Bibliography: leaves 217-244. Tachykinins are implicated in the mediation of airway inflammatory responses and may have roles in airway remodeling and healing. The actions of tachykinins are mediated by specific receptors, designated NK1, NK2 and NK3. Tachykinin degredation, an important mechanism for limiting the effects of these peptides, is principally mediated by neutral endopeptidase (NEP). This thesis investigates the role of tachykinins, in vivo, in an ovine model and in human airway epithelium. Results show that the nett effect of tachykinins in the airway will depend on the relative balance between the expression of receptors, tachykinins and NEP. Assessment of these molecules in the airway epithelium from subjects with normal lungs or chronic bronchitis showed that preprotachykinin-A gene expression was relatively higher in the disease group whereas NEP and NK1 receptor levels were unchanged. These studies provide new insights into the role of tachykinins in airways disease.

Bibliography: leaves 217-244. / x, 246 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Tachykinins are implicated in the mediation of airway inflammatory responses and may have roles in airway remodeling and healing. The actions of tachykinins are mediated by specific receptors, designated NK1, NK2 and NK3. Tachykinin degredation, an important mechanism for limiting the effects of these peptides, is principally mediated by neutral endopeptidase (NEP). This thesis investigates the role of tachykinins, in vivo, in an ovine model and in human airway epithelium. Results show that the nett effect of tachykinins in the airway will depend on the relative balance between the expression of receptors, tachykinins and NEP. Assessment of these molecules in the airway epithelium from subjects with normal lungs or chronic bronchitis showed that preprotachykinin-A gene expression was relatively higher in the disease group whereas NEP and NK1 receptor levels were unchanged. These studies provide new insights into the role of tachykinins in airways disease. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1999

Bibliography: leaves 181-201.

Recently, there has been extensive research in the area of diagnostic expertise. The model of diagnostic reasoning and clinical expertise has been well documented (Patel et al., in press). This study attempts to extend this research in order to include therapeutic reasoning. Using the expert-novice paradigm, this study attempts to investigate the use of knowledge, specifically, both biomedical and clinical sciences, and the directionality of reasoning during decision making about patient management and therapeutic planning in respiratory medicine. / Subjects at four levels of expertise were given two clinical problems with the diagnosis and asked (a) to provide therapeutic plans, and (b) describe the underlying pathophysiological explanations of the diseases. Think-aloud protocols were audio-taped and analyzed using methods of protocol analysis. The results showed that the use of basic medical sciences increased as a function of expertise in the procedure-oriented decision-making tasks. The novices generated rule-based prototypical textbook descriptions based on the clinical information, and the diagnosis given in the task. In contrast, the experts' therapeutic responses showed a predominance of causal-level inferences, reflecting more backward-directed inferences than novices. Although both the novices and experts generated forward-directed inferences, the novices were unable to provide accurate and adequate explanations for their decisions. Finally, the pathophysiological explanations of the disease were generated from a different knowledge source than that used to develop therapeutic decisions. / The implications of these findings for development of theory of expertise and for education in the medical domain are discussed.

No description available.

Thesis (M.Tech.: Chiropractic)-Dept. of Chiropractic, Durban Institute of Technology, 2003. x, 101 leaves / Anecdotal evidence and some developmental theory suggest that lower respiratory tract pathologies may be associated with thoracic spine pain and dysfunction. This hypothetical association may be better described either as respiratory conditions occurring as a result of musculoskeletal dysfunction of the thoracic spine, or as respiratory conditions causing thoracic musculoskeletal dysfunction. Optimal function of the lungs and the process of ventilation is dependant on the normal function of the thoracic spine and the rib cage. Disturbances of the musculoskeletal components of the thoracic spine may lead to increased respiratory efforts, decreased lung function and in turn affect bronchopulmonary function. Obstructive respiratory diseases such as asthma, bronchitis and emphysema place an increased demand on the musculoskeletal components involved in expiration, as air has to be forcefully expired. The purpose of this quantitative, non experimental, demographic retrospective clinical survey was to retrospectively describe lower respiratory tract disorders and thoracic spine pain and dysfunction in subjects presenting to the Durban Institute of Technology Chiropractic Day Clinic, in terms of the prevalence of lower respiratory tract disorders as well as any association between the presenting respiratory conditions and their vertebral distribution in the thoracic spine.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban Institute of Technology, 2003. / Anecdotal evidence and some developmental theory suggest that lower respiratory tract pathologies may be associated with thoracic spine pain and dysfunction. This hypothetical association may be better described either as respiratory conditions occurring as a result of musculoskeletal dysfunction of the thoracic spine, or as respiratory conditions causing thoracic musculoskeletal dysfunction. Optimal function of the lungs and the process of ventilation is dependant on the normal function of the thoracic spine and the rib cage. Disturbances of the musculoskeletal components of the thoracic spine may lead to increased respiratory efforts, decreased lung function and in turn affect bronchopulmonary function. Obstructive respiratory diseases such as asthma, bronchitis and emphysema place an increased demand on the musculoskeletal components involved in expiration, as air has to be forcefully expired. The purpose of this quantitative, non experimental, demographic retrospective clinical survey was to retrospectively describe lower respiratory tract disorders and thoracic spine pain and dysfunction in subjects presenting to the Durban Institute of Technology Chiropractic Day Clinic, in terms of the prevalence of lower respiratory tract disorders as well as any association between the presenting respiratory conditions and their vertebral distribution in the thoracic spine. / M

Measuring the level of exhaled NO (eNO) in the breath is a new method to monitor airway inflammation in asthma and may have a role in the management of asthma. The hypotheses were that eNO will reflect the degree of inflammation in chronic asthma, and will indicate how anti- inflammatory therapy should be altered to improve asthma control. Three studies were performed to test the hypotheses. A cross sectional study was performed to define the normal range of eNO and to compare this range with those who have asthma or atopy. The second study was observational, to compare the level of eNO during and after an exacerbation of asthma. The third study was an interventional study to evaluate eNO in management of paediatric asthma. In this latter study the level of eNO was measured to monitor airway inflammation in asthmatic children with the intention of adjusting antiinflammatory drugs (inhaled glucocorticosteroids) according to the level of eNO. These studies have shown that the mean level of eNO was significantly higher in asthmatic compared with normal subjects, but not significantly different when compared with atopic non-asthmatic subjects. eNO was correlated with the number of positive skin prick tests in atopic subjects whether asthmatic or nonasthmatic. The eNO level was increased during acute exacerbations of asthma and decreased after two weeks with therapy of GCS. In a pilot study eNO appeared to be superior to FEV1 in adjusting the dose of iGCS to control asthmatic children, but this needs to be confirmed with a larger sample size. Another non-invasive method to detect inflammatory markers is the technique of exhaled breath condensate (EBC). Although NO is degraded to NOx, it was found that eNO had no significant correlation with EBC NOx but had a significant correlation with pH. Hypertonic saline challenge, an artificial model of an asthmatic exacerbation was associated with an increase in EBC volume and the release of histamine, implicating mast cell activation. These novel findings suggest that non-invasive markers can be used both for clinical and mechanistic proposes.

Includes bibliographical references (leaves 234-280) / xxviii, 292, [72] leaves : ill. (some col.), plates (some 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, Dept. of Medicine, 2002

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging viral respiratory diseases such as avian influenza H5N1 and H7N9, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Previous studies carried out by PhD students in our lab found that mouse β-defenisn 4 (mBD4) shows highly antiviral activity in vitro. However, the recombinant mBD4 (rmBD4) expressed by E.coli is limited to very small scale of production and is very expensive. Thus, in this study, we firstly screened 16 short peptides derived from mBD4 and other mouse and human β-defensins for identifying their antiviral effects. One short peptide P9 (30 amino acids), derived from mBD4, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses, including influenza A viruses H1N1, H3N2, H5N1, H7N7 and H7N9, SARS coronavirus (SARS-CoV)and MERS coronavirus (MERS-CoV). This P9 showed very high selectivity index (970), which was higher than that of the full-length peptide of synthetic mBD4 (smBD4) and rmBD4 in vitro. Secondly, the prophylactic and therapeutic effects of P9 against the infection of H1N1 virus were further detected in animal model. The survival rate of P9-pretreated mice challenged by lethal dose of H1N1 virus was 100%. The therapeutic effects of P9 protecting mice from lethal challenge of H1N1 virus were also statistically significant. The survival rate of mice could reach up to 67% by intranasal inoculation and 56% by intraperitoneal injection, respectively. To investigate the antiviral mechanism, we firstly elucidated that P9 could inhibit viral infection but not viral replication or release. Secondly, we detected whether P9 inhibited viral infection by binding to the surface of target cells or viral particles. The results showed that P9 only bound to viral particles but not to the cell surface. It was further identified that P9 bound to viral surface glycoprotein HA but not NA. Thirdly, we demonstrated that P9 did not inhibit virus binding to its receptor and block the virus entry into cells by endocytosis. Instead, P9 inhibited the acidification in late endosomes and thusP9 blocked virus-membrane fusion and subsequent viral disassembly and viral RNA release. Finally, we elucidated that the antiviral activity of P9 was attributed to its high binding affinity to viral HA and the abundance of basic amino acids in its composition. In this study, we have demonstrated that a short peptide P9, which is derived from mBD4, showed potent antiviral activity against multiple respiratory viruses. This peptide can be developed to a new promising prophylactic and therapeutic agent with broad-spectrum antiviral activity and low possibility to cause drug resistance. Moreover, this study has also revealed a novel antiviral mechanism for P9 and paved a path for the development of new antiviral agents with broad-spectrum antiviral activity against emerging respiratory viruses, such as avian influenza H5N1 and H7N9, as well as SARS-CoV and MERS-CoV. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy