http://hdl.handle.net/1956/965 Search the Channel search http://bora.uib.no/simple-search http://hdl.handle.net/1956/2330 Title: Lifestyle aspects in functional dyspepsia : influence of relaxation and meals on vagal activity, gastric accommodation and symptoms <br/> <br/>Authors: Hjelland, Ina Mon, 16 Apr 2007 22:58:59 GMT http://hdl.handle.net/1956/2274 Title: Nuclear Receptor Coregulators Role of Protein-Protein Interactions and cAMP/PKA Signaling <br/> <br/>Authors: Hoang, Tuyen Thi Van Thu, 01 Feb 2007 22:58:59 GMT http://hdl.handle.net/1956/2265 Title: Antimicrobial resistance in bacterial infections in urban and rural Tanzania <br/> <br/>Authors: Blomberg, Bjørn <br/> <br/>Abstract: Infectious diseases cause one in every six deaths worldwide. Antimicrobial drugs have helped dramatically in curing patients suffering from bacterial infections. However, emerging antimicrobial resistance in bacteria threatens to undermine the management of bacterial infections. Developing countries have greater burden of infectious diseases. A number of factors, which may promote antimicrobial resistance such as availability of antimicrobials without prescription, use of counterfeit or substandard antimicrobial drugs, suboptimal hygiene, immunosuppression due to malnutrition or HIV, may be more frequent in developing countries. At the same time, consequences of antimicrobial resistance may be felt harder in resource-poor settings, since second-line antimicrobial drugs for resistant bacteria may be unavailable or unaffordable. There are many unresolved questions regarding antimicrobial resistance in general, including regarding its impact on patient outcome. In Sub-Saharan, some studies on antimicrobial resistance have been done, but, by and large, the issue has received far too little attention. We set out to improve available antimicrobial susceptibility data in Tanzania. We implemented a free-of-charge computerized software (WHONET) for resistance surveillance in the University Teaching Hospital in Dar es Salaam. This exercise showed that resistance surveillance is feasible in the setting and provided useful data on antimicrobial resistance. The surveillance data indicated high rates of resistance to common antibiotics in Gram-negative bacteria. We performed a prospective, observational cohort study of bloodstream infections in 1828 admissions of children with fever or suspected serious infection at the hospital. We performed blood culture, malaria testing and HIV testing and collected clinical data from the study subjects. The study showed that a disturbingly high proportion of Gram-negative bacteria produced extended-spectrum beta-lactamases (ESBL), with prevalent genotypes being TEM-63, SHV-12 and CTX-M 15. The ESBL-producing bacteria had a high rate of resistance to almost all other available drugs, except for ciprofloxacin, and bloodstream infection caused by these multiresistant bacteria were associated with extremely high case-fatality rates. The study showed that inappropriate treatment due to antimicrobial resistance, as well as malnutrition and HIV-infection, were risk factors for death in children admitted with bloodstream infections. We investigated an outbreak of pediatric / neonatal meningitis at Haydom Lutheran Hospital, finding that Salmonella serovar Enteritidis, resistant to ampicillin and susceptible to gentamicin, was the cause of the outbreak. Although the numbers were small, the case-fatality rate for meningitis caused by these organisms was 100% (5/5). Antimicrobial resistance varies greatly from one geographical area to another. Thus, data obtained at major hospitals in urban centers may not be representative for the whole country. We analyzed the antimicrobial susceptibilities of isolates of uropathogenic bacterial obtained from the urine of pregnant women in a rural area in Northern Tanzania. This study indicated that there is less antimicrobial resistance in E. coli isolates from this rural area than in isolates from the commercial capital, Dar es Salaam. In formulating guidelines for antimicrobial use this possible rural-urban difference should be taken into account. For some of the bacteria carrying resistance traits for multiple antimicrobials, there are actually no good alternative drugs available. Based on the findings of these studies, we recommend sober, rational use of antimicrobial drugs, restrictions on sale and use of antimicrobials, and attention to hygiene. Tue, 15 May 2007 22:58:59 GMT http://hdl.handle.net/1956/2167 Title: Inflammatory biomarkers with focus on Calprotectin (S100A8/S100A9) and S100A12 (EN-RAGE) : method development and application in acute radiation proctitis and rheumatoid arthritis patients <br/> <br/>Authors: Larsen, Annette <br/> <br/>Abstract: Assessments of diseases are usually performed by a combination of clinical symptoms, signs and objective measurements. Biochemical markers of inflammation are important in evaluation of treatment of acute and chronic diseases. In this thesis we have focused on two inflammatory diseases: acute radiation proctitis and rheumatoid arthritis. We examined established and new biomarkers, with focus on two closely related proteins, calprotectin (S100A8/S100A9) and S100A12 (ENRAGE). These and other biomarkers were compared to clinical symptoms and signs with the aim of defining their usefulness in monitoring the course of the diseases. Characterizing the changes induced by radiation therapy to the pelvic region showed incongruent time profiles in symptoms, histological scoring of inflammation and biochemical measurements. Compared to the examination before start of radiation therapy, biopsies from rectal mucosa showed a maximal inflammation at the first examination during radiation therapy, while symptoms were at the most intense towards the end of treatment. Vitamin E concentrations in blood were significantly lower during treatment but returned to normal within a month. Calprotectin and lactoferrin concentrations in stool samples increased during therapy and were the most promising biomarkers for radiation proctitis in our study. Development of an ELISA immunoassay for the quantification of S100A12 in blood showed that calcium concentration influenced the estimated S100A12 concentrations. Various experiments led to the conclusions that the antibodies used in this assay could only recognize S100A12 when calcium were above a threshold and that S100A12 were found in many molecular sized complexes (oligomers) in blood. S100A12 was found to bind to heparin and this will be further examined in the future. Calprotectin and CRP in blood correlated with disease activity of rheumatoid arthritis. S100A12 was associated with a more severe disease course in terms of extra-articular disease manifestations and the presence of cardiovascular disease. S100A12 correlated with rheumatoid factor and anti-CCP and may thus be of prognostic value. In summary, radiation proctitis occurs in biopsies before symptoms are evident. This is important knowledge for studies with interventions to prevent development of late radiation enteropathy. Stool markers are at present the best suited objective means of assessing interventions. The quantification of S100A12 in blood samples are recommended to be done in serum samples, since both anticoagulants EDTA and heparin may influence conformational changes of S100A12 protein structure and hence the measured concentrations. The usefulness of S100A12 as a biomarker in rheumatoid arthritis and other inflammatory diseases warrants further examinations. Thu, 01 Feb 2007 22:58:59 GMT http://hdl.handle.net/1956/2151 Title: Immunological aspects of acute myelogenous leukemia <br/> <br/>Authors: Ersvær, Elisabeth <br/> <br/>Abstract: Acute myelogenous leukemia (AML) is an aggressive malignancy characterized by accumulation of immature myeloid cells in the bone marrow. The overall disease-free survival is less than 50% even for the younger patients who can receive the most intensive treatment and hence, there is obviously a need for an improved therapy. Short time until lymphoid reconstitution after chemotherapy seems to be a good prognostic factor in several malignancies, including AML, and targeting of autologous T cells is considered a possible therapeutic approach. Thus, the major aim of this thesis was to further characterize the immune system of patients with AML. Disease and therapy induced T lymphocyte defects may contribute to the immune defects in AML. We therefore characterized the T lymphocytes of untreated AML patients as well as the remaining T cells in AML patients receiving intensive chemotherapy. Untreated AML patients were found to have close to normal lymphocyte subset ratios and also the in vitro T cell activation response, release of IFNγ, was close to normal after adjustment of cell numbers. In contrast, the released levels of IFNγ and GM-CSF cytokines from in vitro activated T cells in whole blood from cytopenia AML patients were lower than for healthy controls. However, the IFNγ and GM-CSF levels could be further increased by the protein kinase C agonist Pep005. The direct effects of the IFNγ on AML blasts included altered i) cytokine-dependent AML cell proliferation, ii) viability, and iii) balance between pro- and antiangiogenic chemokine release. Several mutated or overexpressed proteins seem to be processed and presented to the immune system as tumor antigens leading to humoral and/or cellular responses. Autoantibodies are thus common in cancer patients but the autoantibody response in AML patients has been included in relatively few previous studies. Our studies report aberrant cyclin B1 expression in primary AML cells and detection of anti-cyclin B1 in a subset of sera from AML patients. In contrast, no autoantibodies against the typically SLE associated antigen P-protein could be detected in sera from untreated and chemotherapy treated AML patients. To conclude, both the cellular and humoral immune system in AML patients differ from healthy controls. However, our results support the hypothesis that even these immunocompromized patients have remaining immunocompetent cells that can be targeted by immunotherapy. Thu, 22 Feb 2007 22:58:59 GMT http://hdl.handle.net/1956/2142 Title: Early outcome and restenosis after coronary stenting : intervention with stent-coatings, antioxidants and radiation <br/> <br/>Authors: Kuiper, Karel Kier-Jan Thu, 15 Mar 2007 22:58:59 GMT http://hdl.handle.net/1956/2111 Title: Assessment of cobalamin status in experimental and clinical studies by intracellular and extracellular markers of vitamin function <br/> <br/>Authors: Riedel, Bettina Wed, 01 Feb 2006 22:58:59 GMT http://hdl.handle.net/1956/2101 Title: The effects of smoking cessation intervention in patients with coronary heart disease : a randomised, controlled trial <br/> <br/>Authors: Quist-Paulsen, Petter <br/> <br/>Abstract: Background: Smoking cessation is the most important action to reduce mortality after a coronary event. Largely, it has previously been unknown whether a smoking cessation program applicable in an ordinary clinical setting has any impact on smoking cessation rates in patients with coronary heart disease, and whether such a program is cost effective. Objectives: To determine whether a nurse managed smoking cessation intervention changes abstinence rates in patients admitted for coronary heart disease, to assess the predictors of smoking cessation, to evaluate whether smoking cessation has any impact on Quality of Life, to estimate the cost effectiveness of the smoking cessation program, and to appraise the feasibility of a fear arousal message. Design: Randomised controlled trial of usual care compared with individual smoking cessation intervention. Setting: The cardiac ward in Sørlandet Sykehus, Kristiansand, Norway. Participants: 240 smokers under 76 years of age admitted for myocardial infarction, unstable angina or cardiac bypass surgery. 118 were randomly assigned to the intervention and 122 to usual care (control group). 218 patients (91%) completed the study and were assessable at 12 months follow up. Methods: The intervention was based on an especially made 17 page booklet and focused on fear arousal and relapse prevention. Individual smoking cessation was delivered by cardiac nurses without special training. The intervention was initiated in hospital, and the participants were telephoned regularly for at least five months. Abstinence rates were determined by self report and biochemical verification. Survival data from previously published investigations, with life time extrapolation of the survival curves by survival function modelling, were used to be able to estimate the cost effectiveness of the program. Baseline characteristics were prospectively recorded, and health-related Quality of Life was measured at baseline and at 12 months follow up. The patient satisfaction was assessed at 12 months follow up. Results: 12 months after randomisation 57.0% and 37.3% were abstinent in the intervention and control groups, respectively (95% confidence interval for the difference 6.4 to 33.0). The number needed to treat to get one additional quitter was 5.1 (95% CI 3.0 to 15.6). Assuming all drop outs returned to smoking at 12 months, the cessation rates were 50.0% and 37.0% in the intervention and control group, respectively (95% CI for the difference 0.4 to 25.7). In a life time perspective, the incremental cost per year of life gained by the cessation program was Euro 280 and Euro 110 in the low and high risk group, respectively (2000 prices). These costs compare favourably to other treatment modalities in patients with coronary heart disease, being approximately 1/25 the cost of both statins in the low risk group and angiotensin converting enzyme inhibitors in the high risk group. In a sensitivity analysis, the costs remained low in a wide range of assumptions. The participants were in general satisfied with the cessation program, indicating that implementing a fear arousal message is a feasible method. In multivariate logistic regression analysis, a high level of nicotine addiction was a strong negative predictor of smoking cessation in both the intervention and the control group. The quitters and sustained smokers had similar improvements in all Quality of Life domains from baseline to 12 months follow up. Further, after adjustment for differences in baseline characteristics, the Quality of Life at baseline was not significantly associated with smoking cessation at 12 months follow up. Conclusions: A smoking cessation program delivered by cardiac nurses without special training, significantly reduced smoking rates 12 months after hospitalisation for coronary heart disease. The program was very cost effective compared to other treatment modalities in patients with coronary heart disease in terms of cost per life year gained. Among those with a high level of nicotine addiction, more effective cessation programs are needed. Thu, 08 Feb 2007 22:58:59 GMT