melbourne health research week 2008 · 2015-07-22 · Professor Jim Angus, Dean, Faculty of...

melbourne health research week 2008

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RESEARCH WEEK 31 MAY – 5 JUNE 2008

This publication contains the Research Week 2008 program and listing of abstracts accepted for publication, submitted by members of Melbourne Health and affiliated institutes.

The Research Week Committee was chaired by Professor Ingrid Winship and included the following members in 2008: Associate Professor Russell Gruen Associate Professor Geoffrey Hebbard Professor Stephen Jane Ms Carol Jewell Professor Andrew Kaye Dr Jonathon Knott Ms Angela Kreso Ms Jacqui McGrory Ms Morag Morrison Dr Angela Watt

The efforts of those involved in selecting suitable abstracts and in the adjudication of the Awards during Research Week are greatly appreciated.

Professor Ingrid Winship Executive Director of Research

Melbourne Health gratefully acknowledges the generous sponsorship of MH Research Week 2008 by:

Amgen Australia Pty Ltd Celgene Pty Ltd Genzyme Australasia Pty Ltd GlaxoSmithKline Australia Pty Ltd Novartis Pharmaceuticals Australia Pty Ltd

Roche Products Pty Ltd Sanofi-Aventis SmartSalary Pty Ltd

With thanks to Ckaos Ink Pty Ltd who kindly designed and sponsored the cover of the Research Week 2008 program

Melbourne Health Research Week 31 May – 5 June 2008

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Surgical Research Forum Saturday 31 May 2008

8.30 am – 10:00 am Charles La Trobe Lecture Theatre

Chair: Professor Andrew Kaye, Director of Neurosurgery, Royal Melbourne Hospital, Professor of Surgery, The University of Melbourne

1. Tanya Yuen Neurobiological factors predisposing to epilepsy in patients with gliomas. Yuen T, O'Brien TJ, Kaye AH, Bjorksten A, Morokoff A, Powell K, Paradiso L, Dabaco G, Drummond K, Rosenthal M

2. Hui Lau Establishment of a mouse brain tumour model for the study of the neurobiological mechanisms involved in the development of tumour-associated epilepsy. Lau H, D'Abaco G, O'Brien T, Kumar G, Stylli S, Morokoff A

3. Ben Namdarian

Circulating endothelial cells and progenitors: Prognostic markers in prostate cancer. Namdarian B, Georgiou HD, Hovens CM, Costello AJ

4. Anita Skandarajah Benign papilloma requires surgical excision. Skandarajah AR, Field L, Mou AYL, Buchanan M, Evans J, Hart S, Mann GB

5. Susan Shedda The management of stage IV colorectal cancer at presentation – What is happening in routine practice? Shedda S, McLaughlin S, Jones I, Faragher I, Hayes I, Skinner I, Hastie I, Desai J, Gibbs P

6. Michael Wong A novel angiogenesis inhibitor for malignant glioma. Wong M, Kaye A, Hovens C


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Melbourne Health Research Symposium Monday 2 June 2008

9:00 am – 10:00 am Plenary 1 – Charles La Trobe Lecture Theatre

Welcome and Opening of MH Research Week 2008

Keynote Speaker:

Professor Jim Angus, Dean, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne – The Spirit of Research Collaboration - from Project to Institution

Research Paper:

Dr Caroline Brand, Head, Clinical Health Services Evaluation Unit, RMH – Orthopaedic Waiting List Project

10:00 am – 11:15 am

Concurrent Session 1

MUSCULOSKELETAL RESEARCH

Chair: A/Professor Terence O’Brien

Venue: Charles La Trobe Lecture Theatre


EMERGENCY/CRITICAL CARE/ ANAESTHESIA RESEARCH

Chair: Dr Jonathan Knott

Venue: Seminar Room 1

8. Ian Wicks G-CSF regulates inflammatory arthritis. Wicks IP, Eyles JL, Norman U, Hickey MJ, Campbell IK, Roberts AW, Metcalf D

9. Tania Romano Reduced bone mineral content, size and strength caused by intrauterine growth restriction are corrected by an improved postnatal lactational environment in female offspring. Romano T, Wark JD, Owens JA, Morris HA, Wlodek ME

10. Ana Hutchinson and Peter Ebeling Acute chronic obstructive pulmonary disease (COPD) exacerbations are associated with uncoupling of bone resorption from bone formation. Hutchinson A, Thompson M, Smallwood D, Bozinovski D, Anderson GP, Irving L, Ebeling PR

11. Louisa Ng Multidisciplinary rehabilitation programmes following joint replacement at the hip and the knee in chronic arthropathy. Khan F, Ng L, Gonzalez S, Hale T, Turner Stokes L

12. Wendy Pollock Service gap: obstetric patients in ICU. Pollock W, Harley N

13. Meredith Heily Can a simulation based training program improve medical student confidence to perform resuscitation? Heily M, Tse J, McColl G, Lim S

14. Joanne Jordan The patient perspective: understanding the role and impact of health literacy within the Emergency Department setting. Jordan JE, Buchbinder R, Kennedy M, Osborne RH

15. Pek Ghe Tan A map of research evidence in the pre-hospital care of patients with traumatic brain injury. Tan PG, Gruen R, Tavender E, Clavisi O, Bragge P, Wasiak J, Cincotta M, Pattuwage L

16. Lisa Barker The effect of pre-operative oral immunonutrition therapy on postoperative outcomes in gastrointestinal surgery patients. Barker L, Gray C, Wilson L, Thomson B, Jones I, Shedda S, Crowe T


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11:15 am – 11:30 am Morning Tea and Trade Display

Venue: Bar Area, RMH Function and Convention Centre

11:30 am – 12:45 pm


CANCER RESEARCH

Chair: Dr David Curtis



CARDIORESPIRATORY & VASCULAR RESEARCH

Chair: Dr Abe Rubinfeld


17. Sue Shedda The management of stage IV colorectal cancer at presentation – what is happening in routine practice? Shedda S, McLaughlin S, Jones I, Faragher I, Hayes I, Skinner I, Hastie I, Desai J, Gibbs P

18. Rodney Luwor Dynamin II function is required for EGF-mediated Stat3 activation but not Erk1/2 phosphorylation. Luwor RB, Zhu HJ

19. Elgene Lim Characterisation of subpopulations of human mammary epithelial cells. Lim E, Vaillant F, Forrest N, Gyorki D, KConFab, Visvader J, Lindeman G

20. Ramin Shayan Defining tumor lymphatics and targeting differences in lymphatic vessel subtypes formed in human disease, for therapeutic benefit. Shayan R, Karnezis T, Ashton MW, Mann GB, Taylor GI, Corlett RJ, Achen MG, and Stacker SA

21. Haris Haqqani Left ventricular substrate in ischemic cardiomyopathy patients with and without ventricular tachycardia. Haqqani HM, Roberts-Thomson KC, Snowdon RL, Medi C, Balasubramaniam R, Sparks PB, Vohra JK, Kalman JM, Morton JB

22. David Andrews Investigation of the haemodynamic effects of volatile and intravenous anaesthetic agents during ischaemia-reperfusion using pressure-volume loops. Andrews DT, Wright CE, Royse AR, Royse CF

23. Colleen Doyle Promoting public awareness of chronic obstructive pulmonary disease. Doyle C, Dunt D

24. Daniel Steinfort Cumulative proceduralist radiation exposure in the performance of endobronchial ultrasound with guide sheath (EBUS-GS) bronchoscopy utilizing fluoroscopic guidance. Steinfort DP, Einsiedel P, Irving LB

25. Jane McCann Is pulse oximetry a useful tool for diagnosing peripheral vascular disease? McCann J, May K, Frescos N, Wraight P

Melbourne Health gratefully acknowledges the generous sponsorship of MH Research Week 2008 by:

Amgen Australia Pty Ltd Celgene Pty Ltd Genzyme Australasia Pty Ltd GlaxoSmithKline Australia Pty Ltd Novartis Pharmaceuticals Australia Pty Ltd

Roche Products Pty Ltd Sanofi-Aventis SmartSalary Pty Ltd


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12:45 pm – 1:30 pm Lunch and Trade Display


1:30 pm – 2:40 pm


MENTAL HEALTH RESEARCH

Chair: Professor Alex Cockram



QUALITY of CARE RESEARCH

Chair: Dr Angela Watt


26. Dennis Velakoulis Evaluating clinical outcomes of ECT across a large urban mental health network; Data from the NorthWestern Mental Health / Melbourne Health ECT database. Velakoulis D on behalf of the NorthWestern Mental Health ECT Committee

27. Tahir Hakami NMDA receptor antagonists dose-dependently induce aberrant cortical gamma oscillations that correlate with psychotic-like behaviour. Hakami T, Jones NC, Salzberg MR, O'Brien TJ, Pinault D

28. Suresh Sundram The identification of co-morbid substance use disorder in in-patient with psychiatric illness. Sundram S, Matsudaira A, Happell B, Gough K

29. Ashleigh Lin Olfactory identification deficits remain stable following a first episode of psychosis: What the EPPIC-medium term follow-up study tells us further about orbitofrontal function through the course of psychosis. Brewer WJ, Wood SJ, Henry, Harris MG, Pantelis C, McGorry PD

30. Joe Buckby Do self-reported psychotic-like experiences (PLEs) correspond to interview-reported PLEs in help-seeking versus general population young Australians? Buckby JA, Yung AR, Ross R, Cosgrave EM, Ryan J, Baksheev G

31. Jonathan Knott Effect of nightshift on clinical skills: a controlled trial. Marcus L, Liew D, Knott J

32. Jacques Joubert ICARUSS – Integrated Care for the Reduction of Secondary Stroke. Ames D, Joubert L, Davis S, Donnan G, Hankey G, Levi C, Dewey H, Reid C, Jackson D, Joubert J

33. Alison Yung Declining transition rate in ultra high risk (prodromal) services: dilution or reduction of risk? Yung AR, Yuen HP, Berger G, Francey S, Hung T, Nelson B, Phillips L, McGorry P

34. Daniel Gilbertson Reducing readmission rates? – Another role for community liaison pharmacists at a tertiary referral hospital. Frank M, Gilbertson D, Galbraith K

35. Pauline Parker Optimising acute postoperative pain management – a collaborative quality improvement initiative. Parker PE, Hogg M, Chia A, Robertson MB, Wai A, Mackson JM, Kaye KI, McIntosh KA


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2:40 pm – 3:50 pm


GENETICS RESEARCH

Chair: Professor Peter Colman



NEUROSCIENCE RESEARCH

Chair: A/Professor Terence O’Brien


36. Slave Petrovski A multi-SNP predictor for drug outcome in complex diseases. Petrovski S, Szoeke CEI, D’Souza W, Sheffield LJ, Huggins RM, O’Brien TJ

37. Duncan Carradice The mutant marsanne reveals a novel transcription factor critical for normal neutrophil development in zebrafish. Carradice D, Layton J, Heath J, Lieschke GJ

38. Spiros Fourlanos The rising incidence of type 1 diabetes is accounted for by cases with lower risk HLA genotypes, Fourlanos S, Varney MD, Tait BD, Morahan G, Honeyman MC, Colman PG, Harrison LC

39. Caroline Ng A novel mutation in the rat Cav3.2 T-type Ca2+ channel CACNA1H gene increases absence seizure expression and channel function. Ng C, Powell K, Sirdesai S, Kyi M, Garcia E, Reid CA, Pinault D, Foote SJ, Snutch TP, O'Brien TJ

40. Kim Powell Can too much Stargazin cause epilepsy? Powell KL, Kyi M, Reid CA, Paradiso L, D’Abaco G, Kaye AH, Foote SJ, O’Brien TJ

41. Sandra Petty Chronic anti-epileptic medication (AED) usage is associated with reduced balance – an AED-discordant twin and sibling matched pair study. Petty SJ, Hill KD, El Haber N, Paton LM, Lawrence KM, Berkovic SF, O’Brien TJ, Wark JD

42. Tanya Yuen Neurobiological factors predisposing to epilepsy in patients with gliomas. Yuen T, O'Brien TJ, Kaye AH, Bjorksten A, Morokoff A, Powell K, Paradiso L, Dabaco G, Drummond K, Rosenthal M

43. Stan Stylli Determining the role of Tks5 in invadopodia formation, tumour invasion and metastasis. Stylli SS, I STT , Xu S, Courtneidge SA, Kaye AH, Lock P

44. Fary Kahn Effectiveness of vocational rehabilitation for persons with multiple sclerosis. Kahn F, Ng L, Turner Stokes L

3:50 pm – 4:10 pm Afternoon Tea and Trade Display


4:10 pm – 5:00 pm Plenary 2 and Symposium Close: Charles La Trobe Lecture Theatre

Chair:

Professor Ingrid Winship, Executive Director of Research

Guest Speakers:

Professor Stephen Jane, Director, Bone Marrow Research Laboratories The Bone Marrow Research Laboratories – yesterday, today and tomorrow

Professor James Tatoulis, Divisional Director of Cardiac Services and Director of Cardiothoracic Surgery The radial artery in coronary surgery: An 11-year experience in 14,704 patients – clinical and angiographic results.

5:00 pm – 6:00 pm Poster Viewing and Drinks



LUNCH TIME SERIES Tuesday 3 June 2008 12.30 pm – 1.00 pm Lunch


The Great Parachute Debate – Five leading scientists argue for their right to live: YOU decide their fate…

1.00 pm – 2.00 pm Charles La Trobe Lecture Theatre

Chair: Professor Ingrid Winship, Executive Director of Research

Judges Ms Carol Jewell, Allied Health Clinical Educator

Dr Jonathan Knott, Head of Emergency Research and Education

A/Professor Denise Heinjus, Executive Director, Nursing Services

Professor Peter Colman, Director of Diabetes and Endocrinology; Chair, Human Research Ethics Committee

Ms Jan Sharrock, Director Public Affairs

Special Guest Sir Biggles Branson – Billionaire businessman and hobby pilot

(aka Mr Robert Doyle, Chairman, Melbourne Health Board)

Panelists Professor Numbers-R-Us: Expert biostatistician/clinical epidemiologist (aka Professor Rodney Judson, Divisional Director Surgery and Perioperative, Director of Trauma)

Professor Bald-No-More: Nobel prize winning physician/molecular biologist (aka Professor Geoff McColl, Professor of Medical Education and Training, Director Medical Education Unit, School of Medicine, the University of Melbourne)

Professor Cut-N-Paste: Distinguished trauma surgeon (aka A/Professor Kate Leslie, Head of Research, Anaesthesia and Pain Management)

Professor Fat-No-More: Endocrinologist and world expert in obesity research (aka Mr David Ford, Director of Pharmacy)

Professor Penny Pill-Popper: Entrepreneurial and philanthropic medical director of BMX Pharmaceuticals International Ltd (aka Professor Alex Cockram, Executive Director, NorthWestern Mental Health)

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LUNCH TIME SERIES Wednesday 4 June 2008 12.00 pm – 12.30 pm Lunch sponsored by BioGrid Australia


Current research and new trends in Collaborative Clinical Informatics Research


Chair: Mr Rob Merriel

The National Colorectal Cancer Database

A/Professor Peter Gibbs, RMH, LICR, Database Western Health

Epilepsy Bioinformatics Mr Slave Petrovski, PhD student, RMH, University of Melbourne

Tumour associated epilepsy Dr Tanya Yuen, Neurosurgical trainee/ PhD student, Dept of Surgery RMH/WH, University of Melbourne

Diabetes audit and research Professor Peter Colman, RMH, WEHI

BioGrid plans and progress Dr Marienne Hibbert, RMH, University of Melbourne, VPAC

LUNCH TIME SERIES Thursday 5 June 2008 12.30 pm – 1.00 pm Lunch


Research Ethics – National Statements and Codes of Conduct, the new template for PICFs and SOPs for GCP


Chair: Professor Peter Colman

The new NHMRC National Statement and the Australian

Code for the Responsible Conduct of Research

Dr Angela Watt, Manager Research, Directorate

The new template for Participant Information and Consent Forms

Ms Angela Gray, Assistant Manager, Research Directorate

SOPs for GCP at Melbourne Health

Ms Angela Gray, Assistant Manager, Research Directorate

Presentation of Prizes and Close of Research Week

Professor Ingrid Winship, Executive Director of Research

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8

:

1. Tanya Yuen NeurobiologicalYuen T, O'Brien TJ, hal M

ssociated epilep s with gliomas and is frequently medically refractory. Mechanisms of TAE pathogenesis are largely unknown. Hypotheses: 1. That there are predisposing clinicopatho ical and molecular factors for patients with gliomas predisposing to TAE and treatment refractoriness; 2. That in TAE there is an increased excitatory neurotransmitter glutamate, te transporters, ie. reduced expression of EAAT nge; 3. That these elevated glutamate le ctivated cyclic nucleotide-gated cation chann

xamined for TAE and treatment refractoriness. Each st of 20 oing first surgery for gliomas at the Royal Melbourne and Melbourne Private

Hosp . Dafactors that ill be col ll be obtained at ples patients. Tissu ed forGlutamat hrompatients on T E 2, Xc me PCR for mRNResults to dateClinicopaA new seiz s be ure risk for retrospective patients was 53% for low grade and 42% for high grade tumours. Younger age and

mporal lobe location were significantly associated with seizures and seizures occurring preoperatively were significantly associated with seizures occurring postoperatively. Molecular - Retrospec

• Glutamate: Pa pecimens than those

EAAT2: Patients with TAE had significantly lower expression of EAAT2 in the tumour than those thout AE.

• HCN: There was a strong trend for downregulation of HCN1 expression in patients with TAE. nalysis of factors for prospective patients and remaining molecular factors for retrospective patients is currently

being undertaken. Conclucorrela rm study aims to address this f these patients.

Oral Presentations

factors predisposing to epilepsy in patients with gliomas Kaye AH, Bjorksten A, Morokoff A, Powell K, Paradiso L, Dabaco G, Drummond K, Rosent

Royal Melbourne Hospital; University of Melbourne

Tumour a sy (TAE) is a common disabling problem in patient

log

in tumour, due to altered expression of membrane glutama1 and EAAT2 and upregulation of cystine– glutamate excha

vels will result in peritumoural altered expression of hyperpolarization-aels (HCN) and ADAM22 leading to TAE.

Study design: Prospective and retrospective cohorts will be ewill consi 0 patients underg

itals with a follow-up of 1-15 yearsmay predispose to TAE) w

ta for clinicopathological factors (patient, tumour and management lected. Prospective tumour and peritumoural brain samples wi

surgery and tumour same samples will be analys

stored in the RMH tumour bank will be retrieved for retrospective the following molecular factors:

e – high performance liquid cly) for levels EAA 1, AAT

atography and magnetic resonance spectroscopy (prospective -, ADAM22 – western blot for protein expression HCN – real ti

A expression. :

thological - ure/brain tumour database ha en incorporated into the Biogrid 21 Brain Cancer database. Seiz

te

tive data processed so far: tients with TAE had significantly higher glutamate levels in tumour s

without TAE. •

wi T

A

sion: The paucity of knowledge about TAE pathogenesis is due to the lack of large scale studies ting it with clinicopathological and molecular predisposing factors. This extensive observation long te

pressing research need and results could aid in future clinical management o

2. Hui L

Esta umour model for the study of the neurobiological mechanisms involved in ociated Epilepsy.

, D'Aba , , Morokoff A Epil patien decrease the q . Seizures s l despite surgery a s. The wn. More i eld of res

au

blishment of a mouse brain tthe development of Tumour-AssLau H co G O'Brien T, Kumar G, Stylli S

eptic seizures commonly occur inuality of life for affected patients

ts with brain tumour. They cause significant morbidity andecondary to brain tumour are often difficult to contro

underlying causes of tumour-associated seizures remain unknond anti-epileptic medicationgated fiover it is a poorly invest earch.


9

will be identifiable factors in involved in the development of these seizure such as hange in neurotransmitters level, alteration in receptor numbers or function and defect in the normal

suppress seizure propagation. athophysiology of TAE. We will

ngineered to . Following the initial phase of implantation and tumour growth,

ll monitor the mice via EEG for development of epileptiform changes and spontaneous seizures from the

heir brain tested.

We hypothesise that therecmechanisms that This project aims to establish a mouse brain tumour model for the study of the pestablish the tumour model using the SMA 560 glioma cell line. The SMA-560 cells we use will be estably express Green Fluorescent Protein (GFP)we wisurrounding neurons as tumour burden increases. At the end of the proposed monitoring period, the mice will be sacrificed and t 3. Ben Namdarian

Circulating endothelial cells and progenitors: Prognostic markers in prostate cancer. Namdarian B, Georgiou HD, Hovens CM, Costello AJ University of Melbourne and The Royal Melbourne Hospital

Introduction: Prostate cancer is a disease with markedly variable biology requiring better stratification to distinguish rapidly progressive from indolent disease. Vascularity in the primary, prostate tumor has been established as a predictor of poor outcomes and recent evidence suggests that circulating endothelial cells (CECsand progenitors (CEPs) are promising surrogate markers of vascularity in cancer. Here we investigate the relevance of CECs and CEPs as prognostic markers in prostate cancer, in precl

)

inical mouse models and patient

cells, while microvessel density (MVD) was determined using CD31 mistry. The Mann-whitney U test was used to compare levels between groups while the

s used to determine correlation between CECs and tumour variables.

te

oma. A stable post-prostatectomy patients (control group),

patients

PC3 L, p = 0.009); MDA breast model (62.22 / μL, p = 0.017) and Lewis Lung model (131.0 /

ed in the

nd intra-

ith greater vascularity.

y significant difference in CEC levels was identified between the metastatic and stable disease groups (p = 0.05).

a spectrum of CEC levels was observed in the pre-surgery group, approximately half had levels

onclusion: It appears that CEC levels are increased during prostate cancer in both pre-clinical models and

cohorts. Methods: CEC and CEP levels were enumerated by two colour Flow Cytometric Analysis identifying CD31+CD45-cKIT/CD133+/-immunohistochePearson coefficient waMouse Models CEC/CEPs were enumerated weekly, in SCID mouse models which included: subcutaneous LNCaP prostacancer, intra-prostatic LNCaP prostate cancer, intra-prostatic PC3 prostate cancer, intra-mammary fat pad MDA-MB-231 breast cancer and subcutaneous Lewis Lung carcinHuman Study – CEC/CEP levels were enumerated in: PS

with localised prostate cancer prior to surgery, and patients with metastatic disease. Results: Mouse Models – CEC levels were significantly elevated in the LNCaP prostate model (176.7 / μL, p = 0.004);prostate model (66.37 / μμL, p = 0.001) as compared to control mice (37.64 / μL). In addition, CEP levels were significantly elevatLNCaP prostate model (1.90 / μL, p = 0.004) and Lewis Lung model (2.48 / μL, p = 0.002) as compared to control mice (0.78 / μL). CEC levels significantly correlated with tumour weight of the subcutaneous LNCaP model (p = 0.018) amammary fat pad MDA-MB-231 Carcinoma (p = 0.014). A significant difference in MVD was established between the intra-prostatic LNCaP and PC3 tumours (p = 0.004). Thus, mice with higher CEC levels possessedtumours wHuman StudAFurthermore,similar to stable disease (<35/μL) and half closer to metastatic disease (>45/ μL). Despite the limited numbers, patients with CEC levels >45 / μL had significantly higher levels of PSA than those with levels < 35 / μL (p = 0.019). Cpatient groups and are influenced by tumour dimensions and vascularity. CEC enumeration shows promise as a useful prognostic marker in prostate cancer.


10

vans J4, Hart S5, Mann GB1

e has questioned the need for surgical excision in patients ision is

quired by targeting this concordant group in a large screen-detected population. ethods: A retrospective review of a prospectively collected database of all benign papillary core biopsies

95 and September 2007 at North Western Breast Screen and Monash Breast Screen in n between core and

istology reports were reviewed and the radiology was re-

s.

annot exclude malignancy, and therefore surgical excision is required. Synopsis: This paper shows a y by

4. Anita Skandarajah Benign papilloma requires surgical excision. Skandarajah AR1, Field L4, Mou AYL2, Buchanan M3, E1Department of Surgery, Royal Melbourne Hospital, 2Department of Radiology, Royal Melbourne Hospital, 3Department of Pathology, Royal Melbourne Hospital, 4Monash BreastScreen Monash Medical Centre, 5Monash BreastScreen Monash Medical Centre and Breast Surgery Unit

Background: When a papillary lesion is identified on core biopsy of an impalpable breast lesion, standard practice involves excisional biopsy. Recent literaturwith benign core biopsy and radiological concordance. Our aim was to assess whether surgical excreMbetween February 19Melbourne, Australia was performed. All patients had surgical excision enabling correlatiofinal excisional biopsy results on all lesions. All hassessed. Results: During a 14 year period, 5783 core biopsies were performed from 633 163 screening mammogramEighty patients (0.01%) had benign papilloma on core biopsy, no patients had atypia on core biopsy and allpatients had benign radiological features. Of the 80 patients, 15 patients were found to have ductal carcinoma in situ (8) or invasive ductal carcinoma (7) on final pathology yielding 19% malignant rate. Conclusion: Core biopsy showing benign papillary lesion, even where radiology is also suggestive of a benign process, c19% malignancy rate in patients who have benign papillary lesions on core biopsy and benign radiologcorrelation with final histopathology at surgical excision. 5 a

i-

e

of IS patients were ECOG 0-1 versus 23 (82%) in the NS group. Similar

)

he

ent with respect to age or performance status. There was a ifference in the distribution and number of metastatic sites. The proportion of patients in the NS group

otherapy was higher yet the median survival less, indicating these were a worse prognosis group.

. Susan SheddThe management of stage IV colorectal cancer at presentation – What is happening in routine practice? Shedda S, McLaughlin S, Jones I, Faragher I, Hayes I, Skinner I, Hastie I, Desai J, Gibbs P The Royal Melbourne Hospital, Western Hospital, Ludwig Institute for Cancer Research

Aim: To evaluate the management of patients presenting with stage IV colorectal cancer (CRC) utilising a multinstitutional prospective database. Method: Pati nts with stage IV CRC at diagnosis from January 2003 until June 2007 were identified. Three patient groups were studied (i) IS = initial (<12 weeks from diagnosis) resection of the primary tumour (ii) DS = delayed primary resection and (iii) NS = no primary resection. The clinical features at presentation, subsequent management and overall survival of these groups were compared utilising the resources of Biogrid Australia (formerly MMIM). Results: Of 959 patients with CRC, 170 (18%) had metastatic disease at presentation. 125 patients (74%) had IS, 0DS, and 45 (27%) NS. Of the IS group, 72 (58%) were male with a median age of 65 years. For the NS group 29 (64%) were male, the median age was 68. Eighty-three (53%) of the IS group had liver only disease versus 13 (32%) of the NS group. The incidence of multiple metastatic sites was higher in the NS group (41.4% vs 6.7% pvalue <0.01). Seventy-three (89%) p in both groups were smokers and/or had diabetes. In-patient deaths occurred in 4% of both groups. Seventy-six (61%) of the surgical patients versus 33 (79%) of the others received chemotherapy. 5FU and oxaliplatin was the most common first line therapy in both groups, 62 of 76 (82%) and 19 of 33 (58%p<0.01. Median follow up was 23.9 months in the non-surgical group and 22.6 months in the surgical group. Median survival of IS group was 11 months and 5 days versus a median survival of 7 months and 11 days for tNS group

roportions of patients

(p <0.001). Conclusions: The majority of patients presenting with stage IV CRC undergo initial surgery. If not operated on within 12 weeks of presentation, resection of the primary tumour is a rare event (none in this series). Patients undergoing surgery were not markedly differdreceiving chem


11

glioma. 6. Michael Wong

A novel angiogenesis inhibitor for malignant Wong M, Kaye A, Hovens C

8. Ian Wicks

erum G-CSF levels were measured throughout the course of CIA in wild type (WT) mice. CIA was

inistration of G-CSF in

naive WT mice to 2020 ± 170 pg/ml at the nset of CIA. CIA was reduced in G-CSF-/- recipients of WT bone marrow cells (day 63 mean clinical score ±

5) compared to [G-CSF-/-] → [WT] mice (3.4 ± 0.9), demonstrating that non-hemopoietic cells are s of G-CSF during CIA. There was reduced CIA in [G-CSFR-/-] → [WT] mice (mean clinical

sed in isotype control mAb- days). In contrast, treatment with

4

G-CSF regulates inflammatory arthritis, Wcks IP1, Eyles JL1, Norman U2, Hickey MJ2, Campbell IK1, Roberts AW3, Metcalf D3 1Reid Rheumatology Laboratory, Walter and Eliza Hall Institute of Medical Research; 2Centre for Inflammatory Diseases, Monash University; 3Cancer and Haematology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Background: Endogenous G-CSF and neutrophils might contribute to inflammatory joint disease and we previously showed that G-CSF deficient (G-CSF-/-) mice were markedly protected from collagen-induced arthritis (CIA). Objectives: To investigate how G-CSF signalling mediates inflammation during CIA. Methods: Sevaluated clinically and histologically in WT, G-CSF deficient (G-CSF-/-) and G-CSF receptor (G-CSFR-/-) deficient mice and in reciprocal bone marrow chimeras using these mice as donors and recipients. Antibodydepletion (Gr-1) was used to examine the influence of neutrophils on established CIA in WT mice. Intravital microscopy of the microcirculation was used to examine effects of local and systemic admWT and bone marrow chimaeric mice. Confocal microscopy was used to examine CD11b expression on neutrophils. Results: Serum G-CSF levels rose from a mean of 170± 40 pg/ml inos.e.m., 1.0 ± 0.the major producerscore day 63 ± s.e.m., 0.9 ± 0.5) compared to [WT] → [G-CSFR-/-] mice (4.4 ± 1.1), demonstrating that hemopoietic cells are the primary targets of G-CSF during CIA. Disease progrestreated WT mice with established CIA (mean clinical score 4.9 ± 0.6 after 14anti-Gr-1 mAb markedly reduced the progression of CIA (mean clinical score 0.4 ± 0.2 after 14 days). Intravital microscopy of the microcirculation of WT mice showed that G-CSF reduced rolling flux and rapidly increased leukocyte adhesion in postcapillary venules. Pre-treatment with anti-Mac-1 (CD18/CD11b) mAb abolished adherence. Leukocyte rolling, adhesion and emigration were all significantly increased in postcapillary venules hours after intraperitoneal injection of G-CSF. Systemic G-CSF failed to induce leukocyte recruitment in mice lacking expression of G-CSFR on hemopoietic cells. G-CSF rapidly increased surface expression of CD11b on purified neutrophils in vitro. Conclusion: G-CSF, via direct effects on neutrophil function, as well as neutrophil numbers, has a pro-inflammatory role in the pathogenesis of inflammatory arthritis. G-CSF antagonism might represent a novel therapeutic approach to inflammatory disorders. 9. Tania Romano

Reduced bone mineral content, size and strength caused by intrauterine growth restriction are corrected by an improved postnatal lactational environment in female offspring. Romano T1, Wark JD2, Owens JA3, Morris HA4, Wlodek ME1 1Department of Physiology, The University of Melbourne, Parkville, Australia; 2Department of Medicine, The University of MelbouBone and Mineral Service, Royal Melbourne Hospital, Parkville, Australia;3School of Paediatrics and Reproductive Health, Disciplines of Obstetrics and Gyn

rne,

aecology, University of Adelaide; 4Hanson Institute, IMVS, Adelaide, Australia

ction

rowth. Accelerated postnatal growth has been independently associated with adult onset of diseases.

Aims: Giving birth to a low birth weight baby is a complication affecting 10% of human pregnancies. In Western society, the major cause of fetal growth restriction is placental insufficiency. Fetal growth restriincreases the risk of developing adult diseases such as hypertension and diabetes. Importantly, it has beendemonstrated that placental insufficiency impairs milk quality and quantity, further compromising postnatal g


12

cal evidence suggests that osteoporosis is a disorder which may have developmental origins. prenatal and postnatal lactational environments on

l content and bone strength. tudy Design: To induce uteroplacental insufficiency and fetal growth restriction, bilateral uterine vessel ligation

; Restricted) or sham surgery (C; Control) was performed on gestational day 18 in WKY rats. Control, Reduced size of Control litters to match Restricted litters) and Restricted pups were cross-fostered onto

after birth. Femur length, dimensions, mineral content and density T) of the femur at 6 months.

females,

on-e mineral content, dimensions and strength were reduced in R-on-R and Red-on-R males and

(but not male) onto a -

t, les,

normal offspring (RED-on-R) also programs impaired adult bone characteristics. These results may have or reducing fracture risk for individuals born small or those born of normal weight but with

Recent epidemiologiWe have used cross-fostering to assess the influences of theadult bone size, bone mineraS(R(RED: reducingdifferent Control or Restricted mothers 1 day were measured using peripheral quantitative computed tomography (pQCBiochemical markers of bone turnover and sex steroid concentrations were measured. Results: Restricted (R-on-R, R-on-C) pups were born lighter than Controls with males, but not remaining smaller than C-on-C pups at 6 months. Pups born of normal weight, but whose litter size was reduced, grew slowly during lactation then accelerated after weaning when suckled on an R mother (RED-R). Cortical bonfemales, with lower density in Red-on-R females. Cross-fostering a Restricted female mother with normal lactation (R-on-C) restored bone parameters. Estrogen and testosterone were reduced in Ron-R, with no changes in biochemical markers of bone turnover. Conclusions: We have demonstrated that being born small programs reductions in adult bone mineral contendimensions and strength. These deficits were corrected for by improving postnatal nutrition (R-on-C) in femabut not males, highlighting sex specific programming and the importance of postnatal nutrition. Importantly, we have demonstrated that slowed growth during lactation followed by accelerated growth after weaning inbirth weight

plications fimaltered growth trajectories. 10. Ana Hutchinson and Peter Ebeling

Acute chronic obstructive pulmonary disease (COPD) exacerbations are associated with uncouplinresorption from bone formation. Hutchinson A1, Thompson M1, Smallwood D1, Bozinovski S2, Anderson GP2, Irving L1, Ebeling PR 3

1Depts. Respiratory Medicine, CEHSEU and CCREID, Royal Melbourne Hospital; 2Pharmacology Department, CRCID; 3Dept. Medicine(RMH/WH), University of Melbourne, Western Hospital, Footscray, Australia

COPD is an independent risk factor for minimal trauma fractures and osteoporosis. Inhaled corticosteroids (Ireduce bone formation markers, while acute exacerbations (AECOPD) increase inflammatory markers. We first compared biochemical bone turnover markers in 61 patients with stable COPD on high-dose ICS with 58 sex-matched, healthy controls. Second, we measured acute changes in bone turnover markers, highly sensitive C-reactive protein (hsCRP), and

g of bone

CS)

insulin-like growth factor-1 (IGF-1) during AECOPD. . To assess

le COPD patients with sex-matched, healthy controls. Bone rmation markers, serum osteocalcin and PINP; the bone resorption marker, �CTX; hsCRP and IGF-1 were easured in AECOPD.

n PINP (in men and women) and β-CTx levels (in men) were significantly lower than

ontrols 0.43 vs. 0.55 ng/mL, (p=0.03); /mL (p = 0.52). At AECOPD onset (n = 17), there were

crease in hsCRP (+30%) on day-3, the latter correlating with the decrease in bone f rmation, measured by

Early morning, fasting samples were obtained during stable COPD and Day 1 to 7 after AECOPD onsetthe affect of maintenance ICS on bone turnover, we compared serum �C-telopeptide (�-CTX) and type 1 procollagen N-terminal propeptide (PINP) in stabfomIn stable COPD, meacontrols. For PINP: In men with COPD vs. controls 38 vs. 67 ng/mL, (p< 0.001); and in women with COPD vs. controls 33 vs. 51 ng/mL, (p< 0.002). For β-CTx: In men with COPD vs. cand in women with COPD vs. controls 0.29 vs. 0.33 ngsignificant acute decreases in both serum osteocalcin (-25%) and PINP (-32%) on day-3, after commencing high-dose systemic or oral corticosteroids. There was a non-significant increase in �-CTx and IGF-1, but a significant

oinPINP. Uncoupling of bone formation from bone resorption occurs in stable COPD. In AECOPD bone formation decreases further, increasing the risk of bone loss and osteoporosis. This acute decrease in bone formation in AECOPD may be related to either inflammation or high-dose corticosteroids.


13

d

e

11. Louisa Ng Multidisciplinary rehabilitation programmes following joint replacement at the hip and the knee in chronicarthropathy. Khan F, Ng L, Gonzalez S, Hale T, Turner Stokes L Royal Melbourne Hospital

Background: Joint replacements are the treatment of choice for people with intractable joint pain and disability, but multidisciplinary rehabilitation may be required to optimise the benefits of surgery. We reviewed the evidence for multidisciplinary rehabilitation in adults following hip and knee joint replacement. Methods: Systematic review of randomised controlled trials that compared organised multidisciplinary rehabilitation with routine services following hip or knee replacement. Outcome measures of activity anparticipation in accordance with the International Classification of Functioning, Health and Disability were included. Results: Five trials met the inclusion criteria; two addressed inpatient rehabilitation (261 participants) and thre(358 participants) community settings. Pooling of data was not possible due to differences in study design and outcomes used. There was ‘silver’ level evidence that early, organised inpatient rehabilitation care led to more rapid functional improvement with shorter hospital stay and reduced costs. There was also ‘silver’ level evidencethat home rehabilitation improved functional gain and quality of life and reduced hospital stay. Conclusion: Following hip or knee joint replacement, multidisciplinary rehabilitation can improve outcomes at the level of activity and participation. As in other areas of rehabilitation practice, current trial based evidence is limited due to diversity with respect to intervention and the outcome measures used.

2. Wendy Pollock 1Service gap: obstetric patients in ICU. Pollock W, Harley N

al Melbourne Hospital

women admitted to ICU require specialist care that may not be readily eparate profession to

v12) and analysed.

were

in ion was the principle diagnosis for two thirds of women. However, pregnant and

s

sion: Women received fragmented care from many health professionals and service providers. A service cesses

The University of Melbourne & ICU; The Roy Introduction: Pregnant and postnatal available within the critical care team, with midwifery increasingly recognised as a snursing. The aim of this study was to examine the health services provided to parturient women in ICU to identify if a service gap existed. Method: A prospective cross-sectional study was conducted in four tertiary-level intensive care units (ICU) in Melbourne. Only one ICU was in a hospital that provided obstetric services. All pregnant and postnatal women admitted to ICU were eligible for the study. Nurses formed core research teams and assisted with the auto-enrolment of eligible women, time-critical data collection and the obtaining of consent. Additional data were gathered from the medical history following discharge. Data were entered into SPSS (Results: Of the 43 known eligible women, 35 were enrolled, and 33 gave consent; 8 were pregnant. The gestations of the six women with a viable pregnancy ranged from 27 to 36 weeks'; five of these six womenadmitted to the RMH ICU. None of the pregnant women gave birth during the ICU admission. Of the 25 postnatal women, 92% were admitted in the first 24 hours following birth. Four women saw their baby whilst ICU. An obstetric conditpostnatal women were seen by 23 different medical specialties whilst in ICU. The mean number of specialtieseen by individual women was 3.6 (median 4.0). 53% of women were seen by an obstetrician when in ICU: 100% of women with private health insurance (n=11) compared with only 29% of public patients (p<.05). Having the ICU and obstetric services on the one-site did not guarantee an obstetrician seeing a woman in ICU. Only 30% of the pregnant and postnatal women in ICU were seen by a midwife. Whether the woman was pregnant or postnatal did not affect her chance of being seen by an obstetrician or midwife in ICU. 70% (n=23) of women were transferred by ambulance between hospitals to access the ICU bed. Conclugap existed in the care provided to the pregnant and postnatal women admitted to ICU and articulated proare required if pregnant and postnatal women are to have access to maternity care in ICU.


14

eily

1, Lim S2 iversity of Melbourne; 2Dept of Anaesthetics, The Royal Melbourne Hospital

Medical students need to demonstrate competent resuscitation skills prior to graduation. The

l real

ence

two-tailed Spearman rho Correlation was applied to the data.

18 (24%) who

ve CTR. However, itnessing a clinical event gave a higher level of confidence to perform BLS. Studies investigating the correlation etween confidence and competence to resuscitate are in progress.

13. Meredith HCan a simulation based training program improve medical student confidence to perform resuscitation? Heily M1, Tse J1, McColl G1Clinical School, The Royal Melbourne Hospital, Un

Introduction:University of Melbourne Medical program uses clinical simulation to teach resuscitation in the clinical 2.5 years of the course. This survey aimed to measure the ‘confidence to resuscitate’ (CTR) level of final year medicastudents, some of whom had attended an additional anaesthetic skills workshop and/or observed aresuscitation. Methods: A survey was distributed to all final year students (85) in their final week, examining CTR; confidto perform Basic Life Support (BLS) and resuscitation clinical experience. Seventy six (89%) surveys were returned. AResults: Fifteen (20%) of students were always confident to respond to resuscitation situations, whereas 79% (59 students) were sometimes confident. Forty seven (62.7%) students were always confident in their (BLS) skills. There was no statistically significant correlation between level of CTR and attendance at the additional anaesthetics workshop. There was a statistically significant rise in confidence in their BLS skills for 42 (49%) students who had witnessed a real resuscitation (Spearman rho=0.341, p=0.003), but none for the participated in resuscitating a patient. Conclusions: Students interpreted CTR and confidence in performing BLS as different. Simulation training, anaesthetics workshop and participation in a clinical resuscitation event did not improwb 14. Joanne Jordan

The patient perspective: understanding the role and impact of health literacy within the Emergency

ical tment,

f life.

g and

terviews focused on factors that influenced individual’s health seeking behaviour (i.e., presentation to the ED) nd barriers and enablers to individuals seeking, understanding and utilising health information in the ED

Department setting. Jordan JE, Buchbinder R, Kennedy M, Osborne RH Centre for Rheumatic Diseases, Department of Medicine (RMH/WH), The University of Melbourne; Monash Department of ClinEpidemiology at Cabrini Hospital; Department of Epidemiology and Preventive Medicine, Monash University; Emergency DeparRoyal Melbourne Hospital

Background: In recent years, the pressure chronic diseases has placed on Emergency Department (ED) services has been recognised and strategies such as the Hospital Admissions Risk Program (HARP) implemented to address such issues. These initiatives have focused on individuals with complex chronic conditions or frequentusers of hospital emergency services. Individuals with chronic conditions pose additional challenges given that they have an ongoing health condition and they need to engage in self-management to maintain quality oThis generates further learning and cognitive demands on these individuals. Engagement in self-management activities presumes that individuals have a minimum level of health literacy. Health literacy is commonly defined as an individual’s ability to seek, understand and utilise health information. Objective: The objective of this research was to understand the barriers and enablers to individuals accessinunderstanding health information (i.e. health literacy) within the ED setting so that they can engage in prevention and self-management activities within the community to reduce the risk of further poor health outcomes and subsequent presentations to the ED. Method: In-depth qualitative interviews were undertaken with individuals who had recently presented to the Royal Melbourne Hospital Emergency Department between October 2007 and January 2008 with one of the fourfollowing conditions:

- diabetes with/without complications - chest pain - asthma - chronic obstructive pulmonary disease

Inasetting.


15

d case studies were developed from interviews conducted with individuals (n=13). A strong

esent to the ED included lack of GP availability and patient habit or preference ader

nd

Findings: Four detailetheme identified was the reactive and delayed nature of individuals seeking medical help. Key factors that influenced patients decision to prfor ED. Multiple factors stemming from individual patient attributes, health professional approaches and brohealthcare system and community effects were identified that affect an individual’s ability to seek, understaand utilise health information within the ED. These finding are in accordance with additional interviews conducted with patients in the community (n=34). 8 key skills were identified that are critical for patients to effectively function in the healthcare setting. 15. Pek Ghe Tan

A map of research evidence in the pre-hospital care of patients with traumatic brain injury. Tan PG, Gruen R, Tavender E, Clavisi O, Bragge P, Wasiak J, Cincotta M, Pattuwage L The Royal Melbourne Hospital, The University of Melbourne

Introduction: Keeping informed of current research and important research gaps in a clinical area is chalThe aim of this project was to use a technique known as ‘evidence mapping’ to provide such information abouthe prehospital care for patients with traumatic brain injury (TBI). Methods: The mapping methodology w

lenging. t

as developed by the Global Evidence Mapping (GEM) Initiative. It

at are

amedic and emergency health care rofessionals, and all were then systematically reviewed. 22 observational studies have examined the ffectiveness of pre-hospital airway intubation of TBI patients, and the majority of studies found it associated

tality. 5 RCTs and 2 observational studies have not shown any benefit from the use of any cated

may provide survival benefit for patients with TBI, but no RCTs of this topic have . Field hypoxaemia (n=4) and Glasgow Coma Scale (GCS) score

esuscitation (n=1) and mannitol administration (n=1).

involves question formulation and prioritisation; comprehensive literature search; study selection; data extraction and study quality assessment; and summarisation of what the existing evidence tells us, and whthe key research gaps. Results: Nine clinically important questions were identified by a panel of parpewith increased morparticular fluid over Hartmann’s solution or Normal Saline. Existing observational studies (n=6) have indithat mild hyperventilationbeen identified in the prehospital phase of care(n=13), but not field hypotension (n=9), were strong prognostic factors for mortality. Insufficient or no evidence has been identified for areas involving the effect of therapeutic hypothermia (n=0), delayed versus immediate fluid rConclusions: Evidence mapping of pre-hospital care for patients with TBI provides users a rapid overview of existing research, and has identified some gaps that may be useful for guiding future prehospital research. 16. Lisa Barker

The effect of pre-operative oral immunonutrition therapy on postoperative outcomes in gastrointestinal surgery patients. Barker L, Gray C, Wilson L, Thomson B, Jones I, Shedda S, Crowe T The Royal Melbourne Hospital, Deakin University

It is believed that invasive procedures such as major surgery cause immune suppression, leading to an increasrisk of post-operative inflammation and sepsis. Recent research has focused on the use of pre-operative oralimmune-enhancing nutrition supplements (contain

ed

stantially reduce treatment costs. However, the majority of studies conducted in this area have bee focused on the use of immuno-nutrition in both a pre-operative and post tting. This work may not be directly applicable to the local environment because of the varied ra n of post-operative feeding here. In view of that, we have confined nly pre-operative supplement use. Outcome measures of

per r gastrointestinal surgery. The treatment group will receive 15 tetra packs (237ml each) of Impact

ing arginine, omega-3 fatty acids and dietary nucleotides) and their positive influences on inflammation, metabolic and immune responses postoperatively. Use of such immuno-enhancing supplements has been shown to significantly reduce length of hospital stay, post-operative infection rates and sub

n performed outside Australia and have-operative senge of practice with respect to resumptio this project to examining the benefit of o

interest include length of stay and post-operative complications. This prospective randomised controlled trial will involve approximately 120 patients undergoing elective upand lowe


16

al ssed

s, unexpected intensive care admission and mortality. he trial has been granted ethics approval and is currently actively recruiting participants with the aim of atient accrual being completed by the end of 2008.

Advanced Recovery® (Nestle Medical Nutrition, Minnesota), and patients will be instructed to drink three packs per day in the five days leading up to their surgery. The control group will receive no nutritional supplements, and both groups will be given standard pre-operative advice on nutrition and fasting. Standard post-operative management will follow for all patients at the discretion of the treating team, with surgeons and treating teams blinded to patient’s group allocation in the study. Patients with chronic respiratory, cardiac, renand hepatic dysfunction (excluding jaundice) and those with a chronic infection or who are immunosurprewill be excluded. The primary outcome measurement is length of hospital stay, and secondary outcome measures include infective and non-infective complicationTp 17. Susan Shedda (see abstract no.5) 18. Rodney Luwor

Dynamin II function is required for EGF-mediated Stat3 activation but not Erk1/2 phosphorylation. Luwor RB, Zhu HJ Dept of Surgery, Royal Melbourne Hospital, University of Melbourne

Signalling from Receptor Tyrosine Kinases (RTK) is elicited by ligand binding, initiating trans-phosphorylation of tyrosines and docking tyrosines leading to phosphorylation of downstream substrates. Endocytosis has been

ptors is rs

hich is often regarded responsible for the

hospho-Erk1/2 levels compared to A431-DynII-wt and A431-GFP controls. A431-DynII-DN cells also had duced Stat3 transcriptional activity compared to A431-DynII-wt and A431-GFP controls. Furthermore, as

ediated Stat3 phosphorylation occurs relatively slower then Erk1/2 phosphorylation we propose

cytosis. f Stat3 and Erk1/2 and the sustainability of these

mporal control of the EGFR within the cell. This notion may have

widely accepted as one mechanism in which cells inactivate signalling by internalising and subsequently degrading activated receptors. However, it is now becoming evident that endocytosis of signalling recenot simply a matter of signal attenuation and receptor removal but is a key signalling component. We and othehave previously shown that Epidermal Growth Factor Receptor (EGFR) over-expression and activation of Stat3is associated with tumourigenicity. Here we examine the role of endocytosis in EGFR signal attenuation and differential signalling. By inhibiting Dynamin II (Dyn II), a GTPase involved in clathrin-mediated endocytosis, with a small molecular weight inhibitor we observed that EGF-mediated Stat3 phosphorylation and transcriptional activity was reduced in human tumour cells overexpressing EGFR such as A431 and HN5. However, Dyn II inhibition had minimal effect on EGF-mediated EGFR and Erk1/2 phosphorylation, wtumourigenic function of the EGFR. Likewise, A431 cells stably transfected with a Dyn II dominant negative construct had reduced EGF-mediated phospho-Stat3 levels but similar EGF-mediated phospho-EGFR and premaximal EGF-mthat Stat3 activation continues well after the EGFR has been internalised while Erk1/2 phosphorylation is completed before endoTaken together this data suggests that the activation status osignals are potentially due to the spatial and teimplications on therapeutic targeting and efficacy when using either inhibitors to either proteins regulating endocytosis and/or signalling molecules. Analysis of this differential signalling in vivo is continuing. 19. Elgene Lim

Characterisation of subpopulations of human mammary epithelial cells. Lim E, Vaillant F, Forrest N, Gyorki D, KConFab, Visvader J, Lindeman G Walter and Eliza Hall Institute of Medical Research

The human mammary gland is a compound tubulo-alveolar gland organ comprised of heterogenous cell types. Architecturally, it is a tree like network of ducts draining saclike alveoli, embedded within a fibro-fatty stromThe ducts and alveoli consist of two distinct epithelial cell types, an inne

a. r luminal layer and an outer

myoepithelial layer that has smooth muscle like properties. The mammary stem cell has been isolated in the mouse through the reconstitution of a functional mammary gland from single cell transplants.


17

l-ed

ells ensional culture of these two populations in extracellular

atrix gives rise to structures with distinct morphology; the luminal population giving rise to small, omogenous, spherical structures, the myoepithelial population giving rise to larger, heterogenous spherical

growths. Immunohistochemical staining of these structures reveal ifferential staining with luminal and myoepithelial markers, suggesting origins in both luminal and yoepithelial progenitors. These subpopulations of epithelial cells have also been transplanted into the cleared

f NOD SCID mice together with human specific fibroblasts. Preliminary results have ys for

itor activity, and examine the developmental relationships between the different mammary

In the human mammary gland, three distinct epithelial progenitor cells have been identified in vitro, luminarestricted progenitors, myoepithelial-restricted progenitors and bipotent progenitors which gives rise to mixluminal and myoepithelial cell colonies. The ability to reliably dissociate the mammary gland into a single cell suspension has allowed for flow-cytometry analysis and single cell sorting of mammary epithelial cells into sub-populations based on their surface marker characteristics. These subpopulations may then be functionally characterised using both in vitro cellular assays and in vivo transplantation to determine their repopulating ability. Using breast tissue from reduction mammoplasties, BRCA1 mutation carriers and breast cancer, we have identified two distinct human mammary epithelial cell populations denoted as luminal and myoepithelial cbased on expression of cell surface markers. Three dimmhstructures with occasional tubular outdmmammary fat pads oidentified a cell population that have given outgrowths with this technique. These techniques provide assastem cell and progenepithelial cell lineages. 20. Ramin Shayan

Defining tumor lymphatics and targeting differences in lymphatic vessel subtypes formed in human diseasfor therapeutic benefit. Shayan R, Karnezis T, Ashton MW, Mann GB, Taylor GI, Corlett RJ, Achen MG, and Stacker SA The Ludwig Institute for Cancer Research, Department of Surgery, Univeristy of Melbourne; The Jack Brockhoff Reconstructive PlasticSurgery Unit, RMH

e,

e nce

s,

d between athological lymphatic vessels and those formed in normal development may be exploited to manipulate mphatic vessels in key human disease states.

lymphatic vessel growth in tissue healing and regeneration and reconstructive surgery, and tment. Further, the targeting of d prognostication techniques such

tion of cancer-generated lymphatics to reduce metastasis would o the treatment of human cancers.

Lymphatic are important in fluid hemostasis, fat absorption, and immunity; and are implicated in several diseasstates. Until recently lymphatics were relatively ignored due to an inability to identify them histologically. Sithe development of antibody lymphatic markers, immuno-histochemical analysis has shown an association between enhanced lymphatic vessel growth in several tumor types and metastasis. In particular vascular endothelial growth factor (VEGF)-C and -D have been shown to act via their receptor, VEGFR-3, to promote lymphatic growth in normal development and tumors, in which they are also associated with metastasis. Conversely, treating animal tumor models with agents that inhibit this axis reduces lymphatic growth, and metastasis to lymph nodes. More recent characterisation of distinct lymphatic vessel subtypes in human tissuewhich differ in morphology, anatomical location, and molecular profile; has raised the question whether pathological lymphatics conform to normal lymphatic vessel subtypes, or consist of entirely independent pathological lymphatic phenotypes. We use immunohistochemistry and confocal microscopy of fluorescently labelled tissue to examine lymphatics in mouse skin tumors, wounds and lymphedema. We demonstrate a unique molecular and morphological profile for lymphatics that are generated in metastatic VEGF-D-secreting 293EBNA tumors, xenografted into the mouse flank or ear. It is hoped that pro-lymphatic protein growth factors and molecular differences identifieplyAn enhancement of in patients suffering from lymphedema would contribute significantly to treaneo-lymphatics formed in certain human cancers for improving diagnostic anas sentinel node biopsy, and therapeutic inhibicontribute greatly t


18

RL, Medi C, Balasubramaniam R, Sparks PB, Vohra JK, Kalman JM, Morton JB

ials

als.

m2 p=0.04), less dense scar (13 ± 8cm2 vs 70 ± 34cm2 p<0.001), fewer fractionated GM (18 ± 10% of total sampled points vs 44 ± 10% p<0.001), and fewer LP (6 ± 4% vs 15 ± 11% p=0.03). Six

ad VLP within dense scar (mean of 2.8 VLP per patient) compared with 8 in group 2 (mean

onated EGM, LP, VLP and potential conducting channels compared to ICM patients with neous SMVT. These differences in substrate are likely to play an important role in SMVT

21. Haris Haqqani Left ventricular substrate in ischemic cardiomyopathy patients with and without ventricular tachycardia. Haqqani HM, Roberts-Thomson KC, Snowdon The Royal Melbourne Hospital; The University of Melbourne

Background: The substrate for sustained monomorphic ventricular tachycardia (SMVT) in ischemic cardiomyopathy (ICM) has been well described. We sought to characterize the ICM substrate in patients who have never had SMVT. Methods: Using a 3.5mm tip catheter, electroanatomical mapping (mean 382 points) of the entire LV endocardium was performed in 10 stable ICM patients (9 male) without clinical SMVT (group 1). Clinical and scar characteristics were compared to 10 ICM patients (8 male) with spontaneous SMVT (group 2). Endocardial scar was defined as regions with bipolar voltage less than 1.5mV and dense scar less than 0.5mV. Late potent(LP) were defined as electrograms (EGM) occurring after the conducted QRS, very late potentials (VLP) wereEGM occurring >100ms after the QRS, and fractionated EGM were multi-component low amplitude signPotential conducting channel regions of preserved voltage were looked for within dense scar and regions adjacent to the mitral annulus. Results: There were no significant baseline differences between group 1 and 2: mean age (60 vs 66 yrs), LV diameter (68 vs 66mm), ejection fraction (23 vs 25%), infarct territory (anterior MI: 8/10 vs 6/10) or mapped LV endocardial surface area (261 vs 244cm2). However, group 1 patients had significantly less total endocardial scar

1 ± 23cm2 vs 123 ± 55c(7Epatients in group 1 h8.3, p=0.01). A potential dense scar to MA channel was seen in 4 group 1 and 8 group 2 patients, and voltage threshold adjustment identified potential channels within dense scar in most patients (8 in group 1 and 10 in group 2). Conclusion: Despite equally severe LV dysfunction, patients without clinical SMVT had significantly less total and dense scar, fractispontaarrhythmogenesis. 22. David Andrews

Investigation of the haemodynamic effects of volatile and intravenous anaesthetic agents during ischaemireperfusion using pressure-volume loops.

a-

in

lationship [EDPVR]). At the conclusion of anaesthesia, V’s in the ISR groups were excised and stained with 2,3,5-triphenyl tetrazolium chloride in order to measure farct size. Statistical analysis tested for difference in profile between ISR and TC groups for each agent for each

haemodynamic variable versus time using repeated-measures analysis of variance (RM-ANOVA) and allowing for multisample asphericity by applying the Greenhouse-Geisser correction. Infarct size was compared using one-way ANOVA.

Andrews DT, Wright CE, Royse AR, Royse CF The University of Melbourne, Department of Pharmacology; The Royal Melbourne Hospital, Department of Anaesthesia and Pain Management

Introduction: The anaesthetic agents desflurane, sevoflurane and propofol have been shown to have anti-ischaemic effects in the myocardium. We used left ventricular (LV) pressure-volume (PV) loops to investigate whether such cellular protection induced by these agents would preserve or harm myocardial function during acute coronary ischaemia-reperfusion (ISR). Methods: Male New Zealand White rabbits (n=48) were randomly assigned for anaesthesia with one of three different anaesthetic agents (propofol [70mg/kg/hr], desflurane [8.9%] or sevoflurane [3.8%]). Each rabbit was then further randomised to receive an ISR or non-ischaemic time-matched (TC) perfusion protocol. Animalsthe ISR groups (desISR, propISR, sevISR) underwent 30 mins of LAD occlusion then 120 mins of reperfusion. Animals in the TC groups (desTC, propTC, sevTC) were anaesthetised for 150 mins without ischaemia. Mean arterial blood pressure, heart rate, right atrial pressure, and cardiac output were measured and used to calculate systemic vascular resistance. PV loops were used to calculate LV systolic function parameters (preload recruitable stroke work [PRSW] and ejection fraction [EF]) and LV diastolic function parameters (time constant of relaxation [tau] and end diastolic pressure volume reLin


19

infarction size was greater in the propISR group (35.74 ± 11.32%) compared to the desISR

sevTC (p = 0.0.25). There was no difference in any

Results: Myocardial(13.44 ± 3.09%) and sevISR (17.96 ± 6.63%) groups (p<0.001). EDPVR deteriorated with time in the sevISR andpropISR groups compared to their TC groups (sevTC [p = 0.03] and propTC [p = 0.044] respectively). EF decreased over time in the sevISR group compared with haemodynamic varialbe for the desISR group compared to it’s matched TC group (desTC). Conclusion: Anaesthesia with sevoflurane (3.8%) and desflurane (8.9%) produce smaller myocardial infarction size compared to rabbits anaesthetised with propofol (70mg/kg) when subjected to acute coronary ISR. The tissue damage seen with propofol resulted in disturbances in diastolic function. Sevoflurane caused abnormal diastolic and systolic function but less permanent tissue injury compared to propofol. Desflurane resulted in less tissue injury compared to propofol and preserved LV function. 23. Colleen Doyle

Promoting public awareness of chronic obstructive pulmonary disease. Doyle C, Dunt D National Ageing Research Institute and Centre for Health Policy, Programs and Economics, The University of Melbourne

on n

holders on their views of how to improve public awareness, prevention, early detection and treatment

ong also

s of burden of COPD. e compiled a list of suggested interventions which could be used to improve the promotion of public

wareness, prevention, early detection and treatment of COPD. A print and radio campaign to raise awareness blic about the ‘COPD brand’ is clearly a high priority. People with COPD need better

se. There is ample evidence that influenza vaccinations prevent people with COPD should be made aware that they need to seek

t to onable quality of life for those people with COPD.

change. Health professionals also need to be aware of newer

The aims of this project were: (i) To identify and describe effective interventions for increasing community awareness of COPD resulting in better primary prevention, earlier detection and improved treatment (ii) To recommend potential public health interventions to increase public awareness of COPD and strategies for improving prevention and early detection. Four main methods were used to address these aims: (i) compilation of available secondary data on the epidemiology of COPD; (ii) review of the literature on the determinants of COPD (iii) review of the literaturestrategies for promoting public awareness, prevention, early detection and treatment of COPD (iv) consultatiowith stakeof COPD. Main findings: COPD is the fourth leading cause of death worldwide. In Victoria, the Central Goldfields and LaTrobe valley have high rates of disability due to COPD. Cities of Darebin, Moreland and Greater Geelhave very high rateWaamong the general puaccess to pulmonary rehabilitation, maintenance programs and patient support groups in order to raise their awareness of the best way to manage their diseaexacerbations among people with COPD. All influenza vaccinations routinely. Emotional support and encouragement to continue socialisation is importanmaintain a reasThe clear message from evidence and stakeholder consultation was that there is a need for more education ofhealth professionals, particularly general practitioners. Education needs to include information about appropriate referral pathways to quit smoking and to pulmonary rehabilitation, the benefits of pulmonary rehabilitation, spirometry guides and attitudeevidence emerging that there may be genetic susceptibility in families with COPD history, and about the dangers of occupational exposure to dust and fumes. 24. Daniel Steinfort

Cumulative proceduralist radiation exposure in the performance of endobronchial ultrasound with guide sheath (EBUS-GS) bronchoscopy utilizing fluoroscopic guidance. Steinfort DP1, Einsiedel P2, Irving LB1 1Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital; 2Department of Radiology, Royal Melbourne Hospital

Background: Biopsy of peripheral lung lesions using endobronchial ultrasound with guide sheath (EBUS-GS) is usually performed using fluoroscopic guidance. While patient radiation during such a procedure is minimal, the cumulative dose to proceduralists during fluoroscopy-guided bronchoscopy has never been established.


20

pron,

lence of the aprons

was

oses recorded by all other badges did not exceed e minimum threshold of 50μSv for the badge in each 3-month wearing period. Based on typical attenuation

roperties of the protective garments used across the diagnostic x-ray energy range we estimate effective nt doses per procedure of 0.5μSv and 0.2μSv, respectively.

id, using protective garments with a ivalence of 0.35 mm across the diagnostic energy range result in negligible radiation doses

Methods: Personal Radiation dose monitoring was undertaken during consecutive EBUS-GS bronchoscopy procedures on patients with peripheral lung lesions. Passive personal radiation monitors (film) were sited on both the proceduralist and primary nursing assistant in four locations per individual; front, outside lead afront behind lead apron, thyroid outside lead shield, back. Staff performing these procedures wore the lightweight “non-lead” composite aprons covering both the front and back. The lead equivawas quoted to be 0.35mm across the diagnostic x-ray energy range. Results: Forty-five bronchoscopy with EBUS procedures were performed. Mean fluoroscopic screening time74 ± 49 seconds. Only the badges worn outside the lead apron recorded a measurable radiation dose; the badgeworn by the bronchoscopist recorded an effective dose of 200 micro-Sieverts (μSv), and the badge worn by the assistant recorded a dose not exceeding 50-100 μSv. Radiation dthpproceduralist & assistaConclusions: Adequate shielding of proceduralists’ front and back, and thyrominimum lead equreceived by the proceduralists performing bronchoscopy using mobile C-arm fluoroscopic guidance. 25. Jane McCann

Is Pulse Oximetry a useful tool for diagnosing peripheral vascular disease? McCann J, May K, Frescos N, Wraight P The Royal Melbourne Hospital; La Trobe University

Aims: Peripheral angiography is the accepted gold standard for diagnosing peripheral vascular disease but its invasive nature and potential adverse events means it cannot be used in a primary setting. This study looks at the how Pulse Oximetry compares to other non-invasive assessment tools (palpation of pulses, Doppler ultrasound,

tes were assessed with five non-invasive vascular assessment tools. d these

sed

15/15) correlation with lower-limb s.

se in

Ankle Brachial Index and toe pressures) in diagnosing peripheral vascular disease in people with diabetes mellitus. Method: Forty-one participants with diabeThirteen participants (15 lower limbs) had had peripheral angiograms within the preceding 6 months anwere used to rank the accuracy of each of non-invasive tests. Results: Palpation of pulses was found to most accurately represent the findings on angiography so this was ufor the study standard when comparing the results of the non-invasive tests for the entire cohort. Pulse Oximetry was unable to correctly diagnose peripheral vascular disease in people with diabetes over 96% of the time, which led to it being ranked last amongst all the non-invasive investigative modalities. Palpation of pulsesand Doppler ultrasound individually were found to have the highest sensitivity, 93% and 80% respectively. Furthermore, the combination of these tools proved to have 100% (angiography and thus would be the recommended non-invasive vascular tool for patients with diabetes mellituConclusion: Pulse Oximetry was not an effective or useful tool for diagnosing peripheral vascular diseapeople with diabetes. 26. Dennis Velakoulis

Evaluating clinical outcomes of ECT across a large urban mental health network; Data from the North Western Mental Health / Melbourne Health ECT database.

lf of the North Western Mental Health ECT Committee

nitored and assessed by the patient's g.

d standardised evaluation of ECT outcomes are made.

Velakoulis D on behaNorth Western Mental Health and the Melbourne Neuropsychiatry Centre

While clinical outcome for individual patients undergoing ECT are motreating clinicians, evaluating the overall outcomes within a clinical service is a more challenging undertakinThe establishment of an ECT database across four area mental health services within North Western Mental Health has allowed the collation of detailed data regarding the practice of ECT. Information over a 12 month period from this database has been combined with routinely collected outcome data (HONOS) to investigate the relationship between HONOS outcomes and the use of ECT. Recommendations regarding the routine an


21

axic

ous ehavioral and ECoG changes in response to the administration of a single non-anaesthetic dose of ketamine or K-801.

non-epileptic rats (n=8) were surgically implanted with cortical recording electrodes, ek following surgical recovery,

d into an open arena. Following a 30 minute habituation period, etamine (1.25, 2.5 or 5mg/kg), MK-801 (0.08 or 0.16 mg/kg), or

. The temporal evolution of the increase in power was strikingly different between the two

27. Tahir Hakami NMDA receptor antagonists dose-dependently induce aberrant cortical gamma oscillations that correlatewith psychotic-like behaviour. Hakami T, Jones NC, Salzberg MR, O'Brien TJ, Pinault D The Department of Medicine (RMH/WH), The University of Melbourne; The Department of Neurology, The Royal Melbourne Hospital INSERM U666; The Université Louis Pasteur, Strasbourg, France

Background: Clinical and experimental evidence suggests that disruption of NMDA-type glutamate receptors (NMDAr) is implicated in the pathophysiology of schizophrenia,. More specifically, in humans, a single non-anaesthetic dose of ketamine, a non-competitive NMDAr antagonist, induces psychotic symptoms. The underlying neuronal mechanisms are unknown. It has recently been demonstrated that, in awaked rats, a single non-anaesthetic dose of ketamine induces i) persistent aberrant gamma oscillations (increased power and intrinsic frequency) in the electrocorticogram (ECoG) of the frontoparietal cortex and ii) a concomitant atbehaviour. Aims: The aim of this study was to determine whether or not non-competitive NMDAr antagonist-induced aberrant cortical γ oscillations were correlated with locomotion. This issue was addressed by combining, in freely moving rats, ECoG recording and video tracking to quantify and seek for correlation simultanebMMethods: Male Wistarfacilitating measurement of the properties of ECoG gamma oscillations. One werats were connected to wire cabling and entererats were subcutaneously injected with either kvehicle (0.9% saline), and were allowed to move freely for a 90 minute recording period. During this time, locomotor activity was automatically calculated using video-tracking software (Ethovision) and spontaneously occurring ECoG oscillations were simultaneously recorded. Results: Both Ketamine and MK801 dose-dependently increased the power (300-400% of vehicle-treatment) of wake-related gamma oscillations in the neocortextreatments, with ketamine peaking 10 minutes after injection and MK801 peaking 40 minutes after injection. NMDAr antagonist-induced aberrant gamma oscillations were also temporally correlated with the accompanying hyperlocomotor response. Conclusion: This novel observation is consistent with findings obtained in humans supporting the hypothesis that pathological gamma oscillations are correlated with psychotic-like symptoms (hyperlocomotion). It further promotes the exciting possibility that aberrant gamma oscillations are a promising potential endophenotype for schizophrenia that could be used as a biomarker for assessments of potential new treatments for this complex psychiatric disorder. 28. Suresh Sundram

The identification of co-morbid substance use disorder in in-patient with psychiatric illness. Sundram S, Matsudaira A, Happell B, Gough K Northern Psychiatry Research Centre, Mental Health Research Institute, University of Melbourne

es

elapse and hospitalization, increased forensic suicide and treatment non-compliance. f both psychiatric and SUD were treated

in

Background: Substance use disorders (SUD) are highly prevalent in people with psychiatric disorders at ratmany times that found in the general population. This comorbidity is associated with a many deleterious outcomes including higher symptom burden, increased rates of rinvolvement, decreased vocational activity, poverty, homelessness, Outcomes: for patients could be potentially significantly improved iconcurrently. Study aims or objectives: To be able to initiate or refer for appropriate SUD treatment it is essential that mental health workers are able to accurately identify individuals with SUD. We, therefore investigated if clinical teamson an adult acute psychiatric inpatient unit were able to identify the presence or absence of SUD comorbidity patients admitted with a psychiatric disorder that was not primarily a SUD.


22

ectively we have assessed 91 patients admitted to an adult acute psychiatric inpatient unit

e patients were then scrutinized after discharge to determine if SUD were omparisons made using the chi-squared statistic and

ere identified as having a SUD in the previous

er

t and

h clinicians on SUD if improved outcomes for this patient group are to be achieved.

Methodology: Prospusing a standardized interview questionnaire, the Tobacco and Substance Use components of the CIDI-Auto (Version 2). The clinical files of thesscreened for or recognized by the treating team and cKendall’s tau. Results or outcomes: On an interim analysis of 37 subjects, 78% w12 months according to the CIDI compared to case file records of 35%. There was no significant association between diagnosis according to CIDI and case files indicating discordance between the two assessments. Furththis was true for alcohol, tobacco, opioids, sedatives and hypnotics and multiple drug use. Conclusion: This finding if confirmed in the full data set indicates that mental health clinicians are not able to recognize SUD in patients admitted for other psychiatric disorders implying a lack of appropriate treatmenreferral interventions for these individuals. Such a finding signifies the need for a major education focus for mental healt 29. Ashleigh Lin

Olfactory identification deficits remain stable following a first episode of psychosis: What the EPPIC-medium term follow-up study tells us further about orbitofrontal function through the course of psychosis.

zophrenia,

t episode Pennsylvania Smell Identification Test (UPSIT).

d pects of schizophrenia requires further exploration. The findings are discussed in the

ontext of utilising olfactory models of function to track emerging onset of psychopathology as stable OID may lace patients at risk for ‘growing into deficit’ as neurodevelopmental arrest becomes more apparent with age.

J Psychiatry, 158, p107-115 ; Brewer et al, 2003, Am J Psychiatry, 160, p1790-1794

Brewer WJ, Wood SJ, Henry, Harris MG, Pantelis C, McGorry PD ORYGEN Research Centre, Melbourne Neuropsychiatry Centre: Department of Psychiatry, University of Melbourne

Objective: Previous investigation reveals stable olfactory identification deficits (OID) at 6 months following first onset of psychosis (Brewer et al, 2001), and more recently, in an ultra-high-risk group that later developed a schizophrenia spectrum disorder (Brewer et al, 2003). Olfactory naming tasks are a useful proxy measure of the ability to structure language (consciousness) around emotional (limbic) material. Moreover, OID may implicate more generalised difficulties in affect regulation. As a potential premorbid marker of transition to schithe utility of OID in mapping development and compromise of limbic-prefrontal pathways, particularly in orbitofrontal regions, is important for tracking the relative integrity of circuitry implicated in the course of psychosis following early onset. Method: In this study we sought to investigate longitudinal change in olfactory identification in firspsychosis patients using the University of Results: Our preliminary data from 14 patients and 9 controls (mean time between assessments = 73.4 months, range = 61.4 – 85.2 months) showed no change in performance over time. Conclusions: These data support our previous longitudinal study and suggest that there is no change in OFC mediated OID with continued psychotic illness. Interaction between OFC and other neural networks implicatein the degenerative ascpBrewer et al, 2001, Am 30. Jo e Buckby

g

ies, yet are also predictive of transition to psychosis in clinical populations. It is therefore

Do self-reported psychotic-like experiences (PLEs) correspond to interview-reported PLEs in help-seekinversus general population young Australians? Buckby JA, Yung AR, Ross R, Cosgrave EM, Ryan J, Baksheev G ORYGEN Research Centre, University of Melbourne

Introduction: In an apparent paradox, Psychotic-Like Experiences (PLEs) are commonly reported in general population studimportant to further study PLEs in order to better understand their relationship to threshold psychotic disorder.However, little research has investigated whether PLEs reported through questionnaire correspond to those reported in structured and semi-structured interview. The present study aimed to determine the degree to which self-reported and interview-reported PLEs agree with one another.


23

pleted a diagnostic interview that included the positive symptom subscales of the

ample = 62%,

clinical mples. However, some symptoms may be over endorsed in self-report questionnaires due to misinterpretation

f item content.

Method: Data were derived from two sources. The first sample comprised consecutive referrals to ORYGEN Youth Health, Melbourne with non-psychotic complaints (N = 140, mean age = 17.8). The second sample comprised adolescents from across Melbourne who had previously participated in a community survey of students (N = 653, mean age = 16.8). Participants comComprehensive Assessment of At-Risk Mental States (CAARMS). Participants also completed the Community Assessment of Psychic Experiences (CAPE). Results: PLEs were common in both samples. Nearly all participants endorsed at least one of the CAPE items at least ‘sometimes’. PLEs were also common when assessed through interview (help-seeking scommunity sample = 46%). Self-report and interview-report PLEs were moderately correlated (r = 0.2 - 0.5). Disorders of Thought and Perceptual Abnormalities were more strongly correlated with self-report PLEs than were Disorganised Speech. Conclusion: The present findings confirmed the high prevalence of PLEs in both community andsao 31. Jonathan Knott

Effect of nightshift on clinical skills: a controlled trialMarcus L, Liew D, Knott J R

,

re e

ed as controls. Matching was evaluated using a panel of senior medical staff

t difference found in the distribution cts’

: 10-

overnance strategies are significant, as the fraternity embraces the mandate to maintain quality emergency care enty-four hours per day.

oyal Melbourne Hospital

Background: Nightshift effect on performance of Emergency Department (ED) staff is of clinical and risk management significance. Previous studies have evaluated psychomotor skills following nightshift but none has specifically examined ED clinical performance. Objective: To investigate the effect of nightshift on clinical skills of ED registrars. Methods: ED registrars in a tertiary hospital were subject to a controlled trial. During nightshift, subjects wepresented simulated scenarios, and tested with eight relevant questions. Matched scenarios and questions for thsame subjects during dayshift serv(SMS). Two FACEMs independently scored the subjects and their results were compared using the Spearman correlation coefficient. Overall score was analysed using the Wilcoxon signed ranks test. Results: From a potential score of 34, the SMS reference group scored a median of 26 (IQR: 25-27). The SMS scored a median of 13 for each question set (IQR: 13:13), with no significanof scores. A correlation coefficient of 0.99 was found between the FACEM investigators who scored the subjeresponses. Of 22 eligible subjects over the study period, all were recruited; four were excluded due to incomplete data. The median result for nightshift was 9.5 (IQR: 8-11); the corresponding value for dayshift was 12 (IQR13); p = 0.047. Discussion: Nightshift effect on clinical performance is anecdotally well known. This study quantifies such effects, specifically for the ED setting, and paves the way for focused research. The implications for clinical gtw 32. Jacques Joubert

ICARUSS – Integrated Care for the Reduction of SecAmes D, Joubert L, Davis S, Donnan G, Hankey G, LevN

ondary Stroke. i C, Dewey H, Reid C, Jackson D, Joubert J

ational Ageing Research Institute, Royal Melbourne Hospital, The University of Melbourne, The Western Hospital; Royal Perth

in

Hospital; The John Hunter Hospital, Newcastle; The Austin Hospital, The National Stroke Research Institute

Background: Stroke is an important and costly condition. The estimated annual incidence in Australia of 48,000, results in 29,290 hospital admissions. It is the most common cause of chronic disability in older people living Australia and other Western countries and often results in loss of independence and institutional care. Within 5 years of first stroke, 25% of survivors suffer a second stroke.


24

e risk

s including death, hospitalization, long-term disability and

l and in other health systems internationally. ement

carers. It involves the adoption and dissemination of evidence-based goals and best-practice commendations for management of risk factors by GPs, makes use of telephone tracking and bi-directional

ata sharing and it is likely that the model will be enhanced by the active participation of patients and carers. tion roles involve telephone support, monitoring of compliance by GP and patient/carer

alist to GP) takes place initially and remains

valuated 186 patients (intervention = 91). At 12 months systolic blood pressure was tolic

urther evaluation with

Two thirds of ischemic strokes are attributable to five risk factors; hypertension, atrial fibrillation, elevated cholesterol, diabetes, and smoking. Clinical trials have repeatedly shown that correct management of strokfactors reduces stroke risk by as much as 80%. Translation from research into community care has been disappointing. Hypotheses: 1. ‘The integrated’ care model will have a greater effect than the ‘usual’ care model on the prevention of recurrent stroke and adverse outcome dependency in stroke survivors. 2. The ‘integrated’ care model will have a greater effect than the ‘usual’ care model on the optimal management of vascular risk factors and post stroke depression. 3. The integrated care model is generalizable and translatable across the spectrum of community practice settings – urban, ruraMethod: To address these issues we developed a model of ‘integrated’ care to promote best practice managof risk factors. This method integrates care by stroke specialists, general practitioners (GPs), nursing coordinators and redThe central coordinaand data management. Peer to peer telephone contact (speciavailable. Results (Pilot Study): We esignificantly reduced in the ‘integrated’ care group (p<0.05). The percentage of patients reaching target sysblood pressure of 140 mmHg was greater in ‘integrated’ care (p<0.05). Fewer patients in ‘integrated care’ screened positive for depression at 12 months (p=0.003). Physical activity increased in the integrated care group (p=0.001) and BMI was significantly reduced in the intervention group (p=0.007). Fincreased patient/carer empowerment is currently being tested in a multicentre RCT based at RMH. 33. Alison Yung

Declining transition rate in ultra high risk (prodromal) services: dilution or reduction of risk? Yung AR, Yuen HP, Berger G, Francey S, Hung T, Nelson B, Phillips L, McGorry P ORYGEN Research Centre, ORYGEN Youth Health and University of Melbourne

Introduction: Recently it has become possible to identify people experiencing the prodrome of schizophrenia and related disorders. Detection has been achieved by the application of Ultra High Risk (UHR) criteria, which combine subthreshold psychotic symptoms and risk factors such as family history. Using these criteria, reported rates of transition have been 35% to 50% within 12 months. However, a reduction in transition rate has been

d risk of transition was 0.80 times that of the previous year (p=0.027). Year was no nger associated with transition rate once duration of symptoms was adjusted for. Duration of symptoms was und to decrease significantly over time (p<.001).

at UHR individuals are being treated earlier than in the past, three possible explanations for findings, so that the ultimate level of

ias may be responsible, i.e. ous

identified. Finally,

suspected lately. Method: We examined UHR data for subjects recruited from 1995 to 2000 to ascertain if transition rate had reduced and to examine associated factors. Results: Of 142 UHR subjects, 51 became psychotic. For each successive year, the estimatelofoConclusion: Given ththe reduction in transition rate arise. First, lead time bias may explain thetransition may be higher if patients are followed for longer. Second, a length time bthe apparent UHR phenotype may have a number of different outcome trajectories, including rapid spontaneremission, and early detection may increase the probability that those not truly at risk will beit may be that earlier detection enables intervention to be more effective.


25

lbourne Hospital

isk gra

terms int day and

%

s

34. Daniel Gilbertson Reducing readmission rates? – Another role for community liaison pharmacists at a tertiary referral hospital. Frank M, Gilbertson D, Galbraith K The Royal Me

Aim: To determine if readmission rates following weekend discharge can be reduced by Hospital Admission RPro m (HARP) Pharmacist follow up within seven days. Method: Comparative rates for unplanned readmission following weekend or weekday discharges were d ined for a four-month period. A refe ined HARP referral system for patients discharged over the weekend wa roduced along with pharmacist training to increase patient referral. Readmission rates from weekweekend discharges were reassessed post intervention. Data from both periods were examined combined with pharmacy records to determine how many readmitted patients had a prescription processed by pharmacy. Results: In the pre-intervention period there were 8077 discharges (weekends: 1531). The unplanned readmission rate was 20.2% (weekday: 21.9% weekend: 13.2%). During this period, pharmacy processed 600 weekend discharges (39.2%), 30 of these patients were readmitted (5.0%). The post intervention period saw 8790 discharges (weekends: 1748). The unplanned readmission rate was 15.8(weekday 17.4%, weekend 9.7%). During this period, pharmacy processed 679 weekend discharges (38.8%), 33of these patients were readmitted (4.9%). During the intake periods there were a number of notable case reports of interventions made by HARP pharmacists which may have prevented medication misadventure related readmission or harm. Conclusion: As readmission rate changes are consistent across both categories between the periods, it is not possible to conclude the intervention had a significant impact on readmissions. However, numerous case reportdemonstrate the importance of this service’s availability to patients discharged on weekends. Additionally patients discharged on a weekend who had discharge medications dispensed by pharmacy, were less likely to be readmitted than patients who did not have their prescription dispensed. This suggests a possible strategy for improving the weekend pharmacy service and will be the target of future investigation. 35. Pauline Parke

Optimising acute postoperative pain management – a collaborative quality improvement initiatiParker PE, Hogg M, Chia A, Robertson MB, Wai A, Mackson JM, Kaye KI, McIntosh KA The Royal Melbourne Hospital, National Prescribing Service; Victorian Drug Usage

r ve.

Evaluation Group, Department of Human Services

e

RMH. Prescription of regular aracetamol increased nationally and at RMH. Nationally there was an increase in documentation of a discharge nalgesic management plan. At RMH documentation of a discharge analgesic management plan was 70% v 76%

but none of the plans documented the expected duration of analgesic treatment.

Purpose: The Acute Postoperative Pain (APOP) project aimed to promote assessment of pain, safe and effectivanalgesic prescribing and communication of pain management plans at discharge to patients and general practitioners (GPs). This paper focuses on changes observed nationally and at The Royal Melbourne Hospital (RMH). Methods: A prospective audit was undertaken in 62 hospitals nationally. A drug use evaluation cycle was conducted, involving baseline audit, evaluation, intervention, feedback and re-audit. Interventions included academic detailing, feedback of results, educational meetings and point-of-care reminders. At RMH the intervention also included the adoption of a new observation chart that provided information on assessment of pain and sedation and facilitated the recording of pain and sedation scores. Medical record review was used to measure changes in preoperative patient education, pre- and postoperative pain assessment and communicationof pain management plans at discharge to the patient and GP. Results: 2704 and 2780 patients were included in the national baseline audit and re-audit respectively. RMH contributed 50 patients to each audit. 1397 prescribers, 5348 nurses and 567 pharmacists participated in the educational interventions nationally. At RMH 61 prescribers, 175 nurses and 28 pharmacists participated in the educational interventions. At re-audit of inpatient records there was an increase in documentation of patients receiving pre-operative education, documentation of at least one pain score postoperatively and documentation of at least one sedation score if prescribed an opioid, both nationally and atpa


26

Baseline audit Re-audit

cation 31% 6% 44%* 22% postoperatively 57% 40% 77%* 62%

% 70% 40%* 76%

mentation

Measure National RMH National RMH Documentation of preoperative eduDocumentation of ≥ 1 pain scoreDocumentation of ≥ 1 sedation score postop if on opioids 50% 29% 61%** 52% Prescription regular paracetamol 68% 44% 74%** 62% Documentation of discharge analgesic management plan 26 *p<0.0001, **p<0.001 compared to baseline Conclusion: The multifaceted interventions within hospitals led to moderate improvements in inpatient care ofacute postoperative pain. Within RMH there is need for further improvement in 1) documentation of preoperative education, pain scores and sedation scores, 2) prescribing of regular analgesia and 3) docuof expected duration of analgesic treatment at time of discharge. 36. Slave Petrovski

A multi-SNP predictor for drug outcome in complex diseases.

g

his

prospectively collected dataset of outcomes in 115 patients newly treated for epilepsy, with genotyping for ,041 SNPs in 279 candidate genes, was utilized for the model development. A cross-validation based

ed SNPs most influential in predicting seizure control after one year of drug treatment and mine it’s

nd then in two independent

SNPs alone.

ve 80%

better than those using any individual SNPs alone. bly

pt

Petrovski S, Szoeke CEI, D’Souza W, Sheffield LJ, Huggins RM, O’Brien TJ The Royal Melbourne Hospital, Austin Hospital, The University of Melbourne

Most pharmacogenomic studies have attempted to identify single nucleotide polymorphism (SNP) markers that are predictive for treatment outcomes. However, it is unlikely in complex diseases such as epilepsy, affectinheterogeneous populations, that a single SNP will adequately explain treatment outcomes. This work reports an approach to developing a multi-SNP model to classify treatments outcomes for such a disease, and compares twith single SNP models. A4methodology identifithen incorporated these into a multi-SNP classification model. The classifier was cross-validated to detereffectiveness in predicting treatment outcome in the developmental cohort avalidation cohorts. In each the classification by the multi-SNP model was compared with that of models utilizingthe individual Five SNPs were selected for the multi-SNP model. Cross-validation showed that the multi-SNP model had a predictive accuracy of 83.5% in the developmental cohort and positive and negative predictive values aboin both of the independent validation cohorts. In all cases the multi-SNP model classified the treatment outcomesThe results demonstrate that our multi-SNP classifier successfully predicted treatment outcome more reliathan single SNP models. Future pharmacogenomic research in complex diseases such as epilepsy should attemto develop classifiers that utilize multiple genetic determinants. 37. Duncan Carradice

The mutant marsanne reveals a novel transcription factor critical for normal neutrophil development in

n red cell iseases (hereditary spherocytosis/elliptocytosis, porphyrias). Mutants in genes with phenotypes affecting the

neutrophil lineage now being reported (alk8, cohesin, hai1). Our laboratory undertook a forward genetic haploid ethylnitrosourea (ENU) screen and recovered mutants with defects in RNA in-situ hybridisation (ISH)

zebrafish. Carradice D, Layton J, Heath J, Lieschke GJ Walter & Eliza Hall Institute of Medical Research

The genetic basis of many human congenital neutropenia syndromes remains unknown. Characterising the genes mutated in these disorders will provide insight into their pathogenesis in addition to allowing design of rational treatments. In addition developmentally important haematopoietic genes are often dysregulated in leukaemia eg. SCL, RUNX1. Forward genetic screens in zebrafish focusing on haematopoiesis have generated many mutants, initially mainly affecting erythropoiesis, and generating mutants modeling humad


27

c screen is unbiased by prior knowledge, randomly ants utrophils) of inte uch an ach m cover

cess of int in contr a re enetic ch in ) rest to b

nne is a recessive, embry ethal m with atopo efect y re sion of

latively normal expression of early haematopoietic and myeloid lineage specification markers (scl, spi1). The nd morphological assessment. The phenotype is temperature dependant,

gy to the corresponding mammalian omologues across its functional domains. cDNA sequencing has identified a mis-sense mutation at a highly

nsient knockdown of the marsanne gene in WT zebrafish embryos recapitulates the s rescues the defect in granulopoiesis.

bers causally dysregulated in leukaemia and gue of marsanne may be important in the

enesis of congenital neutropenia and/or myeloid malignancies.

expression of deltaC (mesoderm), spi1/pu.1(early myeloid progenitors) and/or mpx (neutrophils). A forward geneti mutating the entire genome and recovering mutwith a phenotype (in this case lack of ne rest. S appro ay dis novel genes, or novel roles for known genes, in a biological pro erest, ast to verse g approawhich prior knowledge of the process influences gene(s of inte e “knocked out”. Of the mutants recovered, marsa onic l utant a haem ietic daffecting relatively specifically late granulopoiesis, having markedl duced ISH expres mpx with rered cell lineage appears normal by ISH anumbers of mpx expressing cells per embryo decrease as the water temperature is elevated (75 +/-15 (22°C), 42+/-10 (28°C), 27+/-10 (33°C), mean +/- SD) allowing manipulation of the level of gene function through simply changing the water temperature (conditional allele). Positional cloning has narrowed the genetic interval to a 40Kb region containing one gene. The gene is a

reviously uncharacterised transcription factor with high homolophconserved residue. Tramutant phenotype and injection of WT mRNA into marsanne mutantThe protein belongs to a transcription factor family with other memlymphoma. We hypothesise that dysregulation of the human homolopathog 38. Spiros Fourlanos

The rising incidence of type 1 diabetes is accounted for by cases with lower risk HLA genotypes, Fourlanos S1,2, Varney MD 3 3 4 1 2 1 , Tait BD , Morahan G , Honeyman MC , Colman PG , Harrison LC

ere analysed in relation to year of birth and age at diagnosis over the last five

fer across decades. o

together, they increased from 20% to 48% =0.0002). Matched for DRB1 genotype and decade of birth, subjects were analysed for age at diagnosis. There as no change across time in age at diagnosis for the high risk DR3,4 genotype, but for the intermediate risk

R3,3, DR4,X and DR3,X, age at diagnosis significantly decreased over time. 00

s in 1985 to 23.2 in 2002. The contribution of DRB1 genotypes to the increasing incidence of d the number of incident cases to specific DRB1 genotypes in the 1980s

it is apparent the population incidence (cases per 100 000 person .5).

1

1The Walter and Eliza Hall Institute of Medical Research; 2 The Royal Melbourne Hospital; 3 Victorian Transplantation and Immunogenetics Service; 4Western Australian Institute for Medical Research

Objective: The rising incidence of type 1 diabetes (T1D) has been attributed to environment, implying a lesser role for genetic susceptibility. However, the rise could be accounted for either by more cases with classic high risk genes or by cases with other risk genes. Separately, for any degree of genetic susceptibility, age at presentation may decrease in a permissive environment. To examine these possibilities, HLA-DRB1 genes known to confer risk T1D wdecades. Research Design and Method: Caucasian subjects (n=462) in the Australia T1D DNA repository diagnosed with T1D before age 18 between 1950 and 2005 were DRB1 genotyped. Results: Mean age at diagnosis, 8.5 years (SD 4.5y), did not difThe proportion of the highest risk genotype, DR3,4, decreased significantly over time from 79% in 1950-1969 t28% in 2000-05 (p<0.0001). On the other hand, the proportion of the heterozygous intermediate risk genotypes DR4,X and DR3,X increased significantly over this period; taken(pwgenotypes, DR4,4 and DThe incidence of childhood-onset type T1D in Australia has doubled in the last 20 years, from 11.3 cases per 1000 person yeartype 1 diabetes was examined. We relateversus the current decade. From this analysisyears) of type 1 diabetes in subjects with the highest risk genotype DR3,4 has remained unchanged (5.3 vs. 6In contrast, the number of cases with intermediate risk genotypes DR3,3 or DR4,4 (1.3 vs. 4.9) and DR3,X or DR4,X (4.4 vs. 11.1) has increased, accounting for the increase in disease incidence. Conclusions: The rising incidence and decreasing age at diagnosis of T1D is accounted for by the impact of environment on children with lower risk HLA class II genes, who previously would not have developed typediabetes in childhood.


28

énie,

nd,

e III-IV linker region of the Cav3.2 T-type Ca2+

s

by ing

esults: In vivo: the R1584P mutation correlated positively with the expression of absence seizures in F2 rats. ats homozygous (+/+, n=12) for the mutation had more seizures per minute (0.43 vs 0.12, p<0.05) and spent a

ing time in seizure activity (3.1% vs 0.5%, p<0.05) compared to those with the wild-

the rat Cav3.2 gene were of exon

ivation specifically in the full length

ects ovide

39. Caroline Ng A novel mutation in the rat Cav3.2 T-type Ca2+ channel CACNA1H gene increases absence seizure expression and channel function. Ng C1, Powell K1, Sirdesai S1, Kyi M1, Garcia E2, Reid CA3, Pinault D4, Foote SJ5, Snutch TP2, O'Brien TJ1

1Department of Medicine (RMH/WH), University of Melbourne; 2Michael Smith Laboratories, University of British Columbia, 3 4Vancouver, BC, Canada; Howard Florey Institute; INSERM U666, Physiopathologie Clinique et Expérimentale de la Schizophr

Université Louis Pasteur (Faculté de Médecine), Strasbourg, France; 5Menzies Research Institute, Tasmania

Rationale: Recent evidence implicates the Cav3.2 T-type Ca2+ channel in the pathogenesis of genetic absence epilepsy, although whether functional abnormalities in this channel play a causative role is unknown. Linking an absence phenotype to a mutation in this channel would provide a priori case for a causative role. To this ewe have identified that GAERS rats (a genetic rat model of absence epilepsy) carry a homozygous single nucleotide missense mutation in a highly conserved region thgene (R1584P). This study examined the in vivo and in vitro electrophysiological effects of this mutation.Methods: In vivo studies: male F2 progeny of both NECxGAERS and GAERSxNEC double-cross matingunderwent EEG recordings at 18 weeks, which were blindly analyzed to determine whether seizure activity correlated with the animals’ genotype. The presence of Cav3.2 splice variants in the rat brain were detectedexon scanning. In vitro studies: the R1584P mutation was introduced into the rat wild type Cav3.2 cDNA ussite directed mutagenesis. Cav3.2 splice variant channel function � R1584P mutation was assessed electrophysiologically in vitro using whole-cell patch clamp technique in HEK293 cells 48 hours after transfection. RRgreater percentage of recordtype genotype (-/-, n=8). On both measures heterozygote rats (+/-, n=24) had values in between the homozygotes, consistent with a co-dominant effect. In vitro: Two splice variants ofidentified in the rat thalamus, differing with respect to the presence (Cav3.2_v1) or absence (Cav3.2_v2)25. The R1584P mutation increases the rate of recovery from inactCav3.2_v1 splice variant (p<0.05). Conclusions: The in vivo results indicate that the Cav3.2 R1584P mutation plays a causative role in the expression of absence seizures in GAERS. Functional studies at the channel level provide a gain-of-function mechanism to explain the pro-epileptic effect of the Cav3.2 R1584P mutation. Future studies including effon Cav3.2 membrane expression, splice variants and cellular electrophysiological properties in vivo may prmore insight into the cellular mechanisms by which the R1584P mutation acts to promote seizures in the GAERS model. 40. Kim Powell

Can too much Stargazin cause epilepsy? Powell KL, Kyi M, Reid CA, Paradiso L, D’Abaco G, Kaye AH, Foote SJ & O’Brien TJ Departments of Medicine and Surgery, Royal Melbourne Hospital, University of Melbourne; Howard FloreyInstitute, University of Melbourne; Menzies Research Institute, The University of Tasmania, Australia

tion

was performed using standard protocols. Sequencing of the coding region and s were done to examine for the presence of mutations and splice variants, respectively.

Rationale: Transmembrane AMPA receptor regulatory proteins (TARPs) play a critical role in trafficking and anchoring AMPA receptors to the synapse and therefore in defining neuronal excitability. Linkage analysis in GAERS, a genetic animal model of absence epilepsy, identified a quantitative trait locus on chromosome 7 containing the gene for the TARP, stargazin. A mutation in this gene, resulting in decreased stargazin expression, is the causative abnormality in the stargazer mouse which has absence epilepsy. We hypothesised that abnormalities in stargazin sequence or expression may contribute to the epileptic phenotype in GAERS and that there will be a concurrent increase in AMPA receptor plasma membrane expression. Methods: RNA was extracted from somatosensory cortex and thalamus, brain regions critical for the generaof absence seizures, of juvenile and adult control and GAERS. Quantitative PCR was performed for stargazin andribosomal 18S RNA. Somatosensory cortex tissue was fractionated into cytosolic and plasma membrane fractions

analysisand Western blotNorthern Blot


29

A expression was increased in the somatosensory cortex of juvenile (76%, n=10, p<0.05) stargazin

, n=10, p<0.05). AMPA receptor subtypes, GluR1 and GluR2 protein R2; p<0.05)

s

ns: GAERS have increased expression of stargazin mRNA in the somatosensory cortex, which contains t

. hese

man

Results: Stargazin mRNand adult GAERS (74%, n=8, p<0.001). Additionally, in juvenile animals there was a smaller increase in mRNA expression in the thalamus (26%expression is significantly increased in plasma membrane fractions (47% for GluR1 & 42% for Glubut not in cytosol fractions from somatosensory cortex of epileptic GAERS. No gene mutations or splice variantwere detected. Conclusiothe focus generating the seizures in rats. This is present in the pre-epileptic juvenile GAERS and therefore is nomerely a secondary consequence of the seizures. These data are the first to implicate an increase in stargazin expression in the pathogenesis of epilepsy, with the stargazer mouse having decreased expression. Associated with an increase in stargazin expression is an increase in AMPA receptor expression only at the plasma membrane. This would be expected to enhance neuronal excitability and therefore be potentially pro-epilepticThe results have the potential to lead to new understandings about how perturbations in the expression of tchannels may result in epilepsy that is likely to have important relevance for our understanding of the hucondition. 41. Sandra Petty

Chronic anti-epileptic medication (AED) usage is associated with reduced balance – an AED-discoand siblin

rdant twin g matched pair study.

n lth.

nt

rding d medical history were completed. Paired t-tests used to calculate mean within-pair differences;

dependent t-tests were used to compare mean within-pair differences for subgroups. esults: 29 AED-discordant same-sex pairs were studied: 12 male, and 17 female; five monozygous, five dizygous

g pairs. Significant mean within-pair differences were seen in Adjusted Activity Scores, and a es, with AED-users having poorer performance (p<0.0125).

e therapeutic range.

d ers who had a fall in the previous 12 months compared to those who had not (p<0.0125). Five AED users,

t

orer ture risk

Petty SJ1, 5, Hill KD2, 3, El Haber N1, 2, Paton LM1, Lawrence KM4, Berkovic SF4, O’Brien TJ1, 5, Wark JD1, 6 1Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne; 2National Ageing Research Institute; 3Musculoskeletal Research Centre, Faculty of Health Sciences, LaTrobe University and Northern Health; 4Epilepsy Research Centre, The University of Melbourne, Austin Health; 5Department of Neurology, The Royal Melbourne Hospital; 6The Royal Melbourne Hospital Bone and Mineral Service

Background and Hypothesis: Patients taking anti-epileptic medication (AED) have increased fracture risk. Increased falls due to drug effects on balance function may contribute to this risk in addition to the knowadverse effect of AEDs on bone heaAim: To investigate falls risk factors using AED-discordant twin/sibling pairs, including clinically-relevasubgroups: (A) AED polytherapy; (B) longer treatment duration; (C) history of falls. Methods: A comprehensive battery of balance and muscle strength measures, which are predictive of falls risk, were performed: Chattecx Balance Platform, Lord’s Balance test (LBT), KinCom, manual muscle strength tester, computerized and clinical tests of gait and balance. Serum AED levels were measured. Questionnaires regafalls, fractures aninRtwin and 19 siblinnumber of the static and dynamic balance measurThere was no difference in lower limb strength or gait measures. One AED level was abovSub-group analyses indicated significant differences on several of the balance measures between those on AED polytherapy compared to those on monotherapy (p<0.0125), those with longer duration therapy (p<0.0125), anAED usand none of the AED non-users had a history of low-trauma fracture, this difference was statistically significan(McNemar’s Chi Square p=0.037). Conclusion: AED-users taking polytherapy, having longer therapy duration or with a history of falls, had pobalance performance. This indicates an increased risk of falls which may contribute to the elevated fracin this population. 42. Tanya Yuen (see abstract no.1)


30

,

trix degradation, effects that were reversed by re-expression of Tks5. While these results suggest ooperative roles for Src and Tks5 in driving invadopodia, precisely how this occurs is unclear. Here, we show

Tks5 at tyrosine Y557 to create a specific binding site for the Nck1 and Nck2 adaptor n of Nck binding by mutation of Y557 strongly inhibited the ability of Tks5 to promote

on of actin dynamics we tested whether Tks5 phosphorylation

ion.

nce that Tks5 phosphorylation and Nck binding initiate actin recruitment to tion

43. Stan Stylli Determining the role of Tks5 in invadopodia formation, tumour invasion and metastasis. Stylli SS1,2 , I STT1 , Xu S1, Courtneidge SA3, Kaye AH1,2, Lock P1

1Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC,Australia, 2Department of NeurosurgeryRoyal Melbourne Hospital, Parkville, VIC, Australia, 3Burnham Institute for Medical Research, La Jolla, CA, United States

Remodeling and degradation of the extracellular matrix (ECM) by tumour cells are important processes in invasion and metastasis. Many tumour cells form ventralised actin-rich protrusions called invadopodia. They are dynamic sites of integrin-mediated adhesion, signal transduction, actin assembly, and most significantly, these structures are associated with the proteolytic degradation of ECM through the targeted secretion of matrix proteases. Tks5 is a PX-SH3 domain adaptor protein and a Src kinase substrate that localizes to invadopodia. Transient expression of Tks5 in mouse B16 melanoma cells significantly increased the ability of the cells to degrade a fluorescently labeled gelatin matrix, an effect that was boosted further by co-expression of Tks5 and Src. By contrast, depletion of endogenous Tks5 in B16 cells by using RNA interference inhibited both basal and Src-induced macthat Src phosphorylatesproteins. Disruptiogelatin degradation. Conversely, Nck2 overexpression with Tks5 and Src enhanced matrix degradation. Because Nck links diverse proteins to the modulatiimpacted on actin localization and levels in individual invadopodia. Whereas wild type Tks5 efficiently recruited actin to invadopodia, the Tks5 mutant failed to do so. By contrast,over expression of Nck increased GFP-actin co-localization with endogenous Tks5 at sites of matrix degradatTogether these data provide evideinvadopodia leading to increased matrix degradation activity. Current work is determining whether disrupof Tks5-Nck association could be used to inhibit invasion and metastasis. 44. Fary Kahn

Effectiveness of vocational rehabilitation for persons with multiple sclerosis. Kahn F, Ng L, Turner Stokes L Royal Melbourne Hospital

Background: Multiple sclerosis is a neurological disease that frequently affects adults of working age, resulting in a range of physical, cognitive and psychosocial deficits that impact on workforce participation. Although, the

ontrolled clinical trials, including before - after controlled trials, that

ssment: Two reviewers selected trials and rated their methodological quality independently. 'best evidence' synthesis was performed, based on methodological quality. Trials were grouped in terms of pe and setting of VR programs.

e CCT) (total 80 participants) met the review criteria. Both trials scored oorly on the methodological quality assessment. There was 'insufficient evidence' for VR programs for )‘competitive employment’, in altering rates of job retention, changes in employment, improvement in rates of

re-entry into the labour force; (b) for altering ‘work ability' by improving participants’ confidence in the accommodation request process, or employability maturity or job seeking activity.

literature supports vocational rehabilitation (VR) approaches in persons with multiple sclerosis (pwMS), the evidence for its effectiveness is yet to be established. Objective: To evaluate the effectiveness of VR programs compared to alternative programs or care as usual on return to work, workability and employment in pwMS; to evaluate the cost effectiveness of these programs. Search strategy: The sources used included: Cochrane Central Register of Controlled Trials "CENTRAL", MEDLINE (1966- 2008), CINAHL (1982- 2008), PEDro (1990- 2008), EMBASE (1988- 2008), the Cochrane Rehabilitation and Related Therapies Field trials Register and the National Health Service National Research Register. Data extraction: Randomized and ccompare VR rehabilitation with alternative intervention such as standard or a lesser form of intervention or waitlist controls. Methodological asseAtyResults: Two trials (one RCT and onp(a


31

ld be assimilated for changes in proportions of persons in supported employment or on disability

to support VR for pwMS. However, the review

ould ers,

No evidence coupensions, nor for cost-effectiveness. Reviewers Conclusion: There was inconclusive evidencehighlights some of the challenges in providing VR for pwMS. Clinicians need to be aware of vocational issues, and to understand and manage barriers for maintaining employment. Proactive and timely VR programs shincorporate practical solutions to deal with work disability, workplace accommodation and educate employand the wider community. Liaison with policy makers is imperative for government initiatives that encourage work focused VR programs. Future research in VR should focus on improving methodological and scientific rigour of clinical trials; on the development of appropriate ands valid outcome measures; and on cost effectiveness of VR programs.


32

e with epilepsy is determined by psychological well-being and seizure frequency rather than the type of epilepsy syndrome. Choi Y, O’Brien TJ, Velakoulis D, Kilpatrick C, Yerra R

48. Detection of hippocampal changes during epilepsy by Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) Chow M, O’Brien TJ, Fang K, Shen Y, Noordman, I, Egan G, Dedeurwaerdere S

49. A post hoc exploration of mismatch definitions in the EPITHET trial

Christensen S, Parsons M, Butcher K, Ebinger M, De Silva D, Fink J, Donnan G, Davis SM 50. Using Bolus perfusion weighted MRI to detect presence and origin of collateral perfusion.

Christensen S, Calamante F, Hjort N, Wu O, Blankholm AD, Desmond P, Davis S, Ostergaard L 51. LGI4, a mediator of peripheral myelination, is a ligand of ADAM22.

D’Abaco GM, Paradiso L, Morokoff A, O’Brien TJ, Kaye AH, Novak U 52. Density heterogeneity: A novel independent CT growth predictor in intracerebral hemorrhage.

Barras CDJ, Christensen S, MacGregor L, Tress BM, Collins M, Davis SM; for the Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators

53. Baseline data from a multi-centre, prospective longitudinal study of ageing in 1000 volunteers (the AIBL

Study) Ellis KA, Rowe CC, Masters CL, Martins RN, Hudson P, Milner A, Bevege L, Ames D

54. Volumetric MRI abnormalities are associated with behavioural disturbance in a rat model of generalized

epilepsy. Bouilleret V, Jones NC, Jupp B, Dedeurwaerdere S, Velakoulis D, Salzberg M, Egan G, O’Brien TJ

55. Mutation R19K in the Nav1.2 Alpha Subunit Associated with GEFS+ is associated with an enhanced Effect

of Phenytoin on Steady-State Inactivation French CR, Kwan, P, O’Brien, T

56. KONQUEST: Keppra versus Older AEDs and Neuropsychiatric, Neurocognitive and QUality of life

outcomes in treatment of Epilepsy as Substitution monoTherapy. Bright T, Roten A, O’Brien TJ, Petrovski S, Yerra R

57. A potential role for glucose hypometabolism in the development of temporal lobe epilepsy: A serial FDG-

PET study. Jupp B, Binns D, Hicks R, Rees S, O’Brien TJ

58. The total number of dentate granule cells increases in epileptic rats following status epilepticus.

Jupp B, Rees S, O’Brien TJ 59. Maternal separation enhances limbic epileptogenesis via heightened corticosterone reponses and

hippocampal cell loss. Kumar G, Jones NC, Morris MJ, Rees SM, Salzberg MR, Velakoulis D, O'Brien TJ

Poster Presentations: 45. Validation of the NUCOG cognitive screening tool in an epilepsy population.

Choi Y, Walterfang M, Cordy N, Yerra R, O’Brien TJ, Velakoulis D 46. Psychosocial outcomes in patients admitted to a video EEG monitoring unit with epileptic seizures and

psychogenic non-epileptic seizures. Choi Y, O’Brien TJ, Velakoulis D, Kilpatrick C, Yerra R

47. The quality of life in peopl


33

isation of FDG-PET in the presurgical evaluation of medically refractory focal epilepsy.

1. Clozapine modulation of the epidermal growth factor system as a molecular target in treatment resistant

2. A comparison of the Computed Tomography Angiography (CTA) and Digital Subtraction Angiography

3. A retrospective angiographic analysis of growth in unruptured intracranial aneurysms.

ssion in a genetic rat model of absence epilepsy.

5. Size and shape of the caudate nucleus in chorea-acanthocytosis: comparison to matched controls and

disorder and their relatives. , Reutens D

sive stroke

an B, Davis SM

, Kettle J, Obrien-Simpson L, Yücel M, Simmons JG, Allen NB

9. The effects of environmental enrichment on kindling epileptogenesis and spatial learning.

rrence in newly treated epilepsy.

logy within youth psychiatry. Allott, K, Proffitt, T-M, Brewer, W

esistant schizophrenia and its incidence in ent.

Sundram S, Bandara J, Wragg A, Aklagi H, Lohdi R, Sathiya S

fective processing in early adolescents who vary on primary dimensions of temperament. ’Brien-Simpson L, Groot Y, Allen NB

bilitation in s.

Killackey E, Jackson HJ , McGorry PD

xiety-like behaviour following experimental traumatic brain injury in the rat.

60. The cost-effective util

O’Brien TJ, Miles K, Ware R, Cook MJ, Binns DS, Hicks RJ 6

schizophrenia. Pereira A, Fink G, Sundram S

6

(DSA) in the diagnosis and evaluation of intracranial aneurysms. Shen L, Laidlaw J, Mitchell P

6

So TY, Yan B 64. Discordance between valproate plasma levels and seizure suppre

van Raay L, Morris M, Reed R, Edward H, O’Brien T, Dedeurwaerdere S 6

patients with Huntington’s disease. Walterfang M, Velakoulis D, Hannan K, Chua P, Danek A, Evans E, Walker R

66. Corpus callosum size and shape in individuals with bipolar affective

Walterfang M, Frangou S, Wood A, Barton S, Velakoulis D, Chen J, Pantelis C 67. Reduction of inpatient mortality: comparison between a mobile stroke service and a comprehen

care unit. Weir LC, De Silva DA, Hand P, Y

68. Gender differences in the neuroanatomical correlates of the affective startle reflex.

Whittle S 6

Yang M, Salzberg MR, Rees SM, O’Brien TJ, Jones NC 70. Correlation of a pre-treatment neurocognitive questionnaire with seizure recu

Petrovski S, Szoeke CEI, Roten A, Huggins RM, O’Brien TJ 71. Applications of neuropsycho

72. The prevalence of metabolic syndrome in chronic and treatment r

the first three months of clozapine treatm

73. Attentional af

Byrne ML, Altson K, Simmons JG, Cook N, O 74. Results of a randomized controlled trial of individual placement and support for vocational reha

first episode psychosi

75. Persistent increased an

Cardamone L, Jones NC, Williams J, Salzberg MR, Myers DE, O'Brien TJ


34

PY, Walterfang M, Yücel M, Wood SJ, Zalesky A, Pantelis C

7. Examining the rates and reasons for attrition in a double-blind randomised controlled trial in an ultra-high

n B, Yung AR, Phillips LJ, Francey SM, McGorry PD

8. Investigation of associations between single nucleotide polymorphisms of the Muscarinic 1 receptor gene

9. Trauma in the ultra high risk for psychosis (“prodromal”) population. y P, Bechdolf A

0. Younger onset dementia presenting as psychotic illness: Clinicopathological case series.

ltra-high risk for psychosis. Kennedy D, Phillips L, McGorry P, Yung A, Seal M, Velakoulis D, Pantelis C, Wood S

ges for patients discharged to aged care facilities – How well is it done?

ective

Lange P

otic management of older patients with severe symptoms of delirium - Are guideline

Tropea J, Slee J, Holmes A, Gorelik A, Brand CA

Dwyer JA

sociated with duration of COPD exacerbations. Melbourne Longitudinal COPD Cohort-(MLCC).

rial II (INIT II) Colman PG, Gellert S, Taylor F and Harrison LC, on behalf of the INIT II Study Group

odel (MMIM) – setting up a new tool for diabetes research and quality assurance.

Grant JA, Goodwin MB, Mohr ML, Wootton AM

o rag mice: potential model for generalized pustular psoriasis.

tes family members through probands registered with the National Diabetes Services Scheme.

76. Auditory hallucinations in schizophrenia: An investigation of abnormal cortical diffusivity. Seal ML, Tang

7

risk cohort. Simmons MB, Nelso

7

and cognitive deficits in schizophrenia. Sundram S, Khademy-Deljo A, Cowie T, Scarr E, Piskulic D, Pantelis C, Dean B

7

Thompson A, Nelson B, Yung AR, Simmons M, Leicester S, Francey SM, McNab C, Krstev H, Sidis A, McGorr 8

Velakoulis D, Walterfang M, Mocellin R, Pantelis C, McLean C 81. T2 relaxometry detects temporal lobe pathology in people at u

82. Documentation of medication chan

Hong J, Chen C, Galbraith K 83. Does fever after repair of fractured neck of femur indicate infection and delay discharge? A retrosp

case series.

84. Antipsych

recommendations currently being met?

85. High cost IPU drugs - What was the patient outcome?

86. Functional decline in patients with COPD is as

Hutchinson A, Bu XN, Thompson M, Anderson GP, Brand C, Irving L 87. Islet antibody testing in the Intranasal Insulin T

88. Molecular Medicine Informatics M

Colman PG, Jerums G, Panagiotopoulos S, Cameron F, Ward G, Oats J, Gasko H, Wohlers T, Hibbert M 89. 25-Hydroxyvitamin D – Should we automate?

90. Multi-organ disease induced by transferring c-rel-/- bone marrow int -/-

Isomura I, Gugasyan R, Varigos G, Gerondakis S 91. Identifying at-risk type 1 diabe

Taylor FJ, Colman PG, Williams F, Johnston R and Harrison LC


35

onate

Hristov E, Osborne RH, Dalton A, Wark JD.

es related foot infections have microbiological evidence of MRSA.

5. Investigating the role of endogenous relaxin in experimental diabetic renal disease.

6. Biodistribution of canine leukocytes labelled in whole blood with technetium-99m stannous fluoride colloid

hitton R, Charles J, Parry B

orman T, Torresi J

s of COPD (AECOPD) ki S, Thompson M, Hutchinson A, Vlahos R, Black J, Smallwood D, Irving LB, Anderson GP

moke

llo I, Smallwood D, Irving L, Anderson GP

tients with and without ventricular tachycardia. M, Robert-Thomson KC, Snowdon RL, Medi C, Balasubramaniam R, Sparks PB, Vohra JK, Kalman JM, Morton JB

mpson M, Anderson S, Jenkins C, Donald K, Firman J

03. The role of inflammation in COPD: The Melbourne Longitudinal COPD Cohort (MLCC) o R, Smallwood D, Vlahos R, Anderson GP

04. Tolerability of muscle microbiopsy during COPD exacerbations in the Melbourne Longitudinal COPD

ompson M, Smallwood D, Anderson GP, Irving L

05. Functional gene-modified embryonic stem cell-derived therapeutic macrophages (ESMf) contribute to the tration.

, Smallwood D, Irving L, Anderson GP

late

amaniam R, Snowden R, Haqqani H, Morton J, Sparks P, Sanders P, Kalman JM

nd clinical outcome. , Morton JB, Sparks PB, Kistler PM

108. Macrophage polarisation in chronic obstructive lung disease (COPD) and lung cancer. Steinfort DP, Truong T, Duan E, Thompson MA, Hibbs M, Irving L, Anderson GP

92. Patient preference for osteoporosis treatment: A time trade off study of once weekly oral bisphosphversus once yearly intravenous bisphosphonate infusion.

93. One in five diabet

Wraight P, Yates C, May K, Hale T, Allard B, Colman P 94. The histopathology of septic acute kidney injury: A systematic review.

Langenberg C, Bagshaw SM, May C, Bellomo R 9

Wong SE, Hewitson TD, Becker J, Tregear GW, Becker GJ, Samuel CS 9

and their use in localising induced acute intradermally inflammation. Abushhiwa M, Salehi N, Lichtenstein M, Finnin P, Lording P, W

97. Early detection of spinal sepsis.

Angsuwatjarakorn M, Kavar B 98. Enteric fever in two tertiary referral hospitals in Melbourne, Australia: a 17- year experience.

Hume S, Schulz T, Vinton P, K 99. Elevated SAA, but not IP-10, discriminates between non-pathogen and pathogen-associated acute

exacerbationBozinovs

100. NOD-CB17prkdscid mice lacking functional T and B cells display COPD-like inflammation after s

exposure. Chan J, Vlahos R, Haylock D, Nilsson S, Bertonce

101. Left ventricular substrate in dilated cardiomyopathy pa

Haqqani H 102. A review of the recruiting standard concerning asthma for the Australian Defence Force (ADF)

Irving L, Koh M, Nasveld P, McLaughlin R, Tho 1

Irving L, Hutchinson A, Bozinovski S, Thompson M, Hansen M, Karlsson AS, Gualan 1

Cohort (MLCC) Hansen M, Th

1

alveolar macrophage pool after in vivo adminisLilja A, Bozinovski S, De Luca E, Scott B, Hertzog P

106. Regional variation in remodelling in an ASD population: A comparison of patients with and without

atrial arrhythmias. Medi C, Roberts-Thomson KC, Spence S, Balasubr

107. Tachycardia-mediated cardiomyopathy secondary to focal atrial tachycardia: Electrophysiologic

characterisation aMedi C, Kalman JM, Roberts-Thomson KC, Haqqani H, Vohra JK


36

duced lung inflammation. allwood D, Irving L, Anderson G

ch operation?

14. Delayed versus immediate urethral catheterization following instillation of local anaesthetic gel in males: a

, Augello M

ue to

urtis DJ

18. Analysis of erythroid mutants identified by ENU mutagenesis.

19. Loss of patched in the hematopoietic microenvironment alters stem cell function.

20. Aurora and snail are independent predictors of tumour recurrence in superficial bladder cancers.

21. The importance of independent laboratory accreditation in translational research.

uring early stages of the Epithelial-Mesenchymal Transition.

ncy outcomes in men undergoing nerve-sparing radical prostatectomy.

Formby LM, Desai J, Landgren AJ, Davis D, Barlow JW

ognostic marker in prostate cancer.

109. Glutathione peroxidase-1 protects against cigarette smoke-in

Vlahos R, Bozinovski S, Seow HJ, Crack P, Sm 110. Implantable cardiac defibrillators in long term survivors of atrial switch surgery.

Wheeler M, Grigg L, Zentner D 111. Long term outcomes of primary arterial switch operation.

Zentner D, Wheeler M, Cheung M, Grigg L 112. Does pregnancy contribute to systemic RV dysfunction in adults with the atrial swit

Zentner D, Wheeler M, Grigg L 113. Staff health promotion reduces absenteeism in the Emergency Department.

Razga T, Liew D, Knott J, Wood P 1

randomized clinical trial. Garbutt R, Taylor DMcD, Lee V

115. Pregnant and postnatal women in ICU.

Pollock W, Harley N 116. A point mutation of the inositol phosphatase SHIP1 leads to a multilineage hematopoietic defect d

increased macrophage activation. Nguyen NN, Maxwell MJ, Jane SM, Kile BT, Hibbs ML, Curtis DJ.

117. Scl or Lyl1 is required for the maintenance of adult haemopoietic stem cells.

Salmon JM, C 1

Scott N, Curtis D, Jane S, Rank G 1

Siggins SL., McCormack MP, Vasudevan S, Hetherington R, Wainwright BJ,Curtis DJ 1

Namdarian B, Bruyere F, Corcoran NM, Pedersen J, Costello AJ, Hovens CM 1

Beckman I, Formby LM, Rassell AC, Winstanley R, Barlow JW 122. Proteome analysis of membrane-associated events d

Chen Y, Wang B, Goode RJA, Kapp EA, Moritz RL, Zhu H, Simpson RJ 123. Anatomical study of the cavernous nerves to optimize post-operative pote

Dowdle B, Costello A, Namdarian B 124. Immunohistochemistry as a determinant of likely responsiveness to new cancer therapeutics

125. Circulating endothelial cells: A new pr

Georgiou HD, Namdarian B, Hovens CM, Costello AJ


37

26. Identification and characterization of a functional interaction of the Tks5 and Nck adaptor proteins in

en with breast cancer - A

Kang YC, Miller JA, Mann GB

elial transition by TGF-β. Li J, Wang B, Nheu T, Zhu H-J

emia by causing self-renewal of thymocytes. McCormack MP, Young LF, Curtis DJ

B2 receptor affects the growth, invasion and migration of colon cancer cells. Senior PV, Zhang BX, Chan STF

rker in colorectal cancer. her I, Hayes I, McLaughlin S, Hastie I, Skinner I, Desai J, Gibbs P

F-β signaling pathway.

MT)

34. Regulation of TGF-b signalling by the Wnt pathway in the development of colon cancer.

35. The molecular regulation of the tumour suppressor pten by phosphorylation and its novel activity.

36. Outcomes of patients with vertebral body fractures admitted to level 1 trauma centres. (VOTOR) Research Group

ent.

rdson M, Ramkumar S, Lowe A, Beckman K, Allan P, Thallas V

40. Is regular table tennis activity associated with increased bone and mussel strength and improved balance in

41. Evaluation of a chronic widespread bone and joint pain bone scan protocol.

42. Is bone quantitative ultrasound (QUS) useful in assessing anti-epileptic drug-induced bone disease?

43. Acute management of myocardial infarction in RA patients – a comparison with the general population. Van Doornum S, Brand C, Ajani A, Sundararajan V, Wicks I

1invadopodia. I STT, Stylli SS, Xu S, Verhagen A, Pass I, Courtneidge SA, Lock P

127. Prevalence of treatable secondary causes of osteoporosis in postmenopausal wom

pilot study.

128. Regulation of mesenchymal-endoth

129. Lmo2 initiates T cell leuka

130. Expression levels of the Eph

131. Albumin: a prognostic ma

Shedda S, Kosmider S, Jones I, Farag 132. SSB1, a novel negative regulator of the TG

Liu S 133. Positive and negative cooperation of p38 MAPK with TGF-β in epithelial to mesenchymal transition (E

Wang B, Zhu HJ 1

Winbanks C, Nheu T, Faux M, Zhu H 1

Xiao Y, Lio D, Stenseballe A, Simpson RJ, Cartimel B, Cheng HC, Zhu HJ 1

Yang Z, Lowe A, De la Harpe D, Richardson M, the Victorian Orthopaedic Trauma Outcomes Registry (Williamson O, Hart M, Gabbe B)

137. The effect of X-ray magnification on the accuracy of preoperative templating in total hip replacem

Cheang WH, Bucknill A 138. Patients’ perceived needs prior to starting methotrexate treatment for rheumatoid arthritis.

Ciciriello S, Wicks I, Buchbinder R, Busija L, Osborne R 139. Pathology of frozen shoulder. A cytogenetic, histological and immunohistochemical analysis.

Kabbabe B, Richa 1

elderly Asian men and women? Li L, Wark JD, Hill K., Wong P, Kwok N

1

Micallef M, Nadesapillai S 1

Sakellarides M, Chin L.K, Petty S, Day L, Kantor S, O'Brien TJ, Wark JD 1


38

ing.

45. Intraoperative measurement of the subacromial space: A predictor of outcome in arthroscopic subacromial

dson M

144. Percutaneous cannulated screw placement in the posterior elements and anterior column of the pelvic rYew J, Bucknill A

1

decompression? Yousef J, Richar

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