肾移植术后应用抗人T淋巴细胞免疫球蛋白护理体会

抗人T淋巴细胞免疫球蛋白(ATG)是一种来源于T淋巴母细胞株免疫的兔的血清制剂.其作用机制在于:抑制经抗原识别后的T细胞激活过程;早期摧毁可破坏移植物细胞的毒性细胞[1].2005年1月至2006年12月我院对15例肾移植术后出现耐激素难治性加速性排斥反应或急性排斥反应的患者应用了ATG治疗,均出现了有效的逆转,肾功能恢复正常.但ATG在应用过程中极易发生严重的并发症和不良反应,现就在使用ATG时,有关护理方面的体会,报告如下.     

抗T淋巴细胞球蛋白治疗加速性排斥反应(附三例报告)

加速性排斥反应是肾移植的一种严重排斥反应类型,因其症状重,肾功能损害发生快,逆转困难而成为处理术后早期抗排斥反应的难点。本科自1997年1月～4月应用抗T淋巴细胞球蛋白(ATG)治疗此种反应3例,报告如下。 资料与方法 1.免疫抑制剂的应用 (1)肾移植术后按我科常规给予三联用药:环胞素A(CsA)[5～7mg/(kg·d)] 强的松(30mg/d) 硫唑嘌呤(100mg/d)。术后前3天给予甲基强的松龙(1.0g/d)静点冲击治疗,3天后改口服强的松(30mg/d)。(2)ATG应用:     

西罗莫司治疗肾移植受者术后蛋白尿的临床经验

目的总结并评价西罗莫司为基础的免疫抑制方案在治疗肾移植术后发生蛋白尿的效果及经验。方法 2009年4月至2011年4月,85例行肾移植手术的患者,并随机分为2组(类固醇/CNI/霉酚酸酯,N=43)和(类固醇/西罗莫司/霉酚酸酯,N=42),CNI组发生蛋白尿后转换为西罗莫司治疗。对这些患者随访1年进行回顾性分析,主要观察移植后蛋白尿的发生率,同时观察移植肾急性排斥反应、感染、DGF、药物不良反应等。结果蛋白尿1年发生率分别为37.2%(16例)和11.9%(5例)(类固醇/CNI/霉酚酸酯和类固醇/西罗莫司/霉酚酸酯)。转化后发生蛋白尿的好转率为56.2%(9/16)。两组发生急性排斥反应、感染、DGF无统计学意义,西罗莫司组高血脂症发生率高于CNI组。结论肾移植术早期应用西罗莫司能较好预防蛋白尿发生。发生蛋白尿后转化西罗莫司治疗时机是逆转蛋白尿治疗的关键。     

抗人T淋巴细胞免疫球蛋白在肾移植术后应用的护理体会

2005年1月至2006年12月我院对15例肾移植术后出现耐激素难治性加速性排斥反应或急性排斥反应的患者应用了抗人T淋巴细胞免疫球蛋白(ATG)治疗,但ATG在应用过程中极易发生严重的并发症和不良反应,现就在使用ATG时,有关护理体会报告如下.     

巴利昔单抗在预防肾移植后排斥反应中的应用

目的:探讨巴利昔单抗诱导治疗预防肾移植后急性排斥反应的有效性和安全性。方法:在使用环孢素、霉酚酸酯及激素三联抗排斥的基础上,将42例肾移植受者随机分2组,每组各21例,试验组术前30min及术后d4各给予巴利昔单抗20mg+氯化钠注射液100mL,静脉滴注,对照组只使用氯化钠注射液静脉滴注。评价急性排斥反应的发生率、严重程度以及巴利昔单抗治疗的安全性。结果:试验组急性排斥反应发生率10%(2/21),发生时间(2.8±s0.8)mo;对照组发生率29%(6/21),发生时间(1.1±0.7)mo,早于试验组(P<0.01)且严重程度高于试验组。血肌酐恢复正常的时间试验组(4.0±0.7)d,对照组(7.8±1.6)d,P<0.01。不良反应发生率2组间差异无显著意义,P<0.05。结论:巴利昔单抗联合环孢素、霉酚酸酯和激素预防肾移植后急性排斥反应安全有效。     

赛尼哌用于肾移植免疫诱导的临床评价

目的:分析观察赛尼哌用于肾移植免疫诱导的临床疗效及其安全性和耐受性.方法:将同期进行的68例肾移植病例分为两组,一组在术前和术后使用了赛尼哌作免疫诱导,另一组使用的是常规的三联免疫治疗,比较两组6个月内的临床情况.结果:使用赛尼哌的患者肾功能恢复和在1个月后明显优于对照组,排斥反应发生率显著降低(P＜0.05),而不良反应和其他感染的发生率两组无统计学差异.结论:赛尼哌用于肾移植的免疫诱导治疗,可以预防和减少急性排斥反应的发生,安全性和耐受性好.赛尼哌、低剂量钙调素抑制剂、皮质激素三联治疗方案是对肾移植患者有益的新选择.     

亲属活体肾移植112例临床分析

目的总结分析112例亲属活体肾移植的经验。方法回顾性分析112例已完成的活体亲属供肾肾移植患者的临床资料,11例为夫妻间供肾,其余为血缘亲属供肾;交叉反应组(CREGs)误配率为3MM(missmatch)、2MM、1MM、0MM的移植例数分别为74,11,4,23;112例均为开放手术取肾,32例取供者右肾,80例取左肾;受者均为第一次接受肾移植手术,术后采用环孢素A(或他克莫司)、霉酚酸酯及泼尼松三联抗排斥反应治疗。结果所有供者手术顺利,术后7~12天出院,平均9.5天。随访至今,肾功能均正常。所有受者均安全度过围手术期。术后1例发生髂外动脉夹层动脉瘤,1例发生移植肾输尿管梗阻,1例发生淋巴囊肿,均经手术治愈。11例发生急性排斥反应,经抗胸腺细胞球蛋白(ATG)冲击治疗,均逆转。随访2~48个月,人/肾存活率100%/100%。结论术前对供、受者进行全面综合评估是亲属活体肾移植成功的保证;亲属活体肾移植等待时间短,组织配型好,供肾缺血时间短,排斥反应发生少,移植肾存活率高,是一种安全可行的治疗手段。     

ATG-F与OKT3在肾移植术后急性排斥反应中的应用效果

目的探讨应用注射用兔抗人T淋巴细胞多克隆抗体(ATG-F)及注射用抗人T细胞CD3鼠单克隆抗体(OKT3)治疗肾移植术后急性排斥反应的效果、安全性和不良反应等。方法笔者所在中心施行同种异体肾移植术后对于激素冲击治疗不敏感的急性排斥患者51例,分为两组,分别给予多克隆抗体ATG-F和单克隆抗体OKT3治疗,并对治疗效果、安全性和药物的不良反应等进行统计学分析。结果 ATG-F治疗28例,排斥反应逆转26例,治愈率89.3%;而OKT3抗组23例,排斥反应逆转16例,治愈率69.6%。两组结果间有显著性差异(P<0.05)。结论 OKT3和ATG-F同为抗淋巴细胞的抗体,但其针对难治性急性排斥反应的治疗效果,存在明显差异。ATG-F临床效果肯定,并且用量灵活,不良反应小。而OKT3治疗效果一般,则具有术后感染发生率增加,及白细胞减少等并发症。     

高龄患者肾移植126例临床分析

目的 :探讨高龄患者肾移植的临床特点及四联免疫抑制疗法对临床治疗效果的影响。方法 :分析 1990年 1月至 2 0 0 0年 12月 12 5 1例肾移植中 12 6例高龄患者临床资料 ,将术后使用免疫抑制剂为三联疗法 (CsA +Aza +激素 )的 5 5例作组Ⅰ ;而使用四联疗法 (CsA +MMF +激素 +抗T细胞单抗 )的 71例作为组Ⅱ ,组Ⅱ中 4 7例患者术后使用 2周Wu -T3抗排斥治疗 ,另 2 4例应用抗IL- 2R抗体预防急性排斥反应。将两组的术后并发症、急性排斥率及 1年人 /肾存活率相比较 ,并与本院同期非高龄患者相同指标比较。结果 :高龄患者肾移植后心脑血管并发症以及感染发生率均明显高于非高龄患者。组Ⅰ和组Ⅱ患者的术后并发症发生率分别为 74 5 5 %和 38 0 3% ;急性排斥发生率分别为 12 73%和 4 2 3% ;1年人 /肾存活率分别为 81 82 % /78 18%和 97 18% /95 77%。结论 :高龄患者肾移植术后较容易发生心脑血管并发症及感染 ,使用新的四联免疫抑制疗法能有效地降低心脑血管并发症、感染和急性排斥反应的发生率 ,1年人 /肾存活率亦明显提高。     

前列地尔对同种异体肾移植中早期肾功能的保护作用

目的 :探讨前列地尔对肾移植术后早期肾功能恢复的影响。方法 :对85例 (A组 )肾移植受者术中及术后2wk内每天应用前列地尔60μg,与同期276例 (B组)未应用前列地尔的肾移植受者进行对比。结果 :A组术后尿量(6d内)和内生肌酐清除率 (至少7d内 )均明显高于B组 (P<0 01) ,而血肌酐 (5d内)以及血流阻力指数 (14d内 )和肾功能延迟恢复的发生率则明显低于B组(P<0 01) ,但两组急性排斥反应发生率 (3mo内 )无显著性差异 (P>0 05)。结论 :肾移植术中及术后早期应用前列地尔有利于移植肾功能的恢复 ,但不降低急性排斥反应发生率。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.