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《Journal of cystic fibrosis》2022,21(6):908-921
This paper is the first in a series providing updated guidance on the definition, evaluation and management of people with a Cystic Fibrosis Transmembrane conductance Regulator (CFTR)-Related Disorder (CFTR-RD). The need for this update relates to more precise characterisation of CFTR gene variants and improved assessment of CFTR protein dysfunction. The exercise is co-ordinated by the European CF Society Standards of Care Committee and Diagnostic Network Working Group and involves stakeholder engagement. This first paper was produced by a core group using an extensive literature review and papers graded for their quality. Subsequent wider stakeholder agreement was achieved.The definition of a CFTR-RD remains “a clinical condition with evidence of CFTR protein dysfunction that does not fulfil the diagnostic criteria for CF”. Clearer guidance on CFTR dysfunction and relevant CFTR variants will be provided. Thresholds for clinical presentations are presented and the paradigm that pathobiological processes may be evident in more than one organ is agreed. In this paper we reflect on the early patient journey, highlighting that CF specialists as well as other relevant specialists should be involved in the care of people with a CFTR-RD. 相似文献
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《European journal of paediatric neurology》2014,18(5):591-596
BackgroundThe apoE protein is the most important lipid transporter in the brain and has also been shown to have several regulatory functions in the central nervous system. The production of apoE is regulated by a number of genes and increases under certain conditions such as cerebral injury in adults.AimsOur aim was to study whether variations in genes regulating the expression of the APOE gene were associated with severity of cerebral palsy (CP).MethodsChildren enrolled in the Cerebral Palsy Register of Norway (CPRN) were invited to participate in this cross-sectional study; 281 of the invited 703 children (40%) returned swabs with buccal cells collected by parents. Six genetic variations thought to affect the production of apoE were genotyped and correlated with clinical data recorded in the CPRN.ResultsCompared with children carrying the GG allele, children with genotype GT or TT in a specific genetic variation (rs59007384 located in the nearby TOMM40 gene) had excess risk for worse fine motor function (Odds ratio (OR): 1.82; 95% Confidence interval (CI): 1.10–2.99; p = 0.019) and epilepsy (OR: 2.32; CI: 1.17–4.61; p = 0.016). There was no association between severity of CP and any of the other five genetic variations analyzed.ConclusionOur findings suggest that genetic variations in one of the sequences regulating the expression of APOE, may be associated with worse clinical outcome in children with cerebral palsy. 相似文献
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Baśkiewicz-Hałasa M Pius E Hałasa M Dziedziejko V Grymuła K Machaliński B 《Transplant immunology》2012,26(1):34-41
Mixed chimerism has been suggested to induce tolerance to transplanted alloantigens. As the precise influence of mixed chimerism induction on the host organism has still not been fully elucidated, the aim of the present study was to explore this phenomenon in relation to the stem cell compartment.The experiment was performed on B6.SJL-PtprcaPep3b mice. Mixed chimerism induction protocols involved 3 Gy TBI (Day − 1 of the experiment), injection of 20-30 × 106 Balb C bone marrow cells (Day 0), and administration of blocking antibodies against CD40L (Day 0 and Day 4), anti-CD8 (Day − 2) with/without anti-NK1.1 (Day − 3). Selected groups of mice were also treated with cyclophosphamid (175 mg/kg) on Day 2. The presence of mixed chimerism was assessed in peripheral blood, bone marrow, and spleen, as well as in various subpopulations of leukocytes (CD4+, CD8+, CD45/B220+, Gr-1+, lin−/Sca-1+/c-kit−, lin−/Sca-1+/c-kit+, lin−/Sca-1−/c-kit+). Furthermore, the percentage of stem/progenitor cells (lin−/Sca-1+/c-kit−, lin−/Sca-1+/c-kit+, lin−/Sca-1−/c-kit+, VSEL, HSC) was analysed for the first time in bone marrow and peripheral blood of chimeric mice.The range of mixed chimerism differed significantly among various cell populations: it was lowest in CD8-positive cells and lin−/Sca-1+/c-kit− cells, and highest in granulocytes. The induction of mixed chimerism revealed a significant impact on the stem/progenitor cell frequency in recipient mice, providing potential therapeutic insights into the long-term immunologic tolerance observed in chimeric mice. Collectively, these findings contribute to further optimization of mixed chimerism induction protocols and might help in the introduction of this phenomenon into clinical practice. 相似文献
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目的通过生物力学研究,对比三种治疗肱骨近端骨折(Neer 3型)内固定结构的稳定性及耐久性。方法按照统一标准制作肱骨近端3部分外科颈大结节骨折模型,分别予空心钉、克氏针及三叶草钢板固定。所有标本进行循环外展实验、循环屈伸实验及压扭负载。结果加压空心钉的结构稳定性较克氏针好而次于三叶草钢板。空心钉及克氏针内固定结构稳定性与骨密度(BMD)有很大的相关性。结论加压空心钉治疗肱骨近端骨折是一种微创的内固定手术,手术时间短,能满足内固定的要求,提供术后患者进行功能锻炼的结构稳定性,是一种治疗老年肱骨近端骨折的可靠方法。 相似文献
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目的:探讨外周血转化生长因子(TGF-β1)浓度及高凝状态与慢性胰腺炎(CP)纤维化的关系,同时研究银杏达莫注射液对抗慢性胰腺炎纤维化的作用。方法:将50例CP患者随机分为观察组、对照组各25例。2组均给予戒烟、低脂高蛋白饮食、避免饱食等常规治疗,观察组同时予银杏达莫注射液静脉滴注,1次/d。2组连续治疗2周,观察2组治疗前后TGF-β1、凝血及血脂、血液流变学等指标的变化情况。结果:外周血TGF-β1浓度、生化指标、凝血指标、血液流变学指标2组治疗后均明显改善(P<0.05),观察组改善更明显(P<0.05)。结论:外周血TGF-β1与CP纤维化相关,银杏达莫能够抑制外周血TGF-β1表达,同时能改善CP患者血液高凝状态,有利于改善慢性胰腺炎纤维化进展。 相似文献