Pathophysiology Of Postprandial Hypotension In The Elderly - Role Of Gastric And Small Intestinal Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$471,176.00
Summary
A fall in blood pressure after a meal (known as postprandial hypotension) is an important clinical problem, particularly in the elderly, occurring in ~50% of nursing home residents and ~30% of healthy older subjects. Postprandial hypotension is associated with a substantial increase in the incidence of falls, stroke, as well as mortality. The mechanisms responsible for the fall in blood pressure after a meal are not well understood, although changes in gastrointestinal blood flow and the release ....A fall in blood pressure after a meal (known as postprandial hypotension) is an important clinical problem, particularly in the elderly, occurring in ~50% of nursing home residents and ~30% of healthy older subjects. Postprandial hypotension is associated with a substantial increase in the incidence of falls, stroke, as well as mortality. The mechanisms responsible for the fall in blood pressure after a meal are not well understood, although changes in gastrointestinal blood flow and the release of gut hormones, have been implicated. While ingestion of carbohydrate, particularly glucose, has been reported to decrease blood pressure most potently, there is inadequate and conflicting information about the effects of other nutrients such as fat and protein. Current therapies are less than optimal. Studies by our research group have established that the fall in blood pressure in response to meals is related to the rate at which nutrients enter the small intestine ie the fall in blood pressure is greater when the stomach empties more quickly. In contrast, gastric distension reduces the fall in blood pressure. Hence, treatment could be directed at facilitating gastric distension and-or slowing the rate of nutrient delivery into the small intestine. Our previous studies have not included any assessment of changes in blood flow to the gut after meals, or of the interaction between gastric distension and small intestinal mechanisms, and have involved healthy older subjects and patients with type 2 (non-insulin dependent) diabetes rather than individuals with known postprandial hypotension. We now have the capacity to measure blood flow in the gut with ultrasound. The studies proposed in the current application represent a logical development from our previous work and have important implications for the management of postprandial hypotension.Read moreRead less
Progesterone Regulation Of Epithelial Cell Lineages In The Breast
Funder
National Health and Medical Research Council
Funding Amount
$534,186.00
Summary
The ovaries play a pivotal role in breast cancer in ways that are unknown. Progesterone increases breast cancer risk, and response to hormonal treatments is critically associated with tumour progesterone receptor content, but how it does this is unknown. We will pursue our findings that progesterone influences cell types in the breast similar to those that become cancerous. This will uncover critical vulnerabilities in breast cancer development and potential targets for prevention and treatment.
Progesterone Receptor Action In The Normal Human Breast
Funder
National Health and Medical Research Council
Funding Amount
$360,500.00
Summary
Breast cancer affects 10000 Australian women annually and is a major cause of cancer-related death. The hormone progesterone, which is produced by the ovaries in women, is responsible for many aspects of normal breast development and function. Progesterone is also a major component of hormone replacement therapy (HRT) and oral contraceptives (OCP), which are taken by millions of women worldwide. It has been established that the use of HRT and OCP containing progesterone-like hormones leads to in ....Breast cancer affects 10000 Australian women annually and is a major cause of cancer-related death. The hormone progesterone, which is produced by the ovaries in women, is responsible for many aspects of normal breast development and function. Progesterone is also a major component of hormone replacement therapy (HRT) and oral contraceptives (OCP), which are taken by millions of women worldwide. It has been established that the use of HRT and OCP containing progesterone-like hormones leads to increased breast cancer risk, yet the ways in which this happens are not known. Breast cancer is thought to begin early in a woman's life, with a number of genetic changes that accumulate over a period of many years; the majority of breast malignancies are not diagnosed until after the age of 50. However, there are recent indications that some areas of apparently normal breast have undergone a few genetic changes, even in women with no evidence of malignancy, but there is nothing known about how progesterone may affect these areas and possibly encourage breast cancer development. This project will firstly explore the influence of progesterone on the normal breast, to clarify how this hormone acts in normal cells. We will then investigate the involvement of progesterone in areas of normal breast that have undergone genetic alterations. This will determine whether one way in which progesterone may increase breast cancer risk is by affecting the behaviour of cells with genetic changes to make them more likely to develop further changes and subsequently progress to full cancer development. If women are to continue to derive the benefits of progesterone exposure, there is a compelling need to appreciate how progesterone acts in the normal breast and how it increases breast cancer risk. Achievement of the aims of this project will provide invaluable knowledge and greatly increase our understanding in this area.Read moreRead less
Object Recognition Processes For Motor Output Formation In Visual Agnosic Patients
Funder
National Health and Medical Research Council
Funding Amount
$199,260.00
Summary
Damage to the temporo-occipito-parietal areas of the brain leads to selective impairment in cognitive activities, including motor control and vision. Impaired higher visual processes necessary for object recognition, with intact primary visual functions, is defined as visual agnosia. Experimental work in this disorder has been confined largely to the perceptual aspects, neglecting the functional (motoric) consequences. In a series of kinematic and perceptual experiments, we will require patients ....Damage to the temporo-occipito-parietal areas of the brain leads to selective impairment in cognitive activities, including motor control and vision. Impaired higher visual processes necessary for object recognition, with intact primary visual functions, is defined as visual agnosia. Experimental work in this disorder has been confined largely to the perceptual aspects, neglecting the functional (motoric) consequences. In a series of kinematic and perceptual experiments, we will require patients with visual agnosia to grasp objects presented in unusual perspectives or variable illumination. The findings will enlarge our knowledge in three ways. First, they will clarify how distributed, but parallel object-recognition processes are coordinated for intended action towards a goal. Little is known about how we adapt our actions to object perception. A tool can be viewed from different angles, or as having different functional uses, but currently we are unable to explain how the mental representation influences the motor output to that tool. By studying a disrupted system, as in visual agnosia, we can speculate about the organisation of the intact system. Second, this project has important implications for new rehabilitative approaches for subjects affected by object recognition disorders. Only if we understand more fully the nature of the poor visuo-motor coordination, can we implement more efficient rehabilitative techniques. Finally, this project will also contribute to the classification of visual agnosia. Although it is commonly agreed that all agnosic patients are different, there is no standard taxonomy for the disorder. An instrument is necessary which represents the basic empirical phenomena, and which provides objective distinctions between different syndromes. Kinematic characterisation of the perceptual and motor control dysfunction in visual agnosia may be the key to open the file of this fascinating yet poorly understood disorder.Read moreRead less