2990 Microsurgery.qxd - O'Brien Institute

Bernard O’Brien Institute of Microsurgery 

St. Vincent’s Hospital 

20TH REPORT 

1997 – 1998

Contents 

FIELDS OF RESEARCH 

Areas covered: 

Trauma and its effects on tissues 

Inflammation 

Wound healing 

Tissue engineering 

Nerve and muscle regeneration 

Vascular Biology and its role in skin, 

muscle and bone circulation 

Respiratory research 

Cancer 

Involving the disciplines of: 

Surgery – Methods and Techniques 

Histopathology 

Biochemistry 

Molecular Biology 

Cell Biology and Physiology 

Vascular Biology 

Transplantation Immunology 

Neurophysiology 

Patrons 2 

Foundation Directors 3 

Chairman’s Report, Microsurgery Foundation 4 

Overview of Research 6 

Director’s Report 8 

Scientific Research 12 

Jack Brockhoff Nerve and Muscle Laboratory 13 

Trauma Laboratory 16 

Helen M Schutt Vascular Research Laboratory 20 

Henry & Miriam Greenfield Family Trust Molecular Biology Laboratory 23 

Airways Inflammation and Asthma Research Laboratory 24 

Full and Part-Time Staff 26 

Publications 28 

Collaborations 30 

Presentations 32 

Profiles 33 

St Vincent’s Hospital, Melbourne 


42 Fitzroy Street 

Fitzroy Victoria Australia 3065 

Telephone: (03) 9288 4018 

Facsimile: (03) 9416 0926 

E-mail: BOBIM@svhm.org.au 

Auditors 

KPMG 

Solicitors 

Corrs Chambers Westgarth 

Microsurgery Foundation 

ACN 004 822 244 

42 Fitzroy Street 

Fitzroy Victoria Australia 3065 

Telephone: (03) 9288 4018 

Facsimile: (03) 9416 0926 

E-mail: MICROFND@svhm.org.au 

Visiting Lecturers 34 

Australian and International Visitors 35 

Named Fellowships 36 

Financial Statements 37 

Donations 40 

OBJECTIVES 

To maintain international leadership by advancing knowledge through basic research 

and strong clinical programs in reconstructive microsurgery. 

To provide postgraduate training and continuing education by developing Academic 

Programs (Master of Surgery, Doctor of Medicine, Bachelor of Science with Honours, 

Master of Science, and Doctor of Philosophy), which will attract the most able students 

both nationally and internationally, and provide them with knowledge and skills of 

enduring value to equip them for leadership roles. 

To maintain and forge new links with other research institutions, both public and 

private, for cooperative research ventures. 

To contribute to the development of the health and well-being of the community 

by excellence in clinical care. 

1

Patrons 

PATRON-IN-CHIEF 

His Excellency, The Governor of Victoria 

The Hon. Sir James Gobbo, AC 

PATRON 

Sir Laurence Muir, VRD, LLB, FSIA, FAIM 

CONSULTATIVE SCIENTIFIC PANEL 

Professor G B Ryan, MB, BS, PhD, MD, FRACP (Chairman) 

Professor J A Angus, BSc(Hons), PhD 

Professor G J A Clunie, MB, ChB, ChM, FCS(Ed), FRCS(Eng), FRACS 

Professor J A Hamilton, DSc, PhD 

Emeritus Professor J Ludbrook, BMedSc, MB, ChB, DSc, ChM, MD, FRCS, FRACS 

Professor T J Martin, MD, DSc, MD(Hon), FRACP, FRCPA 

2

Foundation Directors 

CHAIRMAN 

IMMEDIATE PAST CHAIRMAN 

CHIEF EXECUTIVE OFFICER 

Alan Skurrie, BCom 

Ronald J Walker, AO, CBE 

SECRETARY 

Professor Wayne Morrison, 

MD, BS FRACS 

Geoffrey Renton, 

BHA (UNSW), FACHSE, MNIA, AFAIM 

DIRECTORS 

Professor James Angus 

BSc (Hons), PhD 

Sir Roderick Carnegie, 

MA(Oxon), MBA(Harvard) 

Tony Charlton, 

OAM 

Ivan Deveson, 

AO 

John Haddad, 

AM, FCIA 

Diana Jones, 

AM 

Rosemary Leffler 

Leon L’Huillier,, 

BCom(Melb), MPhil(Lon), MBA 

(Chicago), FAIM 

Allan MacLeod 

MB, BS, FRACS 

Josephine O’Brien 

BA, BArch (Hons) 

Mr Doug Provis 

Geoffrey Stephenson, 

BA 

Dr Clive Wellington 

Dean Wills, 

AO 

3

Chairman’s Report 


MICROSURGERY FOUNDATION 

The mission of the Microsurgery Foundation is 

to support financially the Bernard O’Brien 

Institute of Microsurgery. Public awareness of 

the work of the Institute and its plastic and 

reconstructive surgery and hand surgery team 

at St Vincent’s Hospital is largely through the 

reattachment of amputated body parts. Less 

well known is its sophisticated and expert 

microsurgical reconstruction of patients after 

cancer removal from breasts, head and neck, 

skin and bone cancers, etc. A steady stream of 

surgeons from around the world constantly 

come to train at the Institute and return to 

their own countries to adopt these new 

techniques. The Microsurgery Foundation is a 

dedicated group of business and professional 

people who, since its inception in 1970, have 

been responsible for raising funds for research, 

equipment and building infrastructure. It has 

established several scientific and surgical 

fellowships which attract highly qualified 

international candidates. The Foundation is a 

public company limited by guarantee, has no 

share capital and declares no dividend. 

AWARD 

We congratulate Professor Wayne Morrison on 

being awarded the Tattersalls Achievement Award 

in October 1997 for his work with the face and 

scalp replantation on a young woman from 

central Victoria. This operation received worldwide 

publicity and graphically demonstrated that new 

research developed at the O’Brien Institute can be 

applied directly for the benefit of patients. 

FUND RAISING 

On behalf of the Board I wish to thank those 

trusts, benefactors, corporate bodies and 

individuals who have supported us throughout 

the year. We have listed their wonderful 

donations and the research they sponsored in 

this report. The Board is very grateful for your 

generosity. A major priority in the future is to 

enhance the funding drive and establish new 

fellowship schemes in order to continue 

important research work and training. 

The humanitarianism of the Transport Accident 

Commission, under the Chairmanship of 

Margaret Jackson, in their ongoing support 

of funded projects into trauma deserves special 

mention. This wonderful gesture has allowed 

us to carry on research into tissue and limb 

protection and reconstruction following trauma. 

This research aims to minimise the severity of 

the initial injury, accelerate the rate of recovery 

and improve the quality of the results. 

The National Australia Bank has again given 

a Surgical Research Fellowship this year. This 

will assist in the training of microsurgeons in 

microsurgical research and techniques to 

benefit the community. 

PAIN RESEARCH AND CLINICAL 

MANAGEMENT 

A multidisciplinary centre for acute and chronic 

pain management has commenced at St Vincent’s 

Hospital. It focuses on patient care, educational 

programs and research. Research will be 

conducted through the Bernard O’Brien Institute 

of Microsurgery. The director is Dr Andrew Muir 

and already it is fulfilling a major community need. 

The initiative for this centre largely came from 

Barbara Walker who, because of her own 

experience of pain and through her public profile 

raised awareness of the silent epidemic of pain 

sufferers. The centre has received expert guidance 

and support from Professor Michael Cousins, 

Royal North Shore Hospital, Sydney, and generous 

start-up funding from Victorian WorkCover 

Authority. The centre will be opened by 

The Hon John Howard, Prime Minister of 

Australia, on 16 December, 1998. 

BOARD MEMBERS 

Members devoted their time to the Business Plan 

to place the Foundation and the Pain Research 

Centre in a prominent place for the Year 2000 

and beyond. They worked continuously during 

the year considering policy, finance, fund raising 

and the future of the Foundation. 

During the year Professor James Angus, 

Mr Allan MacLeod and Ms Josephine O’Brien 

(daughter of Mr Bernard O’Brien) joined the 

Board. We welcome our new members and 

look forward to their deliberations. These 

appointments followed the resignation of 

Emeritus Professor Gerard Crock, Dr John 

Connell, Mr Marc Besen, Mr Keith Dawson 

and Ms Norma Tullo. I would like to sincerely 

thank these Directors for their contribution over 

the years in providing leadership and guidance 

to the Foundation. The Board has made 

Dr John Connell and Mr Marc Besen Members 

of the Foundation. Professor Gerard Crock and 

Dr John Connell have been appointed to the 

Scientific Committee of Bernard O’Brien 

Institute of Microsurgery. 

We were all saddened to learn of the passing 

of our esteemed Board member and colleague, 

Mrs Jeanette Edwards, in April 1998. Our 

dedication to Jeanette is on the inside back cover. 

THE PAST 

We have commissioned a history of 30 years 

of Microsurgery, from 1970 through to 2000. 

Dean of Creative Arts, University of Melbourne, 

Associate Professor Angela O’Brien, will provide 

assistance in compiling this document. 

4

Chairman’s Report 


MILLENNIUM BUG 

The Board considered the implications of this 

upon our internal and external operations, 

finance, legal obligations, equipment and 

services provided. 

VISITORS 

We were privileged to have been visited by 

The Hon Rob Knowles, Minister for Health and 

Human Services to discuss medical research. 

Mr Stan Wallis, Dr John McKeane, Chief Medical 

Officer, National Mutual Ltd, Mr Gordon Tansey 

and Dr Ralph Green, RMIT, also visited the 

Institute during the past 12 months. 

THE FUTURE 

We now look forward to augmenting our 

research effort by application to National Health 

and Medical Research Council, corporations, 

governments, benefactors and donors. These 

funds are urgently needed to continue to train 

young surgeons and scientists in microsurgery 

research and to develop new clinical procedures 

and management programs for the benefit of 

the injured and infirm, including the alleviation 

of chronic pain. 

We value your financial participation and look 

forward to your continued partnership which 

is essential if we are to achieve these aims 

and objectives. 

RONALD J WALKER AO CBE 

CHAIRMAN 

Professor Wayne Morrison receiving the Tattersalls Achievement Award from Sir Gustav JV Nossall. 

5

Overview of Research 


Following trauma nerves as well as blood vessels 

are commonly injured and microsurgery is used 

to repair them. Nerves which function in a very 

similar way to electric cables are composed of 

long fibres which are direct extensions from the 

nerve cells housed in the spinal cord. When a 

nerve is cut in the same way that tadpoles’ tails 

regrow, so too the nerve will grow out again 

from its point of injury. We are experimenting 

with ways to enhance the outgrowth of nerves 

following injury, particularly using a special 

growth factor ‘Leukaemia Inhibitory Factor’. 

Ministerial Visit: Dr Alastair Stewart, Chief Scientist; Ms Tamara Konopka, BSc Hons Student; 

The Hon. Rob Knowles, Minister for Health and Human Services; and Mr Geoff Renton, Executive Director. 

WHAT IS MICROSURGERY 

RESEARCH? 

Microsurgery literally means operating through 

the microscope. In our field of Plastic and 

Reconstructive Surgery we use the microscope 

to connect small blood vessels (microsurgery) 

for the purpose of restoring circulation to 

amputated parts (replantation), or to tissues 

or parts that have been transferred from some 

other part of the body (transplantation) such 

as skin, muscle, bones, joints, toes, etc. 

This experimental research is widely applied to 

clinical reconstructive microsurgery in trauma, 

cancer, burns and congenital abnormalities. This 

spectrum of activity covers all ages from infancy 

to the elderly and illustrates one of the most 

important developments in modern surgery. 

Currently we can join 0.5 mm diameter blood 

vessels using stitches one half the thickness of 

a human hair but there is still a risk that these 

vessels will clot. When the circulation is reduced 

or ceases to a tissue, a condition known as 

ischaemia, that tissue will atrophy or die. The 

most familiar example of this is an ischaemic 

heart attack, but the same process occurs in 

strokes and gangrene of the limbs. 

At the Bernard O’Brien Institute of Microsurgery 

we are involved in research to understand 

the normal process of blood flow and factors 

which decrease it (ischaemia) or enhance it 

(angiogenesis). This will lead to new ways 

of reducing the effect of injury to tissues and 

to safer and more effective techniques of 

replantation, tissue transplants and even 

storage of tissue or tissue banks. 

By a better understanding of the process of 

blood flow and new blood vessel formation we 

will be able to help the healing of wounds, such 

as chronic ulcers, and be able to promote and 

manipulate the growth of tissues so that new 

parts can be manufactured in the body. This 

process has been termed ‘tissue engineering’ 

and we have recently used this technique in 

humans to grow ears and noses. 

Cancer growth is dependent on new blood 

vessels and by understanding how this process 

works we can potentially inhibit the new blood 

vessel formation which is essential for cancers 

to grow and spread. In breast cancer and 

melanoma models in mice we have been able 

to manipulate the cancer growth by using 

drugs which we have shown to be important 

in switching on and off the angiogenic process. 

The work of this Institute is broadly based and 

links many surgical disciplines and areas of 

applied science. Much collaborative work is 

in progress with other research institutes and 

departments, both in Australia and overseas. 

With the support of several trusts, industry and 

individuals the Bernard O’Brien Institute of 

Microsurgery has now been able to equip and 

staff dedicated laboratories to pursue our major 

areas of interest relating to microsurgery. There 

is close collaboration between laboratories with 

projects of common interest. 

The laboratories comprise: 

• Trauma Research Laboratory 

• The Jack Brockhoff Foundation Nerve 

and Muscle Laboratory 

• Helen M Schutt Vascular Research 

Laboratory 

• The Henry and Miriam Greenfield Trust 

Molecular Biology Laboratory 

• Respiratory Laboratory 

6

Overview of Research 


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 


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



The EMSU team, Dr Ruitong Fan, Sue McKay and Lisa Barton with surgeons, Mr Allan MacLeod and Mr Tony Penington. 

STAFF 

Mr Tony Penington was appointed senior 

lecturer in the Department of Surgery and senior 

research fellow at Bernard O’Brien Institute of 

Microsurgery in January 1998. Tony, after 

completing his medical degree at Melbourne 

University and fellowship in plastic and 

reconstructive surgery in 1995 undertook a 

Doctorate of Medicine at the Bernard O’Brien 

Institute and completed his research at Oxford 

under the supervision of Professor Peter Morris 

on the effects of ischaemia on endothelial cells. 

He was also appointed senior registrar at the 

Radcliffe Infirmary, Oxford, where he gained 

further experience in plastic and reconstructive 

surgery. Tony brings back expertise in a broad 

field of plastic surgery, including paediatrics as 

well as having a strong research background. He 

has a fertile and inquiring mind and will play a 

major role in forging new directions and 

supervising fellows and students at the Institute. 

Dr Alastair Stewart left us after six years to take 

up an appointment as senior lecturer in Professor 

Jim Angus’ Department of Pharmacology, 

Melbourne University, earlier this year. This was a 

great blow as Alastair has played a key role in 

directing our research focus, introducing new 

ideas and generally driving our program to new 

heights scientifically. His international reputation 

in the field of nitric oxide and his broad 

knowledge of the basic sciences generally 

enhanced our standing as a competitive 

scientific institute. Fortunately Alastair stays on in 

a part-time capacity, supervising ongoing 

projects and as a collaborator. We wish him well 

in his new direction and are confident that he 

will contribute greatly to pharmacology at 

Melbourne University. In like manner we thank 

his team, Trudi Harris, Ross Vlahos, Elizabeth 

Guida, Darren Fernandes, Anne Pirdas-Zivcic, 

Claire Ravenhall, Val Koutsoubos and Tamara 

Konopka, who have contributed so much to 

our Institute, both scientifically and socially. 

Dr Dan Crowe left us in February to take a 

new career path in science teaching. Dan had 

become part of our institution, having done 

his PhD with us and post-doctoral research. He 

made significant original contributions to the 

literature on the fate of blood vessel grafts and 

the development of potential vascular 

substitutes. He contributed broadly to many of 

the projects involving histopathology and was a 

valuable team member. He will especially missed 

in his key role in the Institute’s football team. 

We wish him well in his new career. 

We are delighted to have appointed Professor 

John Hamilton as part-time senior scientific 

director as of October 1998. John Hamilton 

is a senior principal research fellow, National 

Medical Research Council of Australia and 

Director of the Inflammation Research Centre, 

University of Melbourne Department of 

Medicine, Royal Melbourne Hospital. He 

has a very high profile nationally and 

internationally and an enviable record at 

attracting NHMRC and other research grants. 

His research is focused on inflammation, 

especially macrophage function and arthritis, 

but in many ways it overlaps our own research, 

especially with respect to wound healing, 

ischaemia-reperfusion injury and angiogenesis. 

John has been a long supporter of the Bernard 

O’Brien Institute as a scientific adviser and we 

see this as an exciting new collaboration with 

great potential. 

9



Left to Right: John Davis, Warwick Barnard, John Bower, Scott Baker, Sandra Pheney, Lawrie Austin, Tim Bennett, Professor Wayne Morrison, John Kurek and Professor Richard Bennett. 

FELLOWS 

Research fellows from overseas and Australia, 

many doing postgraduate degrees, contribute 

to the research program and as well participate 

in clinical work within St Vincent’s Hospital. 

Each undertakes a one year or more fellowship 

and gains a certificate in microsurgery and hand 

surgery. The following surgeons undertook 

microsurgery research during the period of 

this report. 

Tim Bennett, Melbourne 

‘The role of LIF in peripheral nerve regeneration’ 

Tim spent two and a half years at Bernard 

O’Brien Institute and is currently completing 

his MD. In his last 12 months he was appointed 

as plastic surgeon on the staff of St Vincent’s 

Hospital and as a consultant to the Skin and 

Cancer Foundation. He elucidated many of the 

actions of LIF in peripheral nerve and muscle 

and participated in several collaborative projects 

related to muscular dystrophy under the 

direction of Dr Lawrie Austin. Tim is currently 

undertaking further clinical plastic surgery 

training in Leeds, U.K. 

Yoshio Tanaka, Osaka, Japan 

‘Tissue matrix generation’ 

Yoshio, an Associate Professor in Plastic Surgery 

in Osaka, spent fourteen months with us 

researching tissue engineering. He has made 

several original observations which have 

potential clinical applications, especially for 

10 

reconstruction of tissue defects. Yoshio also 

contributed greatly to clinical microsurgery at 

St Vincent’s Hospital. He returned to Osaka 

mid year and it is hoped that he will be able 

to return in the near future to continue this 

exciting work with us. 

Milind Wagh, Mumbai, India 

‘Angiogenesis and joint transplantation’ 

Milind was involved in several research projects 

including the development of a model of 

angiogenesis in the mouse to enable “knockout 

technology” to be applied. He also experimented 

on rat knee allografting and other core projects as 

well as playing a role in clinical microsurgery. He 

returned to Mumbai as a consultant plastic surgeon. 

Zi-Jun Zhang, Beijing, China 

‘Bone induction’ 

Zi-Jun spent six months at Bernard O’Brien 

Institute and six months in the Department of 

Orthopaedics. He researched demineralised bone 

and hydroxyapatite and their applications for the 

prefabrication of vascularised bone grafts. 

Ruitong Fan, Guizhou, China 

A Professor of Oral and Maxillofacial Surgery in 

Guizhou, China, Ruitong comes to our Institute 

with a large experience in plastic surgical head and 

neck reconstruction. He completed his PhD on the 

growth of rib grafts for temporomandibular joint 

reconstruction. He is now investigating the 

prevention of nerve scar (neuroma) formation in 

damaged nerves using neurotoxins. 

Glykeria Pantazi, Greece 

‘Cold storage of muscle and skin flaps’ 

Glykeria, a plastic surgeon from Greece, is 

researching drugs which can potentially preserve 

tissues and prolong their survival before the 

reattachment or transplantation. 

These fellows are the lifeblood of the Institute. 

Not only do they learn microsurgery and 

partake in the research program but they 

contribute enormously from an intellectual, 

cultural and social viewpoint. Since the Institute 

began more than 200 fellows from more than 

30 countries have trained at the Institute and 

St Vincent’s. Many have returned to their home 

country to establish Microsurgery Centres and 

become leaders in their field. A large alumni 

group now exists which frequently meets at 

international meetings. 

ACKNOWLEDGEMENTS 


I would like to acknowledge the outstanding 

effort that has been again made by the Board 

of Directors of the Microsurgery Foundation 

which is responsible for a significant part of the 

funding of the Institute. Without their tireless 

contributions the Institute could not survive. 

It is with great sadness that we report the 

untimely death of Jeanette Edwards on 15 April 

1998. Jeanette gave many years of untiring 

service to the Board and was admired and liked 

by all who knew her. Her achievements and 

contributions are cited on the inside back cover.



RETIRING MEMBERS 

Mr Keith Dawson retired from 

our Board after many years of 

committed service. Keith, a 

former director of Hong Kong 

Bank Australia Ltd and Perpetual Trustees, 

Victoria, had a unique knowledge of medical 

and philanthropic trusts and the business world. 

He was instrumental in pleading our cause to 

many of these trusts and for the successful 

outcomes. He was ever willing to offer advice 

and attend functions on our behalf, and has 

contributed greatly to our financial security. We 

wish Keith well in his retirement and thank him 

sincerely for his efforts. 

Mr Marc Besen, Executive 

Chairman of Sussan, is well 

known for his philanthropy and 

support of the arts, particularly 

the Australian and Victorian Opera 

and the National Gallery of Victoria. He has 

been on our Board for many years and has been 

a supporter of our cause. With his many other 

commitments he retired from the Board and we 

thank him sincerely for all his contributions. 

Professor Gerard 

Crock and Dr John 

Connell retired from 

the Board this year. 

As senior, and 

highly respected doctors in both the clinical and 

academic surgical scene they played a major 

role, particularly in the early years of the 

Foundation in helping Bernard O’Brien establish 

the Research Institute. Many political as well as 

scientific hurdles needed scaling and Bernard 

could not have recruited two better hurdlers. 

They steered and supported the Institute for 

many years and gave generously of their talents 

and time. Both have agreed to stay on as 

scientific advisers where their skill and 

experience will continue to benefit the Institute. 

We thank them sincerely for their efforts. 

Miss Norma Tullo came onto our 

Board at the suggestion of Sister 

Fabian, the founder of St Vincent’s 

Private Hospital. The name ‘Norma 

Tullo’ was a household word in the 

world of Australian fashion and she broadened 

our contacts and exposure to a new and 

influential group of patrons and supporters. 

Norma took great interest in our work and 

regularly attended and contributed to Board 

meetings in past years. Her contributions to our 

cause have been greatly appreciated. 

NEW MEMBERS 

Mr Allan MacLeod bring a wealth of medical 

experience and wisdom to the Board. He is 

currently the head of plastic and reconstructive 

surgery at St Vincent’s Hospital, and formerly 

of Repatriation General Hospital, Heidelberg. 

He is internationally known for his pioneering 

role in microsurgery and has been associated 

with the Institute as research fellow, adviser 

and colleague since its inception. We are 

delighted that Allan has offered his services. 

Professor James Angus, Professor of 

Pharmacology at Melbourne University, has 

recently been appointed to our Board. Jim has 

had a long association with our Institute as a 

scientific adviser and his influence and reputation 

at Melbourne University and with NHMRC, and 

with the broad scientific community will be a 

very valuable asset. We are grateful that Jim has 

offered to give us his time and support. 

Ms Josephine O’Brien has recently agreed to be a 

new member of our Board. Josephine, the daughter 

of Bernard O’Brien, has established an international 

reputation as an architect and has won many 

national and international awards and scholarships. 

We are delighted that Josephine will represent the 

O’Brien family and maintain our links with our 

founder. Josephine is energetic and vivacious and 

will add greatly to our Board membership. 

DONORS 

We are indebted to many large donors and 

funding bodies, many of whom have repeatedly 

supported us in a major way. These include 

the Victorian State Government, Transport 

Accident Commission, National Health and 

Medical Research Council, Royal Australasian 

College of Surgeons, National Australia Bank, 

The Jack Brockhoff Foundation, Helen M Schutt 

Trust, Henry and Miriam Greenfield, Liz and 

Russell Leggo, Ronald and Barbara Walker, 

St Vincent’s Hospital Research Fund, 

The Estate of the late George Adams, 

Sir Donald and Lady Trescowthick, Joe White 

Bequest, Australian Paper Welfare Scheme, 

Glaxo Wellcome, AMRAD and the late 

Miss Evelyn Coy bequest. 

Also from the will of Miss Evelyn Coy, an 

Annual Surgical Prize is awarded to the final 

year medical student at St Vincent’s Hospital 

Medical School who excels in surgery. This year 

Miss Anthea Greenway was the recipient of this 

cherished prize. 

We are grateful to Ms Sue McKay and Ms Liliana 

Pepe and staff at the Experimental Medical 

and Surgical Unit, and to Dr Ainslie Brown, 

Veterinarian, at St Vincent’s Hospital. For many 

years they have provided an outstanding level 

of co-operation and support to the staff of the 

Bernard O’Brien Institute of Microsurgery. 

We are also grateful to the ward staff and 

operating theatre staff of both St Vincent’s 

Public and Private Hospitals. 

WAYNE A MORRISON MD BS FRACS 

DIRECTOR 

11

Scientific Research 


BOBIM SCIENTIFIC REPORT 1997-98 

General Introduction 

The scientific activities of the Institute have 

expanded over the last year with several new 

projects in: 

• angiogenesis, 

• tissue engineering, 

• ischaemia-reperfusion injury, and 

• nerve regeneration 

An investigation of the role(s) of nitric oxide, a 

gaseous molecule made by blood vessels and 

white blood cells, has continued as a major 

focus in investigations of cell death following 

periods of low blood flow. Recently one of the 

enzymes making nitric oxide has been localised 

to mast cells, a cell type not previously thought 

to play a major role in ischaemic injury to 

skeletal muscle. 

A new model of angiogenesis (new blood 

vessel formation), with relevance to the clinical 

situation, has been developed. This model is 

being used to identify agents which either 

promote or inhibit development of new blood 

vessels, with clinical applications in tissue 

engineering, vascular disease and cancer. 

Further work on leukaemia inhibitory factor (LIF) 

has confirmed its muscle preserving action and 

shown that the agent is transported from the 

site of nerve injury to the muscle by specific 

transport down the nerve. This important 

finding provides further impetus to the 

application of LIF to sites of nerve injury 

being repaired by microsurgery. 

Our work on macrophage cells continues to 

provide us with important new insights into the 

molecular mechanisms controlling macrophage 

function, and role of these cells in inflammation, 

wound repair and blood vessel formation. 

The past year has also witnessed several 

initiatives involving genetically modified 

(transgenic/knockout) mice in which models of 

ischaemia-reperfusion injury and angiogenesis 

have been created and tested. Such 

developments provide a significant technical 

challenge for our highly skilled microsurgeons, 

but will but enable us to break new ground in 

understanding these complex clinical problems. 

12



THE JACK BROCKHOFF NERVE AND MUSCLE LABORATORY 

The Jack Brockhoff Laboratory is dedicated to 

researching the mechanisms of regeneration 

of nerve and muscle following injury and in 

evaluating agents which may enhance the 

repair process. 

Members of the Laboratory: 

T Bennett, B Dowsing, R Fan, A Messina, 

R Romeo, E Vergara and W Morrison. 

… and Major Collaborators: 

L Austin, 1 A Hayes, 2 N Nicola, 3 T Bucci 3 

and T Kilpatrick 3 

1 Melbourne Neuromuscular Research Centre, 

St Vincent‘s Hospital, Melbourne. 

2 School of Life Sciences and Technology, Victoria 

University of Technology, Footscray, Vic. 

3 Walter and Eliza Hall Institute for Medical 

Research, Melbourne. 

The recent discovery and the availability of 

some of these growth factors, such as leukemia 

inhibitory factor (LIF), have provided a means 

of treating regenerating nerves and their targets 

to improve recovery, with very encouraging 

results! Neurons (nerve cells), growing axons 

and target organs depend on continuing input 

from each other and supporting cells for growth, 

maintenance and survival, without these they 

atrophy and/or die. This action is mediated 

by chemical factors (proteins) known as 

growth factors. 

Microsurgeons are often faced with the task of 

repairing nerves injured, for example following 

trauma. These injuries can be devastating 

because, unless successfully repaired, they lead 

to the dysfunction of their target organs, which 

may result in permanent disability such as loss 

of muscle use (motor nerves), or loss of 

sensation to a limb (sensory nerves). The 

average age of victims sustaining this type of 

injury is 28 years and hence, failure to recover 

has a tremendous economic impact. Modern 

microsurgical techniques enable accurate repair 

of most nerves, although the outcome is often 

poor, due to death of the nerve cells (neurons), 

Mr Jack Brockhoff 

13



inadequate regeneration of axons (nerve fibres), 

and/or deterioration and scarring of the target 

prior to reinnervation. 

The orthodox method of nerve repair used in 

clinical practice is by direct suturing of the cut 

ends of the nerve. Alternative methods of nerve 

repair include: 

(a) 

(b) 

(c) 

(d) 

end-to-side repair, in which the distal end 

of a cut nerve is directly apposed to a 

healthy nerve, 

neurotisation, in which the proximal end of 

a cut nerve is implanted directly into the 

target muscle, 

grafting, in which various tissues are used 

to bridge the injury, 

entubulation repair. 

Entubulation repair of transected nerves is the 

standard model for studying peripheral nerve 

regeneration and recovery. It involves removing 

a small length of nerve, thereby leaving a gap 

between the proximal and distal ends of the 

nerve. This gap is bridged by plugging these 

stumps into either end of a hollow silicone tube 

which spans the gap, thus forming a sealed 

chamber. Within this chamber, proteins (survival 

factors, etc.) and cells that collect in response to 

nerve injury can be studied, test substances can 

be administered and their effects on the nerve 

repair process determined. 

Improving nerve repair with 

Leukemia Inhibitory Factor (LIF) 

Over the last four years this Institute has had 

great success repairing cut or crushed rat nerves 

in conjunction with the growth factor known 

as LIF (leukemia inhibitory factor). The nerves 

that regenerate are stronger and transmit 

messages faster and the muscles they supply 

do not wither as much and eventually their 

function is much improved. 

Over the past year we have been trying to 

modify or refine LIF’s use so that it may be 

more useful in the human setting. We have 

investigated answers to the following questions: 

1. How much LIF do we need, and what is 

its cost? 

2. After a nerve is severed, when is the best 

time to administer LIF? 

3. For how long is LIF required by nerves to 

adequately do its job? 

4. Does LIF do an even better job if added 

with other nerve stimulating factors? 

5. What is the most convenient way of 

administering LIF? 

At this stage we can say that LIF should be used 

in very small doses for very short periods. It is of 

benefit whenever it is given after nerve trauma, 

the earlier the better, and is best given as a 

cocktail with other growth promoters. 

We have also been looking at more scientific 

aspects of its use. We wish to know how LIF 

works on our nervous system and how safe it 

is. We have also been trying to answer the 

following questions: 

1. Are more nerve cells actually surviving due 

to LIF? 

2. Are they re-growing faster, bigger or in 

greater numbers? 

3. Are they being directed more efficiently to 

their targets? 

4. Are the muscles being kept healthier by the 

LIF until nerves can get back to them? 

This is an exciting time for this project because 

we can really start to see how LIF may soon 

benefit our patients. The possibility that nerves 

and muscles could recover from work injuries, 

lawn mower cuts or glass laceration, twice to 

three times better than by current clinical 

techniques methods, is exciting news. This 

is the type of result we are striving for. 

Leukemia Inhibitory Factor (LIF) 

is an autocrine survival factor for 

Schwann cells 

Schwann cells are cells which line the nerve 

axons (see attached Figure). They play a 

major role in promoting nerve survival and 

regeneration after injury by neurotrophic 

factors, extracellular matrix components and 

cell-surface adhesion molecules to promote 

axon regeneration. The aim of this study was 

to determine whether the enhanced recovery 

of muscle function observed when LIF was 

administered at the time of nerve repair was, 

in part, due to an effect on Schwann cells at 

the injury site. Following nerve transection, LIF 

is up-regulated by Schwann cells at the injury 

site. The LIF receptors (LIFRb and gp130) are 

also up-regulated at the nerve injury site but 

their cellular localization and consequent 

function have not been fully characterized. 

We investigated whether LIF could act to 

regulate the Schwann cell response. 

Rat sciatic nerve Schwann cells were cultured 

under various conditions and mRNA extracted. 

RT-PCR revealed that Schwann cells express 

mRNAs for LIF and the LIF receptor components 

LIFRb and gp130, and therefore have the 

potential to respond to LIF. Since Schwann cells 

produce large amounts of LIF in culture, we 

determined the role of LIF by either adding more 

LIF to the cells or by blocking LIF activity with 

the soluble LIF receptor LIFBP. LIF was found to 

act as a proliferative factor and a survival factor 

for Schwann cells. The blocking of LIF activity in 

the cultures also appeared to have an effect on 

cell morphology, which could be explained by 

LIF having an effect either directly on cell to 

substrate adhesion or it may simply be a 

phenomenon of reduced cell viability. 

Our data suggest that Schwann cell survival and 

morphology following nerve injury is likely to 

be modulated by LIF, suggesting a LIF-initiated 

autocrine survival loop. We now wish to 

determine the effect of LIF on the expression 

of Schwann cell proteins which may play a 

role in the promotion of nerve regeneration. 

14



Graphic representation of the cellular interactions of regenerating peripheral nerves towards their previously 

occupied distal nerve stump following injury. Interactions with Schwann cells and basal lamina via adhesion 

molecules, and various neurotrophic factors and cytokines such as LIF help to regulate this process. 

The treatment of pain resulting from 

a neuroma 

When a nerve is cut the cell body in the spinal 

cord or dorsal root ganglion (DRG) responds by 

promoting regrowth of the divided fibres 

(axons) from the proximal end of the divided 

nerve stump. These new sprouts form a bulb 

known as a neuroma. If the nerve contains 

sensory fibres, these neuromas are often 

extremely painful. Substances which kill the 

pain-causing sensory nerve cells may be 

potentially useful in treating this problem in 

humans. ‘BOAA’, a neurotoxin obtained from 

plants, has been shown to cause nerve cell 

degeneration or death. If it is absorbed through 

the cut end of the nerve and transported up to 

the nerve cell body, it may be able to eliminate 

the pain. We are currently treating cut nerves in 

an experimental model with this neurotoxin in 

order to determine whether it can prevent the 

formation of painful neuromas. 

Dr Ainslie Brown, Ms Sue McKay, Ms Anna Deftereos, Mrs Lilliana Pepe and Ms Rosalind Romeo. 

15



TRAUMA LABORATORY 

L to R: Dr Kanit Sananpanich, Tanya Harkom, Dr Aurora Messina, Dr Ruitong Fan, Rosalind Romeo, Jon Davis, Dr Glykeria Pantazi and Scott Baker. 


J Barker, B Dowsing, T Harkom, J Hurley, 

S Johnson, K Knight, B Lazarus, D Lepore, 

A Messina, G Pantazi, W Morrison, R Romeo, 

A Stewart, P Vadiveloo, M Wagh, G Willemart 

and B Zhang. 

... and Major Collaborators: 

F Clay 2 , P Cowan 5 , M Ernst 2 , P Hertzog 1 , 

J Hamilton 3 , M Pearse 5 , T Shinkel 5 , A Tomasi 6 

and G Vairo 4 

1 Monash Medical Centre, Clayton, Vic. 

2 Ludwig Institute for Cancer Research, 

Parkville Vic. 

3 University Dept of Medicine, Royal Melbourne 

Hospital, Parkville. 

4 Walter and Eliza Hall Institute, Univ Melbourne, 

Parkville. 

5 Immunology Research Centre, St Vincent’s 

Hospital, Melbourne. 

6 Universita degli Studi di Modena, Modena, Italy. 

Trauma is injurious to tissues in many ways. In an 

extreme case, tissue may be instantly destroyed. 

Crush injury may result in swelling, bleeding and 

contamination leading to partial destruction, but 

with some potential for recovery. 

In other circumstances it is specifically the blood 

supply to tissues that is interrupted and when it 

is not restored, death (necrosis) of the part will 

ensue. Even if the circulation is restored the 

toxic products that have accumulated in the 

devascularised part will trigger an inflammatory 

response in an attempt to prevent these toxins 

causing harm to the body. This process is 

known as the ischaemia-reperfusion (IR) injury 

and it can cause death of the part despite a 

‘successful’ revascularisation. This typically 

occurs following replantation or tissue transfer 

and is more severe the longer the part has been 

detached from the body. 

We have been investigating the mechanisms of 

IR injury and techniques to minimise the damage 

caused by this process. This research has direct 

application to all microvascular reconstructive 

procedures that are currently performed as well 

as increasing the success rates of replantation. It 

is vitally important in organ transplantation and 

in reducing the damage caused by strokes and 

heart attacks. In the future the research will 

enable tissues to be preserved for prolonged 

periods leading to ‘tissue banks’. 

Tissue injury following ischaemiareperfusion 

When blood flow to organs stops or is greatly 

reduced, the nutritional requirements of the 

tissues are not met after a period of a few 

minutes. This causes ischaemic damage. When 

blood flow resumes after a period of ischaemia, 

more damage to the tissues occurs from the 

16



production of highly reactive chemicals and the 

release of toxins from white blood cells which 

have moved from the blood into the tissue. 

Our studies have used a basic experimental 

model in which we apply a tourniquet to one 

hind limb of either a rat or a mouse for 1 to 2 

hours (ischaemia), then allowing normal blood 

flow for 24 hours (reperfusion), before 

investigating the damage to the skeletal muscle. 

We have focused on the roles of specific factors 

thought to play major roles in this inflammatory 

process, notably nitric oxide and activated 

complement, chemicals made in blood vessels 

by white blood cells. We have also focused on 

the role of white blood cells known as mast 

cells, thought to be one of the major promoters 

of this inflammatory process. This investigation 

has also been aided by the use of genetically 

modified mice, also known as ‘knockout’ 

and ‘transgenic’ mice. In a further series of 

experiments we have examined the protective 

roles of naturally occurring chemicals within 

the body in ischaemia-reperfusion injury. 

These findings will provide new ways of 

reducing tissue damage in severed limbs 

and other forms of traumatic injury. 

Mast cell activation, nitric oxide and 

activated complement involvement 

in ischaemia-reperfusion injury 

We have been using inducible nitric oxide 

synthase knockout mice, which are deficient 

in the enzyme inducible nitric oxide synthase 

(iNOS). This enzyme has been implicated in 

many physiological and pathological processes. 

Its product, nitric oxide (NO), can be either 

beneficial or toxic – depending on the levels 

and sites of production. Thus, manipulating 

the levels of NO may be of therapeutic use 

in the promotion of tissue survival. It has 

been suggested by us that in skeletal muscle, 

the formation of iNOS-derived NO during 

ischaemia-reperfusion injury, is overall 

damaging. We have now tested this hypothesis 

by using the iNOS knockout mice. Indeed it 

seems that the iNOS knockout mice are a third 

less susceptible to muscle death following 

ischaemia reperfusion injury. These results 

suggest that iNOS is detrimental in the outcome 

of ischaemia-reperfusion injury and that 

pharmacological intervention of the iNOS 

pathway may be a possible therapeutic target in 

the treatments designed to enhance tissue 

survival following trauma. 

Further ischaemia-reperfusion experiments in 

rats have made the interesting observation that 

increased iNOS production is found almost 

exclusively in mast cells (a tissue-based type of 

white blood cell). From this information we can 

conclude that the inducible form of NOS is 

responsible for the nitric oxide formed during 

ischaemia-reperfusion injury to muscle and that 

this enzyme is located almost exclusively in 

mast cells. 

Supporting evidence that mast cells are very 

important in ischaemia-reperfusion injury has 

come from experiments with mast cell-deficient 

mice, which have no detectable mast cells in 

their skeletal muscle, and CD 46/55/59 

transgenic mice, which inhibit the activation of 

complement in the bloodstream. In both of 

these mice we found a similar protective effect 

to that observed by iNOS knockout mice. 

Activated complement products have the ability 

to amplify the inflammatory response, for 

example causing mast cell activation and 

therefore increasing iNOS production. These 

results suggest that giving drugs which stabilise 

mast cells or which prevent complement 

activation, prior to reperfusion, may be 

protective against ischaemia-reperfusion injury. 

We are currently testing these drugs in our 

experimental model. 

Protective effects of the 

naturally occurring substances 

oxy-haemoglobin, uric acid and 

Stress Protein 70 in muscle injury 

Nitric oxide (NO) is a paradoxical molecule, 

with both beneficial and detrimental effects on 

cells. Normally NO is very beneficial, dilating 

blood vessels and preventing blood clotting. 

However, during ischaemia-reperfusion injury to 

skeletal muscle, NO can react with a ‘free 

radical’ known as superoxide (O - 2 ) to form 

peroxynitrite (ONOO - ), the latter being 

responsible for major cellular damage. We 

investigated the conditions which result in injury 

to skeletal muscle cells (known as myoblasts) by 

using a cell culture system. In Experiment 1 we 

found that a chemical which produces both NO 

and O - 2 , reduced cell survival markedly, 

whereas chemicals producing NO alone did not 

affect cell survival. In Experiment 2 we found 

that oxyhaemoglobin and uric acid, scavengers 

which neutralize NO and O - 2 respectively, 

prevented cell death in myoblasts exposed to 

injury by this toxic combination. 

We conclude that the reduced muscle cell 

survival may be due to either peroxynitrite or 

one of its breakdown products, eg. the potent 

oxidant – hydroxyl radical. Uric acid and 

oxyhaemoglobin are naturally occurring 

molecules which potentially could be used to 

counter ischaemia-reperfusion injury in humans. 

Human and animal tissues have a unique defence 

mechanism which can be induced to protect 

against trauma of many types. Stress Protein 70 is 

produced in response to a small degree of injury 

and functions to protect the tissue (eg. skeletal 

muscle, heart muscle, etc) from any subsequent 

larger degree of injury up to 12-24 hours later. 

This mechanism is potentially useful in protection 

against ischaemia-reperfusion injury to skeletal 

muscle. We have shown in vivo that a brief local 

elevation in muscle temperature to 42°C can 

trigger the induction of Stress protein 70, which is 

protective against the application of a tourniquet 

within 24 hours. A significant improvement in 

muscle survival was obtained compared with a 

control experimental group where Stress protein 

had not been induced prior to tourniquet 

application. In cell culture experiments where 

muscle was genetically engineered to synthesize 

Stress protein 70 continuously, we observed 

marked protection against a variety of toxic free 

radicals which are known to be formed during 

17



ischaemia-reperfusion injury. These experiments 

show the potential of utilizing this naturally 

inducible protein as a protective measure in 

microsurgical procedures. 

Cold preservation of skin and 

skeletal muscle 

Flushing grafts of skin and skeletal muscle 

with a chemically-defined solution prior to 

cold storage helps to preserve them, although 

eventually some cells die. We have commenced 

experiments in rats which aim to elucidate 

how and when cells die in cold-stored skin 

and muscle. For example, do these cells swell 

and release their contents into surrounding 

tissue (necrosis), or do they shrink and die by 

genetically programmed cell death (apoptosis)? 

The answer(s) to this question will assist us in 

the development of better preservation 

solutions. Future clinical application could 

involve the cold preservation of tissues for 

transplantation, for example storage of 

tissues/limbs of accident victims until 

surgery is possible. 

Apoptosis of cells following the cold 

storage of skin flaps 

‘Skin flaps’, commonly used in reconstructive 

surgery, are composites of skin, fat and blood 

vessels. It has long been known that storing 

tissues (severed fingers, limbs, etc) on ice prior 

to microsurgical replacement will give the 

surgeon more time to complete a successful 

operation. In this study we found that rat skin 

flaps can withstand 3-4 days in the cold and 

still be successfully replanted. However, there 

is sometimes partial loss of the flap tissue. In 

this project we have explored the possibility 

that the tissue loss might be due to apoptosis 

(programmed cell death) as well as necrosis. 

The average survival of rat skin flaps subjected 

to cold ischaemia for 24 hours, 2, 3, 4, or 5 

days (followed by 7 days of reperfusion, ie. 

normal blood flow) was 80, 74, 60, 47 and 

12% respectively. Thus, cold storage of skin 

flaps for up to 4 days represents significant 

but potentially reversible tissue damage. 

A further series of skin flaps was subjected to 

4 days cold storage. When specimens were 

harvested during the cold storage phase, no 

apoptotic cells were detected by histology. 

Apoptotic cells were only observed in the period 

8-24 hours reperfusion, with increased incidence 

at the later reperfusion times. The major cell 

types involved were at the base of the dermis, 

in hair follicles and in blood vessels (endothelial 

cells, smooth muscle cells and leucocytes). 

Apoptotic cells in blood vessels will expose the 

collagen surface underneath, causing increased 

blood clotting. This may partly account for 

microvascular failure in discrete zones of the 

skin flap. 

More recently we have started to investigate 

the protective properties of a commercially 

available preservation solution known as 

University of Wisconsin (UW) solution. The 

effect of this flush solution on graft survival 

is currently under investigation. 

A new skeletal muscle free 

flap model 

In order to investigate the effect of cold storage 

on skeletal muscle, a new experimental model 

was established. This muscle flap was based 

on the medial gastrocnemius muscle with the 

femoral artery and vein at the origin of the 

pedicle. A survival curve was established with 

variable periods of cold storage (1, 2, 3 or 4 

days) and 24 hours normothermic reperfusion. 

Viability of the flaps, determined by a 

histochemical stain, was estimated to be 40 

to 60% after 1 day cold storage but there 

was little survival for longer periods. 

As with the skin flap model we propose to 

investigate the effect of preservation with UW 

solution and to assess the fate of cell death 

within the muscle tissue. 

Macrophages and inflammation 

Macrophages are derived from white blood cells 

called monocytes. Macrophages are dynamic 

cells involved in many important processes in 

the body, making them an exciting cell type to 

study. Following surgery a variety of processes 

may occur at the repaired site, including wound 

healing, inflammation, fighting infection, new 

blood vessel formation (angiogenesis) and 

blood vessel thickening (atherosclerosis). 

Macrophages are known to play central roles 

in all of these processes. Our studies aim to 

discover the molecular mechanisms underlying 

macrophage functions. 

Mechanisms of macrophage 

activation 

A key class of molecules essential for cell division 

and growth (proliferation) are the cyclins. We 

have previously shown that agents which block 

macrophage proliferation inhibit expression of 

D-type cyclins. However, we were surprised to 

find that some anti-mitogens (agents which 

inhibit cell proliferation) actually raised levels 

of cyclin D2, the opposite of the expected 

result. The agents which raised cyclin D2, ie. 

lipopolysaccharide (LPS) and interferon alpha, 

also activated macrophages, indicating that 

cyclin D2 may have a role in macrophage 

activation, and not just proliferation. Therefore, 

we believe that in cyclin D2 we have identified a 

new player involved in macrophage activation. 

We are currently trying to better understand (a) 

the molecular mechanisms underlying cyclin D2 

induction (eg. cellular signalling pathways and 

transcription factors involved), and (b) the role 

of cyclin D2 in activated macrophages (by using 

macrophages from cyclin D2 ‘knockout’ mice). 

Type 1 interferons activate macrophages and 

protect them from viral infection. We wish to 

understand the mechanisms of these effects 

by using macrophages from mice with 

non-functional, type 1 interferon receptors 

(IFNARKO). In particular we are looking at the 

role of type 1 interferons in mediating the effects 

of LPS. We are examining the effect of LPS on cell 

survival, nitric oxide production and superoxide 

production in IFNARKO macrophages. 

18



The addition of lipopolysaccharide (LPS) triggers 

the three major MAP kinases (enzymes which 

phosphorylate molecules in the cell) involved in 

cellular signalling pathways. By using specific 

inhibitors of these kinases (agents which block 

the action of these enzymes) we are examining 

which pathways are required for LPS-induced 

cell survival, nitric oxide production and 

superoxide production. 

HCK is member of the src family of protein 

kinases. Both macrophage colony stimulating 

factor (CSF-1) and LPS induce increased 

amounts of the mRNA for HCK (increase its 

expression) in macrophages. We are currently 

examining drugs which can regulate HCK. 

Macrophages and new blood vessel 

formation (angiogenesis) 

Macrophages are known to secrete a number 

of proteins which regulate new blood vessel 

formation (angiogenesis). We have shown that 

angiogenesis is altered in mice lacking iNOS 

(inducible nitric oxide synthase). Given that 

macrophages make iNOS protein, we propose 

that synthesis of pro-angiogenic molecules such 

as vascular endothelial growth factor (VEGF) is 

altered in macrophages lacking iNOS. To 

explore this we are measuring the release of 

angiogenic molecules from macrophages 

derived from iNOS ‘knockout’ mice. 

Figures 1A and 1B: Transverse sections across region where a 7mm segment of artery was resected. After 10 days 

many new blood vessels have formed (*) to bridge the gap. VEGF is located in mast cell granules which are large 

and contain pale cores (1A). Degranulating mast cells release VEGF positive granules (1B). Bar = 20 m. 

19



HELEN M SCHUTT VASCULAR RESEARCH LABORATORY 

Mr Darvell Hutchinson, Chairman. 


J Barker, D Crowe, M Dowd, E Guida, A Kane, 

K Knight, T Konopka, G Mitchell, W Morrison, 

R Romeo, A Smardencas, A Stewart, Y Tanaka, 

P Vadiveloo and Z-J Zhang 


R Anderson, 2 T Bamford, 1 S Tajima 4 and 

A Tsutsumi 3 

1 Department of Pharmacology, University 

of Melbourne. 

2 Peter MacCallum Cancer Institute. 

3 Department of Laboratory Medicine, Division 

of Surgical Pathology, Osaka Medical College, 

Osaka, Japan. 

4 Department of Plastic and Reconstructive 

Surgery, Osaka Medical College, Osaka, Japan. 

Blood vessel biology 

Successful outcomes for surgery depend upon a 

good blood supply to nourish repaired and 

transplanted tissue. In this laboratory we are trying 

to get a better idea of how blood vessels work, and 

how to manipulate blood vessels. The knowledge 

generated from this work will not only impact in 

areas of surgery but will also be relevant to diseases 

such as cancer, arthritis and atherosclerosis since 

changes in blood vessel growth and shape are 

important feature of these diseases. 

Angiogenesis 

The process of new blood vessel formation 

is called angiogenesis. One problem with 

angiogenesis research worldwide is that there 

are few relevant models. The scientists and 

surgeons at BOBIM have now developed such 

a model in mice. This is an important step 

since we can now use the many ‘genetically 

engineered’ mice available worldwide to answer 

crucial questions as to the molecules involved 

in angiogenesis. Already we have shown using 

this model that nitric oxide (NO) derived from 

the enzyme iNOS encourages the process of 

angiogenesis. This could mean that clinically, 

iNOS enhancers are used where blood vessel 

growth is desired to treat a disease, while iNOS 

inhibitors are used where blood vessel growth 

needs to be stopped. 

With the discovery that NO is important for 

angiogenesis, we are now doing further work to 

identify which cells in the angiogenic region 

produce NO. An exciting finding was that mast 

cells in the region produced iNOS, along with 

macrophages and endothelial cells. Our current 

work investigates whether NO stimulates these 

cells into making the cytokines and growth 

factors required for angiogenesis. These studies 

are being performed using mice which have 

been genetically altered so that they do not 

express iNOS. 

Tissue engineering 

Finding good transplantable tissue to replace a 

lost ear, nose or parts of bone creates a major 

problem for reconstructive surgeons. To 

overcome these problems we are trying to 

‘tailor-make’ tissue so that it can used to repair 

wounds. The tissue will be made by seeding a 

chamber with cells and placing it inside the 

body. The cells will grow to fill the chamber, 

which will be contoured to give the desired 

shape of the final tissue (eg. an ear). Ideally we 

will make bone, fat or cartilage in the chamber 

and transfer that to the area of the body which 

is damaged. A major problem with making a 

block of tissue is ensuring it has a good blood 

supply, so the chambers are pre-fitted with a 

blood vessel. Currently we are using different 

chambers which contain either a collagen 

matrix to encourage tissue growth, or bone 

fragments to create newly shaped bone. 

Another problem encountered by reconstructive 

surgeons is a lack of healthy blood vessels to use 

for repairing damaged areas. We are trying 

create a ‘bank’ of ready-to-use blood vessels 

that can be stored in the fridge. We have found 

that during storage blood vessels lose their 

endothelial cells, which are essential for proper 

blood vessel function. So another tissue 

engineering project is dealing with a way to 

restore the endothelial cells to stored vessels 

before they are transplanted into the body. 

The major components placed in the growth chamber 

to prefabricate new tissue. 

20



Inhibition of blood vessel wall 

thickening by L-arginine 

L-arginine is an amino acid in the body which 

is converted into the important chemical known 

as nitric oxide (NO). NO has many useful 

properties in blood vessels. Notably it is 

responsible for dilating blood vessels and 

inhibiting the formation of blood clots. 

Arterial and vein grafts are commonly used to 

repair damaged blood vessels. In some traumatic 

accidents with a large amount of tissue loss, 

there is an insufficient length of blood vessel to 

perform this type of repair. At BOBIM we have 

found that blood vessels from different 

individuals of the same species, stored in the 

cold for a month, are convenient substitutes 

for the individual’s own blood vessels. However, 

one disadvantage of microsurgically repairing a 

blood vessel with that of another individual 

(allografting) is the thickening of the blood 

vessel wall (intimal hyperplasia) during the 

following month. This narrowing of the size of 

the blood vessel lumen increases the likelihood 

of vascular obstruction and failure of the graft. 

In this experimental study we administered 

L-arginine daily for 4 weeks from the time of 

microvascular repair of allografted blood vessels 

to see whether the NO generated could inhibit 

the blood vessel wall thickening. 

After 4 weeks the patency rate (those which 

had normal blood flow) of saline-treated 

controls was 57% compared with 83% in 

L-arginine-treated arterial allografts. Importantly, 

the intimal cross sectional area of the blood 

vessels decreased significantly from 678 m 2 

in saline-treated controls to 277 m 2 for 

L-arginine-treated allografts. The mean blood 

pressure was not altered by L-arginine treatment. 

It is concluded that L-arginine (and therefore 

NO) treatment is very beneficial in reducing 

blood vessel thickening in arterial allografts, 

thus ensuring that this type of graft has a 

better chance of success. 

4 week cold storage allograft, L-arginine treated. Shows less neointima thickening than saline-treated allograft. 

4 week cold storage allograft, saline treated. 

21



Vascular smooth muscle cell 

proliferation 

Smooth muscle cells (SMC) are a normal 

component of blood vessels. However, damage 

to blood vessels can lead to their proliferation, 

and this can ultimately lead to blockage of 

the vessels. We are currently investigating the 

complex effects of NO on SMC proliferation. 

It is known that NO inhibits SMC proliferation. 

However, we have found that this effect 

depends upon the concentration and type of 

NO donor, as well as the concentration and 

type of mitogen. Under some circumstances we 

have found that NO may in fact enhance SMC 

proliferation. These observations may explain 

some of the apparently contradictory functions 

of NO reported in the literature. We aim to 

further characterise the apparent dual roles 

of NO on SMC proliferation. 

Ms Claire Ravenhall BSc (Hons) with her AMRAD Young Investigator’s Award 1997. 

Role of nitric oxide in tumour 

angiogenesis 

Our previous studies suggest that nitric 

oxide (NO) has complex regulatory effects 

on the growth of new blood vessels. Tumours 

require new blood vessels to grow beyond 

a microscopic size. We have used genetically 

modified mice lacking one of the genes for an 

enzyme that produces NO (iNOS KO mice) 

to investigate how this molecule influences 

tumour growth. In normal mice skin tumours 

(melanoma cells) grow to approximately 1g 

within 2 weeks of subcutaneous injection. 

In contrast, in iNOS KO mice the average 

tumour size was less than half that of normal 

mice. We are currently investigating the 

relationship between NO and the gene 

message for vascular endothelial cell growth 

factor (VEGF) which is a powerful stimulant 

of new vessel growth. 

Regulation of NO production may provide 

a new method for reducing the growth and 

spread of tumours. 

22



HENRY AND MIRIAM GREENFIELD FAMILY TRUST MOLECULAR BIOLOGY LABORATORY 


B Dowsing, E Guida, S Johnson, R Romeo and 

P Vadiveloo. 

Many of the projects undertaken at this 

Institute require a diverse range of analyses 

including histological, biochemical and 

pharmacological methods. These techniques 

however are limited to examining changes 

in the microscopic cellular appearance or to 

the detection of various proteins which are 

produced or modified by the cells in response 

to the experimental manipulation under 

investigation. Molecular biology techniques 

allow the scientist to detect the earliest 

message being sent by the genes in the 

nucleus to the protein factories in the 

cytoplasm to produce a particular protein 

product. This message (mRNA) can be 

detected by sophisticated techniques such 

as the polymerase chain reaction (PCR) 

and Northern Blot analysis. They tell us which 

gene is ‘switched on’ or ‘switched off’. 

By combining the information obtained 

from the molecular biology analyses with 

that obtained from measuring protein levels 

directly (Western blotting, biochemistry) 

and cellular localization (histology and 

immunohistochemistry), a much clearer 

appreciation of the cellular response 

following injury and their subsequent 

response to treatment can be obtained. 

Molecular biology has become an 

integral component of analysis of many 

of the projects which are undertaken at 

the Bernard O’Brien Institute. 

Henry and Miriam Greenfield 

Projects utilizing the molecular 

biology laboratory 

1. Mechanisms of LIF action in nerve 

regeneration 

2. Cyclin D2 and macrophage activation 

3. Ischaemia-reperfusion injury 

4. Asthma 

5. Routine genotyping of knockout and 

transgenic mice 

6. Angiogenesis of blood vessels. 

23



AIRWAYS INFLAMMATION AND ASTHMA RESEARCH LABORATORY 


D Fernandes, E Guida, T Harris, V Kalafatis, 

K Knight, A Messina, A Pirdas-Zivcic, 

C Ravenhall, A Stewart, P Vadiveloo and 

R Vlahos. 


1 

M Ayad, 2 J Bartolo, 3 J Bertram, 1 S Brenton, 

1 

J Burdon and 2 J Wilson. 

1 Department of Respiratory Medicine, 

St Vincent’s Hospital Melbourne. 

2 Department of Respiratory Medicine, 

Alfred Hospital. 

3 Department of Anatomy, University 

of Melbourne. 

The major work of this laboratory is concerned 

with airway wall thickening which occurs during 

asthma. In this study we have been testing a 

number of drugs which modulate the growth 

rate (proliferation) of airways smooth muscle 

cells during this inflammatory disease. These 

drugs may not only be of some use in the 

treatment of asthma, but also of other 

inflammatory diseases. Many of the lessons 

we have learned about airways smooth 

muscle cells can apply equally to vascular 

smooth muscle cells. 

Another aspect of airways inflammation research 

is an investigation into the pathogenesis of 

emphysema and a particular variant of that 

known as alpha-1-antitrypsin deficiency. This 

research has continued over the past year in 

collaboration with the Department of 

Respiratory Medicine, St Vincent’s Hospital. 

As the national reference and resource centre 

for alpha-1-antitrypsin deficiency and lung 

disease, referrals and registrations of patients 

with alpha-1-antitrypsin deficiency and requests 

for information and guidance continue. It is 

thought that, in addition to alpha-1-antitrypsin, 

secretory leucocyte protease inhibitor (SLPI) 

might play a significant protective role in the 

lungs of patients with this disease. A study 

of these two proteins in alpha-1-antitrypsin 

deficient patients may help to explain why some 

patients develop symptoms of emphysema at a 

much younger age than others. 

Airway wall thickening in asthma 

Asthma is characterized by an increase in 

bronchial reactivity to a range of 

bronchoconstrictor substances. The mechanisms 

underlying this increased bronchial reactivity 

are not known. Recently, it has been suggested 

that structural changes involving airway wall 

thickening make a major contribution to the 

increase in bronchial reactivity. The airway 

wall thickening is mainly the result of an 

increase in the number of smooth muscle cells 

and fibroblasts. There is a paucity of data on 

the factors that regulate the growth of these 

cells. In these studies we have set out to identify 

and characterize the factors that control the 

growth of airway cells by developing in vitro 

cultures of human airway smooth muscle cells. 

Clinical studies indicate a greater benefit to 

asthmatic patients being treated with both 

steroids and ß 2 -adrenoceptor stimulants. 

We are examining whether these agents give 

greater control of smooth muscle growth 

when added together. 

ß 2 -adrenoceptor stimulants (inhaled drugs 

which relax muscle of the airway passages) 

reduced cell division irrespective of the 

stimulant (bFGF, EGF, thrombin). The 

mechanism of the inhibitory effect involves 

increased production of an enzyme regulator 

called cyclic AMP. We have identified the point 

in the replication cycle of the cell at which the 

ß 2 -adrenoceptor stimulants act to inhibit the 

production of proteins called cyclins and 

promote the formation of cyclin-dependent 

kinase inhibitors. 

A further series of studies are underway 

to search for novel inhibitors of division of 

smooth muscle cells that bind to distinct 

steroid receptors. One such molecule is a 

breakdown product of the female sex hormone, 

estradiol. The metabolite, 2-methoxyestradiol 

reduces all division responses of a number of 

different cell types and has potential as a new 

treatment for asthma. 

A model of airway wall thickening is being 

developed in allergic rats. Inflammatory 

changes in the airways mimic those of asthma 

and are accompanied by increased airway 

constriction. We are now using new microscopic 

techniques to accurately determine changes in 

the number of airway smooth muscle cells in 

the inflamed airways. 

24



Expression of cyclin D1 in human 

cultured airway smooth muscle cells 

Asthma is a complex disease characterized 

by airway inflammation and bronchial 

hyperresponsiveness. An increase in the amount 

of smooth muscle in the airway is due to both 

hypertrophy (an increase in cell size) and 

hyperplasia (an increase in cell number). Increased 

production of cyclin D1 protein appears to be a 

key regulatory step for cells to divide. Exposing 

cultured human airway smooth muscle (HASM) 

cells in vitro to growth stimuli such as thrombin 

simulates the in vivo growth. Bronchodilators such 

as salbutamol are used by asthma sufferers during 

acute asthma attacks. Salbutamol is a ß 2 agonist 

that inhibits cell division and reduces the level of 

cyclin D1 protein. 

Our aims were to examine the effects of 

thrombin and salbutamol on cyclin D1 

(mRNA) levels in cultured HASM cells. 

Northern Hybridisation showed that the 

expression of cyclin D1 message was maximal at 

16 hours. The presence of salbutamol alone did 

not alter the level of cyclin D1 mRNA expression 

compared to control. Thrombin alone increased 

cyclin D1 mRNA expression by two fold. The 

combination of salbutamol and thrombin did 

not alter the amounts of message made in 

response to thrombin. 

We have also investigated the effects of 

glucocorticoids which are used as ‘preventers’ 

of asthma. Glucocorticoids reduce both the 

level of cyclin D1 protein and the level of its 

gene message indicating that these drugs have 

a different cellular action compared with the ß 2 

agonists. We are now investigating whether these 

two different types of anti-asthma drugs produce 

longer effects when used in combination. 

Important protective proteins in the 

lungs of patients with emphysema 

This study examined the role of secretory 

leucocyte proteinase inhibitor (SLPI) as a 

protective antiproteinase in the lungs and how 

it may prevent the development of emphysema. 

Attention focused on the balance between 

destructive enzymes such as neutrophil elastase 

(NE) and protective antiproteinases such as 

alpha-1-antitrypsin (A1AT) and SLPI. It is known 

that only an estimated 10-15% of patients with 

A1AT deficiency develop the destructive lung 

disease known as emphysema. It was 

hypothesized that SLPI, produced locally in the 

lung, might be an important, additional protein 

which assists A1AT in protecting the lung 

against degradation by NE in those chronic 

airways limitation (CAL) patients who fail to 

develop emphysema. In those patients who 

develop emphysema, we hypothesize that they 

are deficient in both A1AT and SLPI. 

In a group of 34 CAL patients, one-third of 

whom were current smokers, we determined 

the net proteinase activity in lung lavage fluid 

using an enzyme assays for neutrophil elastase. 

In addition we used a sensitive biochemical 

assay to determine the respective concentrations 

of A1AT and SLPI in lung lavage fluid and the 

serum fraction of the circulating blood. 

In lung lavage fluid, the mean levels of SLPI 

were approximately one-third those of A1AT on 

a molar basis, whereas SLPI was present in 

barely detectable levels in serum. SLPI levels in 

the lung lavage fluid of CAL patients who were 

current smokers were significantly lower than 

those of non-CAL, non-smoking controls. A net 

balance in favour of proteinases was found in 

only 2 out of 34 patients, both undergoing an 

inflammatory episode at the time the specimens 

were collected. 

Given that SLPI is equally efficient as A1AT in 

neutralising neutrophil elastase activity, these 

results suggest that SLPI is present in the lung 

in levels sufficiently high to play a significant 

protective role in CAL patients. Since SLPI is 

synthesized by lung epithelial cells, it may 

provide the first line of defence against 

proteinase attack from neutrophil elastase, the 

major enzyme which degrades the molecules 

of the lung. Thus, the biochemical tests using 

lung lavage fluid and serum described in this 

study can be used to gain a better assessment 

of the proteinase-antiproteinase balance and 

therefore of the risk of developing emphysema. 

25

Full and Part-Time Staff 


Director 

Wayne Morrison 

MD, BS, FRACS 

Chief Research Scientist 

NH & MRC Senior Research Fellow 

Alastair Stewart 

(to 2/98) BSc(Hons), PhD 

Ross Vlahos (to 2/98) BSc(Hons), 

PhD 

Chief Executive Officer 

Geoffrey Renton BHA(UNSW), 

FACHSE, MNIA, AFAIM 

Senior Research Officers 

Kenneth Knight 

BSc(Hons), PhD, FACB, FAACB, 

MRCPath 

Research Fellows 

Tim Bennett 

FRACS (Australia) 

Senior Research Fellows 

Allan MacLeod 

MB BS, FRACS 

Geraldine Mitchell BSc(Hons), 

MSc PhD 

Michael Dowd 

MB BS (Australia) 

Anthony Berger 

MB BS, FRACS 

Bruce Dowsing 

BSc(Hons), PhD 

Ruitong Fan 

MD (China) 

Anthony Costello 

MB BS, FRACS 

Aurora Messina 


Glykeria Pantazi 

MD (Greece) 

Damien Ireland 

MB BS, FRACS 

Peter Vadiveloo 


Yoshio Tanaka 

MD (Japan) 

Anthony Penington 

MB BS, FRACS 

Research Officers 

Jane Barker 


Milind Wagh 

MS, MCh (India) 

Consultant Pathologist 

John Hurley 

MD, PhD, MB BS, FRACP, FRCPA, 

FRCPath, FRACR(Hon) 

Daniel Crowe (to 2/98) 


Zi-Jun Zhang 

MD (China) 

26

Full and Part-Time Staff 


Senior Technical Officer/ 

Laboratory Manager 

Trudi Harris (to 2/98) 

Dip Appl Biol(RMIT) 

Technical Assistants 

Tanya Harkom 

BSc Honours Students 

Sam Johnson 

BSc 

Senior Research Assistant/ 

Laboratory Manager 

Rosalind Romeo (from 3/98) 

BSc(RMIT) 

Honor Marshall (to 1/98) 

Brooke Lazarus 

BSc 

Research Assistants 

Monna Ayad 

BSc(Hons) 

Administrative Assistant 

Joy Rogers 

Edward Vergara 

BSc 

Elizabeth Guida (to 2/98) 

BSc(Hons) 

Postgraduate Research 

Students 

Darren Fernandes (to 2/98) 

BSc(Hons) 

Technician 

Neil Randall 

Valentina Koutsoubos 

(to 2/98) BSc(Hons) 

Diana A Lepore 

BSc(Hons), MSc 

Anne Pirdas-Zivcic 

(to 2/98) BSc(Hons) 

Claire Ravenhall (to 2/98) 

BSc(Hons) 

Leslie Schachte 

(to 12/97) MS(Biol) 

Arthur Smardencas BSc(Hons), 

MSc 

Tamara Konopka (to 2/98) 

BSc(Hons) 

27

Publications 


ARTICLES 

Barker JE, Strangward HM, Brand MP, Hurst RD, 

Land JM, Clark JB, Heales SJR (1998) Decreased 

nitric oxide formation but increased inducible nitric 

oxide synthase protein in astrocytes of the hph-1 

(tetrahydrobiopterin deficient) mouse. Brain Res 

804: 1-6. 

Bennett T, Dowsing B, Austin L, Messina A, 

Nicola N, Morrison WA (1998) Anterograde 

transport of LIF within transected rat sciatic nerve. 

Muscle and Nerve (In press). 

Crowe D, Hurley JV, Mitchell G, Niazi Z, 

Morrison WA (1998) Long-term studies of cold 

stored rabbit femoral artery and vein autografts. 

Br J Plast Surg 51: 291-299. 

Dowsing AT, Gougoulidis T, Dowsing BJ, Draber 

P, and Trounson AO (1998) The stage-specific 

expression of TEC-1, 2, 3 and 4 antigens on bovine 

preimplantation embryos. J Mol Reproduct Dev 49: 

19-28. 

Duke T, South M, Stewart AG (1997) Activation 

of the L-arginine nitric oxide pathway in severe 

sepsis: time-course of serum nitrogen oxides, 

and their relationship to inotropic support, 

tissue perfusion and outcome. Arch Dis Child 76: 

203-209. 

Duke T, South M, Stewart AG (1997) Altered 

activation of the L-arginine nitric oxide pathway 

during or after cardiopulmonary bypass? 

Perfusion 12: 405-410. 

Gill DR, Ireland DC, Hurley JV, Morrison WA 

(1998) The prefabrication of a bone graft in a rat 

model. J Hand Surg [Am] 23: 312-321. 

Gillzan KM, Stewart AG (1997) The role of 

potassium channels in the inhibitory effects of 

ß 2 -adrenoceptor agonists on DNA synthesis in 

human cultured airway smooth muscle. 

Pul Pharmacol 10: 71-79. 

Grigoriadis G, Stewart AG (1997) Human 

monocytes maintained in culture acquire functional 

responsiveness to platelet-activating factor that 

is independent of increases in protein tyrosine 

phophorylation. Clin Exp Pharmacol Physiol 24: 

563-569. 

Grigoriadis G, Stewart AG (1998) The role of 

tyrosine phophorylation in the signalling of 

superoxide anion generation in platelet-activating 

factor-stimulated peritoneal macrophages. Cell 

Physiol Biochem (In press). 

Gruen RL, Morrison WA, Vellar ID (1998) The 

tensor fasciae latae myocutaneous flap closure of 

major chest and abdominal wall defects. Aust NZ 

J Surg 68: 666-669. 

Guida E, Stewart AG (1998) Influence of hypoxia 

and glucose deprivation on tumour necrosis factoralpha 

and granulocyte-macrophage colonystimulating 

factor expression in human cultured 

monocytes. Cell Physiol Biochem 8: 75-78. 

Fernandes DJ, Guida E, Kalafitis V, Harris T, 

Wilson J, Stewart AG (1998) Glucocorticoids 

inhibit proliferation, cyclin D1 expression and 

retinoblastoma protein phophorylation, but not 

mitogen-activated protein kinase activity in human 

cultured airway smooth muscle. Am J Respir Cell Mol 

Biol (In press). 

Hamilton JA, Byrne R, Whitty G, Vadiveloo P, 

Marmy N, Pearson RB, Christy E, Jaworowski A 

(1997) Effects of wortmannin and rapamycin on 

CSF-1-mediated responses in macrophages. Int J 

Biochem Cell Biol 30: 271-283. 

Heales SJR, Barker JE, Stewart VC, Brand MP, 

Hargreaves IP, Foppa P, Land JM, Clark JB, 

Bolanos JP (1997) Nitric oxide, energy metabolism 

and neurological disease. Biochem Soc Transact 25: 

939-943. 

Hickey MJ, Wilson Y, Morrison WA (1998) Mode of 

vascularization of control and basic fibroblast growth 

factor-stimulated prefabricated skin flaps. Plast 

Reconstr Surg 101: 1296-1304. 

Hurst RD, Heales SJR, Dobbie MS, Barker JE, 

Clarke JB (1998) Decreased endothelial cell 

glutathione and increased sensitivity to oxidative 

stress in an in vitro blood-brain barrier model 

system. Brain Res 802: 232-240. 

Kane AJ, Morrison WA (1997) A practical guide to 

the excision of epidermal cysts and lipomata. Mod 

Med Aust 40:159-165. 

Knight KR, Burdon JGW, Cook L, Brenton S, 

Ayad M, Janus ED (1997) The potential 

importance of secretory leucocyte proteinase 

inhibitor (SLPI), human elastase inhibitor and elafin 

to the antiproteinase screen of patients with alpha- 

1-antitrypsin deficiency. Respirology 2: 91-95. 

Knight KR, Zhang B, Morrison WA, Stewart AG 

(1997) Ischaemia-reperfusion injury in mouse skeletal 

muscle is reduced by L-NAME and dexamethasone. 

Eur J Pharmacol 332: 273-278. 

Kumta SM, Morrison WA (1997) Revascularization 

of the testis following inadvertent division of the 

testicular vessels during hernia repair. Aust NZ J Surg 

67: 140-141. 

Kurek JB, Bennett TM, Bower JJ, Muldoon CM, 

Austin L (1998) Leukaemia inhibitory factor (LIF) 

production in a mouse model of spinal trauma. 

Neuroscience Letters 249: 1-4. 

Leong J, Hayes A, Williams DA, Austin L, Morrison 

WA (1998) Muscle protection following motor nerve 

repair in combination with LIF. J Hand Surg (In press). 

Morrison WA, Penington AJ, Kumta SK, Callan P 

(1997) Clinical applications and technical limitations 

of prefabricated flaps. Plast Reconstr Surg 99: 378-385. 

Morrison WA, Mitchell GM, Hickey MJ (1998) Late 

occlusion of vein grafts in replantation. J Hand Surg 

(In press). 

Reece JC, Handley AJ, Anstee J, Morrison WA, 

Crowe SM, Cameron PV (1998) HIV-1 selection by 

epidermal dendritic cells during transmission across 

human skin. J Exp Med 187: 1623-1631. 

Rostek M, Morrison WA (1997) Microsurgery – its 

role in soft tissue and bone tumour reconstruction. 

Acta Orthop Scand Suppl 273: 95-100. 

Stewart AG, Tomlinson PRT, Wilson JW (1997) 

ß 2 -adrenoceptor agonist-mediated inhibition of 

human airway smooth muscle proliferation: 

importance of the duration of ß 2 -adrenoceptor 

stimulation. Br J Pharmacol 121: 361-368. 

28

Publications 


Tanaka Y, Tajima S (1997) The influence of arterial 

inflow and venous outflow on the survival of 

reversed-flow island flaps: an experimental study. 

Plast Reconstr Surg 99: 2021-2029. 

Tham S, Dowsing B, Finkelstein D, Donato R, 

Cheema SS, Bartlet PF, Morrison WA (1997) 

Leukemia inhibitory factor enhances the 

regeneration of transected rat sciatic nerve and the 

function of reinnervated muscle. J Neurosci Res 47: 

208-215. 

Tham SKY, Morrison WA (1998) Motor collateral 

sprouting through an end-to-side nerve repair. 

J Hand Surg [Am] 23: 844-851. 

Theile DRB, Kane AJ, Romeo R, Mitchell G, 

Crowe D, Stewart AG, Morrison WA (1998) 

A model of bridging angiogenesis in the rat. 

Br J Plast Surg 51: 243-249. 

Vadiveloo PK, Filonzi EL, Stanton HR, Hamilton 

JA. (1997) G1 phase arrest of human smooth 

muscle cells by heparin, IL-4 and cAMP is linked 

to repression of cyclin D1 and cdk2. Atherosclerosis 

133: 61-69. 

BOOK CHAPTERS 

Stewart AG, Schachte L, Tomlinson PR (1997) 

Regulation of airway smooth muscle proliferation 

by ß 2 -adrenoceptor agonists. In: (Ed. AG Stewart) 

Airway Wall Remodelling in the Pathogenesis of 

Asthma, CRC Press, Boca Raton, pp. 295-330. 

Stewart AG, Barker JE (1998) Organ 

ischaemia/reperfusion injury: The role and therapeutic 

potential of NO. In: (Eds R Mathie & TM Griffith) The 

Haemodynamic Effects of Nitric Oxide, Imperial College 

Press, London (In press). 

Stewart AG, Hickey MJ, Barker JE (1998) Nitric 

oxide in ischaemia reperfusion injury. In: (Ed. 

P Grace) Ischaemia Reperfusion Injury, Blackwell 

Scientific, (In press). 

Wede I, Fuchs D, Barker JE, Heales SJR (1997) 

Neopterin and 7,8-dihydroneopterin modulate 

peroxynitrite induced inhibition of mitochondrial 

function. In: Chemistry and Biology of Pteridines 

(Blackwell Berlin) pp. 803-806. 

Vadiveloo PK, Vairo G, Royston AK, Novak U, 

Hamilton JA (1998) Proliferation-independent 

induction of macrophage cyclin D2, and repression 

of cyclin D1, by lipopolysaccharide. J Biol Chem 

273: 23104-23109. 

Willemart G, Knight KR, Morrison WA (1998) 

Dexamethasone prior to reperfusion improves the 

survival of skin flaps subjected to secondary venous 

ischemia. Br J Plast Surg (In press). 

Wilson YT, Lepore DA, Riccio M, Hickey MJ, 

Penington AJ, Hayward PG, Hurley JV, Morrison 

WA (1997) Mild hypothermia protects against 

ischaemia-reperfusion injury in rabbit skeletal 

muscle. Br J Plast Surg 50: 343-348. 

Zhang BM, Knight KR, Dowsing B, Guida E, 

Phan LH, Hickey MJ, Morrison WA, Stewart AG 

(1997) The timing of administration of 

dexamethasone or the nitric oxide synthase 

inhibitor, nitro-L-arginine methyl ester, is critical for 

effective treatment of ischaemia-reperfusion injury 

to rat skeletal muscle. Clin Sci 93:167-174. 

Miss Anthea Greenway awarded Evelyn Coy Annual Surgical Prize by Professor Wayne Morrison. 

29

Collaborations 


Professor D Alcorn 

Chairman, Department of Anatomy, The 

University of Melbourne. 

Transmission electron microscopy and 

related facilities. 

Dr R Anderson 

Peter MacCallum Cancer Research Institute. 

The role of heat-shock proteins in the 

protective effect of ischaemic preconditioning. 

Drs L Austin & J Bower 

Clinical Neurosciences, St Vincent’s Hospital. 

Leukaemia inhibitory factor in nerve and 

muscle regeneration following denervation. 

Drs P Bartlett & N Nicola 

Neuroimmunology, Walter and 

Eliza Hall Institute. 

Role of LIF in peripheral nerve regeneration. 

Dr J Bertram 

Department of Anatomy, University 

of Melbourne. 

Stereological assessment of structural 

changes in the airways. 

Dr P Bird & Dr C Mitchell 

Department of Medicine, Box Hill Hospital. 

Cold stored microvascular grafts. 

Dr J Burdon & Ms S Brenton 

Department of Respiratory Medicine, 

St Vincent’s Hospital 

Proteinase-antiproteinase balance in chronic 

obstructive pulmonary disorders. 

Professor Peter Choong & Dr Jane Fisher 

Dept of Orthopaedics, St Vincent’s Hospital 

Optimal conditions for the prefabrication of 

new vascularised tissues for transplantation. 

Ms F Clay and Dr M Ernst 

Ludwig Institute for Cancer Research 

Regulation of HCK expression in 

macrophages. 

Professor S Cordner & Ms L Ireland 

Victorian Institute of Forensic Medicine. 

Vascularised human bone allografts. 

Professor A J d’Apice 

Director, Immunology Research Centre, 

St Vincent’s Hospital. 

Osteochondral bone allografts in rats. 

Mechanisms of rejection of renal xenografts. 

The role of complement in ischaemiareperfusion 

injury. 

Dr T Duke 

Intensive Care Unit, Royal Children’s Hospital. 

Plasma nitrate and nitrite levels in bacterial 

and viral meningitis. 

Drs J Flack, D Crump & A Robertson 

AMRAD Operations, Burnley. 

Novel anti-asthma drugs. 

Dr M Galea 

School of Physiotherapy, The University 

of Melbourne. 



Dr A Hayes 

School of Life Science and Technology, Victoria 

University of Technology, Footscray. 



Dr P Hertzog 

Monash Medical Centre. 

The role of type 1 interferons in 

macrophage function. 

Dr M Johnson 

Glaxo Wellcome, UK. 

Regulation by ß 2 -adrenoceptor agonists of 

smooth muscle growth. 

Drs T Kilpatrick and G Starkey, 

Professor N Nicola and Ms T Bucci 

Walter and Eliza Hall Institute, Parkville. 

LIF is an autocrine survival factor for 

Schwann cells. 

Anterograde transport of LIF within 

transected rat sciatic nerve. 

Drs B Loveland, M Lanteri & 

Professor I McKenzie 

Austin Research Institute, Austin Hospital. 

The role of complement activation in 

ischaemia-reperfusion injury. 

Drs M Pearse, T Shinkel, P Cowan and 

Professor T d’Apice 

Immunology Research Centre, St Vincent’s 

Hospital, Melbourne. 

The role of activated complement in 

ischaemia-reperfusion injury. 

Drs J Presniell, J Cade & J Wilson 

Intensive Care, Royal Melbourne Hospital. 

Neutrophil function in adult respiratory 

distress syndrome: effects of GM-CSF 

administration. 

Dr J Reeves 

Intensive Care Unit, Royal Children’s Hospital. 

Efficacy of plasmapheresis in lowering 

circulating levels of inflammatory mediators. 

Professor H Salem 

Department of Medicine, Box Hill Hospital, 

Monash University. 


Dr A G Stewart 

Dept. Pharmacology, University of Melbourne 

Macrophages, iNOS and angiogenesis. 

Dr Rik Thompson 

Victorian Breast Cancer Consortium, 

St Vincent’s Hospital 

Optimal conditions for the prefabrication of 

new vascularised tissues for transplantation. 

Dr P Tipping 

Monash Medical Centre. 


Professor A Tomasi 

Università degli Studi di Modena Modena, Italy. 

Do heat shock proteins protect from 

free radical mediated damage in 

reperfusion injury? 

30

Collaborations 


Dr Gino Vairo 1 , Prof. John Hamilton 2 

1 

AMRAD Corporation, Burnley, Vic. 

2 

Dept Medicine, University of Melbourne, 

Royal Melbourne Hospital. 

Cyclin D2 and macrophage activation. 

Mr P Vervaart 

Department of Clinical Biochemistry, 

Royal Children’s Hospital. 

The role of oxidative stress in infant 

respiratory distress syndrome and chronic 

obstructive lung disease. 

Professor M Wiberg 

Department of Hand Surgery, Umea, Sweden. 



Professor D Williams 

Department of Physiology, The University 

of Melbourne. 



Dr J Wilson 

Department of Respiratory Medicine, 

Alfred Hospital. 

Effects of granulocyte-colony-stimulating 

factor on neutrophil function in patients 

with community acquired pneumonia. 

Forensic Medicine: Arthur Smardencas, Dr Alastair Stewart, Ms Lyn Ireland, Professor Stephen Cordner and Professor Wayne Morrison. 

31

Presentations 


INTERNATIONAL 

Professor Wayne Morrison 

Guest Speaker at the Combined Meeting of 

the 14th Annual Meeting of the Thai Society for 

Surgery of the Hand, 9th Annual Meeting of 

the Thai Society for Reconstructive Microsurgery, 

and 1st Regional Education Program of the Asian 

Pacific Federation of Societies for Surgery of the 

Hand, Bangkok, Thailand. 

Derby Hand Course Meeting, Derby UK. 

Thumb reconstruction 

Nerve injury and repair 

Research in hand surgery 

Flap prefabrication 

Mr Tim Bennett 

Tripartite Surgical Research Society Meeting, 

Nottingham, UK. 

Anterograde axonal transport of LIF. 

Dr Jane Barker 

British Pharmacological Society, UK. 

Differing effects of nitric oxide compared with 

peroxynitrite on mast cell degranulation in vitro. 

Barker JE, Stewart AG. 

International Congress of Pharmacology, Munich. 

Inducible nitric oxide synthase knockout mice 

are protected from ischaemia/reperfusion injury 

to skeletal muscle. Barker JE, Knight KR, 

Morrison WA, Stewart AG. 

Dr Bruce Dowsing 

Poster presented at American Chemical Senses 

Conference, San Diego CA, USA. 

Expression of olfactory receptors in mouse cell 

lines. H Treloar, B Dowsing and B Key. 

Poster presented at the 27th Annual Meeting 

for the American Society for Neuroscience, 

New Orleans, USA. 

Studies of the expression of olfactory receptors 

within olfactory receptor neuron 

cell lines. H Clarris, H Treloar, B Dowsing, 

P Bartlett and B Key. 

AUSTRALIA 

Professor Wayne Morrison 

Australian Federation of Operating Room Nurses 

Conference, Melbourne. 

History and new developments in plastic & 

reconstructive surgery. 

Victorian Postgraduate Foundation Country 

Education Program, Shepparton. 

Breast reconstruction – changing trends. 

Australian Hand Surgery Society Course, 

Melbourne. 

Australian Hand Surgery Society Annual Scientific 

Meeting, Tasmania. 

Needle injury to the nerve to flexor 

policis longus. 

Royal Australasian College of Surgeons Annual 

Scientific Congress, Sydney. 

1. Division of Plastic Surgery 

Tissue engineering in plastic surgery. 

2. Division of Hand Surgery 

Peripheral nerve injury and regeneration. 

Victorian Medical Postgraduate Foundation, 

Shepparton. 

Degloving face and scalp. 

National Cosmetic & Reconstructive Surgery 

Conference (Nurses), Melbourne. 

Facial replantation 

1998 Annual Scientific Meeting of Surgical 

Research Society, Leura, NSW. 

Tissue matrix generation in a rat model – 

angiogenesis. 

IV International Congress on Neuromuscular 

Diseases, Adelaide. 

Surgery for compression neuropathies: its 

expectations and complications. 

Mr Tim Bennett 

Western Hospital CNE for GP’s, Melbourne. 

Wound healing and ulcers. 

Dr Alastair Stewart 

Australian Society for Medical Research, Adelaide. 

ß 2 -agonists and steroids reduce cyclin D1 levels 

and DNA synthesis in human airway smooth 

muscle. 

Australian Vascular Biology Society, Leura, NSW. 

Selective inhibitors of inducible nitric oxide 

synthase (iNOS) or iNOS gene knockout inhibits 

functional angiogenesis. 

Australian Society of Clinical and Experimental 

Pharmacologists and Toxicologists. 

ß 2 -adrenoceptor agonists and cAMP arrest 

human cultured airway smooth muscle cells in 

G1 phase of the cell cycle: role of mitogenactivated 

protein kinase, cyclin D1, p27kip1 and 

retinoblastoma protein phosphorylation. 


Australian Society for Biochemistry and Molecular 

Biology, Melbourne. 

Mechanisms of nitric oxide-induced cellular 

toxicity: the mitochondrial respiratory chain. 

Barker JE, Heales SJR, Bolanos JP, Clark JB, 

Stewart AG. 

Australian Vascular Biology Society, Cairns. 

Lack of inducible nitric oxide synthase expression 

attenuates the pathogenesis of ischaemiareperfusion 

injury. Barker JE, 

Stewart AG, Knight KR, Morrison WA. 

The University of Melbourne. 

Mechanisms of iNOS mediated toxicity. 


St Vincent’s Hospital Research Week, Melbourne. 

LIF is an autocrine survival factor for Schwann 

cells. BJ Dowsing, WA Morrison, NA Nicola, 

T Bucci and TJ Kilpatrick. 

Walter and Eliza Hall Institute, Neuroimmunology 

Research Group. 

LIF is an autocrine survival factor for Schwann 

cells. BJ Dowsing, WA Morrison, NA Nicola, 

T Bucci and TJ Kilpatrick. 


Poster: 

The cytokine leukaemia inhibitory factor (LIF) 

enhances the recovery of muscle function 

following delayed repair of the transected nerve. 

T Bennett, A Hayes, A Messina, 

B Dowsing and WA Morrison. 

Dr Ken Knight 

5th Annual Scientific Meeting, Australian Vascular 

Biology Society, Leura, NSW. 

Nitric oxide and oxidative stress are stimuli for 

apoptosis of leucocytes and endothelial cells in 

ischaemia-reperfused skeletal muscle. 

Thoracic Society of Australia and New Zealand, 

Respiratory Cell Special Interest Group, 

St Vincent’s Hospital, Melbourne. 

Relationship between alpha-1-antitrypsin 

phenotype and the development of emphysema. 


The roles of complement activation and nitric 

oxide in ischaemia-reperfusion injury in mouse 


Poster: Australian Society for Biochemistry and 

Molecular Biology, Melbourne. 

The roles of nitric oxide and complement 

activation in ischaemia-reperfusion in mouse 


Poster: Australian Society for Medical Research 

Meeting, Adelaide. 

The roles of complement activation and nitric 

oxide in ischaemia-reperfusion injury in mouse 


Poster: Annual Scientific Meeting, Thoracic Society 

of Australia and New Zealand, Adelaide. 

Secretory leucocyte proteinase inhibitor is an 

important antiproteinase in the lungs of patients 

with chronic airways limitation. 

32

Profiles 


Professor John Victor Hurley 

Professor Hurley was born in Melbourne into a 

distinguished medical family. He graduated 

MBBS at the University of Melbourne in 1944, 

achieving many Honours and Exhibitions during 

the course. After a period of a year as a Junior 

Resident Medical Officer at the Royal Melbourne 

Hospital, he served from May 1945 to 

November 1947 as a medical officer with the 

rank of Flight-Lieutenant in the Royal Australian 

Air Force, including a period in British North 

Borneo in 1945. 

Originally intending to become a surgeon, John 

Hurley was appointed Surgical Associate 

Assistant to Mr Paul Jones at the Royal 

Melbourne Hospital in 1948 but in 1950 he 

abandoned his plans for a surgical career. He 

decided then to enter the field of Pathology and 

during 1950-52 worked for a period as Assistant 

Pathologist at the Royal Melbourne Hospital and 

in a research position in the Department of 

Pathology, University of Melbourne. He was 

then appointed Stewart Lecturer in Pathology at 

the University of Melbourne in February 1955. 

Apart from leave overseas, he has worked 

continuously in the Department of Pathology 

for over thirty years. He was promoted to Senior 

Lecturer in 1957 and to Reader in 1965. On the 

death of Professor George Christie, Professor 

Hurley was appointed to the Chair of Pathology 

in 1981. He became Assistant Dean (Preclinical) 

in the Faculty of Medicine in 1982. 

Professor Hurley was awarded the University of 

Melbourne degrees of Ph.D. in 1959 and M.D. 

in 1965. He holds Fellowships of the Royal 

College of Pathologists of Australia, the Royal 

Australasian College of Physicians and the Royal 

College of Pathologists (Great Britain) and 

Honorary Fellowship of the Royal Australasian 

College of Radiologists. 

During an appointment as Nuffield Dominion 

Travelling Fellow in 1959-60 Professor Hurley 

was fortunate to gain experience in the new 

exciting wave of experimental pathology in 

Britain under the leadership of Sir Royal 

Cameron at University College Hospital Medical 

School, London. It was during this period that 

Professor Hurley first developed his interests in 

acute inflammation, an area in which he is now 

an international authority. His studies 

concerning the behaviour of normal and injured 

small blood vessels are widely recognized as 

being of great significance in understanding the 

pathogenesis of fluid loss and tissue swelling in 

inflammation. His book Acute Inflammation is a 

key reference work in this field. 

As well as his outstanding achievements in 

research, Professor Hurley is an excellent teacher 

who has had an important influence upon more 

than a generation of medical students and upon 

postgraduate training in experimental 

pathology. Professor Hurley was appointed to 

the Microsurgery Reserch Centre (subsequently 

Bernard O’Brien Institute of Microsurgery) at St 

Vincent’s Hospital, The University of Melbourne, 

on 15 February 1987. His achievements and 

experience has endowed this Research Institute 

with many successful doctoral graduates and 

research papers published. 

A Family Connection 

Vanessa O’Brien is a Year 11 Student at Annesley 

College, Adelaide, South Australia, who 

completed her work experience at the Bernard 

O’Brien Institute of Microsurgery. Vanessa 

reported that it was a wonderful experience as 

she is interested in pursuing a career in science. 

In addition to this Vanessa gained an 

appreciation of the work Mr O’Brien (her great 

uncle) carried out at St Vincent’s Hospital. As 

part of Year 11 Vanessa studied maths 1 and 2, 

physics and chemistry, and also enjoys playing 

the cello, singing in the Adelaide Girls’ Choir 

and playing hockey. Vanessa had heard about 

the work of the researchers at St Vincent’s 

Hospital through plastic surgeons in Adelaide 

and has enjoyed the chance to experience this 

work in a ‘hands-on’ manner. Vanessa said ‘I 

appreciated the opportunity to complete work 

experience at the Bernard O’Brien Institute of 

Microsurgery because I realise the work is 

unique and internationally recognised. I found 

all the activities I was involved in fascinating and 

inspirational and would love to return again.’ 

L to R: Mrs Rosemary Leffler, Professor John Hurley and Past Chairman, Mr Alan Skurrie. 

33

Visiting Lecturers 


Ms Anita Quigley 

Melbourne Neuroscience Research Centre, 


Mitochondrial oxidative phosphorylation 

disorders and associated cardiovascular 

diseases. 

Dr Richard Cotton 

Director, Mutation Research Centre, 


Mutations and mutation detection and 

applications to breast cancer. 

Dr Greg Dusting 

Howard Florey Institute of Physiology, 


Nitric oxide and the cell biology of 

atherosclerosis. 

Assoc Prof Chris Mitchell & 

Dr Caroline Speed 

Department of Medicine, Monash University, 

Box Hill Hospital. 

Intracellular calcium and cell growth. 

Dr Damien Myers 

Department of Medicine, 


Vascular cell dysfunction: Why consider 

lipoproteins? 

Dr Helen Cox 

Department Pharmacology, UMDS, 

St Thomas’ School, London, UK. 

Neurone-epithelial interactions and the 

control of ion transport: studies with intact 

mucosa and ‘reconstructions’ in culture. 

Dr Guna Karupiah 

John Curtin School of Medical Research, 

Australian National University, Canberra. 

Nitric oxide and defence against 

microbial pathogens. 

Dr Nick Wilson 

Department of Medicine, The University of 

Melbourne, Royal Melbourne Hospital. 

Early cellular signalling in macrophage 

proliferation. 

Dr Mark Lam 

St Vincent’s Institute of Medical Research. 

Effect of PTHrp on skill cell growth. 

Dr Nikki Horwood 

St Vincent’s Institute of Medical Research. 

Differential display of mRNA. 

Mr Donald Murphy 

Department of Surgery, St Vincent’s & Geelong 

Hospitals. 

Laparoscopic gas pressure effect on renal and 

bowel function in the experimental pig model. 

Dr Brian Key 

Department of Anatomy, 


Molecular basis of axon guidance in the 

vertebrate nervous system. 

Dr David Krenus 

Berthold Australia Ltd, Bundoora, Victoria. 

Imaging of luminescence, fluorescence and 

radioactivity – a survey of current 

technologies. 

Dr Maurice Anidjar 

Department d’Urologie, Hôpital St Louis, 

Paris, France. 

Endourologic strategies to extend adenovirusmediated 

gene transfer in porcine uretal 

strictures. 

Dr Steve Bottomley 

Department of Biochemistry and Molecular 

Biology, Monash University. 

Unfolding antitrypsins 

Mr Andrew Burns 

Nuffield Department of Surgery, The John 

Radcliffe Hospital, Oxford, UK. 

Apoptosis in ischaemia-reperfusion of human 

renal allografts. 

Dr Andrew Muir 

Department of Anaesthesia, 


Current trends in the management of 

chronic pain. 

Dr Jane Barker with Dr Helen Cox, a former colleague from London. 

34

Australian and International Visitors 


Dr Ian Campbell 

Division of Autoimmunity & Transplantation, 

Walter & Eliza Hall Institute. 

The role of GM-CSF in collagen-induced 

arthritis. 

Dr Jane Fisher 

Department of Orthopaedics, St Vincent’s 

Hospital. 

Cardioprotective role of minor substrates. 

Professor Stephen Cordner 

Victorian Institute of Forensic Medicine, 

Melbourne 

Dr David Thompson 

University of Colorado, Denver, Colorado, USA 

Dr Ralph Green 

Royal Melbourne Institute of Technology 

Professor Vladimir Baitinger 

Department of Orthopaedics & Microsurgery 

Siberian State Medical University, USSR 

The Hon. Rob Knowles 

Minister of Health and Human Services, Victoria 

Drs Hidehiko and Yuka Nonomura 

Department of Orthopaedic Surgery, Gifu 

University School of Medicine, Japan 

Mr Peter Burge 

Nuffield Orthopaedic Clinic, Oxford, UK 

Professor Francis Sim 

Professor of Orthopedics and Research, Mayo 

Clinic, USA 

Mr Stan Wallis 

Chairman, Coles Myer Ltd 

Mr Gordon Tansey 

Commonwealth Bank of Australia 

Mr KA Juman-Yassin 

Georgetown, Guyana 

Ms Vicky Stogiannis 

Palm Beach, Florida, USA 

Dr James Blackburn 

Department of Plastic & Reconstructive Surgery 

The Pennsylvania State University, 

Pennsylvania USA 

Mrs Winsome Kellett 

Bentleigh, Vic 

Ms Vicky Stogiannis, Florida USA; Mr Geoff Renton, Melbourne, Australia and 

Dr Glykeria Pantazi, Athens, Greece. 

Associate Professor Yoshio Tanaka and Jiro Maegawa MD, Japan. 

35

Named Fellowships 


BENEFACTORS FELLOWS FELLOWS 

Named in honour of the very substantial contributions they have made to the Institute 1996/97 1997/98 

Ronald and Barbara Walker 

Chairman of Microsurgery Foundation 

Sir Laurence Muir, former Chairman 

and now Patron of Microsurgery Foundation. 

Assoc Prof Yoshio Tanaka 

Dr Glykeria Pantazi 

The late Sir William Kilpatrick 

Dr Peter Vadiveloo 

Dr Ken Knight 

National Australia Bank 

Mr Don Argus 

Chief Executive Officer 

Dr Milind Wagh 


Tattersalls 

Dr Frankie Fraulin 

Dr Ruitong Fan 

Sir Donald Trescowthick 

Dr Michael Dowd 

Dr Zi-Jun Zhang 

Lindsay and Paula Fox 

Dr Keiichi Muramatsu 


Henry & Miriam Greenfield 

Mr Peter Scougall 

Dr Aurora Messina 

Helen M Schutt Trust 

Darvell Hutchinson, Chairman 

Ms Tamara Konopka 

Ms Claire Ravenhall 

Ms Val Koutsoubos 

Dr Geraldine Mitchell 

36

Financial Statements 

MICROSURGERY FOUNDATION 

ACN 004 822 244 

(Company Limited by Guarantee) 

and 


30th JUNE 1998 

AUDITORS: KPMG 

Mr Michael Gainger Dip Bus (Accounting), Dip Bus (Data Processing) 

AICA, Cert Public Practice 

Registered Company Auditor 

Partner 

Audit Division 

Mr Michael Gainger is a audit partner with over twenty years experience in providing audit, accounting and 

consulting advice to government and private sector. 

37


PROFIT AND LOSS STATEMENT FOR THE YEAR ENDED 30TH JUNE 1998 

1997/98 1996/97 

$ $ 

Operating Profit / (Loss) (463,801) 1,234,064 

Income tax attributable to operating profit 0 0 

Operating Profit/(Loss) after income tax (463,801) 1,234,064 

Retained Profits at the beginning of the financial year 2,745,635 1,511,571 

Retained Profits at the end of the financial year 2,281,834 2,745,635 

BALANCE SHEET AS AT 30TH JUNE 1998 

1997/98 1996/97 

$ $ 

CURRENT ASSETS 

Cash 48,560 83,291 

Investments 2,812,956 2,861,083 

TOTAL ASSETS 2,861,516 2,944,374 

CURRENT LIABILITIES 

Other 579,682 198,739 

TOTAL LIABILITIES 579,682 198,739 

NET ASSETS 2,281,834 2,745,635 

SHAREHOLDERS’ EQUITY 

Retained Profits 2,281,834 2,745,635 

TOTAL SHAREHOLDERS’ EQUITY 2,281,834 2,745,635 

38



STATEMENT OF INCOME AND EXPENDITURE FOR THE YEAR TO 30TH JUNE 1998 

1997/98 1996/97 

$ $ 

Income 

Microsurgery Foundation 497,446 278,000 

Donation & Legacies 50,615 518,709 

NH&MRC (Univ of Melbourne, Dept. Surgery) 193,554 373,273 

Research Grants 41,473 269,011 

Other Receipts/Transfers 0 32,996 

Royal Australasian College of Surgeons 0 28,600 

Melbourne University 9,013 100,795 

TOTAL 792,101 1,601,384 

Expenditure 

Salaries and Wages 733,888 657,171 

Provision for Annual Leave – Note 1 21,980 (50,680) 

Provision for Long Service Leave – Note 2 17,608 (18,988) 

Superannuation 24,681 50,166 

Workcover Premium 1,084 3,024 

Salary & Wages Costs 799,241 640,693 

Medical, Surgical & Other Supplies 170,716 139,063 

EMSU, Purchase & Maintenance 59,881 74,947 

Artwork & Photographic 17,786 16,700 

Plant & Equipment 68,345 78,468 

Light & Power 41,128 41,723 

Repairs & Maintenance 28,295 21,655 

Printing, Stationary & Photocopying 23,163 22,825 

Administration Services 19,201 17,498 

Cleaning 2,759 5,981 

Library 1,662 1,868 

Freight/Courier 9,057 3,379 

Travel & Accommodation 7,902 9,797 

Staff Training 2,607 2,243 

Total Other Expenditure Costs 462,502 436,147 

TOTAL EXPENDITURE 1,261,743 1,076,840 

Surplus (Deficit) for the year (469,642) 524,544 

FUND ACCOUNT 

Balance of Fund as at 1st July Surplus (Deficit) (198,739) (723,283) 

Surplus (Deficit) for the year (469,642) 524,544 

Balance of Fund as at 30th June Surplus (Deficit) (668,381) (198,739) 

NOTE 1: Provision for Annual Leave 

The amount brought to account by Bernard O’Brien Institute of Microsurgery for this provision is $21,980 as at 30th June 1998. 

NOTE 2: Provision for Long Service Leave 

The amount brought to account by Bernard O’Brien Institute of Microsurgery for this provision is $17,608 as at 30th June 1998. 

39

Donations 


1ST JULY 1997 – 30TH JUNE 1998 

Donations between 

$25,000 – $50,000 

National Australia Bank 


$15,000 – $25,000 

The R E Ross Trust 

Joe White Bequest 

Evelyn Coy Estate 


$5,000 – $10,000 

Rotary Club of North Balwyn 

Donations between $1,000 – $5,000 

Polo Nominees Pty Ltd 

Carter Family Trust 

William Angliss Fund 

R M Cook 

National Mutual Trustees 

Kodak Australasia Pty Ltd 

Austrim Ltd 

Corrs Chambers Westgarth 

AMCOR 

Tattersalls 

Donations between $101 – $950 

E W Marshall 

C Bendix 

C B & C G Smith 

Rotary Club of Hoppers Crossing 

M Coleman 

All Souls Opportunity Shop 

Donations between $5 – $100 

A F & W K Akhurst 

Mr & Mrs W K Anderson 

Anonymous 

Anonymous 

A D Barrow 

E R Bowman 

D R & D E J Burney 

S L Coker 

M J Kingwell 

H E Kuhle 

Mr C Makris 

M O’Brien 

W J & J I Pearce 

P & O Maritime Services 

P A White 

Drs Ruitong Fan (China) and Kanit Sananpamia (Thailand) in EMSU during the visit of Brimbank and East Keilor Rotary Clubs. 

40

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