肿瘤坏死因子-α干预对热性惊厥患儿外周血单个核细胞ICAM-1和LFA-1表达的影响

目的：探讨肿瘤坏死因子-α(TNF-α) 对热性惊厥(FS) 患儿外周血单个核细胞（PBMC）细胞间黏附分子-1(ICAM-1) 及配体淋巴细胞功能相关抗原-1(LFA-1) 表达的影响。方法：16例FS患儿随机分为FS对照组和TNF-α干预组。TNF-α干预组采用1.0 ng/mL 的TNF-α进行干预。对照组16例,为年龄和性别相匹配的同期体检健康儿童。进行外周血PBMC培养。流式细胞仪检测PBMC表面ICAM-1 和 LFA-1的表达。结果：FS 对照组在体外培养的PBMC表面ICAM-1和LFA-1表达水平分别为(20±9)% 和(43±16)%,明显高于正常对照组［(14±7)%,(30±16)%］（P＜0.05）;TNF-α干预组的PBMC表面ICAM-1表达水平［(27±11)%］明显高于FS对照组(P＜0.05),LFA-1表达［（52±21）%］较FS对照组有增高趋势,但差异无统计学意义。结论：炎症介质TNF-α刺激可使FS患儿的LFA-1 和 ICAM-1表达上调。     

热性惊厥患儿血浆和外周血单个核细胞表面ICAM-1/LFA-1的表达水平

目的探讨细胞间黏附因子-1(ICAM-1)及其配体淋巴细胞功能相关抗原-1(LFA-1)对热性惊厥(FS)患儿的神经免疫调节作用。方法2004-11—2006-12将武汉市儿童医院60例FS患儿分为单纯性FS(SFS)组30例和复杂性FS(CFS)组30例;对照组30例,为年龄和性别相匹配的同期体检健康儿童。采用双抗夹心ELISA法检测血浆可溶性ICAM-1/LFA-1水平,流式细胞术检测外周血单个核细胞(PBMC)表面ICAM-1/LFA-1的表达水平。结果SFS组和CFS组患儿血浆ICAM-1水平分别为(21.54±11.09)ng/mL和(24.34±6.86)ng/mL,均明显低于对照组(29.73±12.39)ng/mL儿童(P<0.05);3组血浆LFA-1水平从高到低依次为CFS组(12.30±8.04)ng/mL、SFS组(12.09±8.83)ng/mL和对照组(9.51±8.07)ng/mL,组间比较差异无统计学意义(P>0.05)。SFS组的PBMC表面ICAM-1表达水平为(29.96±12.31)%,明显高于CFS组(22.50±8.19)%及对照组(14.21±11.31)%儿童(P<0.05),CFS组的PBMC表面ICAM-1表达水平明显高于对照组儿童(P<0.05);而LFA-1在PBMC表面的表达水平则不同,3组比较,SFS组最高为(50.89±21.36)%,CFS组最低为(34.35±11.45)%,对照组为(41.39±16.30)%,组间比较差异有统计学意义。结论ICAM-1/LFA-1作为早期应激状态下的协同刺激信号免疫因子,参与白细胞黏附及其黏附级联反应,使大脑神经元在对热应激不适应基础上呈过度兴奋状态,诱导惊厥的发生。且CFS的神经免疫病理过程要比SFS相对复杂,抑制FS的ICAM-1/LFA-1黏附活动可能为其防治开辟新的途径。     

EB病毒亚型/变异株及其与疾病关系的研究进展

Epstein-Barr病毒(Epsteir-Barr virus,EBV)属于疱疹病毒科γ亚科,与鼻咽癌、地方性伯基特淋巴瘤和霍奇金淋巴瘤等相关,是重要的肿瘤相关病毒.EBV基因组中存在多个多态性区域,根据这些区域中氨基酸的变异,可将EBV分为不同的亚型/变异株.目前,关于不同EBV亚型/变异株与疾病间是否相关尚无定...     

Early onset of severe diabetes mellitus-related microvascular complications

A 16-year-old girl with type 1 diabetes developed painful peripheral neuropathy within 1 month and proliferative retinopathy within 1 year despite excellent glycemic control. We speculate on potential mechanisms that may have contributed to the rapid development of diabetes mellitus-related complications.     

过敏性紫癜患儿血清与尿液中粘附分子sICAM-1 sVCAM-1水平变化的研究

目的了解过敏性紫癜(HSP)患儿血清和尿液中可溶性细胞间粘附分子-1(sICAM-1)、可溶性血管细胞粘附分子-1(sVCAM-1)的水平。探讨粘附分子在HSP发病机制中的作用。方法研究对象为2006年3月至2006年11月在首都儿科研究所附属儿童医院住院的40例HSP患儿,正常对照为同期的33例外科非感染性疾病患儿,检测其外周血及尿液中粘附分子sICAM-1、sVCAM-1的水平。结果(1)HSP组血清sICAM-1、sV-CAM-1水平显著高于对照组(P<0.05)。但在肾炎组与非肾炎组中差异无统计学意义(P=0.659,0.080)。(2)HSP组尿液中sICAM-1、sVCAM-1水平与对照组差异无统计学意义(P=0.479,0.164)。HSP患儿肾炎组尿液中sICAM-1、sVCAM-1水平分别高于非肾炎组和正常对照组,但差异均无统计学意义(P>0.05)。而肾炎组中病理分级较重患儿其尿中两种粘附分子水平均较高。结论HSP患儿血清sICAM-1、sVCAM-1水平升高,尿sI-CAM-1、sVCAM-1水平可能与HSP患儿肾脏病变程度有关。粘附分子的表达增加参与了HSP发病的病生理过程。     

放射测定胎鼠肝脏尿苷二磷酸葡萄糖醛酸转移酶1A1活性

目的探讨大鼠肝脏发育不成熟期葡萄糖醛酸转移酶1A1活性的发育规律,为研究新生儿期葡萄糖醛酸结合反应提供实验依据。方法用HeridrunMatern方法放射测定不同孕龄(孕17～19d各5只)及出生后不同日龄(生后1～5d各10只,生后2周的5只)大鼠的肝脏葡萄糖醛酸转移酶1A1活性。结果大鼠肝脏在孕17～19dUGT1A1活性较低,而且增长幅度小,孕19d酶的活性占成熟鼠活性的6.7%。生后1～2d时增长幅度很大,生后5d基本达成熟鼠水平,占成熟鼠活性的88.1%。将孕17d、孕19d、生后1d、成熟鼠这4组UGT1A1活性进行统计学检验,具有统计学意义。结论不成熟大鼠肝脏葡萄糖醛酸转移酶1A1活性很低,导致此期的胆红素葡萄糖醛酸结合反应水平低下。     

儿童甲型H1N1流感临床特点

<正>甲型H1N1流感是由流感病毒H1N1亚型引起的急性呼吸道传染病。其临床特点与流感病毒的亚型及其变异有关,也与人体的免疫状况和当时的流行情况有关。2009年3月北美发生猪流感,世界卫生组织于2009-04-30宣布不再使用猪流感一词,开始使用甲型H1N1流感。它具有起病急、传染性强、流行广泛、传播迅速的特点。儿童感     

细胞外信号调节激酶-1、细胞周期蛋白D1表达与儿童急性白血病关系研究

目的探讨细胞外信号调节激酶_1(ERK1)、细胞周期蛋白D1(cyclinD1)的表达与儿童急性白血病(AL)的关系。方法50例儿童AL(AL组)和26例AL完全缓解(AL_CR组)患儿为病例组,23例非肿瘤性疾病患儿为对照组,采用超敏SP免疫组织化学法,检测各组骨髓细胞中ERK1、cyclinD1的表达情况。结果AL组ERK1、cyclinD1阳性率分别为68.00%和56.00%,明显高于AL_CR组(3.85%,3.85%)和对照组(0,0)(P<0.01);高危AL患儿中阳性率分别为90.91%、86.36%,明显高于标危AL患儿(P<0.01);16例AL患儿化疗前ERK1、cyclinD1阳性率分别为75.00%、68.75%,化疗缓解后阳性率均为0(P<0.01);AL组中ERK1、cyclinD1表达相同(χ2=2.5,P>0.05)。结论AL患儿ERK1、cyclinD1表达率较高,可作为近期疗效的观察指标;ERK1与cyclinD1过度表达相同,可能在AL发生发展过程中有协同作用。     

应用胰岛素泵治疗儿童及青少年1型糖尿病对糖代谢的影响

为观察应用胰岛素泵治疗儿童及青少年1型糖尿病(T1DM)对糖代谢的影响 ,随访10例胰岛素泵治疗的T1DM患儿 ,分别观察胰岛素泵治疗前、后6个月的糖化血红蛋白值(HbA1c)、胰岛素用量、严重低血糖及酮症酸中毒发生次数的变化情况。结果显示 ,胰岛素泵治疗6个月后HbA1c 显著下降 ,治疗前为8.97 %±1.69 %,治疗后为7.51 %±1.17 % (t=2.52 ,P<0.05) ;胰岛素用量无显著下降 ;未发生严重低血糖和酮症酸中毒。表明胰岛素泵治疗可有效控制血糖 ,明显降低HbA1c,减少低血糖及酮症酸中毒的发生 ,是儿童及青少年T1DM常规治疗的较好选择。     

无脑回-巨脑回畸形患儿的临床特征及分子遗传学研究

目的研究无脑回-巨脑回畸形患儿的临床特征及分子遗传学特征,分析基因型和表型的关联。方法收集2014年1月至2020年3月就诊的60例无脑回-巨脑回畸形患儿的临床资料,包括临床症状、头颅影像学、治疗随访等,其中45例患儿家系行全基因组二代测序分析。结果 60例患儿中男30例、女30例,起病年龄2天至14岁,其中单纯巨脑回45例(75.0%),单纯无脑回4例(6.7%),巨脑回合并无脑回11例(18.3%);仅以运动或语言发育落后为首发症状就诊者10例(16.7%),伴癫痫者48例(80.0%),其中痉挛发作31例。50例合并惊厥的患儿随访1.5个月至5年,2例热性惊厥未用药无发作,12例经抗癫痫药物、4例经手术治疗后无癫痫发作,31例仍有反复癫痫发作,1例因重症肺炎病亡。60例患儿中59例存在不同程度的精神运动发育落后,1例14岁起病的局灶性巨脑回患儿发育正常。行全基因组分析的45例患儿家系中发现4例血小板激活因子乙酰水解酶lB亚单位1(PAFAH1B1/LIS1)基因变异及1例α-微管蛋白1a(TUBA1A)基因变异,均为新发变异,美国医学遗传学与基因组学学会分类均为致病性变异。结论无脑回-巨脑回患儿临床上多有难治性癫痫和不同程度的发育迟缓,多数预后不良,痉挛发作的一线用药和癫痫手术治疗对部分患儿有益;仅少数患儿发现PAFAH1B1基因及TUBA1A基因致病性变异。     

Oseltamivir-resistant 2009 H1N1 influenza pneumonia during therapy in a renal transplant recipient

The emergence of oseltamivir-resistant 2009 H1N1 influenza virus (conferred by the H275Y substitution in NA) during therapy or prophylaxis in immunocompromised patients is a serious concern. The optimal therapy for immunosuppressed patients with oseltamivir-resistant 2009 H1N1 influenza virus is unknown and few options exist. We report a 10-yr-old recipient of kidney transplant who was hospitalized with oseltamivir-resistant 2009 H1N1 influenza pneumonia complicated by severe respiratory failure, ARDS, and renal failure requiring institution of ECMO and CRRT. On presentation, treatment with oseltamivir (second course) and broad-spectrum antibiotics was initiated. Immunosuppressive agents were stopped on hospital day (d) 2. On hospital d 7, given his critical status, immunocompromised state, and difficulty in obtaining intravenous zanamivir, after obtaining ethical approval and parental consent, he was treated with intravenous peramivir (through an Emergency Investigational New Drug Application) for two wk. He tolerated the regimen well and his clinical status improved gradually. Several factors may have contributed to virus clearance and survival including recovery of the immune system, aggressive critical care support, and administration of peramivir. Ongoing surveillance is essential to monitor how oseltamivir-resistant H275Y mutant viruses may evolve in the future.     

Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors

Background

Germline mutations and deletions of SMARCB1/INI1 in chromosome band 22q11.2 predispose patients to rhabdoid tumor and schwannomatosis. Previous estimates suggested that 15–20% of rhabdoid tumors were caused by an underlying germline abnormality of SMARCB1. However, these studies were limited by case selection and an inability to detect intragenic deletions and duplications.

Procedure

One hundred matched tumor and blood samples from patients with rhabdoid tumors of the brain, kidney, or soft tissues were analyzed for mutations and deletions of SMARCB1 by FISH, multiplex ligation‐dependent probe amplification (MLPA), sequence analysis and high resolution Illumina 610K SNP‐based oligonucleotide array studies.

Results

Thirty‐five of 100 patients were found to have a germline SMARCB1 abnormality. These abnormalities included point and frameshift mutations, intragenic deletions and duplications, and larger deletions including regions both proximal and distal to SMARCB1. There were nine cases that demonstrated parent to child transmission of a mutated copy of SMARCB1. In eight of the nine cases, one or more family members were also diagnosed with rhabdoid tumor or schwannoma, and two of the eight families presented with multiple affected children in a manner consistent with gonadal mosaicism.

Conclusions

Approximately one‐third of newly diagnosed patients with rhabdoid tumor have an underlying genetic predisposition to tumors due to a germline SMARCB1 alteration. Families may demonstrate incomplete penetrance and gonadal mosaicism, which must be considered when counseling families of patients with rhabdoid tumor. Pediatr Blood Cancer. 2010;56:7–15. © 2010 Wiley‐Liss, Inc.     

Pediatric hypereosinophilic syndrome (HES) differs from adult HES

The idiopathic hypereosinophilic syndrome (HES) developed in a 15-year-old boy who presented with colitis, cough, rash, and hepatitis. Molecular analysis failed to demonstrate the Fip1-like1-Platelet Derived Growth Factor Receptor alpha chain (FIP1L1-PDGFRA) mutation described in adult patients with HES. There are significant clinical differences between the pediatric and adult presentations of HES.