No description available.

Abdominal pain of non-visceral origin has been recognised as a clinical entity for many years. In many gastroenterology clinics up to 50 per cent of patients attending have no pathological cause to their symptoms and such patients often become chronic attenders and suffer repeated investigation without resolution of their problem. They are often left with a label' of Irritable Bowel Syndrome (lBS) without a precise diagnosis being made. This is both unsatisfactory for the patient and physician. This study set out to determine the incidence of musculoskeletal causes of abdominal pain and to determine what diagnostic tools will help identify this group of patients and thus allow the physicians to refer the appropriate patients at an early stage. The aims were to identify questions that act as predictors of the presence of abdominal pain of musculoskeletal origin, patterns of pain presented in this group of patients and the ability of physiotherapists to detect cases of abdominal pain of musculoskeletal origin. The incidence of abdominal pain of musculoskeletal origin in this study was 14 per cent. Questions that act as predictors include an affirmative response to pain being aggravated by movements such as bending, twisting and turning, and coughing and sneezing, and a negative response to change in bowel habit, symptoms being aggravated by food and no weight change. The ability of the physiotherapist to detect cases was 88.3 per cent. No particular pattern of pain areas emerged to differentiate patients with abdominal pain of visceral and musculoskeletal causes. Early assessment of the musculoskeletal system by a trained physiotherapist is recommended. An early referral will lead to prompt and appropriate treatment and, consequently, to a reduction in costs for the NHS. For patients where the cause of their abdominal pain is not obvious it is unacceptable that they are left with the diagnosis of IBS without the musculoskeletal system being assessed. This study shows that such an assessment is vital to detect cases where the pain has a musculoskeletal origin.

INTRODUCTION: Reactive oxygen species are responsible for the mediation of physiologic and pathologic cellular responses. The tissue damage occurring in all inflammatory disorders, including that observed in patients with inflammatory bowel disease (IBD), is mediated by reactive oxygen species (ROS) generated and released by activated immunocompetent cells. When present in sufficient concentration, these oxidative ROS are toxic to both real or perceived infectious or allergic threats, as well as native tissues in the context of autoimmune disease. The diagnosis and interval assessment of patients with IBD currently rely on expensive and invasive procedures that create cost and logistic drawbacks for both patients and the larger health care system. Thus, there is a pressing need for the development of reliable, cost-effective, and noninvasive methods to better diagnose and manage patients with IBD. OBJECTIVES: The goal of this present study was to assess the relationship between disease activity and ambient oxidative state in the stool of patients with and without IBD. METHODS: Patients admitted to Boston Children’s Hospital (Boston, MA) were recruited and consented for participation in the study. Stool samples were collected, and the redox potential (mV) was assessed using three different redox status measuring systems. The samples were collected between November 2018 and March 2020. RESULTS: Data demonstrated that reliable measurements could be made of redox status in stool samples collected from patients with and without IBD. Data collected from patients with IBD displayed an inverse correlation between relative redox status and disease activity. CONCLUSION: The measurement of relative redox status in the stool of patients with and without IBD is a reliable tool for indicating clinical disease status. Furthermore, the initiation of an improved method for the collection and processing of stool samples from consented patients appears to increase study accrual and data collection. Data from this study can be used as the basis for future studies that assess the clinical impact of pharmacologic, lifestyle, and dietary approaches to managing fecal redox in patients with IBD.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States and the third most common cancer in men and women. Vitamin E is a lipid soluble antioxidant that exists as eight structurally different isoforms of tocopherols and tocotrienols. Recent experimental, and molecular studies suggest that γ-tocotrienol (GT3) may be a more potent cancer-preventive form of vitamin E. 15-lipoxygenase-1 (15-LOX-1) and its product 13-S-hydroxyoctadecadienoic acid (13-S-HODE) are decreased in colon cancer cells. 15 LOX-1 is considered a tumor suppressor gene in colon carcinogenesis. Non-steroidal anti-inflammatory drug (NSAID)-induced 15-LOX-1 expression is critical to aspirin and NSAID-induced apoptosis in colorectal cancer cells. HCT-116 is a microsatellite-instability (MSI) colon cancer cell line. MSI is a marker of chemo-resistance but is associated with improved survival as compared to microsatellite-stable (MSS) colon cancers. The effects of GT3 on cytotoxicity and 15 LOX-1 expression was studied on the human colon cancer cell line HCT-116. HCT-116 colon cancer cell lines were cultured in DMEM media and dosed with increasing concentrations of GT3 (20µM-50µM). Cytotoxicity of the drugs was studied using Cell Titer Glo and MTS assays 24 hours after dosing. Cells were then plated in 6-well plates and grown for 24 hours. Cells were then dosed with 2 mL of GT3 at 20 uM at the respective time periods (2h, 4h, 6h, 12h, 16h, 24h) and lysates were harvested. Gel electrophoresis was run according to BCA protein assay from the time-dependent lysates and blots were tagged with a rabbit 15-lox antibody. Ongoing experiments include RNA PCR. RNA is being isolated at 2, 4, 6 and 12 hours. The RNA as reversed transcribed using a 15 lox 1 primer and that cDNA is being quantified using Quantitative PCR. GT3 induced cytotoxicity in MTS assay and Cell Titer Glo assay when added to HCT-116 cell line. 15 LOX 1 protein expression was found to be up-regulated in the colon cancer cell line HCT-116 when GT3 was added at 12h, 16h and 24h with the maximum expression at 16 hours. Chemotherapeutic drugs can have significant side effects. Understanding the role of GT3 on colon cancer cell lines could lead to the development of novel drugs to supplement current chemotherapy regimens and allow for lower doses of chemotherapeutic agents. Modulation of 15-LOX-1 suggests that GT3 may induce apoptosis through induction of the lipoxygenase pathway. Further experiments are under way to study the mechanism of action of GT3 on the 15 LOX-1 pathway. Since HCT-116 is a MSI- colon cancer cell line, effects of GT3 on MSS- colon cancer cell lines will also be studied.

Stomal varices are a rare phenomenon that can infrequently develop in patients with enterostomies and portal hypertension. Acute gastrointestinal bleeding from stomal varices can be life threatening and is often a diagnostic challenge. We present a case of severe gastrointestinal hemorrhage from stomal varices requiring emergent intervention with transjugular intrahepatic portosystemic shunt (TIPS) and plug embolization. A 61 year old male patient with a history of colorectal adenocarcinoma status post chemotherapy, radiation, along with low anterior colon resection with ostomy creation presented with a one day history of sudden onset of bright red blood from his colostomy site. He had a known history of decompensated cirrhosis related to hepatitis C and alcohol abuse. On arrival, the patient was tachycardic with borderline low blood pressure with evidence of bright red bleeding from his ostomy site. After initial resuscitation, a colonoscopy through the stoma revealed active bleeding from what appeared to be submucosal colonic varices. The patient continued to experience large volumes of blood loss and became more hemodynamically unstable. Cross sectional imaging showed colonic varices being fed by a branch of the inferior mesenteric vein. The patient underwent TIPS followed by Amplatzer plug embolization of the branch of the interior mesenteric vein that was feeding the colonic stomal varices. The patient’s bleeding was stopped by the combination of these therapeutic modalities and he recovered without complication. The current standard of care for treatment of such varices is with either (1) local therapy with ligation or sclerotherapy, (2) surgical interventions such as stomal manipulation or vessel shunting, either transhepatic or portosystemic to reduce portal pressures, or (3) liver transplantation. Our patient required an unusual combination of TIPS and Amplatzer plug embolization to control his massive hemorrhage. This combination of therapies has been shown effective for the management of select cases of esophageal or gastric variceal bleeding; however, our case demonstrates that the application of the TIPS plus Amplatzer plug embolization can be applied more broadly to the rare scenario of colonic stomal varices.

Gastroparesis (GP) is a clinical disorder recognized by measured delayed gastric emptying without mechanical obstruction, in addition to symptoms such as nausea, vomiting, chronic abdominal pain, heartburn, early satiety upon eating a regular-sized meal, and exaggerated postprandial fullness. While GP is considered a clinically rare disorder, there is much suspicion that a much larger number of patients experience GP-like symptoms without an official diagnosis. Furthermore, little work has been done to identify the causes and exacerbations of this gastrointestinal (GI) distress in the young adult population. This study's primary goal was to establish a relationship between modifiable and non-modifiable risk factors and overall GI distress at a large university campus. Utilizing an anonymous online-based survey, risk factors (Physical, psychological, and behavioral), participant demographics, levels of perceived stress, and GI symptoms were measured from 232 participants used in our analysis. Data analysis showed several significant correlations with higher GI distress: 1) being a graduate student, 2) having a higher heart rate, 3) participating in binge drinking, and 4) having higher perceived stress levels. This study is one of the first to assess multifactorial risk factors and find significant relationships within the young adult population. These results suggest that students experiencing higher levels of perceived stress may be suffering from more debilitating GI symptoms, which supports further research into methods for mediating stress amongst the student population.

No description available.

Background and aims: This interdisciplinary thesis was designed to deepen understanding of the co-morbidity of anxiety and depression with chronic diseases of the digestive tract, and inflammatory bowel disease (IBD) in particular. The first part of the thesis aimed to explore the prevalence of psychological problems in IBD compared to irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) groups. It also explored the relationship between the number of co-morbid functional gastrointestinal disorders and the severity of psychological problems in IBD and IBS. It also aimed to determine whether there is a relationship between psychological problems and the response to standard medical treatment/physical outcomes in patients with IBD, IBS and HCV. Furthermore, it aimed to explore whether disclosure of the psychological status of depressed and/or anxious IBD patients to their gastroenterologists influences doctors’ behaviour and affects patients’ responses to treatment/physical outcomes. The second part of the thesis aimed to investigate the potential role of antidepressants in IBD and to determine the feasibility of future randomised controlled trials on the role of antidepressants in IBD. Methods: Overall, a cohort of 139 outpatients (64 IBD, 41 HCV, and 34 IBS) and 18 gastroenterologists participated in the six studies comprising this thesis. A mixed methods design was applied. Two cross-sectional studies, an observational cohort prospective management study, a randomised controlled trial, a systematic review and an exploratory interview study were conducted. Differences between the groups for continuous variables were assesed with one way analysis of variance (ANOVA) and independent samples ttests. Differences in categorical variables were assessed with contingency tables with the Chi-Square test and the Fisher’s Exact Test. Propsective analyses were conducted with repeated measures ANOVA, logistic regression and Poisson regression. Qualitative data were analysed using content analysis. Results: Overall, 42% of participants were anxious and 19% were depressed. Participants with HCV had higher levels of psychological impairment compared with the IBS, the IBD group and the general population (p<0.05). Those IBD participants with fewer co-morbid functional disorders had better physical quality of life than participants with a greater number of these disorders (p=0.025). Moreover, depression/anxiety at baseline did not explain medical outcomes after 12 months in this cohort of patients with chronic diseases of the digestive tract. Doctors’ knowledge of patients’ psychological status was found to have no impact on IBD patients’ outcomes after 12 months. However, interestingly, the level of anxiety in IBD participants significantly dropped between the baseline and nine months indicating a possible benefit from participating in the study. In the literature review, insufficient evidence was found to conclude that antidepressants are efficacious for treatment of psychological co-morbidities or somatic complaints in IBD. However, the qualitative interview study indicated a potential positive impact of treatment with antidepressants on coping with disease symptoms and general wellbeing in patients with IBD. Conclusion: The thesis confirms that there is a significant burden of psychological co-morbidity in patients with chronic gastroenterological diseases. Interdisciplinary approaches to the management of these diseases are therefore warranted in Australian gastroenterology clinics. Anxiety targeted interventions and research in this setting are urgently needed, especially with respect to patients with HCV. Larger studies exploring the gastroenterologists’ role in treatment of co-morbid psychological problems in their patients are recommended. Longer prospective studies on homogenous samples of patients are also needed to clarify the nature of the relationship between psychological problems and relapse of somatic symptoms. Finally, randomised controlled trials exploring the efficacy of antidepressants in IBD are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1321006 / Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2008

Background and aims: This interdisciplinary thesis was designed to deepen understanding of the co-morbidity of anxiety and depression with chronic diseases of the digestive tract, and inflammatory bowel disease (IBD) in particular. The first part of the thesis aimed to explore the prevalence of psychological problems in IBD compared to irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) groups. It also explored the relationship between the number of co-morbid functional gastrointestinal disorders and the severity of psychological problems in IBD and IBS. It also aimed to determine whether there is a relationship between psychological problems and the response to standard medical treatment/physical outcomes in patients with IBD, IBS and HCV. Furthermore, it aimed to explore whether disclosure of the psychological status of depressed and/or anxious IBD patients to their gastroenterologists influences doctors’ behaviour and affects patients’ responses to treatment/physical outcomes. The second part of the thesis aimed to investigate the potential role of antidepressants in IBD and to determine the feasibility of future randomised controlled trials on the role of antidepressants in IBD. Methods: Overall, a cohort of 139 outpatients (64 IBD, 41 HCV, and 34 IBS) and 18 gastroenterologists participated in the six studies comprising this thesis. A mixed methods design was applied. Two cross-sectional studies, an observational cohort prospective management study, a randomised controlled trial, a systematic review and an exploratory interview study were conducted. Differences between the groups for continuous variables were assesed with one way analysis of variance (ANOVA) and independent samples ttests. Differences in categorical variables were assessed with contingency tables with the Chi-Square test and the Fisher’s Exact Test. Propsective analyses were conducted with repeated measures ANOVA, logistic regression and Poisson regression. Qualitative data were analysed using content analysis. Results: Overall, 42% of participants were anxious and 19% were depressed. Participants with HCV had higher levels of psychological impairment compared with the IBS, the IBD group and the general population (p<0.05). Those IBD participants with fewer co-morbid functional disorders had better physical quality of life than participants with a greater number of these disorders (p=0.025). Moreover, depression/anxiety at baseline did not explain medical outcomes after 12 months in this cohort of patients with chronic diseases of the digestive tract. Doctors’ knowledge of patients’ psychological status was found to have no impact on IBD patients’ outcomes after 12 months. However, interestingly, the level of anxiety in IBD participants significantly dropped between the baseline and nine months indicating a possible benefit from participating in the study. In the literature review, insufficient evidence was found to conclude that antidepressants are efficacious for treatment of psychological co-morbidities or somatic complaints in IBD. However, the qualitative interview study indicated a potential positive impact of treatment with antidepressants on coping with disease symptoms and general wellbeing in patients with IBD. Conclusion: The thesis confirms that there is a significant burden of psychological co-morbidity in patients with chronic gastroenterological diseases. Interdisciplinary approaches to the management of these diseases are therefore warranted in Australian gastroenterology clinics. Anxiety targeted interventions and research in this setting are urgently needed, especially with respect to patients with HCV. Larger studies exploring the gastroenterologists’ role in treatment of co-morbid psychological problems in their patients are recommended. Longer prospective studies on homogenous samples of patients are also needed to clarify the nature of the relationship between psychological problems and relapse of somatic symptoms. Finally, randomised controlled trials exploring the efficacy of antidepressants in IBD are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1321006 / Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2008

The cancer stem cell (CSC) model of carcinogenesis and progression posits that within a tumor lies a subpopulation of cells that solely possess the ability to initiate a tumor and to differentiate into tumor cell lineages. Although the behavior of such cells is known, the challenge is to identify factors that characterize the CSC subpopulation. In this thesis, cell lines were identified that, when grown in three-dimensions, gave rise to organized colonies containing lumens originating from differentiating cells (“lumen lines”) and to densely-packed, spherical colonies originating from non-differentiating cells (“dense lines”). A microarray comparison of the pair identified genes upregulated in dense lines, including CD55 and BMI1, and in lumen lines, including CDX1 (Chapter 3). CD55 was used to isolate CD55high CSCs via flow cytometry that are able to self-renew, differentiate, initiate more colonies, proliferate more rapidly and exhibit an increased G2/M cell cycle population as opposed to unfractionated cells. Furthermore, the CD55high cells were able to give rise to more differentiated, lumen colonies in vitro, indicating that CD55 enriches for cells possessing a capacity to differentiate, and were able to enrich the CD24highCD44high putative CSC population further (Chapter 4). CDNA induction of BMI1 and CDX1 expression led to increased clonogenicity/proliferation and decreased clonogenicity/proliferation, respectively, and incorporation of a CDX1 reporter construct into the SW1222 cell line identified CDX1+ cells as a low-expressing population of CD55 (Chapter 5). Finally, co-culture of cell lines in an in vivo-like environment with intestinal myofibroblasts promoted the CSC population by enhancing clonogenicity, proliferation and expression of CD55 (Chapter 6). The results of this thesis implicate CD55 as a potent marker of colorectal cancer stemness, link the expression of BMI1 and CDX1 to cancer stemness and differentiation, respectively, and identify a role for the in vivo stem cell niche in maintaining the CSC population.