Sublingual immunotherapy with a latex extract in paediatric patients: a double-blind,placebo-controlled study

ABSTRACT

Background: Natural rubber latex (NRL) allergy remains an important allergic disease triggering urticaria, asthma, angioedema and anaphylaxis. Specific immunotherapy can help to solve problems related to NRL allergy. So far, no controlled clinical trials have been performed in children suffering from NRL allergy.

Objectives: To evaluate the safety and efficacy of sublingual immunotherapy (SLIT) with a commercial NRL extract in children with NRL allergy.

Research design: Randomized, double-blind, placebo-controlled, 12‐month trial.

Patients and methods: Twenty-six children (aged 4–15 years) with NRL allergy, who had cutaneous and/or respiratory symptoms, including oral allergy syndrome to fruits containing cross-reactive allergens, were recruited. Twelve children were randomized to SLIT with a commercial NRL extract and eight to placebo (3:2). An additional six children with NRL allergy served as untreated controls.

Main outcomes measures: A glove use test was utilized to monitor skin and systemic symptoms triggered by NRL exposure at baseline and 3, 6, 9 and 12 months later. Oral allergy symptoms were also monitored.

Results: No side effects related to treatments were observed in any patient. A significant improvement of symptom score in treated patients in comparison with baseline values was observed at 3 months (?p = 0.01) and consolidated after 1 year of treatment (?p = 0.0005). In comparison with placebo, significant improvements were observed starting at 9 months from study start (?p = 0.015) and at 12 months (?p = 0.005). The number of foods triggering oral allergy symptoms increased in placebo and control subjects, but not in active treated patients (?p = 0.05).

Conclusion: Latex SLIT was safe and efficacious in paediatric patients with NRL allergy.     

基于系统生物学途径探究人体疼痛产生的分子机制

目的 从系统生物学层面探讨导致人体疼痛的分子机制.方法 利用支持向量机(SVM)技术,构建疼痛相关蛋白相互作用(PPI)网络,结合Gene Ontology注释信息和KEGG数据库的通路信息,推断导致人体疼痛的分子通路.结果 疼痛信号网络主要涉及7条信号通路,包括MAPK信号通路、长时程抑制(LTD)、长时程增强(LTP)通路等；其中,Ca2+及Ras、PLCγ、PLCβ、PKA、IP3、CaM和PKC等蛋白分别在多个疼痛通路级联中发挥关键作用.结论 中枢致敏现象在长时程抑制慢性疼痛的发病机制中起关键作用.     

Dietary exposures and allergy prevention in high-risk infants: A joint statement with the Canadian Society of Allergy and Clinical Immunology

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk for developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps to prevent allergy, the protective effect of early introduction of potentially allergenic foods (at four to six months of age) remains under investigation. Recent research appears to suggest that regularly ingesting a new, potentially allergenic food may be as important as when that food is first introduced.     

Clinical Trial Information Mediator

For research in biomedical sciences, cross-domain searches through several different databases are an increasingly necessary task that often becomes a time consuming and labour-intense process. This is especially the case when different domain databases have to be combined, for example combined searches in clinical trials registries, publication databases and research databases. The Clinical Trial Information Mediator (CTIM) addresses this problem and offers a novel way for the combined search in ClinicalTrials.gov, PubMed and BioSamples.CTIM was developed based on a requirements analysis and implemented using open source technology. A search engine with a graphical user interface was developed in order to search linked data in the three databases ClinicalTrials.gov, PubMed and BioSamples; thereby enabling CTIM to bridge the gap between different knowledge domains of clinical trials, publications of research results and biosamples/genetic information. CTIM was applied in three use cases demonstrating that information retrieval could be considerably improved in sense for complex queries. These use cases show that more relevant results were obtained and more associated publications and biosamples could be retrieved in comparison to a separate single search.Main advantages of CTIM are identifying related information between clinical trials and publications employing a clinical trial centred kind of search, simplified access to its databases and thus reduced search time. In addition it can be used by researchers without prior training because of the intuitive usage.     

Egg n-3 Fatty Acid Composition Modulates Biomarkers of Choline Metabolism in Free-Living Lacto-Ovo-Vegetarian Women of Reproductive Age

The lacto-ovo-vegetarian (LOV) dietary regimen allows eggs, which are a rich source of choline. Consumption of eggs by LOV women may be especially important during pregnancy and lactation when demand for choline is high. The aim of this single blind, randomized, crossover-feeding study was to determine how near-daily egg consumption influenced biomarkers of choline metabolism in healthy LOV women of reproductive age (n=15). Because long-chain n-3 fatty acids could influence choline metabolism, the effect of n-3–enriched vs nonenriched eggs on choline metabolites was also investigated. Three 8-week dietary treatments consisting of six n-3–enriched eggs per week, six nonenriched eggs per week, and an egg-free control phase were separated by 4-week washout periods. Choline metabolites were quantified in fasted plasma collected before and after each treatment and differences in posttreatment choline metabolite concentrations were determined with linear mixed models. The n-3–enriched and nonenriched egg treatments produced different choline metabolite profiles compared with the egg-free control; however, response to the eggs did not differ (P>0.1). Consumption of the n-3–enriched egg treatment yielded higher plasma free choline (P=0.02) and betaine (P<0.01) (vs egg-free control) concentrations, whereas consumption of the nonenriched egg treatment yielded borderline higher (P=0.06) plasma phosphatidylcholine (vs egg-free control) levels. Neither egg treatment increased levels of plasma trimethylamine oxide, a gut-flora–dependent oxidative choline metabolite implicated as a possible risk factor for cardiovascular disease. Overall these data suggest that egg fatty-acid composition modulates the metabolic use of choline.     

Biomarkers associated with disease severity in allergic and nonallergic asthma

Asthma is a complex, chronic respiratory disease with a wide clinical spectrum. Use of high-throughput technologies has generated a great deal of data that require validation. In this work the objective was to validate molecular biomarkers related to asthmatic disease types in peripheral blood samples and define their relationship with disease severity. With this purpose, ninety-four previously described genes were analyzed by qRT-PCR in 30 healthy control (HC) subjects, 30 patients with nonallergic asthma (NA), 30 with allergic asthma (AA), and 14 patients with allergy (rhinitis) but without asthma (AR). RNA was extracted from peripheral blood mononuclear cells (PBMCs) using the TRIzol method. After data normalization, principal component analysis (PCA) was performed, and multiple approaches were used to test for differential gene expression. Relevance was defined by RQ (relative quantification) and corrected P value (<0.05). Protein levels of IL-8 and MSR1 were determined by ELISA and Western blot, respectively.PCA showed 4 gene expression clusters that correlated with the 4 clinical phenotypes. Analysis of differential gene expression between clinical groups and HCs revealed 26 statistically relevant genes in NA and 69 in AA. Protein interaction analysis revealed IL-8 to be a central protein. Average levels of IL-8 were higher in the asthma patients’ sera (NA: 452.28 ± 357.72, AA: 327.46 ± 377 pg/ml) than in HCs (286.09 ± 179.10), but without reaching statistical significance. Nine genes, especially MSR1, were strongly associated with severe NA.In conclusion, several molecular biomarkers of asthma have been defined, some of which could be useful for the diagnosis or prognosis of disease severity.     

The efficacy of supplementation with the novel medical food,Souvenaid, in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized clinical trials

Background and rationale: Certain nutritional supplements are being marketed for the management of Alzheimer's disease (AD), but the evidence for their effectiveness is not established. The objective of this review was to evaluate the evidence from randomized clinical trial (RCTs) examining the effect of Souvenaid in patients with AD.

Methods: We conducted electronic searches in Medline, Embase, PsychINFO, CINAHL, and The Cochrane Library. The reporting quality of the included studies was determined using the Cochrane collaboration tool for assessing the risk of bias. Two reviewers independently determined eligibility, assessed the reporting quality of included studies and extracted data.

Results: Three studies with a total of 1011 participants were included. All were of good reporting quality. Meta-analyses revealed non-significant differences in cognition (ADAS-cog scores MD: 0.08, 95% CI: ?0.71 to 0.88) and function (ADCS-ADL scores MD: 0.36, 95% CI: ?0.54 to 1.25) between Souvenaid and placebo. One study showed significant increase in neuropsychological test battery composite z-score with Souvenaid compared with placebo, and another reported significant improvement in delayed verbal recall for a subgroup of patients with very mild AD. There was no significant effect on global clinical function. No serious adverse events were observed.

Conclusions: The evidence from published clinical trials does not show that supplementation with Souvenaid has beneficial effects on functional ability, behaviour, or global clinical change. Souvenaid may cause improvements in verbal recall in patients at early stages of AD. Few RCTs examining the effect of Souvenaid have been conducted, and they are all funded by same manufacturer. Future research should include using unified tools to measure cognition, function, and behaviour in AD.