Comparison of Pipeline Embolization Device Sizing Based on Conventional 2D Measurements and Virtual Simulation Using the Sim&Size Software: An Agreement Study.

BACKGROUND AND PURPOSE: The Sim&Size software simulates case-specific intraluminal Pipeline Embolization Device behavior, wall apposition, and device length in real-time on the basis of rotational angiography DICOM data. The purpose of this multicenter study was to evaluate whether preimplantation device simulation with the Sim&Size software results in selection of different device dimensions than manual sizing. MATERIALS AND METHODS: In a multicenter cohort of 74 patients undergoing aneurysm treatment with the Pipeline Embolization Device, we compared apparent optimal device dimensions determined by neurointerventionalists with considerable Pipeline Embolization Device experience based on manual 2D measurements taken from rotational angiography with computed optimal dimensions determined by Sim&Size experts blinded to the neurointerventionalists' decision. Agreement between manually determined and computed optimal dimensions was evaluated with the Cohen κ. The significance of the difference was analyzed with the Wilcoxon signed rank test. RESULTS: The agreement index between manual selection and computed optimal dimensions was low (κ for diameter = 0.219; κ for length = 0.149, P < .01). Computed optimal device lengths were significantly shorter (median, 14 versus 16 mm, T = 402, r = -0.28, P < .01). No significant difference was observed for device diameters. CONCLUSIONS: Low agreement between manually determined and computed optimal device dimensions is not proof, per se, that virtual simulation performs better than manual selection. Nevertheless, it ultimately reflects the potential for optimization of the device-sizing process, and use of the Sim&Size software reduces, in particular, device length. Nevertheless, further evaluation is required to clarify the impact of device-dimension modifications on outcome.

Lonidamine cytotoxicity: involvement of the lysosomal compartment.

Lonidamine (LND) was found to decrease significantly the pH gradient across intracellular compartments in Ehrlich ascites tumour cells. The effect was maximal in the range 0.2 - 0.3 mM LND, and was observed both in the presence of glucose - i.e. conditions in which a high bioenergetic status of the cells was maintained by glycolysis (due to a strong Crabtree effect in these cells) - and in the absence of glucose. Moreover the LND effect was also observed in the presence of bafilomycin, a specific inhibitor of the H+ -vacuolar ATP-ase. Based on these findings, we suggest that the LND effect on the proton gradient reflects an LND-induced increase in membrane proton conductance. The consequent impairment of intracellular proton gradients might be involved in the mechanism of action of LND, allowing drugs that are weak bases to accumulate preferentially in the cytoplasm and nucleus.

The antineoplastic drug lonidamine interferes with the acidification mechanism of cell organelles.

The effect of the anticancer drug lonidamine (LND) on the pH of intracellular organelles was studied in isolated rat thymocytes by fluorimetric analysis of the (bafilomycin-nigericin sensitive) uptake of the acridine orange dye (AO) into acidic compartments. LND brought about a marked reduction (> 60%) in the above pH gradients with a half maximal decrease at a concentration of 0.25 mM. LND also caused a decrease, although to a lesser extent, in the ATP levels. In isolated rat liver lysosomes, 0.6 mM LND was found to inhibit ATP-driven organelle acidification by about 80%; minor inhibition of ATPase activity was observed in the same conditions. In addition, LND was able to promote proton efflux from isolated lysosomes. On the basis of our results it is suggested that the effect of LND on intracellular proton gradients may be due partially to the decrease in ATP levels, and mostly to a drug-induced increase in the ion (proton) permeability of the membranes.