腺苷和抗IgE抗体对哮喘患者BALF中肥大细胞分泌组胺的影响

目的 :研究支气管哮喘 (哮喘 )患者支气管肺泡灌洗液 (BALF)中肥大细胞的功能特性。方法 :2 9例轻度哮喘患者BALF中的细胞经冲洗后 ,加入含抗IgE抗体、腺苷、缓冲液或腺苷 +抗IgE抗体的LP4试管中进行激发试验。检测BALF肥大细胞中的组胺释放量。结果 :腺苷浓度达 10 0 μmol/L时 ,仍无明显刺激组胺释放的作用 ,仅在浓度高达 10 0 0 μmol/L时 ,方可诱导哮喘患者BALF中肥大细胞释放约 17%的组胺。抗IgE抗体的浓度大于 1× 10 -4g/L时对哮喘患者BALF中肥大细胞的释放组胺有明显的促进作用 ;仅 3× 10 -5g/L的抗IgE抗体与腺苷联合应用的实测值 ,明显高于对应的单独作用组的相加值。结论 :哮喘患者BALF中的肥大细胞对腺苷的刺激反应较差 ,但对抗IgE抗体刺激的反应性明显增强。仅低浓度的抗IgE抗体和腺苷具有协同作用。     

Probiotics: use in allergic disorders: a Nutrition, Allergy, Mucosal Immunology, and Intestinal Microbiota (NAMI) Research Group Report

The underlying denominators and treatment targets in allergic disorders may be outlined as aberrant barrier functions of the skin epithelium and gut mucosa and dysregulation of the immune response to ubiquitous environmental antigens. Dietary methods to control symptoms and reduce the risk of allergic disease have hitherto focused on elimination diets, alone or in combination with other environmental measures. The results have not been satisfactory regarding long-term prevention, and new approaches are urgently needed. Realization of this, together with the demonstration that the immunophysiologic regulation in the gut depends on the establishment of the healthy gut microbiota, has led to the introduction of novel modes of therapeutic intervention on the basis of the consumption of monocultures and mixed cultures of beneficial live probiotic microorganisms. The current aims of intervention are to avert deviant microbiota development, strengthen the gut barrier function, and alleviate abnormal immune responsiveness. Specific probiotics, selected from members of the healthy intestinal microbiota most of them belonging to Lactobacillus or Bifidobacterium, aid in degradation/structural modification of enteral antigens, regulation of the secretion of inflammatory mediators, and direction of the development of the immune system during the critical period of life when these functions are immature and inexperienced and the risk of allergic disease is heightened. In humans, documented effects have been reported for alleviation of intestinal inflammation, normalization of gut mucosal dysfunction, and down-regulation of hypersensitivity reactions, thereby preferentially targeting allergic conditions with intestinal involvement. The probiotic performance of strains differs; each probiotic strain is a unique organism itself with specific properties that cannot be extrapolated from other, even closely related, strains. Moreover, it would seem simplistic to assume that a single supplementation would suffice to counter the plethora of allergic disease. First, it needs to be acknowledged that a more profound understanding of the complex nature of allergic disorders is needed, as it is likely that there are distinct etiologic factors and pathogenetic mechanisms underlying the heterogeneous manifestations. Second, host-related factors influence the probiotic effects; the distinction in the antiallergic potential of probiotics can be explained by the age of the host and the habitual diet with other potentially active compounds and their conceivable joint probiotic effects. Therefore, research activities are currently focusing on identification of specific strains with immunomodulatory potential, and on the question how the food matrix and dietary content interact with the most efficacious probiotic strains or specific strain combinations.     

Efficacy and Safety of Rizatriptan Versus Standard Care During Long-term Treatment for Migraine

Rizatriptan is a novel, selective 5-HT_1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46 000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior ( P <0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.     

Host genetic determinants of T cell responses to the MRKAd5 HIV-1 gag/pol/nef vaccine in the step trial

Understanding how human genetic variation impacts individual response to immunogens is fundamental for rational vaccine development. To explore host mechanisms involved in cellular immune responses to the MRKAd5 human immunodeficiency virus type 1 (HIV-1) gag/pol/nef vaccine tested in the Step trial, we performed a genome-wide association study of determinants of HIV-specific T cell responses, measured by interferon γ enzyme-linked immunospot assays. No human genetic variant reached genome-wide significance, but polymorphisms located in the major histocompatibility complex (MHC) region showed the strongest association with response to the HIV-1 Gag protein: HLA-B alleles known to be associated with differences in HIV-1 control were responsible for these associations. The implication of the same HLA alleles in vaccine-induced cellular immunity and in natural immune control is of relevance for vaccine design. Furthermore, our results demonstrate the importance of considering the host immunogenetic background in the analysis of immune responses to T cell vaccines.     

Systematic review and evidence-based consensus guideline on prevention of allergy and atopic eczema of the German Network on Allergy Prevention (ABAP)

Allergies are a meaningful public-health problem. Until now no evidence-based recommendations for allergy prevention exist. An evidence based guideline for primary and secondary prevention of allergies was developed in the course of the German Network on Allergy Prevention (Aktionsbündnis Allergiepr?ven-tion, ABAP) with support of the German Ministry of Health. Results of the systematic evidence search and the consented recommendations are presented here. After an appropriate search strategy was developed, a systematic literature search was performed in electronic databases (Cochrane library, MEDLINE, EMBASE). Furthermore four selected journals were hand-searched and reference lists of actual reviews as well as grey literature was screened. Some 3 500 references were retrieved initially and a two-stage filter process on the relevance was applied by screening titles and abstracts and subsequently full-text papers. For the critical methodological appraisal modifications of international checklists were used. A total of 323 studies were included and evaluated. These comprised 3 Cochrane Reviews, 7 meta-analyses, 37 randomized controlled trials (RCTs) as well as 102 cohort and 174 case-control-studies. The following levels of evidence were applied: 3x1a, 21x1b, 5x2a, 59x2b, 1x3a, 45x3b, 189x4. These studies were summarized in a form of a systematic review and corresponding recommendations were formulated. The latter were consented by members of the abap steering committee in two consensus meeting where the method of a nominal group process was applied. For the first time recommendations for the prevention of allergies were developed on a high methodological standard. The content and modifications reflect the existing evidence.     

Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas

This clinical report reviews the nutritional options during pregnancy, lactation, and the first year of life that may affect the development of atopic disease (atopic dermatitis, asthma, food allergy) in early life. It replaces an earlier policy statement from the American Academy of Pediatrics that addressed the use of hypoallergenic infant formulas and included provisional recommendations for dietary management for the prevention of atopic disease. The documented benefits of nutritional intervention that may prevent or delay the onset of atopic disease are largely limited to infants at high risk of developing allergy (ie, infants with at least 1 first-degree relative [parent or sibling] with allergic disease). Current evidence does not support a major role for maternal dietary restrictions during pregnancy or lactation. There is evidence that breastfeeding for at least 4 months, compared with feeding formula made with intact cow milk protein, prevents or delays the occurrence of atopic dermatitis, cow milk allergy, and wheezing in early childhood. In studies of infants at high risk of atopy and who are not exclusively breastfed for 4 to 6 months, there is modest evidence that the onset of atopic disease may be delayed or prevented by the use of hydrolyzed formulas compared with formula made with intact cow milk protein, particularly for atopic dermatitis. Comparative studies of the various hydrolyzed formulas also indicate that not all formulas have the same protective benefit. There is also little evidence that delaying the timing of the introduction of complementary foods beyond 4 to 6 months of age prevents the occurrence of atopic disease. At present, there are insufficient data to document a protective effect of any dietary intervention beyond 4 to 6 months of age for the development of atopic disease.     

上海儿童医学中心急性淋巴细胞性白血病2005方案疗效多中心研究

目的 通过多中心研究评价上海儿童医学中心-急性淋巴细胞性白血病-2005(SCMC-ALL-2005)方案对儿童急性淋巴细胞性白血病(ALL)的疗效以及预后.方法 共有5家单位参与临床研究,统一采用SCMC-ALL-2005方案对初诊ALL患儿进行诊治.2005年5月1日至2009年4月30日纳入研究病例随访至2011年9月30日.临床资料经卡方检验验证各中心间病例组成的相似性;并运用Kaplan-Meier生存曲线及Log-Rank卡方检验研究患儿的生存情况.结果 共计655例患儿纳入多中心临床研究,除免疫分型外各中心间患儿组成及疗效经统计检验差异无统计学意义.生存者中位随访时间49.13个月,预期5年无事件生存率(EFS)为(69.9％±2.1％),5年总生存率(0S)(77.6％±2.0％);5年复发率(23.9％±2.0％).其中低危组EFS、OS、复发率分别为(82.0％±2.6％)、(83.6％±3.0％)、(16.1％±2.5％);中危组EFS、OS、复发率为(66.4％±3.1％)、(76.8％±2.7％)、(26.3％±3.0％);高危组5年EFS、OS、复发率为(27.4％±9.3％)、(48.9％±7.3％)、(60.0％±12.8％).各预后因素分析提示:高白细胞、年龄≤1岁BCR-ABL1和MLL-AFF1 (MLL-AF4)融合基因为重要的不良预后指标.复发仍然是影响患儿预后的最重要因素.