血液透析治疗大剂量甲氨蝶呤化疗所致急性肾损伤的疗效

目的 观察血液透析治疗大剂量甲氨蝶呤(HD-MTX)化疗所致急性肾损伤(AKI)的临床疗效.方法 回顾性分析2008年5月-2012年1月在苏州大学附属儿童医院HD-MTX化疗后致AKI的8例ALL患儿的临床资料.患儿均在常规治疗(增加亚叶酸钙解救量及次数,使用止吐、保肝、黏膜保护等药物及充分水化、碱化)的基础上联合血液透析,比较血液透析前后患儿肝肾功能、MTX血药质量浓度、电解质等血液学指标的变化.结果 1.HD-MTX化疗致AKI患儿血液透析后肾功能均恢复正常,血肌酐、尿酸、尿素值显著降低,差异均有统计学意义(Pa＜0.01);肾功能恢复正常的时间为(7.00+3.74)d,透析次数为(3.13±1.13)次.2.血液透析后血MTX水平的降低有统计学意义(P＜0.05),MTX血药质量浓度降低至正常的时间为(5.75±1.75)d.3.透析前后患儿血WBC、PLT、Hb的减低有统计学意义(Pa＜0.05).4.患儿LDH、血钠离子、钾离子、氯离子、钙离子水平、实际碳酸氢盐、标准碳酸氢盐、ALT、AST及血液pH水平在透析前后的变化均无统计学意义(Pa＞0.05).结论 血液透析能有效治疗HD-MTX化疗导致的AKI,并清除患儿体内的MTX.     

HD—MTX静脉滴注后肝功能损害的危险因素分析

目的：探讨影响大剂量MTX（HD－MTX）静脉滴注后肝功能损害的危险因素，方法：MD－MTX静脉滴注及甲酰四氢叶酸（CF）解救后，以速率法测定血清丙氨酸氨基转移酶（ALT）活力作为评价肝功能的指标，所得数据用SPSS10．0版本进行单因素及多因素分析。结果：（1）52例164例次急性淋巴细胞白血病（ALL）及恶性淋巴瘤（ML）患儿静脉滴注MD－MTX后，肝功能损害的发生率为50％，无1例发生致命的肝功能损害；（2）患儿年龄，性别、持续完全缓解（CCR）时间，MTX单次剂量及累积使用次数，CF剂量，联合化疗方案等各因素与ALT值之间无明显相关性，（3）停用MTX并予CF解救，护肝等治疗后，ALT恢复至正常所需的时间中位数为8（4－55）天，肝功能损害程度越重，年龄越大，肝功能恢复至正常所需的时间越长，结论：只要通过合理的水化，碱化及积极护肝治疗，MTX剂量在3000mg/m^2甚至更大，CF总剂量占MTX总剂量的3％左右，是安全的。     

HD-MTX静脉滴注后肝功能损害的危险因素分析

目的　探讨影响大剂量MTX(HD MTX)静脉滴注后肝功能损害的危险因素。方法 :MD MTX静脉滴注及甲酰四氢叶酸 (CF)解救后 ,以速率法测定血清丙氨酸氨基转移酶(ALT)活力作为评价肝功能的指标 ,所得数据用SPSS10 .0版本进行单因素及多因素分析。结果　① 5 2例 16 4例次急性淋巴细胞白血病 (ALL)及恶性淋巴瘤 (ML)患儿静脉滴注HD MTX后 ,肝功能损害的发生率为 5 0 % ,无 1例发生致命的肝功能损害 ;②患儿年龄、性别、持续完全缓解 (CCR)时间、MTX单次剂量及累积使用次数、CF剂量、联合化疗方案等各因素与ALT值之间无明显相关性 :③停用MTX并予CF解救、护肝等治疗后 ,ALT恢复至正常所需的时间中位数为 8(4～ 5 5 )天 ,肝功能损害程度越重、年龄越大 ,肝功能恢复至正常所需的时间越长。结论　只要通过合理的水化、碱化及积极护肝治疗 ,MTX剂量在30 0 0mg/m2 甚至更大 ,CF总剂量占MTX总剂量的 3%左右 ,是安全的     

低剂量四氢叶酸钙延迟解救氨甲喋呤不良反应初探

目的探讨低剂量甲酰四氢叶酸钙(CF)延迟解救大剂量氨甲喋呤(HDMTX)应用安全性及机制。方法32例急性淋巴细胞白血病(ALL)109例次HDMTX治疗病例(HDMTX:标危3.0g/m2,高危5.0g/m2)。A组(55例次)MTX滴注起第42小时应用CF解救[15mg/(m2·次),q6h×3次,水化方案改良];B组(54例次)第36小时应用CF解救[15mg/(m2·次),q6h×7次]。血清MTX浓度测定用荧光偏振免疫分析法。不良反应评估标准按WHO抗癌药物急性与亚急性毒性反应分度标准。结果MTX滴入24h血清MTX浓度两组均无升高;48hMTX5.0g/m2患儿A组与B组差异有极显著性(P<0.001);肝损及口腔粘膜损害差异有显著意义(P均<0.05);Ⅲ~Ⅳ级肝损和口腔粘膜损害与对照组相比尤其是5.0g/m2HDMTX患儿差异有极显著意义(P均<0.001)。结论在充分合理的水化基础上应用CF低限量及42h延迟解救HDMTX的毒副作用临床应用是安全的。     

不同剂量四氢叶酸钙对大剂量甲氨蝶呤化疗大鼠肠黏膜的保护作用

目的 探讨不同剂量四氧叶酸钙(CF)对大剂量甲氨蝶呤(HD-MTX)化疗大鼠肠黏膜的保护作用.方法 6 周龄Wistar大鼠60只随机分为5组,每组12只.A组:正常对照组,腹腔注射9 g/L盐水;B组:1?解救组(即CF解救剂量为MTX总量的1%,下同);C组:2?解救组;D组:8% CF解救组;E组:空白对照组,不予CF解救.B～E组均腹腔注射MTX(120 mg/kg),B～D组于腹腔注射MTX 12 h后肌注CF解救,1次/6 h,共7次.于最后一次肌注CF 18 h后杀死大鼠,取其空肠标本观察形态,切片观察测定绒毛长度隐窝深度.结果 A组肠壁厚弹性好,绒毛密集、排列整齐;B～E组肠壁充血水肿变薄,小肠绒毛变短,隐窝深度变浅.E组最重,B组次之.B～E组与A组比较有统计学差异(Pa＜0.05);C、D与B、E组比较有统计学差异(Pa＜0.05);C、D组比较无统计学差异(P＞0.05).结论 MTX可致大鼠黏膜损害,CF解救可减轻其黏膜损害,过度降低CF解救剂量达不到解救目的.     

慢性肾脏病5期维持性血液透析患儿营养状态的评估

目的 研究儿童慢性肾脏病（CKD）5期维持性血液透析患者营养状态，探讨各营养评估指标的临床意义。方法 对21例CKD 5期维持性血液透析患儿按体重指数进行分组，根据人体测量指标、生物化学指标、炎症指标、残存肾功能及透析充分性指标、静息能量消耗指标等进行营养状态评估，分析营养不良患儿与营养正常患儿相关指标的差异。结果 21例患儿中，营养不良10例，营养正常11例。营养不良组与营养正常组人体测量指标之间差异有统计学意义（P < 0.05）；两组间瘦素、胰岛素样生长因子1的比较差异有统计学意义（P < 0.05）；两组间IL-1、IL-6、TNF-α的比较差异有统计学意义（P < 0.05）；两组间平均24 h残余尿量的比较差异有统计学意义（P < 0.05）。而两组间白蛋白、前白蛋白、胆固醇的比较差异无统计学意义；两组间尿素清除指数（Kt/V）及实测静息能量消耗值的比较差异亦无统计学意义。结论 人体测量指标、生物化学指标、残存肾功能、炎症因子对CKD 5期维持性血液透析患儿营养状况评估具有重要的价值，而静息能量消耗测定对于CKD 5期维持性血液透析患儿营养状况评估和监测的应用价值有待研究。     

四氢叶酸钙对大剂量甲氨蝶呤化疗大鼠肠黏膜保护作用的研究

目的探讨不同剂量和时间四氢叶酸钙(calcium5-formyltetrahydrofolate,CF)对大剂量甲氨蝶呤(high-dose methotrexate,HDMTX)化疗大鼠肠黏膜的保护作用。方法实验分两部分,均分5组,设正常对照组(A组,腹腔注射生理盐水),和空白对照组(B组,腹腔注射MTX,不予CF解救)。第一部分:不同剂量CF对HDMTX化疗大鼠肠黏膜的保护作用。C组:1%CF解救组;D组:2%CF解救组;E组:8%CF解救组(百分数为CF总量占MTX的百分比)。C、D、E组腹腔注射MTX,于注射后12h肌注CF,A、B组肌注生理盐水,6小时一次,共7次。第二部分:不同时间CF对HDMTX化疗入鼠肠黏膜的保护作用,C组:12h解救组;D组:24h解救组;E组:30h解救组。C、D、E组腹腔注射MTX。C、D、E组分别于腹腔注射HDMTX后12、24、30h予肌注CF,CF总剂量为MTX的5%;A、B组于腹腔注射后24h分别肌注生理盐水,各组均6小时一次,共7次。于腹腔注射后78h处死存活大鼠,取空肠标本观察形态,测定绒毛长度和隐窝深度。结果两部分均A组肠壁厚弹性好,绒毛密集、排列整齐,B、C、D、E组肠壁充血水肿变薄,和A组比较,小肠绒毛变短,隐窝深度变浅,差异有统计学意义(P<0.05);第一部分B、C组改变较D、E组更明显(P<0.05);C组与B组比较差异无统计学意义(P>0.05);D组与E组比较差异无统计学意义(P>0.05)。第二部分B、E组改变较C、D组更显著(P<0.05);B组与E组比较差异无统计学意义(P>0.05);C组与D组比较差异无统计学意义(P>0.05)。结论CF对HDMTX所致大鼠肠黏膜损害有保护作用;其保护作用存在剂量和时间依赖性。     

产前诊断先天性胆总管囊肿37例临床分析

目的探讨产前诊断先天性胆总管囊肿患儿的临床治疗。方法将2006年9月至2013年2月收治的产前诊断为先天性胆总管囊肿患儿37例，按手术时年龄分为A组（0~3个月，20例）和B组（>3个月，17例），回顾性分析两组患儿的临床特点、手术前后肝功能指标、术后并发症及肝脏组织病理检查结果等。结果 A组5例患儿出生后有黄疸，B组2例黄疸；两组丙氨酸转氨酶（ALT）和天门冬氨酸转氨酶（AST）差异无统计学意义（P均>0.05），A组手术前、后总胆红素（TBIL）和直接胆红素（DBIL）水平均高于B组，差异有统计学意义（P均<0.05）；A组2例出现吻合口狭窄，1例胆漏，B组无术后并发症。肝脏活检提示胆汁性肝硬化改变11例，其中A组4例（36.36%），B组7例（63.64%），但两组肝硬化发生率差异无统计学意义（P=0.160）。结论对产前诊断为先天性胆总管囊肿患儿，应密切观察，发现黄疸、白便、ALT和AST升高明显、超声提示囊肿短期增大明显者应尽快手术治疗，以减轻肝功能损害，减少肝硬化发生。[临床儿科杂志,2013,31(9)：858-861]     

大剂量甲氨蝶呤治疗急性淋巴细胞白血病的不良反应

目的研究大剂量甲氨蝶呤(HD-MTX)加四氢叶酸钙(CF)解救方案治疗儿童急性淋巴细胞白血病(ALL)的不良反应。方法82例ALL患儿进行139例次的HD-MTX加CF治疗。根据44 h MTX血药质量浓度分为A组(44 h MTX浓度≤1.0 mmol/L),B组(44 h MTX浓度>1.0 mmol/L)。对用药前后两组患儿不良反应观察,并进行对照研究。结果骨髓抑制、肝功能损害、胃肠道反应、感染发生率两组比较无显著性差异。但随着血药质量浓度增加,皮肤黏膜损害、心电图异常和心肌酶谱异常、神经系统症状发生率均显著增加,两组比较有显著性差异。结论HD-MTX加CF治疗儿童白血病时,不良反应较为常见,个体差异较大,应加强个体化治疗。     

连续性血液净化联合血液灌流在儿童溶血尿毒综合征中的应用

目的：观察连续性血液净化（CBP）联合血液灌流（HP）治疗儿童溶血尿毒综合征（HUS）的疗效并初步探讨其治疗的可能机制。方法：在内科治疗基础上,急性期均采用CBP联合HP治疗HUS患儿8例。治疗前后采用化学发光法检测血清IL-6、IL-8、TNF-α水平,并测定血尿素氮（BUN）、肌酐（SCr）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、肌酸激酶（CK）、肌酸激酶同工酶（CKMB）、血红蛋白（Hb）、血小板（PLT）、C反应蛋白（CRP）等水平。8例健康体检儿童作为对照组。结果：经CBP联合HP治疗后,8例HUS患儿均存活,病情好转;Hb、PLT水平较治疗前回升, 血清IL-6、IL-8、TNF-α、BUN、SCr、ALT、CK、CRP水平较治疗前下降,差异有统计学意义(P＜0.05)。结论：CBP联合HP治疗能迅速清除致病因子,又能持续清除炎症介质和毒素,逆转多脏器功能障碍,是治疗儿童HUS的有效方法之一。     

Oral mucositis and salivary methotrexate concentration in intermediate-dose methotrexate therapy for children with acute lymphoblastic leukemia

The relationship between salivary methotrexate (MTX) concentration and severity of oral mucositis after administration of MTX was investigated in six children with acute lymphoblastic leukemia. They received two administrations of MTX at 500 mg/m2 with one third given bolusly and the remainder by 24-hour continuous infusion. No significant difference among patients or administration session was observed in serum MTX concentration. Detectable concentrations of salivary MTX (greater than 0.01 microM) were observed during nine of the ten infusions. A concentration of 0.1 microM or more, apparently lasting at least 12 hours, was observed during one infusion and followed by severe mucositis. During two of the ten infusions for different patients, concentrations of 0.04 to 0.07 microM and 0.02 to 0.04 microM, apparently lasting at least 12 and 18 hours, respectively, were observed, followed by moderate mucositis. During the other seven infusions, either much shorter or no increase in salivary MTX concentration was observed, with only mild or no subsequent mucositis. Analysis by Kendall's rank method showed a statistical correlation between concentration at 6 hours of infusion and severity of oral mucositis. The findings suggest that the early secretion of MTX into saliva has a significant role in the development of oral mucositis in leukemic children.     

血液灌流对毒鼠强中毒患儿心肝肾的保护作用

目的探讨血液灌流(HP)对毒鼠强中毒患儿心肝肾功能的影响。方法毒鼠强中毒患儿45例按不同治疗方式分为HP组(26例)和非HP组(19例),HP组用HP装置,进行床边治疗,非HP组进行对症处理。测血清酶,比较治疗前后心肝肾功能。结果治疗前两组均有不同程度的心肝肾功能损害,两组无显著差异(P>0.05)。治疗后HP组心肝肾功能较非HP组患儿恢复好,两组有显著性差异(P<0.01)。结论早期HP对毒鼠强中毒患儿心肝肾功能具有保护作用。     

Serum transaminases as a prognostic factor in children post cardiac surgery

Background: Elevated serum transaminases that are often observed in critically ill children are frequently attributed to liver injury. Indeed, hypoperfused or hypoxemic livers will produce sudden and marked elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The aim of this study was to determine the frequency and consequences of elevated serum transaminases in children following cardiac surgery. Methods: Charts of all children admitted to the Pediatric Intensive Care Unit following cardiac surgery over a 10‐year period were retrospectively analyzed. Results: Of the 384 children studied, 46 (11.9%) had elevated transaminases. Extreme ALT and AST levels (≥20‐fold elevations over the upper limit of normal) were found in 3.4% and 4.7% of the children, respectively. Tetralogy of Fallot and double outlet right ventricle were significantly more common (P < 0.001) among the elevated transaminases group (26% and 13% vs 17% and 2.5%, respectively). A significant difference (P < 0.001) was noted between overall mortality among 384 patients studied: 15.8%, versus a mortality of 43.4% among children who manifested elevated transaminases levels following cardiac surgery. AST, ALT and lactate dehydrogenase peak levels were significantly higher in the group of children who died in comparison to the survivors (P < 0.05). Kaplan–Meier survival analysis demonstrated lower survival among the patients who had extreme ALT elevations (P < 0.05). Conclusions: Elevation of transaminases following cardiac surgery occurs more frequently than previously reported, particularly in the setting of right‐sided heart failure. Extreme elevation of ALT, AST and lactate dehydrogenase correlated with decreased postoperative survival and places these children in a high‐risk category, requiring closer, more stringent monitoring.     

Concentrations of antimony in infants dying from SIDS and infants dying from other causes

BACKGROUND—A patient with cystic fibrosis (CF) and repeated calcium oxalate renal stones prompted us to investigate other children for risk factors for this recognised complication of CF.
METHODS—Twenty four hour urinary excretion of calcium, oxalate, and glycolate was measured in children with CF and no symptoms of renal tract stones. Normal diet and treatments were continued.
RESULTS—In 26 children (aged 5-15.9 years) oxalate excretion was correlated with age; 14 of 26 children had oxalate excretion above an age appropriate normal range. There was a positive correlation between oxalate excretion and glycolate excretion. Mean calcium excretion was 0.06 mmol/kg/24 h with 21 of 24 children having calcium excretion below the normal range.
CONCLUSIONS—Hyperoxaluria may reflect malabsorption although correlation between excretion of oxalate and glycolate suggests a portion of the excess oxalate is derived from metabolic processes. The hypocalciuria observed here may protect children with CF from renal stones.

     

Hypercalciuria and nephrocalcinosis in cystic fibrosis patients

The objective of this study was to determine the frequency of nephrocalcinosis and hypercalciuria in cystic fibrosis (CF) patients, and to search possible causes of this phenomenon. Forty-three CF children (24 boys, 19 girls; mean age 64.9 months, range 5 months-18 years) were included in this study. Plasma sodium, potassium, chloride, BUN, creatinine, calcium, phosphorus, magnesium, alkaline phosphatase; spot urine sodium, potassium, chloride, creatinine, calcium, magnesium; and serum 25-hydroxyvitamin-D levels were measured in all patients. Urine samples were examined for microscopic hematuria. Fractional sodium, potassium, chloride excretion and estimated glomerular filtration rate (GFR) were calculated. All patients underwent renal ultrasonography. Hypercalciuria, nephrocalcinosis and microscopic hematuria were detected in 15 patients (34.2%), 10 patients (23.2%) and two patients (5%), respectively. There was no significant but borderline correlation between 25-hydroxyvitamin-D levels and hypercalciuria (r: 0.308, p:0.05). There were no correlations between Shwachman clinical scoring system results and hypercalciuria (r: 0.221, p: 0.148) and age and hypercalciuria (r: -0.229, p: 0.135). Patients with chronic Pseudomonas colonization showed no hypercalciuria or nephrocalcinosis. There was no difference for plasma biochemical results, renal function tests, hypercalciuria and nephrocalcinosis between CF patients who had or had not experienced pseudo Bartter's syndrome (PBS) before. There was no relation between detected CF mutations of the patients and hypercalciuria and nephrocalcinosis. These results suggested that it is a primary abnormality of calcium metabolism in the kidney.     

儿童先天性肝纤维化的临床特点

目的探讨儿童先天性肝纤维化(CHF)的临床特点。方法选取2002年1月至2015年6月首次确诊的111例CHF患者为研究对象,根据确诊时年龄分为儿童组60例和成年组51例,采集两组的性别、年龄、临床表现、体征、实验室检查、影像特点等临床资料进行回顾性对比分析。结果儿童组和成年组的脾肿大和肝硬化发生率均高,差异无统计学意义(P0.05);儿童组乏力、黄疸、肝脾肿大的发生率高于成年组,成年组则多见合并肾囊肿和肝囊肿,差异均有统计学意义(P0.05);儿童组的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、亮氨酸氨基肽酶(LAP)、总胆汁酸(TBA)水平以及AST异常率高于成年组,差异有统计学意义(P0.05)。结论 CHF患者常见肝硬化和脾肿大。儿童期确诊CHF者肝脾肿大更明显,ALT、AST和ALP、LAP、TBA升高及异常更多,肾囊肿和肝囊肿相对少见。     

Comparison between serum alpha-glutathione S-transferase and aminotransaminases in detecting cytolysis in hepatitis C-infected children.

BACKGROUND: alpha-Glutathione S-transferase (alphaGST) has been proposed as a more sensitive indicator than serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in detecting hepatocellular damage due to chronic hepatitis C virus (HCV) infection. METHODS: The accuracy of alpha-GST was compared with that of ALT and AST in detecting cytolysis in 103 blood samples issued from 31 children positive for HCV RNA. RESULTS: alpha-GST had a lower sensitivity than ALT or AST (32% vs. 54.4% for each aminotransferase). The sensitivity of ALT and/or AST was 60.2%, whereas that of ALT and/or alpha-GST and AST and/or alpha-GST was lower (58.3% and 57.3%, respectively). Among 41 serum samples with negative ALT and AST, only 2 had positive alpha-GST, whereas alpha-GST failed to detect cytolysis in 31 samples with elevated ALT and/or AST. No correlation was found between alpha-GST, ALT, or AST and the Knodell score. CONCLUSIONS: The combination of ALT with AST is actually the best compromise in detecting cytolysis in untreated HCV-infected patients.     

Serum Aminotransferases in Thai Children With Dengue Infection

Background:

Hepatic manifestations are one of the unusual manifestations of dengue infection.

Objectives:

We conducted this study in order to study the pattern of serum aminotransferases and sequential changes before and after shock in Thai children with dengue infection.

Patients and Methods:

Children who were clinically and serologically diagnosed as dengue infection and were admitted to King Chulalongkorn Memorial Hospital during a peroid of one year were enrolled. They were clinically classified into a non-shock group and a shock group. The majority of serum aminotransferases including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were obtained within a week after the onset of fever and until 3 days after shock in the shock group. Student t-test and median in boxplot form were used for statistical analysis.

Results:

We enrolled 127 children with a mean age of 7.6 ± 3.6 years. The incidence of abnormal AST and ALT levels was 97.4% and 50.0% in the shock group, and 91.8% and 44.9% in the non-shock group respectively. 29% and 15.4% of the patients in shock group and only 10.2% and 4.1% in non-shock group had the respective AST and ALT levels > 200 U/L. Serum aminotransferase levels were significantly higher in the shock group when compared to the non-shock group. AST tended to increase starting from one day before shock and continued to increase within a few days whereas ALT was less likely to be affected.

Conclusions:

Elevated serum aminotransferases are a common finding in children with dengue infection and the levels of AST are higher than those of ALT. Patients with shock have significantly higher aminotransferase levels that increase up to 3 days after shock.     

Abnormalities of intestinal permeability of 51Cr-EDTA in mucoviscidosis

Intestinal permeability to 51Cr-EDTA was studied in 20 children with cystic fibrosis (CF) and a mean age of 10.7 years, in 7 control adults and in 11 control children. 51Cr-EDTA urinary excretion (mean +/- SD) expressed as a percentage of the orally administered activity was: control children: 1.59 +/- 0.55%, control adults: 1.47 +/- 0.62%, CF patients: 10.7 +/- 8.6%. The difference between CF patients and control children on one hand, between CF patients and control adults on the other hand, was statistically significant (p less than 0.001). Only 3 CF patients had values within the limits of those observed in controls. A statistically significant correlation (p less than 0.01) was observed between the 51Cr-EDTA urinary excretion and steatorrhea. No correlation was found between 51Cr-EDTA urinary excretion and the following parameters: age, sex, weight, height, Shwachman score, liver cirrhosis, oral administration of a mucolytic agent. The eventual, especially nutritional, consequences of this increase of the intestinal permeability in the course of CF remain to be clarified.