25 research outputs found
Specific Antibody Production by Blood B Cells is Retained in Late Stage Drug-naĂŻve HIV-infected Africans
Unseparated peripheral blood mononuclear cells (PBMCs) obtained from
drug-naĂŻve African individuals living in a context of multi-infections and presenting
with high viral load (VL), were cultured in vitro and tested for their ability to produce
antibodies (Abs) reacting with HIV-1 antigens. Within these PBMCs, circulating
B cells were differentiated in vitro and produced IgG Abs against not only ENV, but
also GAG and POL proteins. Under similar experimental conditions, HAART treated
patients produced Abs to ENV proteins only. The in vitro antibody production by
drug-naĂŻve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10)
but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp
160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was
not abrogated by the addition of various monoclonal Abs (mAbs) to co-stimulatory
molecules. This suggests that the in vitro antibody production by drug-naĂŻve
individuals' PBMCs resulted from the maturation of already envelope and core
antigen-primed, differentiated B cells, presumably pre-plasma cells, which are
not known to circulate at homeostasy. As in vitro produced Abs retained the
capacity of binding antigen and forming complexes, this study provides
pre-clinical support for functional humoral
responses despite major HIV- and other tropical pathogen-induced B cell
perturbations
Gene therapy for aromatic L-amino acid decarboxylase deficiency: Requirements for safe application and knowledge-generating follow-up
The autosomal recessive defect of aromatic L-amino acid decarboxylase (AADC) leads to a severe neurological disorder with manifestation in infancy due to a pronounced, combined deficiency of dopamine, serotonin and catecholamines. The success of conventional drug treatment is very limited, especially in patients with a severe phenotype. The development of an intracerebral AAV2-based gene delivery targeting the putamen or substantia nigra started more than 10âyears ago. Recently, the putaminally-delivered construct, Eladocagene exuparvovec has been approved by the European Medicines Agency and by the British Medicines and Healthcare products Regulatory Agency. This now available gene therapy provides for the first time also for AADC deficiency (AADCD) a causal therapy, leading this disorder into a new therapeutic era. By using a standardized Delphi approach members of the International Working Group on Neurotransmitter related Disorders (iNTD) developed structural requirements and recommendations for the preparation, management and follow-up of AADC deficiency patients who undergo gene therapy. This statement underlines the necessity of a framework for a quality-assured application of AADCD gene therapy including Eladocagene exuparvovec. Treatment requires prehospital, inpatient and posthospital care by a multidisciplinary team in a specialized and qualified therapy center. Due to lack of data on long-term outcomes and the comparative efficacy of alternative stereotactic procedures and brain target sites, a structured follow-up plan and systematic documentation of outcomes in a suitable, industry-independent registry study are necessary
Perda auditiva neurossensorial bilateral e ataxia cerebelar em um caso de doença de Lyme em estågio tardio Bilateral sensorineural hearing loss and cerebellar ataxia in the case of late stage Lyme disease
Borrélioses et fiÚvres récurrentes
National audienceBorrĂ©lioses et fiĂšvres rĂ©currentes Les borrĂ©lioses rĂ©currentes (br) ou fiĂšvres rĂ©currentes sont dues Ă des bactĂ©ries du genre borrelia, de la famille des spirochĂštes, transmises Ă lâhomme par des arthroÂŹpodes vecteurs (poux de corps, tiques molles, et tiques dures pour lâune dâentre elles). La br Ă poux est cosmoÂŹpolite et transmise lors dâĂ©pidĂ©mies survenant dans le contexte de crises majeures (promiscuitĂ©, conditions dâhygiĂšne prĂ©caires, crise alimentaire, etc.). Les br Ă tiques se rĂ©partissent par rĂ©gion, selon la borrelia en cause et la distribution gĂ©ographique de leur tique vecÂŹtrice. Le temps dâincubation varie de 3 Ă 20jours. La premiĂšre phase fĂ©brile dure 3jours (1-14jours), suivie dâune phase dâapyrexie avec persistance des autres signes cliniques (rash cutanĂ©, pĂ©tĂ©chies, cĂ©phalĂ©es inÂŹtenses, agitation, polyarthromyalgies, douleurs abdomiÂŹnales, nausĂ©es/vomissements, etc.). La rĂ©currence de la fiĂšvre dĂ©crit une pĂ©riodicitĂ© de 7jours en moyenne. La bactĂ©riĂ©mie est abondante lors des pics fĂ©briles, permetÂŹtant de poser un diagnostic par examen direct en miÂŹcroscopie, pcr borrelia ou culture sur milieu spĂ©cial, quand celle-ci est possible. Le traitement repose sur la doxycycline, sauf pour les formes neurologiques (ceftriaxone). Le taux de mortalitĂ© varie de 2 Ă 5 % selon la borrelia incriminĂ©e. LâĂ©volution est le plus souvent favorable aprĂšs traitement
Borrélioses et fiÚvres récurrentes
National audienceBorrĂ©lioses et fiĂšvres rĂ©currentes Les borrĂ©lioses rĂ©currentes (br) ou fiĂšvres rĂ©currentes sont dues Ă des bactĂ©ries du genre borrelia, de la famille des spirochĂštes, transmises Ă lâhomme par des arthroÂŹpodes vecteurs (poux de corps, tiques molles, et tiques dures pour lâune dâentre elles). La br Ă poux est cosmoÂŹpolite et transmise lors dâĂ©pidĂ©mies survenant dans le contexte de crises majeures (promiscuitĂ©, conditions dâhygiĂšne prĂ©caires, crise alimentaire, etc.). Les br Ă tiques se rĂ©partissent par rĂ©gion, selon la borrelia en cause et la distribution gĂ©ographique de leur tique vecÂŹtrice. Le temps dâincubation varie de 3 Ă 20jours. La premiĂšre phase fĂ©brile dure 3jours (1-14jours), suivie dâune phase dâapyrexie avec persistance des autres signes cliniques (rash cutanĂ©, pĂ©tĂ©chies, cĂ©phalĂ©es inÂŹtenses, agitation, polyarthromyalgies, douleurs abdomiÂŹnales, nausĂ©es/vomissements, etc.). La rĂ©currence de la fiĂšvre dĂ©crit une pĂ©riodicitĂ© de 7jours en moyenne. La bactĂ©riĂ©mie est abondante lors des pics fĂ©briles, permetÂŹtant de poser un diagnostic par examen direct en miÂŹcroscopie, pcr borrelia ou culture sur milieu spĂ©cial, quand celle-ci est possible. Le traitement repose sur la doxycycline, sauf pour les formes neurologiques (ceftriaxone). Le taux de mortalitĂ© varie de 2 Ă 5 % selon la borrelia incriminĂ©e. LâĂ©volution est le plus souvent favorable aprĂšs traitement
Facteurs de risque de résistance aux quinolones d Escherichia coli responsables de pyélonéphrites aiguës chez la femme
Selon l Observatoire national de l Ă©pidĂ©miologie de la rĂ©sistance bactĂ©rienne aux antibiotiques, 15.3% des Escherichia coli urinaires de ville Ă©taient rĂ©sistants aux fluoroquinolones en 2010. Ceci interroge sur la pertinence du traitement probabiliste par fluoroquinolone des pyĂ©lonĂ©phrites aiguĂ«s (PNA) communautaires, infections potentiellement graves. Objectifs : Identifier les facteurs de risque individuels de rĂ©sistance aux quinolones d Escherichia coli responsables de PNA communautaires . Patients et mĂ©thodes : Une Ă©tude de cohorte rĂ©trospective de 344 PNA Ă Escherichia coli de femmes adultes a Ă©tĂ© menĂ©e dans les services d accueil des urgences des hĂŽpitaux de Roanne et Saint-Etienne, de janvier 2011 Ă fĂ©vrier 2012. Ătaient Ă©tudiĂ©s des facteurs dĂ©mographiques, administratifs et cliniques. Les souches d Escherichia coli de sensibilitĂ© intermĂ©diaire sur l antibiogramme Ă©taient considĂ©rĂ©es rĂ©sistantes. RĂ©sultats : Les taux de rĂ©sistance Ă l acide nalidixique et Ă l ofloxacine Ă©taient respectivement de 23% et 17.4%. Le caractĂšre compliquĂ© de la PNA n Ă©tait pas un facteur de risque significatif (analyse univariĂ©e). Trois facteurs de risque de rĂ©sistance Ă l acide nalidixique et l ofloxacine Ă©taient indĂ©pendants (analyse multivariĂ©e) : consommation de fluoroquinolone dans les trois mois prĂ©cĂ©dents, hospitalisation dans les six mois prĂ©cĂ©dents et institutionnalisation. En prĂ©sence d au moins une de ces caractĂ©ristiques, le taux de rĂ©sistance Ă l ofloxacine s Ă©levait Ă 30.6%. En leur absence, il s abaissait Ă 9%. Conclusions : Ces considĂ©rations invitent Ă revoir les rĂ©fĂ©rentiels locaux concernant le traitement probabiliste d une PNA. Les limites mĂ©thodologiques de notre travail obligent Ă conforter ces rĂ©sultats par des Ă©tudes prospectives multicentriques qui pourraient aboutir Ă de nouvelles recommandations nationales.ST ETIENNE-BU MĂ©decine (422182102) / SudocSudocFranceF
Bilateral sensorineural hearing loss and cerebellar ataxia in the case of late stage Lyme disease
Difficult-to-treat Gram-negative bone and joint infections: efficacy and safety of prolonged intravenous colistin
International audienc
Methodological Quality Assessment with the AGREE II Scale and a Comparison of European and American Guidelines for the Treatment of Lyme Borreliosis: A Systematic Review
International audienceBackground: Most European and American countries recently updated their guidelines on Lyme borreliosis (LB). The aim of this study was to provide a comparative overview of existing guidelines on the treatment of LB in Europe and America and to assess the methodological quality of their elaboration. Methods: A systematic search was carried out in MEDLINE, Google Scholar, and the national databases of scientific societies from 2014 to 2020. Quality was assessed by two independent reviewers using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Results: Twelve guidelines were included. The scores for the AGREE II domains (median ± IQR) were: overall assessment 100 ± 22, scope and purpose 85 ± 46, stakeholder involvement 88 ± 48, rigour of development 67 ± 35, clarity of presentation 81 ± 36, applicability 73 ± 52 and editorial independence 79% ± 54%. Cohenâs weighted kappa showed a high agreement (K = 0.90, 95%CI 0.84â0.96). Guidelines were quite homogeneous regarding the recommended molecules (mostly doxycycline in the first intention and ceftriaxone in the second intention), their duration (10 to 28 days), and their dosage. The differences were due to the lack of well-conducted comparative trials. The International Lyme and Associated Diseases Society (ILADS) guidelines were the only ones to suggest longer antibiotics based on an expert consensus. Conclusion: European and American guidelines for the treatment of LB were quite homogeneous but based on moderate- to low-evidence studies. Well-conducted comparative trials are needed to assess the best molecules, the optimal duration and the most effective doses