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Simon E Brill Anant RC Patel Richa Singh Alexander J Mackay Jeremy S Brown John R Hurst 《Respiratory research》2015,16(1)
Background
Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described.The purpose of this study was to describe changes in lung function, symptoms, health status and inflammation during the development and recovery from community-treated exacerbations.Methods
This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values.Results
At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset.Conclusion
Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0167-9) contains supplementary material, which is available to authorized users. 相似文献42.
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In a previous study, we tested the hypothesis that an elevated level of renal glutathione (GSH) would protect the kidney from ischemic injury. However, prior elevation of GSH with GSH monoethylester enhanced then injury induced by 35 min of ischemia and blood reflow [Scaduto RC Jr, Gattone VH, Grotyohann LW, et al; Effect of an altered glutathione content on renal ischemic injury. Am J Physiol 1988;255:F911-F921]. Additionally, GSH monoethylester produced morphologic alterations in the absence of ischemia. Thus the greater ischemic injury observed after GSH ester pretreatment could have been due to a synergistic effect between the events caused by ischemia and the pretreatment. The present study was conducted to evaluate the utility of elevating renal GSH levels by administration of GSH. Administration of GSH (1 mmol/kg body weight) caused a 3-fold elevation of renal GSH levels and a 6-fold elevation of renal cysteine levels after 60 min without causing changes in renal morphology or GFR. After 35 min of renal artery occlusion and 90 min of blood reflow, animals pretreated with GSH had a much greater decline in GFR than untreated control animals. This enhancement of renal ischemic injury in GSH-treated animals was similar to that observed following administration of GSH monoethylester. We conclude that administration of GSH is the method of choice for elevation of renal GSH and that elevation of renal GSH leads to an enhanced ischemia-induced injury which is independent of the method employed to elevate renal GSH. 相似文献
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Cinzia Cameli Marta Viggiano Magali J. Rochat Alessandra Maresca Leonardo Caporali Claudio Fiorini Flavia Palombo Pamela Magini Renée C. Duardo Fabiola Ceroni Maria C. Scaduto Annio Posar Marco Seri Valerio Carelli Paola Visconti Elena Bacchelli Elena Maestrini 《Journal of cellular and molecular medicine》2021,25(5):2459-2470
Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases (~15%-30%) presenting a rare large-effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD-associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole-exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion-transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 × 10−5). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband's mtDNA presented five low-level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large-effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders. 相似文献
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On the origins of esterases 总被引:8,自引:0,他引:8
Comparisons among the primary sequences of five cloned eukaryotic esterases
reveal two distinct lineages, neither bearing any significant overall
sequence similarity to the functionally related serine protease multigene
family. We have not eliminated the possibility that the esterases may have
residual conformational similarities to the serine proteases. However, our
profile analysis and analyses of the predicted conformations of the
esterases reveal little similarity to the serine proteases. Four of the
esterase proteins share 27%-53% overall sequence similarity and evidence of
a catalytic mechanism involving the same Arg- Asp-Ser or His-Asp-Ser charge
relay. We propose that these four esterases, three of them cholinesterases,
form part of a multigene family essentially separate from the serine
proteases.
相似文献
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