腹腔镜胆囊切除术中意外胆囊癌12例诊治分析

目的:探讨腹腔镜胆囊切除术(LC)中意外胆囊癌(unexpected gallb ladder carc inom a,UGC)的处理措施。方法:回顾分析本院955例LC术中遇到的12例(1.26%)UGC的临床资料。结果:随诊3~36个月,平均18个月。迄今全部存活。5例PT1、5例PT2、1例PT3(中转开腹)随访至今未发现癌复发及转移。1例PT2因拒绝根治术,现出现肝多发转移。1例PT4因腹腔种植转移,无法根治,故仅部分切除胆囊(胆囊粘连重),以解决急性胆囊炎问题,现有腹水、恶液质表现。所有病例均未见脐部戳孔处肿瘤种植转移。结论:LC术中应常规切开胆囊标本,必要时送术中冰冻。PT1单纯切除胆囊已足够;PT2要额外楔形切除肝组织及区域淋巴结;PT3中转开腹,行根治手术或姑息手术。     

MR T2加权成像显示胆囊壁增厚点状高信号的意义

目的研究病理组织学证实的胆囊腺肌瘤病、慢性胆囊炎和管壁增厚型胆囊腺癌在MRL加权成像（T2WI）显示病变胆囊壁点状高信号的特征。方法38例患者（胆囊腺肌瘤病16例，慢性胆囊炎13例，管壁增厚型胆囊腺癌9例），每例均进行了MR常规T1WI、常规T2WI和3mm薄层T2WI及MR胰胆管成像（MRCP）。所有患者均接受了胆囊切除手术。2名高年资放射科医生共同分析不同序列MRI，观察胆囊壁增厚及T2WI显示病变胆囊壁点状高信号的不同表现，将观察结果与病理组织学检查所见对照。结果所有患者的胆囊壁均明显增厚，厚度范围5～15mm，平均9mm。T2WI显示病变胆囊壁存在各种各样的点状高信号，在胆囊腺肌瘤病，点状高信号分布于整个增厚的胆囊壁，且数量较多（5～15个／cm^2），较大（直径2～7mm），边界清楚，呈现中等至明显高信号；在慢性胆囊炎，点状高信号主要位于增厚胆囊壁的黏膜侧，数量较少（3～5个／cm^2），较小（直径2～4mm），边界清楚，呈中等至明显高信号；在管壁增厚型胆囊腺癌，点状高信号边界欠清，呈现稍高信号，其数量和大小差异较大，分布范围取决于癌组织浸润胆囊壁的深度。结论胆囊腺肌瘤病、慢性胆囊炎和管壁增厚型胆囊腺癌在T2WI呈现的点状高信号有一定差别，正确识别这些点状高信号的特征有助于鉴别诊断良恶性胆囊壁增厚。     

Prediction of steady state bioequivalence relationships using single dose data II-nonlinear kinetics

Two nonlinear pharmacokinetic models were simulated to investigate the relationship between single and multiple dose bioequivalency parameters for drugs such as phenytoin and propranolol which exhibit either saturable elimination kinetics or a capacity limited first pass effect. Mean Tmax, Cmax and area under the plasma-concentration time curve values from 0 to infinity (AUC 0-infinity) were compared after a single and multiple dose(s) of a test or reference drug. The aim was to determine if there were systematic changes in the limits of the single dose confidence interval at steady state that would limit the usefulness of confidence intervals following a single dose in accurately predicting bioavailability following multiple dosing. The 90 per cent confidence interval expressed as a percentage of the reference mean for Tmax, Cmax, and AUC 0-infinity showed model dependent changes from single to multiple dosing in response to the level of data error and changes in absorption. Changes in clearance also seemed to have a marked effect on the observed limits of the single and multiple dose confidence intervals especially for Cmax which showed a characteristic change in the intervals as a function of the clearance ratio. The model used to describe phenytoin had confidence intervals for Cmax and AUC 0-infinity from single to multiple dosing that were similar to that seen for the experimental data. However, the model predictions for Tmax confidence intervals following single and multiple dosing was at variance with the experimental data for formulations A and B.     

Sonographic evaluation of gallbladder kinetics: in vitro and in vivo comparison of different methods to assess gallbladder emptying.

In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.     

对药代动力学实验的两点改进

通过具体的实验数据，讨论在药代动力学实验中如何加入曲线下面积（AUC）的计算，以帮助学生理解并掌握这一概念；在实验室设置不同剂量组，给药后比较剂量与浓度是否呈等比例关系，以此加深学生对于一级动力学消除及其临床意义的理解。     

Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half-lives and median time to eradication (21 vs. 19 days, p = 0.076). Side-effects and discontinuations of assigned treatment (18 of 321 patients) were comparable. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.     

雌激素及其受体与胆囊癌关系的研究现状及进展

目的:探讨并讨论雌激素及其抗体与胆囊癌的关系.方法:阅读关于雌激素和胆囊癌方面的文献并进行总结.结果:雌激素在胆囊癌转变过程中起极为重要的作用.结论:研究胆囊癌患者血清中的雌激素水平对胆囊癌的发生、发展、预后及指导相应临床内分泌治疗具有重要的理论意义.     

Pharmacokinetics of two per cent rectal methohexitone in children

Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child.     

Glucuronidation of Entacapone, Nitecapone, Tolcapone, and Some Other Nitrocatechols by Rat Liver Microsomes

Purpose. Nitrocatechol COMT inhibitors are a new class of bioactive compounds, for which glucuronidation is the most important metabolic pathway. The objective was to characterize the enzyme kinetics of nitrocatechol glucuronidation to improve the understanding and predicting of the pharmacokinetic behavior of this class of compounds. Methods. The glucuronidation kinetics of seven nitrocatechols and 4-nitrophenol, the reference substrate for phenol UDP-glucuronosyltrans-ferase activity, was measured in liver microsomes from creosote-treated rats and determined by non-linear fitting of the experimental data to the Michaelis-Menten equation. A new method that combined densitometric and radioactivity measurement of the glucuronides separated by HPTLC was developed for the quantification. Results. Apparent K_m values for the nitrocatechols varied greatly depending on substitution pattern being comparable with 4-nitrophenol (0.11 mM) only in the case of 4-nitrocatechol (0.19 mM). Simple nitrocatechols showed two-fold V_max values compared with 4-nitrophenol (68.6 nmol min^–1 mg^–1), while all disubstituted catechols exhibited much lower glucuronidation rate. V_max/K_m values were about 10 times higher for monosubstituted catechols compared to disubstituted ones. The kinetic parameters for COMT inhibitors were in the following order: K_m nitecapone >> entacapone > tolcapone; V_max nitecapone > entacapone > tolcapone; V_max/K_m tolcapone > nitecapone > entacapone. Conclusions. Nitrocatechols can in principle be good substrates of UGTs. However, substituents may have a remarkable effect on the enzyme kinetic parameters. The different behaviour of nitecapone compared to the other COMT inhibitors may be due to its hydrophilic 5-substituent. The longer elimination half-life of tolcapone in vivo compared to entacapone could not be explained by glucuronidation kinetics in vitro.     

Ex Vivo Evaluation in Normal Dogs of Insulin Released by a Bioartificial Pancreas Containing Isolated Rat Islets of Langerhans

In bioartificial pancreatic systems, isolated islets of Langerhans are protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to immunoglobulins and lymphocytes. Some of these devices, referred to as vascular systems, are set up to be connected to a vascular site in the recipient, with blood circulating in contact with one side of the membrane, and the islets on the other side. Such a bioartificial pancreas, containing isolated rat islets of Langerhans, was connected to an arteriovenous shunt of a normal anesthetized dog. The aim of this experiment was to investigate the kinetics of the insulin secretory response of the system to a glucose load. Glucose was infused upstream of the system, increasing the glucose concentration inside the bioartificial pancreas from 7 to 14 mmol/l, without altering the blood glucose concentration of the dog. Insulin concentration was determined simultaneously upstream and downstream of the bioartificial pancreas. Insulin production was calculated by multiplying the difference between these values by the blood flow rate. Blood flow rate (Q) was estimated from the change in the glucose concentration produced by the glucose infusion using a mass transfer analysis derived from Fick's principle. Insulin production increased from 20 +/- 8 to 59 +/- 15 microU/100 islets/min within 15 min following the beginning of the stimulation (n = 6, p less than 0.05). Five min after the end of the stimulation, insulin production decreased from 75 +/- 13 to 50 +/- 9 microU/100 islets/min (p less than 0.05) to reach the basal level (21 +/- 3 microU/100 islets/min) 30 min after the end of the glucose stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)