Comparison of caffeine-induced changes in cerebral blood flow and middle cerebral artery blood velocity shows that caffeine reduces middle cerebral artery diameter

Changes in cerebral blood flow (CBF) can be assessed directly with xenon clearance (XeC) or indirectly by measuring changes in middle cerebral artery blood velocity (Vmca) with transcranial Doppler (TCD). The aim of this study was to compare the changes in CBF and Vmca following caffeine ingestion. Nineteen patients (age 48–86, recovering from an acute stroke) and ten controls (age 52–85) were each studied twice. Bilateral measurements of CBF and Vmca were made before and after ingestion of 250 mg caffeine or matched placebo. The percentage change in CBF and Vmca after caffeine was calculated. Full results (CBF and Vmca) were obtained from 14 patients and 9 controls. There was no significant difference between patients and controls, so results were combined. Caffeine reduced CBF by 22% (95% confidence interval (CI) = 17% to 28%) and reduced Vmca by 13% (95% CI = 10% to 17%). The fall in Vmca was significantly less than that in CBF (p = 0.0016), showing that caffeine reduces mca diameter. Analysis based on Poiseuille flow in the arterioles suggests that caffeine reduced arteriole diameter by 5.9% (95% CI = 4.6% to 7.3%) and mca diameter by 4.3% (95% CI = 2.0% to 6.6%). TCD is being used as an alternative to XeC for assessing the effect of vasoconstrictors and vasodilators on CBF. This study has demonstrated that mca diameter can be changed by the vasoactive agents, and that changes in Vmca do not necessarily reflect changes in CBF

Cerebrovascular mental stress reactivity is impaired in hypertension

<p>Abstract</p> <p>Background</p> <p>Brachial artery reactivity in response to shear stress is altered in subjects with hypertension. Since endothelial dysfunction is generalized, we hypothesized that carotid artery (CA) reactivity would also be altered in hypertension.</p> <p>Purpose</p> <p>To compare (CA endothelium-dependent vasodilation in response to mental stress in normal and hypertensive subjects.</p> <p>Methods</p> <p>We evaluated CA reactivity to mental stress in 10 young healthy human volunteers (aged 23 ± 4 years), 20 older healthy volunteers (aged 49 ± 11 years) and in 28 patients with essential hypertension (aged 51 ± 13 years). In 10 healthy volunteers and 12 hypertensive subjects, middle cerebral artery (MCA) PW transcranial Doppler was performed before and 3 minutes after mental stress.</p> <p>Results</p> <p>Mental stress by Stroop color word conflict, math or anger recall tests caused CA vasodilation in young healthy subjects (0.61 ± 0.06 to 0.65 ± 0.07 cm, p < 0.05) and in older healthy subjects (0.63 ± 0.06 to 0.66 ± 0.07 cm, p < 0.05), whereas no CA vasodilation occurred in hypertensive subjects (0.69 ± 0.06 to 0.68 ± 0.07 cm; p, NS). CA blood flow in response to mental stress increased in young healthy subjects (419 ± 134 to 541 ± 209 ml, p < 0.01 vs. baseline) and in older healthy subjects (351 ± 114 to 454 ± 136 ml, p < 0.01 vs. baseline) whereas no change in blood flow (444 ± 143 vs. 458 ± 195 ml; p, 0.59) occurred in hypertensive subjects. There was no difference in the CA response to nitroglycerin in healthy and hypertensive subjects. Mental stress caused a significant increase in baseline to peak MCA systolic (84 ± 22 to 95 ± 22 cm/s, p < 0.05), diastolic (42 ± 12 to 49 ± 14 cm/s, p < 0.05) as well as mean (30 ± 13 to 39 ± 13 cm/s, p < 0.05) PW Doppler velocities in normal subjects, whereas no change in systolic (70 ± 18 to 73 ± 22 cm/s, p < 0.05), diastolic (34 ± 14 to 37 ± 14 cm/s, p = ns) or mean velocities (25 ± 9 to 26 ± 9 cm/s, p = ns) occurred in hypertensive subjects, despite a similar increase in heart rate and blood pressure in response to mental stress in both groups.</p> <p>Conclusion</p> <p>Mental stress produces CA vasodilation and is accompanied by an increase in CA and MCA blood flow in healthy subjects. This mental stress induced CA vasodilation and flow reserve is attenuated in subjects with hypertension and may reflect cerebral vascular endothelial dysfunction. Assessment of mental stress induced CA reactivity by ultrasound is a novel method for assessing the impact of hypertension on cerebrovascular endothelial function and blood flow reserve.</p

A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer. Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib. Results: LVEF (SD) mean change from baseline was -0.8 ($\pm$8.6) LVEF(%) after 2 cycles (n=31) and -1.2 $\pm$7.8) LVEF(%) after 4 cycles of sorafenib (n=24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations ($t_{max}$) after 1 cycle (n=31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n=31) and HR (n=30) at maximum sorafenib concentrations ($t_{max}$) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and ($C_{max}$) of sorafenib and its main metabolites and any cardiovascular parameters. Conclusions: The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment

Efficacité et sélectivité de graminicides pour le dégagement de jeunes peuplements forestiers

The authors pinpoint the interest of fighting against graminaceous plants in forests. Results of experiments conducted in various conditions, using seven foliar graminicides, indicate a good selectivity on ten forest species. It is difficult to classify the different foliar active ingredients but these herbicides are less powerful and less persistent than four other root products also on trial. These differences are accounted for in a use stragegy. / Les auteurs exposent l'intérêt de la lutte contre les graminées en forêt. Les résultats d'expériences mises en place dans des situations variées avec sept graminicides foliaires font ressortir une sélectivité rassurante sue dix essences forestières. Il est difficile d'établir un classement entre les matières actives foliaires mais ces herbicides sont moins brutaux et moins persistants que les quatre produits racinaires essayés en parallèle. Ces différences sont exploitées dans une stratégie d'emploi

Multi-Objective Design Optimisation of a Diffuser-Ejector Exhaust Duct for Helicopter Engines

The paper demonstrates the successful application of an optimisation methodology for the design of a diffuser-ejector exhaust duct. Maximising simultaneously pressure recovery and the entrainment ratio are diverging objectives which could hardly be achieved by a conventional manual trial-and-error approach relying on the designer’s experience. This multi-objective design problem has been solved for the axis-symmetric exhaust duct with a given characteristic length, inlet section and minimal standoff distance by coupling a parametric method with 2D CFD analysis. Open cubic B-splines have been employed to generate the contoured duct shape, for which the control-point vertices have been defined by a total of 17 engineering parameters. A bell mouth inlet has been chosen for the ejector inlet. The parameter constraints result from weight and integration requirements. Three characteristic engine operating points have been chosen for the multi-point and multi-objective shape optimisation. The entire process of model building, meshing, performing the 2D CFD calculation and post-processing to extract the required metrics has been fully automated. A commercial process integration software package is used to link the different tools together in a unified environment. The design space exploration is carried out via a latin-hypercube sampling technique. This random space filling method has been chosen because of its considerable lower number of experiments compared to factorial sampling techniques. Parameter ranking is obtained by a weighted average of the correlation coefficients for each objective. The parameter hierarchy is slightly different for the engine operating points. However, there exists a clear threshold separating the influential parameters from the insignificant ones. A subsequent DOE is performed for the reduced parameter set for which the minimum number of experiments has been chosen as twice the number of experiments to generate a quadratic response surface. The Normal-Boundary Intersection method is applied to find the Pareto front based on the response surface model as surrogate model. The results show that a gain of 20% for the pressure recovery for a given entrainment ratio could be achieved compared to a configuration defined by a manual trial-and-error approach. The great benefit of the present method is its capability to handle easily geometrical constraints and the weight of the different design objectives which may change even during the detailed design phase.</jats:p

Effects of a single oral dose of sparfloxacin on ventricular repolarization in healthy volunteers

1Sparfloxacin, a new fluoroquinolone, slightly increases the duration of the QT interval. Reverse rate-dependence of QT interval prolongation has been shown for many agents that are known to prolong QT interval duration, and QT prolongation at slow heart rates may be a risk factor for torsades de pointes