Virtual fractional flow reserve by coronary computed tomography - hope or hype?

Studies evaluating the diagnostic performance of coronary computed tomography angiography (CTA) are consistent in demonstrating a high negative predictive accuracy, but only a modest positive predictive accuracy for the detection of significant coronary artery disease. Consequentially, there has been a considerable effort made to enhance the diagnostic capability of coronary CTA by developing scanner technology and also post-processing algorithms for coronary stenosis evaluation. Of these new developments, the proposition of being able to measure non-invasive fractional flow reserve by coronary computed tomography angiography (FFRct) has generated much recent interest. Initial reports indicate that the application FFRct not only correlates well with invasive fractional flow reserve but also has the potential to enhance substantially the positive predictive accuracy and overall accuracy of coronary CTA. Although it is theoretically possible to measure FFRct using complex computational fluid dynamics adapted from the aeronautical industry, this approach is likely to face a number of challenges prior to it being accepted into the mainstream as an adjunct to coronary CTA. The aim of the current review is to provide an overview of: 1) the fundamental engineering principles behind computational fluid dynamic modelling of coronary arterial blood flow; 2) the difficulties faced from an engineering perspective in developing a truly representative model; and 3) the challenges this technology is likely to face as it attempts to enter the clinical domain.

Effects of CD25 monoclonal antibody on proliferative and effector functions of alloactivated human T cells in vitro.

Prophylactic treatment with CD25 mAb has led to a significant decrease of acute rejection rates after renal transplantation. However, despite its inhibitory effect on T cell proliferation and effector functions, rejections still occur. To obtain more insight in persistent alloreactivity, we evaluated the effects of the chimeric IgG1kappa CD25 mAb Basiliximab on proliferation and differentiation of alloactivated T cells from healthy individuals in vitro. Moreover, the capacity of other members of the common cytokine-receptor gamma-chain family to overcome the inhibitory effects of CD25 mAb was studied. The CD25 mAb appeared to limit expansion of alloreactive lymphocytes rather than blocking entry into cell cycle, and it did so irrespective of the previous antigen experience of the cells. Both CD4+ and CD8+ alloresponsive lymphocytes showed diminished intracellular expression of IFN-gamma, TNF-alpha, perforin and granzyme B. Remarkably, cytotoxicity was completely abolished. IL-7, IL-15 and IL-21 could bypass the inhibitory effects of the CD25 mAb on both proliferation and cytotoxicity. In conclusion, persistent alloreactivity in the presence of therapeutic concentrations of CD25 mAb may be caused by alloreactive T cells that still produce cytokines that can damage the allograft. In addition, other members of the common cytokine-receptor gamma-chain family can rescue the proliferative and cytotoxic activity of these alloreactive T cells.