Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.

[Proteinuria after infusion of gelatin. Comparison of Plasmion and Haemaccel]. / Protéinurie après perfusion de gélatine. Comparaison entre Plasmion et Haemaccel.

Modified gelatin are said without deleterious effect on kidney, an important proteinuria as been seen however in surgical patients after gelatin perfusion. A study in 15 patients scheduled for abdominal surgery compared the renal effects of two modified gelatin: Plasmion (gr P) and Haemaccel (gr H) administered in a similar manner. In the two groups proteinuria appears as soon as perfusion begins with at the third hour a peak which may be as high as 6 g/l. In the same time low molecular weight proteinuria (less than 30 kdalton) appears. The beta 2 microglobulinuria (beta 2m) is significatively enhanced (p less than 0,001). Albuminuria is also enhanced but without statistic signification. Comparison between the two groups reveals that in gr P proteinuria is of the same importance, but delayed, with a significatively smaller elimination of beta 2m (1,8 mg/mmol creatininuria versus 8,6,p less than 0,001). Enzymuria increases in a variable fashion. Proteinuria is probably due to tubular reabsorption inhibition of filtered protein induced by gelatin, particularly by amino acids arginine and lysin which become free after gelatin hydrolysis. If this phenomenon is pathologic or not is unclear and gelatin cannot be said absolutely innocuous. However this phenomenon must be known when proteinuria specially beta 2m is to be interpreted.