柔红霉素不同滴注时间在急性白血病患儿体内的药代动力学及其对诱导化疗和心脏不良反应的影响

目的探讨柔红霉素(DNR)治疗儿童白血病时不同滴注持续时间的药代动力学及其与诱导化疗疗效和心脏毒性反应的关系。方法采用反相高效液相色谱(HPLC)荧光检测法检测61例白血病患儿分别持续滴注柔红霉素30 min、2 h、6 h后的血药浓度。在DNR化疗前后不同阶段监测患儿心电图、心肌酶谱、心彩超等指标。分析DNR三种不同滴注持续时间在患儿体内的药代动力学之间的差异及其对诱导化疗疗效和心脏毒性反应的影响。结果①DNR药代动力学参数t1/2α、Vd、MRT(0-t)和Tmax随着滴注持续时间的延长而延长或升高,AUC(0-t)和Cmax则随着滴注持续时间的延长而降低,三组不同滴注持续时间之间差异有统计学意义(P均0.05);而CL在三组之间差异无统计学意义(P=0.135)。②DNR不同滴注持续时间对其诱导治疗效应差异无统计学意义(P=0.656)。③DNR滴注持续时间越长,其心脏毒性反应的发生率越低,三组间差异有统计学意义(P=0.035);早期心脏毒性可能增加晚期心脏毒性的发生率。结论DNR不同滴注时间的总疗效可能不变;DNR的心脏毒性与其滴注持续时间可能相关;DNR的早期心脏毒性可作为其晚期心脏毒性的一个危险指标;DNR持续滴注6 h的方式可能较为合理。     

急性心力衰竭患儿血浆脑钠素及心钠素水平的变化

目的探讨急性心力衰竭患儿血浆脑钠素(BNP)及心钠素(ANP)水平变化及其意义。方法选择不同病因的充血性心力衰竭(CHF)患儿46例及肺炎患儿40例、先天性心脏病患儿31例、健康儿童40例,应用酶联免疫吸附法分别检测血浆BNP及ANP水平,用多普勒超声心动图测量心力衰竭患儿心衰期及恢复期心脏指数(CI)及左室射血分数(LVEF)。结果CHF患儿心衰前期BNP即开始升高,心衰时达高峰(P<0.001),恢复期BNP水平渐下降,但仍高于正常值(P<0.001);心衰时心脏CI、LVEF均明显下降(P<0.01);CHF患儿心衰时升高的BNP水平与CI、LVEF均呈明显负相关(r=-0.61,0.79P均<0.05);同时测定的ANP动态变化趋势与BNP类似;CHF患儿心衰时的BNP/ANP比值远远高于正常对照;心衰时BNP与ANP异常率比较有显著差异(P<0.05);心衰时BNP水平与LVEF、CI值相关性优于ANP。结论CHF患儿血清BNP及ANP水平明显升高.且与心衰程度关系密切,BNP反映心脏功能改变较ANP更敏感,更具有特异性。     

儿童急性白血病血清白细胞介素24的测定及意义

目的观察急性白血病患儿血清白细胞介素24(IL-24)的水平及意义。方法确诊未治的儿童急性淋巴细胞白血病(ALL)、儿童急性髓细胞白血病(AML)、非白血病患儿及正常儿童(正常对照组)各20例,采用ELISA法测定其血清IL-24的水平并进行比较。结果两组白血病患儿血清IL-24浓度[ALL组:(28.25±2.6)ng/L;AML组:(26.32±3.2)ng/L]均较正常对照组[(113.15±3.7)ng/L]和非白血病患儿[(105.82±4.2)ng/L]明显降低(P值均0.05);但ALL与AML组之间和非白血病组与正常对照组之间差异无统计学意义(P值均0.05)。结论 ALL及AML患儿血清IL-24浓度明显下降。     

急性淋巴细胞白血病患儿粒细胞缺乏并革兰阴性杆菌感染时血清内源性二氧化硫水平变化及其意义

目的 探讨内源性二氧化硫(SO2)在急性淋巴细胞白血病(ALL)患儿大剂量阿糖胞苷(HD-AraC)化疗后粒细胞缺乏期并革兰阴性杆菌感染时的水平变化及其病理生理学意义.方法 2010年1-12月在本院儿童血液肿瘤科住院的ALL患儿共31例,均行HD-AraC化疗,均出现骨髓抑制期并革兰阴性杆菌感染.分别测定患儿化疗前(WBC>3.0×109 L-1)、化疗后骨髓抑制期未感染时(WBC<1.0×109 L-1)、化疗后骨髓抑制期并革兰阴性杆菌感染时(WBC<1.0×109 L-1)及感染控制后粒细胞恢复期(WBC>2.0×109 L-1)血清SO2、CRP、IL-6和IL-8水平变化,分析其变化趋势.结果 ALL患儿化疗后,骨髓抑制期未合并感染时其血清SO2水平[(8.91±3.80) μmol·L-1]较化疗前[(6.15±3.16) μmol·L-1]明显升高(P<0.05);并革兰阴性杆菌感染后其血清SO2水平[(24.39±7.84) μmol·L-1]较未合并感染时进一步升高,差异有统计学意义(P<0.01);而感染控制后患儿血清SO2水平[(5.09±3.02) μmol·L-1]较感染组显著下降(P<0.01).与恢复期比较,骨髓抑制期粒细胞缺乏并革兰阴性杆菌感染后患儿血清CRP[(35.72±14.97) mg·L-1 vs (2.39±1.66) mg·L-1]、IL-6[(152.24±20.42) ng·L-1 vs (121.26±15.50) ng·L-1]和IL-8[(222.35±39.79) ng·L-1 vs (124.36±13.28) ng·L-1]水平均显著升高(Pa<0.01).结论 内源性SO2可以作为一种生物活性分子,参与ALL患儿粒细胞缺乏时革兰阴性杆菌感染的调节过程.     

小儿急性白血病化疗前后超氧化物歧化酶及丙二醛的研究

探讨小儿初治达完全缓解 (CR)的急性白血病在以后定期化疗中 ,测定化疗前后外周血红细胞超氧化物歧化酶 (SOD)活性及血浆丙二醛 (MDA)的变化。采用黄嘌呤氧化酶比色法测定红细胞SOD活性 ,硫代巴比妥比色法测定血浆MDA含量。结果显示 :30例CR的急性淋巴细胞白血病 (ALL)患儿化疗前SOD正常 ,MDA升高 ;化疗后SOD明显降低 (P <0 .0 1 ) ,MDA明显升高 (P <0 .0 1 )。结论 :检测急性白血病患儿化疗前后SOD、MDA的变化 ,可作为反映化疗药物引起组织细胞损伤的指标之一。     

不同来源门冬酰胺酶在儿童急性淋巴细胞白血病应用的对照研究

目的观察菊欧文菌源性门冬酰胺酶(asp)及大肠杆菌源性asp在儿童急性淋巴细胞白血病(ALL)治疗中的药物疗效及不良反应。方法随机选取新诊断的ALL患儿15例,其中9例患儿接受国产菊欧文菌源性asp治疗,6例患儿接受大肠杆菌源性asp治疗,化疗前后对两组患儿血浆内L-asp活性及门冬酰胺(ASN)水平进行检测,同时对两组患儿不良反应进行比较。结果在用药前,两组患儿血浆内L-asp活性与ASN水平差异无显著性;用药期间两组患儿血浆内的asp活性逐渐升高,ASN水平差异无显著性(P>0.05);停药后,L-asp活性及ASN水平在一周后可缓慢恢复至用药前水平。结论国产菊欧文菌源性asp有望成为ALL患儿化疗方案中有效的备选用药。     

风湿性心脏病患儿血浆脑利钠肽水平变化的意义

目的 观察风湿性心脏病患儿血浆脑利钠肽(BNP)水平的变化,探讨其在风湿热(RF)并心脏病变患儿中的诊断价值.方法 选择RF患儿20例(RF组),包括风湿性心脏病患儿11例(心脏病变组),无心脏病变患儿9例(无心脏病变组).同时选择20例健康儿童作为健康对照组.采用ELISA测定各组血浆BNP、肌钙蛋白I(cTnI)水平,并行心脏彩色多普勒超声及ECG检查.健康对照组随机采血1次,测定血浆BNP和cTnI水平.应用SPSS 11.5软件进行统计学分析.结果 RF组患儿血浆BNP、cTnI水平均明显高于健康对照组(Pa＜0.01);心脏病变组血浆BNP水平较无心脏病变组明显升高(P＜0.01),cTnI水平二组比较差异亦有统计学意义(P＜0.05);BNP异常升高率显著高于cTnI(x2=14.19,P＜0.01)及ECG(x2=10.23,P＜0.01),cTnI异常率与ECG异常率比较差异无统计学意义(x2=1.37,P＞0.05).心脏病变组患儿BNP与cTnI水平呈显著正相关(r=0.32,P＜0.05).结论 BNP在风湿性心脏病患儿中异常增高,与cTnI呈正相关,且较cTnI、ECG灵敏度高.BNP、cTnI二者结合对RF并心脏病变的诊断具有重要意义.     

初治急性淋巴细胞白血病患儿外周血人类端粒酶催化亚单位表达与细胞因子网络紊乱的关系

目的 探讨初治急性淋巴细胞白血病(ALL)患儿外周血人类端粒酶催化亚单位(hTERT)表达水平和细胞因子网络紊乱及二者的关系.方法 采集36例初治ALL患儿和13例健康儿童的外周静脉血2 mL,采用ELISA分别检测各组血浆IL-6和IFN-γ水平,t检验分析ALL和健康对照组IL-6和IFN-γ水平变化.采用半定量反转录.聚合酶链反应(RT-PCR)检测24例初治ALL患儿、13例健康儿童外周血和阳性对照K562细胞株hTERT相对表达水平,t检验比较分析初治ALL与健康对照组和阳性对照K562细胞株之间hTERT相对表达水平的差异.进一步采用Pearson直线相关分析初治ALL患儿组hTERT相对表达水平与血浆IL-6和IFN-γ水平的关系.数据处理采用SPSS 11.5软件.结果 仞治ALL患儿血浆IL-6水平明显高于健康对照组[(73.27±32.05)ns/L vs(28.15±15.91)ng/L,t=4.841 P=0],但血浆IFN-γ水平低于健康对照组[(14.62±7.67)ng/L vs(24.22±10.43)ng/L,t=3.505 P=0.001].初治ALL患儿组外周血hTERT表达水平明显高于健康对照组(0.6057±0.1796 vs 0.0774±0.0219) ng/L,t=4.986 P=0,低于阳性对照K562细胞株(0.6057±0.1796 vs 0.8883±0.0472)ng/L,t=3.071 P=0.006.初治ALL患儿组中外周血hTERT表达水平与血浆IL-6水平呈正相关(r=0.683 P=0.001),与血浆IFN-γ水平呈负相关(r=-0.570 P=0.011).结论 初治ALL患儿hTERT表达水平明显上调,并存在细胞因子网络紊乱,二者相互作用,促进ALL的发生发展.     

卡维地洛治疗原发性心内膜弹力纤维增生症的研究

目的 观察原发性心内膜弹力纤维增生症(endocardial fibroelastosis,EFE)患儿血浆脑利钠肽(brain natriuretic peptide,BNP)变化及卡维地洛的临床疗效,探讨治疗剂量、方案及安全性.方法 21例原发性EFE患儿分为2组,常规治疗组(n=10)及卡维地洛治疗组(n=11),治疗前及治疗后6个月进行多普勒超声心动图检测、观察血浆BNP;观察2组治疗前后血浆BNP水平、临床症状、心胸比例、心率的变化、心功能的改善、患儿对卡维地洛的耐受量及不良反应.结果 原发性EFE患儿血浆BNP水平[(865±702)ng/L]明显高于正常对照组[(154±78)ng/L](P＜0.01),且心功能越差升高越明显,心功能Ⅱ、Ⅲ、Ⅳ级分别为(286±125)ng/L、(437±386)ng/L、(1673-s-859)ng/L;卡维地洛治疗后血浆BNP水平[(219±87)ng/L]低于常规组[(403±216)ng/L](P＜0.05),临床症状明显改善,患儿心胸比例降低,心率减慢,射血分数(EF)、短轴缩短率、平均左室周径缩短率显著提高(P＜0.01),左室收缩末期内径(P＜0.05)、左室质量、室间隔收缩末厚度明显降低(P＜0.01).结论 原发性EFE患儿血浆BNP水平显著升高,与EF呈负相关;卡维地洛可以降低血浆BNP水平,明显抑制EFE患儿心室重塑,改善患儿的心功能;心功能Ⅱ～Ⅳ级原发性EFE患儿卡维地洛长期治疗安全有效.     

血浆脑利钠肽对扩张性心肌病患儿病情的评估

目的探讨脑利钠肽(BNP)与扩张性心肌病患儿病情严重程度的相关性。方法扩张性心肌病患儿30例为研究组,选择健康儿童30例为对照组。两组均测定血浆BNP水平。进行t检验,比较各组血浆BNP水平,采用直线相关分析法分析BNP值与左室射血分数和心功能分级关系。结果扩张性心肌病患儿血浆BNP水平明显高于对照组[(429.4±270.2)ng/Lvs(67.0±10.2)ng/L];扩张性心肌病患儿血浆BNP水平与心功能分级呈正相关(r=0.950P<0.01),与左心室射血分数呈负相关(r=-0.695P<0.001),与左心室舒张末期内径无明显相关性(r=0.030P>0.1)。受试者工作特征曲线(ROC)曲线下面积为0.550,以血浆BNP水平95ng/L为判定心衰界值时,具有较高的灵敏度、特异度。结论血浆BNP可作为迅速评估扩张性心肌病患儿病情的依据之一。     

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.     

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.