Comment: Applications of robotics in the clinical laboratory

The implementation of a robotic workstation in the clinical laboratory involves considerations and compromises common to any instrument design and development activity. The trade-off between speed and flexibility not only affects the way the instrument interacts with human operators and other devices (the ‘real-world interface’), but also places limitations on the adaptation of chemistries to the given instrument. Mechanical optimization for speed and reproducibility places restrictions on the imprecision of consumables. Attempts to adapt a robot to a constrained system may entail compromises that either degrades the theoretically-attainable quality of results, or requires human interaction to compensate for physical or mechanical limitations. The general considerations of function and workflow, programming and support, and reliability place practical limits on the implementation of robotic workstations in the clinical laboratory

Indirect Ultraviolet Detection of Biologically Relevant Organic Acids by Capillary Electrophoresis

Indirect UV detection of fourteen short-chain organic acids (e.g., oxalic acid, citric acid, malonic acid, tartaric acid, methylmalonic acid, α-ketoglutaric acid, succinic acid, ethylmalonic acid, methylsuccinic acid, glutaric acid, apidic acid, methylglutaric acid, lactic acid and pyruvic acid) by capillary electrophoresis is described. The method used phthalate as the UV-absorbing additive in carbonate buffer and the non-absorbing analytes were detected indirectly at 230 nm. The influences of buffer pH, ionic strenght, concentration of phthalate and organic modifier on indirect signal response and migration behavior of the organic acids were investigated. Comparisons of reproducibility on migration time, limit of detection and separation efficiency among three types of capillary (e.g., polyacrylamide-coated, myristyltrimethylammonium bromide-coated and uncoated capillaries) were conducted. The method developed was applied to detect succinic acid, methylmalonic acid, citric acid, glutaric acid and lactic acid in human body fluids, and preliminary results were provided

Cardiac troponins in renal insufficiency Review and clinical implications

AbstractPatients with renal insufficiency may have increased serum troponins even in the absence of clinically suspected acute myocardial ischemia. While cardiovascular disease is the most common cause of death in patients with renal failure, we are just beginning to understand the clinical meaning of serum troponin elevations. Serum troponin T is increased more frequently than troponin I in patients with renal failure, leading clinicians to question its specificity for the diagnosis of myocardial infarction. Many large-scale trials demonstrating the utility of serum troponins in predicting adverse events and in guiding therapy and intervention in acute coronary syndromes have excluded patients with renal failure. Despite persistent uncertainty about the mechanism of elevated serum troponins in patients with reduced renal function, data from smaller groups of renal failure patients have suggested that troponin elevations are associated with added risk, including an increase in mortality. It is possible that increases in serum troponin from baseline in patients with renal insufficiency admitted to hospital with acute coronary syndrome may signify myocardial necrosis. Further studies are needed to clarify this hypothesis

Detection of Soluble Angiotensin-Converting Enzyme 2 in Heart Failure Insights Into the Endogenous Counter-Regulatory Pathway of the Renin-Angiotensin-Aldosterone System

ObjectivesWe sought to determine whether circulating soluble angiotensin-converting enzyme 2 (sACE2) is increased in the plasma of patients with heart failure (HF).BackgroundAngiotensin-converting enzyme 2 (ACE2) is an integral membrane protein that antagonizes the actions of angiotensin II and prevents the development of HF in animal models. However, because of the need for invasive cardiac tissue sampling, little is known about whether ACE2 is involved in the pathophysiology of HF in humans.MethodsWe developed a sensitive and specific assay to measure sACE2 activity in human plasma and screened a heterogeneous group of patients suspected of having clinical HF.ResultsIncreasing sACE2 plasma activity strongly correlated with a clinical diagnosis of HF (p = 0.0002), worsening left ventricular ejection fraction (p < 0.0001), and increasing B-type natriuretic peptide levels (p < 0.0001). Similar to B-type natriuretic peptide, sACE2 activity reflected the severity of HF, with increasing levels associated with worsening New York Heart Association functional class (p < 0.0001). These associations were independent of other disease states and medication use. We found that sACE2 activity was increased in patients with both ischemic and nonischemic cardiomyopathies and also in patients with clinical HF but a preserved left ventricular ejection fraction.ConclusionsSoluble ACE2 activity is increased in patients with HF and correlates with disease severity, suggesting that a cardioprotective arm of the renin-angiotensin-aldosterone system is active in HF

Subclinical Myocardial Necrosis and Cardiovascular Risk in Stable Patients Undergoing Elective Cardiac Evaluation

Objective— The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, “troponin leak”) within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function. Methods and Results— Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m2) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (\u3c0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. “Probable” (cTnI 0.001–0.008 ng/mL) and “definite” (cTnI 0.009–0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4–3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin; P\u3c0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase; P\u3c0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline associations with myeloperoxidase, a marker of leukocyte activation. Conclusion— In stable cardiology patients, prodromal subclinical myocardial necrosis is associated with substantially higher long-term risk for major adverse cardiovascular events. The underlying mechanisms contributing to this minimal troponin leak phenomenon warrants further investigation

Subclinical Myocardial Necrosis and Cardiovascular Risk in Stable Patients Undergoing Elective Cardiac Evaluation

Objective— The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, “troponin leak”) within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function. Methods and Results— Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m2) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (\u3c0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. “Probable” (cTnI 0.001–0.008 ng/mL) and “definite” (cTnI 0.009–0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4–3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin; P\u3c0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase; P\u3c0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline associations with myeloperoxidase, a marker of leukocyte activation. Conclusion— In stable cardiology patients, prodromal subclinical myocardial necrosis is associated with substantially higher long-term risk for major adverse cardiovascular events. The underlying mechanisms contributing to this minimal troponin leak phenomenon warrants further investigation

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation