A randomized,controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis

OBJECTIVE: In previously well infants hospitalized with acute viral bronchiolitis, the effectiveness of repeated nebulized therapy with epinephrine (EPI) was compared with treatment with albuterol (ALB) or saline placebo (PLAC). STUDY DESIGN: In this randomized, double-blind, parallel-group, controlled trial, infants received study nebulizations every 1 to 6 hours and were assessed twice daily by the research team. The primary outcome was length of hospital stay (LOS). Secondary outcomes included the time from admission until the infant had normal hydration, oxygenation, and minimal respiratory distress. RESULTS: A total of 149 infants were randomized; 50 were allocated to receive racemic EPI, 51 were given ALB, and 48 received PLAC. Baseline characteristics and pre-enrollment symptoms, signs, and therapy were similar between groups. There were no group differences in the primary outcome measure, mean LOS (hours)(+/- SD): EPI = 59.8 (62), ALB = 61.4 (54), and PLAC = 63.3 (47); P =.95 by intent-to-treat analysis. Group differences were not statistically significant in any of the secondary outcomes. CONCLUSIONS: There were no group differences in the effectiveness of therapy for infants hospitalized with bronchiolitis. Based on these results, we do not recommend routine use of either nebulized EPI or ALB in this patient group.     

Genetic polymorphisms in the metabolic pathway and non‐Hodgkin lymphoma survival

Metabolic pathway enzymes, such as Cytochrome P450 (CYP), glutathione S‐transferase (GST), and N‐acetyltransferases (NAT) are involved in activation and detoxification of environmental carcinogens as well as drug metabolism. We hypothesized that the genetic variations in such metabolic pathways may affect NHL prognosis and survival. Follow‐up information of 496 female NHL incident cases diagnosed during 1996–2000 in Connecticut were abstracted from the Connecticut Tumor Registry in 2008; survival analyses were conducted by comparing the Kaplan‐Meier curves, and hazard ratios (HR) were computed from the Cox Proportional Hazard models adjusting for demographic and tumor characteristics which were suggested by previous studies to be determinants of NHL survival. We identified six SNPs from four metabolism genes (CYP2E1, GSTP1, GSTT1, and NAT1) that were associated with NHL survival. Specifically, polymorphisms in GSTT1 were associated with follicular lymphoma survival; and polymorphisms in CYP2E1, GSTP1, and NAT1 were associated with survival of chronic lymphocytic leukemia/small lymphocytic lymphoma. Our study suggests that genetic polymorphisms in metabolic pathways may help improve the prediction of NHL survival and prognosis. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.     

Combining different assays and chemical analysis to characterize the genotoxicity of waters impacted by textile discharges

Waters receiving textile discharges can exhibit genotoxic and mutagenic activity, which has been related to the presence of dyes and aromatic amines as synthesis precursors or byproducts. The aim of this study was to identify dyes and aromatic amines in water samples impacted by textile discharges, and to evaluate the genotoxic responses of these samples using the Salmonella/microsome assay in strains TA98 and YG1041, and the Fpg‐modified comet assay in the RTL‐W1 fish cell line. The genotoxicity of river samples downstream of the discharge was greater than the upstream samples in both of the Ames tests. The Fpg‐modified comet assay detected similar levels of DNA damage in the upstream and downstream samples. Mutagenicity was not detected with TA98, except for the Quilombo River samples, but when YG1041 was used as the tester strain mutagenicity was detected for all sites with a very different profile in upstream sites relative to the other sites. The mutagenic response strongly indicated that aromatic amines or dyes were contributing to the mutagenic activity downstream. The impact of textile discharges was also confirmed by chemical analysis, because the highest concentrations of azo dyes and aromatic amines were detected in the river downstream. This study shows the value of combining assays measuring complementary endpoints to better characterize the mutagenicity of environmental samples, with the advantage that this approach provides an indication of what classes of compounds are responsible for the effect. Environ. Mol. Mutagen. 57:559–571, 2016. © 2016 Wiley Periodicals, Inc.     

Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and Th1 chemokine production

Depending on the activation status, plasmacytoid dendritic cells (PDC) and myeloid DC have the ability to induce CD4 T cell development toward T helper cell type 1 (Th1) or Th2 pathways. Thus, we tested whether different activation signals could also have an impact on the profile of chemokines produced by human PDC. Signals that induce human PDC to promote a type 1 response (i.e., viruses) and a type 2 response [i.e., CD40 ligand (CD40L)] also induced PDC isolated from tonsils to secrete chemokines preferentially attracting Th1 cells [such as interferon-gamma (IFN-gamma)-inducible protein (IP)-10/CXC chemokine ligand 10 (CXCL10) and macrophage inflammatory protein-1beta/CC chemokine ligand 4 (CCL4)] or Th2 cells (such as thymus and activation-regulated chemokine/CCL17 and monocyte-derived chemokine/CCL22), respectively. Activated natural killer cells were preferentially recruited by supernatants of virus-activated PDC, and supernatants of CD40L-activated PDC attracted memory CD4(+) T cells, particularly the CD4(+)CD45RO(+)CD25(+) T cells described for their regulatory activities. It is striking that CD40L and virus synergized to trigger the production of IFN-gamma by PDC, which induces another Th1-attracting chemokine monokine-induced by IFN-gamma/CXCL9 and cooperates with endogenous type I IFN for IP-10/CXCL10 production. In conclusion, our studies reveal that PDC participate in the selective recruitment of effector cells of innate and adaptive immune responses and that virus converts the CD40L-induced Th2 chemokine patterns of PDC into a potent Th1 mediator profile through an autocrine loop of IFN-gamma.     

Decreased circulating elastin peptide levels in humans with sepsis

OBJECTIVE: Sepsis is a potentially life-threatening medical condition induced by viral, bacterial or fungal infection, which is characterized by systemic inflammation, hypotension and vasodilation that can lead to cardiovascular collapse. Increased activity of elastases, enzymes which degrade the extracellular matrix components including elastin, has been demonstrated in plasma of septic patients. Since elastin peptides (EP), by binding to an elastin-laminin receptor on vascular endothelial and smooth muscle cells, induce dose-dependent vasodilation, we hypothesized that elevated circulating EP could contribute to the vasodilation that occurs in septic patients. MATERIALS AND METHODS: Blood for measurement of EP was collected from not-septic and septic patients admitted to the intensive care unit (ICU), as well as from healthy subjects. Plasma EP concentrations were measured using a competitive ELISA technique. RESULTS: The plasma EP level in the septic patients was approximately half that of the not-septic patients and the healthy controls, with similar EP levels in the latter two groups. There was no apparent association between EP levels and age or gender in any of the groups. CONCLUSIONS: Plasma EP levels were actually decreased in septic patients, possibly indicating that the balance between EP production vs. elimination favors elimination. This result further suggests that circulating EP may not be important in the development of the vasodilation and hypotension that occurs in septic shock. Alternatively, however, increased degradation of EP by elastase or other enzymes could lead to the appearance of biologically active EP, which may not be recognized by the ELISA assay.     

Peptides derived from the whole sequence of BCR-ABL bind to several class I molecules allowing specific induction of human cytotoxic T lymphocytes

Chronic myeloid leukemia (CML) is characterized cytogenetically by a t(9;22) translocation which generates a hybrid bcr-abl gene, encoding a p210^bcr-abl fusion protein. The induction in vitro of leukemia-specific T cells reactive with p210^bcr-abl is a strategy developed for an immunological therapeutic approach in CML. Peptides from the junction region of this chimeric protein have been considered as potential targets for a cytotoxic response against leukemic cells. However, only a few peptides encompassing the two p210^bcr-abl breakpoints have been shown to bind to the most common HLA class I molecules, which limits the number of patients who could benefit from this approach. We assume that the presence of chimeric BCR-ABL protein in leukemic cells may affect processing and delivery of peptides, possibly giving rise to new epitopes at the cell surface. We selected 162 peptides from the whole sequence of this protein, including 14 peptides of the b2a2 and b3a2 junctions, which had an anchor motif for a common HLA class I molecule. We tested their ability to bind to eight HLA class I molecules (HLA-A1, -A2, -A3, -A11, -B7, -B8, -B27, -B44). We identified 48 peptides from outside the junction region, with intermediate or strong binding capacities to these HLA class I molecules contrasting with only six junction peptides with a moderate binding capacity to HLA-A3/A11, -B8, or -B44 molecules. Moreover, cytotoxic T lymphocyte lines specific for various peptides outside the junction were generated from peripheral blood mononuclear cells of HLA-A2 or -B7 healthy donors and from one CML patient. These results contribute to evaluation of immunity to the BCR-ABL chimeric protein. Further studies are required to investigate whether such epitopes are correctly processed and presented by leukemic cells.     

Non-Asthmatic Patients Show Increased Exhaled Nitric Oxide Concentrations

OBJECTIVE:

Evaluate whether exhaled nitric oxide may serve as a marker of intraoperative bronchospasm.

INTRODUCTION:

Intraoperative bronchospasm remains a challenging event during anesthesia. Previous studies in asthmatic patients suggest that exhaled nitric oxide may represent a noninvasive measure of airway inflammation.

METHODS:

A total of 146,358 anesthesia information forms, which were received during the period from 1999 to 2004, were reviewed. Bronchospasm was registered on 863 forms. From those, three groups were identified: 9 non-asthmatic patients (Bronchospasm group), 12 asthmatics (Asthma group) and 10 subjects with no previous airway disease or symptoms (Control group). All subjects were submitted to exhaled nitric oxide measurements (parts/billion), spirometry and the induced sputum test. The data was compared by ANOVA followed by the Tukey test and Kruskal-Wallis followed by Dunn’s test.

RESULTS:

The normal lung function test results for the Bronchospasm group were different from those of the asthma group (p <0.05). The median percentage of eosinophils in induced sputum was higher for the Asthma [2.46 (0.45–6.83)] compared with either the Bronchospasm [0.55 (0–1.26)] or the Control group [0.0 (0)] (p <0.05); exhaled nitric oxide followed a similar pattern for the Asthma [81.55 (57.6–86.85)], Bronchospasm [46.2 (42.0–62.6] and Control group [18.7 (16.0–24.7)] (p< 0.05).

CONCLUSIONS:

Non-asthmatic patients with intraoperative bronchospasm detected during anesthesia and endotracheal intubation showed increased expired nitric oxide.     

Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families

A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295 EGEA families selected through at least one asthmatic subject. In addition to asthma, seven phenotypes involved in the main asthma physiopathological pathways were considered: SPT (positive skin prick test response to at least one of 11 allergens), SPTQ score being the number of positive skin test responses to 11 allergens, Phadiatop (positive specific IgE response to a mixture of allergens), total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine challenge and %predicted FEV(1). Four regions showed evidence for linkage (P相似文献