Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

Objective:

Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features.

Methods:

A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined.

Results:

Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC).

Conclusion:

The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making.

Advances in knowledge:

The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality.     

美国医疗器械上市前监管概述与启示

美国食品和药物管理局(Food and Drug Administration,FDA)经过多年发展和改革,已形成了成熟的上市前监管体系。本文通过对FDA上市批准路径(上市前批准、上市前通告、人道主义用器械豁免)和申报流程进行系统介绍,总结了加强事前沟通、降低产品风险等级和设立实质审查程序三个方面的启示,希望我国监管机构能充分吸收美国FDA对于医疗器械监管的经验和教训,建立适合中国国情的医疗器械监管体系,确保公众用器械安全。     

CYP2C19基因多态性及与其代谢相关药物的研究

细胞色素P450酶系(CYP450)是人体内参与药物代谢的主要酶,CYP2C19是细胞色素P450酶系中的一种。临床上多种药物在体内代谢时,均需要CYP2C19酶的参与。许多研究显示,CYP2C19酶的活性受CYP2C19基因多态性的影响。本文就CYP2C19基因多态性及其在体内参与几种药物的代谢情况进行分析与总结。     

中心静脉导管胸腔留置治疗胸腔积液

目的评价中心静脉导管留置治疗胸腔积液的疗效。方法257例胸腔积液患者分为两组，治疗组207例，应用胸腔留置中心静脉导管治疗；对照组50例，常规胸穿抽液治疗，观察并比较不同治疗方法的疗效、并发症等指标。结果两组对比多项指标差异有显著性（P〈0．05）。结论采用中心静脉导管治疗胸腔积液可减少胸穿次数、降低反应，提高治愈率。     

骨质疏松症中医体质与辨证分型的相关性研究——附300例临床分析

目的 探讨骨质疏松症中医体质与辨证分型之间的相关性。方法 按照中西医诊断标准,将确诊的骨质疏松症患者进行中医体质分类与中医辨证分型的临床研究,找出其相关性与规律性,并进行总结。 结果 对300例患者进行中医辨证分型发现脾胃气虚证最多,占总病例数的23.00%,其次为肝肾不足证,占22.00%,以后依次为肾阳虚证、肾阴虚证、气血不足证、血瘀证、骨痿证、肝气郁结证、痰湿证、湿热证;在9种体质分类中阴虚质发病率排在第一位,其次为气虚质,以后依次为阳虚质、血瘀质、特禀质、平和质、痰湿质、湿热质与气郁质。结论 提示9种中医体质中阴虚质与气虚质发病率较高, 辨证分型中发病率较高的2个证型是脾胃气虚型与肝肾阴虚型。说明了体质类型与OP发病率有密切的相关性。     

17-β雌二醇对不同月龄大鼠成骨细胞雌激素受体β表达的影响

目的探讨17-β雌二醇对不同月龄大鼠成骨细胞雌激素受体β（ERβ）表达的影响。方法雌性大鼠颅盖骨经多次酶消化、反复贴壁法分离纯化培养得到大量纯净成骨细胞并进行形态学检查和碱性磷酸酶（ALP）染色;免疫组化法（SABC）进行雌激素受体染色;用10-8mol/L17-β雌二醇处理培养的成骨细胞,SDS-PAGE电泳和western blot法检测雌激素受体。结果成骨细胞碱性磷酸酶染色阳性率为90%以上。形态学检查符合成骨细胞的特征。免疫组化染色显示大鼠的成骨细胞存在雌激素受体β,且位于胞核内。Western blot结果表明,与对照组相比,处理组的各月龄大鼠雌激素受体β表达均有上调。结论17-β雌二醇能提高各月龄组大鼠成骨细胞雌激素受体β表达水平,不同月龄间上调水平不同,以4、8月龄组最为显著。     

Recessive dystrophic epidermolysis bullosa phenotype is preserved in xenografts using SCID mice: development of an experimental in vivo model.

Recessive dystrophic epidermolysis bullosa (RDEB) is a subgroup of hereditary blistering diseases characterized by repetitive wounding and healing with subsequent extensive scarring. The purpose of this study was to establish a xenograft model that retains the RDEB phenotype and thus might be used as an experimental in vivo model to explore the molecular and biochemical mechanisms of the chronically wounded phenotype of RDEB. Full-thickness, tumor-free RDEB skin tissues were grafted onto the dorsum of severe combined immunodeficiency (SCID) mice. At 4, 8, 12, and 24 weeks after grafting, the xenografts were removed for examination. Immunofluorescence studies were performed using species-specific antibodies to human class I antigen, mouse class I antigen, human type IV and VII collagens and with cross-reacting antibody against bullous pemphigoid antigen (BPA). Staining with the antibody to human class I antigen, W6/32, and with the antibody to mouse class I antigen, 20.8.4s, confirmed the species-specific results obtained with the type IV and type VII collagen and laminin antibodies. The RDEB grafts showed essentially no staining with the type VII collagen antibody. Antibodies against laminin and BPA showed normal staining patterns in RDEB grafts. There was an overall paucity of anchoring fibrils in the grafts when examined with electron microscopy. Blisters could be induced in these grafts with minor trauma and showed a sublamina densa separation by immunomapping and electron microscopy. As late as 24 weeks post-transplantation, the RDEB grafts remain human, are not significantly replaced by mouse cells, and retain the RDEB disease phenotype.     

中孕期非整倍体染色体异常血清学筛查不同方案比较

目的：对中孕期非整倍体染色体异常血清学筛查不同方案的检出率进行探讨。方法选取513名2009年9月~2013年3月在攀枝花市妇幼保健院产科进行常规产前筛查的孕妇血清样本,分别采用化学发光法和时间分辨荧光免疫法对孕妇血清进行二联、三联、四联检查,比较阳性率及假阳性率。结果二联化学发光法检测唐氏综合征(DS)高危假阳性率为9.10豫,三联为7.36豫,四联为6.28豫,假阳性率呈递减趋势(字2=5.119,P约0.05);二联化学发光法筛查18-三体高危假阳性率(0.63豫)低于三联(0.82豫),差异有统计学意义(字2=4.776,P约0.05)。三联时间分辨荧光免疫法筛查DS、18-三体假阳性率(4.01豫、0.34豫)较二联(8.93豫、0.61豫)均明显降低(字2=6.992、4.776,P约0.05)。二联化学发光法检测DS、18-三体假阳性率分别为9.10豫、0.63豫,时间分辨荧光免疫法则分别为8.93豫、0.61豫,两种检测方法比较,差异无统计学意义(字2=1.787、0.000,P跃0.05);而三联时间荧光分辨法检测DS、18-三体假阳性率(4.01豫、0.34豫)均低于三联化学发光法(7.36豫、0.82豫),差异有统计学意义(字2=5.382、4.783,P约0.05)。结论化学发光法的检测系统发现筛查效率二联、三联及四联方案呈递增趋势。时间分辨荧光免疫法检测系统发现筛查效率三联高于二联方案,时间荧光分辨法三联筛查优于化学发光法。