Digestive System Diseases Commons^™

Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma

Electronic Thesis and Dissertation Repository

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development ...

Hepatic Changes Associated With Chronic Alcohol Exposure In An Alpha-1 Antitrypsin Piz Mouse Model, Zhuoyao Lyu, Alisha M. Gruntman, Brian O'Sullivan-Murphy, Christian Mueller, Terence R. Flotte

Christian Mueller

The PiZ mutation in the alpha-1 antitrypsin (AAT) gene causes the PiZ mutant protein to be sequestered in the endoplasmic reticulum of hepatocytes, causing significant liver pathology in ~10% of PiZZ homozygous AAT disease patients. Current transgenic mouse models of the disease include the liver-specific over-expression of mutant PiZ protein. However, these animal models do not efficiently recapitulate the liver damage found in PiZZ homozygous patients. Since only a small percentage of patients develop liver disease and it is not reproducible in animal models of AATD, it suggests that there are other factors that participate in disease pathogenesis. Here, we ...

The Circadian Clock Gene Bmal1 Coordinates Intestinal Regeneration, Kyle Stokes, Abrial Cooke, Hanna Chang, David R. Weaver, David T. Breault, Phillip Karpowicz

Neurobiology Publications and Presentations

BACKGROUND and AIMS: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied.

METHODS: We tested the timing of regeneration ...

Patient Safety During Procedural Sedation Using Capnography Monitoring: A Systematic Review And Meta-Analysis, Rhodri Saunders, Michel M.R.F. Struys, Richard F. Pollock, Michael Mestek, Jenifer R. Lightdale

Pediatric Publications and Presentations

OBJECTIVE: To evaluate the effect of capnography monitoring on sedation-related adverse events during procedural sedation and analgesia (PSA) administered for ambulatory surgery relative to visual assessment and pulse oximetry alone.

DESIGN AND SETTING: Systematic literature review and random effects meta-analysis of randomised controlled trials (RCTs) reporting sedation-related adverse event incidence when adding capnography to visual assessment and pulse oximetry in patients undergoing PSA during ambulatory surgery in the hospital setting. Searches for eligible studies published between 1 January 1995 and 31 December 2016 (inclusive) were conducted in PubMed, the Cochrane Library and EMBASE without any language constraints. Searches were conducted ...

The Intersection Of Diarrheal Disease And The Wash Sector: A Case Study Of The Betafo Area In The Vakinankaratra Region, Stephanie Hansen

Stephanie L. Hansen

Diarrheal disease is a leading cause of death in Madagascar, with the highest rates of morbidity and mortality in children under-five. Globally, it is the second leading cause of death of children under-five. The prevalence of diarrheal disease is a direct result of inadequate WASH infrastructure in Madagascar, where 48% of the population has no access to safe drinking water and 79% of the population has no access to improved sanitation (WaterAid, 2015). The inaccessibility of medical services in Madagascar is the largest impediment for diarrhea victims seeking treatment; a quarter of the Malagasy population lives 1 to 2 hours ...

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2 ...

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

University of Massachusetts Medical School Faculty Publications

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2 ...

The Clinical, Endoscopic And Histological Spectrum Of The Solitary Rectal Ulcer Syndrome: A Single-Center Experience Of 116 Cases, Shahab Abid, Ali Khawaja, Salima Ahmed Bhimani, Zubair Ahmad, Saeed Hamid, Wasim Jafri

Zubair Ahmad

Background Solitary rectal ulcer syndrome (SRUS) is an uncommon although benign defecation disorder. The aim of this study was to evaluate the variable endoscopic manifestations of SRUS and its association with other diseases. Methods All the patients diagnosed with SRUS histologically from January 1990 to February 2011 at The Aga Khan University, Karachi were included in the study. The medical records were reviewed retrospectively to evaluate the clinical spectrum of the patients along with the endoscopic and histological findings. Results A total of 116 patients were evaluated. The mean age was 37.4 ± 16.6 (range: 13–80) years, 61 ...

Gastric Juice For The Diagnosis Of H Pylori Infection In Patients On Proton Pump Inhibitors, Javed Yakoob, Shahid Rasool, Z Abbas, Wasim Jafri, Shahab Abid, Muhammad Islam, Zubair Ahmad

Zubair Ahmad

Aim:To determine the efficacy of gastric juice polymerase chain reaction (PCR) for the detection of H pylori infection in comparison with histology and gastric antral biopsy PCR in Patients on a proton pump inhibitor (PPI). Methods: Eighty-five consecutive Patients with dyspeptic symptoms were enrolled. Gastric biopsies for histology, PCR and gastric juice were collected at endoscopy for PCR of the H pylori urease C gene (ure C). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive and negative likelihood ratio for PCR of gastric juice for the H pylori ure C gene was compared to histology ...

Cytokine Changes In Colonic Mucosa Associated With Blastocystis Spp. Subtypes 1 And 3 In Diarrhoea-Predominant Irritable Bowel Syndrome, Javed Yakoob, Zaigham Abbas, Muhammad Waqas Usman, Aisha Sultana, Muhammad Islam, Safia Awan, Zubair Ahmad, Saeed Hamid, Wasim Jafri

Zubair Ahmad

We determined cytokines (e.g. interleukin-8, 10, 12 and TNF-α) expression by peripheral blood mononuclear cells (PBMCs) and in rectal mucosa in diarrhoea-predominant irritable bowel syndrome (D-IBS) with Blastocystis spp. Eighty patients with D-IBS and Blastocystis spp. infection were classified as 'cases' and 80 with D-IBS without Blastocystis spp. infection were classified as 'control'. Cases were subdivided into D-IBS and Blastocystis sp. defined type 1 (subtype-specific primer SB83) and type 3 (SB227). Stool microscopy and culture were performed. Rectal biopsies were obtained for histology and cytokines by real-time PCR for mRNA expression of cytokines. PBMCs IL-8 was similar in different ...

Low Rate Of Recurrence Of Helicobacter Pylori Infection In Spite Of High Clarithromycin Resistance In Pakistan, Javed Yakoob, Shahab Abid, Wasim Jafri, Zaigham Abbas, Khalid Mumtaz, Saeed Hamid, Rashida Ahmed

Rashida Ahmed

Background The aim was to investigate the reinfection rate of H. pylori during a follow-up period of 12 months in adults who had undergone eradication therapy. Methods One hundred-twenty patients; 116 with gastritis, 3 with duodenal ulcer and 1 gastric ulcer, were studied. Their mean age was 41 ± 13 years (range 18–77) and male: female ratio of 2:1. H. pylori were cultured and antibiotic sensitivity was determined by Epsilometer test (E-test) for clarithromycin (CLR) and amoxicillin (AMX). Primers of urease C gene of H. pylori and Sau-3 and Hha I restriction enzymes were used for polymerase chain reaction-restriction ...

Hepatic Changes Associated With Chronic Alcohol Exposure In An Alpha-1 Antitrypsin Piz Mouse Model, Zhuoyao Lyu, Alisha M. Gruntman, Brian O'Sullivan-Murphy, Christian Mueller, Terence R. Flotte

UMass Center for Clinical and Translational Science Research Retreat

The PiZ mutation in the alpha-1 antitrypsin (AAT) gene causes the PiZ mutant protein to be sequestered in the endoplasmic reticulum of hepatocytes, causing significant liver pathology in ~10% of PiZZ homozygous AAT disease patients. Current transgenic mouse models of the disease include the liver-specific over-expression of mutant PiZ protein. However, these animal models do not efficiently recapitulate the liver damage found in PiZZ homozygous patients. Since only a small percentage of patients develop liver disease and it is not reproducible in animal models of AATD, it suggests that there are other factors that participate in disease pathogenesis. Here, we ...

Frequent Cannabis Users Have Reduced Odds For Non Alcoholic Fatty Liver Disease, Adeyinka Adejumo, Nnaemeka Onyeakusi, Samson Alliu, Ogooluwa A. Ojelabi

UMass Center for Clinical and Translational Science Research Retreat

Background: Cannabis is the world's most widely used illicit drug. Though marijuana use has been revealed to impact the prevalence of diabetes, hypertension, and obesity - established risk factors for Non-Alcoholic Fatty Liver (NAFLD), it's relationship with NAFLD remains unknown.

Aim: We sought to investigate the association between cannabis use and NAFLD.

Methods: From the National Health and Nutrition Examination Survey (NHANES III, 1988–1994) survey data, we retrieved data from individuals aged 20 to 60 years who had an abdominal ultrasound for evaluation for hepatic steatosis (n=10,682). We then identified three cannabis use groups: never used ...

The Utilization Of Video Capsule Endoscopy In Patients With Peutz-Jeghers Syndrome, Yasir Al-Azzawai, Erik Holzwanger, David R. Cave

UMass Center for Clinical and Translational Science Research Retreat

AIM: Our aim is to demonstrate the utilization of VCE in the patients with Peutz–Jeghers syndrome (PJS) and evaluate the distribution of the polyps in each part of the small intestine and the percentage of patients with PJS who developed complications.

METHODS: Single center, retrospective chart review study of outpatients with PJS who underwent a video capsule endoscopy study between January 2006 and January2016.

RESULTS: A total of 16 patients were identified with PJS; mean age was 40 years. Female gender was predominant with 9 patients. Polyps were found in the duodenum, jejunum and ileum in 33%, 80% and ...

Utilizing Mucosal Protrusion Angles To Discriminate Between True And False Masses Of The Small Bowel On Video Capsule Endoscopy, Michael G. Noujaim, May Min, David R. Cave

UMass Center for Clinical and Translational Science Research Retreat

Background: Video capsule endoscopy (VCE) has significantly improved our ability to detect small bowel tumors. However, diagnosing small bowel tumors has remained a challenge due to their low incidence, nonspecific presentations, and the inability to use VCE to biopsy lesions identified during passage through the small bowel. To address this challenge, Girelli et al. developed a novel scoring system called the “smooth, protruding lesions index at capsule endoscopy” (SPICE) to distinguish true submucosal masses from innocent bulges¹. In our study, we compared the utility of an additional morphologic criterion, the mucosal protrusion angle, with SPICE scores in detecting true ...

Pleural Sepsis Associated With High Mortality In Orthotopic Liver Transplantation Recipients, Erik Holzwanger, Soumil Patwardhan, Sunkaru Touray, Daniel B. Knox

UMass Center for Clinical and Translational Science Research Retreat

Background: Orthotopic liver transplantation (OLT) is currently the only definitive treatment for patients with acute liver failure and end-stage liver cirrhosis. Pulmonary complications are a leading cause of post-operative morbidity and mortality. Post-transplant pleural effusions have been reported in the immediate post-operative period reported in about 32 – 47 % of effusion.

Methods: From a database of 1517 patients who presented at our medical center with pleural effusions from 2010 – 2015, we identified 21 patients who had liver transplants using ICD code 50.59. We performed chart reviews to assess the occurrence of the pleural effusion in relation to their liver transplant ...

Correlation Of Endoscopic Disease Severity With Pediatric Ulcerative Colitis Activity Index Score In Children And Young Adults With Ulcerative Colitis, Basavaraj Kerur, Heather J. Litman, Julia Bender Stern, Sarah Weber, Jenifer R. Lightdale, Paul A. Rufo, Athos Bousvaros

Pediatric Publications and Presentations

AIM: To investigate of pediatric ulcerative colitis activity index (PUCAI) in ulcerative colitis correlate with mucosal inflammation and endoscopic assessment of disease activity (Mayo endoscopic score).

METHODS: We reviewed charts from ulcerative colitis patients who had undergone both colonoscopy over 3 years. Clinical assessment of disease severity within 35 d (either before or after) the colonoscopy were included. Patients were excluded if they had significant therapeutic interventions (such as the start of corticosteroids or immunosuppressive agents) between the colonoscopy and the clinical assessment. Mayo endoscopic score of the rectum and sigmoid were done by two gastroenterologists. Inter-observer variability in Mayo ...

Cannabis Use Is Associated With Reduced Prevalence Of Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study, Adeyinka Adejumo, Samson Alliu, Tokunbo Opeyemi Ajayi, Kelechi Lauretta Adejumo, Oluwole Muyiwa Adegbala, Nnaemeka Egbuna Onyeakusi, Akintunde Micheal Akinjero, Modupeoluwa Durojaiye, Terence N. Bukong

Open Access Articles

Cannabis use is associated with reduced prevalence of obesity and diabetes mellitus (DM) in humans and mouse disease models. Obesity and DM are a well-established independent risk factor for non-alcoholic fatty liver disease (NAFLD), the most prevalent liver disease globally. The effects of cannabis use on NAFLD prevalence in humans remains ill-defined. Our objective is to determine the relationship between cannabis use and the prevalence of NAFLD in humans. We conducted a population-based case-control study of 5,950,391 patients using the 2014 Healthcare Cost and Utilization Project (HCUP), Nationwide Inpatient Survey (NIS) discharge records of patients 18 years and ...

Chagas, Enfermedad Olvidada: Una Perspectiva Histórica De La Prevención Y Control Del Chagas En La Provincia De Salta, Argentina (1909 – 2017) \ Chagas, A Forgotten Disease: A Historical Perspective On The Prevention And Control Of Chagas In Salta Province, Argentina (1909 – 2017), Tara Shea

Independent Study Project (ISP) Collection

El Chagas es una enfermedad vectorial más conocida en zonas rurales de América Latina y en Argentina es endémica en la región noroeste del país (MSAL, 2017). Designada una enfermedad tropical desatendida (Neglected Tropical Disease, NTD) por la OMS, la crónica del Chagas desde su “hallazgo casual” en 1909 siempre se trató de abandono (INP, 2017; MSF, 2012; OMS, 2017; Reyes López, 2009; Stamboulian, 2015; Zabala, 2009). En toda la Argentina se identifican 1.600.000 casos y 7.300.000 personas expuestas al Chagas, dando el país una de las tasas chagásicas más altas del mundo (Bär, 2015; MSAL ...

Alcohol-Related Changes In The Intestinal Microbiome Influence Neutrophil Infiltration, Inflammation And Steatosis In Early Alcoholic Hepatitis In Mice, Patrick Lowe, Benedek Gyongyosi, Abhishek Satishchandran, Arvin Iracheta-Vellve, Aditya Ambade, Karen Kodys, Donna Catalano, Doyle V. Ward, Gyongyi Szabo

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Alcohol-induced intestinal dysbiosis disrupts homeostatic gut-liver axis function and is essential in the development of alcoholic liver disease. Here, we investigate changes in enteric microbiome composition in a model of early alcoholic steatohepatitis and dissect the pathogenic role of intestinal microbes in alcohol-induced liver pathology.

MATERIALS AND METHODS: Wild type mice received a 10-day diet that was either 5% alcohol-containing or an isocaloric control diet plus a single binge. 16S rDNA sequencing defined the bacterial communities in the cecum of alcohol- and pair-fed animals. Some mice were treated with an antibiotic cocktail prior to and throughout alcohol feeding. Liver ...