脑电地形图在脑梗塞的临床应用

通过２２例脑梗塞与１０例脑动脉硬化症对照，结合临床、ＣＴ与ＥＥＧ，对脑梗塞的脑电地形图（ＢＥＡＭ）进行研究。结果：梗塞组ＢＥＡＭ和ＥＥＧ判定结果与ＣＴ、临床定侧定位的符合率分别为６８．２％和１８．２％，Ｐ＜０．０１。其中５例浅表中大灶脑梗塞的ＢＥＡＭ和ＥＥＧ与ＣＴ完全相符率分别为１００％与８０％，Ｐ＞０．０５；１７例深部小灶梗塞和ＣＴ（－）的ＢＥＡＭ和ＥＥＧ与ＣＴ、临床定位符合率分别为５８．８％与０％，Ｐ＜０．００１。提示：脑梗塞的ＢＥＡＭ与ＥＥＧ比较，浅表中大灶梗塞，ＢＥＡＭ无明显优势，深部小灶梗塞ＢＥＡＭ优于ＥＥＧ；ＢＥＡＭ的主要定侧定位频段为８↑或／及α↓；ＢＥＡＭ改变与患者病情有一定关系，但主要取决于梗塞部位；部分病例ＢＥＡＭ的改变早于ＣＴ。     

Computer based screening of compound databases: 1. Preselection of benzamidine-based thrombin inhibitors

We present a computational protocol which uses the known three-dimensional structure of a target enzyme to identify possible ligands from databases of compounds with low molecular weight. This is accomplished by first mapping the essential interactions in the binding site with the program GRID. The resulting regions of favorable interaction between target and ligand are translated into a database query, and with UNITY a flexible 3D database search is performed. The feasibility of this approach is calibrated with thrombin as the target. Our results show that the resulting hit lists are enriched with thrombin inhibitors compared to the total database.     

A genetic algorithm for the automated generation of small organic molecules: Drug design using an evolutionary algorithm

Rational drug design involves finding solutions to large combinatorial problems for which an exhaustive search is impractical. Genetic algorithms provide a novel tool for the investigation of such problems. These are a class of algorithms that mimic some of the major characteristics of Darwinian evolution. LEA has been designed in order to conceive novel small organic molecules which satisfy quantitative structure-activity relationship based rules (fitness). The fitness consists of a sum of constraints that are range properties. The algorithm takes an initial set of fragments and iteratively improves them by means of crossover and mutation operators that are related to those involved in Darwinian evolution. The basis of the algorithm, its implementation and parameterization, are described together with an application in de novo molecular design of new retinoids. The results may be promising for chemical synthesis and show that this tool may find extensive applications in de novo drug design projects.     

Mapping of atrial activation during sustained atrial fibrillation in dogs with rapid ventricular pacing induced heart failure: evidence for a role of driver regions

INTRODUCTION: Dogs with rapid ventricular pacing (RVP)-induced congestive heart failure (CHF) have inducible atrial tachycardia, flutter, and fibrillation (AF). We tested the hypothesis that rapid atrial activation in multiple regions and at different rates is responsible for sustained AF in this CHF model. METHODS AND RESULTS: We studied 12 episodes of sustained (>10 minutes) AF induced in 12 dogs with CHF produced by 3-6 weeks of RVP at 230 beats/minute. High-density mapping of AF was performed using 382 unipolar atrial electrograms recorded simultaneously from epicardial electrodes on the right (RA) and left atria (LA) and Bachmann's bundle. AF mechanisms were based on Fast Fourier Transform (FFT) analysis and activation sequence mapping. A driver was defined as a rapid stable activation region with a single dominant frequency peak in FFT analysis. During AF, three FFT and activation patterns were seen: (1) a single LA driver (7.8 +/- 1.1 Hz) near the pulmonary veins (PVs) with irregular activation in the rest of the atria (n = 4); (2) simultaneous, multisite, biatrial drivers at differing frequencies (LA vs RA dominant frequency gradient: 1.3 +/- 0.8 Hz) near the PVs (8.4 +/- 0.3 Hz) and high RA (8.5 +/- 1.5 Hz) (n = 7); and (3) biatrial irregular activation with multiple and/or broadband frequency peaks without a dominant frequency. (LA: 7.1-11.4 Hz; RA: 5.9-7.7 Hz) (n = 1). Atrial drivers had either a focal activation pattern or were due to a macroreentrant circuit around the PVs. CONCLUSIONS: In this CHF model, FFT analysis and activation sequence mapping demonstrate that sustained AF is characterized by single and multiple, stable LA and RA drivers with predominant sources in the PVs and high RA causing fibrillatory conduction.     

Ventricular Tachycardia/Ventricular Fibrillation Ablation in the Setting of Ischemic Heart Disease

Recurrent ventricular tachycardia (VT) in the setting of coronary artery disease is frequently a life-threatening electrophysiologic emergency. Even in patients with an implantable defibrillator, recurrent VT is frequently accompanied by repeated and disabling shock therapy. Catheter ablative therapy offers the ability to provide immediate control of recurrent VT. Long-term elimination of VT should be anticipated in most patients. This article reviews the strategies, tools, techniques, and expected outcome for catheter ablation of stable and unstable ventricular arrhythmias in the setting ischemic heart disease.     

High-Density Circumferential Pulmonary Vein Mapping with a 20-Pole Expandable Circular Mapping Catheter

The differentiation of pulmonary vein (PV) electrograms from atrial far-field signals during PV isolation (PVI) for atrial fibrillation (AF) may be difficult. In addition, owing to highly variable PV ostial sizes, current fixed-diameter circular PV mapping catheters may not yield optimal electrograms. We evaluated an expandable, circular 15–25 mm diameter, 20-pole mapping catheter for PV mapping during sustained AF in 25 patients. After selective PV angiography to define the ostial position and size, the catheter was introduced into each PV and withdrawn to the most stable proximal position, with optimal wall contact ensured by progressive loop expansion. At each PV ostium, electrograms recorded at high resolution (HR) were compared with those recorded at a resolution similar to that of a standard 10-pole Lasso catheter. After PVI performed during ongoing AF, the presence of residual far-field potentials (FFP) under both set-ups was compared. We mapped 97 PV, including 4 pairs with common ostia. In the HR recordings, the PV potentials had greater amplitude (0.5 ± 0.1 vs 0.3 ± 0.1 mV, P = 0.001) and fragmentation, whereas left atrial FFP were minimized. After successful isolation of all PV, FFP were observed in 33% of left superior and 28% of left inferior PV on the HR recordings, compared to 66% and 61%, respectively under normal resolution. Catheter stability and optimal wall contact, in combination with HR electrograms can optimize circumferential PV mapping during AF and improve the discrimination of FFP postablation.     

Chromosomal rearrangements in Xq and premature ovarian failure: mapping of 25 new cases and review of the literature

BACKGROUND: Chromosomal rearrangements in Xq are frequently associated with premature ovarian failure (POF) and have defined a POF 'critical region'. Search for genes responsible for the disorder has been elusive. METHODS: We report mapping of novel breakpoints of X;autosome-balanced translocations and interstitial deletions and a review of published X chromosome rearrangements. RESULTS: All the novel POF-associated rearrangements were mapped outside and often very distant from genes. The majority mapped to a gene-poor region in Xq21. In the same region, deletions were reported in women who apparently did not have problems conceiving. Expression analysis of genes flanking breakpoints clustered in a 2-Mb region of Xq21 failed to demonstrate ovary-specific genes. CONCLUSIONS: Our results excluded most of the possible explanations for the POF phenotype and suggested that POF should be ascribed to a position effect of the breakpoints on flanking genes. We also showed that while the X breakpoint may affect X-linked genes in the distal part of Xq, from Xq23 to Xq28, interruption of the critical region in Xq21 could be explained by a position effect of the Xq critical region on genes flanking the autosomal breakpoints.     

Initial validation of a novel ECGI system for localization of premature ventricular contractions and ventricular tachycardia in structurally normal and abnormal hearts

Background

View into Ventricular Onset (VIVO) is a novel ECGI system that uses 3D body surface imaging, myocardial CT/MRI, and 12?lead ECG to localize earliest ventricular activation through analysis of simulated and clinical vector cardiograms.

心脏磁共振诊断非缺血性心肌纤维化中的应用进展

心脏磁共振使非缺血性心肌纤维化的无创诊断和预后评价成为了可能。目前的半定量延迟强化显像,影响因素较多,在弥漫性心肌纤维化中很难形成对比,得到可靠信息。T1mapping是一种新型的可定量评估心肌特征的方法,对局部及弥漫性心肌病变,心肌细胞外间质扩大及水肿方面有着良好的应用前景,助于对弥漫性病变进行早期诊断和治疗。