Myocardial damage in falciparum malaria detectable by cardiac troponin T is rare

OBJECTIVES: To estimate the prevalence of myocardial damage in falciparum malaria by serum concentration of cardiac troponin T. METHODS: Retrospective study of stored sera and patient files; assessment of acute myocardial damage by serum concentration or activity of cardiac troponin T, creatine kinase, creatine kinase MB and myoglobin and by routine electrocardiography. RESULTS: A total of 161 patients with falciparum malaria were included in the study; troponin T was elevated in one case (0.6%), no CK-MB elevations were found, myoglobin was elevated in 10 of 161 patients (6.2%), all of whom were elderly and had concomitant elevated serum concentration levels of cystatin C; ECG abnormalities were seen in 23 patients. CONCLUSION: Assessed by troponin T, myocardial damage in falciparum malaria is rare.     

T-cell responses and previous exposure to hepatitis C virus in indeterminate blood donors

Blood donors are routinely screened for hepatitis C virus infection. Some individuals have weak or restricted virus-specific antibody responses, and are classed as indeterminate. Such donors are almost always negative for viral RNA in blood. We postulated that previous transient virus exposure might account for some of these cases. With sensitive ex-vivo analyses of T-cell responses, we identified virus-specific responses in 15 of 30 indeterminate blood donors tested, compared with none in controls (p=0.0013). Additionally, these responses were typically focused on core-derived peptides. These findings suggest previous exposure to the virus in many indeterminate blood donors.     

Contractile dysfunction in hypertrophied hearts with deficient insulin receptor signaling: possible role of reduced capillary density

Diabetics have worse outcomes than nondiabetics after a variety of cardiac insults. We tested the hypothesis that impaired insulin receptor signaling in myocytes worsens cardiac remodeling and function following injury, even in the absence of hyperglycemia. Mice with cardiomyocyte-restricted knock out of the insulin receptor (CIRKO) and wild type (WT) mice were treated with isoproterenol (ISO) for 2 or 5 days. Heart rates and cardiac mass increased comparably following ISO in WT and CIRKO mice. After 5 days, WT hearts were hyperdynamic by echocardiographic and left ventricular pressure measurements. However, CIRKO hearts had a blunted increase in contractility and relaxation following ISO. Interestingly, single myocytes isolated from both CIRKO ISO and WT ISO hearts had increased cellular shortening with prolonged time to peak shortening vs. respective shams. Thus, loss of myocytes or extramyocyte factors, rather than intrinsic dysfunction of surviving myocytes, caused the blunted inotropic response in ISO treated CIRKO hearts. Indeed, CIRKO ISO mice had increased troponin release after 2 days and greater interstitial and sub-endocardial fibrosis at 5 days than did ISO WT. Apoptosis assessed by TUNEL and caspase staining was increased in CIRKO ISO compared to WT ISO hearts; however, very few of the apoptotic nuclei were clearly in cardiac myocytes. After 5 days of ISO treatment, VEGF expression was increased in WT but not in CIRKO hearts. In keeping with this finding, capillary density was reduced in CIRKO ISO relative to WT ISO. Basal expression of hypoxia-inducible factor-1alpha was lower in CIRKO vs. WT hearts and may explain the blunted VEGF response. Thus, absence of insulin receptor signaling in the cardiac myocyte worsens catecholamine-mediated myocardial injury, at least in part, via mechanisms that tend to impair myocardial blood flow and increase ischemic injury.     

Red-cell GSH regeneration and glutathione reductase activity in G6PD variants in the Ferrara area

Summary. Red-cell studies were carried out on three groups of G6PD-deficient subjects with different G6PD variants from the Ferrara area of Northern Italy. Red-cell GSH and activities of G6PD, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were measured. A method was developed to measure red-cell GSH regeneration after oxidation of endogenous GSH in whole blood by diamide and only this clearly distinguished the variants from each other and from normal. Regeneration by 1 h was lowest in the Mediterranean variant, 0–10.2% in contrast to 93–98% in normal. A predisposition to a haemolytic crisis after ingestion of fava beans was not clearcut, but subjects appeared to be at risk if GSH regeneration at 1 h was less than 30% of the endogenous level, and red-cell FAD⁺ was very high indicated by high in vitro GR activity and inhibition by added FAD⁺.
It is suggested that the most informative tests in G6PD deficiency are measurements of GSH regeneration in intact red cells plus GR activity and/or red-cell flavin compounds.     

Clinical audits to improve critical care: Part 2: Analyse,benchmark and feedback

Clinical audits are an essential part of the cycle designed to ensure that patients receive the best quality of care. By measuring the care delivered against established best practice standards, it becomes possible to identify shortcomings and to plan targeted strategies and processes for continuous improvement. The success of a clinical audit depends upon defined goals, motivation of stakeholders, appropriate tools and resources, and clear communication.In part 1 of this series, an overview of the structures and processes needed to prepare and collect data for clinical audits in the critical care setting was provided [A.J. Ullman, G. Ray-Barruel, C.M. Rickard, M. Cooke, Clinical audits to improve critical care: Part 1 Prepare and collect data, Aust Crit Care, 2017, in press]. In part 2, we discuss how to analyse the collected audit data, benchmark findings with internal and external data sets, and feedback audit results to critical care clinicians to promote evidence-based practice and improve patient outcomes.