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Biomedical subjects

Rex Stanbridge

Publications and source records attributed to Rex Stanbridge.

5 recordsLinked to original sources
PubMed2006

Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle.

BACKGROUND: Host defense against microbial pathogens is elicited through the innate immune system by means of Toll-like receptors (TLRs). Airway smooth muscle cells (ASMCs) display proinflammatory and immunomodulatory functions. ASMCs might participate in airway inflammatory responses associated with innate immune activation. OBJECTIVES: We determined the effects of cytokines, TLR ligands, and corticosteroids on TLR expression and function in human ASMCs. METHODS: Real-time PCR and flow cytometry were used to assess TLR mRNA and protein expression, respectively. ASMCs were stimulated with TLR ligands, and chemokine release was measured by means of ELISA. RESULTS: ASMCs expressed TLR1 to TLR10 mRNA, and TLR2 and TLR3 protein expression was demonstrated. TNF-alpha and double-stranded RNA (dsRNA; TLR3 ligand) were potent inducers of TLR2 and TLR3 mRNA expression, and both stimuli had additive or synergistic effects with IFN-gamma on TLR2 and TLR4, but not TLR3, mRNA expression. Peptidoglycan (TLR2 ligand) and LPS (TLR4 ligand) weakly enhanced TLR2 mRNA expression. Peptidoglycan, dsRNA, and LPS induced IL-8 and eotaxin release, with dsRNA being most potent. dsRNA also modulated cytokine-induced chemokine release in a differential manner. Dexamethasone inhibited cytokine- and ligand-induced TLR2, TLR3, and TLR4 expression and chemokine release. However, dexamethasone potentiated TLR2 expression induced by combined IFN-gamma and TNF-alpha stimulation. CONCLUSION: Expression of TLR2, TLR3, and TLR4 is regulated by cytokines and TLR ligands, and their activation mediates chemokine release in ASMCs. CLINICAL IMPLICATIONS: Proinflammatory responses mediated by activation of pathogen-recognition receptors in ASMCs might contribute to infectious exacerbations of airway inflammatory conditions, such as asthma and chronic obstructive pulmonary disease.

Bronchi↗
PubMed2006

Fast-track failure after cardiac surgery: development of a prediction model.

OBJECTIVE: Risk factors for unsuccessful fast-tracking of cardiac surgery patients have not been collectively defined in the literature. The aim of this study was to determine risk factors for fast-track failure and incorporate them into a predictive fast-track failure score. DESIGN: Prospective observational study. SETTING: Cardiothoracic Department of St Mary's Hospital, London. PATIENTS: Data were collected from April 2003 to April 2005 including 1,084 patients undergoing heart surgery who were admitted into the fast-track unit. INTERVENTIONS: Multifactorial logistic regression was used to develop a propensity score for estimating the likelihood of fast-track failure. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty-nine patients failed fast-track management (15.6%). Independent predictors for fast-track failure were impaired left ventricular function with or without recent acute coronary syndrome (odds ratios 2.89 and 1.65 respectively), re-do operation (one, two, or more vs. none, odds ratio 1.75, 7.98), extracardiac arteriopathy (odds ratio 2.63), preoperative intra-aortic balloon pump (odds ratio 3.09), raised serum creatinine in micromol/L (120-150, >150 vs. <120, odds ratio 1.57, 11.24), and nonelective (odds ratio 3.43) and complex surgery (odds ratio 2.70). Model validation showed very good discrimination (area under the curve = 0.815) and calibration (ĉ statistic = 8.527, p = .129). CONCLUSIONS: The fast-track failure score incorporates several preoperative factors and has been successfully internally validated; after undergoing external validation and possible recalibration it may be used as a tool to facilitate planning and flow of cardiac surgery patients, based on the predicted probability of failure. Application of this score may limit fast-track failure rates and help to reduce morbidity and cost.

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PubMed2005

Objective assessment of technical skills in cardiac surgery.

OBJECTIVE: Reduced training time combined with no rigorous assessment for technical skills makes it difficult for trainees to monitor their competence. We have developed an objective bench-top assessment of technical skills at a level commensurate with a junior registrar in cardiac surgery. METHODS: Forty cardiothoracic surgeons were recruited for the study, consisting of 12 junior trainees (year 1-3), 15 senior trainees (year 4-6) and 13 consultants. The assessment consisted of four key tasks on standardised bench-top models: aortic root cannulation, vein-graft to aorta anastomosis, vein-graft to Left Anterior Descending (LAD) anastomosis and femoral triangle dissection. An expert surgeon was present at each station to provide passive assistance and rate performance on a validated global rating scale giving rise to a total possible score of 40. Three expert surgeons repeated the ratings retrospectively, using blinded video recordings. Data analysis employed non-parametric tests. RESULTS: Both live and video scores differentiated significantly between performances of all groups of surgeons for all four stations (P < 0.01) (median live and video score for LAD; Junior 19,17; Senior 29,22; Consultant 36,28). Correlations between live and blinded rating were high (r = 0.67-0.84; P < 0.001) as was inter-rater reliability between the three expert video raters (alpha = 0.81). CONCLUSIONS: The use of bench-top tasks to differentiate between cardiac surgeons of differing technical abilities has been validated for the first time. Furthermore, it is unnecessary to perform post-hoc video rating to obtain objective data. These measures can provide formative feedback for surgeons-in-training and lead to the development of a competency-based technical skills curriculum.

Cardiac Surgical Procedures↗
PubMed2005

Functional renal outcome in on-pump and off-pump coronary revascularization: a propensity-based analysis.

BACKGROUND: Since the advent of off-pump coronary artery bypass grafting (OPCAB), comparisons have been made between it and on-pump coronary artery bypass grafting. Some observe a lesser incidence of acute renal failure requiring renal replacement therapy with OPCAB whereas others do not. The objective was to compare the occurrence of renal adverse outcome between on-pump coronary artery bypass grafting and OPCAB. Renal adverse outcome was defined as minor (20% increase in serum creatinine from preoperative) or major (composite end point of postoperative serum creatinine >200 mumol/L or postoperative mechanical renal support). METHODS: The study was based on 2,041 patients with no known preoperative renal disease having first-time isolated coronary artery bypass grafting of multiple coronary arteries between January 2001 and November 2003, at St. Mary's Hospital, Harefield Hospital, and Hammersmith Hospital, in West London; 1,224 patients had on-pump coronary artery bypass grafting and 817 patients had OPCAB. Selection bias for surgical technique was addressed by calculating the propensity score for each patient and using it as an independent variable for adjustment in the multivariate analysis. Univariate and multivariate ordered logistic regressions were used to identify factors associated with renal adverse outcome ordered as none, minor, and major. RESULTS: The number of grafts was 3.22 +/- 0.82 for the on-pump coronary artery bypass grafting group and 3.35 +/- 0.95 for the OPCAB group. On-pump coronary artery bypass grafting and increasing age were found to be the strongest independent predictors (p < 0.001) of renal adverse outcome. Other independent predictors included hypertension (p = 0.005), diabetes (p = 0.032), and preoperative serum creatinine (p = 0.001). A left ventricular ejection fraction of 0.30 to 0.49 (p = 0.099) and an ejection fraction of 0.50 or greater (p < 0.001) were associated with decreased risk compared with patients with an ejection fraction of less than 0.30. Interestingly, the use of non-left internal mammary arterial conduits significantly decreased the likelihood of renal adverse outcome (p = 0.034). CONCLUSIONS: The results of this propensity-based study show that the OPCAB technique may reduce the risk for minor and major renal adverse outcome after coronary artery bypass grafting.

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