Basil Hetzel Institute
Basil Hetzel Institute
Wong S.,The Queen Elizabeth Hospital |
Lidums I.,The Queen Elizabeth Hospital |
Rosty C.,Envoi Specialist Pathologists |
Rosty C.,University of Queensland |
And 29 more authors.
BMC Gastroenterology | Year: 2017
Background: Colorectal cancer (CRC) diagnosed at <50 years is predominantly located in the distal colon and rectum. Little is known about which lesion subtypes may serve as CRC precursors in young adults. The aim of this work was to document the prevalence and histological subtype of lesions seen in patients aged <50 years, and any associated clinical features. Methods: An audit of the colonoscopy database at The Queen Elizabeth Hospital in Adelaide, South Australia over a 12-month period was undertaken. Findings were recorded from both colonoscopy reports and corresponding histological examination of excised lesions. Results: Data were extracted from colonoscopies in 2064 patients. Those aged <50 comprised 485 (24%) of the total. CRC precursor lesions (including sessile serrated adenoma/polyps (SSA/P), traditional serrated adenomas, tubular adenomas ≥10 mm or with high-grade dysplasia, and conventional adenomas with villous histology) were seen in 4.3% of patients aged <50 and 12.9% of patients aged ≥50 (P <0.001). Among colonoscopies yielding CRC precursor lesions in patients under 50 years, SSA/P occurred in 52% of procedures (11/21), compared with 27% (55/204) of procedures in patients aged 50 and older (P = 0.02). SSA/P were proximally located in (10/11) 90% of patients aged under 50, and 80% (43/54) of those aged 50 and older (P = 0.46). Conclusions: SSA/P were the most frequently observed CRC precursor lesions in patients aged <50. Most CRCs in this age group are known to arise in the distal colon and rectum suggesting that lesions other than SSA/P may serve as the precursor for the majority of early-onset CRC. © 2017 The Author(s).
Ranasinghe D.C.,University of Adelaide |
Shinmoto Torres R.L.,University of Adelaide |
Hill K.,Curtin University Australia |
Visvanathan R.,Basil Hetzel Institute |
And 2 more authors.
Gait and Posture | Year: 2014
Introduction: Falls in hospitals and residential care facilities commonly occur near the bed. The aim of this study was to investigate the accuracy of a continuously wearable, batteryless, low power and low cost monitoring device (Wearable Wireless Identification and Sensing Platform) with a single kinematic sensor capable of real-time monitoring to automatically detect bed entry and exit events. Materials and methods: Three dimensional acceleration readings and the strength of the transmitted signal from the WISP was interpreted to identify bed exit events and sensitivity, specificity and Receiving Operator Curves (ROC) were determined. Results: The sensor located over sternum method performed best with sensitivity and specificity values of 92.8% and 97.5% respectively for detecting bed entry and values of 90.4% and 93.80% respectively for bed exit. On the other hand, the sensor-on-mattress algorithm achieved sensitivity and specificity values of 84.2% and 97.4% respectively for bed entry and 79% and 97.4% for bed exit detection. Conclusion: The WISP located over the sternum method is the preferred method to detect bed entry and exit. However, further work in frail older people is required to confirm the performance of this method. © 2013 Elsevier B.V.
Flabouris A.,Royal Adelaide Hospital |
Flabouris A.,University of Adelaide |
Jeyadoss J.,University of Adelaide |
Jeyadoss J.,The Queen Elizabeth Hospital |
And 4 more authors.
EMA - Emergency Medicine Australasia | Year: 2013
Objective: To evaluate the association of ED length of stay (EDLOS) and outcome of patients admitted to a ward, intensive care (ICU) or stepdown (high dependency) unit (SDU). Methods: Design: Retrospective cohort study using linked administrative and clinical data. Setting: 650-bed, university-affiliated, tertiary referral hospital, whose ED has approximately 60000 patient presentations per annum. Participants: Adult patients admitted via the ED, to a ward (ED to ward), ICU (ED to ICU) or SDU (ED to SDU), and whose EDLOS was <24h. Outcome measures: Hospital outcome and LOS. Results: A total of 43484 patients over 4 years. Median EDLOS was 2:36h for ICU, 5:07h for SDU and 7:19h for ward (P < 0.01) patients. EDLOS differed significantly, based on hospital outcome, for ward (alive, 7:18h vs died, 7:44h, P < 0.001), but not SDU or ICU patients. At an EDLOS of 4 and 8h, 19.4% and 5.2% of ICU, 52.1% and 15.5% of SDU and 77.9% and 32.6% of ward patients remained in the ED. EDLOS was not a significant predictor of death, in comparison with increasing age and admitting unit across all three groups, and higher triage acuity for ED to ward and ED to ICU. Conclusions: EDLOS was greater for ED to ward patients, and of the ED to ward patients who died. At an EDLOS of 4h there were fewer ICU, in comparison with ward, patients remaining in the ED. Future studies that report on EDLOS should differentiate for patients admitted from the ED to the ward, ICU or SDU. © 2012 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.
Ali O.A.,Queen Elizabeth Hospital |
Ali O.A.,University of Adelaide |
Chapman M.,Queen Elizabeth Hospital |
Chapman M.,University of Adelaide |
And 13 more authors.
Heart | Year: 2014
Objectives: Bicuspid aortic valve (BAV) is associated with increased risk of valvular degeneration and ascending aortic aneurysm formation and rupture. We sought to evaluate the roles of endothelial dysfunction and inflammatory activation in modulating these processes. Methods: We performed a case-control study of patients with BAV together with a multivariate analysis within the BAV group to identify factors associated with: development of significant valvular disease; dilatation of the ascending aorta; differential valve relative to aortic disease. Endothelial function of patients and controls was evaluated via flow-mediated dilatation (FMD) and plasma concentrations of asymmetric dimethylarginine (ADMA). Correlations with inflammatory markers and endothelial progenitor cell counts were also examined. Morphological and physiological assessment of the valve and ascending aorta was performed with transthoracic echocardiography and MRI. Results: Patients with BAV (n=43) and controls (n=25) were matched for age and gender. FMD was significantly lower in patients than controls (7.85±3.48% vs 11.58 ±3.98%, p=0.001), and these differences were ageindependent. Within the BAV cohort, multivariate correlates of peak aortic valve velocity were plasma concentrations of ADMA and myeloperoxidase (MPO) (both p<0.01), while increasing age was an independent correlate of ascending aortic diameter (p<0.05). Furthermore, both low FMD and inflammatory activation were multivariate correlates of selectivity for valvular disease. Conclusions: BAV is associated with endothelial dysfunction. The extent of inflammatory activation (specifically MPO release) and that of endothelial dysfunction impact primarily on integrity of the valve rather than aortic structure.
Rojas-Canales D.,Royal Adelaide Hospital |
Rojas-Canales D.,University of Adelaide |
Rojas-Canales D.,Queen Elizabeth Hospital |
Rojas-Canales D.,Basil Hetzel Institute |
And 12 more authors.
Clinical and Experimental Immunology | Year: 2012
Interferon (IFN)-γ is a cytokine with immunomodulatory properties, which has been shown previously to enhance the generation of tolerogenic dendritic cells (DC) when administered early ex vivo in 7-day monocyte-derived DC culture. To generate tolerogenic DC rapidly within 48h, human monocytes were cultured for 24h with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence (IFN-γ-DC) or absence of IFN-γ (500U/ml) (UT-DC). DC were matured for 24h with TNF-α and prostaglandin E 2 (PGE 2). DC phenotype, signal transducer and activator of transcription-6 (STAT-6) phosphorylation and promotion of CD4 +CD25 +CD127 neg/lowforkhead box P3 (FoxP3) hi T cells were analysed by flow cytometry. DC nuclear factor (NF)-κB transcription factor reticuloendotheliosis viral oncogene homologue B (RELB) and IL-12p70 protein expression were also determined. Phenotypically, IFN-γ-DC displayed reduced DC maturation marker CD83 by 62% and co-stimulation molecules CD80 (26%) and CD86 (8%). IFN-γ treatment of monocytes inhibited intracellular STAT6, RELB nuclear translocation and IL-12p70 production. IFN-γ-DC increased the proportion of CD4 +CD25 +CD127 neg/lowfoxp3 hi T cells compared to UT-DC from 12 to 23%. IFN-γ-DC primed T cells inhibited antigen-specific, autologous naive T cell proliferation by 70% at a 1:1 naive T cells to IFN-γ-DC primed T cell ratio in suppression assays. In addition, we examined the reported paradoxical proinflammatory effects of IFN-γ and confirmed in this system that late IFN-γ exposure does not inhibit DC maturation marker expression. Early IFN-γ exposure is critical in promoting the generation of regulatory DC. Early IFN-γ modulated DC generated in 48h are maturation arrested and promote the generation of antigen-specific regulatory T cells, which may be clinically applicable as a novel cellular therapy for allograft rejection. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.
PubMed | Basil Hetzel Institute, University of Adelaide and University of Ottawa
Type: Journal Article | Journal: The American journal of cardiology | Year: 2015
Cardiac arrest (CA) is relatively rare but lethal complication of takotsubo cardiomyopathy (TTC). In most instances, patients are diagnosed with TTC after CA, making it difficult to distinguish if TTC is the precipitant or the consequence of the index event. In this systematic review, patient-level data were obtained to seek out the characteristics of patients in whom the underlying cause of CA is TTC. A comprehensive search of 4 major databases (Embase, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to the last week of September 2014. Of 186 citations, 62 case studies were included in the analysis, providing patient-level data on 77 patients. In 60 patients (78%), the diagnosis of TTC was made after CA. Patients presenting with CA were younger (mean age 49.5 16 vs 64.9 11 years, p <0.0001) and had relatively shorter corrected QT interval (mean 530 101 vs 616 140 ms) on electrocardiography. TTC-related hypotension was the major cause of CA in the acute phase, while a long corrected QT interval triggered CA in the subacute (24- to 72-hour) phase. In 11 patients, CA was not directly instigated by TTC despite a left ventricular appearance matching TTC. In conclusion, in TTC, CA typically develops within the first 3 days of presentation and is the result of long corrected QT interval-induced polymorphic ventricular tachycardia. Secondary TTC, in which patients present with typical left ventricular features after CA, likely represents a distinct cohort in which identifiable inheritable arrhythmias or structural heart disease should be sought.
News Article | November 21, 2016
Researchers have made significant progress in the development of a potential vaccine to protect against HIV infection. For the first time, researchers have shown that a combined approach - using a common cold virus to introduce a vaccine into the body, as well as an injection of a DNA-based vaccine - results in the immune system actively protecting against HIV in the gut and bodily cavities. The laboratory studies, conducted so far in mice and now published in the Nature journal Scientific Reports, represent an important step forward in attempts to introduce a first line of defense against HIV at the site of infection. "With sexual activity being one of the primary methods of HIV transmission, it's necessary to try to protect those parts of the body that are most likely to encounter the virus first," says senior author Dr Branka Grubor-Bauk, from the Discipline of Surgery at the University of Adelaide and Basil Hetzel Institute for Translational Health Research, Queen Elizabeth Hospital. "A possible reason why previous HIV vaccine trials have not been successful is because of this lack of a frontline protection. "In mice, we delivered a rhinovirus (or common cold virus) inside the nose, and this virus had been altered to include HIV proteins. At the same time, the mice also received an injection into the skin containing a DNA-based vaccine. This approach resulted in very specific responses in the immune system," Dr Grubor-Bauk says. "Importantly, this vaccine approach encompasses two different arms of the immune system: white blood cells that attack the HIV virus, and specific antibodies that recognize and shut down HIV-positive cells." The Head of the Virology Group conducting this research is Professor Eric Gowans, also from the University's Discipline of Surgery, based at the Basil Hetzel Institute. "There's an element of HIV known as Tat that helps the virus to replicate quite rapidly. One of the beauties of our vaccine approach is that the antibodies inhibit the Tat effect, preventing HIV from replicating itself," Professor Gowans says. "Overall, we found that infection was considerably reduced in the mice we studied. The findings of our work now support the need for further testing of this targeted approach to an HIV vaccine," he says. This study was supported with funding from The Hospital Research Foundation and the National Health and Medical Research Council (NHMRC). The findings are announced ahead of World AIDS Day (Thursday 1 December 2016). Dr Branka Grubor-Bauk Senior Research Officer, Virology Group Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital firstname.lastname@example.org Professor Eric Gowans Head, Virology Group Discipline of Surgery, The University of Adelaide and Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital email@example.com
Ellem S.J.,Monash University |
Taylor R.A.,Monash University |
Furic L.,Monash University |
Larsson O.,Karolinska Institutet |
And 8 more authors.
Journal of Pathology | Year: 2014
Prostate cancer is hormone-dependent and regulated by androgens as well as oestrogens. The tumour microenvironment also provides regulatory control, but the balance and interplay between androgens and oestrogens at the human prostate tumour interface is unknown. This study reveals a central and dominant role for oestrogen in the microenvironment, fuelling a pro-tumourigenic loop of inflammatory cytokines involving recruitment of mast cells by carcinoma-associated fibroblasts (CAFs). Mast cell numbers were increased in human PCa clinical specimens, specifically within the peritumoural stroma. Human mast cells were also shown to express ERα and ERβ, with oestradiol directly stimulating mast cell proliferation and migration as well as altered cytokine/chemokine expression. There was a significant shift in the oestrogen:androgen balance in CAFs versus normal prostatic fibroblasts (NPFs), with a profound increase to ER:AR expression. Androgen signalling is also reduced in CAFs, while ERα and ERβ transcriptional activity is not, allowing oestrogen to dictate hormone action in the tumour microenvironment. Gene microarray analyses identified CXCL12 as a major oestrogen-driven target gene in CAFs, and CAFs recruit mast cells via CXCL12 in a CXCR4-dependent manner. Collectively, these data reveal multicellular oestrogen action in the tumour microenvironment and show dominant oestrogen, rather than androgen, signalling at the prostatic tumour interface. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Singh K.,University of Ottawa |
Singh K.,Basil Hetzel Institute |
Carson K.,Basil Hetzel Institute |
Hibbert B.,University of Ottawa |
Le May M.,University of Ottawa
American Journal of Cardiology | Year: 2015
Cardiac arrest (CA) is relatively rare but lethal complication of takotsubo cardiomyopathy (TTC). In most instances, patients are diagnosed with TTC after CA, making it difficult to distinguish if TTC is the precipitant or the consequence of the index event. In this systematic review, patient-level data were obtained to seek out the characteristics of patients in whom the underlying cause of CA is TTC. A comprehensive search of 4 major databases (Embase, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to the last week of September 2014. Of 186 citations, 62 case studies were included in the analysis, providing patient-level data on 77 patients. In 60 patients (78%), the diagnosis of TTC was made after CA. Patients presenting with CA were younger (mean age 49.5 ± 16 vs 64.9 ± 11 years, p <0.0001) and had relatively shorter corrected QT interval (mean 530 ± 101 vs 616 ± 140 ms) on electrocardiography. TTC-related hypotension was the major cause of CA in the acute phase, while a long corrected QT interval triggered CA in the subacute (24- to 72-hour) phase. In 11 patients, CA was not directly instigated by TTC despite a left ventricular appearance matching TTC. In conclusion, in TTC, CA typically develops within the first 3 days of presentation and is the result of long corrected QT interval-induced polymorphic ventricular tachycardia. Secondary TTC, in which patients present with typical left ventricular features after CA, likely represents a distinct cohort in which identifiable inheritable arrhythmias or structural heart disease should be sought. © 2015 Elsevier Inc. All rights reserved.