RESUMEN
Background: Paired sampling of acute (aST) and basal (bST) serum tryptase has been recommended when investigating patients with a suspected perioperative hypersensitivity (POH) reaction. In the current consensus formula, an aST value exceeding (1.2×bST+2) confirms mast cell activation. The current consensus formula has been validated in adults but not in children. Methods: We prospectively included 96 children who underwent uneventful anaesthesia and sampled serum tryptase at baseline and 60-90 min after induction. Tryptase changes were then compared with those in 94 children with suspected POH who were retrospectively included from four reference centres in Belgium, France, and Denmark. Results: We observed a median decrease in serum tryptase during uneventful anaesthesia of 0.41 µg L-1 (-15.9%; P<0.001). The current consensus formula identified mast cell activation in 31.9% of paediatric POH patients. After generating receiver operating characteristic curves through 100 repeated five-fold cross-validation, aST>bST+0.71 was identified as the optimal cut-off point to identify mast cell activation. This new paediatric formula has higher sensitivity than the current consensus formula (53.2% vs 31.9%, P<0.001) with a specificity of 96.9%. Analysis in the subpopulation where a culprit was identified and in grade 3-4 reactions similarly yielded higher sensitivity for the new paediatric formula when compared with the current consensus formula (85.3% vs 61.8%; P=0.008 and 78.0% vs 48.8%; P<0.001, respectively). Internally cross-validated sensitivity and specificity were 53.3% and 93.3%, respectively. Conclusions: This is the first study suggesting the need for an adjusted formula in children to identify perioperative mast cell activation as tryptase is significantly lowered during uneventful anaesthesia. We propose a new formula (aST>bST+0.71) which performs significantly better than the current consensus formula in our multicentric paediatric population.
RESUMEN
The gross structure and the expression of the c-myc oncogene were analyzed in primary cells from 15 acute lymphoblastic leukemia patients. Southern blot analysis was used to detect possible alterations in the structure of this gene. Alterations (rearrangement and/or amplification) were observed in seven of the 15 samples studied. When the expression of MYC protein was evaluated by Western blot analysis, we found no correlation between c-myc gene alterations and p67 c-myc, which was expressed in the 15 samples studied. The analysis of expression also revealed various MYC-related proteins (115, 110 and 60 kD). These proteins were expressed at variable levels in all leukemic cells, other transformed cells, and in normal peripheral blood lymphocytes (PBL) induced to proliferate with interleukin 2. We detected the 110 kD and 40 kD MYC-related proteins in fresh normal PBL and in samples from patients in complete remission. These studies indicate that the c-myc alterations and protein expression are unrelated to percentage of leukemic blasts, cell morphology or immunophenotype. Our work shows that the expression of MYC-related proteins from 115, 60 and 40 kD is associated with mechanisms of cell activation, and perhaps these proteins may play a role in cellular proliferation-transformation.