M.A. / The purpose of this study was to ascertain whether patients suffering from irritable bowel syndrome (IBS) differed from non-IBS clients in terms of their coping styles. Gastrointestinal disorders are among the most common of all illnesses; half of the population suffers from acute gastrointestinal illnesses every year (Read, 1985). More than 10% have chronic illnesses, and these illnesses are a major cause of absenteeism from work. In view of this it is surprising that there is such a faucity of psychological and psychophysiological research focusing on gastrointestinal activity. Perhaps one reason for this is that investigators conceptualise the gastrointestinal tract as a system that is unresponsive to psychological intervention. Another reason may be the widespread belief that adequate techniques are not available for studying gastrointestinal psychology and psychophysiology (Haynes & Gannon, 1981). Today there is consensus that IBS is a psychosomatic disorder that accounts for between 40 to 70% of referrals to gastroenterologists. Unfortunately, this is a very misunderstood disorder. Sufferers are often misinformed or poorly educated by their physicians. Misunderstanding and lack of patient education often results in increased anxiety and physical distress. There are cases in which unnecessary surgery, expensive diagnostic procedures and addictive pain killers are mistakenly employed. In addition, IBS patients represent an expensive group because they use up a considerable amount of medical resources in money and time (Moser, 1986).

Doctor of Philosophy / Nineteenth century philosophy and anatomy regarded the nervous system as the only pathway of communication between the brain and body but now, research in the field of psychoneuroimmunology (PNI) has provided evidence to prove the age-old belief that there is a connection between the mind (or mental/emotional states) and the body. Researchers in PNI have now shown that the communication between the nervous and immune systems is bi-directional – i.e. there is a psychological reaction to physical disease and a somatic presentation of psychological disorders - and that the immune system, the autonomic nervous system, the endocrine system and the neuropeptide systems all communicate with each other by means of chemicals called messenger molecules or ligands. This paper outlines research into the treatment of Irritable Bowel Syndrome (IBS) with hypnotherapy, taking into account the mind-body connection and treating both the patient’s physiological and emotional/psychological symptoms rather than treating the physiological symptoms only. In other words, using a more holistic approach to the treatment of IBS. IBS is probably the most common functional gastrointestinal disorder encountered by both gastroenterologists and physicians in primary care. It is estimated that from 10% to 25% of the general population suffer from this condition and that it comprises about 30-50% of the gastroenterologists’ workload, yet the aetiology of IBS is unknown and, so far, there is no cure. Researchers are beginning to view IBS as a multi-faceted disorder in which there appears to be a disturbance in the interaction between the intestines, brain, and autonomic nervous system, resulting in an alteration in the regulation of bowel motility and/or sensory function. Most researchers agree that a subset of IBS sufferers have a visceral hypersensitivity of the gut or, more specifically, an increased perception of sensations in the gut. To date, studies of IBS have proposed previous gastroenteritis, small intestine bacterial overgrowth, psychosocial factors, a genetic contribution, and an imbalance of neurotransmitters as either possible causes or playing a part in the development of IBS. It is generally agreed that a patient’s emotional response to stress can exacerbate the condition. In section 1 of the thesis, the introduction, a detailed description and background appropriate to the study undertaken are provided, including aspects of epidemiology, diagnostic symptom criteria and clinical relevance of the Irritable Bowel Syndrome. Previous studies of various forms of treatment for IBS are discussed with the main emphasis being on treatment with hypnotherapy. All these therapies have concentrated on either mind or body treatments whereas this study demonstrates how hypnotherapy, and the use of imagery, addresses both mind and body. Finally, the rationale for the current study and the specific aims of the thesis are outlined. In section 2, the methodology and assessment instruments used in the clinical trial are discussed, as well as recruitment processes, research plan and timetable, and treatment schedule. Statistical analyses are provided and the main outcomes measures of the clinical trial, its limitations and scientific implications are addressed.

Doctor of Philosophy / Nineteenth century philosophy and anatomy regarded the nervous system as the only pathway of communication between the brain and body but now, research in the field of psychoneuroimmunology (PNI) has provided evidence to prove the age-old belief that there is a connection between the mind (or mental/emotional states) and the body. Researchers in PNI have now shown that the communication between the nervous and immune systems is bi-directional – i.e. there is a psychological reaction to physical disease and a somatic presentation of psychological disorders - and that the immune system, the autonomic nervous system, the endocrine system and the neuropeptide systems all communicate with each other by means of chemicals called messenger molecules or ligands. This paper outlines research into the treatment of Irritable Bowel Syndrome (IBS) with hypnotherapy, taking into account the mind-body connection and treating both the patient’s physiological and emotional/psychological symptoms rather than treating the physiological symptoms only. In other words, using a more holistic approach to the treatment of IBS. IBS is probably the most common functional gastrointestinal disorder encountered by both gastroenterologists and physicians in primary care. It is estimated that from 10% to 25% of the general population suffer from this condition and that it comprises about 30-50% of the gastroenterologists’ workload, yet the aetiology of IBS is unknown and, so far, there is no cure. Researchers are beginning to view IBS as a multi-faceted disorder in which there appears to be a disturbance in the interaction between the intestines, brain, and autonomic nervous system, resulting in an alteration in the regulation of bowel motility and/or sensory function. Most researchers agree that a subset of IBS sufferers have a visceral hypersensitivity of the gut or, more specifically, an increased perception of sensations in the gut. To date, studies of IBS have proposed previous gastroenteritis, small intestine bacterial overgrowth, psychosocial factors, a genetic contribution, and an imbalance of neurotransmitters as either possible causes or playing a part in the development of IBS. It is generally agreed that a patient’s emotional response to stress can exacerbate the condition. In section 1 of the thesis, the introduction, a detailed description and background appropriate to the study undertaken are provided, including aspects of epidemiology, diagnostic symptom criteria and clinical relevance of the Irritable Bowel Syndrome. Previous studies of various forms of treatment for IBS are discussed with the main emphasis being on treatment with hypnotherapy. All these therapies have concentrated on either mind or body treatments whereas this study demonstrates how hypnotherapy, and the use of imagery, addresses both mind and body. Finally, the rationale for the current study and the specific aims of the thesis are outlined. In section 2, the methodology and assessment instruments used in the clinical trial are discussed, as well as recruitment processes, research plan and timetable, and treatment schedule. Statistical analyses are provided and the main outcomes measures of the clinical trial, its limitations and scientific implications are addressed.

[Truncated abstract] Clinical and pathological predictors of survival for stage II and III colon cancer patients treated with or without chemotherapy: a population-based study. Aim: Using a population-based cohort of colorectal cancer (CRC), the major aims of this study were to: 1. Identify clinico-pathological markers that can be used to define a subset of stage II colon cancer patients with excellent prognosis and who therefore do not require referral for adjuvant chemotherapy; 2. Investigate whether there is a survival benefit from the use of adjuvant chemotherapy in a population-based cohort of stage II colon cancer; 3. Investigate stage III colon cancer patients for evidence of predictive markers for response to 5FU chemotherapy; 4. Investigate CRC for age-related differences in clinico-pathological and molecular features. Hypotheses to be tested: 1. A subset of good prognosis stage II colon cancers can be defined using routine pathological markers; 2. Females colon cancer patients gain more survival advantage from 5FU chemotherapy than males; 3. Tumours from young CRC patients have different molecular characteristics to those from older patients; 4. The underlying molecular characteristics of tumour can impact upon the response to 5FU chemotherapy. Methods: The study cohort consisted of 5,971 cases diagnosed between 1993 and 2003 representing over 90% of the CRCs diagnosed in the state of Western Australia. Results: The major findings of this translational research into colon cancer can be summarized as follows: The morphological features of serosal and vascular invasion allow for prognostic stratification of stage II colon cancer into

M.A. / The purpose of the study was to ascertain whether patients suffering from irritable bowel syndrome (IBS) differed from non- IBS clients in terms of their defense mechanisms. Although irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders encountered by primary care physicians and gastroenterologists, it is one of the least well understood. Part of the reason for this is the lack of real consensus of opinion regarding the nature of the complaint (Read, 1985). Today it is widely agreed that irritable bowel syndrome is a psychosomatic disorder, that is, a disorder of physiological functioning and anatomical structure, which are determined for most part by psychological factors (Lachman, 1972; Moser, 1986). Evidence linking psychological variables to gastrointestinal disorders is surprisingly sparse, and all too often confusing and contradicting. Such conflicting results probably reflect the many methodological weaknesses common to all areas of study (Bennett, .1989). Although evaluation of the impact of psychological interventions on both symptomatic and psychological relief has been pursued, its findings provide tangential support for the importance of psychological disorders. Nevertheless, these studies have shown a consistency of positive results not found in the etiological research (Read, 1985). Using a variety of techniques, most with the therapeutic goal of stress reduction, psychological therapy has been shown to produce. symptomatic relief, increase periods of remission, and to reduce the impact of stress resulting from severe symptomatic flare ups in IBS (Bennett, 1989). In .addition, most IBS patients may not identify their gut symptoms in psychological terms. Therefore, they inappropriately and repeatedly subject themselves to unnecessary, expensive and harmful medical procedures in search of an organic cause. Further research into the psychological factors of IBS, including the defense mechanisms underlying it may lead to a reduction in type of anxiety (Folkman, Lazarus, Gruen & DeLongis, 1986). The ways in which people cope with intense emotions may have a significant effect on their psychological and physical health. StresS factors and the suppression of emotions, for example through defense mechanisms, are thought to be especially relevant in the etiology and exacerbation of psychosomatic illness (Ogden & Von Sturmer, 1984). The role that defense mechanisms play in the development of IBS forms the cornerstone of the present research.

published_or_final_version / abstract / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

No description available.

Bile acids have been studied for many years for their role in either promoting (Deoxycholic Acid) or suppressing (Ursodeoxycholic Acid) colon tumor development in animal models. However, the molecular mechanisms of both DCA's and UDCA's biological effects in colon tumorigenesis is still unclear. The cholesterol-like composition of bile acids and evidence of deregulating signal transduction pathways, such as the p42/44 MAP kinase cascade, led us to identify the plasma membrane as a target for bile acid-mediated effects. Specifically, plasma membrane microdomains such as lipid rafts and caveolae are particularly capable of altering mitogenic signaling due to have their role as platforms to concentrate receptors and assemble signal transduction machinery. In this study I tested the hypothesis that the growth suppressive effects of UDCA are mediated by stimulating membrane microdomains to activate protein degradation machinery to facilitate the down-regulation of receptor tyrosine kinase activity. We found that UDCA suppresses EGF-induced ERK activation, promotes interactions between EGFR and Caveolin-1 membrane fractions, whereas DCA causes redistribution. EGFR proteins that are localized to membrane fractions in the UDCA treated cells are extensively ubiquitinylated and we present evidence that this yields recruitment of the ubiquitin ligase c-Cbl to membrane fractions. UDCA increases the rate of EGFR degradation, whereas DCA sustains its' stability. I present evidence that UDCA's growth inhibitory effects on colon cancer cells may be mediated by recruitment of protein degradation machinery to membrane domains that are enriched with signaling receptors, a mechanism which has not been previously described. Importantly, I demonstrate for the first time a novel mechanism by which UDCA promotes growth inhibition, through increasing the rates of degradation of EGFR, thereby down-regulating mitogenic signaling in the cell. These experiments show exciting insights into the mechanism of bile acids and represent potential mechanisms for other chemopreventive agents.