Evidence for direct interaction between mast cells and Leishmania parasites

When stimulated through IgE- (or IgG-) immune complexes with parasite antigens, mast cells can release several cytokines, including IL-4, IL-6, IL-10, IL-12, Interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) that may influence the host response to Leishmania major in modulating lesion size and persistence during experimental infection in the mouse. Moreover, recent data demonstrated that mast cells are able to be antibody-independently activated by direct contact with bacteria, making them important elements in innate immunity. Given these data, we asked whether cell-parasite contact could directly induce mast cell mediator release and whether mast cells could be infected by L. major or L. infantum parasites.    In this study, we showed that a pure homogeneous population of mouse bone marrow derived mast cells (BMMC) in contact with living L. major or L. infantum promastigotes, but not with attenuated parasites or soluble parasite antigens, released preformed mediators such as β-hexosaminidase and the preformed pool of TNF-α within minutes. Furthermore, direct cell-parasite contact induced TNF-α synthesis by mast cells within hours. Moreover, we demonstrated by in vitro co-culture experiments that metacyclic L. major or L. infantum promastigotes are directly infective for a significant proportion of BMMC and are transformed into intracellular amastigotes. Taken together, these data suggest that mast cell can participate in the first line of defence, i.e. innate immunity, during local cutaneous infection with Leishmania parasites.     

Safety of High Energy Internal Cardioversion for Atrial Fibrillation

High energy internal cardioversion has been proposed as an alternative method to cardiovert drug refractory or external cardioversion refractory atrial fibrillation. However, the safety of this technique has not been clearly evaluated. We reviewed findings in 53 patients who underwent 55 sessions of high energy internal cardioversion (2 patients underwent 2 sessions] for termination of longstanding atrial fibrillation. Shocks energy varied from 70–270 J. Three patients had 3 shocks during the same session, 5 had 2, and 47 only 1. Success rate was 89% (success was defined as immediate conversion to normal sinus rhythm).
Low cardiac output occurred in two patients, and resulted in the death of one of these individuals, a patient with significant hypertrophic cardiomyopathy and heart failure. The other patient recovered completely. In 11% of the cases, shock induced transient atrioventricular block, necessitating ventricular pacing until sinus rhythm was restored. In three patients, a moderate but asymptomatic and uncomplicated pericardial effusion was diagnosed on echocardiogram. Finally, four patients had side effects related to venous puncture, which resolved spontaneously. These results suggest that high energy internal cardioversion is effective for conversion of atrial fibrillation. However, the technique may not be optimal in patients with advanced hypertrophic cardiomyopathy and in such cases the technique should be used carefully and only in the case of failure of external cardioversion; no more than two shocks should be delivered during the same procedure. Temporary ventricular pacing should be provided in all patients and an echocardiogram should be performed before patients are being discharged.