较大潮气量机械通气致幼兔肺生物伤中NF-κB的作用及对致炎细胞因子的影响

目的探讨NF-κB在幼兔较大潮气量机械通气致肺生物伤中的作用以及对肿瘤坏死因子α(TNF-α)和白细胞介素8(IL-8)的影响。方法27只普通级幼兔随机等分为3组,(1)对照组(NMV,n=9):不进行机械通气;(2)常规机械通气组CMV(CMV,n=9):潮气量(VT)=8ml/kg;(3)大潮气量机械通气组(LMV,n=9):VT=24ml/kg。采用凝胶电泳迁移率改变分析法(EMSA)检测各时相点肺组织核蛋白提取物中NF-κB活性,WesternBlot法测定肺组织IκBα含量,同时应用RT-PCR和ELISA法检测肺组织匀浆中TNF-α和IL-8mRNA表达及其蛋白含量,并观察肺组织病理改变。结果在各时相点LMV的NF-κB活性明显高于NMV和CMV(P<0·01);CMV的NF-κB活性则高于NMV(P<0·01)。IκBα含量在LMV随通气时间延长呈进行性降低,与NMV和CMV比较有显著性差异(P<0·01)。机械通气后LMV的TNF-α和IL-8含量及表达较CMV、NMV明显增高(P<0·01),TNF-α表达及含量在通气后4h达高峰,6h明显降低,而继TNF-α达峰后,IL-8在通气后6h达最高。肺组织病理学显示,随通气时间延长,LMV的肺泡结构破坏,肺泡壁和肺间质内有大量中性粒细胞浸润和较多红细胞渗出。CMV的肺间质及肺泡壁轻度水肿、有少量粒细胞浸润。NMV未见病理性改变。结论在损害性机械通气肺损伤的发生过程中,IκBα降解和NF-kB活化可能参与了肺组织致炎细胞因子基因表达的调控过程。     

吸入性糖皮质激素对哮喘小鼠核因子-kB及Th2类细胞因子的影响

目的探讨糖皮质激素对哮喘小鼠核因子-kB（YF-kB）表达及Th2类细胞因子的影响。方法30只BALB／c小鼠随机分为正常组、哮喘组、布地奈德治疗组．采用ELISA法测定其支气管肺泡灌洗液（BALF）中IL-4、IL-5、IFN-γ的含量，免疫组织化学检测肺组织NF-kB表达。结果哮喘组与正常组、治疗组比较肺组织NF-kB表达及BALF中IL-4、IL-5含量均有显著差异（P均〈0．01）。NF-kB活化细胞百分比与BALF中IL-4、IL-5含量呈显著正相关（r=0．79，0．68P〈0．01）。结论惰皮质激素抑制肺组织NF-kB激活．NF-kB与IL-4、IL-5的产生相关，糖皮质激素通过抑制Th2类细胞功能来增强Th1反应。     

小潮气量常规机械通气对发育肺生长因子和炎症因子表达的影响

目的：探讨小潮气量常规机械通气对发育肺生长因子（GFs）和炎症因子表达的影响。方法：分别将早产猪（85％孕龄）、足月新生猪及幼猪（4~5周龄）随机分为机械通气组（MV组）和自主呼吸对照组（NMV组）。调节呼吸机参数,使呼出气潮气量维持在6～8 mL/kg,机械通气6 h（早产猪）或24 h（新生猪、幼猪）后检测肺组织GFs（PDGF-B,IGF-I,KGF,HGF,VEGF,TGF-β1）及炎症因子（IL-1β,IL-6,IL-8,TNF-α）mRNA表达,免疫组化方法观察GFs蛋白表达与分布。多组间比较用单因素方差分析或Kruskal-Wallis检验,两组间比较用t检验或Mann-Whitney U检验。结果：①在早产组,MV组PDGF-B,IL-1β,IL-6,IL-8 mRNA水平较NMV组增高（5.11±0.10 vs 4.88±0.01, 4.95±0.27 vs 4.08±0.37, 4.76±0.27 vs 4.00±0.28, 5.31±0.57 vs 4.15±0.46; P<0.01或0.05）,IGF-I mRNA水平降低（3.54±0.13 vs 3.80±0.11; P<0.01）;②在足月新生组及幼年组,MV组GFs及炎症因子mRNA水平较NMV组差异均无显著性。结论： 生后早期机械通气干扰了早产肺GFs的表达,并诱发促炎因子表达,促进了肺损伤的发生;但对足月和幼年肺GFs和炎症因子表达无明显影响。     

机械通气方式对新生猪支气管肺泡灌洗液炎性因子及肺表面活性物质相关蛋白A的影响

目的 观察常频机械通气(CMV)、高频振荡通气(HFOV)、部分液体通气(PLV)3种机械通气方式对急性肺损伤(ALI)新生猪BALF炎性因子及肺表面活性物质相关蛋白A(SP-A)水平的影响.方法 出生1～3 d健康新生猪24只,用9 g/L盐水(38 ℃,35 mL/kg)灌洗制备ALI模型.随机分为4组:对照组(6只,模型制备成功后不予通气,直接处死)、CMV组(6只)、HFOV组(6只)、PLV组(6只),行机械通气24 h后处死动物,用ELISA法检测BALF中TNF-α、IL-8、IL-1及SP-A水平.结果 3种方式机械通气24 h后,BALF中3种炎性因子及SP-A总体均数比较差异均有统计学意义(P均=0.000),PLV组、HFOV组SP-A水平较CMV组高(P均＜0.05),PLV组IL-8、IL-1、TNF-α水平较CMV组低(P均＜0.05),PLV组IL-8、TNF-α水平较HFOV组低(P均＜0.05),HFOV组IL-8、TNF-α水平较CMV组低(P均＜0.05).结论 不同机械通气方式致肺部炎性反应不同,PLV致肺部炎性反应最轻.PLV较CMV、HFOV更能增加SP-A表达,降低SP-A的降解.     

小剂量氢化可的松对脓毒症大鼠海马组织核因子kB表达的影响

目的 研究小剂量氢化可的松（HC）对内毒素诱导的脓毒症大鼠海马组织核因子-kB（NF-kB）、抑制因子kB（IkB）表达的影响。方法雄性Wistar大鼠54只随机分为：对照组（A组）6只，模型组（B组）24只、小剂量HC干预组（C组）24只。腹腔注射脂多糖（LPS）1mg／kg建立脓毒症大鼠模型，尾静脉注射小剂量HC（6mg／kg）作为干预，分别在注射后2、8、16、24h分时段麻醉并灌注固定取脑。B组和C组每个时段点各6只。采用免疫组织化学方法及医学图像分析系统检测大鼠海马NF-kB、IkB的表达。结果模型组NF-kB表达较正常对照组显著上调（P〈0．05），IkB表达先降低后逐步上升，较对照组亦明显增加（P〈0．05），以8h为最高；干预组海马NF-kB表达较模型组显著下调（P〈0．05）；IkB表达较模型组明显增加（P〈0．05）。结论小剂量HC可通过诱生IkB来抑制NF-kB的表达，进而调控LPS诱导的脓毒症脑功能障碍，NF-kB信号转导途径在其发病机制中起重要作用。     

地塞米松对重症胎粪吸入幼兔肺组织中肿瘤坏死因子α和白介素8水平的影响

目的探讨地塞米松对胎粪吸入幼兔肺组织中肿瘤坏死因子-α(TNF-α)和白介素-8(IL-8)水平的影响。方法将24只日龄20～30天的幼兔随机分为对照组、生理盐水组和地塞米松组各8只,对照组气管插管后不灌胎粪;后两组气管插管后注入4 ml/kg的45 mg/ml胎粪混合物,地塞米松组在胎粪灌入后1 h和3 h静脉注射地塞米松0.5 mg/kg,生理盐水组在同样时间静脉注射等量的生理盐水;3组均在呼吸机比例辅助通气模式下通气,维持潮气量4～6 ml/kg、血氧饱和度85%以上和呼气末二氧化碳分压35～45 mm Hg为目标调节呼吸机参数,8 h后处死。取肺组织匀浆和支气管肺泡灌洗液(BALF),并用酶联免疫吸附试验测定TFN-α和IL-8的含量。结果对照组BALF和肺组织匀浆中TNF-α、IL-8含量均低于地塞米松组和生理盐水组,地塞米松组低于生理盐水组[BALF中TNF-α(pg/ml):(29.2±2.0)、(47.8±3.8)、(59.2±4.4),IL-8(pg/ml):(297.4±10.9)、(444.3±48.6)、(596.1±90.8);肺组织匀浆中TNF-α:(40.2±2.3)、(57.4±6.2)、(76.2±7.7),IL-8:(187.9±11.0)、(485.3±30.2)、(645.0±13.7)],差异有统计学意义(P均<0.05)。结论地塞米可以降低幼兔胎粪吸入肺组织匀浆和BALF中TNF-α和IL-8的水平,减轻肺损伤。     

不同潮气量通气启动新生鼠肺纤维化的特点

目的：探讨不同潮气量机械通气后新生大鼠肺胶原合成的变化及其机制。方法：24只新生Sprague-Dawley大鼠随机分为对照组、常规通气组（潮气量10 mL/kg）及过度通气组（潮气量25 mL/kg）,每组8只。机械通气5 h后处死,取肺组织,左肺行肺组织病理损伤评分,以免疫组织化学方法观察结缔组织生长因子（CTGF）表达。PCR法检测右肺组织Ⅲ型前胶原蛋白mRNA（PcolⅢ mRNA）、半胱氨酰白三烯mRNA（CysLT1 mRNA）及CTGF mRNA水平。结果：肺损伤程度和纤维化程度随着潮气量增加而增加(P<0.05）。与对照组比较,过度通气组肺组织CTGF mRNA水平显著性增高（P<0.05）。肺组织PcolⅢ mRNA 和 CysLT1 mRNA水平随潮气量增加而增加,各组间差异有统计学意义（P<0.05）。肺组织中PcolⅢ mRNA表达与肺组织病理损伤程度呈正相关关系（r=0.78,P<0.01）;CTGF、CysLT均和PcolⅢ呈正相关关系(r＝0.59,0.86,P<0.01)。结论：不同潮气量机械通气导致不同程度肺损伤,并启动肺纤维化。肺纤维化程度与肺损伤程度一致。肺纤维化的启动与CysLT作用和CTGF激活有关。［中国当代儿科杂志,2010,12（10）：799-803］     

重症肺炎支原体肺炎患儿肺炎支原体DNA复制水平与病情的相关性

目的 探讨重症肺炎支原体肺炎（SMPP）患儿咽拭子、肺泡灌洗液（BALF）中肺炎支原体DNA （MP-DNA）复制水平与病情的相关性。方法 44例行支气管肺泡灌洗术的SMPP患儿为研究对象,分别在急性期和恢复期检测相关血清细胞因子水平及咽拭子MP-DNA复制倍数,并检测急性期BALF中白细胞介素（IL）-18水平及MP-DNA复制倍数。并按照病程中是否出现呼吸衰竭需要机械通气分为机械通气组（n=19）与非机械通气组（n=25）,比较两组患儿肺泡灌洗液中MP-DNA复制倍数。结果 与恢复期相比,SMPP患儿在急性期时,血清C反应蛋白、红细胞沉降率、乳酸脱氢酶、IL-1、IL-6、IL-8、IL-18水平显著增高（P < 0.05）。急性期咽拭子与BALF的MP-DNA复制倍数呈显著正相关（r=0.613,P < 0.05）;BALF中MP-DNA复制倍数与外周血及BALF的IL-18水平呈正相关（分别r=0.613、0.41,均P < 0.05）。机械通气组BALF中MP-DNA复制倍数高于非机械通气组,且全身激素治疗时间明显长于非机械通气组,血清乳酸脱氢酶、IL-18及BALF中WBC总数、IL-18水平也更高（P < 0.05）。结论 SMPP患儿急性期咽拭子与BALF MP-DNA复制水平可作为病情评估的参考。     

小儿慢性病贫血红系祖细胞与肿瘤坏死因子α、白介素6的关系研究

目的 研究检测肿瘤坏死因子α（TNF-α）、IL-6（白介素-6）两种慢性病发生有关的细胞因子水平，以及红系造血祖细胞集落培养生长探讨它们在慢性病贫血（ACD）发病中的作用。方法 检测病例组为慢性病贫血组（ACD组）患儿，对照组为慢性病无贫血组（NA组）和缺铁性贫血组（IDA组）患儿的血清肿瘤坏死因子α（TNFα）、白介素-6（IL-6）水平，以及骨髓的红系祖细胞水平（BFU-E、CFU-E）。结果 三组BFU-E有差异（F=3．56，P〈0．05；三组CFU-E有显著差异（F=8．87，P〈0．01）。ACD组与NA组相比，血清TNF-α前者高于后者（t=2．25，P〈0．05），两组血清IL-6无差异（t=1．91，P〉0．05）。在20例行骨髓培养的慢性病患儿中，血清TNFα与骨髓BFU-E之间无显著相关性（r=-0．37，P〉0．05）；血清TNF-α与CFU-E之间有负相关（r=-0．57，P〈0．05）；IL-6与BFU-E、CFU-E无相关性。结论 ACD患儿骨髓红系祖细胞BFU-E、CFU-E生成受抑制；血清TNF-α、IL-6的升高参与贫血发生；TNFα可能抑制慢性病患儿骨髓CFU-E形成而导致贫血。     

儿童癫痫发作期血清IL-8、IL-10、TGF-β1-及TNF-α水平与临床的关系

目的探讨IL-8、IL-10、TNF-α及转化生长因子-β1（TGF-β1）在癫痫发作中的作用及临床意义。方法选择新诊断的癫疴病例16例，并没健康对照组10例，采用ELISA方法进行血清IL-8、IL-10、TNF-α及TGF-β1水平测定。结果癫痫组血清IL-10、TGF-β1和TNF-α水平较正常对照组差异有统计学意义（Z=2.97～42．96，P均〈0．01），癫痫组血清IL-8水平较正常组儿童增高，但两者之间差别无统计学意义（Z=1．48，P〉0．05）。结论癫痫患儿发作后存在免疫功能的紊乱，下调免疫功能的因子（IL-10和TGF-β）水平显著增高，提示存在明显的免疫抑制现象，可能使机体细胞免疫功能下降；TNF-α显著增高，提示其可能参与了导致脑组织神经功能异常的活动。     

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.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

�¶�֢��ϵ�ϰ���ע��ȱ�ݶද�ϰ������ڵ�ת��

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     

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.     

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.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

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.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

---

---

Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.