No description available.

Vitamin D is important for bone development with immunomodulatory effects. This study investigated whether feeding CD-1 and interleukin 10 (IL-10) knockout (KO) dams low (25 IU/kg diet) or high (5,000 IU/kg diet) vitamin D affected bone health of dams as well as their offspring. Offspring were weaned to 1 of the 2 diets and followed to young adulthood. Unlike CD-1 dams, IL-10 KO dams experienced greater femur strength with high vitamin D. CD-1 male offspring had reduced femur neck strength and female offspring had smaller, weaker femurs, and weaker lumbar vertebra 2 (LV2) with high maternal vitamin D. IL-10 KO male offspring had larger femurs and female offspring had stronger femurs when weaned to high vitamin D. Low vitamin D did not adversely impact bone health but the optimal level of dietary vitamin D seems to differ between healthy and inflammatory states.

Vitamin D is important for bone development with immunomodulatory effects. This study investigated whether feeding CD-1 and interleukin 10 (IL-10) knockout (KO) dams low (25 IU/kg diet) or high (5,000 IU/kg diet) vitamin D affected bone health of dams as well as their offspring. Offspring were weaned to 1 of the 2 diets and followed to young adulthood. Unlike CD-1 dams, IL-10 KO dams experienced greater femur strength with high vitamin D. CD-1 male offspring had reduced femur neck strength and female offspring had smaller, weaker femurs, and weaker lumbar vertebra 2 (LV2) with high maternal vitamin D. IL-10 KO male offspring had larger femurs and female offspring had stronger femurs when weaned to high vitamin D. Low vitamin D did not adversely impact bone health but the optimal level of dietary vitamin D seems to differ between healthy and inflammatory states.

The purpose of this study was to investigate how children with Inflammatory Bowel Disease (IBD) and their families perceived their school experiences in Québec. IBD is one of many “invisible” chronic diseases. It is considered invisible because it occurs internally without significant observable external symptoms. However, children with IBD experience painful and fluctuating physical symptoms caused by intestinal inflammation, as well as the side effects from medications. As a result, they require special accommodations while they attend public or private school. The Québec Education Act (2010) stipulates that adequate services for a diverse student population must be provided. Consequently, the research sought to answer the following questions: What are the experiences of parents and children with IBD enrolled in general education classrooms? And, what are the experiences of their brother or sister? To research these questions, a case study method was used with five families. The two instruments used to collect the data were, (1) individual semi-structured interviews that followed a modified version of Seidman’s (2006) in-depth interviewing approach and (2) drawings of the family by siblings. The data were analyzed inductively. This study was the first to use a qualitative approach with multiple methods that were guided by Bronfenbrenner’s ecological systems theory (1979) and Turnbull and Turnbull’s family systems theory (2001). The findings revealed that, unlike many studies on families of children with special needs, these families with a child with IBD functioned relatively well. At the microsystem level, mothers assumed responsibility as the primary caregiver. Siblings experienced their own challenges, such as feelings of parental neglect. Nonetheless, they also maintained nurturing roles. Within the mesosystem level, the home and school relationship was impacted. Parents and children with IBD experienced school personnel who lacked awareness of IBD and provided insufficient classroom support, especially at public schools. Hence, parents-(predominantly mothers) played an integral role in advocating for necessary accommodations on their child’s behalf. In contrast to many studies on children with disabilities, children with IBD in this research had many friends in and outside of school. In the exosystem, parents struggled with feelings of guilt at having to balance employment and the high financial expense of caring for a child with IBD. They relied on assistance from government services and their IBD association. At the macrosystem level, family members believed that children with IBD were perceived negatively by society because of the lack of public awareness and the stigma that surrounds the topic of incontinence. This study makes contributions to systems theories and provides practical recommendations to school personnel and parents.

No description available.

Clostridium difficile colitis (CDC) is associated with a higher risk of acute death among hospitalized ulcerative colitis (UC) patients. However, the risk of colectomy with CDC in these patients has varied across studies. No study has assessed the long-term health impact of CDC in UC patients. Therefore, the present study evaluated the impact of CDC on five-year health outcomes of hospitalized UC patients based on Ontario health administrative data. No overall association was observed between CDC and five-year risks of colectomy or death in overall cohort. However, patients who were discharged from hospital without undergoing colectomy demonstrated marginally higher five-year risks of colectomy and hospital re-admission. Mortality risk and length of stay during index hospitalization were also higher in patients with CDC. Analysis of a parallel cohort of UC patients derived using a published case definition corroborated most of these results, but demonstrated a higher five-year mortality risk with CDC.

Clostridium difficile colitis (CDC) is associated with a higher risk of acute death among hospitalized ulcerative colitis (UC) patients. However, the risk of colectomy with CDC in these patients has varied across studies. No study has assessed the long-term health impact of CDC in UC patients. Therefore, the present study evaluated the impact of CDC on five-year health outcomes of hospitalized UC patients based on Ontario health administrative data. No overall association was observed between CDC and five-year risks of colectomy or death in overall cohort. However, patients who were discharged from hospital without undergoing colectomy demonstrated marginally higher five-year risks of colectomy and hospital re-admission. Mortality risk and length of stay during index hospitalization were also higher in patients with CDC. Analysis of a parallel cohort of UC patients derived using a published case definition corroborated most of these results, but demonstrated a higher five-year mortality risk with CDC.

Inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) and coeliac disease are debilitating gastrointestinal diseases that seriously affect the quality of life of those affected. Under normal circumstances, the intestinal immune system is maintained in a state of controlled inflammation, whereby balance exists between protective immunity, mediated by effector cells, and tolerance mediated by cells with regulatory function. However, an aberrant immune response is believed to contribute to the intestinal inflammation present in individuals afflicted by these diseases. This thesis investigated the involvement of CD4⁺ CD25[superscript]high Foxp3⁺ Regulatory T cells (Treg) and Th17 Effector cells in both inflammatory bowel disease (IBD) and coeliac disease. The reciprocal relationship between Treg and Th17 cells under certain cytokine conditions, has prompted the exploration of these two cell types in IBD and coeliac disease. Previous studies have examined these factors individually in a range of diseases, however, to our knowledge the study of both Treg and Th17 in IBD and coeliac disease subjects represents a novel area of research. Crohn’s disease (CD), ulcerative colitis (UC) and coeliac disease subjects were recruited through the Department of Gastroenterology and Hepatology at The Queen Elizabeth Hospital (QEH) in Adelaide, South Australia. In total, one-hundred and seventeen subjects were enlisted in this study to donate blood samples. In addtion, intestinal biopsy samples were collected from fifty-six subjects undergoing colonoscopy at the QEH Department of Gastroenterology and Hepatology. All subjects participated, with informed consent and ethics approval. Treg and Th17 cell numbers were investigated in the peripheral blood of Crohn’s disease, ulcerative colitis, coeliac disease and control subjects using multi-colour, intracellular flow cytometry. A decrease in Treg cell numbers and an increase in Th17 cell numbers was observed in IBD, but not in coeliac disease. Closer investigation into the ratio of Treg and Th17 cells within patients identified a near 1:1 Treg/Th17 ratio in control subjects, but a lower Treg/Th17 ratio in IBD patients. This suggested a disturbance in regulatory and effector cell equilibrium. Furthermore, the excess of Th17 cells and deficiency of Tregs could contribute to the pathologies observed in IBD. The discovery of an imbalance in Treg and Th17 cell numbers in IBD prompted further investigation of these cells in intestinal biopsies collected from IBD, coeliac and control subjects. Real time RT-PCR of intestinal biopsy samples demonstrated increased expression of the Th17 cytokine, IL-17a, in both IBD and coeliac disease. Elevated levels of the Treg transcription factor Foxp3 were also identified in intestinal biopsies from IBD subjects. It was therefore hypothesised that Treg cells may have been actively recruited from the periphery in an attempt to control inflammation in the gut; however, the intestinal cytokine microenvironment may have restricted the regulatory function of these cells. Cytokines known to promote human Th17 differentiation, namely IL-1β, IL-6, TGF-β, IL-21 and IL-23, were explored in intestinal biopsy samples from IBD, coeliac and control subjects. High levels of IL-1β and IL-6 were detected in IBD patient samples, however, no change in levels of IL-21 or IL-23 were observed in IBD or coeliac disease subjects. Elevated levels of TGF-β were only identified in UC. No changes in cytokine expression were observed between control and coeliac subjects, except a significant decrease in IL-6 levels was identified in coeliac disease sufferers. The pro-inflammatory microenvironment identified in intestinal biopsies from IBD subjects may have promoted the continual differentiation and development of Th17 cells, whilst restricting Treg activity. Moreover, the observed deficiency of Treg in IBD patients may have impaired the ability of the immune system to limit excessive pathogenic Th17 driven immune responses in the intestinal mucosa. Therefore, therapeutic approaches that aim to re-establish regulatory and effector cell homeostasis by increasing Treg numbers in IBD patients, and specifically targeting Th17 cells, may prove effective in the treatment of IBD. Approaches such as these could provide greater focus to treatment strategies for IBD management compared to current broad-spectrum immunosuppressive therapies that could increase susceptibility to cancer or infection in IBD patients. In addition, the imbalance of regulatory and effector cells demonstrated in the peripheral blood of IBD patients may potentially provide new options for a noninvasive diagnostic tool. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1457580 / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2009

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

Inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) and coeliac disease are debilitating gastrointestinal diseases that seriously affect the quality of life of those affected. Under normal circumstances, the intestinal immune system is maintained in a state of controlled inflammation, whereby balance exists between protective immunity, mediated by effector cells, and tolerance mediated by cells with regulatory function. However, an aberrant immune response is believed to contribute to the intestinal inflammation present in individuals afflicted by these diseases. This thesis investigated the involvement of CD4⁺ CD25[superscript]high Foxp3⁺ Regulatory T cells (Treg) and Th17 Effector cells in both inflammatory bowel disease (IBD) and coeliac disease. The reciprocal relationship between Treg and Th17 cells under certain cytokine conditions, has prompted the exploration of these two cell types in IBD and coeliac disease. Previous studies have examined these factors individually in a range of diseases, however, to our knowledge the study of both Treg and Th17 in IBD and coeliac disease subjects represents a novel area of research. Crohn’s disease (CD), ulcerative colitis (UC) and coeliac disease subjects were recruited through the Department of Gastroenterology and Hepatology at The Queen Elizabeth Hospital (QEH) in Adelaide, South Australia. In total, one-hundred and seventeen subjects were enlisted in this study to donate blood samples. In addtion, intestinal biopsy samples were collected from fifty-six subjects undergoing colonoscopy at the QEH Department of Gastroenterology and Hepatology. All subjects participated, with informed consent and ethics approval. Treg and Th17 cell numbers were investigated in the peripheral blood of Crohn’s disease, ulcerative colitis, coeliac disease and control subjects using multi-colour, intracellular flow cytometry. A decrease in Treg cell numbers and an increase in Th17 cell numbers was observed in IBD, but not in coeliac disease. Closer investigation into the ratio of Treg and Th17 cells within patients identified a near 1:1 Treg/Th17 ratio in control subjects, but a lower Treg/Th17 ratio in IBD patients. This suggested a disturbance in regulatory and effector cell equilibrium. Furthermore, the excess of Th17 cells and deficiency of Tregs could contribute to the pathologies observed in IBD. The discovery of an imbalance in Treg and Th17 cell numbers in IBD prompted further investigation of these cells in intestinal biopsies collected from IBD, coeliac and control subjects. Real time RT-PCR of intestinal biopsy samples demonstrated increased expression of the Th17 cytokine, IL-17a, in both IBD and coeliac disease. Elevated levels of the Treg transcription factor Foxp3 were also identified in intestinal biopsies from IBD subjects. It was therefore hypothesised that Treg cells may have been actively recruited from the periphery in an attempt to control inflammation in the gut; however, the intestinal cytokine microenvironment may have restricted the regulatory function of these cells. Cytokines known to promote human Th17 differentiation, namely IL-1β, IL-6, TGF-β, IL-21 and IL-23, were explored in intestinal biopsy samples from IBD, coeliac and control subjects. High levels of IL-1β and IL-6 were detected in IBD patient samples, however, no change in levels of IL-21 or IL-23 were observed in IBD or coeliac disease subjects. Elevated levels of TGF-β were only identified in UC. No changes in cytokine expression were observed between control and coeliac subjects, except a significant decrease in IL-6 levels was identified in coeliac disease sufferers. The pro-inflammatory microenvironment identified in intestinal biopsies from IBD subjects may have promoted the continual differentiation and development of Th17 cells, whilst restricting Treg activity. Moreover, the observed deficiency of Treg in IBD patients may have impaired the ability of the immune system to limit excessive pathogenic Th17 driven immune responses in the intestinal mucosa. Therefore, therapeutic approaches that aim to re-establish regulatory and effector cell homeostasis by increasing Treg numbers in IBD patients, and specifically targeting Th17 cells, may prove effective in the treatment of IBD. Approaches such as these could provide greater focus to treatment strategies for IBD management compared to current broad-spectrum immunosuppressive therapies that could increase susceptibility to cancer or infection in IBD patients. In addition, the imbalance of regulatory and effector cells demonstrated in the peripheral blood of IBD patients may potentially provide new options for a noninvasive diagnostic tool. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1457580 / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2009