Clinical School (St Vincent's Hospital) - Research Publications

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    Resolving classic pityriasis rubra pilaris, mimicker of erythema gyratum repens
    Davenport, R ; Le, ST ; Gin, A ; Goh, MSY ; Foley, P (WILEY, 2018-08)
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    Collagen immunoassay as a method to optimise surface functionalisation
    Stynes, G ; Kiroff, G ; Morrison, W ; Kirkland, M (WILEY-V C H VERLAG GMBH, 2017-09)
    Traditional methods of assessing surface functionalisation, including spectroscopy and chemical labelling, often involve significant error and conjecture about bonds. Proteins that improve cell attachment have specific pKa's and optimum binding requirements that may differ from the conditions required for chemical labelling. The utility of collagen ELISA to optimise acetaldehyde glow discharge polymerisation reactor parameters was tested. Accurate stepwise increases in collagen conjugation strength were demonstrated by incubating specimens in 8 M urea for 5–8 days followed by ELISA to test for residual surface collagen. Surface modifications also were assessed by XPS. The results indicated that ELISA after bond‐stressing with urea may suffice for optimising surface functionalisation and that traditional methods of analysis may be superfluous if protein conjugation is the aim of functionalisation.
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    Interns' perceptions of exposure to urology during medical school education in Victoria, Australia
    Azer, S ; Khan, M ; Hoag, N ; Bookun, R ; Lawrentschuk, N ; Grills, R ; Bolton, D (WILEY-BLACKWELL, 2017-01)
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    Human glandular organoid formation in murine engineering chambers after collagenase digestion and flow cytometry isolation of normal human breast tissue single cells
    Huo, CW ; Huang, D ; Chew, GL ; Hill, P ; Vohora, A ; Ingman, WV ; Glynn, DJ ; Godde, N ; Henderson, MA ; Thompson, EW ; Britt, KL (WILEY, 2016-11)
    Women with high mammographic density (MD) are at increased risk of breast cancer (BC) after adjustment for age and body mass index. We have developed a murine biochamber model in which both high MD (HMD) and low MD (LMD) tissue can be propagated. Here, we tested whether cells isolated by collagenase digestion and fluorescence-activated cell sorting (FACS) from normal breast can be reconstituted in our biochamber model, which would allow cell-specific manipulations to be tested. Fresh breast tissue was collected from women (n = 7) undergoing prophylactic mastectomy. The tissue underwent collagenase digestion overnight and, in some cases, additional FACS enrichment to obtain mature epithelial, luminal progenitor, mammary stem, and stromal cells. Cells were then transferred bilaterally into biochambers in SCID mice (n = 5-7) and incubated for 6 weeks, before harvesting for histological analyses, and immunohistochemical staining for cytokeratins (CK), vimentin, Ki-67, murine macrophages, and Cleaved Caspase-3. Biochambers inoculated with single cells after collagenase digestion or with flow cytometry contained glandular structures of human origin (human vimentin-positive), which expressed CK-14 and pan-CK, and were proliferating (Ki-67-positive). Glandular structures from the digested tissues were smaller than those in chambers seeded with finely chopped intact mammary tissue. Mouse macrophage infiltration was higher in the chambers arising from digested tissues. Pooled single cells and FACS fractionated cells were viable in the murine biochambers and formed proliferating glandular organoids of human origin. This is among the first report to demonstrate the success of formed human glandular organoids from isolated primary mammary cells in the murine biochamber model.
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    Toward a skin-material interface with vacuum-integrated capped macroporous scaffolds
    Stynes, GD ; Kiroff, GK ; Morrison, WA ; Page, RS ; Kirkland, MA (WILEY, 2017-07)
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    The Impact of Known Heart Disease on Long-Term Outcomes of Catheter Ablation in Patients with Atrial Fibrillation and Left Ventricular Systolic Dysfunction: A Multicenter International Study
    Prabhu, S ; Ling, L-H ; Ullah, W ; Hunter, RJ ; Schilling, RJ ; McLellan, AJA ; Earley, MJ ; Sporton, SC ; Voskoboinik, A ; Blusztein, D ; Mariani, JA ; Lee, G ; Taylor, AJ ; Kalman, JM ; Kistler, PM (WILEY-BLACKWELL, 2016-03)
    BACKGROUND: Catheter ablation for AF is an effective treatment for patients with AF and systolic LV dysfunction; however, the clinical outcome is variable. We evaluated the impact of cardiomyopathy etiology on long-term outcomes post-catheter ablation. METHODS: Patients undergoing AF ablation across 3 centers (2 Australian, 1 UK) from 2002 to 2014, with LVEF<45% were evaluated. Patients were stratified into those with known heart disease as a cause of cardiomyopathy (KHD), and those with idiopathic dilated cardiomyopathy (IDCM). RESULTS: One hundred and one patients (IDCM = 77, KHD = 24) with AF and LVEF <45% underwent AF ablation. The KHD group (ischemic HD in 67%) were older (61 ± 7 vs. 55 ± 11 years, P = 0.005), with a higher CHADS2 score (2.0 ± 0.8 vs. 1.6 ± 0.7, P = 0.016), but otherwise well matched. After mean follow-up of 36 ± 23 months, AF control was greater in the IDCM group (82% vs. 50% in KHD, P < 0.001). On multivariate analysis IDCM was associated with long-term AF control (P = 0.033). The IDCM group had less functional impairment at follow-up (NYHA class 1.5 ± 0.7 vs. 2.0 ± 0.8, P = 0.005) and improved LVEF (50 ± 11% vs. 38 ± 10%, P < 0.001). Super responders (EF improvement >15%) were overwhelmingly in the IDCM group (94% vs. 6%, P < 0.001) with greater AF control (89% vs. 61%, P < 0.001). All-cause mortality was significantly higher in the KHD group (17% vs. 1.3%, P = 0.002). CONCLUSION: IDCM was associated with greater AF control, and improvement in symptoms and LVEF compared to patients with KHD post-AF ablation. AF is an important reversible cause of HF in patients with an unexplained CM and catheter ablation an effective treatment option.
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    Opioid prescribing in orthopaedic and neurosurgical specialties in a tertiary hospital: a retrospective audit of hospital discharge data
    Stanley, B ; Norman, AF ; Collins, LJ ; Zographos, GA ; Lloyd-Jones, DM ; Bonomo, A ; Bonomo, YA (WILEY, 2018-11)
    BACKGROUND: To understand patterns of opioid prescribing on discharge in the orthopaedic and neurosurgical wards of a tertiary metropolitan hospital. METHODS: A retrospective audit of medical records and discharge summaries for all orthopaedic and neurosurgical patients admitted for at least 2 days on two surgical wards over a 6-month period between 1 January and 30 June 2017. RESULTS: A combined total of 355 patients (281 orthopaedic and 74 neurosurgical patients) were included in the audit. Approximately 82% were discharged on opioids. Of patients discharged on opioids, 71.4% of the orthopaedic group and 73.8% of the neurosurgical group were discharged on combinations of two or more opioids (immediate release together with slow release). Around 65% of the sample discharged on opioids was opioid naïve on admission. About 32.5% of the orthopaedic patients and 68.9% of the neurosurgical patients were discharged on a combination of opioid and other pharmacotherapy that could potentiate the central nervous system depressant effect of the opioids. Only 6.9% of orthopaedic patients and 11.5% of the neurosurgical patients had discharge summaries that included any reference to opioid management after discharge. CONCLUSION: Orthopaedic and neurosurgical units had high opioid prescribing rates on discharge from hospital. This highlights the need for clear communication of the intended medication management plan post-discharge in order to minimize inappropriate and ongoing use of opioids post-surgery.
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    Ixekizumab-treatment-emergent photosensitive cutaneous eruption
    Anthony, E ; Bala, HR ; Goh, MSY ; Balta, S ; Foley, P (WILEY, 2018-11)
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    Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS: a secondary analysis of PRoVENT
    Simonis, FD ; Barbas, CSV ; Artigas-Raventos, A ; Canet, J ; Determann, RM ; Anstey, J ; Hedenstierna, G ; Hemmes, SNT ; Hermans, G ; Hiesmayr, M ; Hollmann, MW ; Jaber, S ; Martin-Loeches, I ; Mills, GH ; Pearse, RM ; Putensen, C ; Schmid, W ; Severgnini, P ; Smith, R ; Treschan, TA ; Tschernko, EM ; Melo, MFV ; Wrigge, H ; de Abreu, MG ; Pelosi, P ; Schultz, MJ ; Serpa Neto, A (SPRINGEROPEN, 2018-03-21)
    BACKGROUND: The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients. METHODS: The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality. RESULTS: 935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the 'Lung Injury Prediction Score' and received lower maximum airway pressure (Pmax), driving pressure (ΔP), positive end-expiratory pressure, and FiO2 levels. Tidal volume size was similar between the groups. Higher Pmax was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. ΔP was not independently associated with in-hospital mortality, but reliable values for ΔP were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence. CONCLUSIONS: Higher Pmax was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS. Trial Registration ClinicalTrials.gov (NCT01868321).
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    ASXL1 c.1934dup;p.Gly646Trpfs*12-a true somatic alteration requiring a new approach
    Yannakou, CK ; Jones, K ; McBean, M ; Thompson, ER ; Ryland, GL ; Doig, K ; Markham, J ; Westerman, D ; Blombery, P (NATURE PUBLISHING GROUP, 2017-12-20)