氨氯地平对大鼠心室肌细胞动作电位及细胞内钙离子浓度的影响

目的探讨不同旋体氨氯地平（Aml）对Spraque—Dawley大鼠心室肌细胞动作电位（AP）及细胞内钙离子浓度的影响。方法采用酶消化法获得大鼠耐钙心室肌细胞，以全细胞膜片钳技术分别记录加入0．1、0．5、1、5和10μmol／L左旋、右旋和混旋Aml后大鼠心室肌细胞AP的变化。并用荧光探针Fura-2／AM测定细胞内钙离子浓度，比较1、5、10、50和100μmol／L左旋、右旋和混旋Aml对细胞内钙离子浓度的影响。结果①加入0．1、0．5、1、5和10μmol／L左旋、右旋和混旋Aml后，AP最大上升速率、AP幅度和超射无明显变化（P〉0．05）。②加入0．1、0．5、1、5和10μmol／L左旋后，50％的AP时程（APD50）分另0为（36．2±8．2）、（33．9±7．7）、（30．2±6．8）、（22．6±5．1）和（15．1±3．4）ms（P〈0．05）；加入混旋Aml后，APD。分别为（39．2±9．2）、（36．7±7．9）、（33．8±7．2）、（25．4±5．9）和（21．7±5．2）ms（P〈0．05）；加入右旋Aml后，APD50分别为（45．1±11．3）、（46．2±10．8）、（44．9±7．3）、（44．8±8．2）和（45．7±9．4）ms（P〉0．05）。③左旋Aml和混旋Aml可降低细胞内钙离子浓度，不同浓度右旋Aml对细胞内钙离子浓度无影响。结论左旋Aml和混旋Aml对L-型钙通道有阻滞作用，从而缩短APD，而右旋Aml对L-型钙离子通道无阻滞作用，因而对APD无影响。     

The Effect of Retrospective Sampling on Estimates of Prediction Error for Multifactor Dimensionality Reduction

The standard in genetic association studies of complex diseases is replication and validation of positive results, with an emphasis on assessing the predictive value of associations. In response to this need, a number of analytical approaches have been developed to identify predictive models that account for complex genetic etiologies. Multifactor Dimensionality Reduction (MDR) is a commonly used, highly successful method designed to evaluate potential gene‐gene interactions. MDR relies on classification error in a cross‐validation framework to rank and evaluate potentially predictive models. Previous work has demonstrated the high power of MDR, but has not considered the accuracy and variance of the MDR prediction error estimate. Currently, we evaluate the bias and variance of the MDR error estimate as both a retrospective and prospective estimator and show that MDR can both underestimate and overestimate error. We argue that a prospective error estimate is necessary if MDR models are used for prediction, and propose a bootstrap resampling estimate, integrating population prevalence, to accurately estimate prospective error. We demonstrate that this bootstrap estimate is preferable for prediction to the error estimate currently produced by MDR. While demonstrated with MDR, the proposed estimation is applicable to all data‐mining methods that use similar estimates.     

Molecular and functional characterization of Kv4.2 and KChIP2 expressed in the porcine left ventricle

Recent studies showed that the Ca²⁺-independent transient outward current (I _to) is very small or even not detectable in the porcine left ventricle. We investigated whether an altered molecular expression or function of voltage-dependent potassium channels belonging to the Kv4 sub-family and their ancillary Ca²⁺-binding β sub-unit KChIP2, which contribute to the major fraction of I _to in other species, may underlie this lack of a significant I _to in the porcine left ventricle. RT-PCR analysis with degenerate primers showed that both Kv4 mRNA and KChIP2 mRNA are expressed in porcine left ventricular tissue and in isolated ventricular myocytes. PCR cloning and sequence analysis predicted proteins with >98% identity to rat and human Kv4.2 and >99% identity to rat and human KChIP2. Heterologous expression of porcine Kv4.2 in Xenopus laevis oocytes gave rise to currents with characteristic properties of rat and human Kv4.2, and co-expression with its KChIP2 sub-unit increased current density (tenfold), slowed inactivation (twofold) and accelerated recovery from inactivation (tenfold). Kv4.2 immunohistochemistry in porcine left ventricular tissue revealed a predominant membrane-bound signal. Relative quantification of gene expression indicated that Kv4.2 and KChIP2 mRNA and protein are expressed at comparable ratios in porcine and rat left ventricular tissues, which displays a large I _to. Collectively, these data demonstrate that the lack of a significant I _to in the porcine left ventricle does not result from dysfunctional or insufficiently expressed Kv4.2 and KChIP2 sub-units.     

心力衰竭家兔心室动作电位时程整复性变化对室性心律失常的影响

 目的：探讨压力负荷诱导的兔慢性心力衰竭(CHF)模型离体心室动作电位时程整复性(APDR)变化对室性心律失常(VA)的影响。方法：雄性新西兰大耳兔20只,随机分为对照(CTL)组和CHF组,每组10只。CHF模型制备采用经腹主动脉缩窄术,造模结束4周后行心脏超声检查评价造模结果。在整体心脏Langendorff灌流条件下行离体电生理研究,分别记录和测量心室不同位点的单相动作电位(MAP)及有效不应期(ERP),并绘制APDR曲线;对2组心脏进行快速电刺激,观察室性心律失常（VA）的诱发。结果：与CTL组相比,CHF组心室相同部位90%单相动作电位时程(MAPD90)、ERP及APDR曲线最大斜率(Smax)均明显增大(均P<0.01),且VA更容易诱发(均P<0.05);此外,CHF组动物APDR曲线Smax的变异系数(COV-Smax)均较CTL组增大(均P<0.05)。结论：CHF时心室APDR曲线Smax及COV-Smax均增大,促进室性心律失常的发生。     

Development and evaluation of a fully automated monophasic action potential analysis program

A fully automated program has been developed for analysing digitised cardiac monophasic action potentials (MAPs) of several animal species. Under diverse conditions, the program’s performance is evaluated by comparison with high-resolution manual analysis of action potential duration, MAP detection, baseline and plateau determination. For each variable, the differences between both forms of analysis are categorised according to species (rabbit, dog or baboon), intervention (control, sematilide or LY-190147), rhythm source (sinus or paced), and rates. They are then examined using ANOVA (null hypothesis: no difference between methods for any category). Intra-group differences are significant for baseline selection (p<0.05), and treatment effects are significant (p<0.05) for one species (baboon). However, the differences found are negligible when compared with expected measurement errors. Thus the program reliably detects and accurately analyses MAPs, independent of species, drug or pacing. The program’s strength is its use of simple heuristic algorithms to identify and profile MAP signals while rejecting spurious transients. These algorithms focus on the procedural aspects of automatic MAP detection and validation, with minimum use of complex mathematics. The program’s estimated throughput exceeds 8200 MAPs min⁻¹ on a 50 MHz i486 DX machine. With available data format conversion packages, signals from almost any data-acquisition source can be analysed.     

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K⁺ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1 ^−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1 ^−/− hearts: Quantification of APD₉₀, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD₉₀, between endocardial and epicardial APD₉₀ and (2) critical intervals for local re-excitation, given by differences between APD₉₀ and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD₉₀ alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD₉₀ restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 μM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1 ^−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1 ^−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1 ^−/− hearts.     

Exercise and Sleep Loss: Effects on Recovery Sleep

The effects of exercise and sleep loss on recovery sleep were studied in young male naval volunteers. For 1 hr out of every 4 hrs during a 40-hr period, 20 subjects rested in bed and 10 subjects bicycled. Eleven measures of recovery night sleep were selected for comparison of the bedrest and exercise groups. Only one reached significance under the conservative Dunn-Bonferroni criterion: the exercise group had a higher percent total sleep time. The results indicate that exercise does increase the effects of sleep loss on recovery sleep, but that there is no simple, direct effect on specific sleep stages.     

Haplotype Misclassification Resulting from Statistical Reconstruction and Genotype Error,and Its Impact on Association Estimates

Haplotypes are an important concept for genetic association studies, but involve uncertainty due to statistical reconstruction from single nucleotide polymorphism (SNP) genotypes and genotype error. We developed a re‐sampling approach to quantify haplotype misclassification probabilities and implemented the MC‐SIMEX approach to tackle this as a 3 × 3 misclassification problem. Using a previously published approach as a benchmark for comparison, we evaluated the performance of our approach by simulations and exemplified it on real data from 15 SNPs of the APM1 gene. Misclassification due to reconstruction error was small for most, but notable for some, especially rarer haplotypes. Genotype error added misclassification to all haplotypes resulting in a non‐negligible drop in sensitivity. In our real data example, the bias of association estimates due to reconstruction error alone reached ?48.2% for a 1% genotype error, indicating that haplotype misclassification should not be ignored if high genotype error can be expected. Our 3 × 3 misclassification view of haplotype error adds a novel perspective to currently used methods based on genotype intensities and expected number of haplotype copies. Our findings give a sense of the impact of haplotype error under realistic scenarios and underscore the importance of high‐quality genotyping, in which case the bias in haplotype association estimates is negligible.     

Differential effects of extracellular cesium on early afterdepolarizations in ventricular myocytes and arrhythmogenesis in isolated hearts of rats and guinea pigs

CsCl has been shown to be arrhythmogenic in-vivo and to cause early afterdepolarizations (EADs) in isolated cardiac preparations, but the underlying electrophysiological mechanisms are ill-defined. To elucidate these actions further, the effects of extracellular solutions containing 3 mM CsCl and either 2 mM KCl (Cs2K solution) or 5 mM KCl (Cs5K solution) on membrane potential and ionic currents in rat and guinea-pig ventricular myocytes were compared. Cs2K solution rapidly and reversibly inhibited outward I_K1, and reduced other K⁺ currents by about 20%. Current-clamped myocytes were rapidly hyperpolarized by this solution and action potentials were prolonged, but EADs were not observed. In contrast, EADs were triggered by E-4031, H₂O₂, and the pyrethroid tefluthrin. Membrane-potential changes reversed after replacing Cs2K with Cs5K solution, with the recovery of 50% of outward I_K1. These results suggest that Cs2K solution inhibited I_K1 and caused a late prolongation of the action-potential duration, but the affected membrane potentials were too negative to elicit EAD mechanisms. In isolated hearts perfused with modified Tyrodes, Cs2K, and Cs5K solutions, bradycardia and arrhythmias were evoked by both CsCl-containing solutions. A comparison of such results with the effects of these solutions on myocytes suggests that I_K1 inhibition and EADs in ventricular myocytes are unlikely to be involved in arrhythmogenesis under our conditions.     

Effects of denervation on resting membrane and action potentials of neonate rat fast and slow twitch muscles

During the first 20 days post partum of the rat, a period of rapid muscle growth, resting potentials and maximum rate of rise and overshoot of action potentials recorded from fast and slow twitch muscle fibres all increased, although did not reach adult values. The action potential of fast twitch muscle fibres had a greater maximum rate of rise and overshoot than that of slow twitch muscle fibres of the same age. Innervation had a marked influence upon maintenance of the electrical properties of muscle fibres in the neonate since denervation reduced the value of the resting potential and maximum rate of rise and overshoot of the action potential. Nevertheless, some differences between action potentials recorded from the two fibre types remained 4 days after denervation.     

社会心理干预对老年脑梗死患者康复效果的研究

目的 探讨老年脑梗死患者心理社会干预的康复效果.方法 将228例患者随机分成研究组和对照组,各114例.研究组在药物治疗、常规功能训练基础上,实施心理治疗、社会支持干预,对照组仅采用药物加常规功能训练.以神经功能缺陷评分标准、简式Fugl-Meyer运动功能评分、汉密尔顿抑郁量表、日常生活能力量表、生活质量量表作为评定工具,于患者入院当天、1月、3月、半年、1年各评定1次.结果 研究组较对照组患者神经功能缺陷程度、上下肢运动功能于治疗3月后好转或明显好转(P＜0.05～0.01);汉密顿抑郁量表总分1月后明显降低(P＜0.01),日常生活能力和总体生活质量3月后有所提高或显著性提高(P＜0.05～0.01).结论 心理社会干预能降低神经功能缺陷程度,增强上下肢运动功能,改善抑郁情绪,提高日常生活能力和生活质量,促进患者康复.     

Dependence of EDR Recovery Times and Other Electrodermal Measures on Scale of Measurement: A Methodological Clarification

Edelberg (1970) and Boucsein and Hoffmann (1979) found shorter recovery times with a constant voltage method as compared with a constant current method. In the present paper it is pointed out that this effect may be due to the use of different scales of measurement rather than to any electrophysiological aspects of the recording procedure. The mathematical relationship between resistance and conductance implies that recovery times are shorter for SCRs than for corresponding SRRs. For demonstration purposes, recovery times were computed from an SR record and compared with those computed from the same record after computerized transformation to SC. Research implications of the demonstrated effect are discussed, and the relevance of measurement scale to two other electrodermal measures, area below the curve and range-corrected amplitude, is pointed out.     

Physostigmine and norepinephrine: Effects of injection into the amygdala on taste associations

The present investigation was conducted to determine whether norepinephrine or acetylcholine systems of the amygdala could be involved in two adaptive feeding behaviors in the rat: development of taste aversion and recovery from neophobia. In a taste aversion paradigm, a single bilateral injection of physostigmine directly into the amygdala at the onset of an apomorphine-induced illness experience produced a time-dependent attenuation in the development of taste aversion; in contrast, norepinephrine had no disruptive effects. In a neophobia paradigm, norepinephrine injected directly into the amygdala after a novel taste experience resulted in a time-dependent attenuation in recovery from neophobia; however, physostigmine produced no disruptive effects. Hence, acetylcholine appears to mediate taste-illness associations, while norepinephrine plays an important role in recovery from neophobia, i.e., taste-“learned safety” associations.     

丹参酮ⅡA对急性脑缺血大鼠心肌单相动作电位的影响

目的:观察丹参酮ⅡA对急性脑缺血大鼠心肌动作电位的影响。方法:采用改良绳栓法建立急性脑缺血大鼠模型,实验分为假手术组、急性脑缺血组和丹参酮ⅡA干预组;对各组大鼠进行神经功能缺损评分,测定心电图,记录单相动作电位,试剂盒测定心肌肌钙蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)的含量。结果:丹参酮ⅡA降低脑缺血大鼠的神经功能缺损评分,并减少心电图异常的发生率与持续时间,延长脑缺血大鼠的有效不应期、复极化50%的时间与复极化90%的时间,降低cTnI和CK-MB含量。结论:丹参酮ⅡA具有稳定脑缺血大鼠心律的作用,可能与改善心肌缺血的作用有关。     

锌对培养的乳鼠心肌细胞自发性搏动和电活动的影响

本文研究了不同浓度的Zn对培养的乳鼠心肌细胞自发性搏动及心肌细胞动作电位的影响。实验结果表明,加Zn在0.125—2ppm范围内,自发性搏动群落的出现率增高,与对照组比较,P<0.001。但Zn的浓度超过一定范围(4 ppm),自发搏动率则呈降低趋势;8 ppm组明显低于对照组,P<0.01.Zn对心肌细胞动作电位的影响表现为动作电位的发放频率减慢,波幅降低,波宽变窄和最大除极速度减慢。     

音乐舞蹈对精神分裂症康复的影响

目的 了解音乐舞蹈对精神分裂症患者的康复作用。方法 应用BPRS、SANS、住院精神病人康复评定量表进行评估。结果 音乐舞蹈可以激活病人情绪、改善病人行为、提高病人主动性及改善病人的阴性症状。结论 音乐舞蹈是精神分裂症患者疾病康复的手段。     

Effects of Dexmedetomidine Infusion on the Recovery Profiles of Patients Undergoing Transurethral Resection

Transurethral resection has been the gold standard in the operative management of benign prostatic hyperplasia and bladder tumor; however, it is associated with several complications that may cause patient discomfort. We evaluated the usefulness of continuous infusion of dexmedetomidine on emergence agitation, hemodynamic status, and recovery profiles in patients undergoing elective surgery by a randomized clinical trial. Sixty patients aged 30 to 80 yr who were scheduled for elective transurethral resection under general anesthesia were included in this study. Participants were randomly assigned to two groups (control group, group C; dexmedetomidine group, group D). A total of 60 male patients were enrolled in this study and randomly assigned to group C (n=30) or group D (n=30). The quality of emergence in group D was marked by a significantly lower incidence of emergence agitation than in group C (P=0.015). Patients in group D therefore felt less discomfort induced by the indwelling Foley catheter than those in group C (P=0.022). No statistically significant differences were found between the two groups with respect to side effects including bradycardia (P=0.085), hypotension (P=0.640), and postoperative nausea and vomiting (P=0.389). Our study showed that intraoperative dexmedetomidine infusion effectively reduced the incidence and intensity of emergence agitation and catheter-induced bladder discomfort without delaying recovery time and discharge time, thus providing smooth emergence during the recovery period in patients undergoing transurethral resection (Clinical Trial Registry No. KT0001683).     

Solution of the Hodgkin-Huxley and cable equations on an array processor

This paper presents a method for the solution of equations for membrane ionic currents and the cable equation which describes the interaction of various segments in a compartmentalized model of the neuron. The method embodies some innovations which would speed calculation of propagating action potentials in any computing environment, but were specifically designed to permit the use of a relatively inexpensive array processor. The array processor produces an improvement in speed of calculation which permits exploration of a wider range of neuronal phenomena than has been previously feasible.     

择期性腹内手术病人的应激反应与心理准备的研究Ⅲ．心理准备对病人术后身体恢复的影响

本文报告了一种以收看录像为主的心理准备方法对剖腹手术病人术后身体恢复的影响。心理准备组的病人显示了较高的合作程度，术后麻醉药用量较少，开始正常身体活动的时间提早，揭示身体恢复较快，在术后拔除胃管、拆线时间、术后住院天数以及并发症的测量中，心理准备组同对照间无显著差别。     

国人正常膝关节几何学参数测量及临床意义

目的：从几何学角度对国人正常膝关节的参数进行测量,探讨其与某些膝关节疾病的关系.方法：选取国人无明显损坏的干燥股骨标本和胫骨标本各83例,测量股骨长度（G）,股骨内、外侧髁宽度（G1、G2）,股骨髁间窝宽度（G3）及深度（G4）,股骨内、外侧髁倾斜角（GD1、GD2）,胫骨近端平台内、外侧后倾角（JD1、JD2）,胫骨近端内、外侧平台的前后经（J1、J3）、左右径（J2、J4）,胫骨近端平台髁间隆起的宽度（J5）及高度（J6）.测量后对有关参数进行统计学分析.结果：除J2对J4外,其余膝关节几何参数测量值之间配对检验其差异存在统计学意义（P＜0.05）.线性参数之间呈正相关关系（P＜0.05）,而线性参数与角度参数之间无相关关系（P＞0.05）.结论：根据所测得的结果,建立了国人正常膝关节几何参数的数据库,为某些膝关节疾病的病程分型与治疗提供参考.