Efficacy of a therapeutic treatment using gas-filled microbubble-associated phospholipase A2 in a mouse model of honeybee venom allergy.

BACKGROUND: Venom immunotherapy is efficient to desensitize people suffering from insect sting allergies. However, the numerous injections required over several years and important risks of severe side reactions complicate the widespread use of immunotherapy. In the search for novel approaches to blunt the overwhelming pro-allergic Th2 response, we evaluated the therapeutic efficacy of a treatment based on a denatured form of the major allergen, phospholipase A2, associated with microbubbles (PLA2denat -MB) in a mouse model of honeybee venom allergy. METHODS: Antibodies measured by ELISA, T-cell responses assessed by CFSE-based proliferation assays and ELISA, and basophil degranulation were examined after PLA2denat -MB-based therapeutic treatment of sensitized mice. Mice were challenged with a lethal dose of PLA2 to evaluate protection against anaphylaxis. RESULTS: Therapeutic subcutaneous administration of two different PLA2denat -MB formulations, in contrast to PLA2denat alone, reduced allergic symptoms and protected all mice from anaphylaxis-mediated death after allergen challenge. At the functional level, the use of PLA2denat decreased IgE-mediated basophil degranulation as compared to the native form of the allergen. In comparison with PLA2denat alone, both PLA2denat -MB formulations decreased allergen-specific Th2 CD4 T-cell reactivity. At the mechanistic level, PLA2denat -MB containing 20% palmitic acid and PEG induced PLA2-specific IgA and increased Foxp3(+) Treg frequencies and TGF-ß production, whereas the formulation bearing 80% palmitic acid triggered the production of IFN-γ, IgG2a, and IgG3. CONCLUSIONS: In contrast to conventional PLA2 subcutaneous immunotherapy, the therapeutic administration of PLA2-MB treatment to mice that already had established allergy to PLA2 protects all subsequently challenged animals.

[Pulsed transcranial Doppler examination in the acute phase of stroke]. / Le Doppler pulsé transcrânien à la phase aiguë de l'infarctus cérébral.

INTRODUCTION: Transcranial pulsed Doppler sonography with or without imagery is used in the acute phase of ischemic stroke in order to define stroke mechanism and intracranial hemodynamic consequences. STATE OF ART: This non-invasive low-cost investigation can be undertaken rapidly, within 10 minutes if guided by focal symptomatology. It detects middle cerebral artery stenosis in >or=50 p. cent of cases with a sensitivity between 75 and 90 p. cent, comparatively with conventional angiography, and middle cerebral artery occlusion with 90 p. cent sensitivity. When a temporal acoustic window is lacking, intravenous injection of a contrast agent allows good visualization of the intracranial vessels and the circle of Willis, in two-third of cases. Moreover, transcranial Doppler data have good prognostic value and facilitate analysis of recanalization after thrombolytic therapy. CONCLUSION: Beside its diagnostic and prognostic interest, transcranial Doppler sonography using a 2 MHz frequency appears to have therapeutic impact by favoring the thrombolysis process. Future developments may include early and prolonged insonation of patients suffering from stroke.

Localization of the ventricular preexcitation site in Wolff-Parkinson-White syndrome with Doppler tissue imaging.

PURPOSE: The objective of this study was to evaluate the ability of Doppler tissue imaging (DTI) to localize the ventricular emergence site of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome). METHODS: Thirty-three patients were studied prospectively by Doppler tissue imaging (128XP and Sequoia 256 echocardiographic systems; Acuson, Mountain View, Calif) before investigation of Wolff-Parkinson-White syndrome and after radiofrequency ablation of the accessory pathways. The normal appearance of the ventricular contractions was defined in a group of 10 control subjects. The preexcitation zone was determined as a zone of maximum acceleration in "DTI acceleration mode" or as a coded contraction zone in "DTI velocity mode," at the time of the delta wave or before the onset of the QRS complex. RESULTS: The earliest ventricular activation site was correctly localized for 12 of the 15 left-sided pathways (8 anterior or anterolateral, 2 lateral or posterolateral, 2 inferior). When wall motion abnormalities were detected in the left ventricle by DTI, the left-sided localization was confirmed by electrophysiologic exploration. For the right-sided pathways, the localization was correct in only 4 of 11 cases (3 posteroseptal and 1 anterolateral). After effective ablation in all patients, the abnormalities corresponding to the electrophysiologic data disappeared totally in only 11 of 16 patients. CONCLUSION: In the presence of Wolff-Parkinson-White syndrome, DTI localizes contraction abnormalities associated with early activation of a part of the ventricle. However, the interpretation of the images remains difficult because the normal coding of the contraction of the ventricular walls depends on the incidence for which they are investigated. This noninvasive examination seems to be an effective tool for localizing the left-sided accessory pathways of the left ventricle, in particular in the anterior, anterolateral, or inferior walls.

Effects of the method of drawing regions of interest on the differential diagnosis of extrapyramidal syndromes using 123I-iodolisuride SPET.

Various parameters are currently used for the semi-quantitative assessment of dopamine D2 receptors and differ according to the delineation of the striatal region of interest (ROI) and the choice of the reference ROI. The aim of this study was to assess the value of different ROI approaches in differentiating patients with normal or increased numbers of D2 dopamine receptors (group 1 = Parkinson's disease, n = 8) from patients with decreased dopamine D2 receptors (group 2 = other extrapyramidal syndromes, n = 9) using 123I-iodolisuride SPET (ILIS-SPET). 123I-iodolisuride (190 +/- 31 MBq) and 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) perfusion SPET were performed in the same position, with a dual-headed gamera camera equipped with fan beam collimators. Both a geometric approach (ellipse, circle or rectangle) and an anatomical approach using the CT scan and perfusion SPET as anatomical guides were used to draw striatal and reference ROIs. A total of 33 different parameters were calculated for each patient, indicating the ratio of counts between the striatal and reference ROIs (frontal, occipital cortex or cerebellum) and the asymmetry between the right and left striatum. More significant differences between group 1 and group 2 were found by using geometric ROIs than by using anatomical ROIs. The most discriminant ratios were the caudate/occipital, caudate/frontal and striatum/occipital ratios (P = 0.001, P = 0.002, P = 0.003 respectively). A close correlation was found between the striatum/caudate and striatum/occipital ratios, but not between the striatum/frontal and striatum/occipital ratios or between the striatum/frontal and striatum/caudate ratios. We conclude that the occipital cortex is the best reference for the semi-quantitative evaluation of dopamine D2 receptors as the frontal cortex could include some dopamine D2 receptor-bound radioligand, and that the caudate/occipital ratio is an appropriate parameter for differentiating Parkinson's disease from non-Parkinson extrapyramidal syndrome by 123I-iodolisuride SPET.

[Nuclear magnetic resonance spectroscopy: methodology and applications to the study of asphyxia neonatorum]. / La spectroscopie par résonance magnétique nucléaire: méthodologie et applications à l'étude de l'asphyxie périnatale.

Cerebral metabolism has been extensively studied by magnetic resonance spectroscopy (MRS). MRS allows the study of neonates brain maturation as well as the onset and the evolution of brain injury. The use of phosphorous spectroscopy allows the quantification of phosphorylated metabolites. Thus, the measurement of the relative concentrations of creatine-phosphate and inorganic-phosphate is a prognostic factor of the outcome of a neonate after birth asphyxia. Absolute concentrations have more recently been studied and seem to be more significant. Proton MRS gives access to brain metabolites such as choline, lactate, N-acetyl aspartate and taurine. Its use is more recent than the phosphorous spectroscopy but first results already show its potential in neonatology.