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Per Med ; 15(3): 199-208, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29843583


Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG's collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration.

Gastroenterology ; 151(5): 933-944.e3, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27480173


BACKGROUND & AIMS: The 5-hydroxytryptamine receptor 4 (5-HT4R or HTR4) is expressed in the colonic epithelium but little is known about its functions there. We examined whether activation of colonic epithelial 5-HT4R protects colons of mice from inflammation. METHODS: The 5-HT4R agonist tegaserod (1 mg/kg), the 5-HT4R antagonist GR113808 (1 mg/kg), or vehicle (control) were delivered by enema to wild-type or 5-HT4R knockout mice at the onset of, or during, active colitis, induced by administration of dextran sodium sulfate or trinitrobenzene sulfonic acid. Inflammation was measured using the colitis disease activity index and by histologic analysis of intestinal tissues. Epithelial proliferation, wound healing, and resistance to oxidative stress-induced apoptosis were assessed, as was colonic motility. RESULTS: Rectal administration of tegaserod reduced the severity of colitis compared with mice given vehicle, and accelerated recovery from active colitis. Rectal tegaserod did not improve colitis in 5-HT4R knockout mice, and intraperitoneally administered tegaserod did not protect wild-type mice from colitis. Tegaserod increased proliferation of crypt epithelial cells. Stimulation of 5-HT4R increased Caco-2 cell migration and reduced oxidative stress-induced apoptosis; these actions were blocked by co-administration of the 5-HT4R antagonist GR113808. In noninflamed colons of wild-type mice not receiving tegaserod, inhibition of 5-HT4Rs resulted in signs of colitis within 3 days. In these mice, epithelial proliferation decreased and bacterial translocation to the liver and spleen was detected. Daily administration of tegaserod increased motility in inflamed colons of guinea pigs and mice, whereas administration of GR113808 disrupted motility in animals without colitis. CONCLUSIONS: 5-HT4R activation maintains motility in healthy colons of mice and guinea pigs, and reduces inflammation in colons of mice with colitis. Agonists might be developed as treatments for patients with inflammatory bowel diseases.

Colite/metabolismo , Colo/metabolismo , Mucosa Intestinal/metabolismo , Receptores 5-HT4 de Serotonina/metabolismo , Agonistas do Receptor 5-HT4 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT4 de Serotonina/farmacologia , Administração Retal , Animais , Colite/induzido quimicamente , Colite/patologia , Colite/prevenção & controle , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana , Feminino , Cobaias , Indóis/farmacologia , Indóis/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Knockout , Agonistas do Receptor 5-HT4 de Serotonina/uso terapêutico , Índice de Gravidade de Doença , Sulfonamidas/farmacologia , Ácido Trinitrobenzenossulfônico
J Clin Anat Pathol (JCAP) ; 1(1)2013 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25664331


Sarcina are gram-positive anaerobic bacteria found to be associated with delayed gastric emptying and gastric outlet obstruction. We describe two cases of Sarcina co-existing with Helicobacter pylori organisms in pediatric siblings presenting within four months of each other with pyloric obstruction secondary to severe gastritis/duodenitis. The co-existence of Sarcina and Helicobacter pylori has not, to our knowledge, been previously reported. Its characteristic tetrad packeted morphology permits Sarcina to be readily identified on routine sections. Detection of these organisms in gastric biopsies should prompt consideration of gastric outlet obstruction and/or delayed gastric emptying as a possible etiologic factor.

J Pediatr ; 141(6): 833-6, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12461502


A protocol was developed for the detection of fatty acid oxidation disorders (FOD) in cases of sudden unexpected death in infancy (SUDI). Tandem mass spectrometry blood acylcarnitine analysis of Guthrie card blood spots was performed. In the first 5 years, 1.2% of Oregon's 247 SUDI cases were identified with FOD, 2 with medium-chain acyl-CoA dehydrogenase deficiency, and one with very long-chain acyl-CoA dehydrogenase deficiency.

Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Ácidos Graxos/metabolismo , Morte Súbita do Lactente/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Espectrometria de Massas , Morte Súbita do Lactente/patologia