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Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2∗-weighted protocols. R2∗ values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2∗ values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), P<0.01). R2∗ values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) P<0.05). Increased R2∗ signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage. [ABSTRACT FROM AUTHOR]

Background: Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery.Methods and Results: In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320).Conclusions: There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury.Trial Registration Number: (EudraCT 2010-019527-58, ISRCTN82061264). [ABSTRACT FROM AUTHOR]

Study Objective: To assess the value of a history and physical examination findings in diagnosing the carpal tunnel syndrome, and to determine whether constellations of clinical findings identify patients at high or low risk for the carpal tunnel syndrome.Design: Comparison of diagnostic tests with neurophysiologic testing.Setting: Patients with upper extremity complaints of diverse causes referred to a neurophysiology laboratory for diagnostic studies.Methods: Before nerve conduction testing, a history, demographic and physical examination data, and a hand pain diagram were obtained from each patient. Diagrams were categorized as indicating the classic carpal tunnel syndrome, or as probable, possible, or unlikely to indicate the carpal tunnel syndrome. Associations between clinical data and nerve conduction results were examined in univariate and multivariate analyses.Results: Of 110 patients in the study, 44 (40%) had the carpal tunnel syndrome. Individually, the best predictors were hand pain diagram rating (positive predictive value, 0.59; 95% CI, 0.48 to 0.68) and Tinel sign (positive predictive value, 0.55, CI, 0.45 to 0.65). The combination of a positive Tinel sign and a probable or classic diagram rating had a positive predictive value of 0.71; CI, 0.53 to 0.85. Other findings from physical examination and the history were less useful. Just 9% of patients under 40 years of age with possible or unlikely diagram ratings had the carpal tunnel syndrome.Conclusions: With the exceptions of age, Tinel sign, and hand pain diagram rating, findings from the physical examination and the history had limited diagnostic utility. Patients under 40 years of age with possible or unlikely diagram ratings were at low risk for the carpal tunnel syndrome. This finding, which should be confirmed in an independent population, suggests that subsets of patients may be managed without nerve conduction studies. [ABSTRACT FROM AUTHOR]