尾型同源盒转录因子-2在大肠癌组织中的表达及其临床意义

目的　探讨大肠癌组织中尾型同源盒转录因子 2 (CDX2 )的表达及其与肿瘤大小、临床分期及分化程度等的关系。方法　大肠癌手术切除标本 45例 ,用逆转录 聚合酶链反应 (RT PCR)检测CDX2mRNA ;免疫组织化学方法检测CDX2蛋白表达。结果　RT PCR显示癌旁正常组织中均有CDX2mRNA表达 ,为 0 .5 5± 0 .18,癌组织为 0 .3 1± 0 .2 0 ,部分癌组织表达缺失 ,前者的表达水平显著高于后者 (P <0 .0 0 1)。其表达程度与肿瘤大小成反比 ,与细胞分化程度呈正比 ,与大肠癌旁淋巴结转移明显相关 ;与患者性别、年龄及部位无关。免疫组织化学结果显示癌组织中CDX2蛋白表达程度显著低于癌旁正常组织 (P <0 .0 0 1) ,CDX2蛋白表达程度与肿瘤大小、细胞分化、淋巴结转移及临床分期有关。结论　CDX2基因的表达异常与大肠癌的发生、发展密切相关 ;其有可能成为判断大肠癌恶性程度、自然病程及预后的的评估指标。     

抑癌基因DPC4在大肠癌组织中的表达及其临床意义

目的　探讨大肠癌组织中DPC4的表达及其与大肠癌淋巴结转移、临床分期、分化程度等的关系。方法　大肠癌切除手术标本 48例 ,用逆转录 聚合酶链反应 (RT PCR )检测DPC4mRNA相对表达量 ;免疫组织化学方法和Westemblot分析检测DPC4蛋白表达情况。结果　半定量RT PCR显示癌旁正常组织中都有DPC4mRNA表达 ,部分癌组织中表达缺失 ;癌组织为 0 .15±0 .0 6,癌旁组织为 0 .5 3± 0 .15 ,差异有显著性 (P <0 .0 0 1)。其表达程度与肿瘤大小、细胞分化程度、淋巴结的转移及临床分期有关 ;与患者性别、年龄、肿瘤部位无关。免疫组织化学结果为 :癌旁组织大多数表达在 ～ ,癌组织大多表达成 -～ ,癌组织表达程度显著低于癌旁正常组织。DPC4蛋白表达程度与肿瘤大小、细胞分化、临床分期及淋巴结转移有关。Westernblot分析结果为 :48例大肠癌组织中有 10例表达呈阴性。结论　DPC4的表达与大肠癌密切相关 ,将来有可能作为大肠癌诊断和治疗过程中一种具有重要价值的生物学标记物。     

生长抑素Ⅱ型受体在大肠癌中的表达

目的　检测生长抑素Ⅱ型受体 (SSTR2 )mRNA在大肠癌标本中的表达 ,并探讨其表达与肿瘤临床及病理特点的关系。方法　对 36例大肠癌患者于术后立即取其手术切除之正常大肠粘膜 (距肿瘤 10cm以上 )、癌旁粘膜 (距肿瘤 2cm以内 )、肿瘤组织及肠系膜淋巴结标本共 135份 ,采用RT PCR法检测其SSTR2mRNA的表达 ,并比较不同组织之间SSTR2mRNA表达阳性率的差别。结果　正常大肠粘膜、癌旁粘膜、肿瘤组织以及无肿瘤转移的肠系膜淋巴结和有肿瘤转移的肠系膜淋巴结的SSTR2mRNA表达阳性率分别为 6 7.6 % ( 2 3/ 34)、75 .0 % ( 2 4 / 32 )、91.4 % ( 32 / 35 )、93.8% ( 15 / 16 )和 81.8% ( 9/ 11)。肿瘤组织中SSTR2mRNA的表达阳性率较正常大肠粘膜明显增高 ( χ2 =6 .37,P<0 .0 5 ) ,但其表达阳性率在不同性别、血清CEA水平、肿瘤大小、部位、组织学分级以及不同肿瘤分期的患者中差异并无显著性意义 (P>0 .0 5 )。结论　SSTR2mRNA的表达在大肠癌组织中明显增高 ,其表达与否和肿瘤的组织学分级及临床病理分期无关     

抑癌基因PTEN在人大肠癌中的表达及其意义

目的 阐明抑癌基因PTEN在大肠癌的发生发展及转移过程中的作用。方法 应用Nothern blot和免疫组化的方法检测47例人大肠癌及癌旁组织中PTEN mRNA和蛋白的表达，分析其与大肠癌的临床病理学分期、分级及其与大肠癌肝转移的关系。结果 PTEN mRNA在大肠癌组织内的表达水平显著低于相应的癌旁组织，在癌组织内，PTEN mRNA表达水平与大肠癌的恶性程度分级、Dukes分期及血清中癌胚抗原(CEA)水平呈显著负相关，PTEN蛋白在大肠癌旁组织中表达阳性率为100％，在大肠癌组织中表达阳性率为76．6％，PTEN在大肠癌组织中表达的降低与大肠癌的Dukes分期、淋巴结转移及血清中CEA水平呈显著负相关。结论 抑癌基因PTEN表达的降低在大肠癌的发生和转移过程中起重要作用。     

大肠癌中Caspase-8和Caspase-10的表达及其与细胞凋亡的关系

目的 探讨大肠肿瘤中Caspase-8和Caspase-10的表达及其与细胞凋亡的关系.方法 采用实时荧光定量逆转录-聚合酶链反应(RT-PCR)检测121例大肠癌、52例腺瘤和121例癌旁组织中Caspase-8和Caspase-10 mRNA表达,原位末端标记法(TUNEL)检测细胞凋亡.结果 与癌旁组织比较,腺瘤中Caspase-8 mRNA表达上调,Caspase-10 mRNA表达下调(P<0.05);大肠癌中Caspase-10 mRNA表达下调(P<0.01),下调程度与肿瘤的分化程度有关(P<0.05).大肠癌、腺瘤和癌旁组织中的凋亡指数分别为1.63%、2.42%和2.98%,各组间差异有统计学意义(P<0.05).大肠癌中凋亡指数与Caspase-10 mRNA表达呈正相关(r=0.408,P<0.01),与Caspase-8mRNA表达无明显相关.结论 Caspase-8 mRNA在腺瘤中表达上调,与肿瘤细胞凋亡无明显相关.Caspase-10与大肠癌的凋亡相关,并与肿瘤恶性程度关系密切.     

周期蛋白A在大肠癌中的表达及其意义

目的　探讨细胞周期蛋白 (cyclin)A在大肠癌中的表达及临床意义。方法　采用免疫组织化学方法检测不同年龄和分期患者的癌组织、癌旁黏膜及正常黏膜中cyclinA的表达。 结果　 (1) 79例标本癌组织中cyclinA表达的阳性率为 70 .9% ;癌旁黏膜阳性率为 5 .1% ;正常黏膜中均未见表达 ,癌旁黏膜及正常黏膜中cyclinA的表达均与癌组织比较差异有显著性 (P <0 .0 1)。(2 )cyclinA的表达在患者不同年龄、肿瘤大小、组织学类型、浸润深度之间差异有显著性 (P <0 .0 5 )。结论　cyclinA的过表达是大肠癌发生的早期事件 ,是影响大肠黏膜细胞正常细胞周期的重要途径之一     

联合检测大肠癌组织中PTEN与CyclinD1的表达及DNA含量的临床意义

目的:探讨大肠癌组织中PTEN和CyclinD1的表达及与DNA含量联合检测的关系及意义.方法:应用免疫组织化学SP法检测58例大肠癌及14例癌旁正常大肠黏膜组织中PTEN和CyclinD1蛋白表达;应用流式细胞术检测以上组织中PTEN和CyclinD1的DNA含量;分析它们之间及与肿瘤分期、分级的关系.结果:PTEN蛋白在大肠癌组织中的表达(65.52%)显著低于癌旁正常组织(100%),CyclinD1蛋白在大肠癌组织中的表达(60.34%)显著高于癌旁正常组织(1.72%),两种蛋白在大肠癌组织中的表达呈负相关(r =-0.71);大肠癌组织的异倍体率(68.97%)显著高于癌旁正常组织(0);PTEN阳性组的DNA指数(DNA index,DI)、S期细胞比率(S-phase fraction ,SPF)均低于阴性组(P<0.05),CyclinD1阳性组的DI及SPF均高于阴性组(P<0.05);两者的表达与肿瘤病理分级、Dukes分期及淋巴结转移相关;淋巴结转移患者的异倍体率及SPF均高于无淋巴转移患者(P<0.05).结论:PTEN和CyclinD1基因的异常改变可能参与大肠黏膜细胞的恶性转化过程,两者的变化存在相关性;DNA含量的变化可能与淋巴结转移有关.联合检测PTEN、CyclinD1蛋白及DNA含量可作为评估大肠癌病理生物学行为和预后的重要指标.     

LIN-28B在原发性肝癌组织中的表达及其临床意义

目的 检测不同恶性程度的原发性肝癌组织中LIN-28B的mRNA和蛋白的表达及其临床意义.方法 应用荧光实时定量PCR(real-time quantitative PCR)技术和Western blot方法检测LIN-28B的mRNA及蛋白在36例肝癌(高分化10例,中分化14例,低分化12例)及相应的癌旁肝组织和10例正常肝脏组织中的表达,并分析与临床病理特点之间的相关性.结果荧光实时定量PCR分析显示,低分化的肝癌组织中LIN-28B阳性率为100%;中分化的肝癌组织阳性率为71.4%;高分化的肝癌组织阳性率只有20%.癌旁组织和正常肝组织中该基因低表达或不表达.Western blot检测的该基因蛋白质表达情况与mRNA的结果相似.结论 LIN28B基因的过表达与肝癌细胞的恶性程度密切相关,表达量越高,其恶性程度愈大.     

大肠良恶性肿瘤中PTEN的蛋白表达及其临床意义

目的　探讨抑癌基因PTEN在大肠良恶性肿瘤组织中的表达及其临床意义。方法　应用S -P免疫组织化学方法检测 2 8例正常大肠黏膜组织 ,3 2例大肠腺瘤的腺体及腺体旁组织 ,12例大肠息肉及息肉旁组织 ,48例大肠癌的癌组织及癌旁组织中PTEN蛋白的表达情况。结果　PTEN蛋白在所有大肠肿瘤组织的表达与其在正常粘膜组织及肿瘤旁组织表达相比均有显著性差异 ;PTEN蛋白在所有大肠肿瘤组织的表达水平 ,尤其在大肠息肉和大肠癌中 ,均显著低于正常大肠组织及其相应的肿瘤旁组织 ,且与肿瘤的大小呈显著负相关 ;癌组织中PTEN蛋白表达与癌组织分化程度呈显著正相关 ,而与其临床Dukes分期、淋巴结转移和远处脏器转移无关。结论　抑癌基因PTEN在大肠息肉 (尤其是腺瘤性息肉 )和大肠癌的发生发展中起着重要作用 ,检测PTEN蛋白表达可能对大肠息肉 (尤其是腺瘤性息肉 )和大肠癌的早期诊断、指导临床术后的进一步治疗及预后的判断有一定价值。     

DMBT1基因在上消化道癌组织中的表达及其意义

目的　探讨DMBT1基因转录表达异常在人上消化道癌组织发生、发展中的作用。方法　应用逆转录 聚合酶链反应 (RT PCR)检测 38例食管癌、2 1例贲门癌、2 5例胃癌肿瘤组织及其相应癌旁正常组织中DMBT1mRNA的表达缺失情况。结果　食管癌、贲门癌及胃癌组织中DMBT1mRNA阳性表达缺失率分别为 63 .2 % (2 4 / 38)、52 .4 % (1 1 / 2 1 )及 72 .0 % (1 8/ 2 5) ;伴有淋巴结转移的癌组织中DMBT1表达缺失率均显著高于相应淋巴结无转移的癌组织 (P <0 .0 2 5) ;肿瘤外侵越严重 ,DMBT1mRNA表达缺失率越高 (P <0 .0 2 5)。结论　DMBT1基因表达缺失与上消化道癌侵袭及淋巴结转移密切相关 ,提示该基因在上消化道癌的发生、发展及转移中起一定作用。     

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 comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

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.     

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.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

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.