糖皮质激素诱导试验与儿童急性淋巴细胞性白血病预后的关系

目的　通过糖皮质激素早期诱导试验评估儿童急性淋巴细胞性白血病的预后。方法　诱导试验是根据初发病时外周血幼稚细胞计数及服用糖皮质激素 (GC) 7d后外周血中幼稚细胞的动态变化。此后 ,所有病例都接受同样强烈的化疗方案。结果　 6 0例患儿中对泼尼松诱导试验敏感 (PGR)者为 4 9例 ,占 81 7% ,其中高危患儿 6例 ,中危患儿 8例 ,低危患儿 35例。在 4 9例PGR患儿中 38例 (77 6 % )处于持续缓解状态 (CCR) ,中位缓解期为 2 2 5个月 ;复发 3例 ,占 6 1%。 6 0例患儿中对泼尼松诱导试验不敏感 (PPR)者为 11例 ,占 18 3%。在PPR 11例中 ,5例早期复发 ,占 4 5 5 % ;2例达CCR ,占 18 2 %。从治疗第 19天、第 30天的骨髓检查 ,PPR组 19dM1、M2 、M3分别为 72 7%、18 1%、9 2 % ;PGR组 19dM1、M2 分别为 96 %、4 % ,无一例为M3 。达CR时间 ,PPR组明显迟于PGR组。结论　GC在用于治疗恶性淋巴细胞增生性疾病中 ,起到了重要作用。     

儿童急性淋巴细胞性白血病治疗中微量残留病与泼尼松窗口治疗反应比较的探讨

目的 探讨儿童急性淋巴细胞性白血病(ALL)微量残留病(MRD)和糖皮质激素窗口疗效的相关性.方法 2005年1月-2007年7月37例ALL初发患儿接受糖皮质激素窗口治疗7 d,根据外周血幼稚细胞计数,分为泼尼松反应良好(PGR)和泼尼松反应不良(PPR)两组,监测MRD并与窗口结果对临床预后预测进行比较.结果 ①33/37例有MRD合适标记,其中治疗1年内MRD<0.01%者为30/33例(90.91%),MRD≥0.01%者为3/33例(9.09%),两组临床缓解与复发差异有统计学意义.②)32/37例为PGR(占86.49%);5/37例为PPR(占13.51%).MRD结果和泼尼松窗口治疗反应差异无统计学意义.③4/37例未检出MRD标记,2/4例缓解(50.00%).结论 MRD结果和泼尼松窗口治疗反应,均能够作为评判ALL预后的参考指标.     

儿童急性淋巴细胞白血病MRP1的表达及意义

目的分析多药耐药相关蛋白(MRP1)mRNA在急性淋巴细胞性白血病(ALL)患儿中的表达及其临床意义。方法入选67例初诊ALL患儿及10例正常对照儿童,采集骨髓。应用定量RT-PCR方法检测并比较骨髓中MRP1 mRNA表达水平。结果标危、中危、高危组MRP1 mRNA表达水平分别为4.28(2.75~6.12)、5.62(4.99~8.60)和7.56(3.66~11.13),三组间差异有统计学意义(P0.01);高危组和中危组的MRP1 mRNA均高于与标危组,差异有统计学意义(P0.05)。T-ALL组MRP1 mRNA表达水平为7.71(6.49~14.35),高于B-ALL组的表达水平[5.18(3.89~8.46)],差异有统计学意义(P0.01)。高表达组(n=34)第7天泼尼松预处理敏感率为70.59%,而低表达组(n=33)敏感率为90.91%,差异有统计学意义(P0.05)。高表达组第33天骨髓完全缓解率为64.71%,低表达组为87.88%,差异也有统计学意义(P0.05)。结论 ALL患儿MRP1表达与免疫分型、治疗反应以及疾病危险程度和复发紧密相关。     

急性淋巴细胞性白血病患儿泼尼松试验敏感与不敏感者临床及形态学、免疫学、细胞遗传学特征研究

泼尼松试验对小儿急性淋巴细胞性白血病（ALL）的预后价值已得到广泛认同,我们根据泼尼松试验结果,将我院2000年3月-2006年1月收治的133例ALL患儿分为泼尼松不敏感（PPR）和泼尼松敏感（PGR）两组,比较了二者的临床及形态学、免疫学、细胞遗传学（MIC）特征,为今后临床按危险度进行分层的治疗方案以及ALL患者的个体化治疗提供依据。[第一段]     

原发性肾病综合征患儿腺苷酸脱氧酶检测的临床意义

目的 检测原发性肾病综合征(PNS)患儿血清腺苷酸脱氧酶(S-ADA)活性的变化,以评估其细胞免疫状态,并探讨其临床意义.方法 选取初发的PNS患儿30例,应用免疫学技术测定不同病程阶段患儿的S-ADA活性,分析其变化.结果 激素治疗前,激素敏感组(SS)、激素依赖组(SD)和激素抵抗组(SR)患儿S-ADA活性差异无统计学意义(P＞0.05),经激素足量治疗8周后,SS组、SD组S-ADA活性下降,SS组下降最明显(P＜0.01),而SR组变化无统计学意义(P＞0.05);短期缓解期组S-ADA活性下降,但仍明显高于对照组(P＜0.05);长期缓解期组S-ADA活性与对照组相比,差异无统计学意义(P＞0.05).结论 PNS患儿存在细胞免疫功能紊乱,检测S-ADA活性可作为判断临床疗效的指标之一.     

急性白血病儿童医院感染71例

目的 了解儿童白血病发生医院感染的临床特点,探讨其防治措施.方法 回顾性分析133例急性白血病患儿发生医院感染的特点.总结医院感染与病程阶段、住院天数的关系及感染部位、感染率,并进行统计学处理.结果 医院感染率为53.4%(71/133例).其中急性淋巴细胞白血病与急性非淋巴细胞白血病例次感染率有显著性差异(P＜0.05);住院第1～3次组医院感染例次高于其他组(Pa＜0.05),住院天数为1～7 d组医院感染例次低于其他组(Pa＜0.05);复发与未复发组人均医院感染例次无显著性差异(P＜0.05);败血症以革兰阴性杆菌为主,药敏结果显示普遍敏感的药物为阿米卡星、哌拉西林/他佐巴坦.结论 急性白血病患儿医院感染发生率高,医院感染发生与白血病类型、病程阶段、住院天数有关;与预后无关,败血症以革兰阴性杆菌为主.     

儿童原发性肾病综合征脂联素与其他脂代谢相关因素的探讨

目的 初步探讨儿童原发性肾病综合征(PNS)脂联素(ADPN)的变化,了解ADPN与PNS其他脂代谢相关因素的联系.方法 对71例PNS急性期患儿、37例缓解期患儿和35例健康儿童的血浆、尿液ADPN浓度进行定量分析,并将急性期患儿分为激素敏感组59例和激素耐药组12例,测定急性期患儿的体质指数(BMI)、肾小球滤过率(GFR)、血清白蛋白(Alb)、肌酐(Cr)、补体C3、三酰甘油(TG)、胆固醇(Tch)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、脂蛋白aLP(a)、载脂蛋白A(apoA)、载脂蛋白B(apoB)以及24 h尿蛋白定量,并进行相关性分析.结果 急性组的血浆、尿ADPN(14.02 ± 3.44 μg/ml,4.71 ± 2.12 μg/ml)显著高于缓解期组(7.13 ± 5.07 μg/ml,2.50 ± 1.06 μg/ml)和正常对照组(7.17 ± 2.94 μg/ml,2.60 ± 1.06 μg/ml)(P ＜ 0.01).激素耐药组血浆、尿ADPN均显著高于激素敏感组(P ＜ 0.05).PNS急性期患儿血浆ADPN分别与尿ADPN、血清TG、Tch、LDL、LP(a)、apoB及24 h尿蛋白定量正相关(r ＝ 0.242 7 ～ 0.609 1,P均＜ 0.05),与血清Alb、HDL负相关(r ＝ -0.745 4、-0.489 7,P ＜ 0.01).结论 PNS患儿的血浆及尿液ADPN浓度明显升高.血浆和尿液ADPN浓度与其他脂代谢指标密切相关.     

儿童急性淋巴细胞白血病血型糖蛋白基因表达及其临床意义

目的 探讨急性淋巴细胞白血病(ALL)不同阶段、不同类型患儿血型糖蛋白C(GYPC)基因的表达水平及其与治疗反应和免疫分型的关系.方法 研究对象为2005年1月至2005年11月哈尔滨市儿童医院血液科、哈尔滨医科大学一院儿科及哈尔滨市血液肿瘤研究所儿科住院的ALL患儿.应用半定量逆转录-聚合酶链反应(RT-PCR)的方法,检测ALL初治患儿、缓解患儿、难治患儿、复发患儿及正常对照儿童GYPC基因的表达;采用流式细胞术检测初治患儿的免疫表型,观察GYPC基因与免疫表型的关系.结果 (1)初治患儿GYPC表达水平明显高于正常对照组(P＜0.01)和完全缓解组(P＜0.01);完全缓解后GYPC表达水平与对照组差异无统计学意义(P＞0.05),复发患儿GYPC表达水平不仅高于正常对照组(P＜0.01)和完全缓解组(P＜0.01),也高于初治组(P＜0.01);(2)38例初治患儿GYPC阳性24例,GYPC阴性14例,GYPC阳性患儿的完全缓解率与GYPC阴性患儿差异无统计学意义(分别为75.0%、92.9%,P＞0.05),但完全缓解患儿治疗前GYPC表达水平低于未缓解患儿(P＜0.05);(3)38例初治患儿中25例为B系淋巴细胞白血病(B-ALL),10例为T系淋巴细胞白血病(T-ALL),T-ALL的GYPC阳性率高于B-ALL(分别为90.0%、48.0%,P＜0.05),且T-ALL的GYPC表达水平高于B-ALL(P＜0.05).结论 GYPC的表达水平随儿童ALL的病情发展而变化,GYPC可以作为监测病情、判断疗效、预测复发、评估预后的一个新指标;GYPC高表达可能是儿童ALL的不利因素,GYPC高表达者疗效差,易复发;GYPC表达水平与免疫分型具有相关性,GYPC在T-ALL具有高表达,可能是T-ALL的缓解率低、预后差的原因之一.     

原发性肾病综合征患儿腺苷酸脱氧酶检测的临床意义

目的 检测原发性肾病综合征(PNS)患儿血清腺苷酸脱氧酶(S-ADA)活性的变化,以评估其细胞免疫状态,并探讨其临床意义.方法 选取初发的PNS患儿30例,应用免疫学技术测定不同病程阶段患儿的S-ADA活性,分析其变化.结果 激素治疗前,激素敏感组(SS)、激素依赖组(SD)和激素抵抗组(SR)患儿S-ADA活性差异无统计学意义(P＞0.05),经激素足量治疗8周后,SS组、SD组S-ADA活性下降,SS组下降最明显(P＜0.01),而SR组变化无统计学意义(P＞0.05);短期缓解期组S-ADA活性下降,但仍明显高于对照组(P＜0.05);长期缓解期组S-ADA活性与对照组相比,差异无统计学意义(P＞0.05).结论 PNS患儿存在细胞免疫功能紊乱,检测S-ADA活性可作为判断临床疗效的指标之一.     

甲状腺激素受体结合蛋白3基因在儿童急性淋巴细胞白血病中的表达及意义

目的 研究甲状腺激素受体结合蛋白3(TRIP3)基因在急性淋巴细胞白血病(ALL)患儿中的表达,探讨其与儿童ALL缓解的关系.方法 采集空腹静脉血2-4 mL,依地酸(EDTA)抗疑,采用Ficoll密度梯度离心法收集单个核细胞,Trizol试剂一步法提取总RNA.采用反转录一聚合酶链反应法(RT-PCR)检测73例不同阶段ALL及20例健康儿童外周血单个核细胞TRIP3基因表达水平,并分析其与儿童ALL缓解的关系.结果 1.TRIP3基因在ALL初治及复发组的表达水平均明显低于健康对照组(Pa＜0.01);在完全缓解的ALL患儿中的表达水平明显高于健康对照组(P＜0.01);2.TRIP3基因在初治组与复发组ALL中的表达水平无明显差异(P＞0.05);在缓解组表达水平明显高于复发及初治组(Pa＜0.01);3.在初治的ALL患儿中,TRIP3基因表达阴性者其治疗后完全缓解率明显低于TRIP3基因表达阳性者(缓解率分别为25.0% us 84.2%,P＜0.05).结论 TRIP3基因与儿童ALL的缓解有一定关系,其表达水平可作为评价ALL患儿化疗效果及评估预后的指标之一.     

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.     

Understanding infant formula

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 healthcare professionals) will experiment with the infant formula available and then 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.     

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.