促红细胞生成素治疗拮抗的尿毒症血液透析患者体内抗氧化能力的变化

近年来 ,重组促红细胞生成素 (ｒＨｕＥＰＯ)已广泛应用于临床治疗尿毒症性贫血 ,多数患者经ｒＨｕＥＰＯ治疗后可取得显著的疗效 ,但一部分患者经常规或加大剂量的ｒＨｕＥ ＰＯ治疗后不能取得预期的治疗效果 ,亦即体内存在对ＥＰＯ拮抗的因素〔1〕。目前对ＥＰＯ拮抗的机制仍不清楚。本研究通过检测ＥＰＯ治疗有效和拮抗的尿毒症血液透析 (ＨＤ)患者体内的脂质过氧化物 (ＬＰＯ) ,红细胞超氧化物岐化酶(ＲＢＣ -ＳＯＤ)活性 ,红细胞Ｎａ+ -Ｋ+ -ＡＴＰ酶活性和红细胞膜丙二醛 (ＭＯＡ)含量 ,探讨尿毒症ＨＤ患者对ＥＰＯ治疗发生拮抗的机制…     

胃癌患者一氧化氮,超氧化物歧化酶及脂质过氧化物的变化

目的：研究胃癌患者一氧化氮、超氧化物歧化酶及脂质过氧化物的变化。方法：检测５１例胃癌患者（患者组）和５０例健康成人（对照组）血浆一氧化氮（Ｐ－ＮＯ）含量、红细胞超氧化物歧化酶（Ｅ－ＳＯＤ）活性、血浆过氧化脂质（Ｐ－ＬＰＯ）及红细胞过氧化脂质（Ｅ－ＬＰＯ）。结果：与对照组相比,患者组的Ｐ－ＮＯ、Ｐ－ＬＰＯ及Ｅ－ＬＰＯ平均值均显著升高（Ｐ〈０．００１）,Ｅ－ＳＯＤ值显著降低（Ｐ〈０．００１）。结论：提     

抵克力得预防重组人促红细胞生成素诱发顽固性高血压和血栓症的临床研究

目的:研究抵克力得预防重组人促红细胞生成素(rHuEPO)治疗维持性血液透析患者肾性贫血所诱发的顽固性高血压和血栓症的机制和疗效.方法:将17例患者随机分为两组,治疗组10例,在rHuEPO治疗同时使用抵克力得,对照组7例,只使用rHuEPO.两组均治疗12周,然后比较治疗前后两组血液学及血流动力学指标的改变及临床疗效.结果:对照组血红蛋白(Hb)、红细胞压积(HCT)、平均血压(MBP)和血小板计数(BPC)均显著升高,出血时间(BT)、凝血时间(CT)显著缩短,并且发生高血压和内瘘血栓形成各3例,而治疗组Hb、HCT、BPC也显著升高,但CT及MBP无明显改变,而且BT显著延长,无高血压及血栓症发生.结论:抵克力得可通过改变血小板的聚集功能,减轻rHuEPO在尿毒症患者体内引起血液学和血流动力学上的不良反应,防止rHuEPO治疗后高血压与血栓症的发生.     

重组人红细胞生成素对血透患者单个核细胞分泌功能的影响

探讨贫血与尿毒症红细胞免疫功能障碍之间的关系。方法采用细胞培养技术，对接受重组人红细胞生成素（ｒＨｕＥＰＯ）和长期输血的维持性血透患者外周血单个核细胞分泌白细胞介素２、单核细胞分泌肿瘤坏死因子的水平进行观察。结果患者单个核细胞分泌细胞因子的能力低下与贫血有一定关系，ｒＨｕＥＰＯ能增强患者单个核细胞分泌细胞因子。结论此作用是通过改善贫血而非ｒＨｕＥＰＯ的直接作用。     

宁红欣对骨科择期手术贫血的防治效果

重组人红细胞生长素 (ｒＨｕＥＰＯ ,宁红欣 )在治疗肾性贫血方面效果明确[1,2 ] ,已有广泛报道。近来将ｒＨｕＥＰＯ应用于围手术期的治疗开始引起注意。我们拟通过探讨宁红欣对骨科择期手术防治贫血的治疗效果 ,并寻找最佳的临床应用剂量。1.临床资料 :2 0 0 0年 5月～ 8月 ,随机选择择期手术的患者 12 0例。随机分组 :宁红欣低剂量组、中剂量组、高剂量组和对照组各 30例。对照组 :仅给予铁剂速力菲 10 0ｍｇ ,每日 2次口服。治疗组 :给与铁剂口服 (剂量同对照组 )和宁红欣静脉注射或皮下注射 ,分别于术前第 7、5、3天、术日 2 4ｈ内、术…     

促红细胞生成素治疗腹透患者贫血的疗效观察

促红细胞生成素治疗腹透患者贫血的疗效观察张怡玲贾长绪尹永红我们对１５例腹透患者用小剂量人基因重组红细胞生成素（ｒＨｕＥＰＯ）治疗肾性贫血进行观察，其结果分析如下。资料与方法男８例，女７例，年龄５７．５±１２．６岁，血肌酐８０４．４±３６４．４μｍｏｌ...     

红细胞生成素对慢性肾功能衰竭患者血清IgG亚类的影响及其意义

有研究表明,红细胞生成素（ＥＰＯ）在治疗慢性肾功能衰竭（ＣＲＦ）贫血的同时,还能增强吞噬细胞活性,影响细胞免疫和体液免疫功能。ＥＰＯ对 ＩｇＧ亚类的影响及意义,尚未见报道。为此,我们测定了ＥＰＯ治疗组和非治疗组ＣＲＦ患者血清 ＩｇＧ及其亚类含量,并与健康人比较,现报道如下。 一、材料与方法 １ 临床资料：７３例ＣＲＦ患者为本院住院病例,符合 １９９３年全国制定的诊断标准。ＥＰＯ治疗组和非治疗组的临床资料见表１。治疗组接受ＥＰＯ（益比奥,沈阳三生制药公司产品）治疗,每次 ２ ０００～４ ０００ Ｕ,皮下注射…     

肾移植患者促红细胞生成素监测的临床意义

目的 探讨肾移植术后内源性促红细胞生成素（ＥＰＯ）的动态变化与康复的关系。方法 分别测定血透析和肾移植病例３２例。将移植病人按术前是否接受ＥＰＯ治疗,分为ＥＰＯ治疗组和非治疗组。动态观察手术前后ＥＰＯ变化过程。比较治疗和非治疗组的差异与血象变化。结果 两组各观察点ＥＰＯ实测值差异无显著性。ＥＰＯ治疗组术后可见两次ＥＰＯ升高高值,分别为３２ｍＩＵ／ｍｌ和２１ｍＩＵ／ｍｌ。贫血的改善不受ＥＰＯ变化的影     

红细胞生成素对慢性肾功能衰竭大鼠脂质紊乱的作用

研究表明,红细胞生成素（ｒｈＥＰＯ）可能对纠正慢性肾功能衰竭（慢肾衰）所致脂代谢紊乱有一定作用。我们拟观察ｒｈＥＰＯ对慢肾衰大鼠模型的脂质紊乱作用,为临床应用提供一定的实验依据。 一、材料与方法 １．实验动物及分组：正常雄性、Ｗｉｓｔａｒ大鼠 ２４只,３００～３２０ｇ,随机分为正常对照组（ｎ＝８）,模型对照组（ｎ＝８）和模型治疗组（ｎ＝８）。 ２．手术及用药：模型对照组和模型治疗组施行５／６肾切除术,正常对照组施以假手术。术后给予模型治疗组每周２次腹腔内注射ｒｈＥＰＯ,剂量１５０ ＩＵ／ｋｇ共８周,…     

新生儿缺氧缺血性脑病血浆β内啡肽,皮质醇,血糖水平变化及临床 …

目的：为探讨新生儿危重症β内啡肽（β－ＥＰ），皮质醇（ＣＯＲ），血糖水平变化及临床意义。方法：用放射免疫法测定６１例新生儿缺氧缺血性脑病（ＨＩＥ）患儿血浆β－ＥＰ，ＣＯＲ及用微量血糖仪检测血糖，并对２２例重症患儿进行动态观察。结果：ＨＩＥ患儿第一天β－ＥＰ，ＣＯＲ水平中重度组高于对照组，重度组高于中与轻度组Ｐ均〈０．０１，重度组治疗３、５天动态观察，β－ＥＰ，ＣＯＲ含量仍高于对照组Ｐ〈０．０１或Ｐ     

Erythropoietin therapy improves graft patency with no increased incidence of thrombosis or thrombophlebitis

Background: Recombinant human erythropoietin (rHuEPO) for the treatment of severe anemia in patients with end-stage renal disease (ESRD) is suggested to improve rehabilitation and cognitive function. The criticism is the alleged increase in the failure rate of arteriovenous (AV) access grafts and in the incidence of lower-extremity deep venous thrombophlebitis (DVT). This study addressed the longevity of AV grafts and the incidence of DVT.

Study Design: We reviewed 481 consecutive patients with ESRD on dialysis with PTFE access grafts, including 173 consecutive patients who were receiving rHuEPO and 308 who were not. rHuEPO was administered during dialysis titrated against the hematocrit to achieve a level of 33% to 38%. The rHuEPO-ESRD group included 173 patients with a mean age of 58 years, including 54% women; 84% of the grafts were in the upper extremity. In the control group of 308 patients, 57% were women. Diabetes and hypertension were controlled in both groups.

Results: Forty-five of 173 rHuEPO patients (26%) experienced graft thrombosis within 1 year. Among 88 episodes of thrombosis, 14 patients experienced multiple episodes. Primary patency was 8.9 months; secondary patency was 11.2 months. In the control population, 95 of 308 patients (31%) experienced graft thrombosis; 27 patients had multiple episodes. Primary patency was 7.8 months and secondary patency was 9.8 months. The hematocrit improved from a mean of 23% in the control group to 34% in the treated rHuEPO group. Two patients in the control group and one patient receiving rHuEPO experienced DVT in the lower extremity.

Conclusions: Primary and secondary AV fistula patency rates were improved by 10% with rHuEPO. rHuEPO did not increase DVT.     

Effect of ticlopidine hydrochloride on erythropoietin-induced rise in blood pressure in patients on maintenance hemodialysis

BACKGROUND/AIMS: A recent observation that antiplatelet-aggregation drugs, including ticlopidine hydrochloride, may prevent erythropoietin (EPO)-induced rise in blood pressure in hemodialysis (HD) patients remains a subject of particular interest. The aim of the present study was to determine the effect of ticlopidine hydrochloride on EPO-induced rise in blood pressure of HD patients with special reference to blood levels of vasoactive substances. METHODS: HD patients who showed hypertension or aggravation of preceding hypertension with EPO treatment were selected for this study. Ticlopidine hydrochloride was administered at a dose of 200 mg daily for 4 weeks. Blood pressure and serum levels of nitric oxide (NO), atrial natriuretic peptide (ANP) and endothelin (ET) were determined before and after drug administration. Patients were divided into two groups, one of which showed a drop in mean blood pressure (MBP) of >10 mm Hg (group I) and one which did not (group II), and a comparison was made between them with respect to the blood parameters. RESULTS: Five of 15 patients showed a drop of MBP of >10 mm Hg (group I), and 10 patients did not show any change in MBP (group II). In group I, there was a significant increase in blood NO levels compared to the concentrations before ticlopidine administration, while there was no change in group II. With respect to ANP and ET, there was no significant change in either of the groups. CONCLUSION: The findings suggest that the preventive effect of ticlopidine hydrochloride on EPO-induced rise in blood pressure may partly be related to the enhancement of NO production in patients on maintenance HD.     

Change in haemoglobin concentration,haematocrit and vasoactive hormones in haemodialysis patients with erythropoietin-associated hypertension

The changes in haemoglobin concentration, haematocrit, plasma renin, activity (PRA) and atrial natriuretic peptide (ANP) were studied in 10 haemodialysis patients with erythropoietin-associated hypertension. All patients received intravenously 1500 IU of recombinant human erythropoietin (rHuEPO) thrice weekly for 24 weeks. Treatment with rHuEPO induced significant rises in haemoglobin concentration (p<0.001) and haematocrit (p<0.01)., However, the difference between post- and pretreatment levels of haemoglobin (ΔHb) was not correlated with that between post-and pre-treatment mean blood pressure (ΔMBP). No correlation was found between ΔHt (difference between post- and pre-treatment values of haematocrit) and ΔMBP. These results indicate that elevation of the haematocrit and haemoglobin concentration of haemodialysis patients does not necessarily lead to an increase in blood pressure. In these patients, no significant differences were observed in PRA and ANP, comparing pre-treatment values with those measured 4, 8, 12 or 24 weeks after commencing rHuEPO. This suggests that neither PRA nor ANP play a central role in the pathogenesis of rHuEPO-induced hypertension.     

脾切除联合贲门周围血管离断术后门静脉系统血栓发生率及其防治

目的 探讨门静脉高压症术后门静脉系统血栓（portal venous system thrombosis,PVST）形成的原因及其防治措施。方法 对132例门静脉高压症患者行脾切除联合贲门周围血管离断术,术中均经胃网膜右静脉置入导管测压并留置导管,其中36例患者（设为试验组,其余设为对照组）术中增加脾静脉近端结扎。术后早期经导管滴注肝素盐水预防血栓,或发生血栓后滴注尿激酶溶栓,出院后口服华法林,使预防和治疗血栓的效果分别达到国际标准化比值（INR）维持于1.5~2.0和2.0~3.0,并直至血小板数量恢复正常。结果 术后2周内发生PVST共132例（100%）,血栓分布：残余脾静脉血栓132例（100%）,门静脉血栓（PVT）39例（29.5%）。在39例PVT中,门静脉主干血栓33例,主干血栓均与残余脾静脉血栓相连,其中15例血栓最大横截面积<50%,14例血栓最大横截面积≥50%,4例为完全性血栓;肠系膜上静脉血栓6例,其中4例合并门静脉主干血栓并与肠系膜上静脉血栓相连,2例存在门静脉分支血栓且肠系膜上静脉血栓与脾静脉血栓相连。39例PVT中,门静脉左支血栓21例,门静脉右支血栓18例;PVT 2处及以上者25例。在试验组36例脾静脉近端结扎的患者中,发生门静脉主干血栓1例（2.8%）;在对照组未采用脾静脉近端结扎的96例中发生PVT 38例（39.6%）,两者对比差异有统计学意义（P<0.001）。对39例PVT采用抗凝及溶栓治疗,其中33例在术后6个月获得随访并进行CT检查,发现血栓消失、机化再通和海绵样变各23例、7例和3例。结论 肝硬化门静脉高压症行脾切除联合贲门周围血管离断术后早期残余脾静脉内易形成血栓,残余脾静脉血栓向门静脉内蔓延是发生术后PVT的主要原因。脾静脉近端结扎的预防效果显著,经胃网膜右静脉留置导管,术后滴注肝素盐水和溶栓剂兼具预防和治疗双重作用,口服华法林效果确切但需检测凝血功能。     

Increased endothelin: nitric oxide ratio is associated with erythropoietin-induced hypertension in hemodialysis patients

Regular administration of recombinant human erythropoietin (rHuEPO) is frequently associated with a rise in arterial blood pressure in hemodialysis (HD) patients. The aim of this study was to examine the effects of rHuEPO on plasma endothelin (ET)-1 and nitric oxide products (NOx) concentration in HD patients. Fifteen patients on maintenance HD with hematocrit of less than 25% were included in the present study. All patients received 3,000 units of rHuEPO intravenously three times a week at the end of each HD session. Plasma levels of ET-1, NOx, thromboxane B2 (TXB2), prostacyclin (6-keto-PGF1alpha), and cyclic guanosine 3',5'-monophosphate (cGMP) were measured before, 2, and 4 weeks after rHuEPO treatment. Plasma concentrations of ET-1, TXB2, and 6-keto-PGF1alpha were measured by radioimmunoassay. Plasma NOx was measured by high-performance liquid chromatography. An rHuEPO-induced increase in mean arterial blood pressure of over 6 mmHg occurred in 7 patients (hypertensive group), whereas the elevation of mean arterial blood pressure was less than 5 mmHg in 8 patients (nonhypertensive group). Plasma ET-1 levels were elevated in all HD patients. Elevated plasma ET-1 levels remained unchanged after rHuEPO treatment in the hypertensive group, whereas the increase in plasma ET-1 levels was attenuated in the nonhypertensive group. Plasma NOx concentrations were also increased in all HD patients. This increase in plasma NOx levels was lessened in the hypertensive group after rHuEPO administration; however, plasma NOx levels remained increased in the nonhypertensive group. Changes in mean arterial blood pressure were significantly correlated with changes in plasma ET-1/NOx ratio. Plasma levels of TXB2, 6-keto-PGF1alpha, and cGMP were unchanged after rHuEPO administration in the hypertensive and nonhypertensive groups. These results suggest that an increase in ET-1/NOx ratio in blood, probably occurring in vascular endothelial cells, may be associated with rHuEPO-induced hypertension in HD patients.     

Increased Endothelin: Nitric Oxide Ratio Is Associated with Erythropoietin-Induced Hypertension in Hemodialysis Patients

Regular administration of recombinant human erythropoietin (rHuEPO) is frequently associated with a rise in arterial blood pressure in hemodialysis (HD) patients. The aim of this study was to examine the effects of rHuEPO on plasma endothelin (ET)-1 and nitric oxide products (NOx) concentration in HD patients. Fifteen patients on maintenance HD with hematocrit of less than 25% were included in the present study. All patients received 3,000 units of rHuEPO intravenously three times a week at the end of each HD session. Plasma levels of ET-1, NOx, thromboxane B2 (TXB₂), prostacyclin (6-keto-PGF1α), and cyclic guanosine 3′,5′-monophosphate (cGMP) were measured before, 2, and 4 weeks after rHuEPO treatment. Plasma concentrations of ET-1, TXB₂, and 6-keto-PGF1α were measured by radioimmunoassay. Plasma NOx was measured by highperformance liquid chromatography. An rHuEPO-induced increase in mean arterial blood pressure of over 6 mmHg occurred in 7 patients (hypertensive group), whereas the elevation of mean arterial blood pressure was less than 5 mmHg in 8 patients (nonhypertensive group). Plasma ET-1 levels were elevated in all HD patients. Elevated plasma ET-1 levels remained unchanged after rHuEPO treatment in the hypertensive group, whereas the increase in plasma ET-1 levels was attenuated in the nonhypertensive group. Plasma NOx concentrations were also increased in all HD patients. This increase in plasma NOx levels was lessened in the hypertensive group after rHuEPO administration; however, plasma NOx levels remained increased in the nonhypertensive group. Changes in mean arterial blood pressure were significantly correlated with changes in plasma ET-1/NOx ratio. Plasma levels of TXB₂, 6-keto-PGF1α, and cGMP were unchanged after rHuEPO administration in the hypertensive and nonhypertensive groups. These results suggest that an increase in ET-1/NOx ratio in blood, probably occurring in vascular endothelial cells, may be associated with rHuEPO-induced hypertension in HD patients.     

Safety and efficacy of erythropoietin in children with chronic renal failure

 A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks (mean±SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease. Received: 12 March 1998 / Revised: 24 June 1998 / Accepted: 6 July 1998     

促红细胞生成素对改善股骨转子间骨折术后贫血的作用

目的探讨促红细胞生成素(rHuEPO)改善股骨转子间骨折术后贫血的临床疗效。方法将100例符合标准的股骨转子间骨折患者随机分为实验组(50例)和对照组(50例)。实验组给予rHuEPO皮下注射治疗,对照组不给予rHuEPO治疗,余治疗相同。比较两组患者术后输血、功能恢复和并发症发生率。结果实验组6例接受输血治疗,对照组14例接受输血治疗,差异有统计学意义(14.5%vs 27.6%,P=0.04);实验组于出院时血红蛋白水平为(108.2±10.5)g/L,对照组为(100.5±9.2)g/L,差异有统计学意义(P=0.01);术后1、3个月实验组FIM评分分别为(85.8±13.4)分和(100.2±15.2)分,显著高于对照组的(70.0±15.2)分和(86.6±20.4)分(P0.01);并发症:实验组发生9例,对照组发生11例;两组比较差异无统计学意义(P=0.65)。结论 rHuEPO在股骨转子间骨折术后应用是安全的,并可减少输血和促进术后恢复。     

透光技术在胃底静脉结扎术中的应用(附28例报告)

目的探讨透光法胃底静脉结扎＋贲门周围血管离断术治疗门静脉高压症食管胃底静脉曲张破裂出血的可行性。方法收集我院2001年7月～2（1（15年7月门静脉高压症食管胃底静脉曲张破裂出血52例,分为2组：传统断流术组（24例,对照组）和透光断流术组（28例,实验组）。观察所有病人住院期间术后并发症发生率、平均住院天数、平均费用以及食管再出血的例数。术后所有病人随访3年。结果两组之间平均住院天数和平均费用无显著性差异。在随访期内对照组再出血发生率高于实验组（P〈0．01）,实验组再出血时间间隔长于对照组（P〈0．01）。结论透光法胃底静脉结扎＋贲门周围血管离断术治疗门静脉高压症食管胃底静脉曲张破裂出血是一种可行的手术方式,可以减少术后并发症的发生。降低再次出血的风险。     

Importance of serotonergic mechanisms in the thrombotic complications in hemodialyzed patients treated with erythropoietin

So far it is not clear how erythropoietin affects the anticoagulant properties of vascular endothelium in uremia. Since serotonin is also thought to play a role in the pathogenesis of thrombosis, the aim of the study was to evaluate major components of extrinsic coagulation pathway, markers of endothelial cell injury, lipoprotein (a) and peripheral serotonergic mechanisms during rHuEPO therapy in hemodialyzed patients. The study was performed on chronically hemodialyzed patients divided into two groups: with rHuEPO treatment and without rHuEPO therapy in relation to the control group. In uremic patients, thrombomodulin and von Willebrand factor, activity of factor VII, tissue factor pathway inhibitor (TFPI) activity, TFPI and tissue factor (TF) concentrations, lipoprotein (a) level were significantly higher when compared to healthy volunteers. Treatment with rHuEPO resulted in a further significant rise in markers of endothelial cell injury: thrombomodulin and von Willebrand factor and TFPI concentration. Extrinsic coagulation factors: activities of factor VII and X, TFPI activity and TF activity and concentration, lipoprotein (a) and vitronectin remained unchanged during rHuEPO therapy. Platelet serotonin content and whole blood serotonin were significantly lower in uremic patients relative to healthy volunteers and during rHuEPO treatment they increased significantly. Whole blood serotonin reached normal values. Plasma serotonin, significantly elevated in uremia, did not change during rHuEPO therapy. Serotonin uptake by uremic platelets was significantly impaired and remained unaltered during rHuEPO administration. Serotonin release by uremic platelets was also significantly depressed but a significant improvement was observed in rHuEPO-treated patients. Our data suggest that endothelial injury, TF pathway components and peripheral serotonergic system disturbances may predispose to thromboembolic complications and play a role in the pathogenesis of atherosclerosis in uremic patients, particularly treated with rHuEPO. Increase in TFPI may compensate the increase in TF in these patients.