Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

International audienceAdult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy

Evaluation de l'efficacité biologique d'une dose de charge préhospitalière de prasugrel en début de procédure d'angioplastie primaire dans le syndrome coronaire aigu avec élévation du segment ST

Le prasugrel est uhne thiénopyridine de 3ème génération qui présente chez le coronarien stable une activité antiagrégante plaquettaire plus importante et plus rapide que le clopidogrel. Cette meilleure efficacité biologique s'accompagne également d'une meilleure efficacité clinique. L'objectif de notre étude était d'évaluer l'efficacité biologique d'une dose de charge préhospitalière de prasugrel en début de procédure d'angioplastie primaire dans le syndrome coronaire aigu avec élévation du segment ST (SCA ST+). METHODE : Les patients pris en charge pour un SCA ST+ en préhospitalier ont bénéficié d'une dose de charge de 60 mg de prasugrel. Un test VerifyNow®était ensuite réalisé sur un échantillon de sang artériel prélevé sur la voie d'abord artérielle en début d'angioplastie primaire. Les résultats de ce test ont été comparés à un contrôle réalisé dans un délai de 120 jours et à ceux d'un groupe de patients ayant un SCA ST-. Trois seuils d'efficacité étaient retenus en phase aiguë du SCA ST+ : PRU < 235, PRU < 208 et PRU < 175. Seul le seuil de PRU < 235 était retenu pour le contrôle à distance du SCA ST + et dans le groupe SCA ST-. RESULTATS : 50 patients ont été inclus dans le groupe SCA ST+ et 24 patients dans le groupe SCA ST-. En phase aiguë du SCA ST+, le prasugrel était efficace chez seulement 40 % des patients avec le seuil de PRU < 235, 32 % avec PRU < 208 et 24 % avec PRU < 175. Le contrôle à distance a retrouvé une efficacité chez 100 % des patients. Dans le groupe SCA ST-, le taux d'efficacité était de 83 % avec un délai entre l'administration du prasugrel et le test comparable à celui du groupe SCA ST+ en phase aiguë. Les patients qui gardaient une réactivité plaquettaire élevée sous prasugrel étaient plus algiques et avaient reçu plus de morphine et à dose plus forte. CONCLUSION : L'effet antiagrégant plaquettaire du prasugrel semble retarder en phase aiguë du SCA ST+. La douleur, l'administration de morphine et la dose élevée de morphine administrée semblent favoriser ce retard d'efficacité.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Comparaison entre l'abciximab et le bolus à haute dose de tirofiban dans l'angioplastie percutanée de l'infarctus du myocarde avec élévation du segment ST (expérience sur le CHU de Bordeaux et le CHG de Pau)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prise en charge des chocs cardiogéniques d'origine ischémique assistés par Impella 2.5 au CHU de Bordeaux

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala

NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic transmission in sensory pathways from auditory thalamus or cortex to the lateral amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas the mechanisms of postsynaptic LTP at thalamo–LA synapses are well understood, much less is known about the sequence of events mediating presynaptic NMDA receptor-dependent LTP at cortico–LA synapses. Here, we show that presynaptic cortico–LA LTP can be entirely accounted for by a persistent increase in the vesicular release probability. At the molecular level, we found that signaling via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover, by using mice lacking the active-zone protein and PKA target RIM1α (RIM1α−/−), we demonstrate that RIM1α is required for both chemically and synaptically induced presynaptic LTP. Further analysis of cortico–LA synaptic transmission in RIM1α−/− mice revealed a deficit in Ca2+-release coupling leading to a lower baseline release probability. Our results reveal the molecular mechanisms underlying the induction of presynaptic LTP at cortico–LA synapses and indicate that RIM1α-dependent LTP may involve changes in Ca2+-release coupling

L-type voltage-dependent Ca2+ channels mediate expression of presynaptic LTP in amygdala

International audienc

Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma.

International audienc

Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome.

This multicentre prospective randomised trial compared the efficacy and safety of two doses of thalidomide in patients with relapsed or refractory myeloma. The study was designed to test the non-inferior efficacy and to confirm the better tolerability of low-dose thalidomide as compared to a higher dose. Four hundred patients were randomly assigned to receive either 100 or 400 mg/day of thalidomide. Dexamethasone treatment was added in both arms for patients with stable disease or treatment failure at 12 weeks. The primary endpoint was 1-year overall survival (OS). Thalidomide 100 mg/day was better tolerated than 400 mg/day with less high-grade somnolence, constipation, nausea/vomiting and peripheral neuropathy (P < 0.001, P = 0.007, P = 0.03 and P = 0.007, respectively). In the per-protocol population (PP), the estimated 1-year OS rates were of 74.5% (n = 149) and 67.3% (n = 156) in the 400 and 100 groups, respectively. The upper limit of the difference between these rates was of 15.6% higher than the non-inferiority acceptable limit of 12.75%, and the hypothesis of non-inferiority of 100 could not be established (P = 0.14). On the other hand, when intent-to-treat (ITT) population was analysed, the non-inferiority was demonstrated because the 1-year OS rates were of 72.8% (n = 195) and 68.8% (n = 205) in the same groups, leading to an upper limit of the difference of 11.49% lower than the non-inferiority acceptable limit. In addition, in patients alive 12 weeks postrandomisation and those who received thalidomide plus dexamethasone, there were no significant differences in response rates, time to progression, progression-free survival and OS between the two groups. Collectively, low-dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile and can be a good salvage therapy in combination with dexamethasone

Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial

High-dose therapy has become a common treatment for myeloma. The objective of this study (Intergroupe Francophone du Myélome [IFM] 9502 trial) was to compare in a prospective and randomized trial the 2 most widely used conditioning regimens before autologous stem cell transplantation in newly diagnosed symptomatic patients younger than 65 years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable patients were compared--140 in arm A and 142 in arm B. Baseline characteristics and disease response to 4 cycles of the VAD regimen performed before randomization and autologous stem cell transplantation were identical in the 2 treatment arms. In arm B, hematologic recovery was significantly faster for both the duration of neutropenia and thrombocytopenia, transfusion requirements were also significantly lower, and the median duration of hospitalization was significantly shorter. In arm A, the incidence of severe mucositis was significantly increased. The median duration of event-free survival was similar in both arms (21 vs 20.5 months, P =.6), but the 45-month survival was 65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be attributed in part to better salvage regimens after relapse in arm B compared with arm A. We conclude that 200 mg/m(2) melphalan is a less toxic and at least as effective conditioning regimen when compared with 8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen should be considered as the standard of care before autologous stem cell transplantation in multiple myeloma