丝裂霉素C在腹腔内温热灌注化疗的药代动力学

目的探讨丝裂霉素Ｃ（ＭＭＣ）用于术中腹腔内温热灌注（ＩＰＨＰ）化疗的药代动力学。方法用高效液相色谱法（ＨＰＬＣ）测定１９例ＩＰＨＰ化疗的中晚期大肠癌病人血清、尿、灌注液和局部组织ＭＭＣ浓度。血药浓度用ＧＳＰ程序计算各药动学参数。结果血药浓度在灌注终止时达到峰值１２３．８６μｇ／Ｌ,然后迅速下降。腹腔局部组织浓度高（７６５．１μｇ／ｋｇ）。２４小时尿中仅排出１．４６ｍｇＭＭＣ。全组病例为一室模型。血药时曲线下面积为每小时２３７．８８μｇ／Ｌ。消除半衰期为６１．２分钟。结论ＩＰＨＰ化疗局部药物浓度高,血药浓度低,消除快,全身毒副作用小。     

消化系统恶性肿瘤术后丝裂霉素和5-氟脲嘧啶的腹腔化学治疗

目的 减少中晚期消化系统恶性肿瘤术后腹腔内复发和肝转移率。方法 术后将患者随机分成腹腔化疗组（观察组）和静脉化疗组（对照组）,观察组５２例,将丝裂霉素６！１０ｍｇ／ｍ＾２和５氟脲嘧啶１￣１．５ｇ／ｍ＾２加入按２０ｍｌ／ｋｇ的生理盐水中,经左右下腹穿刺置管灌注腹腔。对照组５３例,用ＭＭＣ４￣６ｍｇ／ｍ＾２＋ＮＳ２０－３０ｍｌ静脉注及５－Ｆｕ０．７５￣１ｇ／ｍ＾２＋５％葡萄糖注射液５００ｍｌ静脉点滴治     

粘膜粘附性抗癌药HPC-MMC膀胱灌注后尿药的药动学研究

粘膜粘附剂羟丙基纤维素（ＨＰＣ）与抗癌药混合制成的粘膜粘附性抗癌药如ＨＰＣＡＤＭ，膀胱灌注后，抗癌药在尿液里的半衰期及有效药物浓度持续时间明显延长，从而提高了疗效，减少了药物应用剂量和频度［１］。为探讨ＨＰＣＭＭＣ临床应用的可行性，我们进行ＨＰＣＭＭＣ膀胱灌注后尿药药动力学研究，现报道如下：一、材料与方法１．实验动物及标本的收集方法　体重为２．２～２．４ｋｇ（平均２．３５ｋｇ）日本雄性大耳白兔１６只（同济医科大学实验动物中心提供），随机平分为ＨＰＣＭＭＣ组、ＭＭＣ水溶液组（简称ＳＭＭＣ…     

异丙酚目标控制输注系统性能的临床研究

目的 评价异丙酚目标控制输液（ＴＣＩ）系统的性能。方法 自行编制内嵌药代动力学模型的控制程序。１２例择期手术病人,用上述程序控制佳士比３４００注射泵进行异丙酚给药,使用Ｔａｃｋｌｅｙ发表的参数,ＨＰＬＣ荧光法检测血药浓度。结果 １８３个血标本的执行误差的中位数（ＭＤＰＥ）＝－６．８％,执行误差绝对值的中位数（ＭＤＡＰＥ０＝１７．９％,分散度＝０．３５％／ｈ,摆动度＝１８．３％。诱导和切皮前后的血流     

肝硬变时肝内门静脉系统血管顺应性的研究

目的用隔离灌流的鼠肝硬变模型（ＩＰＣＭ）观测肝内血管的顺应性。方法８０只四氯化碳（ＣＣｌ４）诱导肝硬变大鼠,按门静脉单纯灌流和门静脉肝动脉联合灌流分为Ａ、Ｂ两组,通过递增灌流速度观察模型血流动力学变化。结果Ａ组中,对照组基础压力为１６５±０２８ｋＰａ,与此相比,每分钟灌流速分别为３５ｍｌ,４５ｍｌ,５５ｍｌ的３个实验组灌注压随着灌流速度的梯度增加而迅速升高,二者间有高度相关性（ｒ＝０９８５,Ｐ＜００１）,肝内阻力变化不大（Ｐ＞００５）;每分钟灌流速为１５ｍｌ的Ｑ１５组则由于低灌流造成了模型的不可逆损伤。ＩＰＣＭ最大灌流速度范围小于文献报告的正常肝脏灌流的相应范围。Ｂ组中,Ｑ３５～Ｑ５５组的灌注压力也呈迅速升高趋势（Ｐ＜００５）,但未发生Ｑ１５组的低灌流现象;与Ａ组相比,Ｂ组由于开放了肝动脉灌流而部分地缓解了门静脉的压力升高。结论（１）肝硬变门静脉高压症时肝内循环顺应性下降而向肝血流量增加;（２）肝动脉与门静脉两系统间可能存在血流动力学功能的相互代偿     

腹腔高渗热化疗对荷瘤裸小鼠正常组织的影响

为观察荷瘤裸小鼠在腹腔高渗热化疗灌注后正常组织的病理变化,选取５０只鼠龄７－１０周折ＢＡＬＢ／ｃｎｕｎｕ腹腔荷瘤裸小鼠,分组行７．５％ＮａＣｌ,５μｇ／ｍｌ ＭＭＣ,４２℃／３０ｍｉｎ持续腹腔灌注,取肝,肾,脾,回肠组织,常规ＨＥ染色后光镜观察形态学变化。     

丝裂霉素C在腹腔内温热灌注化疗的药代动力学(摘要)

腹腔内温热灌注(IPHP)化疗是防治胃肠道癌术后复发的新途径。研究目的:探讨丝裂霉素C(MMC)用于术中IPHP化疗防治中晚期大肠癌术后复发的药代动力学及与临床疗效的关系。方法:19例初次治疗的中晚期大肠癌病人手术切除肿瘤后,通过加温灌注抗癌仪将溶有80mgMMC的生理盐水8000ml连续灌注人腹腔,保持腹腔内温度恒定(43~45℃),持续60min。用高效液相色谱法(HPLC)测定血清、尿、灌注液和局部组织浓度。观察血、尿中MMC的动态变化。血药浓度经GSP程序模拟出药代动力学模型并计算各药动学参数。结果:IPHP化疗前后灌注液中MMC减少(15.49±4.21)mg。血药浓度在灌注终止时达到降值(123.86±67.06)ng/ml,然后迅速下降。腹腔局部组织浓度高于(765.1±206.9)ng/ml。24h尿中仅排出(1.46±1.24)ng/ml MMC。全组病例的药代动力学模型为一室模型。血药时曲线下面积为(237.88±139.30)ng/ml·h~(-1)。消除半衰期为(61.2±18.6)min。结论:IPHP化疗局部药物浓度高,有利于癌细胞摄取更多的化疗药物,疗效高。血药浓度低,消除快,全身毒副作用小。     

一氧化氮合酶抑制剂对大鼠异氟醚MAC的影响

目的 研究神经元型一氧化氮合酶（ｎＮＯＳ）抑制剂７－硝基吲唑（７－ＮＩ）对大鼠异氟醚ＭＡＣ的影响。方法 ３０只雄性ＳＤ大鼠,。随机分为６组（每组５只）。大鼠置闭麻醉系统中,按标准夹尾法测定异醚ＭＡＣ。每只鼠测定基础ＭＡＣ后,随机经腹腔注射３ｍｌ花生油,或２０、６０、８０、１２０或２５０ｍｇ．ｋｇ＾－１ＮＩ（溶于３ｍｌ花生油）,３０分钟后ＭＡＣ值。结果 ２０～２５ｍｇ．ｋｇ＾－１７－ＮＩ显著降低异氟     

硬膜外吗啡不同PCA剂量临床效应及血药浓度的研究

病人自控镇痛（ＰＣＡ）的药效学与药动学之间的关系是镇痛治疗中值得重视的课题,尤其是在硬膜外ＰＣＡ（ＰＣＥＡ）期间不同剂量ＰＣＡ的临床效应及其血药浓度的变化则须深入研究,为此作者设计并分析比较了在负荷剂量、维持剂量相同的情况下,三种不同ＰＣＡ单次给药剂量对术后病人镇痛效应的影响及其血药浓度变化,现报告如下。资料与方法１０８例择期腹部手术病人（ＡＳＡⅠ～Ⅱ级）,根据ＰＣＡ剂量的不同随机分成３组,Ｍ１组（ｎ＝３６例）ＰＣＡ剂量为１ｍｌ,Ｍ２组（ｎ＝３６例）ＰＣＡ为２ｍｌ,Ｍ３组（ｎ＝３６例）ＰＣＡ为３…     

血栓调节蛋白与肝细胞癌门静脉癌栓的关系

目的　了解血栓调节蛋白（ｔｈｒｏｍｂｏｍｏｄｕｌｉｎ,ＴＭ） 在肝细胞癌（ＨＣＣ） 病人血浆中的水平,探讨ＴＭ 与ＨＣＣ门静脉癌栓形成及侵袭和转移的关系。方法　采用酶联免疫吸附（ＥＬＩＳＡ） 夹心法,检测４５ 例ＨＣＣ病人和６ 例肝良性占位病人的术前和术后血浆ＴＭ 水平。结果　术前ＨＣＣ组血浆ＴＭ水平（１０±６）ｎｇ／ｍｌ 明显高于肝良性占位组（６．１ ±２．２）ｎｇ／ｍｌ,Ｐ＜ ０．０５;单发肝癌结节组（１２ ±６）ｎｇ／ｍｌ和无门静脉癌栓组（１１±６）ｎｇ／ｍｌ 明显高于多发肝癌结节组（８ ±５）ｎｇ／ｍｌ 和门静脉癌栓组（７ ±５）ｎｇ／ｍｌ,Ｐ＜ ０．０５;而ＴＭ 高低与肝癌大小、包膜是否完整、病理分化程度、ＡＦＰ值及肝癌伴肝硬化程度无关,各组比较Ｐ＞０．０５。肝良性占位组术前ＴＭ（６±２）ｎｇ／ｍｌ 与切除术后（５ ．９ ±１ ．８）ｎｇ／ｍｌ 相比差异无显著性,Ｐ＞０ ．０５ ;肝癌组术前（１０ ±５）ｎｇ／ｍｌ 与切除术后（８ ±４）ｎｇ／ｍｌ 相比差异有显著意义,Ｐ＜０ ．０５。结论　ＨＣＣ病人血浆中ＴＭ 水平可升高,ＴＭ 在抗ＨＣＣ门静脉癌栓形成过程中发挥重要作用。     

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 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.