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Franco Brochado M.J.,University of Sao Paulo | Domenici F.A.,University of Sao Paulo | Candolo Martinelli A.D.L.,Gastroenterology Division | Zucoloto S.,University of Sao Paulo | And 2 more authors.
Annals of Nutrition and Metabolism | Year: 2013

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by hepatic fat accumulation in the absence of alcohol consumption. Hyperhomocysteinemia is considered an independent risk factor for liver diseases, and the genetic polymorphisms C677T and A1298C in the MTHFR gene have been linked to hyperhomocysteinemia. The purpose of this study was to investigate serum homocysteine (Hcy) concentrations and the MTHFR C677T and A1298C polymorphisms as risk factors for the development of NAFLD. Methods: One hundred and thirty-four Brazilian patients with biopsy-proven NAFLD and 134 healthy controls were recruited. The MTHFR C677T and A1298C polymorphisms were detected through polymerase chain reaction restriction fragment length polymorphism. Serum Hcy levels were determined by chemiluminescence. Results: Serum Hcy levels were higher in NAFLD patients as compared to control subjects, but there were no differences between patients with steatosis and nonalcoholic steatohepatitis. The NAFLD and control groups did not differ in genotypic and allelic frequencies of the MTHFR C677T and A1298C polymorphisms, either. Elevated plasma Hcy levels were positively correlated with age in the NAFLD subjects. Conclusion: The MTHFR C677T and A1298C polymorphisms are not genetic risk factors for the development of NAFLD. Higher Hcy levels exist in NAFLD subjects, but they are not associated with liver disease severity. Copyright © 2013 S. Karger AG, Basel. Source

Korman L.Y.,Chevy Chase Clinical Research | Brandt L.J.,Montefiore Medical Center | Metz D.C.,University of Pennsylvania | Haddad N.G.,Georgetown University | And 7 more authors.
Gastrointestinal Endoscopy | Year: 2012

Background: Colonoscopy is a frequently performed procedure that requires extensive training and a high skill level. Objective: Quantification of forces applied to the external portion of the colonoscope insertion tube during the insertion phase of colonoscopy. Design: Observational cohort study of 7 expert and 9 trainee endoscopists for analysis of colonic segment force application in 49 patients. Forces were measured by using the colonoscopy force monitor, which is a wireless, handheld device that attaches to the insertion tube of the colonoscope. Setting: Academic gastroenterology training programs. Patients: Patients undergoing routine screening or diagnostic colonoscopy with complete segment force recordings. Main Outcome Measurements: Axial and radial force and examination time. Results: Both axial and radial force increased significantly as the colonoscope was advanced from the rectum to the cecum. Analysis of variance demonstrated highly significant operator-independent differences between segments of the colon (zones) in all axial and radial forces except average torque. Expert and trainee endoscopists differed only in the magnitude of counterclockwise force, average push/pull force rate used, and examination time. Limitations: Small study, observational design, effect of prototype device on insertion tube manipulation. Conclusion: Axial and radial forces used to advance the colonoscope increase through the segments of the colon and are operator independent. © 2012 American Society for Gastrointestinal Endoscopy. Source

Korman L.Y.,Chevy Chase Clinical Research | Haddad N.G.,Georgetown University | Metz D.C.,University of Pennsylvania | Brandt L.J.,Montefiore Medical Center | And 6 more authors.
Gastrointestinal Endoscopy | Year: 2014

Background Sedation is frequently used during colonoscopy to control patient discomfort and pain. Propofol is associated with a deeper level of sedation than is a combination of a narcotic and sedative hypnotic and, therefore, may be associated with an increase in force applied to the colonoscope to advance and withdraw the instrument. Objective To compare force application to the colonoscope insertion tube during propofol anesthesia and moderate sedation. Design An observational cohort study of 13 expert and 12 trainee endoscopists performing colonoscopy in 114 patients. Forces were measured by using the colonoscopy force monitor, which is a wireless, handheld device that attaches to the insertion tube of the colonoscope. Setting Community ambulatory surgery center and academic gastroenterology training programs. Patients Patients undergoing routine screening or diagnostic colonoscopy with complete segment force recordings. Main Outcome Measurements Axial and radial forces and examination time. Results Axial and radial forces increase and examination time decreases significantly when propofol is used as the method of anesthesia. Limitations Small study, observational design, nonrandomized distribution of sedation type and experience level, different instrument type and effect of prototype device on insertion tube manipulation. Conclusions Propofol sedation is associated with a decrease in examination time and an increase in axial and radial forces used to advance the colonoscope. © 2014 by the American Society for Gastrointestinal Endoscopy. Source

Lufrano R.,University of Iowa | Heckman M.G.,Section of Biostatistics | Diehl N.,Section of Biostatistics | Devault K.R.,Gastroenterology Division | Achem S.R.,Gastroenterology Division
Diseases of the Esophagus | Year: 2015

Nutcracker esophagus (NE) is a common esophageal motility disorder chacterized by high amplitude peristaltic contractions in the distal esophagus. While previous studies have examined selected aspects of this condition (e.g. pathogenesis and treatment), there is a paucity of data regarding demographic and clinical features in large cohorts of patients. The aim of this study was to describe demographics, clinical features, comorbidities, time to diagnosis, source of patient referral by specialty, and medication use in a large cohort of patients with NE. We retrospectively analyzed consecutive cases of NE diagnosed from 2008-2010. The electronic medical records of these patients were reviewed, and relevant information was extracted. We identified 115 patients with NE. The median age was 62 years (range 25-87 years), and 63% were female. The median time patients experienced symptoms prior to diagnosis was 24 months (0-480 months). Most patients presented to an internal medicine consultant (42%) or to a gastroenterologist (35%). Presenting symptoms were chest pain (31%) and dysphagia (21%). Gastroesophageal reflux disease (GERD) symptoms were common: heartburn occurred in 51% of patients, 77% had a prior history of GERD, and 78% were receiving acid suppressive medications. GERD was confirmed by testing in at least 35%. Psychiatric comorbidity occurred in 24% with half the patients receiving psychotropic medications. Irritable bowel syndrome (IBS) and fibromyalgia co-existed in 15% and 12% of patients, respectively. Surprisingly, opioids were prescribed to 26% of patients. No statistically significant correlation was found between esophageal motility parameters and symptoms. In this study, NE patients were more commonly middle-aged females experiencing a considerable amount of time between symptom onset and diagnosis. Many were initially evaluated by internists for dysphagia or chest pain and had a history of GERD. Medication prescribed prior to diagnoses frequently involved acid suppression, but narcotic and psychotropic prescriptions were also commonly used. Central sensitization syndromes (fibromyalgia and IBS), psychiatric comorbidity, and reflux commonly coexisted. Our study suggests that future investigations should address the role and interaction of GERD and psychiatric disorders in NE. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus. Source

Lee J.J.,Gastroenterology Division | Lee J.J.,University of Pennsylvania | Natsuizaka M.,Gastroenterology Division | Natsuizaka M.,University of Pennsylvania | And 18 more authors.
Carcinogenesis | Year: 2010

Hypoxia-inducible factors (HIFs), in particular HIF-1α, have been implicated in tumor biology. However, HIF target genes in the esophageal tumor microenvironment remain elusive. Gene expression profiling was performed upon hypoxia-exposed nontransformed immortalized human esophageal epithelial cells, EPC2-hTERT, and comparing with a gene signature of esophageal squamous cell carcinoma (ESCC). In addition to known HIF-1α target genes such as carbonic anhydrase 9, insulin-like growth factor binding protein-3 (IGFBP3) and cyclooxygenase (COX)-2, prostaglandin E synthase (PTGES) was identified as a novel target gene among the commonly upregulated genes in ESCC as well as the cells exposed to hypoxia. The PTGES induction was augmented upon stabilization of HIF-1α by hypoxia or cobalt chloride under normoxic conditions and suppressed by dominantnegative HIF-1α. Whereas PTGES messenger RNA (mRNA) was negatively regulated by normoxia, PTGES protein remained stable upon reoxygenation. Prostaglandin E2 (PGE2) biosynthesis was documented in transformed human esophageal cells by ectopic expression of PTGES as well as RNA interference directed against PTGES. Moreover, hypoxia stimulated PGE2 production in a HIF-1α-dependent manner. In ESCC, PTGES was overexpressed frequently at the mRNA and protein levels. Finally, COX-2 and PTGES were colocalized in primary tumors along with HIF-1α and IGFBP3. Activation of the COX-2-PTGES axis in primary tumors was further corroborated by concomitant upregulation of interleukin-1β and downregulation of hydroxylprostaglandin dehydrogenase. Thus, PTGES is a novel HIF-1α target gene, involved in prostaglandin E biosynthesis in the esophageal tumor hypoxic microenvironment, and this has implications in diverse tumors types, especially of squamous origin. © The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org. Source

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