Biomedical subjects

K L Lee

Publications and source records attributed to K L Lee.

At least 163 records · Page 9Linked to original sources

PubMed1989

Painless exercise ST deviation on the treadmill: long-term prognosis.

To evaluate the clinical correlates and long-term prognostic significance of silent ischemia during exercise, 1,698 consecutive symptomatic patients with coronary artery disease who had both treadmill testing and cardiac catheterization were studied. These patients were classified into three groups: Group 1 = patients with no exercise ST deviation (n = 856), Group 2 = patients with painless exercise ST deviation (n = 242) and Group 3 = patients with both angina and ST segment deviation during exercise (n = 600). Patients with exercise angina had a history of a longer and more aggressive anginal course (with a greater frequency of angina, with nocturnal episodes and/or progressive symptom pattern) and more severe coronary artery disease (almost two-thirds had three vessel disease). The 5 year survival rate among the patients with painless ST deviation was similar to that of patients without ST deviation (86% and 88%, respectively) and was significantly better than that of patients with both symptoms and ST deviation (5 year survival rate 73% in patients with exercise-limiting angina). Similar trends were obtained in subgroups defined by the amount of coronary artery disease present. In the total study group of 1,698 patients, silent ischemia on the treadmill was not a benign finding (average annual mortality rate 2.8%) but, compared with symptomatic ischemia, did indicate a subgroup of patients with coronary artery disease who had a less aggressive anginal course, less coronary artery disease and a better prognosis. Thus, silent ischemia during exercise testing in patients with symptomatic coronary artery disease represents an intermediate risk response in the spectrum of exercise-induced ischemia.

Adult↗

PubMed1989

A randomized controlled trial of intravenous tissue plasminogen activator and early intravenous heparin in acute myocardial infarction.

To evaluate the coronary thrombolytic efficacy of tissue plasminogen activator (t-PA) and early intravenous heparin, 134 patients with acute myocardial infarction were randomly assigned to combination therapy or t-PA only. At a median of 2.78 hours from symptom onset, 64 patients received both t-PA (1.5 mg/kg/4 hr) and a bolus of 10,000 units heparin, whereas 70 patients received t-PA alone at the same dose. All patients underwent coronary angiography 90 minutes after initiation of therapy to determine infarct vessel patency status, after which time the control group patients were eligible to receive heparin. Baseline demographic and angiographic characteristics were similar for the groups. Infarct vessel patency was 50 of 63 (79%) for combination t-PA and heparin and 54 of 68 (79%) for t-PA alone. Bleeding complications, as reflected by need for transfusion, were similar in the two groups: 13% in the patients treated with t-PA and heparin compared with 18% in patients treated with t-PA only (p = 0.53). The only intracranial hemorrhage in the trial occurred in a patient initially treated without heparin. Fibrinogen at 50 minutes after therapy was 32% decreased from baseline for the t-PA and heparin-treated patients compared with a 39% decrease in the control group. Predischarge left ventricular ejection fraction was similar for the two groups: 49.0 +/- 10.1% versus 50.2 +/- 11.9% for combined versus t-PA only therapy, respectively. We conclude that early intravenous heparin does not facilitate the fibrinolytic effect of t-PA at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

PubMed1989

Recurrent ischemia without warning. Analysis of risk factors for in-hospital ischemic events following successful thrombolysis with intravenous tissue plasminogen activator.

Ischemic events after successful thrombolysis have been reported to occur in 18-32% of patients treated for acute myocardial infarction with thrombolytic therapy, and previous studies in which patients received streptokinase suggest that risk of early recurrent ischemia is closely related to the presence of a high-grade residual stenosis. If these events are predictable after intravenous recombinant tissue-plasminogen activator (rt-PA) thrombolytic therapy, then further intervention after its use could be targeted at selected patients. One-hundred ninety-two patients from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I and TAMI III trials had successful rt-PA-mediated thrombolysis without immediate coronary angioplasty (PTCA). One-hundred seventy-four of these patients (92%) had prehospital discharge angiography. The mean age was 56 +/- 11 years; 81% were men; the infarct-related artery was the left anterior descending in 76 (39.8%), the left circumflex in 24 (12.6%), and the right coronary artery in 91 (47.6%). Thrombolysis with rt-PA resulted in a residual 73 +/- 13% diameter and 0.95 +/- 0.51 mm stenosis by quantitative coronary arteriography, and Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 in 59.2% and 3 in 40.8% of stenoses as assessed on angiograms obtained 90 minutes after the initiation of rt-PA therapy. Recurrent ischemic events (ischemia requiring emergency percutaneous transluminal coronary angioplasty or urgent bypass surgery, reocclusion of the infarct-related artery, or cardiac death) occurred in 41 patients (21.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

PubMed1989

Clinical experience and predicting survival in coronary disease.

To study the accuracy with which long-term prognosis can be predicted in patients with coronary artery disease, prognostic predictions obtained from a large, diverse sample of practicing cardiologists were compared with predictions from a multivariable statistical model. Test samples of 10 patients each were selected from a large series of medically treated patients with significant coronary disease. Using detailed clinical summaries, 49 cardiologists each predicted the probability of 3-year survival and infarction-free survival for 10 patients. Cox regression models, developed using patients who were not in the test samples, were also used to predict corresponding outcome probabilities for each test patient. Overall, the model estimates of prognosis were significantly better than the doctors' predictions. The rank correlation of model predictions with 3-year survival was 0.60, compared with 0.52 for the physicians. Model predictions added significant prognostic information to the doctors' predictions, whereas the converse was not true. Where predictions were made by multiple doctors, the inter-physician variability was substantial. Neither practice characteristics nor extent of clinical experience significantly affected the physicians' predictive accuracy. In coronary artery disease, statistical models developed from carefully collected data can provide prognostic predictions that are more accurate than predictions of experienced clinicians made from detailed case summaries.

Coronary Disease↗

PubMed1988

Structure of a multihormonally regulated rat gene.

Gene 33, a rat gene transcriptionally enhanced by glucocorticoids, insulin, or cyclic AMP, was isolated from a library of rat genomic DNA and characterized by sequence comparison to a full-length cDNA. The structural gene spans 13,500 bp encoding 2970 bp of exon sequences interrupted by three introns of about 9600, 101 and 811 bp, respectively. Exons (5' to 3') are 198, 194, 77 and 2501 bp in length; the first of these initiates at the transcriptional start point determined by S1 nuclease mapping. The 5'-flanking DNA contains several putative transcriptional control elements including TATA and CAAT boxes and a binding site for the Sp1 transcription factor in the usual locations proximal to the start point. Sequences resembling known glucocorticoid and cyclic AMP regulatory elements are also found upstream. A chimeric plasmid was constructed containing putative gene 33 regulatory elements fused to the Escherichia coli gene cat, encoding the enzyme chloramphenicol acetyltransferase, and transfected into cultured fibroblasts. Transient expression assays established that this gene 33 DNA is effective in promoting transcription.

Animals↗

PubMed1988

Transient alterations of the QRS complex and ST segment during percutaneous transluminal balloon angioplasty of the left anterior descending coronary artery.

Using continuous 3-lead electrocardiographic (ECG) recordings in 19 patients undergoing elective percutaneous transluminal coronary artery angioplasty (PTCA) of the left anterior descending (LAD) artery, this study described the dynamic changes of the ST segment and the R- and S-wave amplitudes that occur during transient myocardial ischemia. The waveforms from lead V2 were quantified at 10-second intervals during the length of the balloon inflation that produced the greatest extent of ST-segment deviation. The simultaneous changes that occurred in leads aVF and V5 were also observed, but not quantified. Measurements of R- and S-wave amplitudes were performed during maximal ischemia from both the PR- and the J-ST-segment baselines to determine which of these most nearly maintained its control position during ischemia. The results indicate that the R-wave amplitude is best determined from the PR-segment baseline (p = 0.0007), while the S wave is best determined from the J-ST-segment baseline (p = 0.03). However, only a portion of the QRS changes observed during PTCA could be accounted for by the baseline shift. There were additional QRS changes during ischemia in 11 of the patients (58%) suggestive of conduction disturbances in 3 endocardial sites: left septal, right septal and left anterosuperior. It is hypothesized that these changes may represent ischemia-induced delay in conduction ("periischemic block") previously thought to occur only with myocardial infarction.

Angioplasty, Balloon↗

PubMed1988

Regression models in clinical studies: determining relationships between predictors and response.

Multiple regression models are increasingly being applied to clinical studies. Such models are powerful analytic tools that yield valid statistical inferences and make reliable predictions if various assumptions are satisfied. Two types of assumptions made by regression models concern the distribution of the response variable and the nature or shape of the relationship between the predictors and the response. This paper addresses the latter assumption by applying a direct and flexible approach, cubic spline functions, to two widely used models: the logistic regression model for binary responses and the Cox proportional hazards regression model for survival time data.

Humans↗

PubMed1988

Clinical behavior of paroxysmal atrial tachycardia.

Paroxysmal atrial tachycardia is a familiar arrhythmia that has been studied extensively for the past decade using intracardiac recording and programmed electrical stimulation. These studies have thoroughly documented the mechanisms of this arrhythmia and its associated atrioventricular conduction abnormalities, but little is known about the spontaneous clinical behavior of this arrhythmia. A group of 34 patients with paroxysmal atrial tachycardia were studied using telephone transmission of the electrocardiogram to document recurrent tachycardia. When antiarrhythmic therapy was withdrawn, median time to the first recurrence of tachycardia was 19 days, mean heart rate during spontaneous tachycardia was 203.5 +/- 34.9 beats/min, and the median duration of an attack was 20 minutes. In a group of patients who were followed while many consecutive attacks were documented, the time intervals between attacks were found to be uncorrelated and to fit an exponential probability distribution (i.e., the occurrence of paroxysmal atrial tachycardia behaved like a Poisson process). Paroxysmal atrial tachycardia does not occur in a chaotic and unpredictable fashion; it is an event that occurs according to common probability models.

Electrocardiography↗

PubMed1988

Evaluation of a QRS scoring system for estimating myocardial infarct size. VI: Identification of screening criteria for non-acute myocardial infarcts.

Each of the 54 criteria in the Selvester 32-point QRS scoring system for estimation of myocardial infarct (MI) size has attained greater than or equal to 95% specificity in normal subjects. This study was performed to identify a subset of those criteria with cumulative specificity greater than or equal to 95% and maximal sensitivity for use in screening for the presence of non-acute MI. Coronary angiography and left ventriculography were used to identify 500 normal subjects, 60 patients with isolated anterior MI and 62 patients with isolated inferior MI. Patients with the QRS confounding factors of ventricular hypertrophy, fascicular block or bundle branch block on their electrocardiogram were not included. Using stepwise logistic regression analysis, the screening criteria identified were: (1) Q greater than or equal to 30 ms in aVF, (2) R less than or equal to 10 ms and less than or equal to 0.1 mV in V2 and (3) R greater than or equal to 40 ms in V1. Cumulatively, these 3 screening criteria achieved 84% and 77% sensitivities for inferior and anterior MI groups, respectively. Thus, a set of 3 criteria from the Selvester QRS scoring system is capable of identifying single non-acute anterior or inferior MI in 80% of patients, and falsely indicating presence of MI in only 5% of normal subjects.

Adult↗

PubMed1988

Use of initial ST-segment deviation for prediction of final electrocardiographic size of acute myocardial infarcts.

The decision to administer thrombolytic therapy for limitation of acute myocardial infarction (AMI) size must occur when only the history, physical examination and 12-lead electrocardiogram of a patient are available. A method that could quickly assess the amount of jeopardized myocardium would greatly aid the physician. This study developed formulas from 68 anterior and 80 inferior AMI patients using the extent of initial ST-segment deviation (ST delta) to predict the final AMI size estimated by the Selvester QRS score in a population not receiving reperfusion therapy. Inclusion required: initial anterior or inferior AMI; admission electrocardiogram less than or equal to 8 hours after the onset of symptoms with evidence of epicardial injury; elevated creatine kinase-MB; a predischarge electrocardiogram taken greater than or equal to 72 hours after admission; and no AMI extension before the predischarge electrocardiogram. The extent of epicardial injury was quantified by counting the number of leads with greater than or equal to 0.1 mm ST delta, by the sum (sigma) of ST delta in all leads and by the sigma ST delta in the lead groups associated with each AMI location. These results were compared to the AMI size estimated from the predischarge electrocardiogram. Univariable and multivariable analyses generated these formulas for AMI size: anterior = 3[1.5 (number leads ST increases) - 0.4]; inferior = 3[0.6 (sigma ST increases II, III, aVF) + 2.0]. Thus, formulas based on quantitative measurements of ST delta on the admission electrocardiogram are predictive of final QRS-estimated AMI size, and may be useful in determining the efficacy of acute reperfusion therapy.

Electrocardiography↗

PubMed1988

Gene-specific acquisition of hormonal responsiveness in rat liver during development.

Cloned cDNAs were used in hybridization analyses to assess hormonal responsiveness of two similarly regulated genes in livers of late-term fetal rats. Transcription of the tyrosine aminotransferase gene and of gene 33 (Lee et al.: J Biol Chem 260:16433-16438, 1985) is enhanced by glucocorticoids and by each of the usually antagonistic hormonal agents, insulin and cAMP, in adult liver, and that of both genes is developmentally activated at or just prior to birth. The mRNA of gene 33 was found to be significantly increased by each of the hormonal regulators in livers of fetuses treated in utero. Expression of the nearly silent aminotransferase gene in fetal liver was appreciably increased by cAMP but was refractory to control by either glucocorticoids or insulin; capacity of this gene to respond to insulin was not realized until several days postpartum. The data indicate specificity in the developmental acquisition of the capacity of individual genes to respond to hormonal regulators.

Animals↗

PubMed1988

Changes in hepatic differentiation following treatment of rat fetuses with 5-azacytidine.

Rat fetuses of 20 days gestational age were treated in utero with 5-azacytidine. Within 14 to 18 h after treatment several significant changes in the fetal livers were observed, including a dramatic maturation of hepatocyte morphology with little alteration in hematopoietic elements. Assessment of mRNA levels by hybridization to cloned cDNAs, together with other measures of gene expression, established that the change in hepatocyte morphology was associated with strong activation of expression of genes normally activated later in development, including those coding for the liver enzymes tyrosine aminotransferase and phosphoenolcarboxykinase and a gene of unknown specificity that is regulated in liver much like the aminotransferase. Rates of transcription of two of these genes, measured in isolated nuclei, were significantly increased after 5-azacytidine treatment. Expression of alpha-fetoprotein, normally declining during the perinatal period of development, was reactivated following treatment with the drug, while albumin expression was somewhat enhanced. For the most part the changes observed reflect temporal advancement of events normally programmed to occur later in differentiation of the liver. These changes appear to be the consequence of multiple effects of 5-azacytidine, including enhanced gene transcription and stabilization of gene products.

5-Methylcytosine↗

PubMed1988

Comparison of predictions based on observational data with the results of randomized controlled clinical trials of coronary artery bypass surgery.

Clinical decisions are most secure when based on findings from several large randomized clinical trials, but relevant randomized trial data are often unavailable. Analyses using clinical data bases might provide useful information if statistical methods can adequately correct for the lack of randomization. To test this approach, the findings of the three major randomized trials of coronary bypass surgery were compared with predictions of multivariable statistical models derived from observations in the Duke Cardiovascular Disease Databank. Clinical characteristics of patients at Duke University Medical Center who met eligibility requirements for each major randomized trial were used in the models to predict 5 year survival rates expected for medical and surgical therapy in each randomized trial. Model predictions agreed well with randomized trial results and were within the 95% confidence limits of the observed survival rates in 24 (92%) of 26 clinical subgroups. The overall correlation between predicted and observed survival rates was good (Spearman coefficient 0.73, p less than 0.0001). These results suggest that carefully performed analyses of observational data can complement the results of randomized trials.

Angina Pectoris↗

PubMed1988

Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease.

To examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutive patients who had symptomatic significant (greater than or equal to 75% stenosis) coronary artery disease were studied. Using the Cox regression model in a randomly selected half of the patients, the prognostically independent clinical variables were weighted and arranged into a simple angina score: angina score = angina course X (1 + daily angina frequency) + ST-T changes, where angina course was equal to 3 if unstable or variant angina was present, 2 if the patient's angina was progressive with nocturnal episodes, 1 if it was progressive without nocturnal symptoms and 0 if it was stable; 6 points were added for the presence of "ischemic" ST-T changes. This angina score was then validated in an independent patient sample. The score was a more powerful predictor of prognosis than was any individual anginal descriptor. Furthermore, the angina score added significant independent prognostic information to the patient's age, sex, coronary anatomy and left ventricular function. Patients with three vessel disease and a normal ventricle (n = 1,233) had a 2 year infarction-free survival rate of 90% with an angina score of 0 and a 68% survival rate with an angina score greater than or equal to 9. With an ejection fraction less than 50% and three vessel disease (n = 1,116), the corresponding infarction-free survival figures were 76 and 56%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1988

Insights derived from the thrombolysis and angioplasty in myocardial infarction (TAMI) trials.

In the first three phases of Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trials, 708 patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and underwent detailed assessment of clinical, angiographic and ventriculographic outcomes. The cumulative experience and data base afford the opportunity to address several important questions regarding aggressive therapy of myocardial infarction. These include predictive factors of in-hospital mortality, improvement of left ventricular function and the occurrence of recurrent ischemia. Consideration of practical issues, such as thrombolytic therapy for patients with cardiopulmonary resuscitation or previous stroke, use of coronary artery bypass surgery and the effect of operator experience on angioplasty success rate, has also been made possible. The major accomplishments as well as the deficiencies of the current approach to patient management after thrombolysis are reviewed, and the new TAMI trials currently underway are discussed.

Angioplasty, Balloon↗

PubMed1988

Designing clinical trials for paroxysmal atrial tachycardia and other paroxysmal arrhythmias.

Paroxysmal atrial tachycardia may be useful as a model for designing clinical trials of paroxysmal tachycardia. Individual occurrences of paroxysmal atrial tachycardia are clinically independent events, and the time periods between events follow an exponential probability distribution; i.e. paroxysmal atrial tachycardia behaves like a Poisson process. We propose that treatment of paroxysmal atrial tachycardia can be studied efficiently using a clinical trial with a two period cross-over design in which placebo and investigational therapy are delivered in random order. A screening phase, dose ranging phase, and both limbs of a cross-over plane can be completed in 180 days or less in each patient.

Anti-Arrhythmia Agents↗

PubMed1988

Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator fails: results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial.

To examine the outcome of patients with persistent coronary artery occlusion despite treatment with intravenous tissue-type plasminogen activator (t-PA), the clinical course of 96 patients with persistent occlusion after 90 min of therapy was evaluated. All patients underwent cardiac catheterization 90 min after initiation of intravenous t-PA. Immediate coronary angioplasty (PTCA) was attempted when the infarct-related artery failed to reperfuse unless the vessel was technically unsuitable or the infarct was thought to be small. No baseline differences could be found between these 96 patients and 288 patients who achieved perfusion with the same protocol. Although patients with and without successful perfusion after t-PA had similar clinical courses before cardiac catheterization, those without perfusion had more complications (ventricular fibrillation, severe bradycardia, hypotension) during catheterization. PTCA achieved reperfusion with less than 50% residual stenosis in 73% of the 86 patients in whom it was attempted, while 16% were left with a high-grade (greater than 50%) residual stenosis and PTCA failed in 11%. Mortality was highest in the nine patients with complete PTCA failure (44%), compared with a 6% mortality in the 63 patients with an insignificant residual stenosis after PTCA and a 14% mortality in the 14 patients with reperfusion, but a greater than 50% residual stenosis after PTCA. In 10 patients with small infarcts (six), unsuitable anatomy (two), or "spontaneous" drug induced (but later) opening before contemplated PTCA (two), PTCA was not attempted and no mortality occurred. The in-hospital reocclusion rate after successful PTCA was 29%, despite the use of heparin and antiplatelet agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

PubMed1988

The effects of sodium butyrate on the retinoic acid-induced changes in 1,25-dihydroxyvitamin D3 receptors in tumorigenic and nontumorigenic bone derived cell lines.

Retinoic acid has previously been shown to alter 1-25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors in tumorigenic (ROS 17/2A, UMR 106M) and nontumorigenic (RCJ 1.20) bone-derived cells. The mechanism of this regulation is unclear. In the present series of experiments, we have investigated the mechanism of the retinoic acid-induced increase in 1,25-(OH)2D3 receptors by studying the effects of sodium butyrate on this process. In ROS 17/2A rat osteosarcoma cells, retinoic acid induced a 2-4-fold increase in 1,25-(OH)2D3 receptors in proliferating cells but only a 1.5- to 2-fold increase in nonproliferating cells. The retinoic acid-induced increase in 1,25-(OH)2D3 receptors in proliferating ROS 17/2A cells was inhibited by sodium butyrate, but sodium butyrate had no effect on the retinoic acid-induced increase in 1,25-(OH)2D3 receptors in nonproliferating cells. Pretreatment with hydroxyurea of low density cells decreased the effect of retinoic acid, and abolished the sodium butyrate inhibition, indicating that the differing effects of retinoic acid in high and low density cells are related to cell proliferation and not to cell density or time of exposure to retinoic acid. In low density UMR 106M cells, the effects of retinoic acid and sodium butyrate on the number of 1,25-(OH)2D3 receptors were similar to those in ROS 17/2A cells. However, in RCJ 1.20 cells, a nontumorigenic cell line with some of the characteristics normally attributed to osteoblasts, the effects of retinoic acid and sodium butyrate were opposite: retinoic acid caused a decrease in the number of 1,25-(OH)2D3 receptors, which was inhibited by sodium butyrate. The possibility that the different responses observed between the two osteosarcoma cell lines and the RCJ 1.20 cells constitute differences in response pattern between tumorigenic and nontumorigenic cell lines is of interest, but requires further experimentation to verify.

Animals↗