Digestive System Diseases Commons^™

Frequency Of Poor Quality Of Life And Predictors Of Health Related Quality Of Life In Cirrhosis At A Tertiary Care Hospital Pakistan, Om Parkash, Romaina Iqbal, Fatima Jafri, Iqbal Azam, Wasim Jafri

Section of Gastroenterology

Background

Cirrhosis produces variety of symptoms which eventually lead to a negative impact on Health Related Quality of Life (HRQOL). The general aim of this study was to evaluate the magnitude of poor HRQOL and to assess factors related with HRQOL in patients with CLD in Pakistan.

Findings

This was a cross sectional study conducted in gastroenterology outpatient clinics of Aga Khan University Hospital, Karachi on adult patients with cirrhosis. In this study chronic liver disease questionnaire (CLDQ) was used to assess HRQOL of these patients and CLDQ score was used as an outcome measure to determine factors related with …

Serum Microrna-122 And Mir-155 As Biomarkers Of Liver Injury And Inflammation In Models Of Acute And Chronic Liver Disease, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Jeanine Ward, Ivan Levin, Hawau Alao, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Background: MicroRNAs (miRs) are small non-coding molecules that regulate gene expression. MiRs expression levels change not only in diseased tissues but also in circulation. Further, miRs are stable in frozen samples that make them attractive for biomarker discovery. Recent reports suggest altered expression of circulating miRNAs in various diseases. MiR-122 is highly abundant in hepatocytes where it regulates different metabolic pathways while miR-155 is a central regulator of inflammation. The aim of this study was to evaluate circulating miRNAs as potential markers of hepatocyte damage and inflammation in liver diseases. Methods: Serum/plasma and liver samples were collected from C57/BL6 mice …

A Prospective Study Of The Rate Of Progression In Compensated, Histologically Advanced Chronic Hepatitis C, Jules Dienstag, Marc Ghany, Timothy Morgan, Adrian Di Bisceglie, Herbert Bonkovsky, Hae-Young Kim, Leonard Seeff, Gyongyi Szabo, Elizabeth Wright, Richard Sterling, Gregory Everson, Karen Lindsay, William Lee, Anna Lok, Chihiro Morishima, Anne Stoddard, James Everhart

Gyongyi Szabo

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes …

Increased Oxidative Capacity Of Circulating Polymorphonuclear Neutrophils (Pmns) In Non-Diabetic Nash Patients, Timea Csak, Karen Kodys, Angela Dolganiuc, Dora Lippai, Michal Ganz, Christopher Marshall, Gyongyi Szabo

Gyongyi Szabo

Background: Inflammation and oxidative stress are key factors in the pathogenesis of non-alcoholic steatohepatitis (NASH). Polymorphonuclear neutrophils are capable to produce significant amounts of reactive oxygen species (ROS) via the NADPH oxidase complex. Increased hepatic neutrophil infiltration has been described in steatohepatitis. We aimed to investigate the in vitro ROS generation by neutrophils of NASH patients and the hepatic NADPH oxidase activity in murine steatohepatitis. Material and methods: PMNs were isolated from peripheral blood of NASH patients (n=16) and healthy controls (n=16). In vitro ROS production was measured by luminol chemiluminescence after phorbol myristate acetate (PMA) or opsonized zymosan stimulation. …

Caspase-1-Dependent, Il-1ss-Mediated Alcoholic Steatohepatitis Is Ameliorated By Il-1 Receptor Antagonist Treatment In Mice, Jan Petrasek, Shashi Bala, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of pro-inflammatory cytokines, including interleukin (IL)-1β. IL-1β, Type-I IL-1 receptor (IL1R1) and IL-1 receptor antagonist (IL-1Ra) are all part of the IL-1 superfamily that play a role in inflammation. IL-1β maturation is dependent on Caspase-1. Using wild-type (WT), Caspase-1-, IL-1R1- and IL-1Ra deficient mice fed with Lieber-DeCarli alcohol or control diet, we have identified that signaling mediated by the active IL-1β was required for development of alcohol-induced steatosis, inflammation and injury. Increased IL-1β was due to upregulation of Caspase-1 activity and inflammatory activation. The pathogenic role of IL-1 signaling in …

Cd81/Cd9 Tetraspanins Aid Plasmacytoid Dendritic Cells In Recognition Of Hcv-Infected Cells And Induction Of Ifnα, Shuye Zhang, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between pDCs and HCV-infected cells was required for IFNα induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNα production. Depletion of pDCs from PBMCs attenuated IFNα release and purified pDCs produced high levels of IFNα after co-culture with FL replicons or JFH-1 infected cells. IFNα …

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

Section of Gastroenterology

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 (53%) of …

Virulence Markers Of Helicobacter Pylori In Patients With Diarrhoea-Dominant Irritable Bowel Syndrome., Javed Yakoob, Zaigham Abbas, S. Naz, M. Islam, Waseem Jafri

Department of Medicine

Recent studies suggest that irritable bowel syndrome (IBS) is associated with low-grade inflammation. This study aims to determine the distribution of Helicobacter pylori cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) alleles (e.g., s1 and s2) in Patients with diarrhoea-dominant IBS (IBS-D) as the latter causes vacuolation in colonic epithelial cells in vitro. One hundred and seventy Patients meeting Rome III criteria for IBS-D (mean age: 40 +/- 15 years) were enrolled. Gastric biopsy was assessed histologically and DNA extraction was performed by polymerase chain reaction (PCR) for H. pylori genus 16S ribosomal DNA (16S rDNA), cagA and vacA …

Studying The Pathogenesis Of Ulcerative Colitis Under The Influence Of Plumbagin, Justin E. Pile

Mahurin Honors College & Office of Scholar Development

Ulcerative colitis (UC) is a chronic disease in humans that causes inflammation and ulceration of the inner lining of the colon and rectum. Approximately 5% of these patients develop colon cancer in the long term. Lack of effective treatments for patients with ulcerative colitis necessitates a search for the development of an effective alternative therapy. In an acute model, UC was induced in five groups (each of 5 replicates) of 10-week-old female C57BL/6 mice by DSS administration for 7 days. Plumbagin (PL) was administered via drinking water to four diseased groups @ 2-10 mg/Kg (body weight) for another 7 days. …

Relationship Between Vitamin B12, Folate And Homocysteine Levels And H. Pylori Infection In Patients With Functional Dyspepsia: A Cross-Section Study, Shahid Rasool, Shahab Abid, Mohammad Perwaiz Iqbal, Naseema Mehboobali, Ghulam Haider, Wasim Jafri

Section of Gastroenterology

Background

H. pylori infection has been associated with many micronutrient deficiencies. There is a dearth of data from communities with nutritional deficiencies and high prevalence of H. pylori infection. The aim of this study was to determine the impact of H. pylori infection on serum levels of vitamin B₁₂, folate and homocysteine in patients with functional dyspepsia (FD).

Methods

One hundred and thirty-two patients with FD undergoing gastroscopy were enrolled. The serum was analyzed for B₁₂, folate and homocysteine levels before gastroscopy. H. pylori infection was diagnosed by histopathological examination of gastric biopsies and urea breath …

N-Glycosylation Augmentation Of The Cystic Fibrosis Epithelium Improves Pseudomonas Aeruginosa Clearance, Ashley Martino, Christian Mueller, Sofia Braag, Pedro Cruz, Martha Campbell-Thompson, Shouguang Jin, Terence Flotte

Christian Mueller

Chronic lung colonization with Pseudomonas aeruginosa is anticipated in cystic fibrosis (CF). Abnormal terminal glycosylation has been implicated as a candidate for this condition. We previously reported a down-regulation of mannose-6-phosphate isomerase (MPI) for core N-glycan production in the CFTR-defective human cell line (IB3). We found a 40% decrease in N-glycosylation of IB3 cells compared with CFTR-corrected human cell line (S9), along with a threefold-lower surface attachment of P. aeruginosa strain, PAO1. There was a twofold increase in intracellular bacteria in S9 cells compared with IB3 cells. After a 4-hour clearance period, intracellular bacteria in IB3 cells increased twofold. Comparatively, …

Sustained Mirna-Mediated Knockdown Of Mutant Aat With Simultaneous Augmentation Of Wild-Type Aat Has Minimal Effect On Global Liver Mirna Profiles, Christian Mueller, Qiushi Tang, Alisha Gruntman, Keith S. Blomenkamp, Jeffrey H. Teckman, Lina Song, Phillip D. Zamore, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin (AAT) deficiency can exhibit two pathologic states: a lung disease that is primarily due to the loss of AAT's antiprotease function, and a liver disease resulting from a toxic gain-of-function of the PiZ-AAT (Z-AAT) mutant protein. We have developed several recombinant adeno-associated virus (rAAV) vectors that incorporate microRNA (miRNA) sequences targeting the AAT gene while also driving the expression of miRNA-resistant wild-type AAT-PiM (M-AAT) gene, thus achieving concomitant Z-AAT knockdown in the liver and increased expression of M-AAT. Transgenic mice expressing the human PiZ allele treated with dual-function rAAV9 vectors showed that serum PiZ was stably and persistently …

It Is Time To Talk About It: Designing A Health Communication Program For Eating Disorder Recovery In An Appalachian University, Erica Lynn Clites

Theses, Dissertations and Capstones

The purpose of this thesis was to evaluate the treatments used in current eating disorder programs and to develop a more effective model using two relevant communication theories: the Transtheoretical Model of Change and Social Networking Theory. Further, the thesis explored the need for greater mental health literacy on Appalachian college and university campuses as it relates to the three major eating disorders defined by the DSMIV-TR: anorexia nervosa, bulimia nervosa, and binge eating disorders. The analysis of current treatment revealed an overemphasis on physical health and quantitative medical progress. Applying both the Transtheoretical Model of Change and Social Networking …

Correlates Of Morbidity And Mortality In Severe Necrotizing Pancreatitis, K. M. Pal, Pashtoon Murtaza Kasi, Mohammad Tayyeb, S. M. Faisal Mosharraf, Zafar Fatmi

Community Health Sciences

Acute severe pancreatitis is associated with a high morbidity and mortality and frequently is accompanied by underlying pancreatic parenchymal necrosis. Patients with pancreatic necrosis must be identified, because the morbidity and mortality rate in this subgroup is much higher. Our objective was to compare the clinical outcomes of these patients based on the degree of pancreatic necrosis. A total of 35 patients were noted to have pancreatic necrosis. These were divided into 2 groups based on extent of necrosis: group A had less than 50% necrosis and group B had more than 50% necrosis. The rate of mortality (5% versus …

Small Intestinal Bacterial Overgrowth And Lactose Intolerance Contribute To Irritable Bowel Syndrome Symptomatology In Pakistan, Javed Yakoob, Zaigham Abbas, Rustam Khan, Saeed Hamid, Safia Awan, Wasim Jafri

Department of Medicine

Background /Aim: The symptoms of irritable bowel syndrome resemble those of small intestinal bacterial overgrowth (SIBO). The aim of this study was to determine the frequency of SIBO and lactose intolerance (LI) occurrence in Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) according to Rome III criteria.

PatientS and Methods: In this retrospective case-control study, Patients over 18 years of age with altered bowel habit, bloating, and Patients who had lactose Hydrogen breath test (H 2 BT) done were included. The "cases" were defined as Patients who fulfill Rome III criteria for IBS-D, while "controls" were those having chronic nonspecific diarrhea …

Mast Cell Activation And Clinical Outcome In Pediatric Cholelithiasis And Biliary Dyskinesia., Craig A. Friesen, Nancy Neilan, James F. Daniel, Kim Radford, Jennifer Verrill Schurman, Ding-You Li, Linda Andre, Shawn D. St Peter, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The current study was undertaken to determine the degree of activation of gallbladder mucosal mast cells, whether mast cell (MC) density or activation differ between patients with and without a positive clinical response to cholecystectomy, and whether either density or activation correlate with gallbladder emptying.

RESULTS: Fifteen biliary dyskinesia (BD) and 13 symptomatic cholelithiasis (CL) patients undergoing cholecystectomy were prospectively enrolled. Gallbladder wall MC density (by immunohistochemistry) and activation (by electron microscopy) were determined. Clinical response was evaluated 30 days post-cholecystectomy on a 5-point Likert-type scale. A complete or nearly complete clinical response was seen in 100% of CL …

T-Tube Management Of Late Esophageal Perforation, Irfan Qadir, Hasnain Zafar, Mubashir Zareen Khan, Hasanat Mohammad Sharif

Section of General Surgery

Esophageal perforation is a serious condition with a high mortality rate. Management strategy of such a patient depends on the extent of perforation and the time interval between perforation and diagnosis. The use of a T tube to treat delayed esophageal perforation with complete resolution and no need for future definitive surgery has been less frequently described. We adapted this principle in successful management of a 73 year old patient with four days history of fever, shortness of breath, chest pain and radiological evidence of perforation.

Helicobacter Pylori: Association With Gall Bladder Disorders In Pakistan, Javed Yakoob, M. R. Khan, Z. Abbas, W. Jafri, R. Azmi, Z. Ahmad, S. Naeem, L. Lubbad

Department of Medicine

Helicobacter species colonise the biliary tract and therefore this study explores the relationship between of Helicobacter pylori and cholecystitis. Bile and gall bladder tissue samples were obtained from 144 Patients who underwent cholecystectomy. Of these, 89 had chronic cholecystitis with cholelithiasis, 44 had gall bladder carcinoma and 11 had gall bladder polyps. Histopathology examination included special staining and immunohistochemistry (IHC), while Helicobacter species (H. pylori, H. bilis and H. hepaticus) were detected by the polymerase chain reaction (PCR). Sequencing and BLAST query of PCR products was undertaken and samples were considered to contain H. pylori if both PCR and IHC …

The Role Of Granulocyte Colony-Stimulating Factor In The Intestinal Immune System And The Response To Probiotics, Andrew J. Martins

Electronic Thesis and Dissertation Repository

Loss of immunoregulation in the intestine results in inflammation, such as is observed in the chronic, relapsing, inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. However, our understanding of this process remains incomplete. The cytokine granulocyte-colony stimulating factor (G-CSF) is an important stimulator of granulopoiesis in steady-state and during inflammation, but has also been shown to have anti-inflammatory effects and is a potential therapeutic for IBD. In addition, certain strains of bacteria, termed probiotics, have been postulated to have anti-inflammatory effects in the intestine. The mechanisms by which these strains of bacteria elicit anti-inflammatory effects are not fully understood. …

Gastroesophageal Reflux Disease: An Overview, Mayer Eckstein

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt of the introduction of this article: There are many well-known disorders associated with the digestion process, the most common of which is gastroesophageal reflux disease, more commonly known as GERD. There are six major factors that are the primary cause for GERD: impaired esophageal motility, defective mucosal defense, lower esophageal sphincter (LES) dysfunction, reflux of gastric contents, delayed gastric emptying, and hiatal hernia (DeVault and Castell 1999). Impaired esophageal motility occurs when the esophagus has trouble moving the food down and normal peristalsis does not occur. Defective mucosal defense can cause irritation to the esophagus, …