血乳酸和乳酸清除率评估脓毒性休克患儿预后的临床分析

目的 评价血乳酸及乳酸清除率与脓毒性休克患儿预后的关系.方法 2009年10月至2011年6月我院PICU收治的脓毒性休克患儿42例,所有患儿均按照脓毒性休克诊疗方案进行早期目标指导治疗,测定每例患儿复苏前及复苏后1h、2h、6h血乳酸值,计算复苏后1h、2h、6h的乳酸清除率.按照预后将患儿分为存活组(n=20)和死亡组(n=22),评价早期乳酸值和乳酸清除率与预后的关系.结果 (1)存活组复苏前及复苏后1h、2h、6h的乳酸值明显低于死亡组[(3.92±2.58) mmol/Lvs (6.91 ±4.16) mmol/L,(2.79±1.89) mmol/L vs (7.93±4.39) mmol/L,(2.20±1.83) mmol/L vs(9.20±4.97) mmol/L,(1.32±0.51) mmol/L vs (9.94±5.02) mmol/L],差异具有统计学意义(P＜0.05).(2)存活组复苏后1h、2h、6h的乳酸清除率明显高于死亡组[(26.31 ±20.82)％ vs(-24.28±53.39)％,(43.46±17.85)％ vs(-34.31±58.98)％,(61.04±16.71)％ vs(-45.33±83.51)％],差异具有统计学意义(P＜0.05).(3)通过受试者工作特征曲线分析,复苏后6h血乳酸值和乳酸清除率的曲线下面积分别为99.4％、96.7％;复苏后6h血乳酸＞2.20 mmol/L及复苏后6h乳酸清除率＜18.65％,患儿病死率高.结论 脓毒性休克患儿动态监测血乳酸具有重要意义,复苏后6h的血乳酸值及乳酸清除率可作为预后判断的指标.     

脓毒性休克患儿血浆生长抑素水平的变化

目的探讨脓毒性休克患儿血浆生长抑素(SST)水平的变化。方法采用竞争性放射免疫分析法检测脓毒性休克患儿(试验组,n=21)休克期(入院当时)、血压和心率恢复正常时及恢复期(临床症状体征消失、血常规及CRP等感染指标恢复正常时,入院6～12d)清晨空腹状态下血浆SST水平,同期门诊健康体检婴幼儿(健康对照组,n=25)清晨空腹血浆SST水平作为对比,比较脓毒性休克并麻痹性肠梗阻与未并麻痹性肠梗阻脓毒性休克患儿血浆SST水平的差异。结果试验组患儿休克期血浆SST水平[(44.60±16.83)ng/L]明显低于健康对照组[(123.15±26.57)ng/L](t=-12.16P<0.001),血压及心率恢复正常时血浆SST水平[(87.64±12.69)ng/L]较休克期上升(t=-9.36P<0.001),但仍低于恢复期[(124.07±27.84)ng/L](t=-5.45P<0.001),恢复期患儿血浆SST水平与健康对照组比较无显著性差异(t=0.11P>0.05)。并麻痹性肠梗阻患儿血浆SST水平[(28.10±7.0)ng/L]显著低于未并麻痹性肠梗阻患儿[(56.98±9.44)ng/L](t=-7.70P<0.001)。结论监测脓毒性休克患儿治疗过程中血浆SST水平变化有助于了解胃肠道灌注情况;血浆SST水平可预示脓毒性休克患儿麻痹性肠梗阻发生,有助于评估患儿病情的严重程度、判断预后。     

血糖水平对脓毒性休克患儿预后的影响

目的 探讨血糖水平与脓毒性休克患儿预后的关系.方法 对61例脓毒性休克患儿进行血糖监测,同时对各脏器功能进行评估,分析血糖水平与预后的关系.结果 61例脓毒性休克患儿中,存活28例,死亡33例.死亡患儿的血糖值(20.10±13.10)mmol/L,明显高于存活患儿[(8.97±4.19)mmol/L],差异有显著性(P＜0.05).随着发生功能障碍的器官数目的 增加,血糖值越高,病死率也逐渐升高.血糖值的Logistic回归系数为-0.151,OR值为O.859.Logistic回归分析结果表明:血糖不是导致脓毒性休克患儿死亡的危险因素.结论 脓毒性休克患儿多存在血糖升高,但高血糖并不是脓毒性休克患儿死亡的直接原因.     

窒息新生儿血清肌钙蛋白I和磷酸肌酸激酶同工酶变化的意义

目的探讨血清肌钙蛋白I(cTnI)和磷酸肌酸激酶同工酶(CK-MB)对窒息新生儿心肌损伤的早期诊断价值。方法选择轻度窒息新生儿29例(轻度组)、重度窒息新生儿18例(重度组)。采用ELISA法和酶动力法检测新生儿血清cTnI水平和CK-MB活性。结果出生d1窒息新生儿血清cTnI和CK-MB水平在轻度组[(2.25±0.54)μg/L、(223.4±23.5)U/L]和重度组[(4.25±0.83)μg/L、(256.3±21.8)U/L]均显著高于对照组(Pa<0.01);重度组血清cTnI和CK-MB水平均显著高于轻度组(Pa<0.01)。治疗后d7窒息新生儿血清cTnI和CK-MB水平均明显下降,轻度组[(0.69±0.18)μg/L、(151.4±18.4)U/L]与对照组均无显著差异(Pa>0.05),重度组[(1.54±0.72)μg/L、(188.9±21.5)U/L]显著高于轻度组和对照组(Pa<0.01)。结论窒息新生儿伴心肌损伤时血清cTnI和CK-MB水平升高;动态观察可用于窒息新生儿微小心肌损伤的早期诊断。     

病毒性心肌炎患儿血清巨噬细胞移动抑制因子、肿瘤坏死因子-α、白细胞介素-1β表达及其意义

目的 探讨巨噬细胞移动抑制因子(MIF)、TNF-α、IL-1β在病毒性心肌炎(VM)患儿血清中表达的意义.方法 收集衡阳市中心医院和南华大学第一附属医院收治的30例急性期和20例恢复期VM患儿及30例健康儿童血清,采用ELISA测定其血清MIF、TNF-α、IL-1β水平,采用日立7180型全自动生化分析仪检测磷酸肌酸激酶同工酶(CK-MB),并与30例健康儿童作对照.结果 VM急性期患儿血清MIF[(136.7±32.2) ng/L]、TNF-α[(247.6±48.2) ng/L]、IL-1β[(19.7±4.4) ng/L]及CK-MB[(34.2±9.7) U/L]水平均明显高于恢复期及健康对照组,有显著性差异(F=17.2,21.4,13.5,14.1 Pa＜0.01),且血清MIF、TNF-α、LI-1β及CK-MB水平随病情加重而增高,MIF与CK-MB,TNF-α与CK-MB、IL-1β与CK-MB均呈正相关(r=0.68,0.82,0.73 Pa＜0.05);VM恢复期MIF[(41.8±8.2) ng/L]、TNF-α[(67.5±12.1) ng/L]、IL-1β[(6.4±1.2) ng/L]及CK-MB[(12.6±4.1) U/L]水平与健康对照组比较,无显著性差异(Pa＞0.05),且MIF、TNF-α、IL-1β与CK-MB无相关性(Pa＞0.05).结论 VM患儿存在细胞免疫功能紊乱,MIF、TNF-α、IL-1β可能参与VM发病过程,并可作为病情判断及疗效的观察指标之一.     

不同呼气末正压对脓毒性休克合并急性呼吸窘迫综合征婴幼儿预后的影响

目的 评价不同呼气末正压(positive end-expiratory pressure,PEEP)对脓毒性休克合并急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)婴幼儿预后的影响.方法 将广西壮族自治区妇幼保健院PICU收治的60例脓毒性休克合并ARDS婴幼儿分为3组,每组20例,分别应用低、中、高三种水平PEEP(3、6、9 cmH2O,l cmH2O=0.098 kPa)进行呼吸机辅助通气,均采用压力控制机械通气模式,小潮气量(6 ～8 ml/kg)通气策略,同时根据美国危重病儿科高级生命支持协会2009年颁布的脓毒性休克指南指导液体复苏.监测3组患儿上机后6、24、48 h氧合指数(OI)、呼吸系统动态顺应性(Cdyn)、心脏指数(CI)的变化并统计每例患儿的液体入/出量,比较3组患儿机械通气时间、PICU住院时间及28 d病死率.结果 机械通气后6h开始,中、高PEEP组OI、Cdyn均明显好转,与低PEEP组比较差异均有统计学意义(P均＜0.01);中、低PEEP组CI明显高于高PEEP组,液体入量少于高PEEP组,差异均有统计学意义(P均＜0.01),3组液体出量比较差异无统计学意义(P＞0.05);中PEEP组呼吸机辅助通气时间[(5.40±0.61)d]、PICU住院时间[(7.00±0.61)d]均短于高、低PEEP两组[(6.23±0.90)d、(7.51±1.09)d;(8.23-±0.90)d、(9.14±1.21)d](P均＜0.01);3组患儿病死率比较差异无统计学意义(P＞0.05).结论 中PEEP能显著改善脓毒性休克合并ARDS患儿的肺功能,缩短机械通气时间,对血流动力学无严重不良影响.     

血糖水平对脓毒性休克患儿预后的影响

目的 探讨血糖水平与脓毒性休克患儿预后的关系.方法 对61例脓毒性休克患儿进行血糖监测,同时对各脏器功能进行评估,分析血糖水平与预后的关系.结果 61例脓毒性休克患儿中,存活28例,死亡33例.死亡患儿的血糖值(20.10±13.10)mmol/L,明显高于存活患儿[(8.97±4.19)mmol/L],差异有显著性(P＜0.05).随着发生功能障碍的器官数目的 增加,血糖值越高,病死率也逐渐升高.血糖值的Logistic回归系数为-0.151,OR值为O.859.Logistic回归分析结果表明:血糖不是导致脓毒性休克患儿死亡的危险因素.结论 脓毒性休克患儿多存在血糖升高,但高血糖并不是脓毒性休克患儿死亡的直接原因.     

左卡尼汀对新生儿窒息致心肌损害的疗效

目的 探讨左卡尼汀治疗新生儿窒息致心肌损害的疗效.方法 窒息致心肌损害新生儿91例随机分为左卡尼汀治疗组(治疗组,48例)和常规治疗组(对照组,43例),二组患儿均予常规治疗,治疗组在常规治疗的基础上加用左卡尼汀针0.1 g/(kg·d)静脉滴注,1次/d,10 d为1个疗程.观察治疗前以及治疗过程中患儿症状体征的变化.在治疗前和治疗1个疗程,抽取患儿静脉血3 mL,分离血清,采用免疫抑制法和酶速率法分别检测其血清CK-MB和AST水平的变化,采用免疫比浊法和溴甲酚绿比色法分别检测血清前清蛋白和清蛋白水平的变化.采用Stata 7.0软件进行t、鳘2检验.结果 治疗组临床有效率(91.67%)明显高于对照组(74.42%)(P<0.05).治疗组心率恢复正常时间[(3.18 ±1.10) d]短于对照组[(4.32±1.43) d](P<0.05);治疗组CK-MB及AST分别为(22.48±4.72) U/L、(42.18±9.27) U/L,均较对照组[(29.06±6.10) U/L、(51.31±11.81) U/L]更接近正常值(Pa<0.05);治疗组前清蛋白[(125.25±30.64) mg/L]较对照组[(110.73±25.46) mg/L]提高更为明显(P<0.05);治疗组清蛋白[(38.58±6.56) g/L]较对照组[(35.79±6.44) g/L]也提高更为明显(P<0.05).结论 左卡尼汀治疗新生儿窒息致心肌损害具有良好疗效.     

先天性心脏病心肌损害临床分析

目的 探讨先天性心脏病(先心病)患儿心肌损害程度与缺氧及心功能的关系,为心肌保护提供理论依据。方法 测定115例先心病患儿心肌酶谱和58例先心病心肌肌钙蛋白I(CTnI)。结果 115例中A、D、E组心肌酶谱改变以乳酸脱氢酶(LDH)、乳酸脱氢酶同工酶1(LDH1)、肌酸激酶同工酶(CK-MB)、α-羟丁酸脱氢酶(α-HBDH)增高明显,在各组心肌酶谱结果比较及与正常值比较中,两组有显著差异或非常显著差异(P<0.05或P<0.01);CK-MB／CK>0.05。先心病患儿58例中A、D、E组cTnI检出阳性率明显升高(P<0.05),且A、D、E组中cTnI与LDH、LDH1、CK、α-HBDH阳性率比较,各组间有显著差异(P<0.05),与CK-MB比较,无显著差异(P>0.05)。结论 LDH、LDH1、CK-MB、CK-MB／CK、α-HBDH、cTnI是判断先心病患儿心肌损害重要指标;CK-MB与cTnI是诊断心肌损害的血清金标准。     

侵袭性肺炎链球菌性疾病所致脓毒性休克患儿临床特点及预后分析

目的:了解儿童重症监护病房(PICU)内侵袭性肺炎链球菌性疾病(IPD)所致脓毒性休克患儿的临床特点及预后。方法:回顾性收集2013年1月至2019年8月首都医科大学附属北京儿童医院重症医学科及河南省儿童医院重症医学科收治的IPD所致脓毒性休克患儿的病历资料,分析其临床及预后特点。结果:共纳入患儿21例,年龄1.2(0.75,3.90)岁。入PICU时第二代小儿死亡指数(PIM-2)为(23.3±29.6)%,并基础疾病6例。感染部位主要为血液(20例)及颅内(15例)。18例患儿行药敏试验,其中对青霉素敏感9例,对头孢吡肟/头孢噻肟敏感分别为10例和11例,对美罗培南敏感10例,对万古霉素及利奈唑胺均敏感;病初及脓毒性休克前应用敏感抗生素者分别为7和13例。21例患儿乳酸水平为(6.1±4.6)mmol/L,其中10例经治疗休克纠正时间为(10.9±10.1)h。13/21例(61.9%)患儿休克后死亡时间为(14.6±12.2)h,10例死于枕骨大孔疝。死亡组患儿入PICU时PIM2[(37.1±30.3)%比(0.9±1.3)%]及并颅高压危象率[69.9%(9/13例)比25%(2/8例)]显著高于存活组,差异均有统计学意义(均P<0.05);但年龄、休克前有效抗生素使用率等差异均无统计学意义(均P>0.05)。4/8例存活患儿遗留严重颅脑后遗症。结论:IPD致脓毒性休克多见于5岁以下儿童,以血流和颅内感染最常见,对头孢菌素及碳青霉烯类耐药率高。化脓性脑膜炎者易并颅高压危象,致死致残率高,需早期识别并治疗。     

Serum lactate dehydrogenase isoenzyme pattern in neuroblastoma

Total serum LDH activity and isoenzyme distribution were studied in children with neuroblastoma at the time of hospital admission. The total LDH was determined in 26 cases, and 20 (77%) of them showed elevation of its activity. On the other hand, in 9 of these 26 cases, the isoenzyme distribution was determined along with the total LDH. All 9 cases, 4 of them with normal total LDH activity, showed an abnormal isoenzyme pattern with a percentage increase in the intermediate fractions (malignant pattern). The results suggest the usefulness of the determination of serum LDH isoenzymes as a screening procedure in children with malignant tumors including neuroblastoma.     

Lactic acidemia,neurologic deterioration and carbohydrate dependence in a girl with dihydrolipoyl dehydrogenase deficiency

A girl with failure to thrive in the neonatal period was brought to the hospital at 10 weeks of age following a respiratory arrest, preceded by 12 h of vomiting and diarrhea. There was significant acidosis with a blood lactate of 8.8 mM. A high carbohydrate diet decreased her acidosis. Episodes of acidosis, often associated with infections, and accompanied by progressive neurological deterioration, have continued for 18 months. The activity of pyruvate dehydrogenase from cultured skin fibroblasts was 24% of that from normal fibroblasts. The activities of -ketoglutarate dehydrogenase and branched-chain keto acid dehydrogenase were also deficient. The activity of the dihydrolipoyl dehydrogenase component (E₃) of PDH in skin fibroblasts was 5% of that in control cell lines. Limited studies performed on liver and muscle biopsy specimens showed E₃ activity in liver and muscle to be undetectable in both tissues. We conclude that the enzyme defect present in dihydrolipoyl dehydrogenase is responsible for the reduced activity of all three -keto-acid dehydrogenase complexes and the patient's symptoms. Our results provide further evidence that the E₃ component of these complexes is genetically and biochemically the same protein.     

极长链酰基辅酶A脱氢酶缺乏症研究进展

极长链酰基辅酶A脱氢酶缺乏症是一种较罕见的脂肪酸代谢障碍疾病,根据起病年龄和临床表现分为三型：心肌病型、肝型、肌病型。心肌病型病情重,病死率高。临床诊断可通过血串联质谱(MS/MS)检测血肉豆蔻烯酰基肉碱(C14:1)水平进行,进一步确诊可通过基因诊断、酶学分析及脂肪酸氧化流量分析。治疗上主要包括避免空腹,减少长链脂肪酸的摄入,补充中链甘油三酯等。     

Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation

A boy with recurrent episodes of hypoglycaemia and ataxia, microcephaly, mental retardation, permanent lactic acidaemia, intermittent 2-oxoglutaric aciduria as well as elevation of serum branched chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3) deficiency. Analysis of genomic DNA revealed compound heterozygosity for two novel mutations: I393T in exon 11, located at the interface domain of the protein and possibly interfering with its dimerisation, and IVS9+1G>A located at a consensus splice site. A heterozygous polymorphism was also detected. In the patient's cDNA the I393T mutation and the polymorphism appeared to be homozygous, indicating that the mRNA coming from the IVS9+1G>A mutant allele is not stable. CONCLUSION: as opposed to the non-neurological phenotype of patients with a homozygous G229C mutation, this patient developed Leigh syndrome. Dihydrolipoamide dehydrogenase and pyruvate dehydrogenase complex activities in muscle were 29% and 14% of the lowest control values, respectively. Pyruvate dehydrogenase complex activity in fibroblasts was normal, however, indicating that the biochemical examination of defects in energy metabolism should be performed in a more energy demanding tissue.     

中、短链酰基辅酶A脱氢酶缺乏症患儿临床特点分析及基因突变研究

中、短链酰基辅酶A 脱氢酶缺乏症属脂肪酸β 氧化障碍疾病,其基因突变可导致中、短链脂肪酸无法进入线粒体进行氧化供能,引起多器官功能异常。本研究对2 例临床表现为低血糖合并代谢性酸中毒的患儿进行血酰基肉碱及尿液有机酸分析,同时对患儿及其父母进行基因突变检测。家系1 患儿,男,3 d,出生后因新生儿窒息、吸奶无力、嗜睡住院治疗。血酰基肉碱谱提示中链酰基肉碱（C6~C10）升高,其中辛酰肉碱（C8）3.52 μmol/L（参考值0.02~0.2 μmol/L）;尿有机酸分析未见明显异常;Sanger 测序发现ACADM 基因7 号外显子已报道纯合突变c.580A>G（p.Asn194Asp）。家系2 患儿,女,3 个月,因咳嗽伴反复发热10 余天住院治疗。血酰基肉碱谱提示血丁酰肉碱（C4）1.66 μmol/L（参考值0.06~0.6 μmol/L）;尿有机酸分析提示乙基丙二酸55.9（参考值0~6.2）;Sanger 测序发现ACADS 基因已报道纯合突变c.625G > A（p.Gly209Ser）。研究结果提示对不明原因代谢性酸中毒及低血糖患儿应进行遗传代谢病筛查,通过家系ACADM、ACADS 基因分析,将有助于中、短链酰基辅酶A 脱氢酶缺乏症的诊断。     

磷酸甘油酸脱氢酶基因与肿瘤

磷酸甘油酸脱氢酶(phosphoglycerate dehydrogenase,PHGDH)基因编码3-磷酸甘油酸脱氢酶,是糖酵解-丝氨酸生物合成途径中的第一个分支酶.PHGDH氧化糖酵解中间产物3-磷酸甘油酸为磷酸羟基丙酮酸,后通过一系列酶的作用最终合成丝氨酸.丝氨酸在蛋白和细胞增殖所需其他生物分子(如核苷酸、磷脂丝氨酸、鞘氨醇)的合成中起着重要的作用.最新研究发现PHGDH高表达于一系列肿瘤中,且与肿瘤细胞生长、凋亡相关.该文就PHGDH基因结构、功能及与肿瘤的关系作一综述.     

A severe case of hyperinsulinism due to hemizygous activating mutation of glutamate dehydrogenase

Activating mutations in the GLUD1 gene, which encodes glutamate dehydrogenase (GDH), result in the hyperinsulinism‐hyperammonemia syndrome. GDH is an allosterically regulated enzyme responsible for amino acid‐mediated insulin secretion via the oxidative deamination of glutamate to 2‐oxoglutarate, leading to ATP production and insulin release. This study characterizes a novel combination of mutations in GLUD1 found in a neonate who presented on the first day of life with severe hypoglycemia, hyperammonemia, and seizures. Mutation analysis revealed a novel frameshift mutation (c.37delC) inherited from the asymptomatic mother that results in a truncated protein and a de novo activating mutation (p.S445L) close to the GTP binding site that has previously been reported. GTP inhibition of GDH enzyme activity in 293T cells expressing the p.S445L or wild‐type GDH showed that the half‐maximal inhibitory concentration (IC₅₀) for GTP was approximately 800 times higher for p.S445L compared to wild type. GTP inhibition of GDH activity in lymphoblasts from the patient, from a heterozygote for the p.S445L mutation, and in wild‐type lymphoblasts showed that the IC₅₀ for GTP of the patient was approximately 200 times that of wild type and 7 times that of heterozygote. However, while the patient had a loss of GTP inhibition of GDH that was more severe than that of heterozygotes, the patient's clinical phenotype is similar to typical heterozygous mutations of GDH. This is the first time we have observed a functionally homozygous activating mutation of GDH in a human.     

Hyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene

Fatty acids play an important role in regulating insulin secretion, but the mechanisms are unclear. We report a case of a novel splice site mutation in the short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) gene associated with hyperinsulinism. This mutation resulted in a nearly complete absence of immunoreactive protein and a decrease in fibroblast SCHAD activity.