Offprints of author's four journal articles in pocket / Bibliography: leaves 131-147 / x, 148 leaves, [13] leaves of plates : ill. (1 col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, 1986

Improved methods for the in situ hybridisation detection of messenger RNA ( mRNA ) in sections of liver tissue, were derived by use of an experimental system. This involved the use of tritiated-poly ( dT ) probes to detect poly ( A ) sequences attached to the 3 ' end of mRNA in sections of mouse liver that had been processed in various ways. The improved - methods were applied to the detection of hepatitis B virus ( HBV ) - and hepatitis delta virus ( HDV ) - RNA. In situ hybridisation and immunostaining techniques were then applied to studies of the pathogenesis of HBV and duck hepatitis B virus ( DHBV ) infection. In situ hybridisation studies of liver biopsy tissue from HBV - infected immunosuppressed renal transplant patients demonstrated an anatomical association between piecemeal necrosis and HBV replication at the cellular level in some patients. However, widespread replicative infection of hepatocytes also occurred in some patients in the presence of normal hepatocyte morphology and mild inflammatory changes indicating that at the cellular level virus replication was not necessarily a direct cytopathic process. These findings supported the view that hepatocyte Injury may : ( i ) result from immune - mediated damage directed against cells undergoing replicative, but not restricted infection ; ( ii ) eliminate cells undergoing replicative infection and favour clonal regeneration of cells undergoing restricted infection. Localisation of interferon - alpha ( IFN - alpha ) expression in liver tissue chronically infected with HBV and HDV, identified mononuclear cells and fibroblasts ( but not hepatocytes ) as the main producers of IFN - alpha. IFN - alpha - positive cells were associated with areas of liver tissue containing cells supporting virus replication and exhibiting the greatest degree of liver damage, suggesting that locally produced IFN - alpha may be a natural regulator of virus replication in chronic liver disease. Experimental DHBV infection of Pekin - Aylesbury ducks showed that virus inoculated either intravenously or intraperitoneally, gained access to randomly distributed hepatocytes without first replicating in other cell types in the liver. Virus was seen to disseminate to contiguous cells following anatomical boundaries by the third day post - inoculation. Markers of DHBV infection in liver and serum showed reproducible kinetics, and duck hepatocytes in this system appeared to be highly permissive as large amounts of DHBV DNA and DHBsAg were produced intracellularly without the development of ongoing cytopathology. Hepatocytes were the major cell type responsible for early significant DHBV replication, in contrast to pancreas, kidney, spleen and circulating mononuclear cells where significant levels of infection were detected only after the first week of infection and the onset of viraemia. / Thesis (Ph.D.)--Department of Microbiology and Immunology, 1989.

Background: An estimated 50,000 adults in the United States (U.S.) die each year from one of 10 vaccine preventable diseases. For those who survive vaccine preventable infections, health care costs and loss of income become more significant. While children in the U.S. aged 0-2 exhibit vaccine prevalence rates of almost 90%, some adult vaccine prevalence rates in the U.S. population are reported to be nearly 30-40% less than the goals set forth by Healthy People 2010. The purpose of this study was to examine the associations between socio-demographic characteristics of U.S. adults and adult vaccination prevalence for pneumococcal, hepatitis A, hepatitis B, tetanus, and pertussis. Methods: Data from the 2008 National Health Interview Survey were assessed examining various health indicators and characteristics of non-institutionalized adults and children. The sample was restricted to adults ≥18 years of age. Odds ratios were calculated and multivariate logistic regression was also conducted. P-values of Results: There were 21781 total observations; 19.3% received the pneumococcal vaccine, 9.4% received the hepatitis A vaccine, 27.2% received the hepatitis B vaccine, 55.1% received the tetanus vaccine, and 15.2% received the pertussis vaccine. Of the socio-demographic characteristics examined, age, health insurance, marital status, and education were significant for either all five or at least four of the vaccines included in this study. As one might expect those who reported health insurance and those who had a higher level of education usually had a higher likelihood of vaccine receipt as compared to those without health insurance and those with less than a high school education. Age associations varied due to age-related recommendations for certain vaccines such as pneumococcal (recommended for adults ≥65). Compared to the married population (referent), marital status results varied, but for reasons unclear. Whites, the referent group, were the most likely to be vaccinated as compared to Blacks, Hispanics/Latinos, and Asians. Hispanics/Latinos typically had the lowest likelihood of vaccination in this examination. Conclusions: This study further explores the impact of socio-demographic disparities on vaccination status and adds new information to the literature regarding adult vaccination rates for preventable diseases. While research exists related to strengthening interventions such as patient reminder systems, those who do not see the same health care providers on a regular basis remain at risk for lower vaccination prevalence. It is important to better understand the role of social determinants of health, specifically in terms of vaccinations. Future research is needed to further characterize the association of socio-demographic factors with receipt of optional vaccines in adults.

Chronic liver disease is an important disease which affects national healthy in Taiwan. Hepatitis B or C virus infection is strongly relative to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. However, the early effective treatment can decrease the progression of liver cirrhosis and hepatocellular carcinoma and increase the recovery rate. In order to promote the health care quality for the patients with hepatitis, Bureau of National Health Insurance (BNHI) implemented the ¡§Enhance Hepatitis B or C Health Care Program¡¨ in October of 2003. The new policy sets up the standard treatment models and pay medical costs to encourage the patients to participate this program and fit cost-effectiveness. Therefore, aims of the study are to estimate the effects of the new policy on health care utilization and expenditures for the patients with hepatitis B or C. The study used the database from Bureau of National Health Insurance (BNHI) in 2002 and 2004. The study sample is the patients with hepatitis B or C who enrolled the program from January to June in 2004. We compared the differences of health care utilization and expenditures with these statistics in 2002. Besides, we also analyzed the difference in the characteristics of the patients and hospitals. In health care utilization, we found that number of visits was increased but interval between visits was decreased. Total costs, costs of treatments, prescriptions, total claim amount, and averages of prescription costs in health care expenditures were all increased significantly after the new policy implemented. Otherwise, there were not different on health care utilization and expenditures between different gender and level of the hospitals. On the other hand, there were significantly correlation of ages and number of comorbility. It means that the patients¡¦ ages are older, and their number of visits and total costs are higher but interval between visits is shorter than younger. Furthermore, number of comorbility increases and then interval between visits become short. The new policy certainly affects the health care utilization and expenditures of patients with hepatitis B or C. Implementing the new program can encourage patients adopt treatment actively and physicians have standard treatment protocols to follow. Understanding the changes on health care utilization and expenditures can give a health care guideline of cost-effectiveness. In conclusion, the results can provide the information about payments on patients with hepatitis to BNHI and then use it to be a basis after the new program implemented. Moreover, other countries also can evaluate the implementation of the new policy based on our results.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Tıbbi Mikrobioloji Anabilim Dalı, 2009. / Kaynakça var.

Thesis (doctoral)--Universität, Münster (Westfalen).

published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

Πραγματοποιήσαμε πολυσταδιακή δειγματοληπτική έρευνα, προκειμένου να μελετήσουμε τον επιπολασμό και τις οδούς μετάδοσης της ηπατίτιδας Β και C στο γενικό πληθυσμό του Νομού Αχαΐας. Για το σκοπό αυτό εξετάσαμε αντιπροσωπευτικό δείγμα 1500 ατόμων χρησιμοποιώντας τρίτης γενιάς αντιδραστήρια. Δείκτες HBV μόλυνσης διαπιστώθηκαν σε 339 άτομα (22,6%) με επιπολασμό anti-HBc αντισωμάτων 21,6% (95%CI:19,5-23,8) και HBsAg αντιγόνου 2,1% (95%CI:1,5-3). Anti-HCV θετικά αντισώματα διαπιστώθηκαν σε 8 άτομα με ELISA-3 (0,5%, 95%CI:0,2-1,1), από τα οποία 5 (62,5%) επιβεβαιώθηκαν με LIA-3 και 3 (37,5%) είχαν PCR θετική. Συλλοίμωξη ή παρελθούσα μόλυνση και από τους δύο ιούς ανιχνεύτηκε σε 5 άτομα (0,3%). Από τη στατιστική σύγκριση που έγινε διαπιστώθηκε αυξημένη HBV μόλυνση σε στατιστικά σημαντικό βαθμό στους άνδρες, στους πλέον ηλικιωμένους, στους εγγάμους/διαζευγμένους/χήρους, σε άτομα χαμηλότερου επιπέδου μόρφωσης, με >2 παιδιά, με συγκατοίκηση <2 άτομα καθώς και στις ορεινές και αγροτικές περιοχές έναντι των αστικών και πεδινών. Επίσης, το θετικό περιβάλλον, η κατάχρηση αλκοόλ, η ύπαρξη σεξουαλικών σχέσεων και η μη χρήση προφυλακτικού τόσο με τον περιστασιακό όσο και με το μόνιμο σύντροφο ήταν παράγοντες κινδύνου της μόλυνσης από ιό Β. Αντίθετα, δε βρέθηκε στατιστικώς σημαντική διαφορά HBV μόλυνσης σε σχέση με τις μεταγγίσεις και τη νοσηλεία >1d. Από την άποψη της επαγγελματικής κατανομής της Β μόλυνσης, ιδιαίτερα επιβαρημένη ήταν η αγροτική και η εργατική τάξη. Πάντως, από την πολυπαραγοντική ανάλυση που ακολούθησε μόνο το άρρεν φύλο (ΣΚ 4,1, 95%CI:2,4-7,1), η αυξημένη ηλικία (≥30 ετών ΣΚ 9, 95%CI:4,2-19,4) και το θετικό περιβάλλον (ΣΚ 1,3, 95%CI:0,9-1,8) είχαν ανεξάρτητη σχέση με την HBV μόλυνση. Η γενετήσια και η ενδοοικογενειακή οδός αποτελούσαν τους συχνότερους τρόπους διασποράς του ιού Β, ενώ η παρεντερική οδός ήταν η κυρίαρχη στην μετάδοση του ιού C. Χρόνια ηπατίτιδα Β διαπιστώθηκε στο 9,5% των HBsAg θετικών που ελέγχτηκαν στο Τμήμα Λοιμώξεων (σε κανέναν δεν ανιχνεύτηκε HBV-DNA ιαιμία), ενώ το 60% των επιβεβαιωμένων anti-HCV θετικών έπασχε από χρόνια ηπατίτιδα C. Εμβολιασμό έναντι της ηπατίτιδας Β δήλωσαν 183 άτομα (12,2%), στο 85,8% μαθητές και H.C.W, και anti-HBs>10mIU/ml ανιχνεύτηκαν στο 83,6%. Τέσσερα άτομα (2,2% των εμβολιασθέντων) παρουσίασαν και δείκτες παρελθούσας HBV μόλυνσης. Η «αποτυχία» του εμβολίου υπολογίστηκε στο 7,5%. Οι άνδρες, παρά τον τετραπλό κίνδυνο μόλυνσης, εμβολιάζονταν σε μικρότερο βαθμό συγκριτικά με τις γυναίκες, ενώ δεν υπήρχε στατιστικώς σημαντική διαφορά εμβολιασμού μεταξύ αυτών που είχαν θετικό και αρνητικό περιβάλλον. Συμπερασματικά, ο Νομός Αχαΐας κατατάσσεται στις ενδιάμεσης ενδημικότητας περιοχές όσον αφορά στην ηπατίτιδα Β και στις χαμηλής ενδημικότητας όσον αφορά στην ηπατίτιδα C. Οι κύριοι οδοί μετάδοσης είναι η γενετήσια και η ενδοοικογενειακή για τον ιό Β και η παρεντερική για τον ιό C. Παρά την πολύ μικρή συχνότητα στο γενικό πληθυσμό και λόγω του υψηλού ποσοστού μετάπτωσης σε χρονιότητα, η ηπατίτιδα C παίζει όχι μόνο εξίσου σημαντικό αλλά ίσως και πρωταγωνιστικό ρόλο στη νοσηρότητα από χρόνια ιογενή ηπατοπάθεια στην περιοχή μας. Ειδικά για την ηπατίτιδα Β, η υιοθέτηση του μαζικού εμβολιασμού θα αλλάξει το επιδημιολογικό τοπίο, αλλά χρειάζεται παράλληλα πιο ικανοποιητική κάλυψη των ομάδων υψηλού κινδύνου. / A community-based survey was conducted using the multistage random sampling method, in order to determine the prevalence and routes of transmission of hepatitis B and C in the general population of Achaia region in the Southwestern Greece. For this purpose we examined a representative sample of 1500 individuals using third generation assays. HBV infection markers were detected in 339 subjects (22,6%) with anti-HBc prevalence 21,6% (95%CI:19,5-23,8) and HBsAg prevalence 2,1% (95%CI:1,5-3). Anti-HCV antibodies were detected in 8 subjects with ELISA-3 (0,5%, 95%CI:0,2-1,1), 5 of which (62,5%) were confirmed with LIA-3 and 3 (37,5%) were HCV-RNA positive. Dual or past infection with both viruses was detected in 5 subjects (0,3%). Male sex, older age, married/divorced/widowed family status, lower level of education, more than two children, cohabitation with less than two persons, positive environment, alcohol abuse, sex, absence of condom prophylaxis during sexual intercourse with single or multiple partners were all risk factors for HBV infection (statistically significant). On the contrary, there was not significant difference between HBV-negative and HBVinfected individuals when transfusions or hospitalization >1d were concerned. Workers and people in the agricultural sector were particularly affected. Nevertheless, multivariate statistical analysis revealed that male sex (RR 4,1, 95%CI:2,4-7,1), older age (≥30y RR 9, 95%CI:4,2-19,4) and positive environment (RR 1,3, 95%CI:0,9-1,8) were the only independently associated with HBV infection risk factors. Sexual and intrafamiliar exposure were the commonest ways for HBV transmission, while percutaneous exposure was the main route for HCV transmission. Chronic hepatitis B was diagnosed in 9,5% of HBsAg carriers who were examined by the physicians of the Department of Infectious Diseases (nobody was HBV-DNA positive), while 60% of those with confirmed anti-HCV antibodies had chronic hepatitis C. 183 subjects declared B immunization (12,2%), mostly pupils and health care workers (85,8%), and anti-HBs>10mIU/ml were detected in 83,6% of them. Four (2,2%) had, also, positive markers of past HBV infection. Vaccination failure was estimated at 7,5%. Men, despite their fourfold risk of infection, were immunized at a lower rate than women, while there was not significant difference in immunization rate between those with positive and negative environment. In conclusion, Achaia region can be classified as an intermediate HBV and a low HCV endemicity area. The main routes of HBV and HCV transmission are the sexual/intrafamiliar and percutaneous respectively. Despite the very low prevalence of hepatitis C and due to its higher range of chronicity, the number of chronically HBV and HCV infected in the general population seem to be comparable and, even, hepatitis C can play a leading role in chronic viral liver disease in our region. As far as hepatitis B is concerned, the adoption of mass immunization programmes will alter the epidemiological landscape and this should be especially encouraged in persons belonging to high risk groups.

Autopsy liver material from patients having died of chronic liver disease, cirrhosis, hepatocellular carcinoma (HCC) and causes unrelated to liver diseases was examined by dot blot hybridisation for the presence of HBV DNA. The results indicate that of the patients with chronic liver disease 6/9 were positive for HBV DNA in the liver tissue; of the patients with HCC 3/4 were positive for HBV DNA; of the patients with cirrhosis 4/4 showed the presence of HBV DNA in the liver. Thus by this technique 13/17 (76%) of these patients, all of whom were HBsAg positive, were shown to have HBV DNA present in liver tissue. However, autopsy liver samples were found to be unsuitable for Southern blot hybridisation. Biopsy liver/tumour tissue was examined for the presence of integrated or non-integrated HBV DNA by Southern blot analysis using the enzymes Eco R1 and Hind 111. 5/5 patients who were both HBsAg and HBeAg positive had extrachromosomal HBV DNA and 2/5 also showed the presence of integrated HBV DNA. 3/4 patients who were HBsAg positive and HBeAg negative had extrachromosomal HBV DNA and all three also had integrated HBV DNA. One control patient was negative for both markers and also for Southern blot hybridisation with the HBV DNA probe. These results support the hypothesis that HBV is a factor in the development of HCC, and indicate that the dot blot hybridisation method would be suitable for routine evaluation of patients with chronic liver disease or cirrhosis. / Thesis (M. Med.)-University of Natal, Durban, 1987.

Hepatitis B virus (HBV) causes an estimated 600,000 deaths annually, largely due to hepatocellular carcinoma (HCC). HBx, a promiscuous transactivator, is a viral oncoprotein, but its exact functions are poorly understood. Many studies have suggested that NF-κB signaling mediates HBx functions, but the underlying molecular mechanisms remain yet to be elucidated. Here, we provide evidence that HBx-mediated NF-κB activation depends on the physical interaction between HBx and a transcription factor, p65. In the cytoplasm, HBx-p65 interaction may promote IκBα phosphorylation and subsequent p65 nuclear localization. A cytokine assay using qPCR and RT-PCR indicates that HBx is associated with a unique profile of cytokine mRNA expression. As shown by chromatin immunoprecipitation (ChIP), HBx in the nuclues can be recruited to the gene promoter by p65. These findings support the importance of HBx-p65 interaction and suggest that it is potentially a promising target of novel therapeutics for HBV-associated liver diseases, including HCC.