HB-H-6树脂血浆灌流治疗重度黄疸初步临床研究

目的研究HB-H-6树脂吸附胆红素血浆灌流对重度黄疸的治疗效果。方法重度黄疸患者76例,其中男性61例,女性15例,年龄41～75岁,平均59岁。均为急慢性肝功能衰竭、重型肝炎造成的肝细胞性黄疸和肿瘤、结石等阻塞胆管而造成的梗阻性黄疸,其中肝细胞性黄疸70例,梗阻性黄疸6例。总胆红素(TBiL)(359±138)μmol/L,直接胆红素(I鄄BiL)(132±76)μmol/L,间接胆红素(DBiL)(227±97)μmol/L;总蛋白(TP)(64±12)g/L,白蛋白(Alb)(28±11)g/L,球蛋白(Glb)(36±13)g/L。采用一次性使用HB-H-6树脂吸附胆红素血浆灌流器进行治疗。分别于灌流前、灌流120min取血测定血浆胆红素、蛋白质、电解质、血常规,定时观察患者血压、心率、体温和呼吸变化。结果灌流至2h结束,总胆红素下降29%,直接胆红素下降27%,间接胆红素下降30%;总蛋白下降11%,白蛋白下降14%,球蛋白下降8%;灌流对血浆电解质钾、钠、氯、钙、镁和磷均无明显影响(P>0.05)。灌流前后相比,白细胞升高2%,红细胞下降1%,血小板降低6%(P>0.05)。灌流过程中,患者心率、血压、体温和呼吸等生命指标均无明显变化。结论HB-H-6树脂血浆灌流治疗重度黄疸是一种安全、有效的方法,其血浆灌流器很有发展前途。     

用HB-H-6树脂吸附胆红素血浆灌流器治疗76例重度黄疸的临床报告

笔者于2004年至2006年使用天津市紫波公司生产的一次性使用HB-H-6树脂吸附胆红素血浆灌流器(以下简称灌流器)用于治疗重度黄疸76例,取得良好疗效,现总结如下。材料和方法患者76例,其中男61例,女15例,年龄41～75岁,均为药物中毒等致急慢性肝功能衰竭及重型肝炎造成的肝细胞性黄疸和肿瘤、结石等阻塞胆管而造成的梗阻性黄疸患者。灌流器使用紫波公司生产的一次性使用HB-H-6树脂吸附胆红素血浆灌流器,灌流器内填充树脂330 ml±10 ml。灌流方法采用血浆灌流,全血流速为150～200 ml／min,血浆流速为20-25 ml／min,肝素总用量为40～55 mg,灌流结束前静脉推入鱼精蛋白50 mg。     

新型壳聚糖对血浆胆红素和细胞因子吸附性能的体外筛选初步研究

目的观察各类新型吸附剂对重型肝炎患者血浆中的胆红素和细胞因子的吸附性能。方法第一步,收集第一组重型肝炎患者的血浆各3ml,以8种不同的吸附剂(1#～3#为致孔剂浓度分别为3%、1%、5%的壳聚糖,4#为胺基化壳聚糖,5#为苯乙烯/二乙烯苯聚合物,6#为后交连苯乙烯/二乙烯苯聚合物,7#为壳聚糖-苯乙烯/二乙烯苯聚合物,8#为壳聚糖-后交连苯乙烯/二乙烯苯聚合物)各1ml进行吸附,检测对胆红素的吸附能力,做吸附剂筛选实验和吸附实验。第二步,用以上筛选出吸附率较好的两种吸附剂各1ml对第二组患者血浆(各3ml)进行胆红素和细胞因子的吸附实验。结果第一步实验显示胺基壳聚糖(4#)和苯乙烯/二乙烯苯聚合物(5#)有较好的吸附效果,4#吸附剂对总胆红素(TBiL)、直接胆红素(DBiL)、间接胆红素(IBiL)的吸附率分别为50.5%±3.4%、57.0%±11.3%、39.0%±7.2%;5#分别为30.1%±2.5%、32.6%±3.0%、27.6%±2.9%。第二步实验显示4#胺基化壳聚糖吸附后血浆中TBiL、DBiL、IBiL、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平下降比5#明显,有统计学意义(P<0.001)。结论胺基化壳聚糖(4#)体外吸附重型肝炎患者血浆中胆红素、细胞因子效果有明显优势。     

新生儿黄疸患儿治疗前后血清TRF、CRP及胆红素水平变化及其临床意义

目的探讨新生儿黄疽治疗前后血清转铁蛋白(TRF)、C反应蛋白(CRP)及胆红素水平的变化及意义。方法选择2015年1月至2017年3月于医院生产的140例新生儿黄疽患儿作为研究对象,根据黄疽类型分为病理性黄疸组(n=86)与生理性黄疽组(n=54),并选取同期于医院生产的50例正常健康新生儿作为对照组,均采血检测血清TRF、CRP、总胆红素(TBiL)及直接胆红素(DBiL)水平,病理性黄疸组于治疗前后均检测上述指标的变化,分析TRF、CRP与胆红素水平变化的关系。结果生理性黄疸组、病理性黄疸组血清TBiL、DBiL均高于对照组,TRF低于对照组,病理性黄疸组血清CRP、TBiL、DBiL又高于生理性黄疽组,TRF低于生理性黄疽组(P<0.05);治疗后,病理性黄疽新生儿TRF上升,CRP、TBiL、DBiL水平降低,与治疗前比较差异有统计学意义(P<0.05);CRP与新生儿病理性黄疽TBiL、DBiL呈正相关(P<0.05),TRF与TBiL及DBiL均呈负相关(P <0. 05)。结论新生儿黄疽患儿TRF水平较低,CRP水平较高,且病理性黄疽组TRF低于生理性黄疽组,CRP高于生理性黄疽组,两者均与新生儿病理性黄疸组TBiL、DBiL水平存在相关性,可作为病理性黄疽病情评估及疗效预测的依据。     

HB-H-7血浆灌流树脂清除血液内毒素和炎性细胞因子实验研究

目的研制一种新型血浆灌流树脂,探讨同时清除内毒素和炎性细胞因子有效性。方法自制HB-H-7血浆灌流树脂(苯乙烯-二乙烯基苯大孔树脂)。对内毒素水溶液、炎性细胞因子[肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1、IL-6、IL-8]水溶液进行吸附研究。在此基础上,采用大肠杆菌和内毒素标准品两种物质刺激新鲜血液,模拟内毒素血症产生过程,采用最佳刺激方式处理样本后进行血浆吸附,研究该树脂对内毒素和炎性细胞因子吸附的有效性和安全性。结果 HBH-7树脂对血浆内内毒素和炎性细胞因子(TNF-α、IL-1、IL-6、IL-8)比水溶液内的吸附率低,分别为(52.8±2.3)%、(45.1±3.4)%、(8.2±2.6)%、(36.5±3.7)%和(16.1±2.9)%;对红细胞、血小板和白细胞的吸附率分别为(5.3±3.2)%、(1.9±1.7)%和(38.1±4.3)%;对血浆总蛋白、白蛋白和球蛋白吸附率分别为(13.6±2.9)%、(11.2±2.3)%和(17.5±3.1)%,对血浆电解质吸附率较小。结论 HB-H-7血浆灌流树脂能有效吸附内毒素和炎性细胞因子,有望用于治疗内毒素血症。     

连续性树脂血浆灌流吸附治疗肝病性高胆红素血症13例报道

目的观察树脂血浆灌流吸附治疗13例肝病性高胆红素血症患者的疗效。方法13例肝病性高胆红素血症患者（rIBiL≥171μmol／L），采用连续性HB—H-6树脂血浆灌流吸附治疗。观察胆红素变化情况及对血压、心率、呼吸和体温的影响。结果灌流前与灌流后相比，血浆总胆红素下降53％，直接胆红素下降49％，间接胆红素下降66％；血压、心率、呼吸和体温没有明显变化。结论树脂血浆灌流吸附治疗肝病性高胆红素血症是一种安全有效的方法。     

血浆置换联合HB-H-6树脂血浆吸附治疗慢性肝炎重度黄疸临床观察

目的 探讨血浆置换联合HB-H-6树脂血浆吸附(PE + PA)治疗慢性肝炎重度黄疸的疗效及临床价值.方法 75例慢性肝炎重度黄疸患者随机分为治疗组和对照组.治疗组38例,其中男性33例,女性5例,年龄28 ～ 67岁,平均年龄39.27岁;对照组37例,其中男性32例,女性5例,年龄29 ～ 65岁,平均年龄40.12岁.对照组患者只给予常规药物综合治疗,治疗组患者在药物综合治疗的基础上给予PE + PA治疗,并分别观察两组治疗前后症状、体征、肝功能、凝血酶原活动度(PTA)、血常规、电解质及治疗中并发症的发生;检测治疗前,治疗后2、4周的肝功能、PTA等指标并追踪近期转归.结果 治疗组经PE + PA治疗后2、4周较治疗前,总胆红素(TBiL)下降明显(P < 0.01),PTA上升明显(P < 0.05).治疗组治愈好转率86.84 %,对照组治愈好转率67.57 %(P < 0.05).结论 PE + PA治疗慢性肝炎重度黄疸患者能显著改善肝功能,阻止病情恶化,明显提高临床治愈好转率.     

天津市紫波高科技有限公司

天津市紫波高科技有限公司获奖介绍 紫波公司依托天津市第三中心医院血液灌流方面有30余年的研究工作基础,在大量体外实验、动物实验和临床研究的基础上,研制开发成功“一次性使用HB-H-6树脂吸附胆红素血浆灌流器”,     

用HB-H-7树脂血液灌流清除内毒素研究

目的内毒素血症主要由重度感染和重度肝炎引起,严重危害患者健康和生命,是医学临床研究的重要课题。笔者用自主研制的HB-H-7树脂可以有效清除内毒素,体外实验获得满意效果,现报道如下。材料和方法吸附剂为天津市第三中心医院研制的HB-H-7树脂,以及NK-107树脂、NK-110树脂、炭化树脂、聚苯乙烯活化树脂。大肠杆菌内毒素由卫生部北京生物制品研究所提供。吸附实验方法分为静态吸附实验和灌流吸附实验。静态吸附实验取HB-H-7树脂1 m1,加入20μg/ml内毒素溶液10 ml,置37℃恒温水浴震荡2 h,震荡前后各取样测定内毒素浓度并计算吸附量;同样条件,用NK-107树脂、NK-110树脂、炭化树脂、聚苯乙烯活化树脂做内毒素吸附实验,测量吸附量。灌流吸附实验取HB-H-7树脂5 ml,用50 ml内毒素溶液(20μg/ml)灌流2 h,灌流前后各取样测定内毒素浓度并计算吸附量。内毒素测定采用紫外分光光度法。     

妈咪爱和普瑞博思悬浊液辅助治疗新生儿高胆红素血症的疗效观察

目的:及早有效纠正新生儿高胆红素血症,以防胆红素脑损伤。方法:在常规治疗的同时加用妈咪爱和普瑞博思悬浊液口服。结果:治疗组胆红素日均下降值为(50.23±25.37)μmol/L明显高于对照组的(37.64±21.56)μmol/L(P<0.01)。结论:妈咪爱和普瑞博思悬浊液用于辅助治疗新生儿黄疸,可迅速降低血胆红素水平,明显缩短治疗时间。     

树脂吸附结合光照清除腹水胆红素的临床观察

目的观察树脂吸附结合光照清除腹水中胆红素的安全性及临床效果，解决临床肝硬化合并黄疸腹水问题。方法肝硬化合并黄疸腹水患者21例，其中男性17例，女性4例，年龄50-72岁，平均年龄60．2岁。将经过预处理的HB—H-6树脂装入特制灌流器，高压蒸汽灭菌；按常规方法行腹腔穿刺引流腹水，用树脂吸附结合蓝光照射60min：分别于灌流前后取样测定腹水中蛋白、细胞总数、密度和渗透浓度；将处理后腹水进行静脉回输，密切观察患者一般情况及体温、心率、尿量等变化；分别取灌流前后树脂进行透射电子显微镜观察。树脂吸附加光照后腹水静脉回输25例次。结果①处理后腹水外观颜色明显变浅。②处理前后比较，腹水中总胆红素下降40％-50％，结合胆红素下降33％～50％，未结合胆红素最多可下降80％，腹水中蛋白和细胞总数略有下降，腹水密度、渗透浓度未见明显变化。③电镜观察可见树脂呈网状骨架结构，灌流后树脂骨架中散在分布电子致密度大的不整形块状、条索状物，为胆红素。④25例次腹水回输后除1例患者出现发热，其余均无不适，腹水回输后患者尿量增多，部分患者血胆红素降低。结论采用树脂吸附结合光照处理腹水中胆红素，为肝硬化顽固性腹水的治疗带来新方法，     

Biochemical assessment and clinical evaluation of a non-ionic adsorbent resin in patients with intractable jaundice

We investigated in vitro and in vivo the ability of a non-ionic adsorbing resin (styrenedivinylbenzene copolymer) to remove bilirubin and bile acids from human plasma. In preliminary experiments, human plasma from healthy donors, enriched in conjugated bile acids and bilirubin, and pooled plasma from jaundiced patients were recirculated through the resin column. The removal of bilirubin and bile acids was evaluated at two different flow rates (200 ml/min and 40 ml/min), and compared to an activated charcoal column. Four patients with severe jaundice were subsequently treated by 4-hour plasmaperfusion through the resin. The in vitro studies showed that after 1 hour the removal of bile acids was almost complete and bilirubin level decreased significantly, reaching a plateau after 4 hours. In the in vivo study, all treatments were well tolerated. After plasmaperfusion, serum bile acid levels decreased by 64.9-94.6% and total bilirubin by 35.3-57.7%. No clinical or biochemical side effects were observed. Our data suggest that plasmaperfusion through this resin is safe and efficient for removal of bilirubin and bile acids in jaundiced patients. Thus, it may serve as a method of artificial liver support in the treatment of cholestatic syndromes.     

HB-H-8树脂吸附低密度脂蛋白的体外实验研究

目的 目前,用于降低血液中低密度脂蛋白(LDL)的吸附分离材料尚存在需要改进的地方.HB-H-8树脂在吸附LDL方面尚无应用,本研究对HB-H-8树脂的吸附性能进行了初步评价.方法 首先实验室制备HB-H-8树脂,经过处理后用其对LDL高于正常范围的患者血清标本进行体外动态和静态吸附实验.结果 体外动态吸附结果表明,HB-H-8树脂对LDL的吸附饱和时间为2h,最适吸附温度为恒温37℃,体外静态吸附结果显示HB-H-8树脂对LDL平均吸附率为63.2％,而对高密度脂蛋白(HDL)的平均吸附率为1.9％.结论 HB-H-8树脂对LDL具有良好的特异性吸附性能,有望开发为一种低密度脂蛋白的血液净化医用吸附材料.     

血浆胆红素吸附在高胆红素血症治疗中的应用

目的探讨血浆胆红素吸附治疗高胆红素血症疗效及临床价值。方法选择青岛市传染病医院65例非乙型、丙型肝炎急性肝损害重度黄疸住院治疗患者,随机分为2组。治疗组33例,其中男性25例,女性8例,年龄33～75岁,平均年龄59.39岁;对照组32例,其中男性26例,女性6例,年龄34～77岁,平均年龄58.12岁。对照组32例患者只给予药物综合治疗,治疗组33例患者在药物综合治疗的基础上给予血浆特异性胆红素吸附治疗,并分别观察2组治疗前后症状、体征、肝功能、凝血酶原活性（PTA）、血常规、电解质及治疗中并发症的发生。检测治疗前和治疗后2、4周的肝功能、PTA等并追踪近期转归。结果治疗组经血浆胆红素吸附治疗后2周、4周较治疗前,总胆红素（TBiL）下降明显（P〈0.01）,PTA上升明显（P〈0.05）。治疗组4周治愈率39.40%,对照组4周治愈率12.50%（P〈0.05）,治疗组8周治愈率66.67%,对照组8周治愈率40.63%（P〈0.05）。结论血浆胆红素吸附治疗急性肝损害重度黄疸患者能显著改善肝功能,阻止病情恶化,明显提高临床治愈好转率,特别适合于不宜血浆置换治疗的重度黄疸患者。     

Electron microscopic findings of the liver of a patient with Dubin–Johnson syndrome complicated by chronic hepatitis C and iron overload

A patient was first found to have Dubin–Johnson syndrome and chronic hepatitis at the age of 25 years. Two years later, he underwent gastrectomy because of massive bleeding from duodenal ulcer, followed by posttransfusion self-limited biochemical liver damage. Twenty-five years later, his jaundice worsened to a serum bilirubin level of 10 mg/dl. The test for circulating hepatitis C virus RNA was highly positive, and liver histology showed cirrhosis with brown pigment granules in small numbers of hepatocytes. Some pigment granules were positive for histochemical iron stain. Ultrastructural study on the liver showed (1) the presence of iron-specific X-ray-positive pigment granules, and (2) large numbers of myelin-like bodies throughout the hepatocyte cytoplasm. Histologically advanced hepatic lesions of hepatitis C virus infection and posttransfu-sion iron overload may exacerbate bilirubin transport dysfunction of the syndrome.     

HB-H-6树脂吸附特异性的研究

目的 考察HB-H-6树脂对不同相对分子质量蛋白质和不同结构化学物质的吸附性能,进而研究其吸附特异性.方法 采用经过处理后的HB-H-6树脂对5种不同相对分子质量的蛋白质和不同结构的化学物质蛋白质、糖类、脂类（人体血浆中的蛋白质、糖类、脂类和人血清白蛋白（HAS）、右旋糖酐（Dextran）2部分吸附实验）进行体外静态吸附实验,计算吸附率并进行比较.结果 体外静态吸附实验结果表明,HB-H-6树脂对5种不同相对分子质量的蛋白质肌红蛋白（Myo,16700）、鸡卵清蛋白（OVA,44000）、人血清白蛋白（HAS,66 200）、β-半乳糖苷酶（β-gal,130 000）、免疫球蛋白G（IgG,150 000）的平均吸附率分别为（0.00±.0.33）％、（8.02±1.23）％、（43.19±2.31）％、（34.25±1.07）％、（0.00±0.69）％.HB-H-6树脂对血浆中不同结构的化学物质总蛋白、白蛋白、球蛋白、葡萄糖、甘油三酯及胆固醇的平均吸附率分别为（11.18±0.72）％、（10.74±0.66）％、（11.74±1.22）％、（7.17±0.12）％、（1.06±1.04）％、（3.05±0.65）％.HB-H-6树脂对右旋糖酐（Dextran,70 000）体外静态吸附实验的平均吸附率为（5.44±1.46）％,明显低于对HAS的平均吸附率（（43.19±2.31）％）.结论 HB-H-6树脂对不同相对分子质量的蛋白质的吸附率差异明显,对相对分子质量在6×104～1×105之间的蛋白质的吸附率较高.HB-H-6树脂对不同结构的化学物质蛋白质、糖类及脂类的吸附率也有明显不同.其中,HB-H-6树脂对血浆中蛋白质的吸附率高于糖类和脂类;另外,HB-H-6树脂对不同结构的化学物质HAS和Dextran的吸附率也差异明显.由此表明,HB-H-6对不同相对分子质量蛋白质和不同结构化学物质的吸附有吸附特异性.     

Treatment of intractable pruritus in drug induced cholestasis with albumin dialysis: a report of two cases

Cholestatic liver injury can be caused by a variety of drugs and is difficult to treat. We report two patients, a 22 year old male and a 55 year old female, with drug induced cholestasis caused by anabolic-androgenic steroids (silabolin and nandrolone) and by fluoxetine, respectively. Both patients presented with massive jaundice and severe pruritus resulting in sleep deprivation and suicide ideation. Laboratory examination revealed signs of cholestasis. Medical treatment was ineffective; therefore, extracorporeal albumin dialysis using the molecular adsorbent recirculating system (MARS) was started. Three treatments with a mean duration of 16 hours were performed in each patient. The procedure was well tolerated by the patients and resulted in a sustained relief of pruritus as well as in a decline of plasma bilirubin and serum 3alpha-hydroxy bile acid levels. The mean plasma bilirubin concentration decreased from 25.27 mg/dl to 10.7 mg/dl; the mean serum 3alpha-hydroxy bile acid concentration decreased from 299 micromol/L to 88 micromol/L. After 2 months, the pruritus had nearly vanished in both patients, and there was a further decline of bilirubin levels after discharge from hospital. In conclusion, extracorporeal albumin dialysis appears to be a therapeutic option in severe drug induced cholestasis refractory to medical treatment.     

Gene mapping of human bilirubin UDP-glucuronosyl transferase on 1q21-q23 by a cell sorter and in situ hybridization

The human liver bilirubin UDP-glucuronosyl transferase (bilirubin UDPGT) [EC 2.4.1.17] is responsible for the enzyme deficiency in Crigler-Najjar syndrome and/or Gilbert's syndrome. The UDPGT, former shows severe jaundice resulted from a complete absence of bilirubin while the latter has a mild manifestation due to a reduction of the enzyme activity. The gene locus of bilirubin UDPGT was mapped to chromosome 1 by spot-blot hybridization using a cell-sorter, and its regional locus was assigned to 1q21-q23 by high resolution in situ hybridization.     

Dubin-Johnson syndrome--a clinicopathologic study of twenty cases

Dubin-Johnson syndrome (DJS) is a rare benign chronic disorder of bilirubin metabolism, characterized by conjugated hyperbilirubinemia, darkly pigmented liver and presence of abnormal pigment in hepatic parenchymal cells. This is a retrospective study of twenty cases of DJS highlighting their major clinical and pathological findings. Liver biopsies were available in all the cases, obtained during a fourteen-year period (January 1991 to March 2005). The patients' age ranged from 7-63 years (median 21 years). These twenty cases comprised 13 males and 7 females. Major clinical manifestations were recurrent or persistent jaundice, abdominal pain and fever. Duration of illness ranged from 9 months to 58 years (median 10 years). All of them had conjugated hyberbilirubinemia and total serum bilirubin levels ranged between 1.4-13 mg/dl (mean 4.4 mg/dl). Liver biopsies revealed presence of coarse granular brown pigment in the cytoplasm of hepatocytes more concentrated in the pericanalicular region and more prominent in centrilobular hepatocytes. Associated findings were presence of hepatitis B virus related chronic hepatitis (1), history of tubercular lymphadenitis (1), chronic cholecystitis in (2), coronary heart disease (1) and exacerbation during pregnancy (1).     

Quinine-induced arrhythmia in a patient with severe malaria

It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia (premature ventricular contraction) while getting quinine infusion was reported. A man, 25 years old, was admitted to hospital with high fever, chill, vomiting, jaundice. The patient was fully conscious, blood pressure 120/80 mmHg, pulse rate 100 x/minute, regular. On admission, laboratory examination showed Plasmodium falciparum (++++), total bilirubin 8.25 mg/dL, conjugated bilirubin 4.36 mg/dL, unconjugated bilirubin 3.89 mg/dL, potassium 3.52 meq/L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5% 500 mg/8 hour. On the second day the patient had vomitus, diarrhea, tinnitus, loss of hearing. After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x/minute, trigemini, constant type--sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5%/24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x/minute and on the third day ECG was normal, potassium level was 3.34 meq/L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti-arrhythmic property, although it also pro-arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro-arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases.