Surgery (St Vincent's) - Research Publications
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ItemThe role of mast cells and fibre type in ischaemia reperfusion injury of murine skeletal muscles.(Springer Science and Business Media LLC, 2004-09-27)BACKGROUND: Ischaemia reperfusion (IR) injury of skeletal muscle, is a significant cause of morbidity following trauma and surgical procedures, in which muscle fibre types exhibit different susceptibilities. The relative degree of mast cell mediated injury, within different muscle types, is not known. METHODS: In this study we compared susceptibility of the fast-twitch, extensor digitorum longus (EDL), mixed fast/slow-twitch gastrocnemius and the predominately slow-twitch soleus, muscles to ischemia reperfusion (IR) injury in four groups of mice that harbour different mast cell densities; C57/DBA mast cell depleted (Wf/Wf), their heterozygous (Wf/+) and normal littermates (+/+) and control C57BL/6 mice. We determined whether susceptibility to IR injury is associated with mast cell content and/or fibre type and/or mouse strain. In experimental groups, the hind limbs of mice were subjected to 70 minutes warm tourniquet ischemia, followed by 24 h reperfusion, and the muscle viability was assessed on fresh whole-mount slices by the nitroblue tetrazolium (NBT) histochemical assay. RESULTS: Viability was remarkably higher in the Wf/Wf strain irrespective of muscle type. With respect to muscle type, the predominately slow-twitch soleus muscle was significantly more resistant to IR injury than gastrocnemius and the EDL muscles in all groups. Mast cell density was inversely correlated to muscle viability in all types of muscle. CONCLUSION: These results show that in skeletal muscle, IR injury is dependent upon both the presence of mast cells and on fibre type and suggest that a combination of preventative therapies may need to be implemented to optimally protect muscles from IR injury.
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ItemNo Preview AvailableThe relevance of ligament balancing in total knee arthroplasty: how important is it? A systematic review of the literature(PAGEPRESS PUBL, 2009)Ligament balancing affects many of the postoperative criteria for a successful knee replacement. A balanced knee contributes to improved alignment and stability. Ligament balancing helps reduce wear and loosening of the joint. A patient with a balanced knee is more likely to have increased range of motion and proprioception, and decreased pain. All these factors help minimize the need for revision surgery. Complications associated with ligament balancing can include instability caused by over-balancing and the possibility of neurovascular damage during or as a result of ligament balancing. This article attempts to summarize the literature, to define a balanced knee, and outline the benefits and possible complications of ligament balancing. Different techniques, sequences, and tools used in ligament balancing, and their relevance in correcting various deformities are reviewed.
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ItemNo Preview AvailableRobotic urology in the United Kingdom: experience and overview of robotic-assisted cystectomy(SPRINGER LONDON LTD, 2008-02)In this article we look at the evolution of robotic technology in operative urology and the significant early contribution of Mr John Wickham. We explore the ergonomics of robotic technology and discuss financial issues from a British perspective. We share our clinical experience, describe the authors' robotic-assisted cystectomy technique, and conclude by exploring the patients' perception of this new treatment modality.
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ItemNo Preview AvailableDifferential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor-α in human aortic smooth muscle and embryonic kidney cells(WILEY, 2006)NADPH oxidases are important sources of vascular superoxide, which has been linked to the pathogenesis of atherosclerosis. Previously we demonstrated that the Nox4 subunit of NADPH oxidase is a critical catalytic component for superoxide production in quiescent vascular smooth muscle cells. In this study we sought to determine the role of Nox4 in superoxide production in human aortic smooth muscle cells (AoSMC) and embryonic kidney (HEK293) cells under proinflammatory conditions. Incubation with tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml) for 12 h increased superoxide production in both cell types, whereas angiotensin II, platelet-derived growth factor or interleukin-1beta had little effects. Superoxide production was completely abolished by the NADPH oxidase inhibitors diphenyline iodonium and apocynin, but not by inhibitors of xanthine oxidase, nitric oxide synthase or mitochondrial electron transport. TNF-alpha upregulated the expression of Nox4 in AoSMC at both message and protein levels, while Nox1 and Nox2 were unchanged. In contrast, upregulation of Nox2 appeared to mediate the enhanced superoxide production by TNF-alpha in HEK293 cells. We suggest that Nox4 may be involved in increased superoxide generation in vascular smooth muscle cells under proinflammatory conditions.
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ItemThe impact of 18-fluorodeoxyglucose positron emission tomography on the staging, management and outcome of anal cancer(NATURE PUBLISHING GROUP, 2009-03-03)Accurate inguinal and pelvic nodal staging in anal cancer is important for the prognosis and planning of radiation fields. There is evidence for the role of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging and management of cancer, with early reports of an increasing role in outcome prognostication in a number of tumours. We aimed to determine the effect of FDG-PET on the nodal staging, radiotherapy planning and prognostication of patients with primary anal cancer. Sixty-one consecutive patients with anal cancer who were referred to a tertiary centre between August 1997 and November 2005 were staged with conventional imaging (CIm) (including computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound and chest X-ray) and by FDG-PET. The stage determined by CIm and the proposed management plan were prospectively recorded and changes in stage and management as a result of FDG-PET assessed. Patients were treated with a uniform radiotherapy technique and dose. The accuracy of changes and prognostication of FDG-PET were validated by subsequent clinical follow-up. Kaplan-Meier survival analysis was used to estimate survival for the whole cohort and by FDG-PET and CIm stage. The tumour-stage group was changed in 23% (14 out of 61) as a result of FDG-PET (15% up-staged, 8% down-staged). Fourteen percent of T1 patients (3 out of 22), 42% of T2 patients (10 out of 24) and 40% of T3-4 patients (6 out of 15) assessed using CIm, had a change in their nodal or metastatic stage following FDG-PET. Sensitivity for nodal regional disease by FDG-PET and CIm was 89% and 62%, respectively. The staging FDG-PET scan altered management intent in 3% (2 out of 61) and radiotherapy fields in 13% (8 out of 61). The estimated 5-year overall survival (OS) and progression-free survival (PFS) for the cohort were 77.3% (95% confidence interval (CI): 55.3-90.4%) and 72.2% (95% CI: 51.5-86.4%), respectively. The estimated 5-year PFS for FDG-PET and CIm staged N2-3 disease was 70% (95% CI: 42.8-87.9%) and 55.3% (95% CI: 23.3-83.4%), respectively. FDG-PET shows increased sensitivity over CIm for staging nodal disease in anal cancer and changes treatment intent or radiotherapy prescription in a significant proportion of patients.
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ItemNo Preview AvailableNeovascularization in an arterio-venous loop-containing tissue engineering chamber: role of NADPH oxidase(WILEY, 2008-10)Using an in vivo arterio-venous loop-containing tissue-engineering chamber, we have created a variety of vascularized tissue blocks, including functional myocardium. The viability of the transplanted cells is limited by the rate of neovascularization in the chamber. A Nox2-containing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is thought to have a critical role in ischaemic angiogenesis. In this study we investigated whether NADPH oxidase is involved in the neovascularization process in the tissue-engineering chamber. New blood vessels originating from the venous and the arterial ends of the loop could be identified after 3 days, and the vessel density (by lectin staining) peaked after 7 days and was maintained for at least 14 days. This was accompanied by granulation tissue formation and concomitant increase in the mRNA level of Nox4 NADPH oxidase. Although the total level of Nox2 mRNA in the chamber tissue decreased from day 3 to day 7, immunohistochemistry identified a strong expression of Nox2 in the endothelial cells of the new vessels. In human microvascular endothelial cells, the NADPH oxidase inhibitor apocynin reduced NADPH oxidase activity and inhibited the angiogenic responses in vitro. Local treatment with the NADPH oxidase inhibitors apocynin or gp91ds-tat peptide significantly suppressed the vessel growth in the chamber. In conclusion, NADPH oxidase-dependent redox signalling is important for neovascularization in this novel tissue-engineering chamber in vivo, and boosting this signalling might be a new approach to extending vascularization and tissue growth.
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ItemNo Preview AvailableAntibodies against the CB10 fragment of type II collagen in rheumatoid arthritis(BMC, 2004)Antibodies against intact type II collagen (CII) are a feature of rheumatoid arthritis (RA) but have limited diagnostic value. Here we assess whether either of the two major cyanogen bromide fragments of CII, namely CB10 or CB11, are more sensitive substrates for the detection of antibodies in RA. Cleavage of bovine CII with cyanogen bromide yielded CB10 and CB11; these were purified by column chromatography for use in an enzyme-linked immunosorbent assay. Serum antibodies were measured in patients with RA, psoriatic arthritis (PsA), osteoarthritis (OA) and blood donors. Results were compared with those using intact CII. Antibodies against CB10 were found in as many as 88% of 96 patients with long-standing RA, but only 12% of 33 patients with PsA, 6% of 34 patients with OA and 3% of 93 control sera. Lower frequencies for these diseases were obtained on testing for antibodies against CB11: 50%, 6%, 21% and 2%, respectively. The sensitivity of detection in RA of antibodies against CB10 compared with antibodies against intact CII (88% versus 24%) was not at the expense of specificity, which remained high at 94%. The much higher frequency of antibodies against CB10 in RA than in other rheumatic diseases or control sera indicates that CB10 is clearly a more sensitive substrate than the intact collagen molecule and, combined with other assays (rheumatoid factor, anti-cyclic citrullinated peptide [anti-CCP]), might comprise a panel with a highly reliable predictive value. Moreover, our findings should encourage renewed interest in the role of collagen autoimmunity in the pathogenesis of RA.
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ItemThe correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival(NATURE PUBLISHING GROUP, 2006-05-22)Colorectal cancer development is associated with a shift in host immunity with suppression of the cell-mediated immune system (CMI) and a predominance of humoral immunity (HI). Tumour progression is also associated with increased rates of cell proliferation and apoptosis. The aim of this study was to investigate whether these factors correlate and have an influence upon prognosis. Long-term follow-up was performed on 40 patients with colorectal cancer who had levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 measured from stimulated blood cultures before surgery. Their archived tumour specimens were analysed to determine a Ki-67-derived proliferation index (PI) and a M30-derived apoptosis index (AI). Tumour necrosis factor-alpha levels negatively correlated to tumour proliferation (rho=-0.697, P=0.01). Interleukin-10 levels had a positive correlation with tumour proliferation (rho=0.452, P=0.05) and apoptosis (rho=0.587, P=0.01). Patient survival correlates to tumour pathological stage (P=0.0038) and vascular invasion (P=0.0014). An AI< or =0.6% and TNF-alpha levels > or =8148 pg ml(-1) correlate to improved survival (P=0.032, P=0.021). Tumour proliferation and apoptosis correlate to progressive suppression of the CMI-associated cytokine TNF-alpha and to and higher levels of IL-10. Survival is dependent upon the histological stage of the tumour, vascular invasion, rates of apoptosis and proliferation and systemic immunity which are all interconnected.
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ItemNo Preview AvailableClinical applications of molecular imaging in sarcoma evaluation.(E-MED LTD, 2005-06-21)A wide range of molecular imaging techniques are available that can provide complementary information to conventional, anatomical imaging for the evaluation of known or suspected bone and soft tissue sarcomas. In particular, positron emission tomography (PET), particularly in the form of hybrid PET/CT technology, offers many potential advantages over current imaging approaches by delineating not only the extent of disease but also the biological heterogeneity that can exist both between and within sarcomas. This review discusses the clinical situations where nuclear medicine techniques can aid in the management of patients with sarcoma. These include biopsy guidance, whole body staging, therapeutic response assessment and evaluation of residual mass lesions after treatment.