PubMed HealthSearch

Biomedical subjects

J Liebman

Publications and source records attributed to J Liebman.

At least 19 recordsLinked to original sources

Binding of glucocorticoid receptors to model DNA response elements.

DNA sequences were synthesized that contained the consensus 15-base pair glucocorticoid receptor binding site linked to flanking sequences of various lengths. Binding of these synthetic oligomers to glucocorticoid receptor, employing a reconstituted binding system with purified components, indicated that a minimal size of approximately 45 base pairs was necessary to bind the receptor optimally. Sequences containing multiple receptor binding sites competed more effectively for binding. These findings are consistent with recent demonstrations that multiple control elements act synergistically to affect transcriptional control by glucocorticoids and confirm that regions flanking the consensus GRE binding site are instrumental in optimizing binding interactions.

Animals

Electrocardiographic body surface potential mapping in the Wolff-Parkinson-White syndrome. Noninvasive determination of the ventricular insertion sites of accessory atrioventricular connections.

BACKGROUND: A reliable, noninvasive procedure to determine the location of accessory atrioventricular connections in patients with Wolff-Parkinson-White syndrome would add an important diagnostic tool to the clinical armamentarium. METHODS AND RESULTS: Body surface potential mapping (BSPM) using 180 electrodes in various-sized vests and displayed as a calibrated color map was used to determine the ventricular insertion site of the accessory atrioventricular (AV) connections in 34 patients with Wolff-Parkinson-White syndrome. Attempts were made to determine the 17 ventricular insertion sites described by Guiraudon et al. All 34 patients had an electrophysiologic study (EPS) at cardiac catheterization, and 18 had surgery so the ventricular insertion sites could be accurately located using EPS at surgery. A number of physiologic observations were also made with BSPM. CONCLUSIONS: The following conclusions were drawn: 1) BSPM using QRS analysis accurately predicts the ventricular insertion site of accessory AV connections in the presence of a delta wave in the electrocardiogram; 2) the ventricular insertion sites of accessory AV connections determined by BSPM and by EPS at surgery were identical or within one mapping site (1.5 cm or less) in all but four of 18 cases; three of the four exceptions had more than one accessory AV connection, and the other had a very broad ventricular insertion; 3) BSPM and EPS locations of the accessory AV connections correlated very well in the 34 cases despite the fact that BSPM determines the ventricular insertion site and EPS determines the atrial insertion site of the accessory AV connection; 4) as suggested by the three cases of multiple accessory AV connections, EPS and BSPM may be complementary since BSPM identified one pathway and EPS identified the other (in the case with a broad ventricular insertion, BSPM and EPS demonstrated different proportions of that insertion); 5) BSPM using ST-T analysis is very much less accurate in predicting the ventricular insertion site of accessory AV connections unless there is marked preexcitation; 6) standard electrocardiography using the Gallagher grid methodology (but with no attempt at stimulating maximal preexcitation) was not as accurate as QRS analysis of BSPM in predicting the ventricular insertion site of the accessory AV connection; however, exact comparison is hampered by the different number and size of the Gallagher and Guiraudon insertion sites; 7) BSPM using QRS analysis appears to be very accurate in predicting right ventricular versus left ventricular posteroseptal accessory AV connections; 8) typical epicardial right ventricular breakthrough, indicative of conduction via the specialized AV conduction system, occurs in all patients with left ventricular free wall accessory AV connections; 9) epicardial right ventricular breakthrough was not observed in cases with right ventricular free wall or anteroseptal accessory AV connections; 10) epicardial right ventricular breakthrough can occur in the presence of posteroseptal accessory AV connections, whether right or left ventricular; and 11) the delay in epicardial right ventricular breakthrough in cases with left ventricular insertion may provide a marker to estimate the degree of ventricular preexcitation.

Adult

Use of noninvasively determined right ventricular epicardial breakthrough in clinical diagnosis and understanding.

The researchers have presented a series of patients using their 180-electrode system with color mapping, in which the presence of RVBT either provided evidence for diagnosis or gave insight into anatomy and/or pathophysiology. This noninvasive tool is unique for the clinician and scientist and provides information not available with other noninvasive imaging techniques.

Bundle-Branch Block

QRS onset and offset detection accuracy improvement by additional spatial information in body surface potential maps.

A new automatic spatiotemporal algorithm has been developed for detecting QRS onset and offset in body surface potential mapping. The new algorithm, based on a spatial and temporal approach, along with three other algorithms (total energy, 3-lead, and median), was tested in 73 normal and abnormal patients. The reference or gold standard onset and offset times were determined visually by two experienced investigators. The results demonstrate that the new method is less sensitive to noise, to the temporal overlap of the QRS and other components, and to the spatial location changes of QRS initial and final activation. The spatiotemporal method resulted in very consistent findings, with a standard deviation of less than one third of the standard deviation in the next best method.

Algorithms

Multicategory classification of body surface potential maps.

A statistical classification method is suggested for body surface potential maps (BSPM). The initial data reduction utilizes the Fourier expansion and time integration, resulting in physiological-oriented features. Based on Fischer's criterion, optimal discriminant vectors are used to map the features to an optimal subdomain. Experimental criteria determine the dimensionality of the subdomain and the number of features to be mapped into it. Classification is performed in two steps. In the first, a k-nearest neighbor (k-NN) rule is used for every two-category problem, the results of which are fed into a voting rule for final classification. The method is tested with 123 patients divided into four categories: normal (NR), ischemia (IS), myocardial infarction (MI), and left bundle branch block (LB) patients. The success is between 88% (for IS) and 100% (for LB) for QRS segment integration. Departure maps were used to explain the misclassified patterns.

Algorithms

Analysis of the hypoplastic right ventricle utilizing electrocardiographic body surface potential mapping (BSPM).

The authors present electrocardiographic body surface potential maps (BSPMs) of 11 patients with hypoplastic right ventricle (HRV) of three types: type I, HRV with pulmonary atresia; type II, HRV with tricuspid atresia; and type III, HRV with tricuspid artesia and transposition of the great arteries. The BSPMs of all 11 patients demonstrated evidence for epicardial right ventricular breakthrough, indicating conduction through an intact right bundle branch and Purkinje system. Nonetheless, the BSPMs strongly suggested profound morphological, probably embryological, differences among the right ventricles of the three groups. The four patients with type I HRV had no evidence for conduction abnormality. The five patients with type II, HRV however, had very marked conduction abnormality. In four of these five, the standard ECG and VCG had initial forces suggesting left lateral wall myocardial infarction. The BSPMs showed no evidence for infarction but demonstrated very complicated slow initial activation, explaining why the initial QRS vector was to the right and posterior before extending leftward. In addition, in all five the initial positive potentials were unusually inferior and the initial negative potentials unusually superior. After the evidence for epicardial right ventricular breakthrough, the positive and negative potentials rapidly changed positions so that the positive potentials were unusually superior and the negative potentials unusually inferior, consistent with the BSPM of endocardial cushion defects. In four of these five there was marked delay of total ventricular activation time. Of the two patients with type III HRV, one had an initial QRS similar to that of type II. Neither had rapid change of inferior and superior positive and negative potentials after right ventricular breakthrough, and both had intraventricular slowing, one with partial left bundle branch block.

Adolescent

A cardiac potential mapping system.

The technical aspects of a multiple-purpose cardiac mapping system are presented. The authors begin with a brief history of hardware and software development and then concentrate on the major problems in acquiring high-quality recordings from the torso surface or from the epicardial surface and on the processing of the signals for display of color maps or other analysis. To achieve the desired adaptability to a variety of cardiac applications and experiments, they incorporated three parallel microprocessors that can record the signals from 240 electrodes and simultaneously provide display and analysis of the incoming cardiac data. While the parallel processors and modular software offer computational and flexibility advantages, the user interacts with an ordinary AT-compatible computer. This discussion is not a survey of the systems used in the many research laboratories or specific cardiac applications but is focused on experience in developing the specific hardware for such a multi-purpose instrument, and less specifically on the software that makes the system easy to use and adaptable to a variety of experimental and clinical situations.

Action Potentials

Isolated infundibuloarterial inversion (S,D,I): a newly recognized form of congenital heart disease.

A newly recognized form of congenital heart disease is presented that is characterized by viscero-atrial situs solitus (S), D-loop ventricles (D), and inverted normally related great arteries (I), the segmental combination being (S,D,I). This anomaly may be called isolated infundibuloarterial inversion because only the subsemilunar infundibulum and the great arteries are inverted, whereas the atrial and the ventricles are not. All three patients had atrioventricular concordance, ventriculoatrial concordance, dextrocardia, superoinferior ventricles, crisscross atrioventricular relations, underdevelopment of the right ventricle, a large ventricular septal defect, and an inverted tetralogy of Fallot type of malformation of the infundibulum and great arteries. The condition known as crisscross atrioventricular relations was found in these three patients to be a major ventricular malposition characterized by marked clockwise rotation of the ventricles, as seen from the front. Two of these three cases were diagnosed accurately and repaired successfully.

Angiocardiography

Respiration and the ECG: a study using body surface potential maps.

Body surface potential maps and an eccentric spheres model of the heart were used to investigate some of the factors that cause the surface ECG to change with respiration. Although the pattern of the surface maps shifted inferiorly with inspiration, the pattern itself did not change significantly, even with deep respiratory movements. However, the temporal ECGs at specific electrodes changed dramatically. The model simulations show that the contribution to the change in amplitude of the surface potential due to lung conductivity and ventricular volume changes is small. It is suggested that the major cause of the surface potential changes with inspiration is due to the change in heart position.

Adult

Electrocardiographic body surface potential maps of the QRS and T of normal young men. Qualitative description and selected quantifications.

A qualitative and quantitative analysis of the Body Surface Potential Maps (BSPM) of 40 young men, ages 19-41, is presented utilizing a 180 electrode system, with 135 anterior leads and 45 posterior leads. Evidence for epicardial right ventricular breakthrough was demonstrated in 36/40 at 27.9 +/- 6.8 ms, whereas our previous studies on normal children (average age 12.5 years) have demonstrated evidence for epicardial right ventricular breakthrough at 25.0 +/- 8.9 ms. The peak-to-peak magnitude at maximal potential (at 42.3 +/- 4.8 ms) was not significantly different from that of the children (4,430 +/- 1,165 microV), and the peak-to-peak magnitude of ST-T was virtually the same as that of the children (1,182 +/- 376.2 microV). The terminal activation pattern of late QRS on the body surface map appeared in the true posterior, anterior superior, posterior right superior and/or right anterior superior positions, in order of frequency. There were other regions appearing less frequently. In contrast, this pattern in children was seen only in the anterior superior, right anterior superior, posterior right superior, and true posterior in order of frequency. In 18/40, the body surface manifestation of repolarization was seen an average of 9.4 +/- 4.8 ms before the end of the QRS. A new pseudocolor display with 31 color levels representing body surface potentials allowed excellent resolution of isopotential detail.

Adult

Effects of ethanol on in vitro ciliary motility.

Consumption of ethanol can impair lung function and slow total lung clearance. High concentrations of ethanol have been shown to slow or arrest ciliary beating. This study examined the effects of concentrations of alcohol comparable to blood levels achieved from social drinking on ciliary beat frequency. We obtained ciliated cells by brushing the trachea of unanesthetized sheep during fiber-optic bronchoscopy. The cells were suspended in a perfusion chamber and physiological conditions were maintained in vitro. Ciliary beat frequency and synchrony were determined by slow-motion analysis of video images obtained by interference contrast microscopy. Metachronal ciliary coordination was observed in all preparations. The ciliary beat frequency was stimulated at ethanol concentrations from 0.01 up to but not including 0.1%, unchanged at 0.5 and 1%, and slowed at 2%. While confirming inhibition of ciliary motility at very high ethanol levels, we observed no acute impairment of ciliary function at ethanol concentrations comparable to those achieved from social drinking. Indeed, we found an unexpected stimulation of ciliary beating at low levels of ethanol. How this alteration in ciliary beating would affect pulmonary clearance remains unknown at this time.

Animals

Twenty-five-year experience with ventricular septal defect in infants and children.

Three hundred eighty-one children with isolated VSD were catheterized from 1960 through 1985, 228 of whom were first catheterized in the first year of life. Defect size was defined by the right-to-left ventricular systolic pressure ratio. Patients with small VSD had a good outcome, with no pulmonary vascular disease. Seventy-five percent of patients with moderate VSDs did not require surgery, and 58% had normal pulmonary artery pressures documented on a second catheterization. Of those patients with large VSDs who underwent serial catheterizations in the first year of life before surgery, 62% had partial closure, and pulmonary vascular resistance rose in 21%. None developed pulmonary vascular disease after surgery. Fewer large-restrictive than nonrestrictive VSDs required surgery in infancy (12% vs 51%; p less than 0.005), and more closed enough to never require surgery (62% vs 27%; p less than 0.005, chi square). Surgery is rarely necessary for patients with small and moderate-sized VSDs in the first year and is usually never necessary because of the expected decrease in size. Few patients with large-restrictive VSDs have an increase in pulmonary vascular resistance, many defects decrease in size, and most patients never need surgery. Patients who have a nonrestrictive VSD have an excellent prognosis with appropriate management.

Aortic Valve Insufficiency

CGS 10746B: an atypical antipsychotic candidate that selectively decreases dopamine release at behaviorally effective doses.

CGS 10746B, a benzothiadiazepine, has a behavioral profile in mice and monkeys similar to the atypical antipsychotic clozapine. Unlike clozapine, CGS 10746B suppresses dopamine neuron firing rates and, when administered at behaviorally effective doses by the oral or intraperitoneal route, decreases neostriatal dopamine release without changing dopamine metabolism or occupying D2 receptors. CGS 10746B is the first atypical antipsychotic candidate that selectively decreases dopamine release.

Action Potentials

Hepatic dysfunction and cardiovascular abnormalities. Occurrence in infants, children, and young adults.

In infants and children, the effect of heart failure and/or cyanotic heart disease on the liver has not been well documented, nor has there been any comparison between the degree of liver dysfunction and hemodynamic factors. Sixty-five patients with cardiovascular abnormalities were examined. Hepatic function, as indicated by laboratory data and histologic liver studies, was compared with the following categories of cardiovascular dysfunction: hypoxemia, systemic venous congestion, and low cardiac output. If any one of these factors was present, or any combination, abnormalities of liver function were usually noted. Patients with both hypoxemia and systemic venous congestion had marked hepatic dysfunction. Those with low cardiac output had the most severe abnormalities. Serial studies indicated that liver function correlated with cardiac status.

Adolescent

A 20-year review of ostium primum defect repair in children.

Between July, 1963, and July, 1983, a total of 69 patients (35 boys and 34 girls) underwent ostium primum defect repair. There were four perioperative deaths and four patients were subsequently lost to follow-up, leaving 61 children followed for 6 months to 20 years (mean 5 years). Results of surgery were assessed by cardiac catheterization in 17 of 61 patients, while the remaining patients were evaluated noninvasively. Postoperative mitral insufficiency was found to be absent in 19 patients, mild to trivial in 35, moderate in four, and severe in two. Four patients were found to have large residual atrial septal defects. Significant late postoperative arrhythmias were found in 14 of 61 patients. The types of arrhythmias included isolated complete atrioventricular block in 5 of 14, complete atrioventricular block with sinus node dysfunction in 2 of 14, and isolated sinus node dysfunction in 7 of 14. Pacemakers have been implanted in 8 of 14 of these patients. Based on this 20-year review of a large number of children: (1) ostium primum defect repair is associated with a low mortality rate, (2) residual mitral insufficiency although common is usually mild to trivial and nonprogressive, and (3) significant arrhythmias are a frequent complication and often require pacemaker implantation.

Adolescent