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Biomedical subjects

J Liebman

Publications and source records attributed to J Liebman.

At least 19 recordsLinked to original sources
PubMed2001

Some legal, social, and ethical issues related to the genetic testing revolution, as exemplified in the long QT syndrome.

Molecular Biology is revolutionizing medicine. There are a number of conditions, particularly exemplified by the long QT syndrome, where there is no structural abnormality but where a subset of patients is prone to sudden death. The issues of appropriate care are very complex, because there is tremendous overlap between patients with prolongation of the QT who remain asymptomatic and those with prolongation who are very symptomatic. Furthermore, even those who are prone to have one of the abnormal genes, may be asymptomatic. A large literature has developed, from both legal and ethical aspects, related to the fact that in genetic disease per se, not only is the person at risk, but so are many members of his or her family. A large literature has also developed as to which should be prime, the patient's privacy or the responsibility to make sure the entire family is knowledgeable and perhaps tested. At the present moment our care is based upon the fact that the precise identification of the gene is not yet available on a routine basis. This of course, may soon change. But we will still have difficult decisions to make. Obviously, we have a responsibility as physicians to be as precise as our discipline allows, but we have a responsibility to be flexible. Relief of anxiety, as an example, has to be a prime issue. This is certainly the case now when any information related to infants with potential sudden death is still incomplete. We must not approach the care of the patient in such a way that protection of the physician may interfere with appropriate care. The discussion necessarily includes a variety of aspects.

Ethics, Medical↗
PubMed2001

Using 12-lead ECG and synthesized VCG in detection of right ventricular hypertrophy with terminal right conduction delay versus partial right bundle branch block in the pediatric population.

In pediatric electrocardiogram (ECG) analysis, mild right ventricular hypertrophy (RVH) and especially mild RVH with terminal right conduction delay (RVHtcd) are often confused with partial right bundle branch block (PRBBB). This is problematic for computer ECG analysis algorithms and even for most experienced pediatric cardiologists. This study was designed to achieve better classification of mild RVHtcd and PRBBB by combining the 12-lead synthesized vectocardiogram (VCG) transverse plane measurements with scalar ECG measurements. Pediatric ECGs used in the study were recorded with 15 leads and a 500 Hz sampling rate at the Lucile Salter Packard Children's Hospital, Stanford University Medical Center. Out of 4,200 ECGs collected consecutively over a period of 18 months, 447 RVH, 335 RBBB and 589 Normal were interpreted by expert pediatric cardiologists, and were included in the study. Statistical comparison of ECG and VCG measurements were done in stratified ECG sets (412) that have a visually indistinguishable waveform pattern, 117 RVHtcd, 96 PRBBB and 199 normal, showed significant differences in initial and terminal vectors in the transverse plane. The mean angle of the initial vector was anterior (57.2 degrees +/- 41.8) in the normal group, left anterior in the PRBBB group (34.4 degrees +/- 39.5) and in the RVHtcd group (31.9 degrees +/- 41.0) and. The mean angle of the terminal vector was right anterior (158.3 degrees +/- 36.8) in the PRBBB group, rightward (179.7 degrees +/- 29.9) in the RVHtcd group and right posterior (212.6 degrees +/- 37.8) in the normal group. These are clearly applicable features for a classification algorithm. Significantly improved classification results were obtained from a new algorithm using combined ECG and VCG measurements versus an existing algorithm. The limitation of this study stems from the unavailability of a more reliable gold standard. It may be necessary to used body surface potentials obtained with a large number of electrodes to accurately differentiate the study groups.

Adolescent↗
PubMed2001

A comparative 3-month clinical investigation of the safety and efficacy of a battery-operated and a rechargeable oscillating-rotating power toothbrush.

PURPOSE: To compare the safety and efficacy of two oscillating-rotating power toothbrushes, the rechargeable Braun Oral-B D8 and the battery-powered Colgate Actibrush. MATERIALS AND METHODS: This was a randomized, examiner-blind, parallel-group study, carried out over 3 months of product use, involving a total of 113 healthy subjects with a plaque score of > or = 1.5 and a gingivitis score of > or = 1.1. Subjects were given written and verbal instructions in the use of their respective power brushes and were told to brush twice per day. At baseline, hard and soft tissues were examined, and plaque scores and gingival scores were recorded after 12-18 hrs of no oral hygiene. Subjects returned after 3 months, at which time soft and hard tissues were re-examined and plaque and gingivitis scores were recorded. RESULTS: No evidence was found of soft or hard tissue trauma and both brushes were considered to be safe when used according to the manufacturers' instructions. After 3 months, whole mouth plaque scores had decreased by 7% in the D8 group but had increased by 4.3% in the Actibrush group. The decrease from baseline in the D8 group was statistically significant, but the increase in the Actibrush group was not. The difference between the two groups was statistically significant both for the whole mouth and all individual sites. Whole mouth gingivitis scores were also reduced significantly from baseline in both groups, by 22.5% in the D8 group and by 17.5% in the Actibrush group. For whole mouth scores and all individual sites (interproximal, buccal and lingual), the D8 was significantly more effective than the Actibrush.

Adolescent↗
PubMed2001

A single-use and 3-month clinical investigation of the comparative efficacy of a battery-operated power toothbrush and a manual toothbrush.

PURPOSE: To compare the safety and efficacy of a manual toothbrush and a battery-operated power toothbrush in two separate studies, one utilizing a single-use design and the other a 3-month parallel-group design. MATERIALS AND METHODS: The toothbrushes compared in the two studies were the Oral-B CrossAction manual toothbrush and the Colgate Actibrush battery-operated power toothbrush. The single-use study, which used a single-blind, cross-over design, involved 71 healthy subjects, who were instructed to abstain from oral hygiene for 23-25 hours prior to brushing with each of the two toothbrushes. Plaque was measured using the Proximal Marginal Index (PMI) pre- and post-brushing. The 3-month parallel-group study involved a total of 113 subjects who had plaque (PMI), gingivitis and bleeding (Loe and Silness) scored at baseline and after 1 and 3 months of product use. RESULTS: In both studies, the two toothbrushes were found to be safe. In the single-use study, significantly greater amounts of plaque were removed by the CrossAction manual toothbrush than by the Actibrush for the whole mouth as well as for marginal and approximal sites (P < 0.001). In the 3-month study, significantly greater plaque reduction was achieved with the CrossAction brush, the advantage being significant at 1 month for all sites except lingual sites (P < 0.05). At 3 months, there were consistent numerical advantages in favor of the CrossAction at all sites except lingual sites. Reductions in gingivitis were found to be similar with both toothbrushes.

Adolescent↗
PubMed1999

The Women and Infants Demonstration Project: an integrated approach to AIDS prevention and research.

The Women and Infants Demonstration Project is a multisite, behavioral intervention research effort funded by the Centers for Disease Control. The project is evaluating a theory-based, integrated intervention model to increase the use of condoms for prevention of both sexually transmitted diseases (STDs) and unintended pregnancy among women and their partners at risk of infection with HIV. The importance of utilizing carefully targeted, credible and persistent risk reduction interventions to effect lasting behavior change has become evident over the last ten years of the AIDS epidemic. The theory-based intervention components being evaluated in this intervention study involve one-on-one stage-tailored outreach; the development and distribution of community-tailored HIV prevention materials, called role-model stories; and the development of organizational and peer networking, all within a community mobilization framework. This article describes each of the intervention components being evaluated during this 5-year study. Such an intervention effort represents an important contribution in the design of community-level AIDS prevention intervention efforts which support individual-level behavioral changes by women at risk for HIV and other sexually transmitted infections.

Adolescent↗
PubMed1998

Characterization of recombinant human cathepsin B expressed at high levels in baculovirus.

The lysosomal cysteine protease cathepsin B has been studied intensely for many years because of its unique characteristics and its potential involvement in disease states. A reproducible, high yield expression system for active recombinant protein is key to biochemical and biophysical studies as well as rational drug design. Although several microbial and mammalian expression systems for recombinant human cathepsin B have been described, these have been limited by low or variable yields. Further, in some of these systems hyper-glycosylation of the enzyme near the active site affects its activity. We describe a baculovirus expression system and purification scheme that solve all of these problems. Yields of active, protected enzyme were reproducibly in excess of 25 mg/L. Since this protein was not hyper-glycosylated, it had greater activity than cathepsin B produced in yeast systems as indicated by a threefold increase in Kcat. In addition, the biophysical properties of the baculovirus-expressed cathepsin B, as measured by dynamic light scattering, were more amenable to crystallographic study since the data indicated proteins of more uniform size. Therefore, this system for the production of recombinant human cathepsin B constitutes a major improvement in both quantity and quality over those previously reported. Further, we demonstrate that the manner of expression and purification of this enzyme has profound effects on its kinetic and physical parameters.

Baculoviridae↗
PubMed1995

Collagen II promoter and enhancer interact synergistically through Sp1 and distinct nuclear factors.

The collagen II gene is expressed primarily in chondrocytes. Its transcription is activated through the interaction of cell type-specific regulatory elements located in the promoter region and in the first intron. In this study, we found that a short promoter sequence including two GC boxes was required for efficient enhancer-mediated transcription. Gel-shift analysis, site mutations, and footprint analysis showed that one of the GC boxes bound functionally to an Sp1-related factor and that an oligonucleotide containing this GC box did interact with an enhancer-nuclear factor complex. Additionally, an enhancer-derived oligonucleotide was found to complex CIIZFP, a zinc-finger protein that binds to the enhancer within the first intron and Sp1, but only in presence of CIIZFP. Antibodies against Sp1 specifically inhibited the formation of this complex. Western/Southwestern analysis also showed that a protein complex including Sp1 was able to bind the enhancer and the promoter regions in non-denaturing conditions. This complex was dissociated by denaturation. These results suggest that the formation of a nuclear protein-mediated loop structure between the promoter and enhancer may regulate transcription of the collagen II gene transcription.

Animals↗
PubMed1993

ECG body surface potential mapping many years after successful surgery for coarctation of the aorta.

Patients with coarctation of the aorta (CoA) who previously underwent successful surgery are often diagnosed on standard electrocardiograms as having partial right bundle branch block. After surgery 24 patients with CoA had body surface potential mapping (BSPM) with the Case Western Reserve University 180 electrode system; of these 7 had additional aortic stenosis and none had ever had intracardiac communication. The average age at the initial surgery for CoA was 4.0 +/- 3.3 years and at the time of the BSPM it was 12.7 +/- 5.9 years. For the 17 patients with CoA without aortic stenosis the average age at the initial surgery was 5.0 +/- 3.4 years and at the time of the BSPM it was 14.2 +/- 6.0 years. In 11 of the 24 patients, a cardiac catheterization was performed, and each patient demonstrated normal pulmonary artery and right ventricular systolic pressure except for one child with 40 mmHg systolic. In the others all indications were that right ventricular pressure was normal. In 11 of the 24 patients, congestive heart failure had been present in infancy. All 24 cases had evidence for epicardial right ventricular breakthrough on the BSPM, a finding believed to indicate right ventricular activation from endocardium to epicardium via the normal Purkinje system. There were no findings on the BSPM suggesting that right bundle branch block was present. Right ventricular hypertrophy with or without terminal right conduction delay was present on the BSPM in 19 of the 24 patients (9 with additional left ventricular hypertrophy--left ventricular hypertrophy alone in 5). Right ventricular hypertrophy could be considered in 6 of 19 patients in the electrocardiogram, and in 11 of 19 in the vectorcardiogram. The mechanism for the persistent electrocardiographic right ventricular hypertrophy is postulated to involve right ventricular hyperplasia in utero or in early neonatal life, which never disappears.

Adolescent↗
PubMed1993

Cardiopulmonary responses to exercise in children with activity sensing rate responsive ventricular pacemakers.

The physiological benefits of activity sensing rate responsive ventricular pacing (VVIR) over fixed rate pacing (VVI) were investigated in 14 children during incremental cycle exercise. Based on their heart rhythm response during exercise, children were divided into two groups. Group I patients (13 +/- 4 years) remained in a paced-only rhythm when exercised. Group II patients (16 +/- 7 years) were paced at rest but converted to sinus rhythm with exercise. In Group I patients, the significant physiological benefits of VVIR over VVI pacing were evidenced by a 51% increase in peak heart rate (HRmax) and a 16% increase in exercise duration and maximum oxygen uptake (VO2max). Additionally, a 27% reduction in peak oxygen pulse (O2Pmax) was found, reflecting a similar decrease in stroke volume. The cardiorespiratory responses of Group I and II patients were compared in terms of percent of predicted normal values. Although Group I patients in the VVIR mode attained a better exercise performance than in the VVI mode and a normal O2Pmax (108% pred), their HRmax (62% pred) and VO2max (70% pred) fell far below normal values. In comparison, Group II patients, who went into sinus rhythm, achieved normal values for HRmax (84% pred), VO2max (90% pred), and O2Pmax (97% pred). The higher pacing rates attained by Group I patients in the VVIR mode may have allowed them to reach not only a higher cardiac output but also a more normal stroke volume at peak exercise than in the VVI mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Pennsylvania's medically uninsured population: findings from a statewide survey.

Pennsylvania is currently considering legislative options to expand coverage and improve access to medical care for state residents who lack health insurance. Relevant data are presented from a telephone survey of 10,809 Pennsylvania households. Almost nine percent (8.5%) of the state's population lacks health insurance, representing over one million people. Those most likely to be uninsured are children and young adults, non-whites and the poor. A substantial number of poor people are not covered by the state's Medicaid program. The uninsured report poorer health status, more obstacled to receiving care and greater use of hospital services for primary care.

Adolescent↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗