Surgery (RMH) - Research Publications

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    "Iodide mumps" after angioplasty
    Chuen, J ; Roberts, N ; Lovelock, M ; King, B ; Beiles, B ; Frydman, G (Elsevier, 2000-02-01)
    Vascular surgeons are increasingly performing endo- vascular fluoroscopy-guided procedures. We report a rare complication of radiographic contrast exposure (iodide-induced sialadenitis or “iodide mumps”), which has significance in the postoperative observation and management of patients after these procedures.
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    Vascular endothelial growth factor d is dispensable for development of the lymphatic system
    Baldwin, ME ; Halford, MA ; Roufail, S ; Williams, RA ; Hibbs, ML ; Grail, D ; Kubo, H ; Stacker, SA ; Achen, MG (AMER SOC MICROBIOLOGY, 2005-03)
    Vascular endothelial growth factor receptor 3 (Vegfr-3) is a tyrosine kinase that is expressed on the lymphatic endothelium and that signals for the growth of the lymphatic vessels (lymphangiogenesis). Vegf-d, a secreted glycoprotein, is one of two known activating ligands for Vegfr-3, the other being Vegf-c. Vegf-d stimulates lymphangiogenesis in tissues and tumors; however, its role in embryonic development was previously unknown. Here we report the generation and analysis of mutant mice deficient for Vegf-d. Vegf-d-deficient mice were healthy and fertile, had normal body mass, and displayed no pathologic changes consistent with a defect in lymphatic function. The lungs, sites of strong Vegf-d gene expression during embryogenesis in wild-type mice, were normal in Vegf-d-deficient mice with respect to tissue mass and morphology, except that the abundance of the lymphatics adjacent to bronchioles was slightly reduced. Dye uptake experiments indicated that large lymphatics under the skin were present in normal locations and were functional. Smaller dermal lymphatics were similar in number, location, and function to those in wild-type controls. The lack of a profound lymphatic phenotype in Vegf-d-deficient mice suggests that Vegf-d does not play a major role in lymphatic development or that Vegf-c or another, as-yet-unknown activating Vegfr-3 ligand can compensate for Vegf-d during development.
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    Microarray analysis of human leucocyte subsets: the advantages of positive selection and rapid purification.
    Lyons, PA ; Koukoulaki, M ; Hatton, A ; Doggett, K ; Woffendin, HB ; Chaudhry, AN ; Smith, KGC (Springer Science and Business Media LLC, 2007-03-05)
    BACKGROUND: For expression profiling to have a practical impact in the management of immune-related disease it is essential that it can be applied to peripheral blood cells. Early studies have used total peripheral blood mononuclear cells, and as a consequence the majority of the disease-related signatures identified have simply reflected differences in the relative abundance of individual cell types between patients and controls. To identify cell-specific changes in transcription it would be necessary to profile purified leucocyte subsets. RESULTS: We have used sequential rounds of positive selection to isolate CD4 and CD8 T cells, CD19 B cells, CD14 monocytes and CD16 neutrophils for microarray analysis from a single blood sample. We compared gene expression in cells isolated in parallel using either positive or negative selection and demonstrate that there are no significant consistent changes due to positive selection, and that the far inferior results obtained by negative selection are largely due to reduced purity. Finally, we demonstrate that storing cells prior to separation leads to profound changes in expression, predominantly in cells of the myeloid lineage. CONCLUSION: Leukocyte subsets should be prepared for microarray analysis by rapid positive selection.
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    Patients' preferences for adjuvant endocrine therapy in early breast cancer: what makes it worthwhile?
    Duric, VM ; Fallowfield, LJ ; Saunders, C ; Houghton, J ; Coates, AS ; Stockler, MR (SPRINGERNATURE, 2005-12-12)
    Adjuvant endocrine therapy improves recurrence and survival rates, but has side effects and is inconvenient. The aim of this study was to determine the preferences of premenopausal women who had adjuvant endocrine therapy in a randomised trial. In all, 85 (or eighty-five) women completed semistructured interviews 6-30 months after finishing adjuvant endocrine therapy. Hypothetical scenarios based on known potential survival times (5 or 15 years) and rates (60% or 80% at 5 years) without adjuvant endocrine therapy were used to determine the smallest gains women judged necessary to make their adjuvant endocrine therapy worthwhile. Although a third of the women considered gains of 1% in survival rates or 6 months in survival times sufficient to make their adjuvant endocrine therapy worthwhile, more than half the women required gains of at least 5% in survival rates or 3 years in survival time as necessary to make adjuvant endocrine therapy worthwhile. Larger benefits were required by women who had longer treatment, worse side effects, and by those who were treated with goserelin alone. The route of administration (tablet vs injection) did not affect preferences and some women judged small benefits sufficient to make their adjuvant endocrine therapy worthwhile, but many women required larger benefits than their counterparts in similar studies of preferences for adjuvant chemotherapy.
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    Two decades of percutaneous transjejunal biliary intervention for benign biliary disease: a review of the intervention nature and complications.
    Fontein, DBY ; Gibson, RN ; Collier, NA ; Tse, GTW ; Wang, LLK ; Speer, TG ; Dowling, R ; Robertson, A ; Thomson, B ; de Roos, A (Springer Science and Business Media LLC, 2011-10)
    OBJECTIVE: To assess outcomes of percutaneous transjejunal biliary intervention (PTJBI) in terms of success and effectiveness in patients with a Roux-en-Y hepaticojejunostomy for benign biliary strictures and stones. METHODS: Clinical and radiographic records of 63 patients with a Roux-en-Y choledochojejunostomy or hepaticojejunostomy for benign disease who underwent at least one PTJBI between 1986 and 2007 were reviewed. Effectiveness was determined by successful access rate, rates of stricture dilatation and/or stone extraction, morbidity, complications and hospitalisation. RESULTS: PTJBI was attempted 494 times. Successful access to the Roux-en-Y was accomplished in 93% of interventions. After access to the Roux-en-Y was granted, all strictures were effectively dilated. Ninety-seven percent of extraction attempts of intrahepatic calculi were successful. The median number of interventions per patient was five. The median interval between interventions was 51.5 weeks (range 2.7-1,279.6 weeks). The early complication rate was 3%. Morbidity, measured in terms of cholangitis episodes was 14%, in 25 out of 63 patients. Mean hospitalisation was 4.1 nights per year. CONCLUSION: PTJBI is safe and effective in treating benign biliary strictures and/or calculi. High success rates and short hospitalisation periods, together with few complications make it a well-accepted and integral part of managing complex biliary problems.
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    Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.
    Irish, A ; Dogra, G ; Mori, T ; Beller, E ; Heritier, S ; Hawley, C ; Kerr, P ; Robertson, A ; Rosman, J ; Paul-Brent, P-A ; Starfield, M ; Polkinghorne, K ; Cass, A (Springer Science and Business Media LLC, 2009-01-21)
    BACKGROUND: Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. METHODS/DESIGN: The study population is adult patients with stage IV or V chronic kidney disease (CKD) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted) patency time, and adverse events, particularly bleeding. DISCUSSION: This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty acids. Recently a placebo-controlled trial has shown that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Our study presents significant differences in the anti-platelet agents used, the study design, and surgical and patient demographics that should contribute further evidence regarding the efficacy of anti-platelet agents. TRIAL REGISTRATION: Australia & New Zealand Clinical Trials Register (ACTRN12607000569404).
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    A Brassica exon array for whole-transcript gene expression profiling.
    Love, CG ; Graham, NS ; O Lochlainn, S ; Bowen, HC ; May, ST ; White, PJ ; Broadley, MR ; Hammond, JP ; King, GJ ; Baxter, I (Public Library of Science (PLoS), 2010-09-16)
    Affymetrix GeneChip® arrays are used widely to study transcriptional changes in response to developmental and environmental stimuli. GeneChip® arrays comprise multiple 25-mer oligonucleotide probes per gene and retain certain advantages over direct sequencing. For plants, there are several public GeneChip® arrays whose probes are localised primarily in 3' exons. Plant whole-transcript (WT) GeneChip® arrays are not yet publicly available, although WT resolution is needed to study complex crop genomes such as Brassica, which are typified by segmental duplications containing paralogous genes and/or allopolyploidy. Available sequence data were sampled from the Brassica A and C genomes, and 142,997 gene models identified. The assembled gene models were then used to establish a comprehensive public WT exon array for transcriptomics studies. The Affymetrix GeneChip® Brassica Exon 1.0 ST Array is a 5 µM feature size array, containing 2.4 million 25-base oligonucleotide probes representing 135,201 gene models, with 15 probes per gene distributed among exons. Discrimination of the gene models was based on an E-value cut-off of 1E(-5), with ≤98% sequence identity. The 135 k Brassica Exon Array was validated by quantifying transcriptome differences between leaf and root tissue from a reference Brassica rapa line (R-o-18), and categorisation by Gene Ontologies (GO) based on gene orthology with Arabidopsis thaliana. Technical validation involved comparison of the exon array with a 60-mer array platform using the same starting RNA samples. The 135 k Brassica Exon Array is a robust platform. All data relating to the array design and probe identities are available in the public domain and are curated within the BrassEnsembl genome viewer at http://www.brassica.info/BrassEnsembl/index.html.
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    New computational tools for brassica genome research.
    Love, CG ; Batley, J ; Lim, G ; Robinson, AJ ; Savage, D ; Singh, D ; Spangenberg, GC ; Edwards, D (Hindawi Limited, 2004)
    With the increasing quantities of Brassica genomic data being entered into the public domain and in preparation for the complete Brassica genome sequencing effort, there is a growing requirement for the structuring and detailed bioinformatic analysis of Brassica genomic information within a user-friendly database. At the Plant Biotechnology Centre, Melbourne, Australia, we have developed a series of tools and computational pipelines to assist in the processing and structuring of genomic data, to aid its application to agricultural biotechnology research. These tools include a sequence database, ASTRA, a sequence processing pipeline incorporating annotation against GenBank, SwissProt and Arabidopsis Gene Ontology (GO) data and tools for molecular marker discovery and comparative genome analysis. All sequences are mined for simple sequence repeat (SSR) molecular markers using 'SSR primer' and mapped onto the complete Arabidopsis thaliana genome by sequence comparison. The database may be queried using a text-based search of sequence annotation or GO terms, BLAST comparison against resident sequences, or by the position of candidate orthologues within the Arabidopsis genome. Tools have also been developed and applied to the discovery of single nucleotide polymorphism (SNP) molecular markers and the in silico mapping of Brassica BAC end sequences onto the Arabidopsis genome. Planned extensions to this resource include the integration of gene expression data and the development of an EnsEMBL-based genome viewer.
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    BASC: an integrated bioinformatics system for Brassica research.
    Erwin, TA ; Jewell, EG ; Love, CG ; Lim, GAC ; Li, X ; Chapman, R ; Batley, J ; Stajich, JE ; Mongin, E ; Stupka, E ; Ross, B ; Spangenberg, G ; Edwards, D (Oxford University Press (OUP), 2007-01)
    The BASC system provides tools for the integrated mining and browsing of genetic, genomic and phenotypic data. This public resource hosts information on Brassica species supporting the Multinational Brassica Genome Sequencing Project, and is based upon five distinct modules, ESTDB, Microarray, MarkerQTL, CMap and EnsEMBL. ESTDB hosts expressed gene sequences and related annotation derived from comparison with GenBank, UniRef and the genome sequence of Arabidopsis. The Microarray module hosts gene expression information related to genes annotated within ESTDB. MarkerQTL is the most complex module and integrates information on genetic markers, maps, individuals, genotypes and traits. Two further modules include an Arabidopsis EnsEMBL genome viewer and the CMap comparative genetic map viewer for the visualization and integration of genetic and genomic data. The database is accessible at http://bioinformatics.pbcbasc.latrobe.edu.au.
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    A comparative map viewer integrating genetic maps for Brassica and Arabidopsis.
    Lim, GAC ; Jewell, EG ; Li, X ; Erwin, TA ; Love, C ; Batley, J ; Spangenberg, G ; Edwards, D (Springer Science and Business Media LLC, 2007-07-24)
    BACKGROUND: Molecular genetic maps provide a means to link heritable traits with underlying genome sequence variation. Several genetic maps have been constructed for Brassica species, yet to date, there has been no simple means to compare this information or to associate mapped traits with the genome sequence of the related model plant, Arabidopsis. DESCRIPTION: We have developed a comparative genetic map database for the viewing, comparison and analysis of Brassica and Arabidopsis genetic, physical and trait map information. This web-based tool allows users to view and compare genetic and physical maps, search for traits and markers, and compare genetic linkage groups within and between the amphidiploid and diploid Brassica genomes. The inclusion of Arabidopsis data enables comparison between Brassica maps that share no common markers. Analysis of conserved syntenic blocks between Arabidopsis and collated Brassica genetic maps validates the application of this system. This tool is freely available over the internet on http://bioinformatics.pbcbasc.latrobe.edu.au/cmap. CONCLUSION: This database enables users to interrogate the relationship between Brassica genetic maps and the sequenced genome of A. thaliana, permitting the comparison of genetic linkage groups and mapped traits and the rapid identification of candidate genes.