Surgery (St Vincent's) - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 52
-
ItemDieulafoy's disease of the bronchus: a rare cause of massive hemoptysis.(Wiley, 2014-06)We present the case of a 30-year-old non-smoker who presented with unexplained, massive hemoptysis and was diagnosed with a rare vascular malformation.
-
ItemInfluence of Reproductive Status on Tissue Composition and Biomechanical Properties of Ovine Vagina(PUBLIC LIBRARY SCIENCE, 2014-04-07)OBJECTIVE: To undertake a comprehensive analysis of the biochemical tissue composition and passive biomechanical properties of ovine vagina and relate this to the histo-architecture at different reproductive stages as part of the establishment of a large preclinical animal model for evaluating regenerative medicine approaches for surgical treatment of pelvic organ prolapse. METHODS: Vaginal tissue was collected from virgin (n = 3), parous (n = 6) and pregnant sheep (n = 6; mean gestation; 132 d; term = 145 d). Tissue histology was analyzed using H+E and Masson's Trichrome staining. Biochemical analysis of the extracellular matrix proteins used a hydroxyproline assay to quantify total collagen, SDS PAGE to measure collagen III/I+III ratios, dimethylmethylene blue to quantify glycosaminoglycans and amino acid analysis to quantify elastin. Uniaxial tensiometry was used to determine the Young's modulus, maximum stress and strain, and permanent strain following cyclic loading. RESULTS: Vaginal tissue of virgin sheep had the lowest total collagen content and permanent strain. Parous tissue had the highest total collagen and lowest elastin content with concomitant high maximum stress. In contrast, pregnant sheep had the highest elastin and lowest collagen contents, and thickest smooth muscle layer, which was associated with low maximum stress and poor dimensional recovery following repetitive loading. CONCLUSION: Pregnant ovine vagina was the most extensible, but the weakest tissue, whereas parous and virgin tissues were strong and elastic. Pregnancy had the greatest impact on tissue composition and biomechanical properties, compatible with significant tissue remodeling as demonstrated in other species. Biochemical changes in tissue protein composition coincide with these altered biomechanical properties.
-
ItemHigher Human T-Lymphotropic Virus Type 1 Subtype C Proviral Loads Are Associated With Bronchiectasis in Indigenous Australians: Results of a Case-Control Study(OXFORD UNIV PRESS INC, 2014-03)BACKGROUND: We previously suggested that infection with the human T-lymphotropic virus type 1 (HTLV-1) subtype C is associated with bronchiectasis among Indigenous Australians. Bronchiectasis might therefore result from an HTLV-1-mediated inflammatory process that is typically associated with a high HTLV-1 proviral load (PVL). Human T-lymphotropic virus type 1 PVL have not been reported for Indigenous Australians. METHODS: Thirty-six Indigenous adults admitted with bronchiectasis from June 1, 2008, to December 31, 2009 were prospectively recruited and matched by age, sex, and ethno-geographic origin to 36 controls. Case notes and chest high-resolution computed tomographs were reviewed, and pulmonary injury scores were calculated. A PVL assay for the HTLV-1c subtype that infects Indigenous Australians was developed and applied to this study. Clinical, radiological, and virological parameters were compared between groups and according to HTLV-1 serostatus. RESULTS: Human T-lymphotropic virus type 1 infection was the main predictor of bronchiectasis in a multivariable model (adjusted risk ratio [aRR], 1.84; 95% confidence interval [CI], 1.19-2.84; P = .006). Moreover, the median HTLV-1c PVL (interquartile range) for cases was >100-fold that of controls (cases, 0.319 [0.007, 0.749]; controls, 0.003 [0.000, 0.051] per 100 peripheral blood lymphocytes; P = .007), and HTLV-1c PVL were closely correlated with radiologically determined pulmonary injury scores (Spearman's rho = 0.7457; P = .0000). Other predictors of bronchiectasis were positive Strongyloides serology (aRR, 1.69; 95% CI, 1.13-2.53) and childhood skin infections (aRR, 1.62; 95% CI, 1.07-2.44). Bronchiectasis was the major predictor of death (aRR, 2.71; 95% CI, 1.36-5.39; P = .004). CONCLUSIONS: These data strongly support an etiological association between HTLV-1 infection and bronchiectasis in a socially disadvantaged population at risk of recurrent lower respiratory tract infections.
-
ItemNo Preview AvailableAdvances in ureteroscopy(AME PUBLISHING COMPANY, 2014-09)Ureteroscopy (URS) is a procedure which has been constantly evolving since the development of first generation devices 40 years ago. Progress towards smaller and more sophisticated equipment has been particularly rapid in the last decade. We review the significant steps that have been made toward improving outcomes and limiting morbidity with this procedure which is central to the management of urolithiasis and other upper urinary tract pathology.
-
ItemNo Preview AvailableHeterogeneity of Osteosarcoma Cell Lines Led to Variable Responses in Reprogramming(IVYSPRING INT PUBL, 2014)Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.
-
ItemNADPH oxidase-dependent redox signaling in TGF-β-mediated fibrotic responses(ELSEVIER, 2014)Uncontrolled fibrosis in organs like heart, kidney, liver and lung is detrimental and may lead to end-stage organ failure. Currently there is no effective treatment for fibrotic disorders. Transforming growth factor (TGF)-β has a fundamental role in orchestrating the process of fibrogenesis; however, interventions directly targeting TGF-β would have undesired systemic side effects due to the multiple physiological functions of TGF-β. Further characterization of the downstream signaling pathway(s) involved in TGF-β-mediated fibrosis may lead to discovery of novel treatment strategies for fibrotic disorders. Accumulating evidence suggests that Nox4 NADPH oxidase may be an important downstream effector in mediating TGF-β-induced fibrosis, while NADPH oxidase-dependent redox signaling may in turn regulate TGF-β/Smad signaling in a feed-forward manner. It is proposed that pharmacological inhibition of the Nox4 function may represent a novel approach in treatment of fibrotic disorders.
-
ItemNo Preview AvailableMathematical modeling of postmenopausal osteoporosis and its treatment by the anti-catabolic drug denosumab(wiley, 2014)Denosumab, a fully human monoclonal antibody, has been approved for the treatment of postmenopausal osteoporosis. The therapeutic effect of denosumab rests on its ability to inhibit osteoclast differentiation. Here, we present a computational approach on the basis of coupling a pharmacokinetics model of denosumab with a pharmacodynamics model for quantifying the effect of denosumab on bone remodeling. The pharmacodynamics model comprises an integrated systems biology-continuum micromechanics approach, including a bone cell population model, considering the governing biochemical factors of bone remodeling (including the action of denosumab), and a multiscale micromechanics-based bone mechanics model, for implementing the mechanobiology of bone remodeling in our model. Numerical studies of postmenopausal osteoporosis show that denosumab suppresses osteoclast differentiation, thus strongly curtailing bone resorption. Simulation results also suggest that denosumab may trigger a short-term bone volume gain, which is, however, followed by constant or decreasing bone volume. This evolution is accompanied by a dramatic decrease of the bone turnover rate by more than one order of magnitude. The latter proposes dominant occurrence of secondary mineralization (which is not anymore impeded through cellular activity), leading to higher mineral concentration per bone volume. This explains the overall higher bone mineral density observed in denosumab-related clinical studies.
-
ItemNo Preview AvailableInduction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent(NATURE PUBLISHING GROUP, 2014-05-01)Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of calcium-signaling pathways controlling EMT induction in cancer cells may therefore be an important therapeutic strategy for preventing metastases.
-
ItemPhase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer(NATURE PUBLISHING GROUP, 2014-11-11)BACKGROUND: Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. METHODS: Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. RESULTS: Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. CONCLUSIONS: Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.
-
ItemCase-case-control study on factors associated with vanB vancomycin-resistant and vancomycin-susceptible enterococcal bacteraemia(BMC, 2014-06-28)BACKGROUND: Enterococci are a major cause of healthcare-associated infection. In Australia, vanB vancomycin-resistant enterococci (VRE) is the predominant genotype. There are limited data on the factors linked to vanB VRE bacteraemia. This study aimed to identify factors associated with vanB VRE bacteraemia, and compare them with those for vancomycin-susceptible enterococci (VSE) bacteraemia. METHODS: A case-case-control study was performed in two tertiary public hospitals in Victoria, Australia. VRE and VSE bacteraemia cases were compared with controls without evidence of enterococcal bacteraemia, but may have had infections due to other pathogens. RESULTS: All VRE isolates had vanB genotype. Factors associated with vanB VRE bacteraemia were urinary catheter use within the last 30 days (OR 2.86, 95% CI 1.09-7.53), an increase in duration of metronidazole therapy (OR 1.65, 95% CI 1.17-2.33), and a higher Chronic Disease Score specific for VRE (OR 1.70, 95% CI 1.05-2.77). Factors linked to VSE bacteraemia were a history of gastrointestinal disease (OR 2.29, 95% CI 1.05-4.99) and an increase in duration of metronidazole therapy (OR 1.23, 95% CI 1.02-1.48). Admission into the haematology/oncology unit was associated with lower odds of VSE bacteraemia (OR 0.08, 95% CI 0.01-0.74). CONCLUSIONS: This is the largest case-case-control study involving vanB VRE bacteraemia. Factors associated with the development of vanB VRE bacteraemia were different to those of VSE bacteraemia.