Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of ...a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion\Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad, and Virion\Serion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (P < 0.01), which was itself more sensitive than the Virion\Serion kit (P = 0.04). The Bordier and Bio-Rad kits had similar specificity (P = 0.8), both higher than that of the Virion\Serion kit (P = 0.02). The area under the receiver operating characteristic (ROC) curves confirmed the superiority of the Bordier kit over the Bio-Rad and the Virion\Serion kits (0.977, 0.951, and 0.897, respectively; P < 0.01 for each comparison). In a subset analysis of 279 serum samples tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; P = 0.10). The use of recombinant, somatic, and metabolic antigens in a single EIA improved the balance of sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.
Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus ...in respiratory samples from French patients at risk for aspergillosis.
A total of 97 respiratory samples including bronchoalveolar lavages (BAL), bronchial aspirates (BA), tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive aspergillosis (n = 12), chronic pulmonary aspergillosis (n = 3), allergic bronchopulmonary aspergillosis (n = 7), or colonization (n = 11) and 28 controls. Each specimen was evaluated by culture, pan-Aspergillus qPCR, and CYP51A PCR and sequencing.
One A. flavus and 19 A. fumigatus with one multiazole resistant strain (5.3%) were cultured from 20 samples. Culture positivity was 62.5, 75, 42.9, and 15.8% in ABPA, CPA, IA, and colonized patients, respectively. Aspergillus detection rate was significantly higher by pan-Aspergillus qPCR than by culture in IA (90.5 vs. 42.9%; P < 0.05) and colonization group (73.7 vs. 15.8%; P < 0.05). The CYP51A PCR found one TR34/L98H along with 5 novel cyp51A mutations (4 non-synonymous and 1 promoter mutations), yet no association can be established currently between these novel mutations and azole resistance. The analysis of 11 matched pairs of BA and BAL samples found that 9/11 BA carried greater fungal load than BAL and CYP51A detection was more sensitive in BA than in BAL.
Direct molecular detection of Aspergillus spp. and azole resistance markers are useful adjunct tools for comprehensive aspergillosis diagnosis. The observed superior diagnostic value of BAs to BAL fluids warrants more in-depth study.
Traumatic lesions around the base of the thumb have special features due to the location and structure of the joint and its inherent potential instability. This causes different fracture patterns, ...which are mostly isolated around the metacarpal base but can also involve just the trapezium or both. Exceptionally, there may be isolated dislocation. Fracture patterns are variable and influence the type of surgery. The most common fracture is Bennett’s fracture accounting for 4% of all hand fractures and sometimes associated with trapezium fracture, usually in male subjects. Different fracture mechanisms have been proposed. Apart from intra-articular fractures of the metacarpal base and the trapezium, proximal metaphyseal fractures can exceptionally be treated conservatively by immobilization. All other fractures require open or closed reduction combined with different types of temporary pinning or open reduction and internal fixation with screws or locking plate in case of comminution. Immobilization depends on the type of surgical treatment and can be removable or non-removable. Close follow-up is mandatory to avoid the inconveniences of secondary swelling with non-removable plaster and resin casts. Extra-articular malunion may be tolerated, but articular malunion must be corrected surgically by intra-articular osteotomy to restore the joint. In case of posttraumatic joint degeneration, treatment will focus on a case-by-case basis on the patient’s complaints. Arthrodesis or prosthetic surgery can be proposed in case of severe problems caused by osteoarthritis.
Les traumatismes autour de la base du pouce ont des caractéristiques bien particulières étant donnée la position du premier doigt de la main, l’anatomie particulière de l’articulation et son instabilité potentielle inhérente. Ils peuvent se présenter sous différents types de fractures, qui sont le plus souvent isolées autour de la base du premier métacarpien, mais qui peuvent aussi intéresser le trapèze de façon isolée, ou bien les deux. Exceptionnellement, des luxations sont observées de manière isolée. Les différentes caractéristiques des fractures sont très variables et influenceront le type de chirurgie proposée. La fracture la plus commune est celle de Bennett, qui représente 4% de toutes les fractures de la main, et est parfois associée à une fracture du trapèze, le plus souvent chez des sujets masculins. Plusieurs mécanismes de fractures ont été proposés. Hormis les fractures intra-articulaires de la base du premier métacarpien et du trapèze, les fractures de la métaphyse proximale peuvent être traitées exceptionnellement de façon conservatrice par immobilisation. Toutes les autres fractures doivent être réduites (à foyer fermé ou ouvert) et ceci en association avec différents types de brochage (temporaires) ou réduction à ciel ouvert et ostéosynthèse par vis ou par plaque verrouillée en présence de fracture comminutive. L’immobilisation dépendra du type de traitement chirurgical et pourra être amovible ou non. Un suivi rapproché est essentiel afin d’éviter les inconvénients de plâtres et résines non amovibles (gonflement secondaire). Les cals vicieux extra-articulaires peuvent être tolérés, mais les cals vicieux intra-articulaires devraient nécessiter une restauration à tout prix l’articulation par une ostéotomie intra-articulaire. En présence d’arthrose post-traumatique, le traitement se fera sur mesure en fonction des gênes que le patient présentera à la suite de cette évolution. Une arthrodèse ou arthroplastie totale pourra être proposée si la gêne occasionnée par l’arthrose post-traumatique est trop importante.
Abstract Immune thrombocytopenic purpura (ITP) is a disease characterized by antibody-mediated platelet destruction. The T- and B-cell subsets have been extensively studied in primary ITP, but the NK ...cell compartment has been less thoroughly explored. We investigated the NK cell receptor repertoire and the functionality of NK cells in the peripheral blood and spleen in patients with primary ITP. An immunophenotypic analysis of peripheral blood lymphocytes from patients revealed that the numbers of CD19+ B lymphocytes, CD4+ and CD8+ T lymphocytes and CD3− CD56+ NK cells were within the normal range. No major alteration to the expression of distinct inhibitory or activating NK cell receptors was observed. The functionality of NK cells, as evaluated by their ability to degranulate in conditions of natural cytotoxicity or antibody-dependent cell cytotoxicity (ADCC), was preserved in these patients. By contrast, these stimuli induced lower levels of IFNγ production by the NK cells of ITP patients than by those of healthy controls. We then compared the splenic NK cell functions of ITP patients with those of cadaveric heart-beating donors (CHBD) as controls. The splenic NK cells of ITP patients tended to be less efficient in natural cytotoxicity conditions and more efficient in ADCC conditions than control splenic NK cells. Finally, we found that infusions of intravenous immunoglobulin led to the inhibition of NK cell activation through the modulation of the interface between target cells and NK cells.
Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization ...between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics.
We studied the link between T-cell activation, differentiation and senescence phenotypes and non-AIDS-related comorbidities in HIV-suppressed patients.
Patients included in the ANRS CO3 Aquitaine ...Cohort were consecutively enrolled in this cross-sectional study between October 2011 and May 2013 called Chronic Immune Activation and Senescence (CIADIS) study.
We summarized immune markers CD4 and CD8 activation (DR), differentiation (naive and terminally differentiated memory T cells), and senescence (CD57CD28) in a weighted immune score by principal component analysis called CIADIS. Previously described Veterans Aging Cohort Study (VACS) index and immune risk profile (IRP) scores were calculated. We used adjusted logistic regression to assess the association between the CIADIS score and the presence of at least three non-AIDS-defining comorbidities.
Of 876 patients with an undetectable viral load, 73.4% were men and median age was 50.5 years interquartile range (IQR) 44.7-56.7 years. Median CD4 T-cell count was 579/μl (IQR 429-759 cells/μl), and median duration of HIV viral suppression was 5.3 years (IQR 2.3-8.7). The weighted CIADIS score was associated with at least three comorbidities (odds ratio 1.3 for 1 SD more, 95% confidence interval 1.0, 1.6) independently of age, sex, AIDS stage, and the Veterans Aging Cohort Study score. The CIADIS and the immune risk profile scores were significantly associated with at least three comorbidities in adjusted models restricted to patients younger than 60 years. None of the tested scores were associated with at least three comorbidities in patients older than 60 years.
The weighted CIADIS score based on activation, senescence, and differentiation markers might help physicians identifying patients at a higher risk for non-AIDS-related comorbidities.
Non-English title Murat, J B; Choukri, F; Costa, J M ...
Journal de mycologie médicale,
09/2015, Letnik:
25, Številka:
3
Journal Article
Recenzirano
Original Abstract: Introduction: La resistance d'Aspergillus fumigatus vis-a-vis des antifongiques azoles est un probleme emergent en Europe. Les donnees francaises etant limitees, une etude ...prospective multicentrique a ete initiee dans le but de detecter la resistance aux azoles dans une population non selectionnee de patients. Methodes L'etude incluant 12 laboratoires francais de mycologie medicale a ete effectuee de septembre 2013 a novembre 2014. Dans chaque laboratoire, la resistance de tous les isolats d'Aspergillus a ete testee (phase de screening) par mise en culture sur des boites de Petri a 3 secteurs (itraconazole ; voriconazole ; absence d'antifongique). Les isolats capables de croitre sur au moins un des secteurs comportant un antifongique ont ensuite ete centralises pour : - confirmation de la resistance par methode de dilution en milieu liquide EUCAST ; - identification de l'espece par sequencage du gene de beta -tubuline ; - detection de mutations par sequencage du gene Cyp51A et de son promoteur. Resultats Durant la periode de l'etude (1 an), 3062 isolats d'Aspergillus spp. ont ete examines, dont 2576 isolats appartenant a la section Fumigati. D'apres les resultats de screening, 2439 isolats se sont averes sensibles aux azoles et 137 ont pousse sur itraconazole et/ou voriconazole. A ce jour, 22 isolats d'A. fumigatus (sensu stricto) issus de 9 laboratoires ont ete completement caracterises. La mutation TR sub(34)/L98H a ete mise en evidence pour 16 isolats issus de ces 9 centres ; elle etait associee pour 3 d'entre eux (provenant du meme centre) a la mutation H147Y, et pour un isolat aux mutations S297T et F491I. La mutation H285Y a ete identifiee pour 3 isolats issus du meme patient, tandis que les mutations G448S, M220V et Y121F ont ete retrouvees chacune pour un isolat. Les 18 patients concernes presentaient divers terrains sous-jacents (mucoviscidose, greffe pulmonaire, maladies hematologiques, autres) et avaient prealablement recu, pour au moins 8 d'entre eux, des antifongiques azoles. Conclusion: Ces resultats preliminaires montrent la presence, dans plusieurs centres hospitaliers en France, d'isolats cliniques d'A. fumigatus resistants aux azoles associes a des mutations dont la plus frequente est la TR sub(34)/L98H.
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