卡介苗接种预防毛细支气管炎婴儿日后发生喘息的探讨

为观察卡介苗（BCG）单用或联用干扰素γ（IFN-γ）和维生素A（VitA)对毛细支气管炎（毛支）患儿结核菌素纯蛋白衍化物（PPD）皮肤试验，喘息发作及单核细胞源性细胞因子白细胞介素18（IL-18）水平的变化。给予44例毛支患儿单纯BCG或合并IFN-γ/VitA治疗，于治疗前和3个月后进行PPD皮试，测定外周血单个核细胞体外产生IL-18的水平。随访时间平均1年，观察喘息发作情况，未接受BCG接种的19例毛支婴儿作为对照组。结果 BCG接种后PPD平均硬结直径大于干预前及毛支对照组恢复期，以合并IFN-γ，VitA治疗组更为突出。BCG接种组1年内喘息发作频率低于对照组恢复期。干预后IL18水平明显升高，尤以合并IFN-γ，VitA治疗组为高；PPD皮试强度与IL-18水平呈正相关。提示BCG可促进毛支患儿PPD皮试阳转率，增强IL-18活性，具有预防毛支患儿日后发展为哮喘的作用。IFN-γ，VitA可协同BCG的上述作用。     

基因重组γ-型干扰素治疗小儿毛细支气管炎对T淋巴细胞调节作用的观察

目的　观察基因重组γ 型干扰素 (IFN γ)对呼吸道合胞病毒 (RSV)毛细支气管炎 (毛支 )患儿TH1/TH2亚群功能的调节作用。方法　将 4 0例RSV毛支患儿随机分为IFN γ观察组 2 0例及对照组 2 0例。选择 15例健康婴儿为正常组。治疗前用单克隆抗体双色免疫荧光FITC/PE行双标记 ,流式细胞仪检测患儿外周血单个核细胞 (PBMCs)辅助性T淋巴细胞CD4 及其TH1亚群CD4 CD4 5RA ,TH2亚群CD4 CD4 5RO 的表达 ,用ELISA方法检测患儿血清中细胞因子IFN γ、IL 4水平。经IFN γ治疗后 7～ 10d复查。结果　与正常组相比 ,RSV毛支患儿外周血辅助性T淋巴细胞CD4 ,TH1亚群CD4 CD4 5RA 明显下降 (P <0 0 5 ) ,TH2亚群CD4 CD4 5RO 没有明显变化 (P >0 0 5 ) ,TH1/TH2比值明显降低 (P <0 0 5 ) ,血清中IFN γ、IL 4水平均有降低 ,其中IFN γ水平下降非常明显 (P <0 0 1) ,IFN γ/IL 4比值降低 (P <0 0 5 )。经IFN γ治疗后 ,观察组IFN γ水平明显升高 ,TH1/TH2、IFN γ/IL 4比值升高 ,观察组及对照组IL 4水平均没有明显变化。结论　婴幼儿RSV毛支患儿存在TH 细胞及其免疫功能状态紊乱 ,主要表现为TH1及其功能下降 ;TH2及其功能相对增强 ,TH1/TH2的失衡是导致婴幼儿下呼吸道感染发生TH2样反应的重要免疫机制。     

吸入糖皮质激素预防呼吸道合胞病毒毛细支气管炎后反复喘息的临床观察

目的 观察吸入糖皮质激素能否预防呼吸道合胞病毒(RSV)毛细支气管炎(简称毛支)后反复喘息的发生.方法 选择2003年7月-2004年12月住院的RSV毛支患儿200例,入院后查外周血嗜酸性粒细胞、血清总IgE,血TH1/TH2水平及肺功能.毛支治愈后随机分为治疗组(100例)和对照组(100例),治疗组吸入布地奈德气雾剂3个月,对照组未给予治疗.3个月后随访,复查肺功能.停止治疗后继续观察2年,了解吸入激素3个月对患儿反复喘息发生的影响.结果 ①毛支治愈后的3个月内,治疗组无症状天数为(78.92±8.03)d,对照组为(74.83±9.54)d,两组比较差异有统计学意义(P＜0.01).②3个月后治疗组肺功能各项指标均比对照组明显好转(P＜0.05).③治疗组按吸入激素疗效分为毛支后喘息组和未再喘息组,这两组患儿入院时外周血嗜酸性粒细胞、血清总IgE、血Th1/Th2差异均有统计学意义(P＜0.05),而肺功能差异无统计学意义(P＞0.05).④停止治疗后2年两组患儿喘息再发比例差异无统计学意义(P＞0.05).结论 RSV毛支患儿治愈后吸入布地奈德气雾剂3个月,可改善肺功能.外周血嗜酸性粒细胞增多、血清总IgE升高、Th2功能亢进者,治疗期间可以减少毛支后喘息再发.吸入激素3个月不能减少停药后2年内喘息的发生.     

激素吸入治疗及干预毛细支气管炎的疗效观察

目的 分析普米克吸入治疗毛细支气管炎(简称毛支)及预防日后哮喘发作的疗效.方法 50例患儿随机分成2组,对照组只予以基础治疗,治疗组除基础治疗外予以普米克雾化吸入,观察2组急性期疗效,治疗组于毛支痊愈后继续吸入3个月普米克气雾剂进行干预治疗,观察1年内哮喘的发病率.结果 急性期治疗组病情恢复明显比对照组快,一年随访结果,治疗组喘息发作率明显低于对照组(P＜0.05).结论 提示普米克令舒雾化吸入治疗毛支急性期效果好,小剂量序贯疗法能明显减少日后哮喘的发病率.     

卡介苗/纯蛋白衍生物对支气管哮喘患儿临床症状及肺功能的影响

目的探讨卡介苗(BCG)及其纯蛋白衍生物(PPD)对支气管哮喘(哮喘)患儿的临床控制等级和肺功能的影响,为BCG/PPD在哮喘中的防治提供理论根据。方法安徽医科大学附属省立医院哮喘门诊随机抽取年龄5～14岁哮喘患儿,使用PPD试验筛选出68例PPD试验阴性的哮喘患儿,入组前评估患儿哮喘严重程度,随机分为BCG/PPD干预组(常规治疗并予BCG/PPD干预)和非干预组(仅予常规治疗)。治疗前检测肺功能、评估哮喘病情严重程度。干预组除常规治疗外接种BCG,用PPD试验判定接种成功后,每月皮内注射PPD 5 U,共6个月。每月评估并根据患儿临床控制等级予相应治疗,治疗3个月、6个月时评估2组患儿最大呼气流量占预计值百分比(PEF%)、肺功能、临床症状及临床控制等级的变化。结果 1.临床控制等级:3个月时干预组日间症状、夜间症状、活动受限及临床控制例数与非干预组比较差异均有统计学意义(Pa<0.05);6个月时干预组夜间症状、PEF%改善情况及临床控制例数与非干预组比较差异均有统计学意义(Pa<0.05)。2.肺功能:2组肺功能各指标治疗3个月、6个月时较治疗前均明显改善(Pa<0.05);治疗3个月、6个月时干预组PEF%较非干预组改善(Pa<0.05);6个月时干预组肺功能改善较非干预组明显(Pa<0.05)。结论常规治疗基础上加用BCG/PPD可显著改善哮喘患儿临床症状及肺功能,且在6个月内能持续改善患儿肺功能。     

过敏性紫癜患儿结核菌素试验皮试阳性率与CD30表达及细胞因子水平的研究

目的　通过观察过敏性紫癜 (SHP)儿急性期T细胞CD30表达、血清IgE水平以及OT皮试阳性率 ,探讨Th2功能异常在SHP发病中的作用。方法　流式细胞仪检测CD30阳性细胞百分率 ,细胞培养上清中白细胞介素 4(IL 4)、干扰素 (IFN γ)及血清中IgE用ELISA法测定。结果　经PHA刺激后 ,SHP患儿急性期CD30阳性细胞率明显高于正常儿童 (P <0 .0 0 1 ) ,T细胞产生IL 4明显升高而IFN γ显著下降 ,其血清IgE水平显著升高 ;接种卡介苗 (BCG)的SHP患儿OT皮试阳性率显著低于正常对照。结论　SHP急性期以Th2亚群占优势 ,表明SHP的发生与结核菌素反应成反比     

毛细支气管炎患儿尿白三烯E4检测及其意义

目的通过检测毛细支气管炎(毛支)患儿尿白三烯E4(LTE4)水平及特应质对其的影响来探讨毛支患儿预后。方法对47例毛支患儿急性期恢复期及25例对照组进行尿LTE4测定,对急性期患儿同时检测嗜酸性粒细胞计数(EC)。结果毛支急性期尿LTE4水平(62.11±12.23)pmol/L较对照组(22.19±1.50)pmol/L、恢复期(34.86±5.75)pmol/L明显升高(P均<0.01),恢复期较对照组明显升高(P<0.01);与轻度毛支组(59.16±12.25)pmol/L比较,重度组患儿尿LTE4水平(98.04±8.04)pmol/L明显升高(P<0.01);特应质组(88.75±10.45)pmol/L毛支患儿尿LTE4水平较非特应质组(55.28±11.44)pmol/L明显升高(P<0.01);急性期毛支患儿尿LTE4水平与外周血EC计数无相关性(r=0.367,P>0.05)。结论毛支急性期尿LTE4产生增加,恢复期尿LTE4水平仍维持于高水平;重症毛支患儿尿LTE4水平明显升高,提示尿LTE4水平与病情严重程度有关;白三烯是影响特应质毛支患儿预后的重要的炎症介质;外周血EC不能很好的反映...     

细支气管炎患儿血清嗜酸性细胞趋化因子测定及肺功能检查的临床意义

目的探讨细支气管炎(简称毛支)患儿嗜酸性细胞趋化因子(eotaxin)水平及肺功能改变的临床意义。方法采用双抗体夹心酶联免疫吸附试验方法,对30例毛支急性期、20例恢复期患儿的外周血标本进行血清eotaxin水平测定,同时采用美国森迪公司2600婴儿肺功能仪进行肺功能检查,并与20例健康对照组儿童相比较。结果毛支恢复期组患儿血清eotaxin水平比急性期组明显下降(P<0.01),但两组均明显高于健康对照组儿童(P均<0.01);毛支恢复期组患儿呼出75%潮气量时的呼气流速/潮气呼气峰流速(25/PF)及潮气呼气中期流速/潮气吸气中期流速(ME/MI)比急性期组明显升高(P<0.01),但25/PF仍低于对照组(P<0.01),而ME/MI与对照组相比无显著性差异(P<0.05);毛支患儿急性期组血清eotaxin水平与25/PF呈负相关(r=-0.42,P<0.05),与ME/MI无相关性(r=0.05,P>0.05)。结论毛支患儿急性期肺功能主要表现为阻塞性通气功能障碍,eotaxin参与了毛支的发病过程。     

毛细支气管炎患儿血清白细胞介素-13及肺功能检测的意义

目的探讨毛细支气管炎(毛支)患儿血清IL-13及肺功能检测的意义。方法采用双抗体夹心酶联免疫吸附试验(ELISA),对30例毛支急性期、20例恢复期患儿外周血行血清IL-13水平测定;同时采用美国森迪公司2600婴儿肺功能仪进行肺功能检查,并与20例健康对照组儿童比较。结果毛支恢复期组患儿血清IL-13水平较急性期组明显下降(P<0.01),但两组均明显高于对照组(P均<0.01);毛支恢复期组肺功能指标中呼出75%潮气量时的呼气流速/潮气呼气峰流速(25/PF)及潮气呼气中期流速/潮气吸气中期流速(ME/MI)均较急性期组明显升高(P均<0.01),但25/PF仍低于对照组(P<0.01),而ME/MI与对照组比较无显著性差异(P>0.05)。毛支患儿急性期组血清IL-13水平与25/PF呈显著负相关(r=-0.38 P<0.05),与ME/MI无相关性(r=-0.002 P>0.05)。结论IL-13参与毛支发病过程,降低其水平有助于毛支的痊愈;毛支患儿急性期肺功能主要表现为小呼吸道阻塞性通气功能障碍。     

二丙酸倍氯米松和干扰素吸入疗法治疗毛细支气管炎的临床研究

目的 研究二丙酸倍氯米松和干扰素吸入疗法治疗毛细支气管炎（毛支）的临床疗效，评价其临床价值。方法 将83例毛支患儿随机分为两组，两组病例采用相同的综合治疗，治疗组（n=42）在综合治疗基础上，急性期行干扰素吸入治疗及缓解期行二丙酸倍氯米松长期吸入治疗，对治疗前后主要症状及体征的持续时间，平均住院天数进行比较。结果 急性期在治愈率、喘憋缓解、肺部哮鸣音及湿哕音消失时间及住院时间等方面，治疗组明显优于对照组（P〈0．01）。恢复期治疗组喘息率低于对照组。结论 急性期吸入干扰素有利于疾病的恢复，恢复期吸入二丙酸倍氯米松可减少喘息的发作。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

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.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

How well are we doing? – Metabolic control in patients with diabetes

OBJECTIVE: To compare the present level of metabolic control in children and adolescents with insulin-dependent diabetes mellitus (IDDM) attending Brisbane paediatric diabetes clinics with published overseas data. METHODOLOGY: Blood HbA1c concentrations, population characteristics, current treatment practices and short-term complications were recorded in all patients, aged 19 years and under, attending the diabetes clinics of the two Brisbane Children's Hospitals or the private practice of one of the authors (MJT) in the first quarter of 1998. RESULTS: Two hundred and sixty-eight patients were assessed (M/F 142/126). Ages ranged from 1 to 19 years (mean 11. 2 years); duration of IDDM was 0-16 years (mean 4.4 years); and 141 (53%) were pubertal. Of those aged less than 13 years, only 4% had more than two injections daily. Insulin doses (U/kg/day) rose with increasing age. Larger doses were required in regimens involving more than two injections per day than those involving one to two injections per day. Ketoacidosis or severe hypoglycaemia in the last 3 months were reported in eight (2.7%) and 17 (6.3%) of patients, respectively. Mean HbA1c (+/- SD) was 8.6 +/- 1.4% (range 5.2-14.0%), with 33% of children having a HbA1c concentration < 8%. HbA1c concentrations were significantly related (P < 0.05) to insulin dose and to duration of diabetes, but not to severe hypoglycaemia, ketoacidosis, age, frequency of injections, or number of clinic visits per year. Mean HbA1c concentration was significantly higher (P < 0.05) in those children in puberty (8.7 +/- 1.5%) than in those not in puberty (8.5 +/- 1.2%). CONCLUSION: Only 33% of patients had a HbA1C concentration less than 8% and 6.3% had a severe hypoglycaemic episode in the 3 months. These results are similar to published overseas data.