We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
Functional Connectivity Between Visual Cortical Areas In The Non-human Primate
Funder
National Health and Medical Research Council
Funding Amount
$387,585.00
Summary
Visual information going from the eyes to the brain is processed in different parts of the brain to extract useful information. However, to be able to select what is important from among the vast number of objects in the scene, top-down signals from higher areas need to act on incoming signals in earlier areas. This project aims to identify what sort of neural pathways are involved in this and how it is done at the cellular level.
Impaired Bone Remodelling Leads To Failure Of Orthopaedic Prostheses
Funder
National Health and Medical Research Council
Funding Amount
$515,917.00
Summary
The failure of bone prostheses is becoming a major health problem. More than 26,000 hip, and an equal number of knee, replacements were performed in Australia in 2002 with the number increasing between 5%-10% each year for the previous 10 years. Disturbingly, the incidence of revision hip surgery in Australia is now more than 15%, meaning that, despite the impressive success of joint replacement surgery, a significant number of arthroplasties fail. It is becoming more common for young, active in ....The failure of bone prostheses is becoming a major health problem. More than 26,000 hip, and an equal number of knee, replacements were performed in Australia in 2002 with the number increasing between 5%-10% each year for the previous 10 years. Disturbingly, the incidence of revision hip surgery in Australia is now more than 15%, meaning that, despite the impressive success of joint replacement surgery, a significant number of arthroplasties fail. It is becoming more common for young, active individuals to receive joint replacement surgery to improve their quality of life. This, combined with increasing life expectancy, and the known higher rate of failure of joint replacements in younger patients, means that the morbidity of a failed replacement, and the mobidity and associated mortality of revision surgery, will become an increasingly important health issue, with a major impact upon health budgets. The overwhelming majority of hip and knee prostheses have metal or ceramic on polyethylene bearing surfaces. It is now apparent that most implants fail due to bone loss around them leading to loosening, and evidence is accumulating that polyethylene wear particles are a major contributing factor to this process. It is therefore vital that we obtain better understanding of the causes of implant failure in order to extend the life of these implants and this project is designed to do so.Read moreRead less
Organization And Function Of Primate Auditory Cortex
Funder
National Health and Medical Research Council
Funding Amount
$271,671.00
Summary
The conscious perception of speech and other sounds depends on processing within a brain region known as the auditory cortex. Compared to other brain areas, relatively little is known about the organization and function of this structure. Recent studies have proposed that the auditory cortex may be anatomically subdivided into functional modules, each of which is specialized for processing different types of information. However, the evidence for multiple processing streams is fragmentary, and n ....The conscious perception of speech and other sounds depends on processing within a brain region known as the auditory cortex. Compared to other brain areas, relatively little is known about the organization and function of this structure. Recent studies have proposed that the auditory cortex may be anatomically subdivided into functional modules, each of which is specialized for processing different types of information. However, the evidence for multiple processing streams is fragmentary, and not entirely consistent. The proposed experiments will combine anatomical and physiological approaches to evaluate the functional organization of auditory cortex in the primate brain. We will map the electrical responses of single brain cells to various complex sounds across the brain surface, and inject dyes to label pathways linking brain areas to one another. The data will allow us to determine whether specific subdivisions of the auditory cortex are specialized for processing different types of infomation, and whether specific subdivisions are linked together to form processing streams specialized for sound recognition and space perception. The results will advance our understanding of the neuronal processing involved in the perception of sound, with possible implications for speech perception. This will help to understand the consequences of brain damage, and may inform the development of hearing aids and artificial voice recognition systems. In addition, this study will help to develop a primate model for studying brain mechanisms of sound recognition that should be useful in research on cochlear implants.Read moreRead less
Thalamic And Basal Forebrain Contributions To Auditory Cortical Reorganization Produced By Partial Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$364,768.00
Summary
When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, ....When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, it would have important consequences for the way in which input from a hearing aid or cochlear prosthesis (bionic ear) is processed in the brain. This Project is designed to clarify the nature of the systems in the brain that contribute to this form of cortical plasticity, using an animal model. One aim is to determine whether the plasticity is intrinsic to the cortex or occurs in the pathways over which information is conveyed to the cortex. This will be assessed by determining whether such plasticity is also found in the auditory thalamus, the final subcortical auditory nucleus from which information is sent to the cortex. The second aim is to determine whether the occurrence of plasticity is controlled by modulatory influences from the basal part of the forebrain. Neurons in this area project to many parts of the cortex, and evidence from other sensory systems suggests that these projections exert a permissive function, allowing the cortex to reorganize when input is altered. This aim will be pursued by determining whether cortical reorganization occurs after hearing loss when this basal forebrain system is inactivated. The significance of these studies is that they will elucidate the way in which the brain reorganizes itself when it is confronted with altered input. This information is important for our understanding of normal auditory information processing mechanisms and of the way in which input from prosthetic devices is processed in the hearing-impaired.Read moreRead less
MULTI-CENTRED CLINICAL EVALUATION OF A NOVEL KERATOPROSTHESIS
Funder
National Health and Medical Research Council
Funding Amount
$515,091.00
Summary
The prosthesis developed by applicants, known also as Chirila keratoprosthesis, is an artificial implantable device designed to replace a diseased cornea or a failed corneal graft, and can be used in patients with no hope for a conventional replacement of the cornea with donor tissue. The device may ultimately find a wider application, as it has the potential to give better visual results than human donor grafts. Even when not rejected, the donor grafts may lead to problematic healing patterns a ....The prosthesis developed by applicants, known also as Chirila keratoprosthesis, is an artificial implantable device designed to replace a diseased cornea or a failed corneal graft, and can be used in patients with no hope for a conventional replacement of the cornea with donor tissue. The device may ultimately find a wider application, as it has the potential to give better visual results than human donor grafts. Even when not rejected, the donor grafts may lead to problematic healing patterns and astigmatism, both limiting the final vision of patients. From the 45 million blind people worldwide, at least 10 million are due to corneal diseases or trauma. The figures released by WHO suggest a doubling of this number by year 2020. Many countries are unable to provide sufficient donor corneas, sometimes for cultural-religious reasons. In developed countries, the replacement with donor tissue is a common procedure, but many patients remain untreated because their prognosis for successful grafting is poor. Figures released in Australia show that long-term success of donor transplantation is unlikely in the patients identified as high-risk recipients. Furthermore, even technically successful cases show disppointing final vision. The significance of the applicants' artificial cornea is that allows high-risk, or otherwise untreatable corneal blind patients, to have their vision restored, and it could ultimately reduce the need for donor corneal tissue. A phase I pilot study has been completed, and Phase II is currently underway with support from NH and MRC. These studies showed that the Chirila KPro is an effective means of reversible replacement of a diseased cornea.The proposed Phase III will evaluate both safety and effectiveness in different categories of patients in comparison with published outcomes of donor grafting, and will establish unequivocally the clinical potential of this prosthesis.Read moreRead less
QUANTITATIVE ASSESSMENT OF LOOSENING IN HIP ARTHROPLASTIES USING MECHANICAL VIBRATION DIAGNOSTICS
Funder
National Health and Medical Research Council
Funding Amount
$185,665.00
Summary
Recent advances and improvements made to the mechanical design of artificial joints have led to greater strength, fatigue life and wear resistance. However, this extension to the working life of joint replacements has led to patients becoming increasingly vulnerable to the problem of joint loosening. There are over 500 000 hip joint replacements performed every year, on a worldwide basis. Of these 7 to 13% will require revision surgery because of loosening at some stage of their working life. Th ....Recent advances and improvements made to the mechanical design of artificial joints have led to greater strength, fatigue life and wear resistance. However, this extension to the working life of joint replacements has led to patients becoming increasingly vulnerable to the problem of joint loosening. There are over 500 000 hip joint replacements performed every year, on a worldwide basis. Of these 7 to 13% will require revision surgery because of loosening at some stage of their working life. This is becoming a major concern to health services around the world since revision surgery is associated with a higher risk to the patient and costs are far greater than for the primary operation. Current diagnostic techniques using radiographic imaging are both invasive and lack diagnostic accuracy. The ability to detect joint loosening and to discriminate between the various causes of joint loosening following arthroplasty is of great importance to the success of subsequent care plans. This study will be the first in the world to assess the validity of a new diagnostic test that uses low energy mechanical vibration to quantify the degree of loosening in both components of the implanted hip joint. Once the technique has been proven it could readily be extended to evaluate the degree of fixation of other implanted prostheses used to replace the knee, ankle or joints of the upper limbs.Read moreRead less
Both hearing and balance are vulnerable during ear surgery, and the loss of either carries a heavy personal, social and economic cost. We will develop new ways of protecting the ear during surgery, though the local delivery of medication to the inner ear. The protocol will be developed in the laboratory and tested in a clinical trial. This research will stand to benefit all people undergoing major operation on their ear, and especially cochlear implant candidates with residual hearing.