Stroke-induced activation of the α7 nicotinic receptor increases Pseudomonas aeruginosa lung injury.

Infectious complications, predominantly pneumonia, are the most common cause of death in the postacute phase of stroke, although the mechanisms underlying the corresponding immunosuppression are not fully understood. We tested the hypothesis that activation of the α7 nicotinic acetylcholine receptor (α7nAChR) pathway is important in the stroke-induced increase in lung injury caused by Pseudomonas aeruginosa pneumonia in mice. Prior stroke increased lung vascular permeability caused by P. aeruginosa pneumonia and was associated with decreased lung neutrophil recruitment and bacterial clearance in mice. Pharmacologic inhibition (methyllycaconitine IC(50): 0.2-0.6 nM) or genetic deletion of the α7nAChR significantly (P<0.05) attenuates the effect of prior stroke on lung injury and mortality caused by P. aeruginosa pneumonia in mice. Finally, pretreatment with PNU-282987, a pharmacologic activator of the α7nAChR (EC(50): 0.2 µM), significantly (P<0.05) increased lung injury caused by P. aeruginosa pneumonia, significantly (P<0.05) decreased the release of KC, a major neutrophil chemokine, and significantly (P<0.05) decreased intracellular bacterial killing by a mouse alveolar macrophage cell line and primary mouse neutrophils. In summary, the α7 nicotinic cholinergic pathway plays an important role in mediating the systemic immunosuppression observed after stroke and directly contributes to more severe lung damage induced by P. aeruginosa.

Drowning after falling from a medium-height bridge: multiple trauma victims.

INTRODUCTION: Drowning following a fall from a bridge can lead to cardiac arrest caused by hypoxia, hypothermia, or severe traumatic injury. Every year patients are brought to our hospital who have nearly drowned in the local river after a jump from a bridge (approximate height 16-22 meters). We report traumatic injuries in patients admitted to our hospital for out-of-hospital cardiac arrest due to drowning. METHODS: We retrospectively reviewed the charts of all patients admitted to the intensive care units of our hospital for out-of-hospital cardiac arrest due to drowning after a jump from a bridge in the Seine River between 2002 and 2010. All clinical or radiologic evidence of trauma was recorded. RESULTS: A total of 37 patients where admitted to our hospital for out-of-hospital cardiac arrest due to drowning. Fourteen patients had radiologic examinations. Five of these examinations showed evidence of severe trauma. In one case, clinical examination showed evidence of severe peripheral neurologic trauma. Seven of these patients (19%) were discharged from the hospital alive. CONCLUSIONS: Patients found nearly drowned in a river spanned by a medium-height bridge should undergo spinal immobilization and complete radiologic examination as soon as possible.

A two adenine insertion polymorphism in the 3' untranslated region of factor VII gene is associated with peripheral arterial disease but not with venous thrombosis. Results of case-control studies.

Polymorphic variants of genes encoding blood coagulation proteins have been extensively studied as risk factors for venous or arterial thrombosis A variation in the 3' untranslated region (UTR) involved in the post-transcriptional regulation of factor VII (FVII) gene has been recently identified, a two adenine insertion/deletion at nucleotide 11293. In this study, we investigated its effect on the risk of thrombosis in the frame of two case-control studies, including patients suffering from peripheral arterial disease (PAD) or venous thromboembolic (VTE) disease. The 3'UTR FVII gene polymorphism was investigated i) in 181 patients who had symptomatic atherosclerotic disease of the lower limbs, ii) in 178 patients who had had at least one episode of objectively diagnosed deep venous thrombosis and iii) in controls matched for age and sex. Plasma FVII antigen (FVII: Ag) levels were lower in the presence of the 3'UTR 2A insertion (68.4 +/- 12.3%, 81.3 +/- 14.5% and 89.5 +/- 13.7% in 2A/2A, 2A/0 and 0/0 subjects respectively, p < 0.0001). No significant relationship was found with VTE disease. In the contrary we observed a lower risk of PAD for the 2A/2A compared to the 0/0 genotype after adjustment for traditional risk factors (hypercholesterolemia, smoking status, diabetes and hypertension), with an OR of 0.24 [95% CI 0.06-0.99]. In conclusion, the 2 adenine insertion in the 3'UTR of FVII gene, related to lower plasma FVII levels, is a genetic variation that may contribute to reduce the risk of PAD.