换血治疗新生儿高胆红素血症

我院新生儿科自1990年6月～1997年6月共进行换血治疗各种病因引起的中重度高胆红素血症40例,取得良好的疗效。现报告如下。临床资料一、一般资料：男29例,女11例。入院日龄：≤24小时14例,～48小时12例,～72／小时4例,＞72小时10例。胎龄：＜37周4例,≥37周36例。二、症状体征：入院时均有黄疽,黄疽出现时间：出生～12小时18例,～24小时7例,～48小时7例,＞48小时8例,其中3例出生时即有黄疽。入院时易激惹、烦燥、生理反射减弱早期核黄瘦征象3例。三、实验室检查：入院时血红蛋白rtl40g／L20例,最低1例829／L,＞1409／L20例。…     

47例新生儿高胆红素血症临床研究

目的本文主要是研究影响新生儿出现高胆红素血症发病率的因素。方法通过对已有的在我院住院过的47例临床资料进行回顾分析。结果新生婴儿出现高胆红素血症主要是由于感染、围生期因素、血液因素和其他因素造成的,分别占了639／6、15％、13％、9％。结论通过分析这个病症的发病因素有着非常重要的临床价值对于预防和控制这种疾病,并制定出有效的预防措施,达到早诊断,早治疗减少新生儿高胆红素血症及其后遗症的发生。     

新生儿高胆红素血症的护理

高胆红素血症是指新生儿胆红素代谢及排泄的正常途征改变,使血清内胆红素浓度超过正常值范围,在胆红素>5mg/dl时,巩膜皮肤可出现黄疸。其中以结合胆红素增高为主,引起的黄疸叫高结合胆红素血症,新生儿结合胆红素增高的病人可归纳为肝胆道阻塞、遗传代谢紊乱、先天性持续性郁     

重症新生儿高胆红素血症换血疗法的护理

对8例重度高胆红素血症患儿,及早进行评估,早期掌握换血指征,准备好抢救用物,换血过程全程熟悉配合,密切观察病情,及早发现并发症的早期症状,及时处理,从而提高换血成功率,防治核黄疸引起的死亡和严重后遗症。     

高胆红素血症早产儿血清阴离子隙分析的意义

目的 探讨早产儿高胆红素血症(下称高胆)患儿的阴离子隙(AG)变化,为治疗提供依据.方法 测定94例高胆早产儿血清电解质、肾功能、肝功能,计算AG值,其中36例同时做动脉血气分折.结果 高AG44例(46.81％),正常AG 44例(46.81％),低AG 6例(6.38％).AG增高与血Na+浓度成正比,与HCO3-呈反比.AG与血清尿素氮(BUN)、肌酐(Scr)无相关性.结论 高胆早产儿高AG代谢性酸中毒发生率高,应常规测定血电解质、肾功能及动脉血气,计算AG值以指导治疗,以免盲目用碱纠酸.     

新生儿高胆红素血症的病因及治疗

新生儿高胆红素血症的病因及治疗长治医学院附属医院（０４６０００）方金龙，赵冬梅晋城市医科所范静珍新生儿高胆红素血症（以下简称新生儿高胆）为新生儿常见危重症之一，重者可致胆红素脑病甚至死亡。我科近十年来共收治新生儿高胆７０例，采用以输注血浆为主的非换血综合疗法，取得满意效果。现报告分析如下。临床资料一、一般资料：本组男５３例，女１７例。男：女２３：１。发病日龄：新生儿早期（生后７天以内）３１例，新生儿晚期（生后７～２８天）３９例。原发病：新生儿早期患儿中感染１６例占５１．６％，血肿６例占１９．３％，溶血症７例（其中ＡＢＯ血型不合５例，Ｒｈ因子不合２例）占２２．６％，自然出血症２例占６．５％。新生儿晚期病例中，感染３２例占８２．２％，肝炎综合征５例占１２．８％，血肿２例占５．０％。二、血清胆红素水平：０．７０２～０．８７８μｍｏｌ／Ｌ３７例，～１．１７μｍｏｌ／Ｌ２３例，～１．４６３μｍｏｌ／Ｌ６例，～１．７５５μｍｕｌ／Ｌｌ例。超过１．１７０μｍｏｌ／Ｌ者１０例。直接胆红素升高１６例，间接胆红素升高５２例，双相升高２例。三、治疗：因条件所限，本组病例皆未行换血治疗而采用综合疗法：①一般治疗：抗感染、清除血肿、     

新生儿高胆红素血症的诊断进展

新生儿黄疸是由于体内胆红素的累积引起皮肤或其他器官黄染的现象。由于新生儿胆红素代谢的特点,约有50％足月儿和80％早产儿可出现肉眼可见的黄疸,一般足月儿血清总胆红素不超过205μmol/L,早产儿不超过256μmol/L,称为生理性黄疸。胆红素超过上述值者称为高胆红素血症(简称高胆)。足月儿如超过342 μmol/L,早产儿由于血脑屏障功能差,如同时有病理因素存在,影响血脑屏障功能,超过171μmol/L(10 mg/     

新生儿高胆红素血症临床分析

本文分析了我院儿科2003年6月-2006年2月住院新生儿高胆红素血症99例临床资料作以回顾性分析,现总结报告如下：     

苯巴比妥治疗新生儿高胆红素血症

目的探讨苯巴比妥治疗新生儿高胆红素血症的临床疗效。方法除一般治疗如供给营养,诱导建立正常菌群,减少肝肠循环,减少肠壁再吸收胆红素外,同时给予苯巴比妥口服治疗。结果 24例患儿,治疗第2天,血清胆红素平均值降到了(169±50.63)μmol/L,有10例,治疗第3天,血清胆红素平均值降到了(175±61.76)μmol/L,有9例,治疗第4天,血清胆红素平均值降到了(173±21.76)μmol/L。43例患儿血清胆红素浓度明显降低。结论苯巴比妥可以有效地使新生儿血清胆红素的浓度降至安全水平,避免了可能出现的高胆红素血症造成的一系列病理损害,值得临床推广应用。     

新生儿高胆红素血症91例临床分析

自1996～2004年我科诊治新生儿高胆红素血症91例。本文对其综合分析,旨在提高对新生儿高胆红素血症的防治水平。1临床资料1.1诊断标准依据《实用新生儿学》第二版高胆红素血症诊断标准[1],生后24h内出现黄疸,血清总胆红素(TBi1)足月儿>220.6μmol/L,早产儿>255μmol/L,符合以上标准诊断为高胆红素血症。1.2一般资料本组91例中,女48例,男43例;足月儿89例,早产儿2例;日龄<7天19例,<14天17例,<21天17例,>21天38例。黄疸出现时间最早在生后14h,最迟4天,平均2.85天。TBi1均>220.6μmol/L,其中220.7～342μmol/L83例,>342μmol/L8例,最高达471…     

妈咪爱联合婴儿抚触佐治新生儿高胆红素血症的疗效观察

目的探讨妈咪爱联合婴儿抚触对降低新生儿高胆红素血症的疗效。方法选取93例足月分娩的新生儿,随机分为两组,一组为对照组,另一组为治疗组,治疗组在常规治疗的基础上加用婴儿抚触及妈咪爱治疗,观察两组患儿黄疸消退时间及胆红素下降情况。结果治疗组疗效优于对照组,两者差异有显著性（P〈0.01）。结论婴儿抚触和妈咪爱联合治疗新生儿高胆红素血症可迅速降低血清总胆红素水平,明显缩短治疗时间。     

小儿高胆红素血症时心肌酶活性分析

目的分析小儿高胆红素血症(简称高胆)和心肌酶变化间的关系。方法保健部门诊健康小儿50例作为对照组,住院小婴儿126例为观察组,分别于入院时(治疗前)、治疗5天、治疗14天后抽不抗凝血3ml,各组均用全自动生化分析仪测定胆红素、心肌酶、肝功能,56例患者做心电图检查。结果治疗前、治疗5天时血清心肌酶与对照组相比差异有统计学意义(P<0.001),治疗前、治疗5天、治疗14天后两两相比均具有统计学意义(P<0.05)。治疗14天后和对照组相比差无异统计学意义(P>0.05);心肌酶高低和胆红素值呈正相关,经治疗后,随胆红素下降心肌酶明显下降。结论高胆患儿常伴有心肌酶活性异常,临床治疗高胆时应将心肌酶检测及保护心肌治疗定为常规项目。     

高胆红素血症及感染对新生儿红细胞免疫粘附功能的影响

目的:探讨新生儿高胆红素血症和感染因素对红细胞免疫粘附功能的影响.方法:选取2010年1月至2010年12月在南通大学附属吴江市第一人民医院新生儿科住院的135例患儿,血清总胆红素(TBIL)均＞220.6 μmol/L.按照TBIL浓度和有无感染因素分为两组,同时选择50例正常新生儿作为对照组.分别用花环法测定红细胞C3b受体花环率(E-C3bRR).结果:新生儿高胆红素血症患儿的E-C3bRR较正常新生儿低,但只有当TBIL＞342.0 μmol/L时,其E-C3bRR (9.64±2.89)与正常对照组(11.12±3.53)比较差异有统计学意义(t=2.084,P＜0.05),并且与TBIL值之间呈负相关(r=-0.363,P＜0.05);有感染因素的高胆红素血症患儿的E-C3bRR( 9.58±3.02)与正常对照组比较差异有统计学意义(t=2.497,P＜0.05);在TBIL浓度相当时,TBIL在220.6～ 342.0 μmol/L时有感染组的E-C3bRR(9.67±3.20)较无感染组(10.93 ±3.01)降低,两者比较差异有统计学意义(t=1.996,P＜0.05);而TBIL＞342.0μmol/L时有感染组的E-C3bRR(8.21±2.95)与无感染组(9.78±2.87)比较差异无统计学意义(t=1.622,P＞0.05).结论:血清胆红素明显升高时红细胞免疫粘附功能下降.新生儿感染时,其红细胞免疫粘附功能也下降,合并感染的高胆红素血症红细胞免疫粘附功能更差.     

Drug-induced Hyperbilirubinemia and the Clinical Influencing Factors

Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the important causes of hyperbilirubinemia, especially for patients with certain pathologic conditions or with genetic variations. This article reviews hyperbilirubinemic pathophysiology with respect to the effects of clinical drugs. In addition, this review introduces a new formula that may be utilized to estimate the annual occurrences of drug-induced hyperbilirubinemia in a hospital. Variations in the genes of UDP-glucuronosyltransferases, organic anion-transporting polypeptides and multidrug resistance proteins are the predisposing factors for drug-induced hyperbilirubinemia; therefore, their genetic and ethnic polymorphisms are discussed.     

Does Ethnic Variability Exist in the Systemic Exposures of OATP1A2 Substrates–Fexofenadine in Taiwanese?

The aim of this study was to investigate differences in organic anion transporting polypeptide 1A2 activity among the Taiwanese population via an analysis of 3 pharmacokinetic studies completed in a total of 103 healthy male Taiwanese subjects. The pharmacokinetics of fexofenadine was measured as an indicator of organic anion transporting polypeptide 1A2 activity. Using the Kolmogorov-Smirnov test and quantile plots, the frequency distributions of area under the concentration-time curve and concentration were shown to be tri-modal and to represent 3 pharmacokinetic phenotypes. In a comparison with published data, the mean area under the concentration-time curve of fexofenadine in the Taiwanese subjects was similar to that in American, German, and Indian subjects, but significantly different from that in some Asian populations, including Korean and Japanese ethnic groups. These results suggested that Taiwanese subjects showed genetic variation in fexofenadine pharmacokinetics that was associated with differences in organic anion transporting polypeptide 1A2 activity.     

Dual kinetics of OATP2B1: Inhibitory potency and pH-dependence of OATP2B1 inhibitors

Organic anion transporting polypeptide (OATP) 2B1 is expressed in the intestine and liver, and OATP2B1-mediated transport of estrone 3-sulfate is pH-dependent and consists of: the high-affinity component (Hc) and low-affinity component (Lc). This study aimed to evaluate the influence of pH on the transport kinetics of each component, along with the inhibitory nature of ten OATP2B1 inhibitors. The Michaelis constants (K_m) were 4-fold and 1.5-fold lower at pH 6.3 than at pH 7.4, for Hc and Lc respectively. The inhibitory potencies of diclofenac, indomethacin, and ibuprofen towards Hc were 1.5–4.3 fold lower at pH 6.3 than at pH 7.4. Contrastingly, inhibitory potencies towards Lc were 9.0–52 fold lower at pH 7.4. Similarly, the inhibitory effect of naproxen was stronger towards Hc at pH 6.3 and towards Lc at pH 7.4. On the other hand, celecoxib selectively inhibited Lc transport at pH 7.4. Rifampicin inhibited both components at pH 6.3 and 7.4 to a similar extent, while bromosulphophthalein, naringin, and gefitinib selectively inhibited Hc irrespective of pH. Fexofenadine inhibited neither component. In conclusion, the transport affinities of both Hc and Lc were enhanced under acidic conditions. The influence of pH on the inhibitory potency towards each component varied among the inhibitors.     

Hydrophilic anti-migraine triptans are substrates for OATP1A2, a transporter expressed at human blood-brain barrier

1. OATP1A2 is expressed in the luminal membrane of human blood-brain barrier (BBB). The human tissue with the highest OATP1A2 mRNA expression is the brain.

2. We have established a robust BacMam2-OATP1A2 transduced HEK293 system. Among the 36 central nervous system (CNS) marketed drugs tested, hydrophilic triptans, 5-HT_1B/1D receptor agonists for the treatment of migraine attacks, were identified as OATP1A2 substrates. Kinetics (K_m and V_max) were determined for six marketed triptans.

3. Structure-activity relationship (SAR) obtained from 18 triptan structural analogs revealed that the positively charged basic amine atom was essential for efficient OATP1A2-mediated triptan uptake and uptake rate was in the order of tertiary > secondary > primary.

4. Preliminary quantitative SAR analysis of the triptan analogs demonstrated positive correlation between OATP1A2-mediated uptake rate and van der Waals volume (vdw_vol).

5. OATP1A2 was specifically expressed on the apical side of MDCKII monolayer after BacMam2-OATP1A2 transduction and can facilitate transport of triptans across the MDCKII monolayer from apical to basolateral side. Involvement of OATP1A2 for brain penetration of triptans in human requires further investigation.

     

Post-transcriptional regulation of OATP2B1 transporter by a microRNA,miR-24

Human OATP2B1, a member of organic anion transporting polypeptide family, is expressed in several tissues, including small intestine and liver, and contributes to cellular uptake of endogenous compounds and various drugs. Altered expression of OATP2B1 affects pharmacokinetics of substrate drugs; however, limited information is available on the regulation of OATP2B1 expression. This study aimed to explore microRNAs (miRNAs) that regulate OATP2B1 expression using HEK293 cells transfected with an expression plasmid of OATP2B1 including 3′-UTR (HEK/OATP2B1) and Caco-2 as a model of human intestine. Computational analysis predicted that three miRNAs, miR-143, miR-125b and miR-24, may bind to the 3′-UTR of OATP2B1 mRNA. A luciferase assay using a plasmid containing the 3′-UTR of OATP2B1 gene demonstrated that only miR-24 significantly reduced its expression. The overexpression of miR-24 decreased the expression of OATP2B1 mRNA and protein in HEK/OATP2B1 and Caco-2 cells and uptake of [³H]estrone-3-sulfate by HEK/OATP2B1 cells. However, a statistically significant increase of endogenous OATP2B1 expression was not observed by miR-24 inhibitor in Caco-2 cells. In conclusion, it was found that miR-24 negatively regulates OATP2B1 expression, resulting in suppression of OATP2B1 activity, while its contribution to regulation of apparent expression of OATP2B1 is considered to depend on tissues and cell types.