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1.
目的 观察半乳糖化白蛋白磁性阿霉素纳米粒在正常肝脏中的靶向性 ,并观察半乳糖化白蛋白磁性阿霉素纳米粒在全身各脏器的分布特征及外加磁场对其分布的影响。方法 大鼠正中开腹 ,肝动脉插管并固定 ,肝动脉注射12 5I半乳糖化白蛋白磁性阿霉素纳米粒 (相当于阿霉素0 .5mg/kg) ,左外叶加磁场 ,磁场应用 3 0min ,移去磁场后 ,动物立即处死 ;对照组 :肝动脉注射半乳糖化白蛋白磁性阿霉素纳米粒 ,左外叶不加磁场 ,3 0min后 ,移去磁场后 ,动物立即处死 ,立即取靶区肝、非靶区肝、肾、心、肺、小肠、脾及周围血作γ计数。肝组织作病理切片。结果 注入的纳米粒75 %~ 85 %分布于肝脏 ,其他脏器极少。病理切片显示磁区小动脉见大量纳米粒存在 ,对照组及非磁区肝中纳米粒很少见。结论 半乳糖化白蛋白磁性阿霉素纳米粒在正常肝组织中有明显的磁靶向性 ;在磁场作用下 ,半乳糖化白蛋白磁性阿霉素纳米粒主要分布于肝脏 ,其他脏器含量很少 ;实验组肾、心、肺、小肠、脾及外周血与对照组的放射活性比较明显降低 ,表明磁性物质的存在使这些脏器的相对药物暴露明显减少  相似文献   

2.
磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性   总被引:9,自引:0,他引:9  
目的:观察磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性,并观察磁性白蛋白纳米粒在各脏器中的分布特征。方法:建立大鼠移植性肝癌模型。大鼠正中开腹,胃十二指肠动脉插管固定。实验组,肝肿瘤区外加磁场,肝动脉注射磁性阿霉素白蛋白纳米粒(相当于阿霉素0.5mg/kg),磁场应用30min,移去磁场后,动物立即处死。对照组肝肿瘤区不加磁场,肝动脉注射同样剂量的纳米粒后30min处死。动物处死后,立即取肿瘤组织、非磁区正常肝组织、心、肾、脾、肺、小肠和胃作了计数,肿瘤组织、肝组织送病理切片检查。结果:肝肿瘤区应用磁场30min后,磁区肿瘤组织的放射活性较非磁区肝组织的放射活性明显增加,磁区肿瘤组织的放射活性为非磁区正常肝组织的放射活性的8.7倍。对照组在没有磁场存在的情况下,肿瘤组织的放射活性为正常肝脏的2.8倍。实验组肺的放射活性较对照组明显降低。肾、心、脾、小肠和胃两组之间无明显差异。另外,实验组脾、肺和胃与肿瘤组织的放射活性之比较对照组大为降低。注入纳米粒800%以上分布于肝脏。结论:在磁场的作用下,磁性阿霉素白蛋白纳米粒在大鼠移植性肝肿瘤中的聚集明显增加。即使肝肿瘤区没有外加磁场,由于肿瘤组织和正常肝组织血管密度的差异,磁性阿霉素白蛋白纳米粒在肿瘤组织中的分布明显高于正常肝组织。实验组脾、肺、胃与肿瘤组织的放射活性比值大大低于对照组,说明磁场的存在使这些脏器的相对药物暴露明显降低。  相似文献   

3.
目的 研究半乳糖化磁性白蛋白阿霉素纳米粒(Gal-MADM)对肝癌细胞株HepG2侵袭力的影响。方法应用Gal-MADM于HepG2细胞,并设A组:RPMI 1640对照组、B组:普通盐酸阿霉素(ADM)组、C组:磁性白蛋白阿霉素纳米粒联合磁场(MADM M)组、D组:半乳糖化白蛋白阿霉素纳米粒(Gal-ADM)组、E组:Gal-MADM联合磁场(Gal-MADM M)组。药物作用后以β-actin基因作为参照,逆转录-聚合酶链反应(RT-PCR)检测组织蛋白酶(C)B mRNA的表达差异,应用Transwell小室检测体外侵袭力的变化,并用裸鼠肝癌皮下转移模型检测对体内侵袭力的影响。结果Gal-MADM作用HepG2肝癌细胞后CB mRNA表达降低较其他各组更为明显且有显著性,侵过小室滤膜细胞数目减少于其他各组且差异有显著性(P<0.01),裸鼠肝癌生长明显受到抑制(P<0.01)。结论Gal-MADM抑制肝癌细胞株HepG2的侵袭力的作用较ADM、MADM和Gal-ADM为强。  相似文献   

4.
目的 比较研究半乳糖化磁性白蛋白阿霉素纳米粒 (AGMAN)和阿霉素 (ADM )对大鼠的毒性作用。方法 将AGMAN和ADM分为几个不同的剂量组 ,观察静脉给药后的两种药物的急性LD5 0 ,同时将未死亡的动物进行肝肾功能 ,心肌酶学的检查 ,观察其改变。结果 半乳糖化磁性白蛋白阿霉素纳米粒比阿霉素的LD5 0显著的提高。动物的肝肾功能损害明显减轻。结论 AGMAN具有很安全的用药范围 ,对动物的主要器官及全身的毒副作用相对ADM也有明显的减轻  相似文献   

5.
目的 半乳糖化白蛋白磁性阿霉素纳米粒 (Gal MADM NP)治疗大鼠移植性肝癌对肿瘤细胞凋亡bcl 2及bax蛋白表达的影响。方法 采用SABC法进行免疫组织化学染色观察bcl 2及bax蛋白的表达。结果 注射Gal MADM NP(肿瘤区加磁场 )组免疫组织化学显示bcl 2蛋白表达阳性率 2 3 .5 3 % ,低于ADM组 5 4.5 5 %及NS组 71.43 % (P <0 .0 1) ,bax蛋白表达阳性率88.2 4% ,高于ADM组 45 .45 %及NS组 2 8.5 7%。结论 Gal MADM NP组在适当外加磁场的作用下 ,能够降低bcl 2蛋白表达 ,增加bax蛋白表达 ,促进移植肝癌肿瘤细胞凋亡。  相似文献   

6.
目的 研究半乳糖化白蛋白磁性阿霉素纳米粒(Gal-MADM-NP M)在体外对人肝癌细胞系HepG2的杀伤作用。方法应用光镜、电镜下的形态学观察,DNA电泳以及四甲基偶氮唑蓝(MTT)比色法检测杀瘤活性。结果 形态出现明显改变,电镜证实出现细胞凋亡;白蛋白磁性阿霉素纳米粒联合磁场(MADM-NP M)组和半乳糖化白蛋白阿霉素纳米粒(Gal-ADM-NP)组抑制率及半数抑制率剂量相似(P>0.05),Gal-MADM-NP M组抑制率明显提高,半数抑制剂量明显降低(P<0.01)。结论MADM-NP M、Gal-ADM-NP、Gal-MADM-NP都具有明显抑制体外培养肝癌细胞生长增殖的作用。Gal-MADM-NP M对人肝癌细胞杀伤作用较性MADM-NP及Gal-ADM-NP为强,作用机制可能与半乳糖配体的特异性介导和人肝癌细胞上半乳糖受体的识别内吞作用及联合外磁场有关。  相似文献   

7.
目的 观察半乳糖白蛋白磁性阿霉素纳米粒(Gal-MADM)在正常肝脏中的靶向性,并观察Gal-MADM在全身各脏器的分布特征。方法 使用放射示踪技术,用125I标记纳米粒。肝动脉注射,分别于注药后5、15、30、60、120min处死,立即取肝、肾、心、肺、小肠、脾、及周围血作γ计数。用同样的方法进行白蛋白磁性阿霉素纳米粒(MADM)在大鼠体内分布实验。结果 Gal-MADM和MADM肝摄取分别在注射后5 min后最高,分别为15 054.4 CPM/g和6 186.7 CPM/g,各时相前者的肝摄取率均为同时刻后者的2-3倍。在肝、肾、心、肺、小肠、脾、及周围血的分布两药差异有高度显著性(P<0.05)。结论Gal-MADM在正常肝组织中有明显的主动靶向性,Gal-MADM主要分布肝脏,其它的脏器含量少。  相似文献   

8.
目的 观察半乳糖白蛋白磁性阿霉素纳米粒联合交变磁场对肝癌细胞和人肝细胞的影响.方法 将人肝癌细胞HepG2及人肝细胞L-02细胞,随机分成A1、A2组(即RPMI 1640对照组),B1、B2组(游离阿霉素),C1、C2组(半乳糖白蛋白磁性阿霉素纳米粒),D1、D2组(阿霉素纳米粒),E1、E2组(半乳糖白蛋白磁性阿霉素纳米粒),实验组每组含有0.5 mg/L或等量的阿霉素;除C1、C2组外,其他各组置交变磁场(频率为100 kHz、磁场强度为15 kA/m)中,作用30 min.通过细胞计数、Hoechst荧光染色、DNA蛋白电泳、流式细胞仪检测,观察细胞生长曲线、细胞形态、细胞凋亡及细胞周期的变化.结果 (1)E1、E2组,HepG2和L-02细胞增殖抑制作用最强,DNA梯形带最明显,细胞凋亡率分别达40.12%、45.3%;S期细胞分别为39.53%、53.46%,明显高于其他组(P<0.01);(2)L-02细胞的形态改变、细胞增殖抑制、细胞凋亡率明显强于HepG2细胞(P<0.05).结论 半乳糖白蛋白磁性阿霉素纳米粒在交变磁场介导下,对HepG2和L-02细胞产生热化疗协同增效的作用.  相似文献   

9.
目的 制备具有稳定磁性、能够携带化疗药物的半乳糖化白蛋白磁性纳米粒,并对纳米粒的磁性、药物含量、包封率、粒径大小等物理性质进行检测。方法 运用正交试验设计方法设计实验,以粒径大小、纳米药物的载药量和包封率3个指标考察固化温度、固化时间、搅拌速度及糖化比率4个因素的4个水平,从中选出最优化组合,并以最优化组合重复实验,验证试验条件的稳定性以及实验的可重复性。先行制备半乳糖化白蛋白,将阿霉素、半乳糖化白蛋白、磁粉按一定比例混合,通过在精制棉籽油中超声乳化、加热变性固化、乙醚洗涤等工艺制作出载药纳米粒,用乙醇提取法提取纳米粒中的阿霉素,并用紫外分光光度计测定含量,激光粒度分析仪分析粒径大小。结果 运用最优化条件制备的纳米粒,其平均粒径为(197±32)mm,载药量(48.79±4.47)mg/L,包封率(94.34±3.32)%。结论 上述优化条件稳定,试验的可重复性高。  相似文献   

10.
目的 通过吸附阿霉素的纳米铁碳复合磁性载体经猪肝动脉插管介入,观察靶区肝组织、非靶区肝组织及血清中阿霉素的药代动力学变化.方法 将香猪20头随机分为5组,分别经肝左动脉内注入阿霉素水溶液、外加磁场的高中低剂量载药铁碳复合磁性载体及不加用磁场的高剂量载药铁碳复合磁性载体,在不同时间点分别取靶区肝组织、非靶区肝组织及静脉血,质谱法测定阿霉素浓度.结果 外加磁场载药铁碳复合磁性载体组靶区肝组织内阿霉索浓度明显高于非靶区肝组织内阿霉素浓度,最高达101.4倍;也高于阿霉素水溶液组及未加用磁场组,最高达23.8倍及28.3倍.在不同剂量磁靶向治疗组中靶区肝组织内阿霉素浓度呈剂量依赖性增高,持续时间延长.结论 载药铁碳复合磁性载体在外加磁场引导下易聚集于靶区,在局部释放药物,对周围组织器官影响较小.  相似文献   

11.
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 (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.  相似文献   

12.
Don Dame 《Artificial organs》1996,20(5):613-617
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.  相似文献   

13.
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.  相似文献   

14.
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.  相似文献   

15.
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.  相似文献   

16.
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.  相似文献   

17.
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.  相似文献   

18.
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.  相似文献   

19.
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.  相似文献   

20.
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.  相似文献   

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