The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.     

Pulmonary embolism.

Pulmonary embolism (PE) is an important health problem and often a major clinical challenge, not only because of the low specificity of its clinical manifestations but also because of the increasing number of medical circumstances that are risk factors for this illness and the importance of early identification, since prompt and appropriate treatment can decrease mortality from this disease by about 25%. In recent years research on PE has been extensive, directed mainly at trying to determine and characterize its risk factors, establish new clinical probability algorithms, develop new diagnostic methods and put existing ones into perspective, seek new therapeutic approaches (pharmacological and non-pharmacological), and above all establish protocols that can guide the clinician from the stage of clinical suspicion to measures to prevent recurrence. It was the authors' aim to review the most significant literature on this subject, in order to produce a text that reflects the state of the art concerning PE and that can be used as a guide in the clinical approach to this pathology.     

输尿管镜治疗输尿管结石185例

目的探讨输尿管镜气压弹道碎石治疗输尿管结石的效果。方法2004年2月～2005年3月，我们对185例输尿管结石（其中伴肾绞痛96例）采用输尿管镜取石或气压弹道碎石进行总结和分析。结果失败12例，其中6例改开放手术，6例术后3d行体外冲击波碎石。一次碎石成功率93．5％（173／185），其中上段结石为75．0％（24／32），中段为95．8％（46／48），下段为98．1％（103／105）。肾绞痛者成功率为100％（96／96）。术中输尿管损伤率2．9％（5／173），其中3例（1．7％）中转开放手术。术后肾绞痛1例。全组随访6～12个月，平均10．2月，无复发。结论输尿管镜气压弹道碎石安全有效，并发症少，是治疗输尿管中下段结石的首选方法，尤其对肾绞痛者疗效更好。     

Some sufficient conditions for global exponential stability of delayed Hopfield neural networks.

In this paper, we have derived some sufficient conditions for existence and uniqueness of equilibrium and global exponential stability in delayed Hopfield neural networks by using a different approach from the usually used one where the existence, uniqueness of equilibrium and stability are proved in two separate steps, rather we first prove global exponential convergence to 0 of the difference between any two solutions of the original neural networks, the existence and uniqueness of equilibrium is the direct results of this procedure. We obtain the conditions by suitable construction of Lyapunov functionals and estimation of derivates of the Lyapunov functionals by the well-known Young's inequality and Holder's inequality. The proposed conditions are related to p-norms of vector or matrix, p in [1, infinity] and thus unify and generalize some results in the literature.     

离子通道与弱精子症

弱精子症是引起男性不育的常见病因之一。随着以精子自身为对象的研究深入,发现离子跨膜转运对精子的生理活动起着重要的作用。离子通道病于20世纪90年代提出,现已逐渐发现临床上许多先天性和/或后天获得性疾病与异常的离子通道有关。因此,关于精子的生理和疾病与离子通道的关系研究逐渐成为当前研究的热点之一。现就近年来与精子运动相关的离子通道,包括阳离子通道和阴离子通道的研究进展作一综述。     

乳腺癌术后双肺及骨转移

疾病的正确诊断和合理治疗是患者和医务工作者共同的心愿。在广东省人民医院肿瘤中心，吴一龙教授指导临床医生应用循证医学理论进行肿瘤的多学科综合治疗，开展临床病例讨论。讨论会上各学科共同围绕一个病例或一个病种进行会诊，临床、病理、B超、放射影像等资料齐全。除相关科室提前准备的中心性发言外，到会人员各抒己见，气氛热烈。参会人员受益匪浅，提高了对疑难病例的诊治水平。为了将他们的诊治经验传播出去，让更多的临床医生获益，我刊开辟“循证病例讨论”栏目，希望广大医务工作者关注此栏目。[编者按]     

B组轮状病毒WH-2株vp7基因的原核表达与抗体的制备

目的：在大肠杆菌中表达人B组轮状病毒WH-2株VP7蛋白并制备其兔抗血清。方法：根据B组轮状病毒（GBRV）WH-2株vp7基因的全序列设计引物,用PCR的方法扩增得到vp7基因的编码区。将其克隆到原核GST融合表达载体pGEX-KG内,转化大肠杆菌E.coliDH5α,IPTG诱导表达人B组轮状病毒WH-2株VP7蛋白,经SDS-PAGE分离纯化表达的蛋白免疫新西兰兔,制备人B组轮状病毒WH-2株VP7蛋白抗血清。结果：经鉴定确认,vp7基因以正确的方式插入到载体中,此重组表达载体经IPTG诱导后,可表达相对分子量为53.4 kDa的GST-VP7融合蛋白。制备的抗血清经同样诱导表达的表达载体pGEX-KG表达产物吸收后1：500倍稀释后用Western Blot分析,与53.4 kDa的GST-VP7融合蛋白获得特异性显色信号。结论：人B组轮状病毒WH-2株VP7蛋白成功在大肠杆菌中GST融合表达,所表达的蛋白和制备的抗体不但为研究结构与功能提供了物质基础,也为GBRV所引起的疾病预防、诊断和治疗等流行病学研究和临床诊断奠定了基础,具有重要实际应用价值。