No description available.

No description available.

No description available.

Thesis (M.D. 1980) from the Department of Surgery, University of Adelaide.

No description available.

Oedema is the presence of excess fluid in the body tissues (Guyton & Hall, 1997). During long air flights, blood pools in the body tissues due to decreased muscle movement. This causes bilateral ankle oedema and results in an increased risk of deep vein thrombosis as well as discomfort to the passengers after their flight (Hope et al., 2001). Hamamelis virginica is clinically indicated as a homoeopathic remedy which acts upon the venous system (Nash, 2002). Apis mellifica, Apocynum cannabinum, Natrum muriaticum and Natrum sulphuricum are all homoeopathic remedies used in the treatment of oedema. The aim of this study is to ascertain the efficiency of the Homoeopathic complex formula, Hamamelis virginica 30cH, Apis mellifica 6cH, Apocynum cannabinum 6cH, Natrum muriaticum 6cH and Natrum sulphuricum 6cH in the treatment of swelling (bilateral oedema) in the lower extremities in women during and after long air flights. This study is a double blind, placebo controlled trial. Forty female participants, between the ages of eighteen to thirty-nine, with a previous history of ankle swelling after long air flights and who were planning long air flights of eight hours or more, were recruited by means of advertisement for this study. Participants meeting the inclusion criteria underwent an examination and were matched in terms of age and risk factors; weight, cigarette smoking, oral contraception, alcohol and coffee consumption. The participants within the matched pairs were then assigned to one of two groups. One group was randomly assigned the experimental group and the other the control. Participants were required to take six powders sublingually without water. The first powder was taken two hours before the actual flight. The second, third and fourth powders were taken every two and a half hours during the course of the fight and the fifth powder was taken after the flight landed. The sixth powder was taken the day after the flight. The participants were measured by the researcher (Appendix D), measuring the circumference of their calf, ankle and foot. The participants were instructed to do three measurements, the first on the day of their flight, the second on the day they arrive at their destination and the third, on the day after their last dose of medication. The measurements were recorded and a questionnaire completed (Appendix E). The data obtained from the participants measurement and questionnaire form was statistically analysed using the repeated measures test, paired t-test, descriptive statistics the crosstab, and the Huynh-Feldt test. Statistical analysis showed significant differences, P<0.05, between the control and medicated groups for the measurements in centimetres of the left ankle and right ankle. The results obtained from the research show that the homoeopathic complex medication in this study significantly reduces lower extremities oedema during long air flights, as compared to the control group. The control group, on the other hand, did show an increase in measurements of the lower extremities during the air flight. This implies that the placebo did not provide any benefit towards reducing the oedema of lower extremities in women during long air flights. Therefore the null hypothesis was rejected Preliminary findings suggest that the homoeopathic complex preparation of Hamamelis virginica 30cH, Apis mellifica 6cH, Apocynum cannabinum 6cH, Natrum muriaticum 6cH and Natrum sulphuricum 6cH, is effective in reducing the oedema of ankles during long air flights but more research is needed to confirm these findings. / Dr. E.M. Solomon Dr. J.L. Schultz

Secondary lymphoedema and venous oedema of the limb are the consequence of an imbalance between tissue fluid infiltrate and drainage, which leads to interstitial fluid accumulation, tissue changes, limb discomfort and morbidity. Numerous conservative therapies have been developed to address some of these negative outcomes, with a proportion of these being labour and cost intensive. This makes the investigation of cost effective and easy to implement home based regimes very important. One such therapy is limb exercise, which can be beneficial for limb oedemas through changes in both interstitial pressure and calf muscle activation. Therefore, this thesis explored the benefits of different exercise regimes for limb oedema of both lymphatic and vascular origin. This was achieved through a systematic review of existing conservative therapies for limb oedemas and four clinical trials investigating the benefits of home based exercise regimes. Results demonstrated that various positive and significant outcomes could be gained from the implementation of such regimes, including improvements in both subjective and objective parameters. These results reveal how these chronic and disabling conditions can be maintained by the patient in the home environment in between health care visits. It also demonstrates how self maintenance may alleviate the burden on the health care system.

Doctor of Philosophy(PhD) / The vast majority of children undergoing surgical repair of cardiac lesions do spectacularly well. However a significant proportion, ~ 25%, struggle to progress in the early postoperative period and require additional pharmacological and occasionally mechanical circulatory support. All children typically have some degree of postoperative myocardial dysfunction, with the severe spectrum termed the low cardiac output state (LCOS). LCOS is clinically defined as the requirement for new or escalated inotrope therapy, a widened arteriovenous oxygen difference, cardiac arrest or the need for reinstitution of mechanical circulatory support. LCOS is largely responsible for the morbidity and mortality involved in paediatric cardiac surgery. Despite the predictability of LCOS in the initial postoperative hours, the underlying pathophysiology remains unclear. The period of decline in cardiac function that typifies LCOS is temporally associated with the development of oedema in the tissues of the body, including the heart. This relationship between oedema and dysfunction has increasingly become blurred, with a tendency to elevate the temporal association to a causal link. We sought to explore the causes and contributions to myocardial dysfunction in this setting, including the roles of oedema and ischaemia within the heart. In focusing on oedema and ischaemia we also examined the effects of these insults on relevant myocardial membrane proteins, including those that permit rapid water transport – aquaporins (AQPs), and those involved in membrane mechanics – dystrophin, and membrane repair – dysferlin. Experimental settings which enabled the in vitro dissection of these insults and proteins of interest were combined with a clinically accurate in vivo model. This thesis describes a series of thematically linked experiments that examined LCOS, myocardial oedema and the role of various membrane proteins. We performed isolated cardiomyocyte studies, isolated heart studies as well as a clinically relevant large animal (lamb) cardiopulmonary bypass (CPB) model. Across these models we also explored the role of therapeutically protecting myocardial membranes with Poloxamer 188 (P188) and assessed any influence on myocardial function, oedema and membrane proteins. vi The results from these three models suggest that the clinically accepted dogma of a causative link between myocardial oedema and dysfunction overstates the contribution of myocardial oedema to LCOS. We found that ischaemia/reperfusion was of primary importance in causing myocardial dysfunction. Myocardial oedema without ischaemia had a mild and reversible contribution to myocardial dysfunction, but this was minor in comparison to the gross dysfunction attributable to ischaemia. Isolated cardiomyocytes, with induced oedema, functioned well. Whilst ischaemic cardiomyocytes, with less swelling still had severe contractile dysfunction. Isolated hearts, perfused with an oedema inducing crystalloid perfusate developed myocardial oedema and had minimal reversible systolic and diastolic dysfunction. Isolated hearts which experienced global ischaemia had comparable degrees of myocardial oedema, and significantly greater degrees of myocardial dysfunction that increased in severity with increasing duration of ischaemia. In the lamb CPB model, only those lambs which underwent aortic cross clamping and had a period of ischaemia had poor myocardial function. These lambs also had swollen hearts, raised myocardial AQP1 mRNA and reduced membrane dysferlin protein expression. Membrane dystrophin protein expression was not altered, somewhat unexpectedly with CPB with or without ischaemia. Lambs placed on CPB without ischaemia had good myocardial function, minimal oedema and unchanged membrane protein expression during the survival period. In a blinded lamb CPB trial of P188 there were improved haemodynamics and indicies of myocardial function associated with its use. This was also associated with preservation of dysferlin expression and reduced membrane injury. In parallel isolated heart trials of this therapy, there was a reduction in myocardial oedema associated with its use in non-ischaemic experiments. There was also a suggestion of improved diastolic function in ischaemic experiments, but no change in myocardial water content. In conclusion, we have highlighted the primacy of ischaemia/reperfusion over oedema in contributing to LCOS. We have refuted the accepted dogma that myocardial oedema causes significant dysfunction in itself, with important oedema likely to result from ischaemia. We have shown that AQP1 may be involved in the pathogenesis of the capillary leak syndrome. Finally we have hinted at a role for prophylactic P188 in the vii setting of LCOS, possibly highlighting the role of membrane repair in recovery after surgery. Isolated heart trials of P188 further support a non-rheological mechanism of action and also lend support to the causal separation of myocardial oedema and dysfunction. The integral membrane protein dysferlin, rather than dystrophin, is relevant in the setting of LCOS in the current era.

Doctor of Philosophy(PhD) / The vast majority of children undergoing surgical repair of cardiac lesions do spectacularly well. However a significant proportion, ~ 25%, struggle to progress in the early postoperative period and require additional pharmacological and occasionally mechanical circulatory support. All children typically have some degree of postoperative myocardial dysfunction, with the severe spectrum termed the low cardiac output state (LCOS). LCOS is clinically defined as the requirement for new or escalated inotrope therapy, a widened arteriovenous oxygen difference, cardiac arrest or the need for reinstitution of mechanical circulatory support. LCOS is largely responsible for the morbidity and mortality involved in paediatric cardiac surgery. Despite the predictability of LCOS in the initial postoperative hours, the underlying pathophysiology remains unclear. The period of decline in cardiac function that typifies LCOS is temporally associated with the development of oedema in the tissues of the body, including the heart. This relationship between oedema and dysfunction has increasingly become blurred, with a tendency to elevate the temporal association to a causal link. We sought to explore the causes and contributions to myocardial dysfunction in this setting, including the roles of oedema and ischaemia within the heart. In focusing on oedema and ischaemia we also examined the effects of these insults on relevant myocardial membrane proteins, including those that permit rapid water transport – aquaporins (AQPs), and those involved in membrane mechanics – dystrophin, and membrane repair – dysferlin. Experimental settings which enabled the in vitro dissection of these insults and proteins of interest were combined with a clinically accurate in vivo model. This thesis describes a series of thematically linked experiments that examined LCOS, myocardial oedema and the role of various membrane proteins. We performed isolated cardiomyocyte studies, isolated heart studies as well as a clinically relevant large animal (lamb) cardiopulmonary bypass (CPB) model. Across these models we also explored the role of therapeutically protecting myocardial membranes with Poloxamer 188 (P188) and assessed any influence on myocardial function, oedema and membrane proteins. vi The results from these three models suggest that the clinically accepted dogma of a causative link between myocardial oedema and dysfunction overstates the contribution of myocardial oedema to LCOS. We found that ischaemia/reperfusion was of primary importance in causing myocardial dysfunction. Myocardial oedema without ischaemia had a mild and reversible contribution to myocardial dysfunction, but this was minor in comparison to the gross dysfunction attributable to ischaemia. Isolated cardiomyocytes, with induced oedema, functioned well. Whilst ischaemic cardiomyocytes, with less swelling still had severe contractile dysfunction. Isolated hearts, perfused with an oedema inducing crystalloid perfusate developed myocardial oedema and had minimal reversible systolic and diastolic dysfunction. Isolated hearts which experienced global ischaemia had comparable degrees of myocardial oedema, and significantly greater degrees of myocardial dysfunction that increased in severity with increasing duration of ischaemia. In the lamb CPB model, only those lambs which underwent aortic cross clamping and had a period of ischaemia had poor myocardial function. These lambs also had swollen hearts, raised myocardial AQP1 mRNA and reduced membrane dysferlin protein expression. Membrane dystrophin protein expression was not altered, somewhat unexpectedly with CPB with or without ischaemia. Lambs placed on CPB without ischaemia had good myocardial function, minimal oedema and unchanged membrane protein expression during the survival period. In a blinded lamb CPB trial of P188 there were improved haemodynamics and indicies of myocardial function associated with its use. This was also associated with preservation of dysferlin expression and reduced membrane injury. In parallel isolated heart trials of this therapy, there was a reduction in myocardial oedema associated with its use in non-ischaemic experiments. There was also a suggestion of improved diastolic function in ischaemic experiments, but no change in myocardial water content. In conclusion, we have highlighted the primacy of ischaemia/reperfusion over oedema in contributing to LCOS. We have refuted the accepted dogma that myocardial oedema causes significant dysfunction in itself, with important oedema likely to result from ischaemia. We have shown that AQP1 may be involved in the pathogenesis of the capillary leak syndrome. Finally we have hinted at a role for prophylactic P188 in the vii setting of LCOS, possibly highlighting the role of membrane repair in recovery after surgery. Isolated heart trials of P188 further support a non-rheological mechanism of action and also lend support to the causal separation of myocardial oedema and dysfunction. The integral membrane protein dysferlin, rather than dystrophin, is relevant in the setting of LCOS in the current era.

x, 148 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1980) from the Dept. of Surgery, University of Adelaide