美罗培南在家兔胆汁中的药物浓度-时间分布的实验研究

目的研究美罗培南在家兔胆汁中的浓度及其分布规律,为预防和治疗胆道感染用药提供参考和依据。方法家兔行胆总管造瘘术,先留取空白胆汁,静脉注射美罗培南后分别于不同时间点采集胆汁标本。行专属性试验后,取空白胆汁加美罗培南对照品和流动相,配成0.5~500μg/ml不同浓度的系列胆汁样品,经高效液相色谱仪分析,采用外标法行药物色谱峰面积定量,以胆汁样品药物浓度对色谱峰面积进行线性回归,得回归方程。注射美罗培南后的家兔胆汁样品经预处理后用高效液相色谱仪测定峰面积,按标准曲线回归方程计算得出胆汁药物浓度,从而了解美罗培南的胆汁药物浓度-时间分布情况。结果专属性试验显示,在本研究的流动相色谱条件下测定药物,胆汁杂质峰、美罗培南药物色谱峰分离效果良好。标准曲线回归方程为S=2209.10C-1251.34,r=0.9999,美罗培南的最低定量限为0.5μg/ml。家兔静脉注射美罗培南(75mg/kg)后即时在胆汁中达(38.36±14.17)μg/ml,远远超过其对革兰阴性杆菌的最小抑菌浓度(MIC90)0.031~2μg/ml,之后美罗培南的胆汁药物浓度随时间而迅速降低。用药后180min,胆汁中的药物均被完全消除。结论美罗培南在胆汁中能达到较高的有效杀菌浓度,可作为预防和治疗胆道感染的较佳的药物。由于消除速度较快,临床用药应缩短间隔时间。     

Effects of α1-adrenergic receptor on the proliferation of cholangiocarcinoma cells

Objective To investigate the correlation between α1-adrenergic receptor and the pathological behavior of cholangiocarcinoma, and the effects of norepinephrine (NE) on the proliferation of cholangiocarcinoma cell line QBC939. Methods Thirty-six samples of cholangiocarcinoma were resected in Southwest Hospital from August 2002 to March 2008. The expression of α1-adrenergic receptor in the 36 samples of cholangiocarcinoma tissue and 4 samples of normal bile duct tissue were detected by SABC technique. The proliferation of cholangio-carcinoma cell line QBC939 was detected after processing the cells with NE, phentolamine and prazosin. All the data were analyzed by chi-square test. Results The high positive expression rate of α1-adrenergic receptor was 68% (17/25) in patients with lymph node metastasis, which was significantly higher than 9% (1/11) in patients without lymph node metastasis (χ2=10.604, P<0.05). The high positive expression rate of α1-adrenergic receptor was 85% (11/13) in patients with middle and low positioned cholangiocarcinoma, which was significantly higher than 30% (7/23) in patients with hilar cholangiocarcinoma (χ2=9.753, P<0.05). NE promoted the proliferation of cholangiocarcinoma cell line QBC939 by stimulating the expression of α1-adrenergic receptor, and in a concentration-dependent manner. The proliferative effect was weakened as time passed by, and it was eliminated by phentolamine and prazosin. Conclusions The expression of α1-adrenergic receptor is diverse due to lymph node metastasis and the location of the tumor, α1-adrenergic receptor with high expression may play an important role in the proliferation and metastasis of cholangiocarcinoma.     

去胆管及去门静脉肝叶肝细胞功能分化的研究

目的 观察胆管结扎及门静脉结扎后肝细胞形态及功能分化现象,探讨去胆管及去门静脉肝叶的保留价值.方法 应用氰基丙烯酸酯对仅保留两个肝叶的大鼠行一叶胆道栓塞并结扎,另一肝叶行门静脉结扎,进行分肝静脉血化验检查、组织病理及超微结构观察.结果 去胆管肝叶形态及糖原染色变化不大,分肝静脉血白蛋白(30.9±1.8)g/L与对照组(31.9±2.0)g/,L比较差异无统计学意义(P>0.05).去门脉肝叶萎缩明显,但血胆红素指标维持正常,与未处理对照组比较[(7.7±3.2)比(8.7±2.3)μmol/L]差异无统计学意义(P>0.05).结论 去胆管肝叶在观察期内无明显萎缩,仍保留有蛋白质合成分泌等功能;去门脉肝叶肝细胞能够承担胆汁代谢功能.     

医源性胆管损伤的诊治体会

目的探讨手术中胆管损伤后即时手术和再次手术处理的方法。方法回顾性分析1984年5月-2003年11月经作者手术或参与手术21例的临床资料。结果术中即时发现并处理6例。其中，成功4例，术后狭窄再次手术治愈1例，处理结果不满意1例。术后处理15例，均择期行胆肠吻合治愈。结论术中处理结果与损伤程度和胆管横径大小密切相关。术后因各种原因导致胆管狭窄者应行胆管空肠吻合术。     

应激性溃疡时幽门区局部一氧化氮含量变化对胆汁返流的影响及机理探讨

目的探讨胆汁返流与幽门区局部神经递质一氧化氮的变化对应激性溃疡发病的影响及可能的机理。方法采用冷束缚应激方法复制应激性溃疡的动物模型，将60只成年SD大鼠分为两部分，第1部分：对照组10只，溃疡组30只，用于观测影响应激性溃疡发生的相关因素；第2部分：左旋硝基精氨酸甲酯（L—NAME）预处理组10只（L—NAME组），生理盐水预处理组10只（生理盐水组），用于观测幽门区局部一氧化氮含量变化对其他因素的影响。分别检测各组胃内胆汁酸浓度、胃黏膜溃疡指数（Guth评分）以及胃内pH值，用生化试剂盒检测幽门区一氧化氮的含量。结果溃疡组应激结束后1h幽门区一氧化氮含量达到峰值（P〈0．01），应激结束后2h胃内胆汁酸浓度和pH值均达到峰值（P〈0．01），应激结束后4h胃内溃疡指数达到峰值（P〈0．01）。L-NAME组的胃内胆汁酸浓度、溃疡指数及一氧化氮含量较生理盐水组显著降低（P〈0．01，P〈0．05），而胃内pH值的差异无统计学意义（P〉0．05）。幽门区一氧化氮含量与胆汁酸浓度呈正相关（r=0．715，F=12．55，P=0．017）。结论幽门区一氧化氮含量变化与胆汁的返流量之间存在正相关关系，而L—NAME的幽门区局部干预使幽门区一氧化氮含量减少，幽门松弛程度降低，胆汁返流量也随之减少，进而降低溃疡指数，起到保护胃黏膜的作用。     

Mucin-producing Bile Duct Tumor of the Caudate Lobe Protruding into the Common Hepatic Duct

Mucin-producing tumor in the bile duct is referred to clinically as mucin-producing bile duct tumor (MPBT). Intraductal papillary neoplasm of the biliary tract that resembles an intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a rare category of MPBT and is not well characterized. We, herein, report a case of MPBT of the caudate lobe of the liver that showed papillary growth and communicated with the bile duct of the caudate lobe and protruded into the common hepatic duct. Histologically, MPBT cells showed papillary overgrowth with abundant mucinous secretions, resembling an IPMN of the pancreas. The MPBT cells showed the same immunostaining pattern as that of cells from IPMN of the pancreas.     

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methylformamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5–5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 μg/kg, i.v.) or substance P (6.5 μg/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5–5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 μg/kg, i.v.)- or substance P (6.5 μg/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge. Received: 29 April 1996 / Accepted: 10 October 1996     

Risk factors for capillary leakage syndrome after bone marrow transplantation

 Age, hematopoietic growth factors, cyclosporin A, mode of bone marrow transplantation (BMT) (autologous, allogeneic-related, unrelated), and underlying disease were assessed as potential risk factors for capillary leakage syndrome (CLS) in 96 patients after BMT. CLS was defined as unexplained weight gain of >3% within 24 h and nonresponsiveness to furosemide. CLS occurred in 9/21 patients after unrelated compared with 2/33 after allogeneic-related BMT (p=0.0017) for hematopoietic disorders (n=54) and in 6/7 patients after allogeneic-related compared with 3/35 after autologous BMT (p=0.0001) for solid tumors (n=42). Hematopoietic growth factors and cyclosporin A were no signficant risk factors on their own. We conclude that unrelated BMTs or high-intensity conditioning regimens used in combination with allogeneic-related BMT are the main risk factors for CLS. Received: 6 January 1997 / Accepted: 10 March 1997     

胆汁反流性胃炎的胃运动功能研究

目的:探讨胃排空改变以及胃窦平滑肌电节律紊乱在胆汁反流性胃炎发病中的可能机制。方法:对59例有慢性上消化道症状的慢性胃炎病人,根据胃镜下可见显著胆汁反流,胃液呈深黄色或深绿色,胃液pH≥3.0,甘胆酸浓度>58μg/ml,胃粘膜病理积分>9,判断为病理性胆汁反流(部分病人经:显象进一步证实)。胃镜下未见胆汁反流,胃液清亮,其余指标均未达上述标准者判断为非胆汁反流性。选出18例胆汁反流性胃炎病人(BRG组)和17例非胆汁反流性胃炎病人(NRG组),上述检查正常的10名健康志愿者(HC组)作为对照受检者进食一份双核素标记的标准餐,用照相机以1帧/2分钟连续动态照相120分钟,部分受试者又在空腹时检测胃窦肌电。结果:BRG组有明显的固、液体双相排空延迟,以固相延滞期(SLP)延长较为突出,而固体半排空时间(HSET)延长在很大程度上受到SLP延长的影响:NRG组仅有HSET显著延长。进一步胃电检测结果表明,各组间平均慢渡频率(MSWF)无显著性差异,出现胃电节律失常(DRM)在各组的分布为HC组1/7、NRG组3/10和BRG组7/13,严重程度BRG>NRG>HC。结论:胆汁反流性胃炎者有较严重的胃窦功能不良,且胃肌电可予进一步证实,胃底和十二指肠动力异常也可能与胆汁反流性胃炎的发病有关。     

Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects

Abstract. Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through dis-inhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by realtime ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 ± 6.9 vs. 21.6 ± l.7mL, P <0.02), larger residual volume (12.3 ± 1.8 vs. 4.0 ± 0.5ml, P < 0.0006) and slower emptying time ( T /2: 33 ± 2 vs. 21 ± 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 ± 578 vs. 7908 ± 491 % 120min^-1, P <0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.