Emma Southcott

Cardiac troponin may be released by ischemia alone, without necrosis.

Whilst it is formally stated that cardiac troponin is only released when cardiac myocytes undergo necrosis, there are a number of clinical situations where troponin is present in the circulation, without any apparent cardiac injury. In these cases, troponin half-life in the circulation is usually substantially shorter than that seen when troponin is released following myocardial infarction with frank necrosis. A mechanism has been described in liver, where large cytoplasmic molecules can pass from the intra- to extra-cellular space without cellular necrosis occurring. This occurs by the formation of membranous blebs which bud off from the plasma membrane of the cell. Blebs develop during cellular ischemia. If the ischemia is limited and re-oxygenation occurs, the blebs may be released into the circulation without rupture of the plasma membrane, resulting in a one-off release of cytoplasmic contents including macromolecules. Evidence from cardiac studies is presented supporting the presence of membranous blebs in cardiac myocytes, enabling troponin to be released from cardiac cells due to ischemia alone, without necrosis.

Establishment of pediatric reference intervals on a large cohort of healthy children

BACKGROUND Reference intervals are essential in assessing the significance of laboratory results. There have been limited studies generating reference intervals from pediatric populations. We have studied a large cohort of healthy children on 3 separate occasions at 2yearly intervals. METHODS 852 healthy 8year old children were enrolled in a community-based multidisciplinary longitudinal study investigating how early physical activity contributes to health. The same children came back for reassessment at ages 10 and 12years. Blood samples were analyzed for a total of 37 different chemistries, immunoassays or derived values. RESULTS Reference intervals were derived for all the analytes for males and females separately. CONCLUSION Whilst our results are largely in agreement with previously published work, we have shown that for a number of analytes, previously published work is distorted by subclinical disease.

Prognostic efficacy of cardiac biomarkers for mortality in dialysis patients

Background: The high prevalence of cardiovascular mortality in the end‐stage renal disease population is well established. The aim of this current study was to document the relative prognostic significance of established cardiac biomarkers troponin T (TnT), troponin I (TnI), B‐type natriuretic peptide (BNP) and N‐terminal pro‐BNP (NT‐pro‐BNP) in this population.

Newer cardiac troponin I assays have similar performance to troponin T in patients with end-stage renal disease

Background: Troponin T is present in the blood of a majority of patients with endstage renal disease (ESRD) undergoing regular dialysis and presence of troponin T is a predictor of adverse outcome in these patients. With several new formulations of troponin I assays available, this study was performed to see whether these newer assays were able to detect troponin I in these patients more effectively than the older assays. Methods: One hundred and forty-three patients undergoing regular haemodialysis or peritoneal dialysis had plasma collected and troponin T and troponin I measured by a variety of assays. Results: The newer troponin I assays (Abbott Architect, Bayer Centaur and Beckman Accu-TnI) were able to detect troponin I (>75% of samples) as effectively as the Roche assay was able to detect troponin T, while other troponin I assays had a much lower rate of detection of troponin - DPC Immulite 2000 16% and Abbott AxSYM 35%. However, the troponin T assay had more samples detected at concentrations corresponding to an assay CV of 10% (59% of samples) than did the newer troponin I assays (highest on the Bayer Centaur at 37%). Conclusions: Newer assays demonstrate that troponin I is present in a similar number of samples as is troponin T, in the blood of patients with dialysis-dependent renal failure, and these newer troponin I assays identify patients at risk of experiencing a cardiac event.

Pharmacokinetics of Digoxin Cross-Reacting Substances in Patients With Acute Yellow Oleander (Thevetia peruviana) Poisoning, Including the Effect of Activated Charcoal

Intentional self-poisonings with seeds from the yellow oleander tree (Thevetia peruviana) are widely reported. Activated charcoal has been suggested to benefit patients with yellow oleander poisoning by reducing absorption and/or facilitating elimination. Two recent randomized controlled trials (RCTs) assessing the efficacy of activated charcoal yielded conflicting outcomes in terms of mortality. The effect of activated charcoal on the pharmacokinetics of Thevetia cardenolides has not been assessed. This information may be useful for determining whether further studies are necessary. Serial blood samples were obtained from patients enrolled in an RCT assessing the relative efficacy of single-dose and multiple-dose activated charcoal (SDAC and MDAC, respectively) compared with no activated charcoal (NoAC). The concentration of Thevetia cardenolides was estimated with a digoxin immunoassay. The effect of activated charcoal on cardenolide pharmacokinetics was compared between treatment groups by determining the area under the curve for each patient in the 24 hours following admission, the 24-hour mean residence time, and regression lines obtained from serial concentration points, adjusted for exposure. Erratic and prolonged absorption patterns were noted in each patient group. The apparent terminal half-life was highly variable, with a median time of 42.9 hours. There was a reduction in 24-hour mean residence time and in the apparent terminal half-life estimated from linear regression in patients administered activated charcoal, versus the control group (NoAC). This effect was approximately equal in patients administered MDAC or SDAC. Activated charcoal appears to favorably influence the pharmacokinetic profile of Thevetia cardenolides in patients with acute self-poisoning and may have clinical benefits. Given the conflicting clinical outcomes noted in previous RCTs, these mechanistic data support the need for further studies to determine whether a particular subgroup of patients (eg, those presenting soon after poisoning) will benefit from activated charcoal.

Contrasting longitudinal and cross-sectional relationships between insulin resistance and percentage of body fat, fitness, and physical activity in children-the LOOK study.

Background: Knowledge of individual changes in insulin resistance (IR) and longitudinal relationships of IR with lifestyle‐associated factors are of important practical significance, but little longitudinal data exist in asymptomatic children. We aimed to determine (a) changes in the homeostatic model of insulin resistance (HOMA‐IR) over a 2‐yr period and (b) comparisons of longitudinal and cross‐sectional relationships between HOMA‐IR and lifestyle‐related risk factors.

Serum resistin in older patients with hip fracture: Relationship with comorbidity and biochemical determinants of bone metabolism.

OBJECTIVES To determine the relationship of serum resistin concentrations to biochemical determinants of bone metabolism, comorbidity and outcomes in patients with hip fracture (HF). METHODS In 256 consecutive patients (mean age 81.9±7.8 years; 71.1% women) serum levels of resistin (determined by ELISA), biochemical parameters of bone turnover and mineral metabolism as well as routine haematological and biochemical parameters were measured. Clinical data were recorded prospectively. RESULTS In multivariate analysis cervical HF (OR=1.81; 95% CI 1.05-3.11), diabetes (OR=2.60; 95% CI 1.23-5.51) and history of stroke (OR=2.67; 95% CI 1.17-6.13) were significant independent predictors of higher resistin levels (≥16.26 ng/ml, median value). The independent correlates of serum resistin levels in patients with cervical HF were serum osteocalcin and magnesium (both negatively associated) and in patients with trochanteric HF, serum PTH, calcium and age (all positively associated). Resistin and glomerular filtration rate were the only independent (inverse) predictors of serum osteocalcin. Resistin levels on admission did not predict short-term outcomes. CONCLUSIONS In older patients with HF there is a significant association of higher resistin levels with cervical fracture, type 2 diabetes and history of stroke, which is partly influenced by the reciprocal interaction between resistin and osteocalcin. However, the design of the study does not prove causality and further prospective studies are needed to clarify these relationships.

Iodine deficiency in pregnant women in the ACT

In response to growing concern of an iodine deficiency emergence in Australia, this study was conducted to document the iodine status of pregnant women in the ACT. One hundred women presenting to the antenatal clinic at The Canberra Hospital answered a brief dietary questionnaire and provided a spot urine sample for the measurement of urine iodine excretion. The results revealed that the majority of women were consuming a diet low in iodine, confirmed by suboptimal concentrations of iodine in their urine.

Cross-sectional study of high-sensitivity cardiac troponins T and I in a hospital and community outpatient setting

OBJECTIVES Cardiac troponins are specific for the heart, but not for the acute coronary syndrome. We wanted to assess how common elevated cardiac troponin concentrations were, in a population with significant non-cardiac disease. DESIGN & METHODS We measured both hs-cTnT and hs-cTnI on all samples submitted to the laboratory during one 24h period, and assessed the magnitude of the cTn concentration with the location and severity of disease of the patient. RESULTS Community patients and patients from the maternity ward had the lowest cTn concentrations with results above the 99th percentile being only 0-2% of the total. As expected, the highest proportion of results >99th percentile came from Coronary Care and Intensive Care. However, substantial numbers of persons on Medical and Surgical wards, without a primary diagnosis of cardiac disease, also had cTn >99th percentile. Particularly for cTnT, there was a highly significant odds ratio predicting mortality when results above and below the 99th percentile were compared. CONCLUSIONS Significant illnesses apart from the acute coronary syndrome are important causes of a rise in cTn to above the 99th percentile, and appear to reflect the total body burden of disease. Even when the high hs-cTn concentration is not due to the acute coronary syndrome, there is a significant association with all-cause mortality.