It is known that about 10% of patients over the age of 55 have difficulty with cognition and thinking 3 months after surgery and anaesthesia. Over 2 million operations involving anaesthesia are administered in Australia every year and increasingly the patients are elderly and thus exposed to the risk of cognitive decline after surgery. We have preliminary data showing that people who have mild changes in cognitive function before the surgery (known as mild cognitive impairment) are susceptible t ....It is known that about 10% of patients over the age of 55 have difficulty with cognition and thinking 3 months after surgery and anaesthesia. Over 2 million operations involving anaesthesia are administered in Australia every year and increasingly the patients are elderly and thus exposed to the risk of cognitive decline after surgery. We have preliminary data showing that people who have mild changes in cognitive function before the surgery (known as mild cognitive impairment) are susceptible to further cognitive decline after anaesthesia and surgery. In order to explore the relationship between preoperative cognitive function and postoperative cognitive decline we plan to measure cognition in patients scheduled for elective hip replacement surgery. This is done by asking patients to complete a standard battery of cognitive tests. We will be then able to identify those patients who already have mild cognitive impairment before surgery and by repeated testing after the operation will be able to demonstrate if preoperative cognitive status is a determinant of postoperative cognitive dysfunction. The primary aim of the research is to test whether cognitive impairment before surgery leads to cognitive deficit after surgery in patients over the age of 65 undergoing total hip replacement surgery. The study will also establish the prevalence of pre-operative mild cognitive impairment and the magnitude of postoperative cognitive dysfunction after surgery in this patient group. The study will explore the relationship between preoperative cognitive status and postoperative cognitive deficit , providing information about the incidence, natural history and risk factors of postoperative cognitive deficit. This work will enable further research to isolate specific causative factors and identify therapeutic and prophylactic strategies.Read moreRead less
B-1 B Cells As A Source Of Polyreactive IgE Antibodies, In Allergic Individuals
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare ....Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare groups of patients defined according to their allergic conditions and age, to see whether B-1 B cell activity is associated with particular allergic diseases. We hypothesise that patients with allergic skin conditions have raised numbers of allergy-inducing B-1 cells. Such patients will be compared with those with allergies to inhalent allergens and others with food allergies. Studies will be performed in adult groups as well as in children, for B-1 B cell numbers are known to vary with age. As most of our understanding of the regulation of B cell function, in the context of allergic disease, has arisen from studies conducted with conventional B-2 cells, we also wish to reconsider aspects of B cell regulation. We are specifically interested in the regulation of the 'switching' of B-1 B cells, when they change from the production of antibodies of a 'non-allergic' type (IgM antibodies) to allergy-promoting IgE antibodies. We wish to determine whether the B-1 B cells of allergic individuals are particularly susceptible to such switching, when under the influence of regulatory molecules called cytokines. We expect that B-1 B cells will be associated with some, though not all allergic conditions, and that these cells will emerge as a new target for therapies. Such a finding would be most important. The development of new therapies will require a better understanding of the regulation of these cells, and this will be another important outcome of this project.Read moreRead less
‘Granny was never the same after her operation’ is a strong public perception. These reports of persistent memory and concentration loss following surgery are now supported by a body of scientific research recording an incidence of ‘postoperative cognitive decline’ (POCD) as high as 75% in cardiac surgery patients. At present the cause is unknown but recently anaesthesia has been implicated. Our research team will investigate these claims.
This project will examine new ways in which the major effector cells of allergy migrate to sites of inflammation, such as the lung and the skin and are activated locally by a novel S100 protein mediator. We have found a natural protein of the innate immune system, present in macrophages and neutrophils in the lungs of patients with acute fatal asthma, which activates mast cells causing release of mediators that trigger asthma attack. We have identified a potential receptor for this protein on hu ....This project will examine new ways in which the major effector cells of allergy migrate to sites of inflammation, such as the lung and the skin and are activated locally by a novel S100 protein mediator. We have found a natural protein of the innate immune system, present in macrophages and neutrophils in the lungs of patients with acute fatal asthma, which activates mast cells causing release of mediators that trigger asthma attack. We have identified a potential receptor for this protein on human mast cells grown in culture. We will characterise the chemical nature of this receptor and verify that it is functionally important in mast cell activation. Because mast cells reside in almost all body tissues and are also important mediators of host responses to infection and in chronic inflammation such as rheumatoid arthritis and psoriasis, our studies may indicate novel and unexpected ways in which they are activated. Another key cell in allergic and parasitic diseases is the eosinophil. We have found that two other S100 proteins are expressed in eosinophils from the blood of normal individuals and that the genes that encode these proteins are regulated by mediators that regulate eosinophil migration and survival at allergic sites. However although the numbers these cells are high in lung biopsies from patients with asthma, we find that these proteins are generally not expressed. Because one of the S100 proteins, S100A9, was recently found to be important in the ability of other blood cells to migrate to signals that recruit them into tissues, we will examine whether this protein regulates the ability of eosinophils to migrate. Results from this project will provide new knowledge concerning mechanisms of allergy and may lead to the design of novel strategies to regulate the process. Results may have broader ramifications applicable to other inflammatory and infectious diseases.Read moreRead less
Role Of Maternal Dietary Omega3 Fatty Acids In Modulation Of Allergen-specific T Cell Responses In The Offspring
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
Environmental lifestyle changes are implicated in the concerning increase in allergic diseases such as asthma and allergic diseases over the 25 years. Despite the enormous personal, social and economic cost, the exact causes are not clear. Diet is one of the most important yet unstudied environmental exposures linked to the recent increase in both asthma and allergic disease. Authorities in this area have recommended diet as research priority in the search for allergy prevention strategies. Alle ....Environmental lifestyle changes are implicated in the concerning increase in allergic diseases such as asthma and allergic diseases over the 25 years. Despite the enormous personal, social and economic cost, the exact causes are not clear. Diet is one of the most important yet unstudied environmental exposures linked to the recent increase in both asthma and allergic disease. Authorities in this area have recommended diet as research priority in the search for allergy prevention strategies. Allergic diseases result from inappropriate inflammatory immune responses to protein substances such as dust mite (allergens), and it now evident that these patterns of immune responses are commonly initiated before birth. This study will address the influence of maternal diet in pregnancy on the developing human immune system, and how it contributes to the development of allergic immune responses in offspring. One of the most significant dietary changes associated with increasing urbanisation is the increasing intake of pro-inflammatory omega-6 fatty acids (which may promote allergic immune responses) and declining dietary levels of omega-3 fatty acids (which inhibit inflammatory immune responses). Omega-3 fatty acids have beneficial effects in many inflammatory diseases, and are important for healthy pregnancy. It is possible that maternal diets which are becoming increasingly deficient in omega-3 fatty acids may prime the fetus to respond more readily to allergens, and increase the risk of later allergic responses. This study will determine whether increasing dietary omega-3 fatty acids during pregnancy using fish oil supplements, can alter immune responses to house dust mite and other allergens at birth and later infancy. The findings will contribute to our understanding of the relationship between antenatal nutrition and immune development and may lead to dietary recommendations as a cost effective, non invasive strategy to help prevent allergic disease.Read moreRead less