2990 Microsurgery.qxd - O'Brien Institute

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Overview of Research Bernard O’Brien Institute of Microsurgery PLASTIC SURGERY UNIT The workload within the Plastic Surgery Unit at St Vincent’s Hospital continues to have a large bias towards major reconstructive surgery following cancer resection or trauma. The reputation of the Bernard O’Brien Institute of Microsurgery enhances referrals to this unit, and the successful outcome of the procedures is in part attributable to the good work of the many research fellows at the Institute. The interchange of ideas between the microsurgery fellows gathered from around the world, and the Australian trainees who attend our clinic, makes the academic atmosphere with the unit enjoyable and educational. Many of the reconstructive procedures which have become commonplace within the Plastic Surgery Unit have developed with ideas from the Bernard O’Brien Institute of Microsurgery, and the constant stimulation of the research environment encourages the clinical team to be constantly searching for solutions to unresolved surgical dilemmas. The work of the Plastic Surgery Unit at St Vincent’s Hospital would tend to drop back to the mundane were it not for the Bernard O’Brien Institute of Microsurgery, to which we extend our thanks, and to whom we look forward for future co-operation. Victorian Minister for Health and Human Services, The Hon. Rob Knowles; Professor Wayne Morrison and Chairman, Mr Ronald Walker. 7
Director’s Report Bernard O’Brien Institute of Microsurgery The breadth of research topics under investigation has increased and this has attracted new staff with new expertise and new collaborations. Surgery in the fields of tissue repair and regeneration includes most tissues of the body including skin, muscle, bone, nerve and blood vessels. Research into the mechanisms of repair and regeneration of these structures and ways to artificially alter or engineer these processes is capturing the imagination of the lay press as well as big business as they see the exciting potential of manufacturing body parts and organs. The mind stretches to the possibility of manufacturing tissues in the laboratory by the use of artificial heart/lung machines, or incubating them in animals. Harvard University’s world wide coverage of the human ear growing in a mouse was an example of this. Similarly, following the unique face reattachment that we performed on a young woman in late 1997 which also received huge international publicity, the question was asked ‘are we ready for face transplants?’ Unfortunately, despite further publicity of a hand transplant being performed in France (September 1998), the state of immunological developments, namely the ability to prevent rejection, has not yet reached sufficient reliability to justify such non-vital organ transplants. In this area we have two highly original projects with exciting potential. The first involves peripheral nerve regeneration using the Melbourne-discovered growth factor, Leukaemia Inhibitory Factor (LIF). We have shown its powerful capacity to promote new nerve growth following injury and to protect muscle from degeneration. The effect is obtained using minute doses applied directly to the injured nerve at the time of surgical repair. In conjunction with AMRAD we hope to perform a trial of this in humans in the near future. The second project is a model of generating living tissue which, when incorporated into moulds, can be grown to whatever shape or design is chosen. Currently the tissue produced is predominantly dermis-like which can be transferred to any part of the body by microsurgical techniques for the repair of skin and muscle defects. We are working on the possibility of converting these growing tissues into more specialised types, eg. fat, cartilage or bone, so that organs such as breasts, ears, blood vessels, etc. may be manufactured. For many years this Institute has continued its investigation into the effects of trauma on tissues, especially interference with blood supply (ischaemia). The tissue damage which occurs in response to this type of trauma is known as ischaemia-reperfusion injury. This same fundamental process occurs following heart attacks and strokes. In our field of reconstructive surgery the most graphic and definitive example of this is amputation of body parts where the circulation is totally disrupted, but lesser injuries cause a spectrum of long term disability even though the tissue itself survives. Reversal of the effects of ischaemia can have a major impact on reducing the degree of initial injury and the consequent long term permanent disability and deformity. The scaling down of our ischaemia model from the rat to the mouse has allowed us to use knockout genetic techniques where a specific gene responsible for producing a particular molecule has been eliminated. This allows us to test the effect of certain physical or chemical agents on animals without that particular molecule. Mice which have iNOS, an enzyme which produces nitric oxide, and complement ‘knockout’ have clear protection from ischaemia. New drugs are being trialled, especially those which prevent nitric oxide formation, and these appear to have a dramatic effect in reversing the tissue damage caused by interference to the circulation. Using mast cell deficient mice our most recent studies suggest a very significant protection if mast cells are deleted. Nitric oxide has ubiquitous functions but its roles in blood vessels, especially blood vessel wall thickening, new blood vessel growth (angiogenesis), and reperfusion injury are of special interest to us in our research into tissue repair, tissue engineering, replantation, transplantation and in cancer. Inflammation is the fundamental body response to injury and is integral to the repair process. The macrophage cell is one of the key players in inflammation and its functions and mechanisms of activation represent a new direction of our research. We have found that cyclin D2, a nuclear protein primarily thought to be concerned with cell division also has a role in cell activation, especially in the macrophage. This offers new avenues for the pharmacological manipulation of inflammatory diseases and processes such as wound healing. Many other topics are being investigated and they are detailed under the section headed ‘Research’. It has been a pleasure to be involved in the many projects which cross-link with more and more colleagues at other Research Institutes. We are delighted to be host to postgraduate students from other University Departments, especially Pathology (Melbourne) Professor Colin Masters, Pharmacology (Melbourne) with Professor James Angus and Forensic Medicine (Monash) with Professor Stephen Cordner. These collaborators have been so generous with their time and facilities and their Institutes are acknowledged elsewhere in this report. 8
Page 1 and 2: Bernard O’Brien Institute of Micr
Page 3 and 4: Patrons PATRON-IN-CHIEF His Excelle
Page 5 and 6: Chairman’s Report Microsurgery Fo
Page 7: Overview of Research Bernard O’Br
Page 11 and 12: Director’s Report Bernard O’Bri
Page 13 and 14: Scientific Research Bernard O’Bri
Page 27 and 28: Full and Part-Time Staff Bernard O
Page 29 and 30: Publications Bernard O’Brien Inst
Page 31 and 32: Collaborations Bernard O’Brien In
Page 33 and 34: Presentations Bernard O’Brien Ins
Page 35 and 36: Visiting Lecturers Bernard O’Brie
Page 37 and 38: Named Fellowships Bernard O’Brien
Page 39 and 40: Financial Statements PROFIT AND LOS
Page 41: Donations Bernard O’Brien Institu

2990 Microsurgery.qxd - O'Brien Institute

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