. more...
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- 2015
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29. Summary of the 2015 International Paediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute
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James C. Huhta, Charles D. Fraser, John M. Costello, Steven D. Colan, James A. Quintessenza, Joseph W. Rossano, Sunjay Kaushal, Mingguo Xu, Susan B Collins, Kevin D. Hill, Yuk M. Law, Tom R. Karl, Allen D. Everett, Steven E. Lipshultz, Sara K. Pasquali, Anne M. Murphy, Rodney C. G. Franklin, Mitchell B. Cohen, Genaro A. Ramirez-Correa, Mark R Payne, Alfred Asante-Korang, Kevin P. Daly, Marshall L. Jacobs, Stephanie M. Ware, Girish S. Shirali, Jeffrey P. Jacobs, and Kristin M. Burns more...
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Heart Defects, Congenital ,medicine.medical_specialty ,Endowment ,medicine.medical_treatment ,education ,Pediatrics ,medicine ,Humans ,Intensive care medicine ,health care economics and organizations ,Scientific disciplines ,Heart Failure ,Heart transplantation ,geography ,Summit ,geography.geographical_feature_category ,business.industry ,General Medicine ,Congresses as Topic ,Hospitals, Pediatric ,medicine.disease ,United States ,Transplantation ,Heart failure ,Ventricular assist device ,Family medicine ,Pediatrics, Perinatology and Child Health ,Cardiology and Cardiovascular Medicine ,business - Abstract
In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute, to describe the “state of the art” of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure. more...
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- 2015
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30. CNS, lung, and lymph node involvement in Gaucher disease type 3 after 11years of therapy: Clinical, histopathologic, and biochemical findings
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Wujuan Zhang, David P. Witte, Steve W. Wu, Kenneth D.R. Setchell, Amanda Brewer, Mitchell B. Cohen, Gregory A. Grabowski, Laurie Bailey, Thomas A. Burrow, Ying Sun, and Carlos E. Prada
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Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Longevity ,Spleen ,Biology ,Glucosylceramides ,Biochemistry ,Glycosphingolipids ,Article ,Endocrinology ,Genetics ,medicine ,Lysosomal storage disease ,Humans ,Enzyme Replacement Therapy ,Lung ,Molecular Biology ,Lymph node ,Gaucher Disease ,Macrophages ,Psychosine ,Brain ,Enzyme replacement therapy ,medicine.disease ,Lipids ,Astrogliosis ,Phenotype ,medicine.anatomical_structure ,Liver ,Immunology ,Disease Progression ,Lymph Nodes ,Lymph ,Progressive disease ,Follow-Up Studies - Abstract
A Caucasian male with Gaucher disease type 3, treated with continuous enzyme therapy (ET) for 11 years, experienced progressive mesenteric and retroperitoneal lymphadenopathy, lung disease, and neurological involvement leading to death at an age of 12.5 years. Autopsy showed significant pathology of the brain, lymph nodes, and lungs. Liver and spleen glucosylceramide (GluCer) and glucosylsphingosine (GluS) levels were nearly normal and storage cells were cleared. Clusters of macrophages and very elevated GluCer and GluS levels were in the lungs, and brain parenchymal and perivascular regions. Compared to normal brain GluCer (GC 18:0), GluCer species with long fatty acid acyl chains were increased in the patient's brain. This profile was similar to that in the patient's lungs, suggesting that these lipids were present in brain perivascular macrophages. In the patient's brain, generalized astrogliosis, and enhanced LC3, ubiquitin, and Tau signals were identified in the regions surrounding macrophage clusters, indicating proinflammation, altered autophagy, and neurodegeneration. These findings highlight the altered phenotypes resulting from increased longevity due to ET, as well as those in poorly accessible compartments of brain and lung, which manifested progressive disease involvement despite ET. more...
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- 2015
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31. Risk categorization predicts disability in pain-associated functional gastrointestinal disorders (FGIDs) after 6 months
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Anne M. Lynch-Jordan, Mitchell B. Cohen, James Peugh, Natoshia R. Cunningham, Susmita Kashikar-Zuck, Anjana Jagpal, Michael K. Farrell, and Adam Mezoff
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Male ,medicine.medical_specialty ,Referral ,Adolescent ,Gastrointestinal Diseases ,Anxiety ,Medical care ,Risk Assessment ,Severity of Illness Index ,Article ,Decision Support Techniques ,03 medical and health sciences ,Disability Evaluation ,0302 clinical medicine ,Risk Factors ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,Risk factor ,Child ,Pediatric gastroenterology ,Pain Measurement ,Psychiatric Status Rating Scales ,business.industry ,Gastroenterology ,Prognosis ,Abdominal Pain ,Categorization ,Functional disability ,Pediatrics, Perinatology and Child Health ,Female ,Risk categorization ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Algorithms ,Follow-Up Studies - Abstract
INTRODUCTION For a large portion of youth, pain-associated functional gastrointestinal disorders (FGIDs) are associated with significant impairment over time. Clinically feasible methods to categorize youth with FGIDs at greatest risk for persistent pain-related impairment have not yet been identified. METHODS Measures of functional disability, pain intensity, and anxiety were collected on 99 patients with FGIDs (ages 8-18) during a visit to a pediatric gastroenterology office to assess for the presence of risk. Follow-up data were obtained on a subset of this sample (n = 64) after 6 months, either in person or via mail. The present study examined whether a greater number of risk factors at baseline predicted greater pain-related disability at follow-up. RESULTS Patients were divided into 4 groups based on number of risk factors present at the initial assessment: 0 (18.2%), 1 (24.2%), 2 (26.3%), and 3 (31.3%). The presence of 2 or 3 risk factors significantly predicted greater disability at follow-up compared to those with 0 risk factors (R = 0.311) and those with just 1 risk factor (Cohen's d values of -1.07 and -1.44, respectively). DISCUSSION A simple approach to risk categorization can identify youth with FGIDs who are most likely to report increased levels of pain-related impairment over time. These findings have important clinical implications that support the utility of a brief screening process during medical care to inform referral for targeted treatment approaches to FGIDs. more...
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- 2017
32. Effect of Guanylate Cyclase-C Activity on Energy and Glucose Homeostasis
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April Haller, Rohit Kohli, Adam P. Chambers, Denovan P. Begg, Randy J. Seeley, Kris A. Steinbrecher, Stephen C. Woods, Joram D. Mul, and Mitchell B. Cohen
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Male ,medicine.medical_specialty ,Receptors, Peptide ,Endocrinology, Diabetes and Metabolism ,Central nervous system ,Receptors, Enterotoxin ,Biology ,Eating ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Glucose homeostasis ,Natriuretic Peptides ,Receptor ,Cyclic GMP ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Guanylate cyclase 2C ,NPR1 ,Rats ,Glucose ,Endocrinology ,medicine.anatomical_structure ,Receptors, Guanylate Cyclase-Coupled ,chemistry ,Gastrointestinal hormone ,Guanylate Cyclase ,Knockout mouse ,Energy Metabolism ,Obesity Studies ,030217 neurology & neurosurgery ,Uroguanylin - Abstract
Uroguanylin is a gastrointestinal hormone primarily involved in fluid and electrolyte handling. It has recently been reported that prouroguanylin, secreted postprandially, is converted to uroguanylin in the brain and activates the receptor guanylate cyclase-C (GC-C) to reduce food intake and prevent obesity. We tested central nervous system administration of two GC-C agonists and found no significant reduction of food intake. We also carefully phenotyped mice lacking the GC-C receptor and found them to have normal body weight, adiposity, and glucose tolerance. Interestingly, uroguanylin knockout mice had a small but significant increase in body weight and adiposity that was accompanied by glucose intolerance. Our data indicate that the modest effects of uroguanylin on energy and glucose homeostasis are not mediated by central GC-C receptors. more...
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- 2014
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33. Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients
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Mitchell B. Cohen, María Victoria Preciado, Paola Andrea Chabay, Fernanda Metrebian, E. De Matteo, and Marina Narbaitz
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Cancer Research ,education.field_of_study ,medicine.medical_treatment ,Population ,Epstein-Barr Virus Positive ,Immunosuppression ,Biology ,medicine.disease_cause ,medicine.disease ,Epstein–Barr virus ,Lymphoma ,Oncology ,immune system diseases ,hemic and lymphatic diseases ,Immunology ,medicine ,Young adult ,education ,Diffuse large B-cell lymphoma ,CD8 - Abstract
Diffuse large B-cell lymphoma (DLBCL), the most common group of malignant lymphomas, account for 30% of adult non-Hodgkin lymphomas. The 2008 World Health Organization (WHO) classification included a new entity, Epstein-Barr virus (EBV)+ DLBCL of the elderly, affecting patients aged 50 years or older. However, some reports of younger EBV+ DLBCL cases, without evidence of underlying immunosuppression, can be found. The role of EBV in tumor microenvironment composition in DLBCL is still not well understood. Our aim was to assess EBV presence and latency pattern as well as tumor T-cell population in an adult DLBCL series of Argentina. The study was conducted on biopsies from 75 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real-time polymerase chain reaction. LMP1, LMP2A, EBNA2, EBNA3A, CD4, CD8 and Foxp3 expression was assessed by immunohistochemistry. Nine percent of cases showed EBV expression, with similar frequency among patients younger than 50 years and 50 years or older (13% and 8%, respectively). T-cell subsets were not altered by EBV presence. Latency type II was the most frequently observed, together with lytic gene expression in EBV+ DLBCL, with ≥20% of EBERs+ cells. These findings suggest that EBV+ DLBCL in our series was similar to the previously described in Asia and Latin-America, displaying latency II or III expression profile and no age-specific characteristics. Finally, EBV+ DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the age cutoff revision may be a current goal. more...
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- 2014
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34. Characterization of EBV infection at the site of viral entry and reactivation in pediatric patients
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Paola Andrea Chabay, M.I. Galliard, María Soledad Caldirola, E. De Matteo, M.V. Preciado, Mitchell B. Cohen, Aldana Georgina Vistarop, and N.M. Ferressini Gerpe
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Microbiology (medical) ,Infectious Diseases ,Viral entry ,business.industry ,Medicine ,General Medicine ,business ,Ebv infection ,Virology - Published
- 2018
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35. Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba
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Ana A. Weil, Jakub K. Simon, Michael Lock, Motaher Hossain, Jason B. Harris, Taufiqur Rahman Bhuiyan, Andrew S. Azman, Peng Xu, Mitchell B. Cohen, Kamrul Islam, Richelle C. Charles, Daniel T. Leung, Myron M. Levine, Beth D. Kirkpatrick, Caroline E. Lyon, Edward T. Ryan, Wilbur H. Chen, Firdausi Qadri, Meagan Kelly, Stephen B. Calderwood, Leslie M. Mayo Smith, Pavol Kováč, and Marc Gurwith more...
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Bacterial Diseases ,Male ,0301 basic medicine ,Serotype ,Physiology ,RC955-962 ,Antibody Response ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Biochemistry ,El Tor ,0302 clinical medicine ,Cholera ,Arctic medicine. Tropical medicine ,Immune Physiology ,Medicine and Health Sciences ,Immune Response ,Vaccines ,Bangladesh ,Immune System Proteins ,biology ,Vibrio cholerae O1 ,O Antigens ,Middle Aged ,Antibodies, Bacterial ,Bacterial Pathogens ,Body Fluids ,3. Good health ,Blood ,Infectious Diseases ,Medical Microbiology ,Vibrio cholerae ,Female ,Public aspects of medicine ,RA1-1270 ,Pathogens ,Anatomy ,Antibody ,Research Article ,Neglected Tropical Diseases ,Diarrhea ,Adult ,Cholera Toxin ,Infectious Disease Control ,Adolescent ,Immunology ,030231 tropical medicine ,Gastroenterology and Hepatology ,Microbiology ,Antibodies ,Young Adult ,03 medical and health sciences ,Signs and Symptoms ,Immune system ,Diagnostic Medicine ,Immunity ,Vibrio Cholerae ,medicine ,Humans ,Microbial Pathogens ,Vibrio ,Bacteria ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,Proteins ,Cholera Vaccines ,Tropical Diseases ,biology.organism_classification ,medicine.disease ,Immunity, Humoral ,Immunoglobulin A ,030104 developmental biology ,Immunoglobulin M ,North America ,biology.protein ,Antitoxins ,Cholera vaccine ,Blood Groups - Abstract
Background Antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naïve humans. Methodology We measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera. Principal findings We found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naïve and endemic zone cohorts, presumably reflecting previous exposure in the latter. Conclusions Our results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations. Trial registration number ClinicalTrials.gov NCT01895855., Author summary Cholera is an acute, secretory diarrheal disease caused by Vibrio cholerae O1. There is a growing body of evidence that immune responses targetting the O-specific polysaccharide (OSP) of V. cholerae are associated with protecton against cholera. Despite this, little is known about immune responses targeting OSP in immunologically naive individals. Cholera affects populations in severely resource-limited areas. To address this, we assessed anti-OSP immune responses in North American volunteers experimentally infected with wild type V. cholerae O1 El Tor Inaba strain N16961. We found that antibody responses were largely IgM and IgA, cross-reacted to both Inaba and Ogawa serotypes, and correlated with vibriocidal responses. We found no association of responses to severity of disease, but did find that blood group O individuals mounted lower IgA fold-changes to OSP than did non-blood group O individuals. Individuals with blood group O are at particular risk for severe cholera, and are less well protected against cholera following oral vaccination. We also compared anti-OSP responses in previously unexposed individuals to responses in matched endemic zone patients, and found a number of significant differences. Such differences may explain in part the varying degrees of protective efficacy afforded by cholera vaccination between these two populations. more...
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- 2019
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36. Oral Presentations
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Ada Silos-Santiago, Caroline B. Kurtz, Stuart M. Brierley, Andrea M. Harrington, Elizabeth A. Mann, Mitchell B. Cohen, and Joel Castro
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03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Nociception ,chemistry ,Endocrine and Autonomic Systems ,Physiology ,Gastroenterology ,030211 gastroenterology & hepatology ,Pharmacology ,Linaclotide ,030217 neurology & neurosurgery - Published
- 2013
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37. The Live Attenuated Cholera Vaccine CVD 103-HgR Primes Responses to the Toxin-Coregulated Pilus Antigen TcpA in Subjects Challenged with Wild-Type Vibrio cholerae
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Wilbur H. Chen, Jason B. Harris, Beth D. Kirkpatrick, Mitchell B. Cohen, Marc Gurwith, Stephen B. Calderwood, Leslie M. Mayo-Smith, Michael Lock, Douglas Haney, Myron M. Levine, Jakub K. Simon, and Caroline E. Lyon more...
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Adult ,Male ,Volunteers ,0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Clinical Biochemistry ,Immunology ,Vaccines, Attenuated ,medicine.disease_cause ,El Tor ,Microbiology ,Placebos ,03 medical and health sciences ,Cholera ,Double-Blind Method ,Immunity ,medicine ,Humans ,Immunology and Allergy ,Vaccines ,Antigens, Bacterial ,biology ,business.industry ,Cholera toxin ,Vibrio cholerae O1 ,Cholera Vaccines ,biology.organism_classification ,medicine.disease ,Antibodies, Bacterial ,Immunoglobulin A ,Bacterial vaccine ,Vaccination ,030104 developmental biology ,Vibrio cholerae ,Immunoglobulin G ,Female ,Fimbriae Proteins ,business ,Cholera vaccine - Abstract
One potential advantage of live attenuated bacterial vaccines is the ability to stimulate responses to antigens which are only expressed during the course of infection. To determine whether the live attenuated cholera vaccine CVD 103-HgR (Vaxchora) results in antibody responses to the in vivo -induced toxin-coregulated pilus antigen TcpA, we measured IgA and IgG responses to Vibrio cholerae O1 El Tor TcpA in a subset of participants in a recently reported experimental challenge study. Participants were challenged with V. cholerae O1 El Tor Inaba N16961 either 10 days or 90 days after receiving the vaccine or a placebo. Neither vaccination nor experimental infection with V. cholerae alone resulted in a robust TcpA IgG or IgA response, but each did elicit a strong response to cholera toxin. However, compared to placebo recipients, vaccinees had a marked increase in IgG TcpA antibodies following the 90-day challenge, suggesting that vaccination with CVD 103-HgR resulted in priming for a subsequent response to TcpA. No such difference between vaccine and placebo recipients was observed for volunteers challenged 10 days after vaccination, indicating that this was insufficient time for vaccine-induced priming of the TcpA response. The priming of the response to TcpA and potentially other antigens expressed in vivo by attenuated V. cholerae may have relevance to the maintenance of immunity in areas where cholera is endemic. more...
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- 2017
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38. Comparison of recommendations in clinical practice guidelines for acute gastroenteritis in children
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Jorge Amil Dias, James A. Berkley, Eduardo Salazar Lindo, Philip M. Sherman, Bhupinder Sandhu, Sylvia Cruchet, Mitchell B. Cohen, Toshiaki Shimizu, Chris Boey, Alfredo Guarino, Ilaria Liguoro, Andrea Lo Vecchio, Lo Vecchio, A, Dias, Ja, Berkley, Ja, Boey, C, Cohen, Mb, Cruchet, S, Liguoro, I, Salazar Lindo, E, Sandhu, B, Sherman, P, Shimizu, T, and Guarino, A. more...
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Acute diarrhea ,medicine.medical_specialty ,animal structures ,purl.org/pe-repo/ocde/ford#3.03.04 [https] ,MEDLINE ,Guidelines ,Article ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Child ,Children ,purl.org/pe-repo/ocde/ford#3.02.03 [https] ,Acute Disease ,Gastroenteritis ,Practice Guidelines as Topic ,business.industry ,purl.org/pe-repo/ocde/ford#3.02.19 [https] ,Gastroenterology ,Gastroenteritis/diagnosis/therapy ,Acute gastroenteritis ,Child mortality ,Clinical Practice ,gastroenteritis, diarrhea, guidelines ,Pediatrics, Perinatology and Child Health ,embryonic structures ,business ,human activities - Abstract
Objective: Acute gastroenteritis (AGE) is a major cause of child mortality and morbidity. This study aimed at systematically reviewing clinical practice guidelines (CPGs) on AGE to compare recommendations and provide the basis for developing single universal guidelines.Methods: CPGs were identified by searching MEDLINE, Cochrane-Library, National Guideline Clearinghouse and Web sites of relevant societies/organizations producing and/or endorsing CPGs.Results: The definition of AGE varies among the 15 CPGs identified. The parameters most frequently recommended to assess dehydration are skin turgor and sunken eyes (11/15, 73.3%), general appearance (11/15, 66.6%), capillary refill time, and mucous membranes appearance (9/15, 60%). Oral rehydration solution is universally recognized as first-line treatment. The majority of CPGs recommend hypo-osmolar (Na+ 45–60 mmol/L, 11/15, 66.6 %) or low-osmolality (Na+ 75 mmol/L, 9/15, 60%) solutions. In children who fail oral rehydration, most CPGs suggest intravenous rehydration (66.6%). However, nasogastric tube insertion for fluid administration is preferred according by 5/15 CPGs (33.3%). Changes in diet and withdrawal of food are discouraged by all CPGs, and early refeeding is strongly recommended in 13 of 15 (86.7%). Zinc is recommended as an adjunct to ORS by 10 of 15 (66.6%) CPGs, most of them from low-income countries. Probiotics are considered by 9 of 15 (60%) CPGs, 5 from high-income countries. Antiemetics are not recommended in 9 of 15 (60%) CPGs. Routine use of antibiotics is discouraged.Conclusions: Key recommendations for the management of AGE in children are similar in CPGs. Together with accurate review of evidence-base this may represent a starting point for developing universal recommendations for the management of children with AGE worldwide. more...
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- 2016
39. Murine Guanylate Cyclase C Regulates Colonic Injury and Inflammation
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Elizabeth A. Mann, Mitchell B. Cohen, Simon P. Hogan, Monica P. Garin-Laflam, Kris A. Steinbrecher, Eleana Harmel-Laws, and Lucas D. Bezerra
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medicine.medical_specialty ,Guanylin ,medicine.medical_treatment ,Immunology ,Inflammation ,Biology ,Article ,Gastrointestinal Hormones ,Colonic Diseases ,Interferon-gamma ,Mice ,chemistry.chemical_compound ,Intestinal mucosa ,Internal medicine ,medicine ,Animals ,Immunology and Allergy ,Interferon gamma ,Intestinal Mucosa ,Natriuretic Peptides ,Mice, Knockout ,Tumor Necrosis Factor-alpha ,digestive system diseases ,Cytokine ,Endocrinology ,chemistry ,Guanylate Cyclase ,Hormones, Ectopic ,Intercellular Signaling Peptides and Proteins ,Tumor necrosis factor alpha ,medicine.symptom ,Signal transduction ,medicine.drug ,Uroguanylin - Abstract
Guanylate cyclase C (GUCY2C or GC-C) and its ligands, guanylin (GUCA2A or Gn) and uroguanylin (GUCA2B or Ugn), are expressed in intestinal epithelial cells and regulate ion secretion, intestinal barrier function, and epithelial monolayer homeostasis via cGMP-dependent signaling pathways. The aim of this study was to determine whether GC-C and its ligands direct the course of intestinal inflammation. In this article, we show that dextran sodium sulfate (DSS)-induced clinical disease and histological damage to the colonic mucosa were significantly less severe in GC-C−/− mice and moderately reduced in Gn−/− animals. Relative to wild-type controls, GC-C−/− and Gn−/− mice had reduced apoptosis and increased proliferation of intestinal epithelial cells during DSS colitis. Basal and DSS-induced production of resistin-like molecule β (RELMβ) was substantially diminished in GC-C−/− mice. RELMβ is thought to stimulate cytokine production in macrophages in this disease model and, consistent with this, TNF-α and IFN-γ production was minimal in GC-C−/− animals. RELMβ and cytokine levels were similar to wild-type in Gn−/− mice, however. Colonic instillation of recombinant RELMβ by enema into GC-C−/− mice restores sensitivity to DSS-mediated mucosal injury. These findings demonstrate a novel role for GC-C signaling in facilitating mucosal wounding and inflammation, and further suggest that this may be mediated, in part, through control of RELMβ production. more...
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- 2011
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40. Validation of the Pediatric Cardiac Quality of Life Inventory
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Jo Wray, Jane W. Newburger, Dennis Drotar, J. William Gaynor, Ryan S. Tomlinson, Elizabeth Tong, Mitchell B. Cohen, David Shera, Bradley S. Marino, Judy A. Shea, Gil Wernovsky, Anne E. Kazak, Charlotte Andersen, Kathleen A. Mussatto, Mark A. Helfaer, Philip R. Khoury, and Lynn Mahony more...
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Adult ,Male ,Gerontology ,medicine.medical_specialty ,Adolescent ,Heart Diseases ,Cross-sectional study ,Validity ,Primary cutaneous B-cell lymphoma ,Test validity ,Severity of Illness Index ,Article ,Quality of life (healthcare) ,Surveys and Questionnaires ,Humans ,Medicine ,Prospective Studies ,Child ,business.industry ,Construct validity ,Middle Aged ,Self perception ,Cross-Sectional Studies ,Multicenter study ,Pediatrics, Perinatology and Child Health ,Emergency medicine ,Quality of Life ,Female ,business - Abstract
OBJECTIVE: The purpose of this multicenter study was to confirm the validity and reliability of the Pediatric Cardiac Quality of Life Inventory (PCQLI). METHODS: Seven centers recruited pediatric patients (8–18 years of age) with heart disease (HD) and their parents to complete the PCQLI and generic health-related quality of life (Pediatric Quality of Life Inventory [PedsQL]) and non–quality of life (Self-Perception Profile for Children [SPPC]/Self-Perception Profile for Adolescents [SPPA] and Youth Self-Report [YSR]/Child Behavior Checklist [CBCL]) tools. PCQLI construct validity was assessed through correlations of PCQLI scores between patients and parents and with severity of congenital HD, medical care utilization, and PedsQL, SPPC/SPPA, and YSR/CBCL scores. PCQLI test-retest reliability was evaluated. RESULTS: The study enrolled 1605 patient-parent pairs. Construct validity was substantiated by the association of lower PCQLI scores with Fontan palliation and increased numbers of cardiac operations, hospital admissions, and physician visits (P < .001); moderate to good correlations between patient and parent PCQLI scores (r = 0.41–0.61; P < .001); and fair to good correlations between PCQLI total scores and PedsQL total (r = 0.70–0.76), SPPC/SPPA global self-worth (r = 0.43–0.46), YSR/CBCL total competency (r = 0.28–0.37), and syndrome and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-oriented scale (r = −0.58 to −0.30; P < .001) scores. Test-retest reliability correlations were excellent (r = 0.78–0.90; P < .001). CONCLUSIONS: PCQLI scores are valid and reliable for children and adolescents with congenital and acquired HD and may be useful for future research and clinical management. more...
- Published
- 2010
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41. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract
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Marco Kessler, Etchell A. Cordero, Robert W. Busby, Wilmin Bartolini, Gerhard Hannig, Mark G. Currie, Caroline B. Kurtz, Jenny Tobin, Alexander P. Bryant, Shalina Mahajan-Miklos, Robert Solinga, Christine M. Pierce, and Mitchell B. Cohen more...
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Male ,Agonist ,medicine.medical_specialty ,Receptors, Peptide ,medicine.drug_class ,Administration, Oral ,Biological Availability ,Receptors, Enterotoxin ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Mice ,chemistry.chemical_compound ,Gastrointestinal Agents ,Internal medicine ,medicine ,Animals ,Secretion ,Intestinal Mucosa ,General Pharmacology, Toxicology and Pharmaceutics ,Gastrointestinal Transit ,Linaclotide ,Irritable bowel syndrome ,Mice, Knockout ,Gastrointestinal tract ,Dose-Response Relationship, Drug ,Intestinal Secretions ,General Medicine ,Guanylate cyclase 2C ,medicine.disease ,Bioavailability ,Gastrointestinal Tract ,Mice, Inbred C57BL ,Endocrinology ,Receptors, Guanylate Cyclase-Coupled ,chemistry ,Guanylate Cyclase ,Female ,Peptides ,Gastrointestinal function - Abstract
Aims Linaclotide is an orally administered 14-amino acid peptide being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic constipation. We determined the stability of linaclotide in the intestine, measured the oral bioavailability, and investigated whether the pharmacodynamic effects elicited in rodent models of gastrointestinal function are mechanistically linked to the activation of intestinal guanylate cyclase C (GC-C). Main methods Linaclotide binding to intestinal mucosal membranes was assessed in competitive binding assays. Stability and oral bioavailability of linaclotide were measured in small intestinal fluid and serum, respectively, and models of gastrointestinal function were conducted using wild type (wt) and GC-C null mice. Key findings Linaclotide inhibited in vitro [ 125 I]-STa binding to intestinal mucosal membranes from wt mice in a concentration-dependent manner. In contrast, [ 125 I]-STa binding to these membranes from GC-C null mice was significantly decreased. After incubation in vitro in jejunal fluid for 30 min, linaclotide was completely degraded. Pharmacokinetic analysis showed very low oral bioavailability (0.10%). In intestinal secretion and transit models, linaclotide exhibited significant pharmacological effects in wt, but not in GC-C null mice: induction of increased fluid secretion into surgically ligated jejunal loops was accompanied by the secretion of elevated levels of cyclic guanosine-3′,5′-monophosphate and accelerated gastrointestinal transit. Significance Linaclotide is a potent and selective GC-C agonist that elicits pharmacological effects locally in the gastrointestinal tract. This pharmacological profile suggests that orally administered linaclotide may be capable of improving the abdominal symptoms and bowel habits of patients suffering from IBS-C and chronic constipation. more...
- Published
- 2010
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42. Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers
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Beth D. Kirkpatrick, Leslie M. Mayo Smith, Pavol Kováč, Marc Gurwith, Jason B. Harris, Stephen B. Calderwood, Motaher Hossain, Kamrul Islam, Mitchell B. Cohen, Peng Xu, Jakub K. Simon, Myron M. Levine, Wilbur H. Chen, Caroline E. Lyon, Michael Lock, Edward T. Ryan, Firdausi Qadri, Douglas Haney, Regina C. LaRocque, Richelle C. Charles, Taufiqur Rahman Bhuiyan, and Meagan Kelly more...
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Male ,Volunteers ,Bacterial Diseases ,0301 basic medicine ,Physiology ,Administration, Oral ,Antibody Response ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Biochemistry ,El Tor ,0302 clinical medicine ,Cholera ,Immune Physiology ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,Immune Response ,Vaccines ,Immune System Proteins ,biology ,lcsh:Public aspects of medicine ,Vaccination ,Vibrio cholerae O1 ,O Antigens ,Antibodies, Bacterial ,Bacterial Pathogens ,3. Good health ,Diarrhea ,Infectious Diseases ,Medical Microbiology ,Vibrio cholerae ,Female ,Pathogens ,Antibody ,medicine.symptom ,Research Article ,Neglected Tropical Diseases ,Adult ,lcsh:Arctic medicine. Tropical medicine ,Infectious Disease Control ,lcsh:RC955-962 ,Immunology ,030231 tropical medicine ,Gastroenterology and Hepatology ,Research and Analysis Methods ,Microbiology ,Antibodies ,03 medical and health sciences ,Signs and Symptoms ,Double-Blind Method ,Diagnostic Medicine ,Vibrio Cholerae ,medicine ,Humans ,Immunoassays ,Microbial Pathogens ,Vibrio ,Bacteria ,business.industry ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,Proteins ,Cholera Vaccines ,lcsh:RA1-1270 ,Tropical Diseases ,medicine.disease ,biology.organism_classification ,United States ,Immunoglobulin A ,030104 developmental biology ,Immunoglobulin M ,Immunoglobulin G ,Antibody Formation ,Immunologic Techniques ,biology.protein ,Cholera vaccine ,business - Abstract
Background Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio cholerae O1 and occasionally O139. A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae are involved in mediating protection against cholera. We therefore assessed whether antibody responses against OSP occur after vaccination with live attenuated oral cholera vaccine CVD 103-HgR, and whether such responses correlate with protection against cholera. Methodology We assessed adult North American volunteers (n = 46) who were vaccinated with 5 × 108 colony-forming units (CFU) of oral cholera vaccine CVD 103-HgR and then orally challenged with approximately 1 × 105 CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961, either 10 or 90 days post-vaccination. Principal findings Vaccination was associated with induction of significant serum IgM and IgA anti-OSP and vibriocidal antibody responses within 10 days of vaccination. There was significant correlation between anti-OSP and vibriocidal antibody responses. IgM and IgA anti-OSP responses on day 10 following vaccination were associated with lower post-challenge stool volume (r = −0.44, P = 0.002; r = −0.36, P = 0.01; respectively), and none of 27 vaccinees who developed a ≥1.5 fold increase in any antibody isotype targeting OSP on day 10 following vaccination compared to baseline developed moderate or severe cholera following experimental challenge, while 5 of 19 who did not develop such anti-OSP responses did (P = 0.01). Conclusion Oral vaccination with live attenuated cholera vaccine CVD 103-HgR induces antibodies that target V. cholerae OSP, and these anti-OSP responses correlate with protection against diarrhea following experimental challenge with V. cholerae O1. Trial registration ClinicalTrials.gov NCT01895855, Author summary Cholera is a severe watery diarrheal disease, caused by pathogenic strains of V. cholerae. Protective immunity against cholera is serogroup specific, and serogroup specificity is determined by the O-specific polysaccharide (OSP) of V. cholerae lipopolysaccharide (LPS). Despite this, no previous work has directly assessed correlation of OSP-immune responses and protection against cholera. In this study, we assessed adult North American volunteer’s antibody responses targeting OSP after vaccination with live attenuated oral cholera vaccine CVD 103-HgR, and we assessed correlation of protection against cholera with such antibody responses. Oral vaccination was associated with the induction of significant IgM and IgA responses against OSP, and these responses correlated with vibriocidal responses. There was significant negative correlation of OSP responses and post-challenge stool volume, and none of the volunteers who developed an anti-OSP antibody responses of any isotype of ≥1.5 fold developed moderate or severe cholera following experimental challenge. In summary, vaccination with live attenuated oral cholera vaccine CVD 103-HgR induces antibodies that target V. cholerae OSP, and these responses highly correlate with protection against cholera. more...
- Published
- 2018
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43. Innovations in Electrophysiology
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Mitchell B. Cohen
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business.industry ,Cardiac Pacing, Artificial ,Arrhythmias, Cardiac ,General Medicine ,Cryosurgery ,Data science ,Defibrillators, Implantable ,Electrophysiology ,Stereotaxic Techniques ,Death, Sudden, Cardiac ,Pediatrics, Perinatology and Child Health ,Tetralogy of Fallot ,Humans ,Medicine ,Channelopathies ,Child ,Cardiology and Cardiovascular Medicine ,business - Published
- 2009
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44. Molecular cloning and promoter analysis of downregulated in adenoma (DRA)
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Gary D. Wu, Ifor R. Williams, Waddah A. Alrefai, Xiaoming Wen, Kris A. Steinbrecher, Mitchell B. Cohen, Pradeep K. Dudeja, Wen Jiang, and Jonathan P. Katz
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Adenoma ,Congenital chloride diarrhea ,Physiology ,Molecular Sequence Data ,Mice, Transgenic ,SLC26A3 ,Molecular cloning ,Antiporters ,Mice ,Genes, Reporter ,Cell Line, Tumor ,Physiology (medical) ,Gene expression ,medicine ,Animals ,Humans ,Chloride-Bicarbonate Antiporters ,Cloning, Molecular ,Intestinal Mucosa ,Promoter Regions, Genetic ,Base Sequence ,Hepatology ,biology ,Human Growth Hormone ,Reverse Transcriptase Polymerase Chain Reaction ,Gastroenterology ,Promoter ,Transporter ,Promoter analysis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Sulfate Transporters ,Cancer research ,biology.protein ,Transcription Factors - Abstract
Downregulated in adenoma (DRA), also referred to as SLC26A3, is an intestinal anion transporter essential for intestinal chloride absorption. Mutations in DRA result in congenital chloride diarrhea. DRA expression has been shown to be induced by differentiation and to be modulated by cytokines. However, mechanisms of DRA gene transcription and its tissue-specific targeting have not yet been investigated. In this study, we cloned a 3,765-bp promoter fragment of human DRA gene and characterized its activity in human colonic LS174T and Caco-2 human colon cell lines. Primer extension identified a single transcriptional initiation site that was identical in both colon cancer cell lines and normal colon. Although hepatic nuclear factor HNF-4 is involved in the basal activity of DRA promoter, sodium butyrate induces its activity in LS174T cells via the binding of Yin Yang 1 (YY1) and GATA transcription factors to their respective cis-elements in promoter region. We also demonstrated a reduction in DRA promoter activity in Caco-2 cells by IFN-γ, suggesting that regulation of DRA promoter by IFN-γ may contribute to the pathophysiology of intestinal inflammation. Furthermore, we showed that the DRA promoter fragment is sufficient to drive human growth hormone transgene expression specifically in villus epithelial cells of the small intestine and in differentiated upper crypt and surface epithelial cells of the colon. Our studies provide evidence for the involvement of HNF-4, YY1, and GATA transcription factors in DRA expression in intestinal differentiated epithelial cells. more...
- Published
- 2007
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45. Suppurative Peripheral Arthritis in Inflammatory Bowel Disease
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Brad Pasternak, Mitchell B. Cohen, Alexi Grom, and Nada Yazigi
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Arthritis, Infectious ,medicine.medical_specialty ,business.industry ,Crohn disease ,Peripheral arthritis ,Gastroenterology ,MEDLINE ,Arthritis ,medicine.disease ,Inflammatory bowel disease ,Ulcerative colitis ,Child, Preschool ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Infectious etiology ,Colitis, Ulcerative ,Female ,Hip Joint ,Colitis ,Child ,business ,Ultrasonography - Published
- 2007
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46. Controversies in pediatric inflammatory bowel disease
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Richard B. Colletti, William F. Balistreri, Ernest G. Seidman, Mitchell B. Cohen, Harland S. Winter, Barbara S. Kirschner, and Richard J. Grand
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medicine.medical_specialty ,Crohn's disease ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Immunology and Allergy ,medicine.disease ,business ,Ulcerative colitis ,Inflammatory bowel disease - Published
- 2007
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47. Bacterial, Viral, and Toxic Causes of Diarrhea, Gastroenteritis, and Anorectal Infections
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Mitchell B. Cohen
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Diarrhea ,business.industry ,medicine ,Bloody diarrhea ,medicine.symptom ,Antimicrobial ,business ,Virology ,Infectious gastroenteritis - Published
- 2015
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48. Concordant parent-child reports of anxiety predict impairment in youth with functional abdominal pain
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Anne M. Lynch-Jordan, Mitchell B. Cohen, Susmita Kashikar-Zuck, Natoshia R. Cunningham, Michael K. Farrell, and Adam Mezoff
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Male ,Parents ,Risk ,congenital, hereditary, and neonatal diseases and abnormalities ,Abdominal pain ,medicine.medical_specialty ,Outpatient Clinics, Hospital ,Adolescent ,Cross-sectional study ,Gastrointestinal Diseases ,Anxiety ,Diagnostic tools ,Severity of Illness Index ,Article ,Child Report ,Hospitals, Urban ,Severity of illness ,Medicine ,Humans ,Mass Screening ,Psychiatry ,Child ,Mass screening ,Ohio ,Pain Measurement ,Psychiatric Status Rating Scales ,business.industry ,Gastroenterology ,Small sample ,Hospitals, Pediatric ,digestive system diseases ,Abdominal Pain ,Diagnostic and Statistical Manual of Mental Disorders ,Gastrointestinal Tract ,Cross-Sectional Studies ,Pediatrics, Perinatology and Child Health ,Female ,Self Report ,medicine.symptom ,business - Abstract
Functional abdominal pain (FAP) is associated with significant anxiety and impairment. Prior investigations of child anxiety in youth with FAP are generally limited by small sample sizes, based on child report, and use lengthy diagnostic tools. It is unknown whether a brief anxiety-screening tool is feasible, whether parent and child reports of anxiety are congruent, and whether parent and child agreement of child anxiety corresponds to increased impairment. The purpose of this investigation was to examine anxiety characteristics in youth with FAP using parent and child reports. Parent-child agreement of child anxiety symptoms was examined in relation to pain and disability.One hundred patients with FAP (8-18 years of age) recruited from pediatric gastroenterology clinics completed measures of pain intensity (Numeric Rating Scale) and disability (Functional Disability Inventory). Patients and caregivers both completed a measure of child anxiety characteristics (Screen for Child Anxiety and Related Disorders).Clinically significant anxiety symptoms were more commonly reported by youth (54%) than their parents (30%). Panic/somatic symptoms, generalized anxiety, and separation anxiety were most commonly endorsed by patients, whereas generalized anxiety, separation anxiety, and school avoidance were most commonly reported by parents. The majority (65%) of parents and children agreed on the presence (26%) or absence (39%) of clinically significant anxiety. Parent-child agreement of clinically significant anxiety was related to increased impairment.A brief screening instrument of parent and child reports of anxiety can provide clinically relevant information for comprehensive treatment planning in children with FAP. more...
- Published
- 2015
49. A Randomized, Double-Blind, Placebo-Controlled Trial of Fluticasone Propionate for Pediatric Eosinophilic Esophagitis
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Seema S. Aceves, Michael R. Konikoff, Marc E. Rothenberg, Amal Assa'ad, Margaret H. Collins, Mitchell B. Cohen, Sean C. Jameson, Philip E. Putnam, Cassie L. Kirby, Richard J. Noel, Carine Blanchard, Rachel Akers, and Bridget K. Buckmeier more...
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medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,business.industry ,Esophagogastroduodenoscopy ,Gastroenterology ,Placebo-controlled study ,Eosinophil ,medicine.disease ,Placebo ,Fluticasone propionate ,medicine.anatomical_structure ,Internal medicine ,Vomiting ,Medicine ,medicine.symptom ,business ,Eosinophilic esophagitis ,Fluticasone ,medicine.drug - Abstract
Background & Aims: Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic, histologic, and allergic features. Although several therapies are advocated, no placebo-controlled trials have been conducted. We aimed to determine the efficacy of swallowed fluticasone propionate (FP) in the treatment of eosinophilic esophagitis. Methods: We conducted a randomized, double-blind, placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis. Thirty-six patients were randomly assigned to receive either 880 μg of FP (21 patients) or placebo (15 patients) divided twice daily for 3 months. The primary end point was histologic remission, defined by a peak eosinophil count of ≤1 eosinophil in all 400× fields in both the proximal and distal esophagus. Results: Fifty percent of FP-treated patients achieved histologic remission compared with 9% of patients receiving placebo ( P = .047). FP decreased esophageal eosinophil levels, with a more pronounced effect in nonallergic individuals (65.9 ± 25.3 vs 1.4 ± 1.1 eosinophils/high-power field in the proximal esophagus [ P = .03] and 84.6 ± 19.7 vs 19.6 ± 12.9 eosinophils/high-power field in the distal esophagus [ P = .04]). Resolution of vomiting occurred more frequently with FP than placebo (67% vs 27%; P = .04). FP-induced resolution of mucosal eosinophilia was associated with resolution of endoscopic findings, epithelial hyperplasia, younger age ( P = .0003), shorter height ( P = .002), and lighter weight ( P = .02). Effective treatment with FP decreased the number of CD8 + T lymphocytes and mast cells in both the proximal and distal esophagus ( P more...
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- 2006
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50. Potential of Blood Eosinophils, Eosinophil-Derived Neurotoxin, and Eotaxin-3 as Biomarkers of Eosinophilic Esophagitis
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Bridget K. Buckmeier, Philip E. Putnam, Mitchell B. Cohen, Cassie L. Kirby, Michael R. Konikoff, Carine Blanchard, James E. Heubi, and Marc E. Rothenberg
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Male ,Eotaxin ,Pathology ,medicine.medical_specialty ,Adolescent ,Eosinophil-derived neurotoxin ,Eosinophil-Derived Neurotoxin ,Sensitivity and Specificity ,Leukocyte Count ,Eosinophilia ,medicine ,Esophagitis ,Humans ,Immunologic Factors ,Prospective Studies ,Child ,Eosinophilic esophagitis ,High-power field ,Hepatology ,Chemokine CCL26 ,business.industry ,Gastroenterology ,Infant ,respiratory system ,Eosinophil ,medicine.disease ,Eosinophils ,Cross-Sectional Studies ,medicine.anatomical_structure ,ROC Curve ,Chemokines, CC ,Child, Preschool ,Biomarker (medicine) ,Female ,medicine.symptom ,business ,Biomarkers - Abstract
Background & Aims: Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. Methods: A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. Results: AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P r = 0.54, P r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/μL, P P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. Conclusions: These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE. more...
- Published
- 2006
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