Thesis (Ph.D.)--University of Adelaide, Dept. of History, 2002. / Includes bibliographical references (leaves 320-415).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

This thesis pertains to the pathogenesis of alcoholic pancreatitis, a considerable burden in terms of morbidity, mortality and health related costs. It has long been known that only a minority of alcoholics develop clinically evident pancreatitis, suggesting that (an) additional trigger factor(s) is required to elicit overt disease. Endotoxin (lipopolysaccharide LPS), from gut-derived gram negative bacteria may be one such trigger factor, since alcoholics exhibit increased levels of serum endotoxin. In addition, the degree of endotoxinaemia has been reported to correlate with the severity of pancreatitis. Studies described in this thesis report, i) the development of a novel rodent model of alcoholic pancreatitis produced by challenging alcohol-fed animals with single or repeated doses of LPS. The animals exhibit features of both acute (acinar vacuolisation, necrosis, pancreatic oedema, haemorrhage and inflammatory infiltration) and chronic (acinar atrophy and pancreatic fibrosis) pancreatitis; ii) the reversion of pancreatic injury (including fibrosis) upon withdrawal of alcohol in the model and the persistence of pancreatic damage with continuation of alcohol feeding; iii) activation of pancreatic stellate cells (PSCs, known to play a central role in fibrogenesis) in vivo and in vitro by alcohol and LPS; iv) the inhibition of PSC apoptosis in vivo and in vitro upon exposure to alcohol and LPS and the induction of PSC apoptosis in vivo upon withdrawal of alcohol from the diet and v) the presence of LPS receptors TLR4 and CD14 on PSCs, which would explain the responsiveness of PSCs to LPS. Thus the work in this thesis provides strong evidence in support of endotoxin as a clinically relevant trigger factor for the initiation of alcoholic pancreatitis and as a factor that promotes disease progression. The thesis also provides the first experimental evidence to support the clinical reports of a beneficial effect of abstinence on chronic pancreatitis. Delineation of the mechanisms mediating the induction, progression and reversibility of alcoholic pancreatitis has the potential to direct the development of new therapeutic interventions for alcohol-related pancreatic injury.

Thesis (Ph. D.)--University of South Florida, 2003. / Includes vita. Title from PDF of title page. Document formatted into pages; contains 97 pages. Includes bibliographical references.

published_or_final_version / Public Health / Master / Master of Public Health

Background: Many western observational studies suggest moderate alcohol use is associated with better health including lower risk of cardiovascular diseases, diabetes and cognitive decline. However, the apparent benefit is susceptible to confounding by healthier attributes in moderate users. Randomized controlled trials of moderate alcohol use are infeasible. To assess the validity of these association for causal inference, I examined these associations in a setting (Southern China) with a different social patterning of alcohol use from more commonly studied western populations and using a Mendelian randomization design. Objectives: This thesis utilized two large Southern Chinese cohorts, the Guangzhou Biobank Cohort Study (GBCS) (n=30,499) and the Elderly Health Centre (EHC) Cohort (n=64,353) to examine sex-specific association of moderate alcohol use with cognitive function using observational designs. I also examined systematic differences between alcohol users and the credibility of alcohol-metabolizing genes as instruments for Mendelian randomization in GBCS. Mendelian randomization was used to examine the effect of alcohol use on cognitive function and cardiovascular risk factors and morbidity among men in GBCS. Methods: I used multivariable linear regression to examine the adjusted association of alcohol use categories (never, occasional, social weekly (EHC only), moderate, heavy and former) with cognitive function, measured by delayed 10-word recall test (phases 1-3 of GBCS), Mini-Mental State Examination (phase 3 of GBCS) and Abbreviated Mental Test (EHC), stratified by sex and age. I used multinomial logistic regression to examine the sex-specific systematic difference by alcohol category in GBCS. I used multivariable linear regression to examine the genetic association of ALDH2 with different cardiovascular risk factors and morbidities, cognitive outcomes and liver enzymes and to assess if alcohol phenotypes mediated any apparent genetic association in men. I used 2 stage least squares (2SLS) regression to examine the association of alcohol units (10g ethanol/day) with cognitive function and cardiovascular risk factors (blood pressure, lipids and fasting glucose) and morbidities (self reported cardiovascular disease and ischemic heart disease) in men in GBCS. Results: Occasional alcohol use, rather than moderate alcohol use, was consistently associated with higher cognitive function in both studies. Systematic differences among alcohol users were present. Occasional alcohol users had better health attributes while moderate users had slightly poorer attributes compared to never users. Aldehyde dehydrogenase 2 (ALDH2) was a credible instrument for Mendelian randomization. From Mendelian randomization, low to moderate alcohol use was not associated with cognitive function in men. However, it was positively associated with HDL cholesterol and diastolic blood pressure but not with fasting glucose or cardiovascular morbidity in men. Conclusions: Moderate alcohol use was not associated with cognitive function, suggesting that previous positive studies could be confounded by better health attributes in moderate users. The lack of association of alcohol use with cardiovascular morbidity despite raising HDL cholesterol is consistent with non-observational studies showing the non-causal role of HDL cholesterol in cardiovascular disease. These may suggest the apparent cardioprotection of alcohol is confounded although it remains possible that cardioprotection is population-specific via pathways other than HDL cholesterol, which require further investigations. / published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Background: With the increasing public health concern over the alcohol related health burden and mortality globally, the World Health Organization (WHO) has listed alcohol use as the top three risk factors in Non-Communicable Disease (NCD) and the alcohol related mortality and morbidity could be avoided through early intervention and prevention. The Department of Health (DH) of Hong Kong Special Administration Region (HKSAR) has declared the alcohol epidemic was alarming with the increasing in prevalence of alcohol use and binge drinking especially among young people with the westernization of Hong Kong society. In combating local alcohol use epidemic, DH has put priority to reform health care sector system and to ensure that the local health care system is responsive to the local alcohol use problem. Brief intervention (BI) was found to be effective in dealing with at-risk alcohol use especially in primary health care settings in the various past systematic reviews. However, most reviews mainly focus on physician-led BI while the role of nurse in BI delivery in alcohol drinking had not been under great attention. The effectiveness of nurse-led BI to at-risk drinking has not been fully examined as compared with physician-led interventions in the past reviews. Evaluation of treatment components in terms of intensity, treatment components and service settings may also shed light to public health policy makers in development of local model of BI in dealing with drinking problem in the Chinese population. Objective: To investigate the effectiveness of physician-led or nurse-led BI on quantity of alcohol consumption, number of drinking days, number of binge drinking episode and health care utilization. The potentially effective treatment intensity, treatments components and setting of intervention were also investigated. Methods: All the studies published from 1990 to 2012 in MEDLINE, would be evaluated on the effectiveness of BI delivered by physicians and/or nurses to adult at-risk drinkers in primary health care settings, were searched and identified using a combination of keywords. Results: A total of 13 randomized controlled trials out of 134 articles from MEDLINE were included in this systematic review. The included studies used different outcome measurements to compare the effectiveness of BI by physicians and/or nurses in treating at-risk drinking. Similar demographics and clinical characteristics of the subjects between the intervention and control groups were reported. The studies were from 5 countries. The age range of subjects was from 14 to 75 years old. Majority of subjects drank beyond the recommended limits defined by Alcohol Abuse and Alcoholism (NIAA), United State (US). Through there were discrepancies among the results generated in the included studies on the effectiveness of physician-led and/ or nurse-led BI, the benefits of nurse-led BI in treatment of at-risk drinking cannot be dispelled and could be considered as an alternative or supplement to the physician-led BI in busy primary health care setting today. BI with at least two 5-15 minute sessions was found to be more effective than very BI with one 5-minute session only. High quality BI with all five essential treatment components (information giving, advice, goal setting, assistance and follow up) were found to be more effective than partially included treatment. BI were found effective in dealing at risk alcohol use in all General Out Patient Clinic (GOPC) while the effectiveness of BI on alcohol drinking in Special Out Patient Clinic (SOPC) needs further research to warrant the result. Conclusion: Based on this systematic review, the potential effects of nurse-led BI remain unclear in comparison with physician-led BI for at-risk drinkers. More researches on the effectiveness of BI by nurse and its cost-effectiveness as well as BI delivered by different primary health care personnel in treating at-risk alcohol drinking with long study period, especially in the Chinese population, is needed to provide further evidence on the development of local BI in local primary health care settings. / published_or_final_version / Medicine / Master / Master of Public Health

No description available.

This thesis pertains to the pathogenesis of alcoholic pancreatitis, a considerable burden in terms of morbidity, mortality and health related costs. It has long been known that only a minority of alcoholics develop clinically evident pancreatitis, suggesting that (an) additional trigger factor(s) is required to elicit overt disease. Endotoxin (lipopolysaccharide LPS), from gut-derived gram negative bacteria may be one such trigger factor, since alcoholics exhibit increased levels of serum endotoxin. In addition, the degree of endotoxinaemia has been reported to correlate with the severity of pancreatitis. Studies described in this thesis report, i) the development of a novel rodent model of alcoholic pancreatitis produced by challenging alcohol-fed animals with single or repeated doses of LPS. The animals exhibit features of both acute (acinar vacuolisation, necrosis, pancreatic oedema, haemorrhage and inflammatory infiltration) and chronic (acinar atrophy and pancreatic fibrosis) pancreatitis; ii) the reversion of pancreatic injury (including fibrosis) upon withdrawal of alcohol in the model and the persistence of pancreatic damage with continuation of alcohol feeding; iii) activation of pancreatic stellate cells (PSCs, known to play a central role in fibrogenesis) in vivo and in vitro by alcohol and LPS; iv) the inhibition of PSC apoptosis in vivo and in vitro upon exposure to alcohol and LPS and the induction of PSC apoptosis in vivo upon withdrawal of alcohol from the diet and v) the presence of LPS receptors TLR4 and CD14 on PSCs, which would explain the responsiveness of PSCs to LPS. Thus the work in this thesis provides strong evidence in support of endotoxin as a clinically relevant trigger factor for the initiation of alcoholic pancreatitis and as a factor that promotes disease progression. The thesis also provides the first experimental evidence to support the clinical reports of a beneficial effect of abstinence on chronic pancreatitis. Delineation of the mechanisms mediating the induction, progression and reversibility of alcoholic pancreatitis has the potential to direct the development of new therapeutic interventions for alcohol-related pancreatic injury.

Thesis (Ph. D.)--University of Washington, 1989. / Vita. Includes bibliographical references (leaves [61]-69).