Translation of pharmacokinetics to clinical medicine

The translation of pharmacokinetics to clinical medicine involves answering the following question: “When the pharmacodynamic or chemotherapeutic activity of a drug is known, how must its dosage regimen be adapted to its pharmacokinetic characteristics so that the desired therapeutic effect may be achieved and maintained?” This presentation discusses examples of pharmacokinetic analyses which influence the practice or principles of practical therapeutics. Physicians have intuitively appreciated the basic importance of pharmacodynamics because they are primarily interested in the action of a drug on the patient. However, in pharmacokinetics we consider the fact that there is not only a unidirectional action but also a mutual interaction between drug and organism. The action of the organism on the drug may be summarized in terms of the pharmacokinetic parameters: absorption, distribution, metabolism, and excretion. These parameters are examined with respect to drug accumulation, relation of pharmacokinetic data to therapeutic effects, saturation phenomena, the effect of kidney disease, the variation of pharmacokinetic parameters in individual patients due to age, pH of body fluids, and the states of wakefulness.     

Women and men exhibit different cortical activation patterns during mental rotation tasks

The strongest sex differences on any cognitive task, favoring men, are found for tasks that require the mental rotation of three-dimensional objects. A number of studies have explored functional brain activation during mental rotation tasks, and sex differences have been noted in some. However, in these studies there was a substantial confounding factor because male and female subjects differed in overall performance levels. In contrast, our functional brain activation study examined cortical activation patterns for males and females who did not differ in overall level of performance on three mental rotation tasks. This allowed us to eliminate any confounding influences of overall performance levels. Women exhibited significant bilateral activations in the intraparietal sulcus (IPS) and the superior and inferior parietal lobule, as well as in the inferior temporal gyrus (ITG) and the premotor areas. Men showed significant activation in the right parieto-occitpital sulcus (POS), the left intraparietal sulcus and the left superior parietal lobule (SPL). Both men and women showed activation of the premotor areas but men also showed an additional significant activation of the left motor cortex. No significant activation was found in the inferior temporal gyrus. Our results suggest that there are genuine between-sex differences in cerebral activation patterns during mental rotation activities even when performances are similar. Such differences suggest that the sexes use different strategies in solving mental rotation tasks.     

颈动脉支架成形术中血液动力学的变化及其对策

目的:观察颈动脉支架成形术中血液动力学不稳定的发生率及其相关因素。方法:15例症状性颈动脉狭 窄患者在行血管内支架成形术时,观察其血压、心率的变化以及药物控制的疗效、围手术期有无并发症。结果:15例支 架放置全部成功,其中11例在进行颈动脉分叉部球囊扩张或支架释放时出现不同程度的心率减慢和血压下降,6例出 现颈动脉窦反应,在使用阿托品和多巴胺后均恢复正常。术中及术后无与血液动力学相关的脑低灌注或高灌注并发症。 结论:血液动力学不稳定是CAS中较为常见的并发症,可通过药物加以控制。     

Experiences in Computer Audiometry (ECoG and ERA)

By the ear-drum arrangement of electrode action potentials of the 8th nerve may be recorded down to the threshold intensities of click stimuli. A decrease in the amplitude of these potentials was observed with ipsilateral presentation of a masking noise. Contralateral conditioning sound stimulation caused either an increase or a decrease of click-evoked action potentials. The increase was observed with intensities of conditioning stimuli exceeding 50-60 dB SL, whereas the decrease was stated at higher stimulation levels. The former effect was ascribed to the activity of the olivo-cochlear fibres and the latter effect to reflex contraction of the middle ear muscles

Scalp-derived slow auditory evoked responses were studied in different conditions of sound stimulation. The peak latencies of these responses were longer, and the peak amplitude was lower for tone bursts as compared to effects of intensity-modulated tonal stimuli. With equal intensities of tonal increments, the peak latencies of derived responses were shorter and the amplitude was greater at higher steady-tone levels. In most cases, there was a close correspondence of the objective and subjective thresholds for both tone bursts and intensity-modulated stimuli. On the grounds of data obtained, the problems related to cross-examination and control test procedures during computer audiometry are discussed     

革兰氏阴性杆菌发生过程控制的研究

本研究选择奇异变形杆菌和绿肿杆菌等作为实验体系，从群体发生发展过程的宏观表现上探讨了生物控制的时空表达及非线性问题。结果表明，杆菌发生过程的时相周期性可以表现为空间的波形靶图样，并具有分形的特征。实验结果表明，菌群在生长过程中的代谢产物是富含生物信息的控制中介机制。我们认为，生物系统局部存在着准平衡和准封闭的微生态环境，生物液晶的存在和相变是细菌群体发生过程的重要协同中介因素。     

Disturbed trafficking of dystrophin and associated proteins in targetoid phenomena after chronic muscle denervation

Dystrophin and associated proteins form a complex with an important role at the sarcolemma. Expression of this protein complex is highly regulated during development and regeneration. In order to better understand assembling patterns of these proteins, we have studied their expression in targetoid-like phenomena found in human muscle after chronic denervation, a situation known to give rise to abnormal protein trafficking. In eight biopsies of patients with chronic denervation, mainly resulting from amyotrophic lateral sclerosis, we found a number of targetoid phenomena. Selective accumulation of a number of sarcolemmal and sarcoplasmatic proteins occurred in targetoid phenomena. The larger majority of them contained gamma-sarcoglycan (gammaSG), but none contained the developmental heavy chain myosin isoform. In a series of 166 targetoid phenomena which could be studied with 17 different antibodies recognizing sarcolemmal and cytoplasmatic proteins, a high level of colocalization of gammaSG with desmin and alpha-actinin was found. Colocalization rate was much lower with other proteins, including other members of the dystrophin-associated protein complex. These data show that selective changes in expression of otherwise closely related proteins occur during disturbed trafficking leading to target formation. Because members of the dystrophin-associated protein complex do not accumulate in a similar fashion within targets, we suggest that a complex molecular control of gene expression and trafficking of this complex is involved after chronic muscle denervation.     

Abnormalities of motor imagery associated with somatic passivity phenomena in schizophrenia

Some patients with schizophrenia report that their limbs are under the control of an alien force (motor passivity). This is hypothesised to be due to the dysfunction of an internal self-monitoring system that normally permits distinctions between internally generated and external influences on intentional behaviour. Motor imagery is the mental simulation of specific motor actions and it is based upon the internal representation of intended but unexecuted motor actions. Therefore, the generation of motor imagery should be impaired in schizophrenia characterised by passivity phenomena. The generation of motor imagery was compared using the visually guided pointing task (VGPT) and the Florida praxis imagery questionnaire (FPIQ) between patients with schizophrenia characterised by high levels of passivity symptoms (passivity) and patients without passivity symptoms (no-passivity). In both the passivity and no-passivity groups, the speed of real motor sequences on the VGPT was constrained by the distance of the movement and the width of the target in accordance with Fitts' law. For the no-passivity group, the same relationship was found for imagined movements. However, in the passivity group, imagined movements were not constrained by Fitts' law. The effect of a 2-kg load to the limb performing real or imagined movements on the VGPT was identical in both groups. The duration of imagined movements was slowed although the duration of real movements was unaffected. The FPIQ showed that the passivity group had difficulty answering questions that required them to imagine kinaesthetic aspects of performing simple gestures. These results suggest that passivity phenomena in schizophrenia are associated with a specific inability to represent the timing of motor actions internally. This is consistent with the hypothesis that patients with passivity phenomena have difficulty with maintaining an internal representation of intentional behaviour.     

氟芬合剂对全身麻醉脊柱手术患者血流动力学的影响

[目的]观察全身麻醉期间氟芬合剂对脊柱手术患者血压及心率的影响.[方法]选择40例需在全身麻醉下施行脊柱手术患者,随机分为观察组和对照组,每组各为20例.观察组患者在手术开始前5 min静脉注射给予氟芬合剂6 mL,对照组给予等量生理盐水,观察手术开始后5,15,30,45 min时患者血压及心率的变化情况.[结果]观察组患者手术开始后血压显著下降,心率逐渐减慢,45 min时血压及心率接近麻醉前水平,与对照组比较,血压与心率变化均有显著性差异.[结论]在麻醉期间氟芬合剂可有效地降低血压,减慢心率,维持时间较长,可防止手术刺激所引起的血压升高及心率增快.     

Mesothelial cells: their structure,function and role in serosal repair

The mesothelium is composed of an extensive monolayer of specialized cells (mesothelial cells) that line the body's serous cavities and internal organs. Traditionally, this layer was thought to be a simple tissue with the sole function of providing a slippery, non-adhesive and protective surface to facilitate intracoelomic movement. However, with the gradual accumulation of information about serosal tissues over the years, the mesothelium is now recognized as a dynamic cellular membrane with many important functions. These include transport and movement of fluid and particulate matter across the serosal cavities, leucocyte migration in response to inflammatory mediators, synthesis of pro-inflammatory cytokines, growth factors and extracellular matrix proteins to aid in serosal repair, release of factors to promote both the deposition and clearance of fibrin, and antigen presentation. Furthermore, the secretion of molecules, such as glycosaminoglycans and lubricants, not only protects tissues from abrasion, but also from infection and possibly tumour dissemination. Mesothelium is also unlike other epithelial-like surfaces because healing appears diffusely across the denuded surface, whereas in true epithelia, healing occurs solely at the wound edges as sheets of cells. Although controversial, recent studies have begun to shed light on the mechanisms involved in mesothelial regeneration. In the present review, the current understanding of the structure and function of the mesothelium and the biology of mesothelial cells is discussed, together with recent insights into the mechanisms regulating its repair.     

尼卡地平和硝酸甘油在体外循环中血压控制的比较

目的比较尼卡地平和硝酸甘油在体外循环中控制高血压的效果及对血流动力学的影响。方法40例冠状动脉旁路术(CABG)病人在体外循环(CPB)中平均动脉压升至10.7kPa时给予尼卡地平或硝酸甘油。将病人随机分为尼卡地平和硝酸甘油组,每组20例。观察两药起效时间,维持平均动脉压(MAP)在665～9.31kPa时所需剂量,开放升主动脉后心脏自动复跳情况以及停机后血流动力学的变化。结果将MAP从10.7kPa降至6.65～9.31kPa时,应用尼卡地平0.5mg,所需时间为(3.8±1.3)min,维持MAP在6.65～9.31kPa时所需剂量为(1.2±0.4)μg·kg