逆转录病毒携带白细胞介素-12转染树突状细胞体外诱导特异免疫杀伤肝癌细胞

目的探讨逆转录病毒携带白细胞介素(IL)12转染树突状细胞(DC)体外诱导免疫杀伤肝癌细胞的效能及其机制。方法感染指数(MOI)为100,含IL12的重组逆转录病毒修饰肝癌患者外周血DC(DCIL12),酶联免疫吸附试验法(ELISA)检测DCIL12(5×103个/ml)培养上清中IL12和γ干扰素(IFNγ)水平,以冻融肝癌细胞株HepG2(1×107个/ml)所获得的肿瘤相关抗原(TAA)刺激DCIL12,MTT法检测TAA负载的DCIL12刺激同源T淋巴细胞(1×105个/ml)增殖分化能力,细胞毒试验检测DCIL12诱导的细胞毒T淋巴细胞(CTL)及其上清液对HepG2肝癌细胞株杀伤作用,ELISA法检测CTL上清液IFNγ水平。结果DC经IL12基因修饰后48h分泌高水平IL12(24.35±5.40)ng/L及IFNγ(725±30)ng/L,均显著高于未转染DC组(P<0.01及P<0.05)。DCIL12诱导的CTL及其上清液对HepG2均有显著杀伤作用,杀伤率显著高于未转染DC组,分别为(82.43±8.70)%vs(57.4±4.3)%(P<0.01)和(76.45±8.50)%vs(18.23±5.30)%(P<0.01),DCIL12诱导的CTL上清液IFNγ水平显著高于未转染DC组,分别为(1125.0±32.7)ng/Lvs(281.3±14.7)ng/L(P<0.01)。结论IL12基因修饰增强DC体外诱导自体T淋巴细胞产生特异性抗肝癌免疫,其机制与IL12基因修饰促进DC分泌IL12、增强T淋巴细胞活化及分泌IFNγ密切相关。     

粒巨细胞集落刺激因子分泌性同种异体肺癌细胞疫苗与自体疫苗抗肺癌免疫保护作用比较

目的 探讨粒-巨细胞集落刺激因子(GM-CSF)基因修饰同种异体和自体瘤苗诱导抗肿瘤免疫反应的差异.方法 以接种Lewis肺癌细胞系的C57BL小鼠为动物模型.将含小鼠GM-CSF重组质粒转染小鼠肺癌细胞系LA795和LLC细胞,制备同种异体和自体瘤苗.分别免疫荷瘤小鼠,检测淋巴细胞的活化;脾细胞及其中的CD8+T细胞的杀伤活性.结果 GM-CSF分泌性LA795和LLC瘤苗接种后,小鼠成瘤时间明显较晚,生存期明显延长,脾淋巴细胞活化比例显著升高(P＜0.01);脾细胞及CD8+T细胞的杀伤活性明显升高(P＜0.05);同种异体和自体瘤苗在诱导淋巴细胞活化及杀伤活性方面差异无统计学意义(P＞0.05).结论 GM-CSF分泌性同种异体和自体瘤苗均可诱导特异性抗肿瘤免疫反应.     

hIL-2基因修饰人肝细胞的腹腔移植抗肿瘤作用

目的　探讨hIL 2基因修饰人肝细胞腹腔移植的抗肿瘤作用。方法　采用鼠尾胶原包裹转hIL 2基因人肝细胞并移植入癌性腹水型小鼠模型腹腔,观察移植 1、4、7、10 d后小鼠脾淋巴细胞的增殖反应、脾淋巴细胞杀伤活性、血清hIL 2浓度及移植小鼠生存期。结果　移植4 d后,小鼠血清hIL 2浓度达到(76 2±2 2) pg/ml,脾淋巴细胞的增殖反应 OD值和脾淋巴细胞杀伤活性达到峰值,分别为(0 674±0 046)%和(35 6±1 9)%,与对照组和 L 02 细胞移植组相比,差别均有非常显著意义(P<0 05);移植 L 02/IL 2 肝细胞的小鼠生存率显著高于对照组和 L 02 细胞移植组(P=0 0003)。结论　IL 2基因修饰肝细胞移植于腹腔,可上调淋巴细胞的增殖和杀伤功能,达到抗肿瘤的目的,对肝细胞结合转基因的应用研究有积极意义。     

次级淋巴趋化因子(SLC/CCL21)基因与肿瘤裂解产物构建树突状前列腺癌瘤苗的抗肿瘤免疫作用研究

目的 探讨转染次级淋巴趋化因子基因的树突细胞(DC)瘤苗在小鼠前列腺癌中的抗肿瘤效应.方法 通过脂质体法将次级淋巴趋化因子基因转染至小鼠骨髓来源的树突状细胞,构建DC瘤苗;逆转录-聚合酶链反应检测SLC;种瘤24 d后SLC组的瘤体平均体积为(1430±86)mm3,45 d后仍有50%的荷瘤小鼠存活,与其他两组比较差异有统计学意义(P＜0.05);免疫组织化学荧光染色可见SLD组中CD4+、CD8+T细胞和CD11+DC的浸润率分别为(15.24±0.67)%、(¨.02±0.73)%和(14.50±0.51)%,与DC组比较差异有统计学意义(P＜0.05).结论 转染SLC的DC瘤苗能有效诱导抗肿瘤的免疫效应,其免疫效应是通过趋化大量CD4+、CD8+T细胞及CD11+DC至肿瘤部位而发挥作用.     

转4-1BBL基因小鼠肝癌细胞瘤苗体外诱导抗肿瘤免疫应答的研究

目的　研究转 4 1BBL基因小鼠肝癌细胞疫苗体外诱导淋巴细胞特异性杀伤活性及刺激同系小鼠脾细胞产生细胞因子 (IL 2、TNF α和GM CSF)的能力。方法　采用脂质体介导法将真核表达质粒 pCDNA3 1( ) m4 1BBL导入小鼠肝癌细胞Hepa1 6 ,经G4 18筛选后获得稳定高表达克隆 ,以丝裂霉素C(MMC)处理后 ,制成肿瘤细胞疫苗 (TCV) ,经体外与同系小鼠脾淋巴细胞共同培养后 ,测定淋巴细胞特异性杀伤活性及对脾细胞产生细胞因子 (IL 2、TNF α和GM CSF)的影响。结果转染 4 1BBL的Hepa1 6细胞能够高表达 4 1BBL蛋白 ,并且经MMC处理后制成的瘤苗在培养 4 8h仍能表达m4 1BBL。与野生型的Hepa1 6细胞相比 ,上述瘤苗能诱导淋巴细胞产生针对亲本的小鼠肝癌细胞Hepa1 6的特异性杀伤作用 (P <0 0 5 ) ,但是对于小鼠肝癌细胞H2 2及成纤维细胞NIH3T3无效 ;此瘤苗在体外能显著增强脾细胞分泌细胞因子IL 2、TNF α和GM CSF的能力。结论　转 4 1BBL基因小鼠肝癌细胞疫苗能诱导有效的抗肝癌免疫反应。     

Ly49A转基因淋巴细胞对异基因骨髓移植后GVHD和GVL的影响

目的　观察Ly49A基因转染淋巴细胞对异基因骨髓移植后移植物抗宿主病 (GVHD)和移植物抗白血病效应 (GVL)的影响。方法　经逆转录病毒介导将Ly49A基因转染至C57BL/ 6小鼠的淋巴细胞 ,以C57BL/ 6(H 2 b)小鼠为供者 ,以接种EL961 1红白血病细胞的BALB/c(H 2 d)小鼠为受者 ,进行脾淋巴细胞和骨髓细胞联合移植 ,建立异基因急性GVHD模型 ,观察Ly49A基因转染的淋巴细胞对GVHD和GVL的影响。结果　在未进行移植的单纯照射组 ,小鼠的存活时间为 (6 .50±2 .41 )d ;仅以环磷酰胺治疗的小鼠存活时间为 (2 0 .90± 2 .88)d ;非转染淋巴细胞和骨髓细胞联合移植组的存活时间为 (1 7.1 0± 4 .65)d ;空载体转染淋巴细胞和骨髓细胞联合移植组的存活时间为(1 7.40± 5 .32 )d ;Ly49A转染淋巴细胞与骨髓细胞联合移植组的存活时间为 (35 .2 0± 1 2 .52 )d ,较上述各组明显延长 (P =0 .0 0 0 )。结论　Ly49A基因转染的淋巴细胞在异基因骨髓移植模型上具有一定程度的降低GVHD并保留GVL的作用     

白细胞介素-12抑制裸鼠肝癌Ang-2和血管内皮生长因子表达及其意义

目的　探讨白细胞介素 12抑制裸鼠肝癌中血管生成素 2 (Ang 2 )和血管内皮生长因子(VEGF)基因表达及其意义。方法　将小鼠白细胞介素 12基因转染小鼠肝癌H 2 2细胞后,接种到裸鼠肾包膜下,第11天取出肿瘤组织。通过逆转录 聚合酶链反应(RT PCR)观察实验组和对照组瘤组织中Ang 2和VEGF基因在mRNA水平上的差异。结果　实验组Ang 2和VEGF基因的PCR产物条带亮度均弱于对照组(P <0 .0 5 ) ,实验组Ang 2 (0 .7878±0 .14 71)和VEGF(0 .8867±0 .192 4)基因的PCR产物条带辉度比值低于载体对照组(1.0 3 19±0 .15 74、1.1744±0 .1189)和空白对照组(1.0 3 61±0 .15 3 6、1.1874±0 .175 2 ,P <0 .0 5 )。结论　IL 12抑制Ang 2和VEGF基因在裸鼠肝癌组织中的表达,从而抑制了裸鼠肝癌的血管生成     

多聚乙烯亚胺介导IL-12基因增强裸鼠抗骨肉瘤免疫

目的 :观察以多聚乙烯亚胺 (polyethylenimine ,PEI)为载体 ,体内转染小鼠白细胞介素 12 (inter leukin 12 ,mIL 12 )基因 ,治疗裸鼠骨肉瘤模型的疗效。方法 :以PEI为载体 ,体外转染mIL 12基因入人骨肉瘤细胞 ,并观察此基因表达情况。建立裸鼠骨肉瘤动物模型 ,将PEI包裹mIL 12基因直接注入肿瘤局部 ,检测此基因的蛋白表达情况和小鼠脾脏自然杀伤细胞 (NK)活性。结果 :在PEI/DNA治疗组小鼠的肿瘤局部 ,mIL 12蛋白水平明显升高 ,小鼠脾NK细胞活性增强。结论 :PEI可以成功的将mIL 12基因导入裸鼠骨肉瘤模型 ,mIL 12基因治疗可提高机体的抗肿瘤免疫应答     

反义IDO-AFP基因融合修饰树突状细胞抗肝癌免疫作用

目的探讨反义IDO-AFP基因融合修饰树突状细胞(DC)后,DC通过调控色氨酸代谢达到高效、特异性抗肝癌作用。方法采用细胞培养方法,从小鼠骨髓中获得DC,用反义IDO核酸和AFP基因融合的载体,转染入DC内,检测转染入融合基因DC的对T细胞增殖的影响和体外对肝细胞癌的免疫应答的改变。以~(51)Cr释放法测定细胞毒性T淋巴细胞(CTL)杀伤活性。制作小鼠肝癌模型,分别予以反义IDO-AFP修饰的DC、单纯DC、空白对照组进行治疗,检测血清中自细胞介素(IL)-10、干扰素(IFN)-7水平；CD4、CD8和IFN-7和IL-10双阳性细胞比例,观察其抑制肿瘤的效果。结果反义IDO-AFP修饰的DC可激活小鼠脾淋巴细胞；能对肝癌细胞株H22细胞进行特异性杀伤,杀伤率为89．3%,显著高于单纯DC、生理盐水(空白对照组)组的34．7%和8．9% (P均＜0．01)而对艾氏腹水瘤细胞无效；反义IDO-AFP修饰DC组色氨酸含量为(17．8±1．2)μm,而单纯DC组和空白对照组的色氨酸为(6．2±0．6),um和(5．2±1．2)μm,表明反义IDO-AFP修饰DC可明显增加培养液中的色氨酸。使Thl细胞比例上升,抑制体内肿瘤的生长。结论反义IDO-AFP基因融合修饰树突状细胞后,DC通过调控色氨酸代谢达到高效、特异性抗肝癌的目的,可成为一种有效的瘤苗。     

IL-12基因修饰树突状细胞体外诱导免疫杀伤肝癌细胞

目的探讨IL-12基因修饰树突状细胞(DC)体外诱导免疫杀伤肝癌细胞的效能及其机制。方法IL-12基因修饰肝癌病人外周血DC(DC-IL-12),ELISA法检测DC-IL-12培养上清中IL-12和IFN-γ水平,以冻融HepG2所获得的肿瘤相关抗原(TAA)刺激DC-IL-12,MTT法检测TAA负载的DC-IL-12刺激同源T淋巴细胞增殖分化能力,细胞毒试验检测DC-IL-12诱导的细胞毒T淋巴细胞(CTL)及其上清液对HepG2肝癌细胞株的杀伤作用,ELISA法检测CTL上清液IFN-γ水平。结果DC经IL-12基因修饰后48h分泌高水平IL-12(24·35±5·4)pg/ml及IFN-γ(725±30)pg/ml,均显著高于未转染DC组(P<0·01)。DC-IL-12诱导的CTL及其上清液对HepG2均有显著杀伤作用,杀伤率显著高于未转染DC组,分别为(82·43±8·7)%vs(57·4±4·3)%和(76·45±8·5)%vs(18·23±5·3)%(P<0·01),DC-IL-12诱导的CTL上清液IFN-γ水平显著高于未转染DC组,分别为(1125·0±32·7)pg/ml、(281·3±14·7)pg/ml(P<0·01)。结论IL-12基因修饰增强DC体外诱导自体T淋巴细胞产生特异性抗肝癌免疫,其机制与IL-12基因修饰促进DC分泌IL-12、增强T淋巴细胞活化及分泌IFN-γ密切相关。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.