BackgroundThe removal of the flattening filter (FF) leads to non-uniform fluence distribution with a considerable increase in dose rate. It is possible to adapt FFF beams (flattening-filter-free) in 3D conformal radiation therapy (3D CRT) by using field in field techniques (FiF). The aim of this retrospective study is to clarify whether the quality of 3D CRT plans is influenced by the use of FFF beams.MethodThis study includes a total of 52 CT studies of RT locations that occur frequently in clinical practice. Dose volume targets were provided for the PTV of breast (n=13), neurocranium (n=11), lung (n=7), bone metastasis (n=10) and prostate (n=11) in line with ICRU report 50/62. 3D CRT planning was carried out using FiF methods. Two clinically utilized photon energies are used for a Siemens ARTISTE linear accelerator in FFF mode at 7MVFFF and 11MVFFF as well as in FF mode at 6MVFF and 10MVFF. The plan quality in relation to the PTV coverage, OAR (organs at risk) and low dose burden as well as the 2D dosimetric verification is compared with FF plans.ResultsNo significant differences were found between FFF and FF plans in the mean dose for the PTV of breast, lung, spine metastasis and prostate. The low dose parameters V5Gy and V10Gy display significant differences for FFF and FF plans in some subgroups. The DVH analysis of the OAR revealed some significant differences. Significantly more fields (1.9 – 4.5) were necessary in the use of FFF beams for each location (p<0.0001) in order to achieve PTV coverage. All the tested groups displayed significant increases (1.3 – 2.2 times) in the average number of necessary MU with the use of FFF beams (p<0.001).ConclusionsThis study has shown that the exclusive use of a linear accelerator in FFF mode is feasible in 3D CRT. It was possible to realize RT plans in comparable quality in typical cases of clinical radiotherapy. The 2D dosimetric validation of the modulated fields verified the dose calculation and thus the correct reproduction of the characteristic FFF parameters in the planning system that was used.
The blocker of receptor-mediated calcium entry SK&F 96365 was used to evaluate the contribution of calcium influx to the formation of biologically active endothelial prostanoids and endothelium-derived relaxing factor (EDRF). SK&F 96365 inhibited histamine-stimulated calcium entry into human umbilical vein endothelial cells but not its discharge from intracellular stores as determined spectrofluorometrically by changes of intracellular calcium concentration in fura-2-loaded cells. Concordantly, SK&F 96365 inhibited histamine-induced endothelial synthesis of 6-keto-prostaglandin F la and thromboxane B, in a dose-dependent manner. To assess the functional significance of endothelial formation of prostacyclin and EDRF to platelets, the cAMP-and cGMPdependent phosphorylation of two platelet proteins, raplB and a 50-kD vasodilator-stimulated phosphoprotein (VASP), was analyzed in coincubation experiments of endothelial cells with platelets. Autacoids released by histamine-stimulated E ndothelium-derived autacoids are crucial for the maintenance of local vascular homeostasis and endothelium-platelet interactions. Endothelial cells (ECs) respond to hormonal, chemical, and physical stimuli with the generation and release of prostacyclin and endothelium-derived relaxing factor (EDRF; nitric oxide or nitric oxide-releasing compounds), both of which are known to dilate vessels and inhibit platelet function in a paracrine manner. 15 Concomitantly, ECs also release the potent vasoconstrictor and stimulator of platelet aggregation thromboxane A 2 (TXA 2 ).6 ' 7The increase of cytosolic calcium concentration ([Ca 2+ ],), a key step in the stimulus-response coupling of ECs, leads to the activation of calcium-dependent enzymes such as phospholipase A 2 and nitric oxide synthase. 89 A variety of blood-borne mediators interact with endothelial surface receptors and raise [Ca 2+ ], by both inducing second messenger-mediated discharge of calcium from internal stores and promoting influx from the extracellular milieu.1 Calcium entry into nonexcitable cells occurs voltage independently via receptorcoupled channels of the plasma membrane that are not well characterized.
10Formation and release of EDRF and prostanoids by the vascular endothelium are coupled to an increase in Received May 31, 1994; accepted Jury 25, 1994. From the Institut fur Prophylaxe und Epidemiologie der Kreislaufkrankheiten, University of Munich, FRG.Correspondence to H.-J. Kruse, Institut fur Prophylaxe und Epidemiologie der Kreislaufkrankheiten, UniversitSt Munchen, Pettenkoferstr 9, 80336 Munchen, Germany.O 1994 American Heart Association, Inc.endothelial cells caused the phosphorylation of rap IB and VASP in platelets, which was only partly inhibited by either indomethacin or A r°-monomethyl-L-arginine but was almost completely suppressed by SK&F 96365. The concomitant endothelial release of thromboxane A 2 had no effect on protein kinase C-and calcium-dependent phosphorylation of platelet proteins. The results demonstrate that blockade of recepto...
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