The receptor tyrosine kinase c-Kit controls IL-33 receptor signaling in mast cells.

Members of the Toll/interleukin-1 receptor (TIR) family are of importance for host defense and inflammation. Here we report that the TIR-family member interleukin-33R (IL-33R) cross-activates the receptor tyrosine kinase c-Kit in human and murine mast cells. The IL-33R-induced activation of signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase B (PKB), and Jun NH(2)-terminal kinase 1 (JNK1) depends on c-Kit and is required to elicit optimal effector functions. Costimulation with the c-Kit ligand stem cell factor (SCF) is necessary for IL-33-induced cytokine production in primary mast cells. The structural basis for this cross-activation is the complex formation between c-Kit, IL-33R, and IL-1R accessory protein (IL-1RAcP). We found that c-Kit and IL-1RAcP interact constitutively and that IL-33R joins this complex upon ligand binding. Our findings support a model in which signals from seemingly disparate receptors are integrated for full cellular responses.

Contribution of computed tomography with oral media contrast to the diagnosis of esophago-pericardial fistula.

The esophago-pericardial fistula is a very rare and usually fatal complication of esophageal cancers. We report a case of a 56-year-old man who presented with chest pain 1 month after concurrent radiochemotherapy for squamous cell esophageal carcinoma. Thoracic computed tomography (CT) with oral iodinated media contrast revealed esophago-pericardial fistula visualizing the fistulous tract. We conclude that CT with oral contrast media may be the first imaging technique of choice to confirm the diagnosis of esophago-pleural fistula.

Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study.

OBJECTIVES: This study was designed to compare two treatment strategies in patients with atrial fibrillation(AF): rhythm-control (restoration and maintenance of sinus rhythm) and rate-control (pharmacologic or invasive rate-control and anticoagulation). BACKGROUND: Atrial fibrillation is the most common arrhythmia. It is unclear whether a strategy of rhythm- or rate-control is better in terms of mortality, morbidity, and quality of life. METHODS: The Strategies of Treatment of Atrial Fibrillation (STAF) multicenter pilot trial randomized 200 patients (100 per group) with persistent AF to rhythm- or rate-control. The combined primary end point was a combination of death, cardiopulmonary resuscitation, cerebrovascular event, and systemic embolism. RESULTS: After 19.6 +/- 8.9 months (range 0 to 36 months) there was no difference in the primary end point between rhythm-control (9/100; 5.54%/year) and rate-control (10/100; 6.09%/year; p = 0.99). The percentage of patients in sinus rhythm in the rhythm-control group after up to four cardioversions during the follow-up period (rate-control group) was 23% (0%) at 36 months. Eighteen primary end points occurred in atrial fibrillation; only one occurred in sinus rhythm (p = 0.049). CONCLUSIONS: The STAF pilot study showed no differences between the two treatment strategies in all end points except hospitalizations. These data suggest that there was no benefit in attempting rhythm-control in these patients with a high risk of arrhythmia recurrence. It remains unclear whether the results in the rhythm-control group would have been better if sinus rhythm had been maintained in a higher proportion of patients, as all but one end point occurred during AF.

Subtelomere FISH in 50 children with mental retardation and minor anomalies, identified by a checklist, detects 10 rearrangements including a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33.

Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed by subtelomere fluorescence in situ hybridization (FISH), are a significant cause of idiopathic mental retardation (MR). Some 20 subtelomere studies, including more than 2,500 subjects, have been reported. The studies are not directly comparable because different techniques and patient ascertainment criteria were used, but an analysis of 14 studies showed that aberrations were detected in 97 out of 1,718 patients (5.8%, range 2-29%; 95% confidence interval (CI) 4.60-6.84%). We performed a subtelomere FISH study of 50 unrelated children ascertained by a checklist that evaluates MR or developmental delay, dysmorphism, growth defect, and abnormal pedigree and found 10 bona fide causal rearrangements (detection rate 20%, 95% CI 10-33.7%). The findings included five unbalanced familial translocations or inversions, two unbalanced de novo translocations, and two de novo deletions. Patient 5 showed multiple anomalies (large head, vision defect, omphalocele, heart defect, enlarged kidneys, moderate MR, speech defect, mild transient homocysteinemia) and a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33. The report of a subtelomeric balanced rearrangement associated with a disease phenotype is a novel one. FISH mapping using panels of overlapping BAC clones identified a number of candidate genes at or near his breakpoints, including ASPA, TRPV3, TRPV1, and CTNS at 17p13.3, and three genes of unknown function at 20q13.33. Only the homocysteinemia could be speculatively linked to one of these genes (CTNS, the gene for cystinosis). Three within the subset of 16 children (18.8%) with mild (IQ, 50-69) or unspecified degree of MR tested positive, suggesting that the checklist approach could be especially useful within this group of patients.

[Oncolor is ten years old: the age of discretion for the Lorraine network in oncology]. / Oncolor a dix ans : l'âge de raison pour le réseau de santé lorrain en cancérologie.

Oncolor, network in oncology in Lorraine, was born ten years ago, from a group of professionals in the field of oncology who worked closed together with regional administrative authorities. Oncolor was created with respect of equilibrium between the different regional partners avoiding struggle for power. Oncolor was conducting different actions: recognition of hospital sites according to three levels based on technical and humans means at disposal (highly specialised sites, specialised sites, and associated sites); the definition of good practice for hospital pharmacies leading to the generalization of centralized preparation of chemotherapy under responsibility of a pharmacist; the organization of multidisciplinary practice through the written and implementation of clinical guidelines accessible on the web site of the network (www.oncolor.org) even by the patients (86 guidelines on line today); creation and access to a software to help physicians for decision called Kasimir; the formalization of multidisciplinary meetings with a common process. All these tools help physicians in their relationship with the patient. The web site was opened to professionals but also to patients in December 2001. Oncolor was also implicated in different training programs for physicians, pharmacists, nurses and other professionals. The annual budget increased from 47,000 euros in 1998 up to more than 700,000 euros in 2002. To conclude, to build a network in oncology is an exciting task. It must become more professional, keeping in mind the original objective: every patient, whatever his place of consultation is, have to benefit of the best treatment adapted to his personal situation.