annual report - O'Brien Institute

For the betterment
of humanity
MICROSURGERY
FOUNDATION
Bernard O’Brien Institute of Microsurgery Annual Report 2000

Contents
9 Donations
10 Patrons
11 Directors
12 Chairman’s Report and Mr Alan Skurrie
14 Overview of Research
15 Director’s Report
18 Barbara Walker Centre for Pain Management
20 Scientific Report 1999-2000
20 Tissue Engineering - VTEC
22 Transport Accident Commission Trauma Laboratory
25 The Jack Brockhoff Nerve and Muscle Laboratory
26 Helen M Schutt Vascular Research Laboratory
29 Publications
31 Surgical Research Fellowships
32 Staff
33 Collaborators
35 Conferences and Presentations
37 Visitors
38 Financial Statements
Bernard O’Brien Institute of Microsurgery
Telephone (03) 9288 4018
Facsimile (03) 9416 0926
Email: BOBIMSVH@svhm.org.au
Microsurgery Foundation
42 Fitzroy Street Fitzroy Victoria Australia 3065
Telephone (03) 9288 4018
Facsimile (03) 9416 0926
Email: MICROFND@svhm.org.au
Auditors: KPMG
Solicitors: Corrs Chambers Westgarth
Design: Robe-John & Associates Pty Ltd
Principal Photography: Mike Dugdale
Shannon Morris
Phillip Biggs
Project Manager: Sam Broughton
About the Microsurgery Foundation trademark:
Hummingbirds are the smallest birds on Earth, as little as five centimetres
long, weighing less than a five cent coin and with wings that beat 80 times
a second. The hummingbird epitomises perfection in nature and is an apt
symbol of the miniature world in which the microsurgeon operates.
MICROSURGERY
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Restoring people’s
confidence, hope
and identity
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2000 Microsurgery Annual Report
Clinical cases
CASE 1
Glenn Twomey
Confidence
Future
Turning tragedy into promise
Glenn’s left arm was amputated below the shoulder in a
terrible accident near his home at Portland in 1997, and
then reattached through the miracle of microsurgery. He
was just 15 years old at the time.
Glenn’s accident was a shocking, defining moment in his life and
that of his parents and 4 brothers and sisters.
Clinging to life, Glenn was flown by air ambulance to Melbourne
and met by a team of our microsurgeons. Led by Anthony Berger,
the team reattached Glenn’s arm in a painstaking 7-hour
operation.
Glenn is facing his future with confidence. Now studying for his
VCE, he wants to pursue his dream of becoming a carpenter.
Before the accident, basketball had always been Glenn’s favorite
sport. He is now back on the court with his team mates, and has
resumed skateboarding, too.
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2 39

MICROSURGERY
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38 3

CASE 2
John McKinnon
Hope
Fatherhood
Protecting the community
One autumn morning John was gardening, tidying up as
he went, using a mulcher, feeding branches into its maw.
Without warning John’s right hand and arm were caught
and savaged by the machine.
Hearing John’s anguished cries, a neighbour called the ambulance
which rushed John from Torquay, first to the Geelong Hospital
then on to Melbourne, where a team of microsurgeons waited to
reconstruct his hand and crushed forearm.
John remained conscious from the time of the accident until the
operation began, and distinctly remembers thinking to himself
that he would never nurse his 2 year old daughter, Maggie, again.
John has now undergone a total of 9 separate operations which
have restored movement and function to his hand and arm.
John has not only nursed Maggie again, he proudly held his new
son Gus in his arms just a few months ago and has returned to his
work as a policeman.
Visitors
Visiting Lecturers - July 1999 - July 2000
Bernard O’Brien Institute of Microsurgery - Lunchtime Seminars
Congenital pseudarthritis of the tibia in children
Defects in hypopharanx - oesophagus after tumor
resection
Dr Ingemar Fogdestam
Department of Orthopaedic Surgery
University of Gothenberg, Sweden
Aging and muscle function
Dr Gordon Lynch
Department of Physiology, The University of Melbourne
A microarray expression database for the National
Cancer Institute’s drug-discovery program
Dr Mark Waltham
Victorian Breast Cancer Consortium , St Vincent’s
Institute of Medical Research, St Vincent’s Hospital
Patent protection: a primer for the scientist
Dr Vivien Santer
Griffith Hack, Patent and Trade Mark Attorneys
Model systems for the study of human breast cancer
invasion and metastasis
Associate Professor Erik Thompson
Head, Victorian Breast Cancer Research Consortium,
St Vincent’s Hospital
Omega-conotoxin in the modulation of chronic
neuropathic pain
Dr David Scott
Department of Pharmacology,
The University of Melbourne
Current research in surgical oncology
Professor Robert Thomas
Department of Surgery Oncology
Peter MacCallum Cancer Institute
The role of beta-cells in diabetes
Dr Sof Andrikopoulos
University Department of Medicine,
Royal Melbourne Hospital
PTHrP and the breast
Mr Michael Henderson
Deputy Director, Department of Surgery, The University
of Melbourne St Vincent’s Hospital
Hyaluronan as a drug delivery vehicle in the
treatment of breast cancer
Dr Tracey Brown
Department of Biochemistry & Molecular Biology,
Monash University
Breast cancer in developing countries
Professor David Watters
Head, Department of Surgery,
The University of Melbourne, Geelong Hospital
Axillary dissection - should it be avoided for
tubular cancers & DCIS?
Mr Paul Kitchen
Department of Surgery, The University of
Melbourne, St Vincent’s Hospital
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Gastrointestinal cancer research in Surgical
Oncology
Dr Wayne Phillips
Department of Surgical Oncology, The University
of Melbourne Peter MacCallum Cancer Institute
Hyaluronan: something for everybody
Dr Robert Fraser
Department of Biochemistry & Molecular Biology
Monash University
Visitors
Dr Paul Rosenberg, Melbourne
Fi & Dudley Drew, Wonga Park, Victoria
Dr Yang Kwang Lim, Hospital Kuala Terenggany,
Jalan Sultan Mahmud, Malaysia
Victorian Ladies Bowling Association:
Valmai Lewis, State President
Dawn Berner, Vice President
Moira Cumming, Vice President
Margaret Walker, Immediate Past President
Joyce Larkin, Vice President
Eunice Putch, State Treasurer
Gwen Arnold, Mirboo North
Lisa Koch, Industry Research Analyst, Australian
Expert Group in Industry Studies Sydney
Eleanor Dreger, Guy’s & St Thomas’ Hospitals,
London
Dr Declan & Mrs Emer Meagher, St Vincent’s
Hospital, Dublin, Ireland
Robert Fraser, Department of Biochemistry and
Molecular Biology, Monash University
4 37

Mr Anthony Penington
September 1999
American Society for Surgery of the Hand Meeting,
Boston, MA, USA. Visited Boston Children’s
Hospital, Boston, MA, USA.
May 2000
Royal Australasian College of Surgeons Scientific
meeting, Melbourne. Seminar: Maintenance of tissue
on an extracorporeal circulation.
Dr Peter Vadiveloo
August 1999
Australian Cell Cycle Workshop 99 (Vic):
P. Vadiveloo, A. Arvanitis, J. A Hamilton, I. Kola,
B. Sarcevic and G. Vairo. Cyclin D2 expression in
activated macrophages: a novel non-cell cycle role?
September 1999
ComBio99 (Qld): P. K. Vadiveloo, H. Christopolous,
E. Johnson, U. Novak, I. Kola, P. Hertzog and
J. Hamilton; Expression of cyclin D2 in activated
macrophages is mediated by Type I interferons,
and inhibited by dexamethasone.
October 1999
SVHM Research Week posters: A. Arvanitis and
P. Vadiveloo; The effect of microtubule-altering
agents on the expression of cyclin D2 in activated
macrophages.
P. Vadiveloo, H. Christopolous, E. Johnson,
U. Novak, I. Kola, P. Hertzog and J. Hamilton;
Expression of cyclin D2 in activated macrophages
is mediated by type I interferons, and inhibited by
dexamethasone.
November 1999
The Australian Society for Medical Research 38th
National Scientific Conference (NSW): A. Arvanitis
and P. Vadiveloo; The Effect of Microtubule-altering
agents on the expression of Cyclin D2 in activated
macrophages.
Awards and Honours
1999/2000
Professor Wayne Morrison
1999 Sir Arthur Sims Travelling Fellow, UK
Diana Lepore
Awarded PhD
“Nitric oxide, heat shock protein 70 and
ischaemia-reperfusion injury.”
Dr David McCoombe
Awarded Fellowship of the Royal Australasian
College of Surgeons, Jan 2000
Dr Ken Knight
Awarded Fellowship of the Royal College
of Pathologists, UK, Feb 2000
Dr Bruce Dowsing
Awarded The Wellcome Trust Equipment
Grant $105,000
Automated tissue staining apparatus
Angela Arvanitis
Awarded BSc(Hons), Dec 1999
“LPS stimulation of cyclin D2 in macrophages
is regulated by microtubule structure.”
Tim Shakespeare
Awarded BMedSc
“The inhibition of leukemia inhibitory factor
enhanced nerve regeneration by the action of
the specific nitric oxide 2 inhibitor
aminoethylisothiourea.”
MICROSURGERY
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36 5

CASE 3
Martin Turner
Identity
Communication
A precious gift
Relieved to be told by doctors that the tumour growing in
his palate was non-malignant, Martin was stunned to learn
that his condition nevertheless required surgery which
would leave a gaping hole in the roof of his mouth.
Unless that space could be filled, his speech would be
permanently affected and so would his capacity to swallow.
In a 7 hour operation headed by Professor Wayne Morrison, skin
taken from Martin’s forearm was used to restructure his palate.
Martin has now regained his capacity to speak and swallow.
Martin says, “We take our ability to speak for granted. It is not
until it is threatened that you fully realise what a precious gift
speech is. I don’t dwell on the past or what might have been, but
when I speak to my wife, three children and six grandchildren,
I give quiet thanks for the skill of the microsurgery team.”
Conferences and Presentations
July 1999-June 2000
Dr Bruce Dowsing
October 1999
SVHM Research Week: B.J. Dowsing, R. Romeo
and W. Morrison; Expression of leukemia inhibitory
factor (LIF) in human nerves following injury.
January 2000
Australian Neuroscience Society Conference poster:
B.J. Dowsing, S. Scheele, T. Shakespeare and
W. Morrison; Effects of LIF and GDNF on Nerve
Regeneration and Muscle Function Following Rat
Sciatic Nerve Entubulation Repair.
Dr Ken Knight
September 1999
7th Aust Vascular Biology Society Meeting, Paradise
Wirrina Cove Resort, South Australia; Prefabrica
tion of new connective tissue from an arteriovenous
shunt loop.
October 1999
SVHM Research Week poster: R. Mian, O. Cassell,
W. Morrison, J. Hurley, A. Penington, R. Romeo,
Y. Tanaka, and K. Knight; The generation of new
vascularized tissue from an arteriovenous loop.
November 1999
4th Pan Pacific Connective Tissue Societies
Symposium, Connective tissue biology in the new
Millenium: towards future therapies and applica
tions, Queenstown, New Zealand; Prefabrication
of new connective tissue from an arteriovenous shunt
loop.
June 2000
University Dept of Medicine, Royal Melbourne
Hospital, Parkville, Vic. Seminar entitled: Tissue
engineering - a major emerging technology.
Mr Peter Meagher
March 1999
Australian Hand Surgery Society Conference,
Melbourne, Vic., Biomechanical characterisation
of Tissues in Dupuytren’s Disease. A new method
of managing complex intra-articular phalangeal
fractures. The heterodigital adipofascial flap
(HAP-Flap) in hand reconstruction. Forearm flexor
reconstruction in the young patient after
Compartment Syndrome.
MICROSURGERY
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Dr Aurora Messina
October 1999
SVHM Research Week posters: C. Byers, M. Galea
and A. Messina; Behavioural and motoneuron
population changes following chronic sciatic nerve
transection injury in the rat.
R. Fan, A. Messina and W. Morrison; Increase in
sensory neuron population projecting to neuroma.
Dr Geraldine Mitchell
October 1999
SVHM Research Week posters: G. Mitchell, P.
Vadiveloo, S. Furuta, R. Romeo, W. Morrison and
A. Stewart; The role of nitric oxide in a functional
model of angiogenesis.
A. Smardencas, G. Mitchell, A. Messina,
S. Cordner, L. Ireland, B. Cooke, G. Pantazi,
S. Furuta, O. Cassell, R. Romeo and W. Morrison;
Endothelial seeding of cold-stored microarterial
grafts.
D. Zafiropoulos, P. Vadiveloo, G. Mitchell and
A. Stewart; Altered DNA synthesis of cerebral
microvascular endothelial cells isolated from mice
lacking inducible nitric oxide synthase.
Professor Wayne Morrison
June 1999
International Society for Reconstructive
Microsurgery, Los Angeles, USA.
1. Scalp and face replantation.
2. Tissue engineering.
June 1999
12 th Congress of the International Confederation
for Plastic, Reconstructive and Aesthetic Surgery,
San Francisco, USA. Prefabrication of tissues.
October 1999
SVHM Research Week poster: D. McCombe,
T. Brown and W. Morrison; The histochemical
response of the deep fascia to surgery.
May 2000
Royal Australasian College of Surgeons Scientific
meeting, Melbourne. Seminar: Tissue engineering -
clinical applications.
6 35

Drs Trevor Kilpatrick and G Starkey,
Ms T Bucci
Walter and Eliza Hall Institute, Parkville,
Vic.
LIF is an autocrine survival factor for Schwann
cells. Anterograde transport of LIF within
transected rat sciatic nerve.
Dr Maciek J Kubicki
Department of Engineering, The University
of Melbourne.
Tendon function after inhibition of adhesions.
Drs John Kurek, J Flack, David Crump &
A Robertson
AMRAD Operations, Burnley.
Use of LIF in nerve repair.
Mr Donald L Murphy
Department of Surgery, Geelong Hospital.
Renal and bowel function during laparotomy
and laparoscopy.
Dr Paul Patterson
California Institute of Technology, USA.
Use of LIF in nerve repair.
Dr Janet Ruby
Department of Microbiology, The University
of Melbourne.
Virus infection of macrophages: role of cyclin
D2.
Dr Paul Simmons
Stem Cell Research Laboratory, Peter
MacCallum Cancer Institute.
Tissue engineering with stem cells
Dr Shirley I Smith
Queensland Institute of Medical Research
Post Office, Royal Brisbane Hospital,
Herston, Qld.
Molecular mechanisms in macrophages.
Prof Geoffrey Stevens and Dr Jilska Perera
Department of Chemical Engineering, The
University of Melbourne.
Extracellular matrices and tissue engineering
Dr Alastair G Stewart
Department of Pharmacology, The University
of Melbourne.
Macrophages, iNOS and angiogenesis.
A/Prof Yoshio Tanaka
Department of Plastic & Reconstructive
Surgery, Osaka Medical College, Osaka,
Japan.
Tissue engineering and the arteriovenous shunt
model.
A/Prof Erik Thompson
Victorian Breast Cancer Research
Consortium, St Vincent’s Hospital.
Extracellular matrices in tissue engineering.
Prof A Tomasi
Università degli Studi di Modena Modena,
Italy.
Nitric oxide and heat shock proteins in free
radical mediated damage in ischaemiareperfusion
injury
Dr Gino Vairo
Walter and Eliza Hall Institute, Parkville,
Vic.
Cyclin D2 and macrophage activation.
Mr Murray Worner
Department of Physical Sciences, St Vincent’s
Hospital, Melbourne.
Maintaining tissues on an extracorporeal
circulation.
MICROSURGERY
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34 7

Collaborators
Bernard O’Brien Institute of Microsurgery
Prof Daine Alcorn
Chairman, Department of Anatomy,
The University of Melbourne.
Transmission electron microscopy and related
facilities.
Dr Robin Anderson
Peter MacCallum Cancer Research Institute.
The role of heat-shock proteins in the protective
effect of ischaemic preconditioning.
Dr Lawrie Austin
Clinical Neurosciences, St Vincent’s Hospital.
Leukaemia inhibitory factor in nerve and muscle
regeneration following denervation.
Dr Perry Bartlett and Prof Nic Nicola
Neuroimmunology, Walter and Eliza Hall
Institute, Parkville, Vic.
Role of LIF in peripheral nerve regeneration.
Dr Tracey Brown
Department of Biochemistry and Molecular
Biology, Monash University
Hyaluronan in tendon repair.
Dr Jonathan Burdon and Ms Sue Brenton
Department of Respiratory Medicine,
St Vincent’s Hospital.
Proteinase-antiproteinase balance in chronic
obstructive pulmonary disorders.
Ms Fiona Clay and Dr Matthias Ernst
Ludwig Institute for Cancer Research.
Regulation of HCK expression in macrophages.
Dr Brian Cooke
Department of Microbiology
Monash University, Clayton, Vic.
Endothelial coating of vascular prostheses
Prof Stephen Cordner and Ms Lyn Ireland
Victorian Institute of Forensic Medicine.
Vascularised human bone allografts.
Endothelial coating of vascular protheses
MICROSURGERY
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Dr Peter Cowan and Dr Trixie Shinkel
Immunology Research Centre,
St Vincent’s Hospital, Melbourne.
The role of activated complement in ischaemiareperfusion
injury.
Dr Mary Galea
School of Physiotherapy, The University
of Melbourne.
Neural and non-neural factors contributing to
reorganization in two models of peripheral nerve
injury
Prof John Hamilton
University of Melbourne, Department of
Medicine, Royal Melbourne Hospital.
Inflammatory mediators. Cyclin D2 and
macrophage activation.
Prof Oliver Hennessy
Department of Medical Imaging, University
of Melbourne, St Vincent’s Hospital.
Imaging of small blood vessels in soft tissues
Dr Alan Hayes
School of Life Science and Technology, Victoria
University of Technology, Footscray.
Leukaemia inhibitory factor in nerve and muscle
regeneration following denervation.
Dr Paul Hertzog
Monash Medical Centre.
The role of type 1 interferons on macrophage
function in IFNAR1 -/- mice.
Dr Alicia Jenkins, A/Prof Richard Gilbert
and Dr Darren Kelly
University of Melbourne, Department of
Medicine, St Vincent’s Hospital.
Tissue engineering of a new pancreas
Dr Robert Kapsa
Clinical Neurosciences, St Vincent’s Hospital,
Melbourne.
Tissue engineering of skeletal muscle.
8
Microsurgery Foundation and Bernard O’Brien Institute of Microsurgery premises at
42 Fitzroy Street, Fitzroy, Victoria.
33

Staff
Bernard O’Brien Institute of Microsurgery
Mirna Boujaoude
Sachiko Maeda
Marian Todaro
Matias Abregu
Carl Byers
Director
Wayne Morrison
MD, BS, FRACS
Chief Executive Officer
Geoffrey Renton
BHA(UNSW), FACHSE,
MNIA, AFAIM
Senior Research Fellows
Allan MacLeod
MB BS, FRACS
Anthony Berger
MB BS, FRACS
Anthony Costello
MB BS, FRACS
Damien Ireland
MB BS, FRACS
Anthony Penington
MB BS, FRACS
Timothy Bennett
MB BS, FRACS
James Burt
MB BS, FRACS
Consultant Pathologist
John Hurley
MB BS, MD, PhD,
FRACP,
FRCPA, FRCPath,
FRACR(Hon)
Senior Research Officers
Kenneth Knight
BSc(Hons), PhD, FACB,
FAACB, FRCPath
Geraldine Mitchell
BSc(Hons), MSc, PhD
Bruce Dowsing
BSc(Hons), PhD
Aurora Messina
BSc(Hons), PhD
Peter Vadiveloo
BSc(Hons), PhD
Research Fellows
David McCombe
MB BS, FRACS
Oliver Cassell
MB, ChB, FRCS(Ed)
Rob Donato
MB BS, FRACS
Peter Meagher
MSc, FRCS(Plast)
Senior Research
Assistant/Laboratory
Manager
Rosalind Romeo
BSc
Research Assistants
Monna Ayad
BSc(Hons)
Effie Keramidaris
BSc(Hons)
Technical Assistant
Tanya Harkom
Administrative
Assistants
Joy Rogers
Mary Wilcox
Postgraduate
Research Students
Arthur Smardencas
BSc(Hons), MSc
Ruitong Fan
MD (China)
Debra Zafiropoulos
BSc(Hons)
Mirna Boujaude
BSc(Hons)
BSc Honours
Students
Angela Arvanitis
BSc(Hons)
Sachiko Maeda
BSc
Marian Todaro
BSc
Matias Abregu
BSc
BMedSc Student
Tim Shakespeare
Technician
Neil Randall
Barbara Walker
Centre for Pain
Management
Director
Andrew Muir
MB BS, FFPMANZCA
Specialist in Pain Management
and Anaesthesia
Jane Trinca
MB BS, FANZCA,
Clinical Psychologist/Director
START Programme
Kathryn Kirkwood
M Psych Clin (Hons)
Clinical Nurse Consultant/
Co-ordinator START
Programme
Jean Bradbury
BSc, Grad Dip Pain Management
(Uni Sydney)
Physiotherapists
Margaret McPhate
B App Sc (Phty), M Manip Th
Julian Hodder
B App Sc (Phty)
Secretary
Yvonne Cowan
Medical Typist
Helen Scallion
Donations between $100,000 - $500,000
The Jack Brockhoff Foundation
The Wellcome Trust
Transport Accident Commission
Donations between $50,000 - $99,999
National Australia Bank
Donations between $25,000 - $49,999
BHP Community Trust
Tattersall’s
Donations between $10,000 -$24,999
H I H Insurance Ltd
L E W Carty Charitable Fund
W A Morrison
J O Wicking
Donations between $5,000 - $9,999
ANZ Trustees
The Orloff Family Charitable Trust
MICROSURGERY
FOUNDATION
Donations to Microsurgery Foundation
& Bernard O’Brien Institute of Microsurgery
1 st July 1999 – 30 th June 2000
Donations between $1,000 - $4,999
R J Champion de Crespigny
The William Angliss (Victoria) Charitable Fund
Rotary Club Hawthorn
C Maltby
R J Walker
Donations between $101 - $999
A S Leslie
The Essendon and District Medical Society Inc
C Bendix
All Souls Opportunity Shop
Donations up to $100
D R & D E Burney
J E Griffen
W J & J I Pearce
M J Kingwell
M O’Brien
F P & H C Ryan
C Makris
R & I Calvi
I Calvi
A D Barrow
32 9

Patrons
Microsurgery Foundation
Patron-in-Chief
His Excellency,
The Governor of Victoria
The Hon. Sir James Gobbo, AC
Foundation Directors
Bernard O’Brien Institute of Microsurgery
Chairman
Ronald J Walker,
AO, CBE
Patron
Sir Laurence Muir,
VRD, LLB, FSIA, FAIM
Chief Executive Officer
Professor
Wayne Morrison,
MD, BS, FRACS
Immediate Past
Chairman
Alan Skurrie, BCom
Consultative Scientific Panel
Microsurgery Foundation and Bernard O’Brien Institute of Microsurgery
Professor J A Angus, BSc(Hons), PhD, FAA
Professor G J A Clunie, MB, ChB, ChM, FCS(Ed), FRCS(Eng), FRACS
Emeritus Professor G W Crock, FRACP, FRCS, FRACS, FRACO
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
Professor G B Ryan, MB BS, PhD, MD, FRACP
Company Secretary
Geoffrey Renton,
BHA (UNSW),
FACHSE, MNIA,
AFAIM
Surgical Research Fellowships
Named in honour of the very substantial contributions
the following benefactors have made to the Institute
Ronald and Barbara
Walker
The late Sir William
Kilpatrick
○ ○ ○ ○ ○ ○ ○
○ ○ ○ ○ ○ ○ ○
○ ○ ○ ○ ○ ○ ○
○ ○ ○ ○
Dr David McCombe
Fellow
Dr Peter Vadiveloo
Fellow
Sir Laurence Muir
Tattersall’s Dr Oliver Cassell
Mr Darvell Hutchinson
Fellow
Helen M Schutt
The late
Evelyn M Coy
Ms Mirna Boujaoude
Fellow
Mr Frank Cicutto
Managing Director
National Australia Bank
MICROSURGERY
FOUNDATION
Dr Rob Donato
Fellow
Dr Peter Meagher
Fellow
Dr Aurora Messina
Fellow
10 31

Messina A, Knight KR, Dowsing BJ, Zhang B,
Phan LH, Hurley JV, Morrison WA, Stewart AG
(2000) Localisation of inducible nitric oxide
synthase to mast cells during ischemia /reperfusion
injury of skeletal muscle. Lab. Invest 80: 423-431.
Messina A, Sangster CLC, Morrison WA,
Galea MP (2000) Requirements for obtaining
unbiased estimates of neuron numbers in frozen
sections. J Neurosci Methods 97:133-137.
Mian R, Morrison WA, Hurley JV, Penington AJ,
Romeo R, Tanaka Y, Knight KR (2000)
Formation of new tissue from an arteriovenous loop
in the absence of added extracellular matrix. Tissue
Eng 6: 595-603.
Mian R, Knight KR, Penington AJ, Hurley JV,
Messina A, Romeo R, Morrison WA (2000)
Stimulating effect of an arteriovenous shunt on
the in vivo growth of isografted fibroblasts:
a preliminary report. Tissue Eng, in press July 10,
2000.
Morrison WA, Mitchell G, Barker JE,
Konopka T, Stewart AG (1999)
Angiogenesis in surgery and wound healing.
In (Ed T-P. Fan) The New Angiotherapy
(Humana Press) London, in press.
Morrison WA, Hurley JV, Ahmad TS,
Webster HR (1999) Scar formation after skin injury
to the human foetus in utero or the premature
neonate. Br J Plast Surg 52: 6-11.
Pantazi G, Knight KR, Romeo R, Hurley JV,
Hennessy O, Willemart G, Penington AJ,
Morrison WA (2000) The beneficial effect of
heparin in perfusion solutions for cold stored skin
flaps. Ann Plast Surg 44: 304-310.
Penington A, Malluci P (1999) Closure of elective
skin defects in the leg with a fasciocutaneous V-Y
island flap. Br J Plast Surg 52: 458-61.
Stewart AG, Harris T, Fernandes DJ, Schachte
LC, Koutsoubos V, Guida E, Ravenhall CE,
Vadiveloo P, Wilson JW (1999) Beta 2-adrenergic
receptor agonists and cAMP arrest human cultured
airway smooth muscle cells in the G(1) phase of the
cell cycle: role of proteosome degradation of cyclin
D1. Mol Pharmacol 56: 1079-1086.
Tanaka Y, Crowe DM, Wagh M, Morrison WA
(1999) A new source of vein graft for rabbit
experimentation. Microsurgery 19: 167-170.
Tanaka Y, Tsutsumi A, Crowe DM, Tajima S,
Morrison WA (2000) Generation of autologous
tissue (matrix) flap by combining an arteriovenous
shunt loop with artificial skin in rats: preliminary
report. Br J Plast Surg 53: 51-57.
Sangster CLC, Galea MP, Fan R, Morrison WA,
Messina A (1999) A method for processing
fluorescently labelled tissue into methacrylate: a
qualitative comparison of four tracers. J. Neurosci.
Methods 89: 159-165.
Stewart AG, Barker JE, Hickey MJ. (1999)
Nitric oxide in ischaemia-reperfusion injury.
In: Ischaemia-Reperfusion Injury. Ed. PA Grace
and RT Mathie, Blackwell Scientific, London,
Chapter 16, pp 180-195.
Stewart AG, Barker JE. (1999)
Organ ischaemia/reperfusion injury: The role and
therapeutic potential of NO. In: The Haemodynamic
Effects of Nitric Oxide. Eds R. Mathie & T.M.
Griffith, Imperial College Press, London, in press.
Vadiveloo PK (1999) Macrophages - proliferation,
activation and cell cycle proteins. J Leukoc. Biol.
66: 579-582.
Vadiveloo PK, Christopolous H, Novak U, Kola I,
Hertzog PJ, Hamilton JA. (2000) Type I
interferons mediate the lipopolysaccharide induction
of macrophage cyclin D2. J. Interferon Cytokine
Res. 20: 355-359.
Wagh M, Pantazi G, Romeo R, Hurley JV,
Morrison WA, Knight KR (2000) Cold storage of
rat skeletal muscle and pre-ischemic perfusion with
modified UW solution. Microsurgery, in press, Sept
2000.
Willemart G, Kane AJ, Morrison WA (1999)
Island dorsalis pedis skin flap in combination with
toe or toe transfer based on the same vascular
pedicle. Plast Reconstr Surg 104: 1424-1429.
Willemart G, Knight KR, Ayad M, Wagh M,
Morrison WA (1999) The beneficial antiinflammatory
effect of dexamethasone administration
prior to reperfusion on the viability of cold stored
skin flaps. Int J Tissue React 21: 19-26.
Directors
Professor
James Angus,
BSc(Hons), PhD, FAA
Tony Charlton,
OAM
Geoffrey
Stephenson, BA
John Haddad, AO,
FCIA
Sir Roderick Carnegie,
MA(Oxon),
MBA(Harvard)
Josephine O’Brien,
BA, BArch(Hons)
Leon L’Huillier,
BCom(Melb),
MPhil(Lon),
MBA(Chicago), FAIM
Clive Wellington Rosemary Leffler
Professor
Allan MacLeod,
MB BS, FRACS
Doug Provis Diana Jones, AM
Dean Wills, AO
MICROSURGERY
FOUNDATION
30 11

Chairman’s Report
Microsurgery Foundation
Chairman
Ronald J Walker, AO, CBE
Our mission is to
financially support
the Bernard O’Brien
Institute of Microsurgery and
the Barbara Walker Centre
for Pain Management and
Research.
The Foundation is a public
company limited by
guarantee, has no share
capital and declares no
dividend. The Foundation
is governed by a Board of
Directors who give their time and expertise to advance its
mission.
Board Members
The Board received with regret the resignations of Messrs
Allan Skurrie and Ivan Deveson, who leaves the Board after
8 years.
I wish to acknowledge the outstanding contribution of Mr
Allan Skurrie towards the work of the Foundation over 19
years of dedicated service. In his 8 years as Chairman, he led
the Board with distinction and secured necessary funds to
continue the pioneering work of the Bernard O’Brien
Institute of Microsurgery. Allan’s compassion, wise council
and friendship will be sorely missed.
I thank and congratulate all Directors for their involvement
and contribution during a year in which a number of new
scientific research projects were initiated and the highly
regarded Fellows program continued.
Fundraising
The Transport Accident Commission’s support of trauma
research in the areas of replantation and limb reconstruction
can be directly related to a decrease in recuperation and
rehabilitation periods for accident victims.
The National Australia Bank has generously funded the
Foundation. The Board committed this support to a surgical
fellowship, ensuring that an outstanding young surgeon has
the opportunity to undertake Microsurgery research.
Tattersall’s decision to renew its support and outstanding
commitment by continuing to fund a 5-year surgical
fellowship is welcomed and sincerely appreciated.
A substantial gift received from The Wellcome Trust has
been used to purchase essential specialist equipment for the
nerve research project.
In recognition of support from the Evelyn M Coy Bequest,
the Board established The Evelyn M Coy Scholarship,
directed to supporting a person undertaking their first year of
medical research.
The L.E.W. Carty Charitable Fund has provided research
funds over 3 years for tissue engineering research.
The Pratt Foundation has generously agreed to support our
work. We were delighted that their Chairman, Mrs Heloise
Waislitz, was able to visit and see our work first hand.
The Board is grateful for the substantial, ongoing financial
support received from trusts, benefactors, corporations and
friends. On behalf of the Board I extend to all donors our
heartfelt thanks.
Industrial Hand Injury
We are seeking an equity partner for Mr. Tony Penington’s
research into industrial hand injuries.
Intellectual Property
Rapid changes in biotechnology necessitated a review of our
intellectual property policies and the Board adopted new
policies effective 6 July 1999.
Patents
Our existing patent with AMRAD is being integrated with
The University of Melbourne. We are looking to explore
other avenues for this work.
Tissue Engineering
Tissue engineering is an increasingly important and exciting
area of activity. We have registered a new company, Victorian
Tissue Engineering Centre Pty. Ltd., to assist in development
of this new discipline.
Microsurgery Book
A major project for the Foundation was production of the
Microsurgery Book - a significant publication highlighting
our work.
On behalf of the Board, I congratulate Kyle Young, Nigel
Dawson and Lisa Neighbour from Grey Advertising
(Victoria) Pty Ltd, Steve Blenheim and Elizabeth Grima
from Lancashire Blenheim Design and photographer Paul
Torcello for their creative collaboration.
The Microsurgery Book has already won a number of
prestigious Australian and International awards and will be
used in our marketing and public relations activities.
Younger Group
The Board is delighted that a group of younger people have
agreed to assist us under the leadership of Mr Kyle Young.
We welcome the involvement of Ms Anna Carosa, Mr
Antony Hampel, Ms Rachel Hayes, Mr Richard Chapman
and Ms Joanne Walker. I thank them for their interest in
Microsurgery and look forward to their contribution to the
Foundation’s activities.
Publications
Bernard O’Brien Institute of Microsurgery
Articles published and submitted July 1999-June 2000
Bennett TM, Dowsing BJ, Austin L, Messina A,
Nicola NA, Morrison WA (1999) Anterograde
transport of leukemia inhibitory factor within
transected rat sciatic nerve. Muscle Nerve, 22: 78-87.
Burt JD, Burn AJ, Muzaffer AR, Byrd HS,
Hoban PC, Beran SJ, Adams WP Jr, Kenkel JM
(2000) Total soft tissue reconstruction of the middle
and lower face with multiple simultaneous free flaps
in a pediatric patient. Plast Reconstr Surg.
105: 2440-2447.
Burt JD, Byrd HS (2000) Cleft lip: unilateral
primary deformities. Plast Reconstr Surg 105:
1043-1055.
Cooper T, Savige J, Nassis L, Paspaliaris B,
Neeson P, Neil J, Knight KR, Daskalakis M,
Doery JC (2000) Clinical and autoantibody
associations of antibactericidal/ permeability
increasing protein and antiazurocidin antibodies.
Rheumatol Int 19: 129-136.
Dowsing BJ, Morrison WA, Nicola NA, Starkey
G, Bucci T, Kilpatrick T (1999)
Leukemia inhibitory factor is an autocrine survival
factor for Schwann cells. J Neurochem, 73: 96-104.
Dowsing BJ, Hayes A, Bennett TM, Morrison
WA, Messina A. (2000) The effects of LIF dose and
laminin plus fibronectin on axotomized sciatic
nerves. Muscle Nerve 23: 1356-1364.
Fernandes D, Guida E, Koutsoubos V, Harris T,
Vadiveloo P, Wilson JW, Stewart AG (1999)
Glucocorticoids inhibit proliferation, cyclin D1
expression, and retinoblastoma protein
phosphorylation, but not activity of the extracellularregulated
kinases in human cultured airway smooth
muscle. Am J Respir Cell Mol Biol 21: 77-88.
Hobar PC, Burt JD, Masson JA, Merritt JA,
Trawnik R (1999) Pericranial flap correction of
superior sulcus depression in the anophthalmic orbit.
J Craniofac Surg 10: 487-490.
MICROSURGERY
FOUNDATION
Knight KR, Messina A, Hurley JV, Zhang B,
Morrison WA, Stewart AG (1999)
Muscle cells become necrotic rather than
apoptotic during reperfusion of ischaemic
skeletal muscle. Int J Exp Path 80: 169-175.
Lazarus B, Messina A, Barker JE, Hurley JV,
Romeo R, Morrison WA, Knight KR (2000)
The role of mast cells in ischaemia-reperfusion
injury in murine skeletal muscle. J Pathol 191:
443-448.
Leong J, Hayes A, Austin L, Morrison W
(1999) Muscle protection following motor nerve
repair in combination with leukemia inhibitory
factor. J Hand Surg (Am) 24: 37-45.
Leong JC, Knight KR, Hickey MJ, Morrison
WA, Stewart AG (2000)
Neutrophil-independent protective effect of rmetHuG-CSF
in ischaemia-reperfusion injury in
rat skeletal muscle. Int J Exp Pathol 81: 41-49.
Lepore DA, Kozlov AV, Stewart AG, Hurley
JV, Morrison WA, Tomasi A (1999)
Nitric oxide synthase-independent generation of
nitric oxide in rat skeletal muscle ischemiareperfusion
injury. Nitric Oxide 3: 75-84.
Lepore DA, Stewart AG, Tomasi A, Anderson
RL, Hurley JV, Morrison WA (1999)
The survival of skeletal muscle myoblasts in
vitro is sensitive to a donor of nitric oxide and
superoxide, SIN-1, but not to nitric oxide or
peroxynitrite alone. Nitric Oxide 3: 273-280.
Lepore DA, Hurley JV, Stewart AG, Morrison
WA, Anderson RL (2000)
Prior heat stress improves the survival of
ischemic-reperfused skeletal muscle in vivo:
role of HSP70. Muscle Nerve, in press, July 2000.
Liu T, Knight KR, Tracey DJ (2000)
Peroxynitrite contributes to the initiation of
thermal hyperalgesia due to partial nerve injury
in the rat. Neuroscience 97: 125-131.
12 29

L-R Dr Kevin Cronin, Research Fellow from Ireland working under the operating microscope with
the assistance of Sue McKay and Liliana Pepe
L-R Rosalind Romeo, Laboratory Manager, working in the Histopathology Laboratory with
Dr Bruce Dowsing, Senior Research Officer, watched by Chantelle Sauza, work experience
student from St Columba’s College, Essendon.
We are indebted to:
Mr Barry O’Callaghan and staff from Corrs Chambers
Westgarth and Mr Michael Gainger and staff from KPMG
for their advice on the affairs of the Foundation.
Bernard O’Brien Institute of Microsurgery is supported
by Microsurgery Foundation.
Public appreciation of the work of the Institute and its plastic
and reconstructive surgery and hand surgery team at St.
Vincent’s Hospital is mainly through the reattachment of
amputated body parts. Less well known is its sophisticated
and expert microsurgical reconstruction of patients after the
surgical removal of cancers from breasts, head and neck, skin
and bone.
Surgeons from around the world train at the Institute then
return to their own countries to adapt these new techniques
for use.
Affiliations
Affiliated with The University of Melbourne and Monash
University, Bernard O’Brien Institute of Microsurgery is a
recognised body in education, laboratory teaching and
research.
Our students are enrolled for Honours in Bachelor of
Science, Master of Surgery, Master of Science and PhD
in fields such as nerve repair, wound and tendon healing,
tissue engineering.
Barbara Walker Centre for Pain Management
This unit had a pleasing year of progress and success,
conducting medical research to improve clinical outcomes
for persons currently experiencing acute and chronic pain and
the development of early rehabilitation programs for the
prevention of pain, together with educational programs for
medical practitioners.
An agreement was signed with the Commonwealth
Department of Health and Aged Care to treat public patients
who have exhausted all other options in their pain
management treatment.
Promotion of the Centre’s activities to medical practitioners
saw a rapid increase in the level of clinical activity. We have
treated over 1,000 patients, with more than half being seen
for the first time.
The innovative START program has so far involved 65
graduates. The program provides profound and lasting
improvements to pain sufferers. Our success has been
recognised by the Federal Government.
Scientific Research, Technology and Innovation
Major areas of activity this year were in Tissue Engineering,
Extracorporeal Circulation, Nerve Regeneration, Scar
Formation, Skin, Tendon and Nerve Healing, Basic Science
Mechanism, Stem Cell Growth
Development
A generous grant funded the appointment of a
Development Manager to generate new funding
opportunities and enable the organisation to sustain
momentum in its research programs.
MICROSURGERY
FOUNDATION
Inspiring Progress
To continue microsurgery research and develop new
surgical procedures and management programs, we seek
your continued participation and financial support.
Please assist us in achieving the mission of the
Microsurgery Foundation.
Ronald J Walker AO CBE
CHAIRMAN
Alan Skurrie
The Microsurgery
Foundation and
Bernard O’Brien
Institute of
Microsurgery owe an
enormous debt to Mr
Alan Skurrie who
retired from the Board
in June.
As a Board member with 20 years of service Alan
Skurrie’s contribution to the affairs of the Foundation
has been outstanding. His thoughtful and wise counsel,
particularly on financial matters has been of great
benefit to the organisation.
As Chairman of the Microsurgery Foundation between
1985 -1992 Alan provided incisive leadership and
support to the late Bernard O’Brien and Professor
Wayne Morrison as they built the Institute into what has
become the world’s pre-eminent centre of microsurgery
training and research. He provided wise and strategic
leadership and forged new relationships that enhanced
microsurgery research and training.
As a leading Australian businessman Alan was
instrumental in fundraising on behalf of the Foundation,
particularly from the corporate sector. The secure flow
of funds into the Foundation enabled the pioneering
research and training activities to continue unrestricted.
The Microsurgery Foundation and Bernard O’Brien
Institute of Microsurgery sincerely thank Alan Skurrie
for the contribution that he has made to advance the
cause of medical research through microsurgery. We are
indeed in his debt.
28 13

Overview
Bernard O’Brien Institute of Microsurgery
What is Microsurgery Research
Microsurgery literally means operating through a
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 parts
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 off. When
the circulation to a tissue is reduced or ceases a condition
known as ischaemia, that tissue will atrophy or die occurs.
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 in tissue banks.
By a better understanding of the process of blood flow
and new blood vessel formation we will be able to help
wounds heal, especially 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 new ears and noses.
Cancer growth and spread is dependent on new blood
vessels and by understanding how this process works we
can potentially inhibit new blood vessel formation. In
breast cancer and melanoma models in mice we have been
able to manipulate the cancer growth by using drugs
which have shown to be important in switching on and off
the angiogenic process.
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”.
The work undertaken at Bernard O’Brien Institute
Microsurgery is broadly based and links many surgical
disciplines and areas of applied science. Much
collaborative work is in progress with other research
institutes, both in Australia and overseas.
Plastic and Reconstructive Surgery Unit
The Plastic and Reconstructive Surgery Unit at St
Vincent’s continues to be a leader in its field with 1,483
patients having been admitted for treatment. The majority
of these patients required surgery and of these, 479 were
emergency patients with 429 requiring surgery from
injuries caused by accidents.
There were 31 replantation cases, the majority being
fingers but also including a whole arm. 77 vascularised
free tissue transfers were used for the reconstruction of
major deformities, 30 of which were for head and neck
cancer, 20 breast reconstructions and 17 for trauma. In
all, 53% of cases involved the hand or an upper limb,
31% general plastic surgery and the balance including
facial, head and neck and burns reconstruction.
The Research Fellows from the Bernard O’Brien Institute
of Microsurgery continue to be an integral part of our
surgical teams and play an important role in the many
difficult procedures that are undertaken by the Plastic
and Reconstructive Unit at St Vincent’s. We are indeed
indebted to the staff of the Plastic Surgery Unit at
St Vincent’s Hospital for their help throughout the year.
Professor Allan MacLeod
many ‘genetically engineered’ mice available
worldwide to answer crucial questions as to the
molecules involved in angiogenesis.
In the tissue culture laboratory we are currently
investigating how nitric oxide (NO) regulates
angiogenesis. We have recently established another
model of angiogenesis in our laboratory. Pieces of
vascular tissue are placed in a special gel in cell culture
plates, and new blood vessel growth is observed over a
2 week period. We are now about to test NO donors
and inhibitors to observe their effect on vessel growth.
In addition, we will test tissue from iNOS-/- mice to
see if lack of NO via a genetic alteration confers
different rates of vessel growth.
Haemangioma Research
We have begun examining the causes of
haemangiomas, which occur when blood vessels
spontaneously grow out of control. They are known
to contain high levels of inflammatory cells such
as mast cells. We have found that when these
haemangiomas are placed in culture and exposed
to FDA-approved. Lodoxamide, a mast cell stabiliser,
there is regression of blood vessel growth. Mirna
Boujaoude, PhD student, has recently joined our group
and is involved in these studies, together with surgical
fellows Drs. Tony Penington and Robert Donato.
Engineering new blood vessels
Another problem encountered by reconstructive
surgeons is a lack of healthy blood vessels for use in
repairing damaged tissues in trauma and cancer related
reconstruction. We are trying to create a ‘bank’ of
ready-to-use blood vessels that can be stored and taken
“off the shelf” when required for reconstructive
surgery. We have found that during storage blood
vessels lose their internal lining of cells, which are
essential for proper blood vessel function, particularly
to stop blood clotting within the blood vessel.
Therefore another tissue engineering project currently
underway is investigating ways to restore these internal
lining cells in stored blood vessels.
Rabbit Stent Model
Every year millions of Australians undergo heart
bypass surgery. This involves replacing the blood
vessels that supply the heart itself with new vessels
taken either from the leg or the arm. The short-term
success of this procedure is well documented however
10 years later 50% of these patients need to have the
MICROSURGERY
FOUNDATION
procedure repeated because the new vessels
themselves become narrowed and occlude. We have
developed a model in a rabbit where a polyester stent
is wrapped around an implanted vessel in the groin
and shown that the narrowing of the blood vessel
over time is reduced. Further studies are needed but
clinical implications are significant.
14 27

expression is increased following trauma, and in which
cells it is expressed. We found that, as in animals, LIF is
expressed within injured human nerves by a variety of
cells, including Schwann cells and inflammatory cells, and
that chronic neuromas continue to contain high levels of
LIF for several years. These data suggest further
examination is warranted to determine whether continued
expression of LIF in unhealed injured nerves promotes or
exacerbates the development of neuromas, or is simply a
response to continued ‘trauma’.
LIF and Schwann cell survival
Schwann cells are cells which line the nerve fibres and
play a major role in promoting nerve survival and
regeneration after injury. They are the major source of
LIF, and GDNF, at the injury site. Our own research has
shown that Schwann cells require LIF for survival in
culture, and that when we blocked LIF function within the
entubulation repair site the survival of Schwann cells was
markedly reduced. This suggests that one of the actions of
LIF following nerve trauma is to prevent injury-induced
cell death.
Role of NOS 2 in nerve regeneration
The nitric oxide producing protein NOS 2 is thought to
play a role in blood vessel formation. It is also thought to
be regulated in some tissues by LIF expression. We used
the NOS 2 inhibitor AET administered for one month
following nerve repair to determine whether NO-derived
from NOS 2 played a role in nerve regeneration in our
model, and whether the addition of LIF at the time of
repair could overcome the effects of NOS 2 inhibition.
When NOS 2 production is blocked with AET, in addition
to repairing the nerve stumps, re-vascularisation and nerve
regeneration are delayed within the silicone tube for up to
4 weeks. Addition of LIF to the tube at the time of repair
failed to overcome the effects of the AET. This series of
experiments suggest that nitric oxide is important to
angiogenesis and subsequent axon growth and may be
required for the action of LIF.
The treatment of pain resulting from a neuroma
Neuromas are bulbous swellings which occur at the cut
end of nerves, and these can become extremely painful,
resulting in neuropathic pain and sometimes loss of work
and, in extreme cases, suicidal tendencies. We are
investigating the characteristics of the neuron population
and local resident cells which contribute to the neuroma.
Once a nerve is injured or cut and not repaired, a neuroma
bulb forms at the cut end and persists for the life of the
nerve. We have now shown that many uninjured nerve
fibres grow into this end bulb neuroma, in addition to the
injured nerves. We have commenced a very detailed study
of motor nerves cells before injury, and after neuroma
formation and will compare the effects of this procedure
on the contralateral uninjured nerve cells.
Alternative nerve repair methods
In some circumstances it is not possible to repair an
injured nerve branch by using the parent nerve and so an
unrelated healthy nerve is used instead. Two methods of
joining the injured nerve to the healthy nerve are possible.
In the first, the healthy nerve is partially cut through and
the ends of the injured nerve fibres are sutured to the cut
ends of the healthy donor nerve fibres (end-end repair). In
the other method, the injured nerve is sutured to the side of
the uninjured nerve (end-side repair). We have shown that
both these techniques result in a significant return of
function to the denervated muscles. However, the end to
end repair results in decreased function of the donor
“muscles” whereas these muscles are spared by using end
to side repair. Using a nerve tracer method, we determined
that recovery of the denervated muscles is mediated by
regeneration from nerve cells in the donor nerve and not
from of the original nerve cells.
When the distal stump of a severed nerve branch is
rejoined to the parent nerve at a site distant to the point of
severence, the denervated muscle regains some of its
original function. We have shown that a number of nerve
fibres grow down the parent nerve in newly formed tracks
rather than joining the existing tracks of nerves. These
nerve tracks originate at the level of the branch nerve
injury and most likely include some of the original cut
branch nerves fibres.
Helen M Schutt Vascular Research
Laboratory
Senior Scientists: Geraldine Mitchell, Peter Vadiveloo.
Clinical Research Fellow: Tony Penington.
Members of the Laboratory:
Angela Arvanitis, Mirna Boujaude, Rob Donato, Tanya
Harkom, Peter Meagher, Wayne Morrison, Rosalind
Romeo, Arthur Smardencas, and Debra Zafiropoulos.
...and Major Collaborators:
Brain Cooke d , Alastair Stewart a
aDepartment of Pharmacology, University of Melbourne
dDepartment of Microbiology, Monash University,
Clayton, Vic.
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
features of these diseases.
Angiogenesis
The process of new blood vessel formation is called
angiogenesis. Until recently there has not been a clinically
relevant experimental model. The scientists and surgeons
at BOBIM have now developed such a model in rats and
mice. This is an important step since we can now use the
Director’s Report
Bernard O’Brien Institute of Microsurgery
Director
Professor
Wayne Morrison,
MD, BS, FRACS
Reconstruction following injury, tumour
resection, burns or congenital deformity
involves the transfer of tissues from one
part of the body to another. Virtually every body
part or tissue is capable of being transferred, e.g.
skin, muscle, bone and joints, nerves, fat, or
composite structures such as toes, scalp, etc. At
the Bernard O’Brien Institute research was
originally directed towards the role of
microsurgery in this process of tissue transfer.
Many of these techniques are now in common
use throughout the world and for this reason our
research is moving into the new frontier of tissue
engineering. This is a natural progression in the
sophistication of reconstructive techniques and of
microsurgery where only miniscule amounts of
the patient’s tissues are required to manufacture
the derived product. Microsurgery plays an
integral role in the process, firstly by supplying
the core vascular pedicle on which the tissue is
grown and then, if need be, in transferring the
product to the desired site for reconstruction.
Tissue engineering demands collaborations with
experts in several fields, especially cell culture
including stem cells, matrix biology, vascular
biology and bioengineering. We are very
fortunate to have in Melbourne many experts in
these fields who are generously contributing their
ideas. Tissue engineering offers the potential to
repair defects without the need to sacrifice other
areas of the body. It is an alternative to free tissue
transfer, artificial prostheses and organ and tissue
transplants.
MICROSURGERY
FOUNDATION
The Institute also has a major interest in nerve
repair following injury and in parallel with the
pain management service under the direction of
Dr Andrew Muir is interested in nerve pain,
especially neuroma formation. Research
includes the development of neuroma models
and studies mapping the sources of nerve fibres
which migrate into developing neuromas.
Studies have shown in human neuromas that the
growth factor (leukaemia inhibitory factor) is
abundantly produced. The role of this growth
factor in nerve repair and in pathological
processes is being investigated. The Schwann
cell which forms a sheath around nerve fibres is
a major producer of this growth factor and other
factors involved in the maintenance of nerve
function and in repair processes following
injury. Much of our research is directed towards
understanding the behaviour of this cell.
Injury to tissues following interference with
blood supply (ischaemia) has particular
relevance to our clinical work which involves
reattachment of amputated parts and the
transferring of tissues from one part of the body
to another. Investigations understanding the
nature of this injury and methods to minimise
its effect have been a long time interest in our
laboratory.
Inflammation is a fundamental body response to
injury and is integral to the repair process.
Macrophage function is one of our special
interests and research continues into the
molecular mechanisms which activate
macrophages.
Scarring following injury is a major source of
morbidity and compromises the results of
operations, particularly in organs which require
movement for function, such as the hand. We
are investigating agents which prevent collagen
formation and are hopeful that these will have a
role in reducing the morbidity associated with
injury and surgery.
26 15

Many other research topics are being investigated
and they are detailed under the section headed
“Scientific Research”. It has been a pleasure to be
involved in the many projects with cross-links with
more and more colleagues and other research
institutes both in Australia and overseas. These
collaborators have been very generous of their time
and facilities and their institutes are acknowledged
elsewhere in this report.
Fellows
Research Fellows from overseas and Australia,
many doing postgraduate degrees, contribute to
the research program and participate in clinical
work at St. Vincent’s Hospital. Each undertakes
a fellowship of one year or more and gains a
fellowship certificate in hand and microsurgery.
During the period of this report the following held
appointments at the Bernard O’Brien Institute of
Microsurgery:
Oliver Cassell, Plastic Surgeon, United Kingdom -
Tissue engineering models and matrix.
Rob Donato, Plastic Surgeon, Australia -
Extracorporeal circulation.
Slobodan Djurickovic, Orthopedic Surgeon,
Canada.
Sunao Furuta, Plastic Surgeon, Japan -
In vivo model of angiogenesis and role of nitric
oxide.
Hans Mark, Plastic Surgeon, Sweden -
Model of bone non-union.
Peter Meagher, Plastic Surgeon, Ireland -
Tissue engineering - muscle generation in stem
cells.
David McCombe, Plastic Surgeon, Australia -
Tendon healing.
Kanit Sananpanich, Plastic Surgeon, Thailand -
End-to-side nerve repair.
These fellows are the lifeblood of the Institute.
Not only do they learn microsurgery and partake in
research programs, but they contribute enormously
from an intellectual, cultural and social viewpoint.
Since the Institute began more than 200 fellows
from all corners of the globe have trained in
research and in clinical microsurgery at St.
Vincent’s Hospital. Many have returned to their
home country to establish microsurgery centres
and become leaders in their field.
A highlight of the year was the appointment of Allan
MacLeod, Head of Plastic Surgery at St. Vincent’s
Hospital and a Director of the Microsurgery
Foundation, as Associate Professor, acknowledging
his major contributions in clinical and research
plastic and microsurgery. This is a great honour and
we congratulate Allan on his achievement.
Alumni
A large alumni group now exists as a consequence
of the large international fellowship that has
developed through training at the Institute. Many
fellows have become lifelong friends with their
Australian colleagues and also with those who
trained with them from other parts of the world.
It is very gratifying, when attending international
meetings to meet up again with so many colleagues
and recount tales, tall or true, of their experience at
St. Vincent’s and the Institute and on a personal
note, how enjoyable it is to be made so welcome on
visiting these fellows in their own countries. The
hospitality has been extraordinary and I consider it
a great privilege to have been able to share in their
development and interests. This year I was
particularly privileged to meet many of our alumni
at the Asian Pacific Federation of Societies for
Surgery of the Hand meeting in Madras and at
the South African Society for Surgery of the Hand.
Our friend and colleague Julian Pribaz, Professor of
Plastic Surgery at Brigham and Women’s Hospital,
Harvard, Boston, was appointed the B.K. Rank
Travelling Professor for the Annual Scientific
Meeting of the Royal Australasian College of
Surgeons in Melbourne in May. Julian trained in
plastic surgery at St. Vincent’s and was a member of
our plastic surgery team before moving to Boston.
We were inspired by his clinical and research
presentations.
Acknowledgements
The Board of Directors of the Microsurgery
Foundation under the Chairmanship of Mr Ronald
Walker have been again instrumental in financing
our research efforts. They give generously of their
time and expertise and it is impossible to under
estimate their contributions.
Alan Skurrie, past Chairman of Microsurgery
Foundation and long term member of the Board
retired this year. It is with great regret that we say
goodbye to Alan who over many years has been a
tower of strength, especially through the lean years
when with perseverance, wisdom and charm he
enabled us to gain many major grants which
The Jack Brockhoff Nerve and Muscle
Laboratory
The Jack Brockhoff Laboratory is dedicated to
researching the mechanisms by which injured nerves
and muscles regenerate and to identifying chemical
factors and various administration protocols which
enhance the repair process.
Senior Scientists: Aurora Messina, Bruce Dowsing
Clinical Research Fellow: Tim Bennett.
Members of Laboratory: Richard Brouwer, Carl
Byers, Rob Donato, Ruitong Fan, Sachiko Maeda,
Marian Todaro, Rosalind Romeo, Kanit Sananpanich,
Tim Shakespeare, and Wayne Morrison.
…and Major Collaborators:
Lawrie Austin 1 , Alan Hayes 2 , Nic Nicola 3 , Mary
Galea 4 , Dr. Paul Patterson 5 , and Catherine Sangster 4 .
1Melbourne Neuromuscular Research Centre, St.
Vincent’s Hospital, Melbourne.
2Department of Biological Sciences, Victoria
University of Technology, Footscray, Vic.
3Walter and Eliza Hall Institute for Medical Research,
Melbourne.
4School of Physiotherapy, University of Melbourne.
5California Institute of Technology, USA.
Nerve repair and regeneration
Microsurgeons are often faced with the task of
repairing injured nerves. Unless successfully repaired,
nerve injuries lead to dysfunction of their target organs,
resulting in permanent disability such as loss of muscle
use (motor nerves), or loss of sensation to a limb
(sensory nerves) or pain. On average nerve injuries
occur in young adults and hence, failure to recover has
a tremendous economic impact. Modern microsurgical
techniques enable accurate repair of most nerves but
the functional outcome is often poor, due to death of
the nerve cells (neurons), inadequate regeneration of
axons (nerve fibers), and/or deterioration and scarring
of the target prior to reinnervation.
Neurons 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. These actions are mediated by
chemical factors (proteins) known as growth factors.
The recent discovery and the availability of various
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!
MICROSURGERY
FOUNDATION
Entubulation repair of transected nerves is the
standard model, used in our laboratory, 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.
Hand and limb injuries often involve trauma to their
supplying nerves and despite current surgical techniques
the degree of function recovered is generally
unsatisfactory. Our research aims to understand the
mechanisms of regeneration of nerve and muscle
following injury and to evaluate agents which may
enhance the repair process.
Improving Nerve Repair with neurotrophic
factors
Following nerve injury cells near to the trauma site
produce various proteins, called growth factors, that
encourage healing and nerve regeneration. The
availability of some of these growth factors, such as
leukemia inhibitory factor (LIF) and glial cell derived
neurotrophic factor (GDNF), has enabled us to
develop methods to administer these factors to the
site of injury and to evaluate their efficacy as nerve
regeneration promoters. We found that the repair of
cut or crushed rat nerves in conjunction with either
LIF or GDNF results in significantly enhanced nerve
regeneration, the muscles they re-connect with do not
waste as much, and eventually their function is
significantly improved. However, addition of these
factors together does not further enhance the recovery
obtained with either factor alone.
Before these promising factors can be used in the
clinical setting, a relatively simple and cheap method
of administering them at the time of surgery must be
found. In collaboration with AMRAD Pty Ltd we are
about to test a method to administer LIF to the site of
nerve repair, and if successful we believe we will be
ready to commence clinical trials.
Expression of LIF following human nerve
injury
To date the expression profile of LIF within nerves
has been confined to animal models such as rats and
mice. We therefore determined whether LIF is
expressed in normal human nerves and whether its
16 25

Macrophages and Inflammation
Senior Scientist: Peter Vadiveloo
Members of the Laboratory: Matias Abregu, Angela
Arvanitis, Bruce Dowsing, Tanya Harkom, Effie
Keramidaris, Wayne Morrison, Rosalind Romeo.
...and Major Collaborators: Fiona Clay c , Matthias
Ernst c , Paul Hertzog b , John Hamilton d , Alastair Stewart a ,
and Gino Vairo e .
aDepartment of Pharmacology, University of Melbourne
bMonash Medical Centre, Clayton, Vic.
cLudwig Institute for Cancer Research, Parkville Vic.
dUniversity Department of Medicine, Royal Melbourne
Hospital, Parkville.
eWalter and Eliza Hall Institute, University of Melbourne,
Parkville.
Mechanisms of macrophage activation
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 since knowledge of fundamental
biological processes will ultimately result in better
treatment of patients following trauma and surgery.
We have made the unique discovery that activated
macrophages make a protein called cyclin D2. We believe
this protein regulates macrophage functions. We are trying
to better understand the role of cyclin D2 in activated
macrophages. An exciting advance in these studies over
the past year has been the beginning of experiments using
cyclin D2 ‘knockout’ mice. These mice (which come from
our colleagues at the Dana Farber Cancer Institute in
Boston) have been genetically engineered with the cyclin
D2 gene knocked out. Our preliminary data indicate cyclin
D2 may regulate production of inflammatory cytokines by
macrophages. Confirmation of this finding will provide a
significant advance in our understanding of how
macrophages work. In other work on this project, Honors
student Matias Abregu is identifying cytokines that
stimulate cyclin D2 synthesis in macrophages.
In other studies that link in with work on nitric oxide
(NO), we have shown that NO production by
macrophages is mediated by type I IFNs, and that NO
does not play a role in preventing proliferation during
macrophage activation.
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.
Wound Healing in Tendons
Senior Scientists: David McCombe, Tony Penington,
Wayne Morrison.
Members of the Laboratory: Rosalind Romeo, John
Hurley.
...and Major Collaborators:
Tracey Brown m , V Gunzler k , Erik W Thompson j and JF
Williams k
jVictorian Breast Cancer Research Consortium, St
Vincent’s Hospital Melbourne.
kDepartment of Engineering, University of Melbourne.
mDepartment of Biochemistry and Cell Biology, Monash
University
Tendon adhesions are a significant complication of tendon
injury or infection. After surgical repair of a tendon, scar
tissue often forms around the tendon, binding it to the
sheath (tunnel) in which it slides. In these experiment we
have been attempting to mimic these tendon adhesions in
the human using an animal model. We isolated a healthy
tendon and injected an irritant substance (eg. carrageenan,
iodine, oxytetracyclin, endotoxin or other abrasive agents)
into the sheath to create adhesions. The animal was
euthanised 1-3 weeks later and the limb isolated. A force
transducer was used to pull the digit into full flexion so
that the claw touches the sole of the foot, a measure of the
strength of the adhesions.
We also studied the effects of inhibitors of prolyl-4hydroxylase
and collagen synthesis on flexor tendon
adhesion formation and skin wound healing. Rats were
divided equally into three groups to receive post-operative
oral doses of two test drugs or no drug (control). Animals
were sacrificed fourteen days after a zone II tendon crush
injury with suture immobilization, and a dorsal skin patch
excision. Tendon adhesion formation was estimated
biomechanically using work of flexion (WOF) of the digit.
Skin healing was measured using wound area and histology.
Compared to the control group, WOF against adhesions was
reduced by approximately 70% in both drug groups. All
skin wounds healed equally well, but in both drug groups
there was minimal deposition of scar collagen. These drugs
may become useful clinically to reduce adhesions following
flexor tendon surgery and in hand and foot surgery where
modulating collagen scar formation is important.
stabilised our position financially both among the
business community and with government. We
will greatly miss Alan’s calm and charm and
sincerely thank him for his outstanding
contributions. We wish him well for the future.
This year through a generous donation of our
Chairman we have been able to employ a
Developmental Manager, Mr Sam Broughton.
Sam has an excellent track record both in
Victoria and South Australia where he has
worked with several bodies, most recently the
Red Cross. We are hopeful that this will lead to
new avenues of fundraising and increase our
professionalism in the marketplace.
This year we have instituted a younger group
under the auspices of the Microsurgery
Foundation. We are especially indebted to them
for their generosity for coming on board and
believe this will be an exciting development for
us in the future.
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, National Health &
Medical Research Council, Transport Accident
Commission, The Jack Brockhoff Foundation,
National Australia Bank, Evelyn M. Coy Estate,
The Wellcome Trust, BHP Community Trust,
Tattersall’s, L.E.W. Carty Charitable Fund, HIH
Insurance Ltd.
We are grateful to Ms Sue McKay and Ms
Liliana Pepe and their staff in the Experimental
and Medical Surgical Unit. For many years they
have provided an outstanding level of
cooperation and support to the staff of the
Bernard O’Brien Institute of Microsurgery.
We also thank Dr Jim Shaw, Chairman of St.
Vincent’s Hospital Animal Ethics Committee and
his board members who oversee all our projects
and ensure the highest standards of animal care
are maintained.
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
MICROSURGERY
FOUNDATION
24 17

Barbara Walker Centre for Pain Management
Bernard O’Brien Institute of Microsurgery
Director
Dr Andrew Muir
I
am pleased to
report that
significant
progress has been
made in the
management and
treatment of pain at
the Barbara Walker
Centre for Pain
Management, in this
our second full year
of operation.
The mission of the Centre is to provide
specialist multi-disciplinary assessment and
treatment services for the management of
complex pain across all disciplines of medicine.
Through its association with the Bernard
O’Brien Institute of Microsurgery, the Barbara
Walker Centre for Pain Management conducts
medical research to improve clinical outcomes
for acute pain sufferers.
Research
· Two posters presentations were submitted to
the IASP’s 9 th World Congress on Pain in
August 1999 and subsequently accepted for
publication. The presentations related to
“Assessing Dynamic Standing Balance in
Clinic Patients: the Step Test” and “The
Depression Anxiety Stress Scale in Patients
with Persistent Pain”.
· Collaborative research with the Australian
Centre for Neuropharmacology in an
international multi-centre trial of a novel
pharmaceutical for the treatment of post
herpetic neuralgia.
· Development of protocols in respect to
undertaking research into:
a) Prospective survey of posture types
of patients presenting assessment at
Barbara Walker Centre for Pain
Management.
b) Register of women taking
anticonvulsant medications for
the treatment of persistent,
neuropathic pain.
Clinical Activity
Clinical activity is a core function of the Barbara
Walker Centre for Pain Management.
The number of patients that we treat is
dependent upon referrals that we receive. We are
indeed fortunate to have the support of those in
general medical practice, who have welcomed
our specialist initiatives in the treatment of pain
and who refer their patients to us. During the
past year we have seen in excess of 1,000
patients which is a significant increase over the
numbers we treated in our first year.
All clients receive an individual assessment of
their condition and tailored programs are devised
for treatment encompassing a range of specialist
services. The START program is an important
component of our clinical activity and we have
seen the number of participants increase during
the year under review.
Medical Education
Education is an important function of the
Barbara Walker Centre for Pain Management.
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 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.
Factors Involved in Ischaemia-Reperfusion
Injury
We have been investigating the mechanisms of
ischaemia-reperfusion (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.
(a) Mast cell factors
To determine the role of mast cells (a type of white
blood cell) in IR injury to skeletal muscle, mast celldeficient
mice and their corresponding genetically
normal (i.e. wild type) mice were subjected to
tourniquet ischaemia and reperfusion. Muscle viability
after this injury was 9% in wild type controls and 94%
in mast cell-deficient animals (P

This study is now being extended to include seeding of the
blood vessel loop and matrix scaffold with pancreatic islet
cells. We will monitor the cell survival and the ability of
the surviving cells to produce insulin.
Stem cell research
These cells come from the bone marrow and are
pluripotent i.e. have the potential to develop into all
tissues skin, muscle, bone, fat, etc. Under normal
conditions a combination of the local environment and
chemical factors decide their destiny. With the help of Dr
Paul Simmons and his team at Peter McCallum Institute,
we are taking the bone marrow cells from immature rats,
extracting the stem cell fraction, and growing these cells
up in the laboratory. We then “label” the cells by infecting
them with a virus that produces a fluorescent protein and
place them in our A-V loop chamber model where we
leave them for variable periods of time to show their
survival and see into what cells they develop. Their ability
to fluoresce allows us to detect the fate of these cells in
the new tissue.
This year we hope to decide their destiny by adding
various different chemical factors to the chamber. For
example, by adding Bone Morphogenic Protein (BMP) we
hope to grow a bone, which could then be microsurgically
transplanted.
Myoblast research and tissue engineering
Myoblasts are immature muscle cells that are precursors
of mature skeletal muscle. We harvest myoblasts from
rats and grow them up in culture in the laboratory. They
are then placed in our A-V loop chamber model where
they are left for different time periods. We are hoping that
these cells will give rise to a mature muscle that is
sustained on our blood vessel loop and is therefore
suitable for microsurgical transplantation.
Scaling down tissue production
The tissue engineering model is also to be scaled down in
size to the mouse. This is because mice are relatively easy
to manipulate genetically which will allow us to study
some of the fundamental processes involved in tissue
differentiation and growth. We hope that a better
understanding of these processes will allow us to direct
which type of tissue forms within the chamber and how
fast it grows. Stem cell research in mice is very far
advanced and this new model will also provide us with
many exciting opportunities to explore this area.
Scaling up tissue production
In our tissue engineering experiments in the rat with the
blood vessel loop in a plastic chamber, we found that
blood vessels and new tissue filled the chamber within 2
weeks under optimal conditions. However, we do not
know the full growth potential of this system until we have
established whether further growth is possible in larger
chambers with 4 times the original volume. The next stage
of these experiments is to scale the tissue production up to
the rabbit and possibly the pig, prior to humans, in order to
show that larger blood vessels have the potential to
produce a proportionally larger amount of new tissue.
Tissues maintained on an extracorporeal
circulation
We have commenced a project involving maintenance of
tissues on an artificial circulation. With the co-operation of
the cardiac perfusionists, cardiac bypass equipment is
being modified to allow it to nourish detached tissues. It is
anticipated that this will be used when an amputated part
cannot be immediately replanted because of blood loss or
other injuries and we hope to incorporate this technology
into our tissue engineering projects. Rabbit muscles were
successfully perfused for 24 hours and in the next few
months work will progress on modifying the composition
of the perfusion solution. Another application of this
technology is the growth of new tissues in vitro by our
tissue engineering blood vessel loop method.
Transport Accident Commission Trauma
Laboratory
Senior Scientists: Ken Knight, Aurora Messina, Diana
Lepore.
Clinical Research Fellows: Tony Penington, Damien
Ireland.
Members of Laboratory: Tanya Harkom, John Hurley,
Effie Keramidaris, Peter Meagher, Wayne Morrison,
Rosalind Romeo.
... and Major Collaborators:
Robin Anderson i , Peter Cowan f , John Hamilton d , Alicia
Jenkins h , Trixie Shinkel f , Alastair Stewart a , and Aldo
Tomasi o .
a Department of Pharmacology, University of Melbourne
d University Department of Medicine, Royal Melbourne
Hospital, Parkville.
f Immunology Research Centre, St Vincent’s Hospital,
Melbourne
h Department of Medicine, University of Melbourne,
St Vincent’s Hospital.
i University of Melbourne, Peter MacCallum Cancer
Institute.
o University 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.
A high priority has been set to disseminate
information on pain management to a number
of key audiences including: general
practitioners, medical students, hospital
medical officers, specialists, nursing staff and
medical ancillary professionals. Each has an
important role to play in the advancement of
pain management and control.
During the recent months we have completed:
· Literature review and research into
Training Needs Analysis of General
Practitioners in differing locations.
· Preparation of materials for Education
packages.
Our Staff
I firmly believe that our staff are our greatest
asset. As a relatively new unit our staff
members are highly committed to advancing
the progress of the Centre in its formative
years. As resources have permitted a number
of new staff members have joined the Centre.
Microsurgery Foundation
Our creation and existence is a direct result
of the vision of the Board of Directors of the
Microsurgery Foundation. I am grateful for
their ongoing support, particularly for their
fundraising activities that underpin our ability
to continue as a viable organisation.
We would like to thank the State and Federal
Governments, as well as Victorian Workcover
for their invaluable financial support that
allows our work to continue.
The Future
MICROSURGERY
FOUNDATION
All at the Barbara Walker Centre for Pain
Management are pleased and proud of the
advances that have been made in the two
years since our establishment. We have a
vision of a pain free society and are
confident, that given continuing support, we
can continue to make real advances into the
understanding of pain and its control and
management.
To do so will bring relief to many thousands
of people who are afflicted by this condition.
Dr Andrew Muir
Director
22 19

Bernard O’Brien Institute of Microsurgery
Scientific Report 1999-2000
General Introduction
The scientific activities of the Institute have focused on
the following areas of investigation:
· Tissue engineering
· Tissue injury following ischaemia-reperfusion
· Inflammation and macrophage function
· Tendon healing
· Nerve repair and regeneration
· Blood vessel biology, including studies of
angiogenesis and haemangiomas
Finding tissue suitable to replace a lost ear, nose or bone
creates a major challenge for reconstructive surgeons. To
overcome these problems we are using a process known as
“tissue engineering” to produce new tissues that can be
used to repair such wounds. The tissue can be made to
grow inside a plastic chamber which has been fitted with a
blood vessel loop connected to the body’s own blood
supply, a biodegradable scaffold (such as Matrigel), and
seeded with various cells of a particular tissue type
(muscle, fat, bone marrow stem cells, etc). Specific
growth or differentiation factors may also be added and
this “construct” is incubated under the skin. After 4 to 8
weeks the chamber fills with new tissue, which we intend,
in the future, to contour to a desired shape (eg. a nose, ear,
finger joint, etc). We are also experimenting with this
chamber model in the hope of developing organs such as
the pancreas by special cell seeding techniques. If
successful, this would be of major benefit to individuals
with Type 1 diabetes.
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 (known as
“ischaemia-reperfusion injury”). 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.
Using a new patent drug we have been able to
demonstrate a very significant reduction in scar formation
and adhesions to surrounding tissues, a common problem
that faces patients who have had tendon surgery. Our work
on macrophage cells continues to provide us with
important new insights into the molecular mechanisms
controlling macrophage function, and the role of these
cells in inflammation, wound repair and blood vessel
formation.
Work on leukaemia inhibitory factor (LIF) and glial cell
derived neurotrophic factor (GDNF) has shown that these
agents aid peripheral nerve repair and preserve their
associated muscles. We have shown that LIF 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 and GDNF to
sites of nerve injury being repaired by microsurgery.
A 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.
We have begun examining the causes of haemangiomas, a
condition in which blood vessels spontaneously grow out
of control. They are known to contain high levels of
inflammatory cells such as mast cells. We have found that
when these haemangiomas are placed in culture and
exposed to FDA-approved inhibitors of mast cell activity,
haemangioma growth is eliminated/prevented.
Tissue Engineering - VTEC
Director: Wayne Morrison
Senior Scientists: Tony Penington, Ken Knight, Aurora
Messina, John Hurley.
Members of Laboratory: David Brown, Oliver Cassell,
Kevin Cronin, Rob Donato, Stefan Hofer, Effie
Keramidaris, Peter Meagher, Rosalind Romeo.
… and Major Collaborators:
Tracey Brown m , Justin Cooper-White g , Richard Gilbert h ,
Alicia Jenkins h , Rob Kapsa n , Darren Kelly h , Andrea
O’Connor g , Jilska Perera g , Paul Simmons i , Geoff Stevens g ,
Alastair Stewart a , Yoshio Tanaka l , Erik W Thompson j ,
and Murray Worner k .
g Department of Chemical Engineering, University
of Melbourne.
h Department of Medicine, University of Melbourne,
St Vincent’s Hospital.
i Stem Cell Research Laboratory, University of Melbourne,
Peter MacCallum Cancer Institute.
j Victorian Breast Cancer Research Consortium,
St Vincent’s Hospital Melbourne.
k Department of Physical Sciences, St Vincent’s Hospital
Melbourne.
l Department of Plastic and Reconstructive Surgery, Osaka
Medical College, Osaka, Japan
m Department of Biochemistry and Cell Biology,
Monash University
n Melbourne Neurosciences, University of Melbourne,
St Vincent’s Hospital.
Tissue Engineering
Finding tissue suitable 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 that can be used
to repair wounds by a process known as “tissue
engineering”. Tissue formed by this technique would
be ideal as, for example, “filler tissue” for the repair
of defects in the face or neck resulting from the
removal of a skin cancer.
The Arterio-venous Loop Model (A-V Loop
Model)
This is an experimental model of tissue engineering in
the groin of a rat. A loop of blood vessel around which
new cells and tissues can grow is generated by taking a
vein out of the groin and placing it in the opposite
groin connecting the femoral artery to the femoral vein.
This loop is then placed into a plastic chamber in the
groin. The chamber contains both “a scaffold”
material, or matrix which gives both physical and
nutritional support to the newly growing blood vessels
as well as the different cells which use the new blood
supply to divide and grow into a “neoorgan”. We are
currently experimenting with different cells including
muscle, pancreas, fat, bone and more recently stem
cells. The vessels in this loop are of such dimensions
that they can be microsurgically transplanted into
another animal with the attached neoorgan. In this
manner we are attempting to grow transplantable
organs.
Influence of the extracellular matrix scaffold
on new tissue formation
A no-matrix control and three different extracellular
matrices were investigated for their ability to increase
the rate and amount of tissue generated. In control
experiments new granulation-like tissue grew
progressively up to 12 weeks, filling two-thirds of the
chamber. The addition of Matrigel at time zero to the
blood vessel loop and chamber increased the rate of
vascularisation and weight of tissue produced, peaking
at 4 weeks (P