ABSTRACT
BACKGROUND: Cardiothoracic ratio (CTR) in chest radiographs is still widely used to estimate cardiac size despite the advent of newer imaging techniques. We hypothesise that a universal CTR cut-off value of 50% is a poor indicator of cardiac enlargement. Our aim was to compare CTR with volumetric and functional parameters derived from cardiac magnetic resonance imaging (MRI). METHODS: 309 patients with a chest radiograph and cardiac MRI acquired within a month were reviewed to assess how CTR correlates with multiple cardiac MRI variables: bi-ventricular EDV (absolute and indexed to body surface area), EF, indexed total heart volume and bi-atrial areas. In addition, we have also determined CTR accuracy by creating multiple ROC curves with the described variables. RESULTS: All cardiac MRI variables correlate weakly but statistically significantly with CTR. This weak correlation is explained by a substantial overlap of cardiac MRI parameters in patients with normal and increased CTR. For all variables, CTR was only mildly to moderately better than a chance to discriminate cardiac enlargement (AUC 0.6-0.7). Large CTR values (> 55%) are specific but not sensitive, while low CTR values (< 45%) are sensitive but not specific. Values in between are not sensitive nor specific. CONCLUSIONS: CTR correlates weakly with true chamber size assessed by gold standard cardiac MRI and has a weak discriminatory power. Thus, clinical decisions based on intermediate CTRs (45-55%) should be avoided. Large CTRs (> 55%) are likely indicative of true heart chamber enlargement. Low CTRs (< 45%) are likely indicative of normal heart size.
ABSTRACT
In the epidermis, local and systemic factors including extracellular nucleotides and parathyroid hormone-related protein (PTHrP) regulate keratinocyte proliferation and differentiation. Extracellular nucleotides increase proliferation via activation of P2 receptors and induction of calcium transients, while endoproteases cleave PTHrP, resulting in fragments with different cellular functions. We investigated the effects of adenosine 5'-triphosphate (ATP) alone and in combination with synthetic PTHrP peptides on calcium transients in HaCaT cells. ATP induced calcium transients, while PTHrP peptides did not. C-terminal and mid-molecule PTHrP peptides (1-100 pM) potentiated ATP-induced calcium transients independently of calcium influx. 3-Isobutyl-1-methylxanthine potentiated ATP-induced calcium transients, suggesting that a cyclic monophosphate is responsible. Cyclic AMP is not involved, but cyclic GMP is a likely candidate since the protein kinase G inhibitor, KT5823, inhibited potentiation. Co-stimulation with ATP and either PTHrP (43-52) or PTHrP (70-77) increased proliferation, suggesting that this is important in the regulation of cell turnover and wound healing and may be a mechanism for hyperproliferation in skin disorders such as psoriasis. Finally, PTHrP fragments potentiated bradykinin-induced calcium transients, suggesting a role in inflammation in the skin. Since PTHrP is found in many normal and malignant cells, potentiation is likely to have a wider role in modulating signal transduction events.
