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目的 分析儿童原发性免疫缺陷病(PID)的临床发病及诊断情况,增强儿科医师对该类疾病的认识.方法 回顾性分析重庆医科大学附属儿童医院1993年5月至2007年12月诊断的135例PID患儿的临床资料,包括发病时症状体征、性别、发病年龄、家族史、免疫学结果 及诊断情况.结果 135例患儿中以抗体缺陷最多,占34.8%.吞噬细胞缺陷占18.5%,其他明确的免疫缺陷综合征占14.8%,联合免疫缺陷占11.9%,免疫失调性疾病占5.9%,补体缺陷占0.7%,其他PID占13.3%.男女比例为110:25,临床诊断与基因诊断比例为98:37.1993-1996年诊断9例,1997-2000年诊断23例,2001-2003年诊断31例,2004-2007年诊断72例,诊断病例数逐年增加.其中2001-2003年基因诊断7例,2004-2007年基因诊断30例.结论 PID为一组主要见于婴幼儿的遗传病,是引起儿童反复、严重、致残、致死性感染的重要原因.近年来诊断的PID病例数逐年增加,基因分析是确诊该类疾病的重要手段.     

抗血小板自身抗体鉴别儿童慢性血小板减少性紫癜的类型

该研究检测了慢性血小板减少性紫癜(TP)治疗中血小板和血浆中的抗血小板自身抗体(AAb)。方法有明确免疫性血小板减少症(血小板≤150×10~9/L),病程在6个月以上的儿童(67例)和成人(23例)即诊断为慢性 TP,患者伴随疾病有系统性红斑狼疮5例,慢性淋巴细胞性白血病1例,人类免疫缺陷病毒感染1例,肉瘤1例,新生儿 TP1例,12例因标本含血小板不足(<10~8)被除外。患者至少3     

在慢性免疫性血小板减少症患儿中甄别原发性免疫缺陷症

原发性免疫缺陷症(primary immunodeficiency,PID)是一组由免疫通路上特定功能性位点突变引起免疫调控异常的遗传性疾病,免疫性血小板减少为其常见表现,且病程迁延、反复,呈现慢性免疫性血小板减少状态。而免疫性血小板减少症(immune thrombocytopenic purpura,ITP)是儿童期最常见的出血性疾病,据统计近20%患儿会发展为慢性ITP(chronic ITP,CITP)。随着实验诊断技术的进步,发现实际上在儿童CITP中有近一半存在遗传性免疫异常,即相当比例是PID患者。但在CITP患儿中甄别PID较困难,特别是当患儿未出现感染、肿瘤等PID特征表现时。CITP中常见的较难甄别的PID有T细胞凋亡异常的自身免疫性淋巴细胞增生综合征(autoimmune lymphoproliferative syndrome,ALPS)、B细胞合成异常的普通变异型免疫缺陷病(common variable immunodeficiency,CVID)以及传递免疫信息脂筏异常的Wiskott-Aldrich综合征(Wiskott-Aldrich syndrome,WAS)。此外,仅携带有明确杂合致病基因突变患儿也易在临床中表现为"CITP"。从CITP患儿中甄别出PID将有利于及早开展有效的治疗管理,从而改善"CITP患儿"的不良预后。     

小儿过敏性和免疫性疾病诊断治疗进展

1　原发性免疫缺陷病 (PID)已明确的PID达到 12 0种以上 ,随着分子遗传学的快速发展 ,每年都有大约 10种新的PID被发现。儿科医生对PID认识能力和实验室诊断技术的提高 ,也使检出率明显增高。国内PID的报道较以往增多 ,一些误诊为其他疾病者 ,经分子生物学技术可得以确诊。有报道 3例WASP基因分析确诊的湿疹血小板减少伴免疫缺陷 (WAS)患儿中 ,有 1例轻型患儿仅有血小板减少 ,而被长期误诊为特发性血小板减少性紫癜即是典型的例子。国内首次报道 1例Ⅰ型白细胞粘附分子缺陷病 (LAD I) ,患儿白细胞缺乏粘附分子CD18,中性粒细胞不…     

单中心174例原发性免疫缺陷病临床预警症状的初步探讨

目的 分析并总结原发性免疫缺陷病（PID）患儿的临床感染特征和预警症状,了解预警症状对PID早期识别的应用价值。方法 参考2011年免疫学会国际联合会(IUIS)PID分类委员会公布的方案、泛美免疫缺陷病组(PAGID)和欧洲免疫缺陷病协会(ESID)提出的PID诊断和分类标准,在首都医科大学附属北京儿童医院2000年10月至2011年11月病例检索系统检索出院诊断中含有上述PID分类疾病的病历,对于诊断低丙种球蛋白血症和联合免疫缺陷的患儿除外继发性免疫缺陷病,逐份查阅病历重新诊断,并做出明确、可以和可能诊断,以明确、可以诊断的病例进行预警症状的分析。结果 ①174例PID患儿进入分析,男女比例为4.4∶1,其中抗体缺陷为主的免疫缺陷101例(58.0%),严重联合免疫缺陷病（SCID）34例(19.5%),吞噬细胞功能缺陷19例(10.9%),定义明确的免疫缺陷综合征10例(5.7%),免疫失调性疾病10例(5.7%)。②75例(43.1%)存在反复呼吸道感染,以抗体缺陷为主的免疫缺陷最为常见,与SCID间差异有统计学意义;卡介苗接种后异常反应在慢性肉芽肿病（CGD）中最多见,与抗体缺陷为主的免疫缺陷和SCID比较差异有统计学意义;腹泻病在定义明确的免疫缺陷综合征中较常见,败血症在SCID和CGD患儿中较常见,但PID各类型间比较差异无统计学意义。③72例(41.4%)患儿存在营养发育落后,PID各类型间差异无统计学意义;淋巴结、肝和脾肿大以CGD和免疫失调性疾病最为常见;鹅口疮在SCID中常见,与抗体缺陷为主的免疫缺陷差异有统计学意义;肛周脓肿以CGD多见,与其他PID类型比较差异有统计学意义。107例(61.5%)有明确微生物学证据。④PID患儿共电话随访到85例(48.8%),其中死亡28例(32.9%)。⑤124例为明确和可以诊断PID,其中106例(85.5%)具备≥2条预警症状。静脉应用抗生素清除病灶(96.0%)、体重不增或生长发育极度迟缓(41.1%)、反复呼吸道感染(41.9%)和PID家族史(22.6%)在不同类型PID中均占有较高的比例。结论 预警症状对PID有着很好的提示作用,需要静脉应用抗生素清除病灶、体重不增或生长发育极度迟缓和PID家族史对PID有预警意义,中耳炎、中枢神经系统感染和反复呼吸道感染在抗体缺陷为主的免疫缺陷中较为多见, 深部脓肿、卡介苗接种后异常反应对CGD有预警意义。慢性反复发作性腹泻对PID预警作用值得进一步关注。     

儿童原发性免疫缺陷病的临床特点

目的了解儿童原发性免疫缺陷病(PID)的临床特点,以助于早期识别和诊断。方法对本院儿科住院诊断为PID的26例病例进行回顾性分析,记录病史、出生史、家族史、临床表现、实验室检查、诊断、治疗和转归等情况。结果PID中选择性IgA缺乏症6例,普通变异性免疫缺陷病、婴儿暂时性低丙种球蛋白血症各5例,T、B细胞联合免疫缺陷病、湿疹血小板减少伴免疫缺陷综合征各4例,慢性肉芽肿病2例。25例临床表现为反复感染,感染部位主要是呼吸道和消化道;确定有条件致病菌感染6例,自身免疫性疾病5例,有家族病史6例。住院期间死亡、放弃治疗各1例,其他病情好转出院。结论对反复感染、条件致病菌感染或伴自身免疫性疾病患儿,结合家族史,应尽早行免疫学检查,以早期识别和诊断PID。     

传染性单核细胞增多症并发再生障碍性贫血

由EB病毒引起的自限性疾病——传染性单核细胞增多症(以下简称传单)偶可并发血小板减少性紫癜或溶血性贫血,却很少并发全血细胞减少。本文报告1例传单并发严重再生障碍性贫血(以下简称再障),并复习文献上所报道的其他9例传单伴全血细胞减少。     

淋巴细胞增生相关性免疫缺陷病10例临床表型及基因诊断分析

目的探讨淋巴细胞增生相关性免疫缺陷病的临床特征及基因突变类型。方法回顾性分析深圳市儿童医院风湿免疫科2014年5月至2016年12月10例淋巴细胞增生相关性免疫缺陷病患儿临床资料,包括临床表现、免疫学检查、基因突变分析、治疗及预后。结果 10例患儿中位起病年龄3岁8个月(4个月至11岁8个月),均表现为肝脾肿大或淋巴结病。外周血细胞减少7例,合并EB病毒血症或感染5例,反复呼吸道感染伴支气管扩张1例。Ig G(9.14~53.27g/L)及B细胞比例(10.6%~78.8%)正常或显著升高。基因检测显示PIK3CD、FASL、NRAS、KRAS、Caspase10或XIAP基因突变。均接受个体化治疗,并定期于免疫科门诊随诊。结论淋巴细胞增生相关性免疫缺陷病常表现为不明原因肝脾肿大或淋巴结病、外周血细胞减少、EB病毒血症或感染,早期完善基因检测有助于确诊,需结合病情和基因突变类型进行个体化治疗。     

Wiskott-Aldrich综合征致病基因的回复突变现象及其临床意义

Wiskott-Aldrich综合征(WAS)即湿疹、血小板减少、免疫缺陷综合征,为x连锁隐性遗传,是以湿疹、血小板减少、反复感染、易患淋巴系统恶性肿瘤和自身免疫性疾病为特征的原发性免疫缺陷病(PID).该病致病基因编码的蛋白质为WASP,是由502个氨基酸构成的富含脯氨酸的蛋白质.WASP表达于所有非红系造血细胞,包括CD28~+干细胞、血小板、淋巴细胞、中性粒细胞、巨噬细胞和树突状细胞,在细胞生长和骨架形成的信号转导过程中发挥重要作用.突变基因在体内发生自发性回复突变,从而导致体细胞嵌合已在多种PID患者中报道,如腺苷脱氨酶缺乏所致的重症联合免疫缺陷(ADA-SCID)~([1])、X连锁的严重联合免疫缺陷(X-SCID)~([2])、白细胞黏附分子缺陷病(LAD)~([3])、因核因子KB必需分子(NEMO)基因突变导致的高IgM综合征和外胚层发育不良~([4-5])等.随着我国基因诊断明确的WAS病例数不断增多,WASP基因的回复突变现象应引起高度关注,现就其发生机制和临床意义综述如下.     

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1免疫缺陷病的概念及分类免疫缺陷病(immunodeficiencydisease,IDD)是指免疫系统中任何一个成分或多个成分的缺乏或功能缺陷导致免疫功能障碍,引起机体防御功能下降或部分下降,并由此而引起的一组临床综合征。因遗传因素,如基因突变、缺失等所致免疫功能缺陷称为原发性免疫缺陷病(primaryimmu nodeficiencydisease,PID),因后天因素所致的免疫缺陷称为获得性和继发性免疫缺陷病(secondaryimmunodeficien cy,SID)[1,2]。PID包括原发性B细胞缺陷、原发性T细胞缺陷、联合免疫缺陷、补体系统缺陷和吞噬细胞缺陷等;SID由营养不良、感染、药…     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

GENETICS OF CARNEY COMPLEX AND RELATED FAMILIAL LENTIGINOSES, AND OTHER MULTIPLE TUMOR SYNDROMES

Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis.     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

All you ever wanted to know about infant formulas (but were afraid to ask)

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and health care professionals) will experiment with the infant formula available and often attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.     

Differential effects of inhaled budesonide on serum osteocalcin in children and adolescents with asthma

In recent years, measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogeneous glucocorticoids. Studies in children with asthma on inhaled glucocorticoids, however, have shown inconsistent results. The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide using three different osteocalcin assays: the Pharmacia Osteocalcin CAP FEIA, the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays. Two studies were conducted: 1) a randomised double blind two-period crossover study of 22 prepubertal children aged 5-12 years. In one period 800 μg budesonide was given once in the morning, in the other 400 μg was given twice daily; 2) a randomised double blind placebo controlled two period crossover study of inhaled budesonide 400 μg twice daily in fourteen 13-16 year old adolescents with pubertal stages II-V. In both studies, treatment periods were of four weeks duration, and blood samples were collected at the last day of each period. In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods. In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment. The suppression reached statistical significance with the CAP FEIA (P = 0.03) and the OSTK-PR (P =0.01) assays, but not with the ELSA-OSTEO assay (P = 0.06). Correlation analyses showed statistically significant correlation coefficients varying between 0.58 and 0.91 (P=0.03 and P < 0.0001, respectively). The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied, and inhaled glucocorticoids have differential effects in children and adolescents.     

alpha -SMOOTH MUSCLE ACTIN DISTRIBUTION IN THE PULMONARY VASCULATURE COMPARING HYPOPLASTIC AND NORMAL FETAL LUNGS

We investigated the intra-acinar pulmonary vascular muscularization in the developing human fetal lung between the 17th and 24th gestational weeks, that is, during the canalicular phase of lung development. Fifteen hypoplastic and 25 normal developed lungs were included in this study using monoclonal alpha -smooth muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image analysis was performed for morphometrical measurements and statistical evaluation. Alphasm-actin-immunoreactive intra-acinar vessels down to a luminal diameter of less than 10 mu m were detected in hypoplastic as well as in normally developed lungs. Crucial differences presented as follows: significantly higher density of intra-acinar vessels, especially due to alpha -sm-actin-negative vessels less than 30 mu m in luminal diameter, in the control group; significantly higher alpha -sm-actin immunoreactivity per section unit as well as per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin-positive cells of the intra-acinar vessel wall in the developing human lung were demonstrated to be smooth muscle cells, their immediate precursors, and pericytes. We conclude that the increased alpha -sm-actin immunoreactivity represents muscularization of the vessel wall in functional terms and may be regarded as one structural cause among others for the establishment of persistent fetal circulation in hypoplastic lungs.     

Représentations émotionnelles de la maladie chez 22 enfants drépanocytaires

Background

The emotional and psychological impact of chronical disease among children is considerable. The aim of this study was to explore the emotional representations of sickle cell children followed up at Bordeaux University Hospital in both qualitative and quantitative ways.

Methods

Prospective observational study, conducted from February to May 2010 among 22 sickle cell children (SS, SC and Sβ) followed at Bordeaux University Hospital and among their parents. A questionnaire evaluating depressive symptoms and emotional representations was proposed to children and to their parents separately, measuring their child's emotions. Children were asked to draw themselves during sickle cell crisis and without any painful episode, in order to illustrate their perception of their disease.

Results

Emotional and psychological impact on sickle cell children was important in this study. Eighty-six percent of children have commonly had negative feelings such as sadness, anger or fear. Thirty-six percent of them had depressive symptoms. Parents largely underestimated this impact. Drawings and answers to the questionnaire emphasized an important lack of disease understanding, social consequences, and depressive affects.

Conclusion

Psychological and emotional difficulties in sickle cell children should be identified and supported. Resources for psychological and educational support are necessary to improve the quality of life of sickle cell patients in France.     

Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to Intralipid

Parenteral lipids are susceptible to light-induced peroxidation, particularly under phototherapy. Ascorbic acid is protective. The aim of this study was to investigate whether dark delivery tubing and/or coadministration of multivitamin preparations could prevent peroxidation of Intralipid without undue vitamin loss. In experiments carried out on the benchtop, lipid peroxidation occurred in ambient light and was more extensive under phototherapy. Dark tubing decreased peroxide formation, but only by about 65%. In simulated clinical conditions in which solutions were pumped through standard clear or dark minibore plastic tubing, Intralipid accumulated lipid peroxides as measured by the FOX assay (280 µM) or as triglyceride hydroperoxides (52 µM). Multivitamin preparations (MVIP or completely, and were fully protective when used with dark tubing. There was loss of riboflavin (65% from Soluvit and 35% from MVIP) in clear tubing but this was decreased to 18% and 11%, respectively, in dark tubing. Ascorbate loss was 20% (MVIP) and 50% (Soluvit) and only slightly less in dark tubing. Ascorbate loss was also seen in the absence of Intralipid and is due to riboflavin-induced photo-oxidation.Conclusion: Multivitamin preparations protect Intralipid against light-induced formation of lipid hydroperoxides, and administering multivitamins with Intralipid via dark delivery tubing provides a practical way of preventing peroxidation of the lipid while limiting vitamin loss. This procedure should be considered for routine use as well as with phototherapy. Soluvit/Vitlipid) inhibited peroxide formation almost     

SociaBillyQuizz,un jeu pour l’entraînement aux habiletés sociales chez l’enfant et l’adolescent : étude exploratoire

Background

The SociaBillyQuizz is a therapeutic game designed for social skills training groups with children and adolescents. Using an entertaining method, this media requests several dimensions: exposure, cognition, communication skills, imagination, emotional expression and sign decoding. In this preliminary study, the setting includes two groups of six adolescents, one with social anxiety disorder and the other with Asperger syndrome.

Objective

To evaluate, in an exploratory study, the effects of a therapeutic device involving this game for these two clinically different groups of adolescents.

Methods

During 26 of 1 hour weekly sessions, two adolescents groups participate to a program including the SociaBillyQuizz and cognitive behavioral therapies. The groups are moderated by two therapists. The SociaBillyQuizz is a board game for two to six players; its goal is to collect points by answering instructions from the different thematic cards. There are four thematic cards: action cards (players have to do something), brainstorming cards (players have to use their imagination and demonstrate cognitive flexibility), interview cards (players have to express themselves about what they think or feel) and mystery cards (unexpected instructions). According to the groups’ clinical characteristics, some aims are specifically highlighted. In the anxiety disorder group, the cognitive dimension is privileged and in the Asperger syndrome group, we emphasise the pretend, cognitive flexibility and theory of mind. The effects are measured by the Rathus Assertiveness Schedule and the Fear Avoidance Hierarchy (FAH) for the social anxiety disorder group and by the Faux Pas Recognition Test and the Social Responsiveness Scale (parent version) for the Asperger group.

Results

These assessment tools indicate, for both groups, a significant increase of the scores corroborating the observed clinical effects. For eleven of the twelve adolescents, a clinical interview 6 months after the retest shows a continuity of therapeutic benefit.

Discussion

These early results suggest that a social skills training device featuring the SociaBillyQuizz produces clinical improvements in these two groups of adolescents. In future researches, with control group and more complete follow-up, nature and effectiveness of its contribution should be specified.

Conclusion

In this preliminary study, the SociaBillyQuizz appears to be an interesting therapeutic tool that can increase implication, motivation, participation and cohesiveness of the group. It also makes easier the cognitive-behavioural-strategies learning.     

Les effets de l’incarcération chez les mineurs

Aim of this study

In this article we wish to question the effects of incarceration on minors. The history of prison reveals that it is the work of a humanist and philanthropic discourse that ensued from the effects of revolutionary ideas. However, from the moment of its reform – that transformed it from a place of confinement to a penal institution – it has only demonstrated its dysfunctional aspect. Our objective is to initiate a reflection on the effects of incarceration, whether it be collective or individual and in particular when it involves adolescents.