Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
IntroductionFever is associated with a poor outcome in severely brain-injured patients, and its control is one of the therapies used in this condition. But, fever suppression may promote infection, and severely brain-injured patients are frequently exposed to infectious diseases, particularly ventilator-associated pneumonia (VAP). Therefore, we designed a study to explore the role of a fever control protocol in VAP development during neuro-intensive care.MethodsAn observational study was performed on severely brain-injured patients hospitalized in a university ICU. The primary goal was to assess whether fever control was a risk factor for VAP in a prospective cohort in which a fever control protocol was applied and in a historical control group. Moreover, the density of VAP incidence was compared between the two groups. The statistical analysis was based on a competing risk model multivariate analysis.ResultsThe study included 189 brain-injured patients (intervention group, n¿=¿98, and historical control group, n¿=¿91). The use of a fever control protocol was an independent risk factor for VAP (hazard ratio 2.73, 95% confidence interval [1.38, 5.38; P¿=¿0.005]). There was a significant increase in the incidence of VAP in patients treated with a fever control protocol (26.1 versus 12.5 VAP cases per 1000 days of mechanical ventilation). In cases in which a fever control protocol was applied for >3 days, we observed a higher rate of VAP in comparison with the rate among patients treated for ¿3 days.ConclusionFever control in brain-injured patients was a major risk factor for VAP occurrence, particularly when applied for >3 days.
ISSN: 1364-8535

hal-01118640
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118640
PUBMED : 25498970
DOI : 10.1186/s13054-014-0689-4
PUBMEDCENTRAL : PMC4279880

Résumé : Les deux principaux objectifs de ce travail sont de proposer des outils pour la selection d'animaux résistants aux strongles gastro-intestinaux, parasites du tube digestif, et de faire progresser la compréhension des mécanismes de résistance chez la chèvre créole. La variabilité génétique du caractère de résistance au parasitisme digestif a été étudiée afin de vérifier quels critères décrivant le mieux la résistance, peuvent être utilisés pour la sélection. L'ensemble des résultats obtenus suggèrent que le critère d'excrétion d'oeufs et le critère d'éosinophilie sont les plus adaptés pour un schéma de sélection puisqu'ils possèdent une héritabillté moyenne et représentent le mieux la résistance. De plus, ils ne semblent pas en opposition avec le poids, principal critère de production. Le déterminisme génétique de la résistance aux strongles gastro-intestinaux a été étudié et a permis de mettre en évidence l'existence d'un gène majeur pour la résistance chez la population de chèvre créole. De plus, la primo-détection de qtl a permis d'identifier 13 régions du génome ayant un effet sur les critères de résistance. Les mécanismes responsables de la résistance aux strongles gastro-intestinaux ont également été à l'étude. L'ensemble des résultats met en évidence le rôle des éosinophiles dans la mise en place de la résistance aux strongles gastro-intestinaux. L'activité des immunogobulines e semblent dirigés vers les larves l3 d'haemonchus contortus et suggère la mise en place d'une réaction protectrice. Chez la chèvre créole. Ces deux mécanismes semblent donc jouer un rôle important dans la mise en place de la résistance aux strongles gastro-intestinaux
The two main objectives of this work are to propose tools for the selection of resistant animals to gastrointestinal nematodes and advance knowledge on mechanisms of resistance of creole goats. this work has analysed the genetic variability of resistance to digestive parasitism in order to determine which criteria best describes the resistance and can be use for selection. the overall results suggest that the egg excretion and the eosinophilia are the criteria most suitable for a breeding scheme because they have moderate heritability estimates and best represent the resistance. moreover, they do not seem in conflict with the weight, the main criterion of production. the genetic determinism of resistance to gastrointestinal parasites has been studied and has highlighted the existence of a major gene for resistance in creole goats. in addition, the primodetection of qtl identified 13 genomic regions that affect the resistance. the mechanisms behind the resistance to gastrointestinal parasites were also studied and first hypothesis regarding the involvment of the immune response in resistance have been made in goats. the overall results highlighted the role of eosinophils in the development of resistance to gastrointestinal nematodes. the activity of immunoglobulin e seems directed toward l3 larvae of haemonchus contortus and may be imply in the establishment of a protective response agasint nematode parasites. in creole goats, these two mechanisms seem to play an important role in the development of resistance to gastrointestinal nematode infections

http://www.theses.fr/2011AGUY0407/document

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay. The compound 6E11, a natural product derivative, was characterized as a positive hit. Interestingly, this flavanone compound: inhibits necroptosis induced by death receptors ligands TNF-α (Tumor Necrosis Factor) or TRAIL (TNF-Related Apoptosis-Inducing Ligand); is an extremely selective inhibitor, among kinases, of human RIPK1 enzymatic activity with a nM Kd; has a non-ATP competitive mode of action and a novel putative binding site; is weakly cytotoxic towards human primary blood leukocytes or retinal pigment epithelial cells at effective concentrations; protects human aortic endothelial cells (HAEC) from cold hypoxia/reoxygenation injury more effectively than necrostatin-1 (Nec-1) and Nec-1s. Altogether, these data demonstrate that 6E11 is a novel potent small molecular inhibitor of RIPK1-driven necroptosis.
ISSN: 2045-2322

hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616456/file/s41598-017-12788-4.pdf
DOI : 10.1038/s41598-017-12788-4

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Clostridium difficile infection (CDI) is the primary cause of nosocomial diarrhoea in industrialised countries, usually occurring as a complication of antibiotic therapy in elderly patients. Landmark events contributed to boosting interest in CDI over the last 10 years, including the emergence of unusually severe and recurrent CDI due to the NAP1/BI/027 strain, as well as reports suggesting that CDI is also significantly encountered in patients previously considered at no risk, such as community-acquired CDI in patients with no recent antibiotic use, or CDI during pregnancy. Despite this growing interest from the medical community, we do not know the real dimensions of the disease for the following reasons: (i) despite comprehensive guidelines published in Europe and in the USA, most laboratories still use diagnostic tests with suboptimal sensitivity as a 'rule-out' test, hence a significant proportion of CDIs remain undiagnosed; (ii) use of PCR as a stand-alone test by others will probably overestimate the real incidence of CDI and jeopardise any comparison between institutions with different diagnostic procedures; and (iii) transversal studies, with optimum design and diagnostic tests, are rapidly outdated due to the dramatic changes in CDI epidemiology that may occur from one year to another. To get an accurate picture of the real dimensions of the CDI issue, we need more systematic use of an adequate and homogeneous diagnostic strategy in the field as well as the implementation of continuous monitoring of CDI incidence through surveillance programmes.
ISSN: 0924-8579

inserm-00863350
http://www.hal.inserm.fr/inserm-00863350
http://www.hal.inserm.fr/inserm-00863350/document
http://www.hal.inserm.fr/inserm-00863350/file/Clostridium_difficile_infections._Do_we_know_the_real_dimensionssur the_problem-accepted.pdf
DOI : 10.1016/j.ijantimicag.2013.04.009

Éditeur(s) : HAL CCSD
Résumé : International audience
Background: In French Guiana, a recent study has shown that a major part of the histoplasmosis incidence temporal fluctuations could be explained by climatic factors and thus postulated that disseminated histoplasmosis cases could be in a large proportion due to new infections. The description of the seasonal pattern of histoplasmosis could potentially help to test this new hypothesis. Patients and methods: A study using prospective data from the French Hospital Database for HIV was conducted in order to determine seasonal variations of the incidence of first cases of disseminated histoplasmosis in HIV persons in Cayenne, French Guiana. Single failure Cox proportional hazards models were used. Results: After adjusting for CD4 counts and antiretroviral treatment, the incidence of disseminated histoplasmosis was significantly higher during the Short Wet Season-Long Dry Season than during the Short Dry Season-Long Wet Season (Adjusted Hazard ratio 1.7 (1.1-2.5), P= 0.01). Conclusion: This result gives both valuable epidemiologic information to clinicians and a supplementary argument in favour of the hypothesis that an important proportion of cases were due to recent exposure. Therefore, the use of a primary prophylaxis must be discussed in French Guiana.
J AIDS Clinic Res

Droits : info:eu-repo/semantics/OpenAccess
inserm-00915009
http://www.hal.inserm.fr/inserm-00915009
http://www.hal.inserm.fr/inserm-00915009/document
http://www.hal.inserm.fr/inserm-00915009/file/2012_Hanf_-_Disseminated_Histoplasmosis_seasonal_incidence_variations_a_supplementary_argument_for_recent_infection.pdf
DOI : 10.4172/2155-6113.1000175

Éditeur(s) : HAL CCSD
Résumé : International audience
Hantaviruses' distribution is reassessed after performing a cladistic analysis on 93 strains isolated from rodents, and one used as out-group: Thottapalayam isolated from a shrew. While most hantaviruses found in wild animals were collected in northern Asia, Europe, North America, and South America, only Thottapalayam and Thailand were found in South and Southeastern Asia. Thottapalayam is highly divergent from the other known hantaviruses and may represent the emerging tip of a different lineage. Serological surveys carried out to detect evidence of Hantavirus in human populations revealed positive samples not only in West and Central Africa but also in Thailand, with a first case recently confirmed. This suggests that Hantaan-related viruses may infect humans out of their well-documented range. Thus, if rodents are probably the primary reservoir, other mammals may be involved in the cycle of hantaviruses. Additional work is needed out of the traditional areas where hantaviruses have been recorded. New viruses, different hosts, and different human syndromes may be discovered in the future mainly in Southeastern Asia and in Africa where Muridae rodents are present and highly diversified.
Annals New York Academy of Sciences

ird-00714427
http://hal.ird.fr/ird-00714427
http://hal.ird.fr/ird-00714427/document
DOI : 10.1196/annals.1373.004
IRD : fdi:010045640

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Varicella zoster virus (VZV) is a leading cause of acute viral encephalitis but little is known about its clinical, biological and imaging features. Furthermore, the most favourable treatment regimen has not been determined. We studied a prospective cohort of 20 HIV-negative patients presenting with acute VZV encephalitis caused by primary infection or reactivation. VZV was identified in 16 of 20 cases by PCR detection of the DNA in the cerebrospinal fluid. The four remaining cases occurred during or soon after a VZV rash. The median age of the 17 adults was 76 (19-86) years; the three other patients were children (0.5-5 years). Three patients were immunocompromised. Nine adult patients presented with a rash. Eighteen patients presented with fever and an acute encephalitic syndrome: diffuse brain dysfunction, focal neurological signs, seizures and cranial nerve palsies. Three patients presented with either ventricular or subdural haemorrhage, one with myelitis, and one with asymptomatic stenosis of the middle cerebral artery. The imaging was either normal or revealed non-specific abnormalities such as cortical atrophy but no evidence of stroke. All patients were given acyclovir at various dosages and durations but the case fatality rate remained high (15%) and sequelae were frequently observed either at discharge or at follow-up 3 years later.
ISSN: 1198-743X

hal-00875232
https://hal.archives-ouvertes.fr/hal-00875232
PUBMED : 22085160
DOI : 10.1111/j.1469-0691.2011.03705.x