骨肉瘤大剂量甲氨喋呤化疗的血清药物浓度监测

测定骨肉瘤大剂量甲氨喋呤（ｍｅｔｈｏｔｒｅｘａｔｅＭＴＸ）化疗４２例次，化疗方案分两组，第一组ＭＴＸ剂量为２００ｍｇ／ｋｇ，静脉滴注时间为２、４、６小时；第二组静脉滴注时间为６小时，ＭＴＸ剂量为２００ｍｇ／ｋｇ、３００ｍｇ／ｋｇ、４００ｍｇ／ｋｇ、５００ｍｇ／ｋｇ。结果表明，零时血清药物浓度随滴注时间的延长而下降，为６．２×１０－４ｍｏｌ／Ｌ，５．１×１０－４ｍｏｌ／Ｌ、５．０×１０－４ｍｏｌ／Ｌ，各时间组之间无显著性差异；零时血清药物浓度随ＭＴＸ剂量增加而显著增高，为５．０×１０－４ｍｏｌ／Ｌ、７．７×１０－４ｍｏｌ／Ｌ、１．１×１０－３ｍｏｌ／Ｌ、２．７×１０－３ｍｏｌ／Ｌ。零时血清药物浓度越高，血清药物浓度下降速度越快，２４小时为１×１０－６ｍｏｌ／Ｌ左右，２４小时以后，下降速度缓慢，至７２小时为１×１０－７ｍｏｌ／Ｌ左右。２４小时以后的血清药物浓度差异不大     

一氧化氮对精子运动功能的影响

目的探讨一氧化氮对精子运动影响的机制。方法体外孵育精子中加入不同剂量的一氧化氮供体硝普钠（ＳＮＰ），在显微镜下观察其在不同时间和不同剂量下对精子运动的影响。ＭＴＴ法观察一氧化氮对呼吸链的影响。结果一氧化氮在低浓度下（ＳＮＰ１０－９～１０－７ｍｏｌ／Ｌ）显著促进精子运动，在中等剂量下（ＳＮＰ１０－６～１０－５ｍｏｌ／Ｌ）对精子运动影响甚微，高浓度下（ＳＮＰ＞１０－５ｍｏｌ／Ｌ）则明显抑制精子运动。随一氧化氮浓度的升高，精子呼吸链活性进行性下降。结论一氧化氮对精子运动功能的影响具有剂量依赖效应。     

三烯高诺酮和米非司酮对离体大鼠及人体子宫内膜生长的抑制作用

大鼠子宫内膜离体培养４天后分组给药：对照组；丹那唑１０－６，３×１０－６，１０－５ｍｏｌ／Ｌ；三烯高诺酮３×１０－８，１Ｏ－７，３×１Ｏ－７ｍｏｌ／Ｌ；米非司酮１０－６，１０－５，１０－４ｍｏｌ／Ｌ。于给药５天后取培养子宫内膜切片，镜下观察其形态变化，全自动图象分析仪细胞计数。结果表明，丹那唑抑制大鼠子宫内膜的生长，而三烯高诺酮和米非司酮未见明显抑制效应。人体子宫内膜离体培养４天后分组给药，１Ｏ－９ｍｏｌ／Ｌ雌二醇、１０－７ｍｏｌ／Ｌ孕酮均能促进子宫内膜的生长。在给雌二醇或孕酮的同时加３×１０－６ｍｏｌ／Ｌ丹那唑或１０－７ｍｏｌ／Ｌ三烯高诺酮或１Ｏ－５ｍｏｌ／Ｌ米非司酮。结果表明，丹那唑、三烯高诺酮和米非司酮均能抑制子宫内膜的生长，而在雌二醇或孕酮缺乏的条件下，三烯高诺酮和米非司酮对子宫内膜的生长没有明显抑制作用。此结果表明三烯高诺酮和米非司酮对子宫内膜生长的抑制作用有赖于雌二醇或孕酮的存在。     

全反式维甲酸诱导人膀胱癌细胞T24凋亡的研究

目的　探讨全反式维甲酸（ＡＴＲＡ） 诱导人膀胱癌细胞Ｔ２４ 凋亡的可能性。方法　应用细胞和分子生物学技术检测不同浓度ＡＴＲＡ 对Ｔ２４ 细胞生长和凋亡的影响。结果　３ ×１０－５ ～３ ×１０－ ７ｍｏｌ／ＬＡＴＲＡ可显著抑制Ｔ２４ 细胞增殖。用３×１０－５ ｍｏｌ／Ｌ和３×１０－ ６ ｍｏｌ／ＬＡＴＲＡ 作用细胞６ 天,可出现典型凋亡特征;３ ×１０－５ 、３×１０－ ６ ｍｏｌ／ＬＡＴＲＡ 组及对照组的细胞凋亡率分别为２０ ．１６ ％ 、１５ ．３１％和１ ．４９ ％ ;ＤＮＡ 琼脂糖凝胶电泳呈现凋亡特征性的ＤＮＡ 梯形带。结论　ＡＴＲＡ对人膀胱癌细胞Ｔ２４ 有剂量生长抑制作用,且可成功地诱导人膀胱癌细胞Ｔ２４ 发生凋亡。     

利多卡因对大鼠海马锥体神经元电压依赖性钠通道的作用

目的 研究不同浓度利多卡因对中枢神经系统海马锥体神经元电压依赖性钠通道的影响。明确利多卡因对神经元的保护和损伤与电压依赖性钠通道的关系。方法 应用全细胞膜片钳方法记录下同浓度利多卡因（１０＾－５ｍｏｌ／Ｌ～１０＾－２ｍｏｌ／Ｌ）时大鼠急性分散海马锥体神经元电压依赖性钠通道电流的变化。结果 利多卡因对钠通道阈电位影响不大,以浓度依赖的方式抑制电压依赖性钠电流,随利多卡因浓度的增加其掏钠电流的作用加强     

利多卡因对乳酸损害脑细胞的保护作用：体外培养脑细胞的研究

应用体外神经细胞培养技术，研究培养６日后利多卡因对短程重度（ｐＨ４．９、１０分）、长程轻度（ｐＨ７．１、２．４ 小时）乳酸化胚鼠皮层细胞的保护作用。结果表明：６．９ × １０-5Ｍ利多卡因具有提高短程重度乳酸化细胞存活作用，经利多卡因预孵育细胞存活率继续增加，前后两次利多卡因外理作用甚显；３．４５ × １０－５ Ｍ和６．９×１０－５Ｍ利多卡因均可提高长程轻度乳酸化细胞存活率，且３，４５×１０－５Ｍ较６．９× １０-５Ｍ利多卡因作用显著。     

硝普钠阴茎海绵体内注射治疗阳萎的临床研究

本研究选择４２例阳萎患者，采用硝普钠进行阴茎海绵体注射（ＩＣＩ），并选择罂粟碱／酚妥拉明进行对照，结果表明，硝普钠ＩＣＩ后：（１）阴茎外形性状（长度、周径等）明显改变。（２）Ｖｉｒａｇ硬度计点表明硝普钠与罂粟碱／酚妥拉明效果之间无明显差别。（３）所有测试患者无一例出现低血压或局部不适等副反应，与罂粟碱／酚妥拉明相比各有优劣，但总体差异不大，这充分表明，硝普钠作为一种ＮＯ供体可导致阴茎平滑肌松弛，血窦充盈阴茎勃起，其副反应较小，有其临床应用之价值。     

雌二醇及孕酮对离体子宫内膜腺体和基质细胞合成前列腺素的影响

为了研究甾体激素对子宫内膜合成前列腺素（ＰＧＳ）的影响，采用雌二醇（Ｅ２）１０－８ｍｏｌ／Ｌ和孕酮（Ｐ４）１０－７ｍｏｌ／Ｌ培养增生晚期（ｎ＝７）和分泌晚期（ｎ＝５）子宫内膜的分离腺体和基质细胞。结果表明，Ｅ２１０－８／Ｌ和Ｅ２１０－８ｍｏｌ／Ｌ＋Ｐ４１Ｏ－７ｍｏｌ／Ｌ刺激增生晚期的子宫内膜腺体细胞产生ＰＧＦ２α明显增加，对分泌晚期子宫内膜腺体细胞以及增生晚期和分泌晚期子宫内膜基质细胞均无明显影响。ＰＧＥ２，水平不受甾体激素的影响。     

环孢素及山莨菪碱对肝细胞游离钙的影响

分离ＳＤ大鼠肝细胞，负载荧光钙指示剂Ｆｕｒａ－２／ＡＭ后以无钙Ｈａｎｋｓ液悬浮，分别以入以下试剂：１．二甲亚砜。２．环孢素（ＣｓＡ）１ｍｇ／Ｌ。３．ＧｓＡ１０ｍｇ／Ｌ。４．ＣｓＡ１０ｍｇ／Ｌ，山莨菪碱１０ｍｇ／Ｌ。５．ＣｓＡ１０ｍｇ／Ｌ，山莨菪碱４０ｍｇ／Ｌ。测定肝细胞内游离钙发现ＣｓＡ可增加肝细胞内游离钙，为剂量依赖性，山莨菪可部分拮抗ＣｓＡ引起的升钙作用。     

不同温度下血管舒张及收缩反应的差异及其功能变化

目的　研究不同温度下离体血管舒张和收缩功能的变化及其对苯肾上腺素 (phenyle phrine ,PE)和硝普钠 (sodiumnitroprusside ,SNP)的反应差异。 方法　记录在 3 7℃、2 8℃、2 5℃、2 1℃四组温度下大鼠离体肺动脉、主动脉血管条舒张、收缩功能曲线 ,同时测定四组不同温度下离体血管条对苯肾上腺素和硝普钠的反应曲线。结果　从 3 7℃逐渐降温至 2 1℃时 ,离体肺动脉血管条和主动脉血管条强烈舒张 ,而从 2 1℃逐渐升温至 3 7℃时 ,离体肺动脉血管条和主动脉血管条强烈收缩。同时 ,在四组不同温度下 ,离体肺动脉血管条和主动脉血管条对苯肾上腺素和硝普钠的反应有显著差异 ( P <0 .0 1)。结论　随着温度的升高 ,离体肺动脉血管条和主动脉血管条发生强烈收缩 ,而随着温度的降低 ,离体肺动脉血管条和主动脉血管条发生强烈舒张。同时 ,随着温度的升高 ,离体肺动脉血管条和主动脉血管条对苯肾上腺素的收缩反应和硝普钠的舒张反应明显增强 ;而随着温度的降低 ,离体肺动脉血管条和主动脉血管条对苯肾上腺素的收缩反应和硝普钠的舒张反应则明显减弱。     

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.