抑制趋化因子受体CCR5减轻小鼠同种异体移植心脏急性排斥反应的研究

目的 研究抑制趋化因子受体CCR5减轻小鼠同种异体移植心脏急性排斥反应的作用机制.方法 采用小鼠颈部心脏移植模型,将96只小鼠用随机数字表法分为4组,每组24只,供、受者各12只,A组术后给予anti-CCR5 mAb和CsA,B组术后给予anti-CCR5 mAb,C组术后给予CsA,D组为对照组,术后给予生理盐水.于术后第7d取各组移植心组织6例,检测CCR5及IL-2和IL-10的表达差异,其余6例用于观察移植心脏存活时间.结果 A、B、C组小鼠移植心脏存活时间明显延长,其CCR5及IL-2的表达较D组明显减少,IL-10的表达明显增加.结论 抑制趋化因子受体CCR5对同种异体移植心脏有明显的保护作用,可能与细胞因子的表达有关.     

氨基胍与环孢素A联用对大鼠心脏移植后急性排斥反应的影响

目的：探讨氨基胍与环孢素A联用对同种大鼠心脏移植后急性排斥反应的影响。方法：受体SD大鼠心脏移植后分为4组：（1）对照组：术后不作任何处理;（2）低剂量环孢素A（CsA)组;术后0－7d肌肉注射CsA2mg.kg^-1.d^-1;（3）氨基胍（AG）组：术后0－7d皮下注射AG600mg.kg^-1.d^-1;（4）低剂量CsA加AG组;术后0－7d肌肉注射CsA2mg.kg^-1.d^-1及皮下注射AG600mg.kg^-1.d^-1。术后4d测定急性排斥反应时移植心的诱生型一氧化氮合酶（iNOS)的表达及血清一氧化氮（NO）含量,并观察移植心存活时间。结果与低剂量环孢素A组相比较,低剂量环孢素A与氨基胍联用组不仅显著地抑制移植心iNOS表达与NO产生（P＜0．05）;而且显著地减轻急性排斥反应（P＜0．01）,延长了移植心存活时间（P＜0．05）。结论低剂量环孢素A与氨基胍联用,协同抑制急性排斥反应时移植心iNOS活性及NO产生;显著地延长移植物存活时间。     

反义肽核酸阻断CC趋化因子受体5途径延长同种异体胰岛移植物存活

目的:探讨CC趋化因子受体5（CCR5）反义肽核酸对同种异体胰岛移植急性排斥反应的影响。方法:建立小鼠胰岛移植模型用于检测以CCR5为靶位的PNA CCR5在体内对急性胰岛移植排斥的效应。通过混合淋巴细胞培养（MLR）来评估体外T细胞增殖应答能力。应用RT-PCR和Western blot检测mRNA和蛋白表达水平。结果:与生理盐水对照组［(6.5±0.58)d］和随机PNA错配组［（6.5±0.50）d］相比,PNA CCR5处理组有功能胰岛移植物存活时间明显延长［（12.0±1.75）d］（P均<0.01 ）。移植后第7天,PNA CCR5组的CCR5 mRNA表达水平（0.56±0.05）明显低于对照组和错配组（1.68±0.07和1.80±0.14）（P均<0.01）。PNA CCR5组移植物CCR5蛋白水平亦较对照组和错配组明显下降（P均<0.01）。PNA CCR5组小鼠淋巴细胞增殖能力亦明显降低。结论:PNA CCR5能延长同种异体胰岛移植物的存活时间,在抑制同种异体急性排斥反应中具有潜在的治疗效应。     

环孢素A联合供者骨髓细胞输注延长大鼠移植心脏存活时间

目的：探讨环孢素A（CsA）联合供者骨髓细胞（DBMC）输注对同种大鼠移植心脏存活时间的影响。方法：制作Lewis大鼠到BN大鼠的异位（腹部）心脏移植模型，并按对受者处理的不同分为四组，对照组不进行特别处理，CsA组术后连续7d给予CsA5mg·kg^-1·d^-1，联合处理组分别于术中及术后第6天输注1×10^8个DBMC，术后连续7d给予CsA5nag·kg^-1·d^-1，DBMC组分别于术中及术后第6天输注1×10^8个DBMC；另设BN大鼠间的心脏移植作为对照（BN对照组）。观察移植心脏的存活时间，观测术后第6天血清白细胞介素2（IL-2）、移植心脏组织中肿瘤坏死因子（TNF-α）mRNA表达以及组织学改变，流式细胞仪检测术后第6、12、18天时受者外周血有核细胞中的供者来源细胞、CD3^＋ CD25^＋细胞、CD4^＋ CD25^＋细胞的百分比以及共刺激分子CD86表达、CD4^＋ CD45RC^＋／CD4^＋ CD45RC^-等。结果：联合处理组移植心脏存活时间为（21．6±3．2）d，明显长于对照组和DBMC组（P〈0．05），其血清IL广2为（313±95）pg／ml，心肌组织中TNF-α mRNA的表达量为0．12±0．10，均明显低于对照组和DBMC组（P〈0．05），排斥反应程度轻于其它3个移植组。联合处理组大鼠外周血有核细胞上CD86表达受到明显抑制；术后6、12d，联合处理组的CD4^＋ CD45RC^＋／CD4^＋ CD45RC^-比值低于对照组和DBMC组，CD3^＋ CD25^＋细胞百分比也低于对照组和DBMC组；接受DBMC输注者外周血中供者来源的有核细胞明显多于未接受DBMC者。结论：短疗程CsA联合DBMC输注能减轻大鼠心脏移植急性排斥反应程度，延长移植心脏存活时间。     

环孢素A与盐酸小檗碱联用预防大鼠心脏移植排斥反应

目的探讨环孢素A(CsA)与盐酸小檗碱联用对同种异基因大鼠心脏移植排斥反应的抑制效果。方法建立Wistar大鼠心脏到SD大鼠的异位(腹腔内)心脏移植模型,术后单独使用CsA、盐酸小檗碱以及联合使用CsA和盐酸小檗碱进行免疫抑制治疗,观察各组移植心脏的存活时间。结果单独使用不同剂量CsA者移植心脏的存活时间较安慰剂组明显延长(P<0.01);CsA和盐酸小檗碱联用组移植心脏的存活时间较单用小剂量CsA组明显延长(P<0.01);单用盐酸小檗碱组与安慰剂组相比,移植心脏存活时间的差异无统计学意义(P>0.05)。结论CsA与盐酸小檗碱联用预防大鼠心脏移植后的排斥反应具有协同作用。     

HLA衍生肽RDP1258延长大鼠移植心脏存活时间

目的　观察HLA衍生肽RDP1258对大鼠同种移植心脏存活时间的影响。方法人工合成HLA衍生肽RDP1258;建立大鼠心脏腹部移植模型,随机分为4组。(1)对照组:心脏移植前后不用任何药物;(2)环孢素A(CsA)组:心脏移植前后给予CsA灌胃;(3)RDP1258组:心脏移植前后给予PDP1258腹腔注射;(4)RDP1258 CsA组:心脏移植前后联合给予RDP1258和CsA。分别观察人工合成的RDP1258纯度、移植心存活时间及移植心组织的光镜及电镜检查情况。结果RDP1258纯度达95%以上,分子量与理论值相符。大鼠移植心脏存活时间:对照组为(8.00±2.90) d,CsA组为(13.38±3.62)d,RDP1258组为(33.29±10.09)d,RDP1258 CsA组为(85.38±18.34) d。RDP1258组和RDP1258 CsA组与对照组比较,移植心脏存活时间显著延长。RDP1258组和RDP1258 csA组移植心病理改变较轻,超微结构无明显改变。结论RDP1258能抑制急性排斥反应,围手术期给予RDP1258和CsA,能够明显延长大鼠移植心脏存活时间。     

ICAM-1在小鼠到大鼠心脏移植中的表达及来氟米特与环孢素A对其表达的影响

目的：探讨细胞间粘附分子1（ICAM-1）在小鼠到大鼠异种心脏移植中的表达，以及来氟米特（LeD和环孢素A（CsA）对其表达的影响。方法：以NIH小鼠为供者，Wistar大鼠为受者，施行异位（颈部）心脏移植，实验分4组进行，CsA组受者术后接受CsA腹腔注射，Lef组受者术后接受Lef灌胃，联合用药组受者术后接受Lef和CsA治疗，另设空白对照组，受者术后不进行任何处理。以移植心脏停跳作为排斥反应的终点，采用免疫组化和蛋白印迹杂交法检测移植心肌组织中ICAM-1蛋白的表达。结果：空白对照组、CsA组、Lef组及联合用药组移植心的存活时间分别为（2．17±0．41）d、（2．50±1．05）d、（4．17±1．33）d和（6．50±2．56）d，联合用药组明显长于其它三组（P〈0．05），Lef组明显长于空白对照组（P〈0．05）。移植心脏组织中ICAM-1蛋白的表达强度（电泳条带积分吸光度值），空白对照组为155．40±5．33，CsA组为150．73±5．13，Lef组为104．65±6．15，联合用药组为29．24±2．76，联合用药组的积分吸光度值明显低于其它三组（P〈0．05），Lef组的积分吸光度值明显低于CsA组和空白对照组（P〈0．05）。结论：小鼠到大鼠的异种心脏移植中ICAM-1表达明显，联合应用Lef和CsA可显著抑制ICAM-1在移植心脏中的表达。     

急性排斥反应过程中淋巴细胞趋化因子基因表达的意义

目的　探讨急性排斥反应过程中淋巴细胞趋化因子 (LTN)mRNA在移植心脏局部表达的意义及环孢素A(CsA)对其的影响。方法　以SD大鼠为受者 ,Wistar大鼠为供者 ,施行异位 (腹腔 )心脏移植术 ,分为术后使用CsA组 (15mg·kg-1·d-1)和不用组 ,并设SD大鼠间的心脏移植组 (同系移植组 ) ,以正常SD大鼠为对照组。采用一步法逆转录 聚合酶链反应 (RT PCR)检测术后不同时间移植心脏局部LTNmRNA的表达。结果　正常对照组和同系移植组在各时间点均未见LTNmRNA表达 ;LTNmRNA在未用CsA组的表达变化与急性排斥反应的进程相关 ,排斥反应的早期出现LTNmRNA表达上调 ,术后 5d时达到峰值 ,而应用CsA组 ,LTNmRNA的表达峰值出现延缓 ,且明显低于未用CsA组 (P <0 .0 5 )。结论　LTNmRNA的表达上调与排斥反应过程中淋巴细胞浸润密切相关 ,可能对急性排斥反应的早期诊断有帮助 ;CsA可抑制LTN基因的表达 ,可能是其免疫抑制作用的又一分子免疫学机制     

器官组织移植

原位心脏移植的临床研究；血管内皮生长因子转染骨髓间充质干细胞心肌移植对心肌梗死后大鼠心功能及血管新生的作用；门静脉预输注供者凋亡骨髓细胞延长大鼠移植心脏的存活时间；心脏移植急性排斥反应和红细胞流变学特性的关系；建立同种大鼠心脏移植超急性排斥反应动物模型；心、肺联合移植治疗艾森门格综合征四例     

器官组织移植

他克莫司联合青藤碱抑制大鼠心脏移植急性排斥反应;大鼠的工作型与非工作型同种异体心脏移植模型比较;心肌内心电图监测和诊断大鼠心脏移植术后的排斥反应;心脏移植术后采用无创分子技术实时监测免疫排斥反应的现状（学术交流）;存活十年以上同种原位心脏移植三例;骨髓间充质干细胞自体移植治疗心肌梗死的实验研究;[编者按]     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.