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Biomedical subjects

K L Lee

Publications and source records attributed to K L Lee.

At least 109 records · Page 6Linked to original sources

Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators.

BACKGROUND: Despite remarkable advances in the treatment of acute myocardial infarction, substantial early patient mortality remains. Appropriate choices among alternative therapies and the use of clinical resources depend on an estimate of the patient's risk. Individual patients reflect a combination of clinical features that influence prognosis, and these factors must be appropriately weighted to produce an accurate assessment of risk. Prior studies to define prognosis either were performed before widespread use of thrombolysis or were limited in sample size or spectrum of data. Using the large population of the GUSTO-I trial, we performed a comprehensive analysis of relations between baseline clinical data and 30-day mortality and developed a multivariable statistical model for risk assessment in candidates for thrombolytic therapy. METHODS AND RESULTS: For the 41,021 patients enrolled in GUSTO-I, a randomized trial of four thrombolytic strategies, relations between clinical descriptors routinely collected at initial presentation, and death within 30 days (which occurred in 7% of the population) were examined with both univariable and multivariable analyses. Variables studied included demographics, history and risk factors, presenting characteristics, and treatment assignment. Risk modeling was performed with logistic multiple regression and validated with bootstrapping techniques. Multivariable analysis identified age as the most significant factor influencing 30-day mortality, with rates of 1.1% in the youngest decile (< 45 years) and 20.5% in patients > 75 (adjusted chi 2 = 717, P < .0001). Other factors most significantly associated with increased mortality were lower systolic blood pressure (chi 2 = 550, P < .0001), higher Killip class (chi 2 = 350, P < .0001), elevated heart rate (chi 2 = 275, P < .0001), and anterior infarction (chi 2 = 143, P < .0001). Together, these five characteristics contained 90% of the prognostic information in the baseline clinical data. Other significant though less important factors included previous myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular disease. Combining prognostic variables through logistic regression, we produced a validated model that stratified patient risk and accurately estimated the likelihood of death. CONCLUSIONS: The clinical determinants of mortality in patients treated with thrombolytic therapy within 6 hours of symptom onset are multifactorial and the relations complex. Although a few variables contain most of the prognostic information, many others contribute additional independent prognostic information. Through consideration of multiple characteristics, including age, medical history, physiological significance of the infarction, and medical treatment, the prognosis of an individual patient can be accurately estimated.

Aged↗

Revisit of MALDI for small proteins.

Matrix-assisted laser desorption/ionization (MALDI) was used for several small proteins (such as insulin) and for peptides. It was found that the detection efficiencies of MALDI for the insulin B chain and the insulin A chain are drastically different. Similar phenomena were also observed for various types of peptides. The positive-ion signal of MALDI in detecting proteins or peptides was found to be greatly enhanced by the presence of a basic amino acid in their chains. The experimental results indicate that this enhancement may arise from proton transfer in solution by an acid-base reaction between the protein/peptide and matrix molecule. This pre-protonated mechanism provides a low energy barrier for the ionization of peptides in a MALDI process, and greatly reduces the energy threshold of MALDI. Matrix effects on the ionization mechanism are discussed.

Amino Acid Sequence↗

Production of fumonisins by Fusarium species of Taiwan.

Twenty-nine Fusarium species isolated from various sources in different districts of Taiwan were tested for their ability to produce fumonisins in corn cultures. Only Fusarium moniliforme produced fumonisin B1 (FB1) and fumonisin B2 (FB2). The finding that the other 28 Fusarium species produced neither FB1 nor FB2 is preliminary because only one strain per species was studied. The detection of FB1 and FB2 in cultures of F. moniliforme was demonstrated by TLC and HPLC, and FB1 was further confirmed by mass spectrometry. In a separate experiment, in which 38 strains of F. moniliforme were tested for fumonisins, approximately 66% (25/38) produced FB1 and/or FB2. Of the 25 strains, 14 produced only FB1 and 11 produced both FB1 and FB2, and the amounts of FB1 and FB2 produced by different strains varied greatly. This is the first report that fumonisins are found in corn cultures experimentally infected with F. moniliforme strains from Taiwan. It is safe to assume that fumonisin producing strains of F. moniliforme are widely distributed among the economic crops such as corn, rice, sugarcane, and sorghum throughout the Island.

Food Microbiology↗

Hand ischaemia following radial artery cannulation.

Digital ischaemia following radial arterial cannulation is uncommon. It is usually the result of thrombotic occlusion of a dominant radial artery. However, factors other than arterial thrombosis per se may operate in the critically ill patient to produce digital ischaemia. The following case presentation includes a review of possible mechanisms of digital ischaemia following radial artery cannulation and discusses the therapeutic options available.

Catheterization, Peripheral↗

Determining VA physician requirements through empirically based models.

OBJECTIVE: As part of a project to estimate physician requirements for the Department of Veterans Affairs, the Institute of Medicine (IOM) developed and tested empirically based models of physician staffing, by specialty, that could be applied to each VA facility. DATA SOURCE/STUDY SETTING: These analyses used selected data on all patient encounters and all facilities in VA's management information systems for FY 1989. STUDY DESIGN: Production functions (PFs), with patient workload dependent on physicians, other providers, and nonpersonnel factors, were estimated for each of 14 patient care areas in a VA medical center. Inverse production functions (IPFs), with physician staffing levels dependent on workload and other factors, were estimated for each of 11 specialty groupings. These models provide complementary approaches to deriving VA physician requirements for patient care and medical education. DATA COLLECTION/EXTRACTION METHODS: All data were assembled by VA and put in analyzable SAS data sets containing FY 1989 workload and staffing variables used in the PFs and IPFs. All statistical analyses reported here were conducted by the IOM. PRINCIPAL FINDINGS: Existing VA data can be used to develop statistically strong, clinically plausible, empirically based models for calculating physician requirements, by specialty. These models can (1) compare current physician staffing in a given setting with systemwide norms and (2) yield estimates of future staffing requirements conditional on future workload. CONCLUSIONS: Empirically based models can play an important role in determining VA physician staffing requirements. VA should test, evaluate, and revise these models on an ongoing basis.

Efficiency, Organizational↗

Use of medical resources and quality of life after acute myocardial infarction in Canada and the United States.

BACKGROUND: Much attention has been directed to the use of medical resources and to patients' outcomes in Canada as compared with the United States. We compared U.S. and Canadian patients with respect to their use of medical resources and their quality of life during the year after acute myocardial infarction. METHODS: A total of 2600 U.S. and 400 Canadian patients were randomly selected from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial. Base-line data from their initial hospitalizations were analyzed, and the patients were then interviewed by telephone 30 days, 6 months, and 1 year after myocardial infarction to determine their use of medical care and quality of life. RESULTS: The Canadian patients typically stayed in the hospital one day longer (P = 0.009) than the U.S. patients but had a much lower rate of cardiac catheterization (25 percent vs. 72 percent, P < 0.001), coronary angioplasty (11 percent vs. 29 percent, P < 0.001), and coronary bypass surgery (3 percent vs. 14 percent, P < 0.001). At one year 24 percent of the Canadian and 53 percent of the U.S. patients had undergone angioplasty or bypass surgery at least once (P < 0.001). The Canadian had more visits to physicians during the follow-up year (P < 0.001), but fewer visits to specialists (P < 0.001). At 30 days, functional status was equivalent in the patients from the two countries. However, after one year the U.S. patients had substantially more improvement than the Canadian patients (P < 0.001). The prevalence of chest pain and dyspnea at one year was higher among the Canadian patients (34 percent vs. 21 percent and 45 percent vs. 29 percent, respectively; P < 0.001). CONCLUSIONS: The Canadian patients had more cardiac symptoms and worse functional status one year after acute myocardial infarction than the U.S. patients. The Canadian patients also underwent fewer invasive cardiac procedures and had fewer visits to specialist physicians. These results suggest, but do not prove, that the more aggressive pattern of care in the United States may have been responsible for the better quality of life.

Aged↗

Holding GUSTO up to the light. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, a recent randomized "megatrial" of thrombolytic therapies in acute myocardial infarction, showed a statistically significant decrease of 30-day mortality in patients treated with accelerated-dose tissue plasminogen activator (tPA) compared with streptokinase. The therapeutic and cost implications of the results have been intensely scrutinized, and several commentaries have been written on the interpretation of the study. Questions have been raised about the treatment benefit in certain subgroups, the validity of the results because of the open-label design, the relevance of a 1% absolute benefit in mortality rates, the cost-effectiveness of the drug, and the generalizability of the results. These issues are all important considerations for translating the results of this study into clinical practice worldwide. This article sheds additional light on the interpretation of GUSTO, clarifies misconceptions that may have clouded understanding of the trial results, and discusses the contributions of this trial in advancing our understanding of modern myocardial reperfusion therapy.

Cost-Benefit Analysis↗

Clinical importance of thrombocytopenia occurring in the hospital phase after administration of thrombolytic therapy for acute myocardial infarction. The Thrombolysis and Angioplasty in Myocardial Infarction Study Group.

OBJECTIVES: The purpose of this study was to examine the incidence and clinical implications of thrombocytopenia that occurs in hospital after administration of thrombolytic therapy for acute myocardial infarction. BACKGROUND: The use of thrombolytic therapy in patients with acute myocardial infarction has improved mortaltiy rates, but hemorrhage remains a major complication. Because thrombocytopenia may be associated with hemorrhage after thrombolytic therapy, we examined the incidence and clinical implications of thrombocytopenia after administration of thrombolytic therapy for acute myocardial infarction. METHODS: The patient population comprised 1,001 patients enrolled in Phases 2, 3 and 5 of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trial and the urokinase trial. Patients received recombinant tissue-type plasminogen activator, urokinase or combination therapy in various dosing schemes. All patients received heparin, aspirin and a calcium-channel blocking agent. Thrombocytopenia occurring anytime after thrombolytic therapy was defined as a nadir platelet count either < 100,000/microliters or < 1/2 baseline. Blood loss was quantified by a bleeding index. Multiple logistic regression was used to evaluate the independent contribution of thrombocytopenia in a model predicting in-hospital mortality. RESULTS: Thrombocytopenia occurred in 16.4% of patients, with no difference among the thrombolytic regimens. Patients with thrombocytopenia had a lower median acute ejection fraction and a higher likelihood of three-vessel coronary artery disease than patients without thrombocytopenia. Patients with thrombocytopenia had more hemorrhage, a higher in-hospital mortality rate and a more complicated hospital course than patients without thrombocytopenia, even after consideration of other important variables, including age, acute ejection fraction, number of diseased vessels, bypass surgery and use of intraaortic balloon counterpulsation. CONCLUSIONS: Thrombocytopenia after thrombolytic therapy is a common event and is associated with excess hemorrhage and mortality. Platelet counts should be monitored daily after administration of thrombolytic therapy because the appearance of thrombocytopenia identifies a subset of patients at increased risk for hemorrhage and death.

Aged↗

Effects of coronary angioplasty, coronary bypass surgery, and medical therapy on employment in patients with coronary artery disease. A prospective comparison study.

OBJECTIVE: To compare return-to-work rates after coronary angioplasty, coronary bypass surgery, and medical therapy in patients with coronary disease. DESIGN: Prospective cohort study. SETTING: Tertiary care referral center. PATIENTS: Between March 1986 and June 1990, we enrolled 1252 patients who were younger than 65 years, who had not had previous coronary revascularization, and who were employed. All patients were followed for 1 year. MAIN OUTCOME MEASURE: One-year employment status. RESULTS: After 1 year, 84% of patients who had coronary angioplasty were still working compared with 79% of patients who had bypass surgery and with 76% of patients who received medicine. After adjusting for the more favorable baseline characteristics of patients who had angioplasty (less severe coronary artery disease, better left ventricular function, and less functional impairment), however, no significant differences were noted in 1-year employment rates among the three groups. These adjusted 1-year return-to-work rates were 84% for angioplasty, 80% for surgery, and 79% for medicine (P > 0.05). In a random subset of 72 patients, 23 patients who had angioplasty returned to work after a median of 18 days (mean, 27 days) compared with 54 days (mean, 67 days) for 24 patients having bypass surgery and with 14 days (mean, 45 days) for 25 patients receiving medicine (P = 0.002). CONCLUSIONS: Patients who had coronary angioplasty were able to return to work earlier than those who had bypass surgery, but by 1 year no significant difference was noted in employment rates. Neither revascularization strategy improved employment rates when compared with initial treatment using medical therapy.

Angioplasty, Balloon, Coronary↗

Isolation of P1 bacteriophage clones containing large contiguous segments of the human and mouse loci for the T-cell coreceptor molecule CD8.

The T-lymphocyte coreceptor molecules CD8 (composed of CD8 alpha and CD8 beta chains) and CD4 undergo a complex pattern of regulated expression during T-cell maturation. In the thymus, the most immature cells progress from expressing neither molecule (the double-negative [DN] stage) to an intermediate stage at which both are coexpressed (the double-positive [DP] stage). As a result of thymic selection and further differentiation, DP cells give rise to the most mature thymic cells and peripheral T cells that express either CD8 or CD4 (the single-positive [SP] stage). Our previous studies of the transcriptional regulatory mechanisms controlling CD8 alpha expression during the DN-->DP and DP-->SP transitions suggest the existence of important cis-acting elements located a considerable distance from the CD8 alpha gene and that these elements might serve to regulate both CD8 alpha and CD8 beta. While both genes and intergenic DNA span approximately 60 kb in the mouse, the relevant cis elements could lie either within or beyond this region. As a result, we sought to isolate large contiguous segments of DNA in P1 bacteriophage that covered at least this region from the mouse and human CD8 locus. Our initial physical characterization of these clones demonstrates the value of the P1 system as all isolated clones were found to contain single contiguous 85- to 95-kb segments of DNA that are faithful replicas of the chromosomal locus. The presence of abundant native flanking DNA both upstream and downstream of the intact coding regions will make these clones extremely useful for identifying physiological CD8 cis-active regulatory elements by virtue of their ability to direct appropriate lineage- and stage-specific expression in transfected and transgenic T cells.

Animals↗

Adenosine in wide complex tachycardia: potential pitfalls in diagnostic value.

Adenosine is an efficacious diagnostic and therapeutic agent in the acute management of wide complex tachycardias. Its potent negative dromotropic effect terminates supraventricular tachycardias involving the atrioventricular node, allowing differentiation from tachycardias of atrial and ventricular origin. Its extranodal actions, however, may lead to potential pitfalls in arrhythmia diagnosis. We report three unusual cases of patients with adenosine-sensitive tachycardias. One patient had idiopathic ventricular tachycardia originating from the right ventricular outflow tract, one had ectopic atrial tachycardia, and one had atrial fibrillation with rate-related intraventricular aberration. Recognition of the extranodal actions of adenosine and careful ECG evaluation before and after adenosine administration should maximize the diagnostic accuracy of adenosine in wide complex tachycardias.

Adenosine Triphosphate↗

Catheter induced mechanical stunning of accessory pathway conduction: useful guide to successful transcatheter ablation of accessory pathways.

Established electrophysiological criteria indicating anatomical proximity to an accessory pathway include early ventricular or atrial activation during antegrade or retrograde accessory pathway conduction, recording of accessory pathway potentials, and pace map concordance. This article describes two cases of RF catheter ablation of accessory pathways, during which positioning of the mapping catheter at specific sites on the endocardial aspect of the atrioventricular annulus led to prolongation of accessory pathway refractoriness and/or slowing of conduction. RF energy application at these sites successfully abolished accessory pathway conduction. When observed on an "internal" basis during catheter mapping, catheter induced stunning of accessory pathway conduction provides evidence of satisfactory electrode-tissue contact in addition to anatomical proximity, and may give additional predictive value to successful transcatheter accessory pathway ablation.

Adult↗

Pleomorphic ventricular tachycardia with antegrade His-bundle activation: elucidation by multiple His-bundle recordings.

The use of multiple His bundle-right bundle branch recordings in electrophysiologic studies has facilitated definition of the mechanism and elucidation of the direction of impulse propagation in bundle branch reentrant tachycardia, "Mahaim" fiber reciprocating tachycardia, and retrograde His depolarization in fascicular or ventricular tachycardias. This report details the electrophysiologic evaluation of pleomorphic ventricular tachycardia in a patient with advanced coronary heart disease. The ventricular tachycardia at baseline revealed variation in the QRS duration without alteration of the electrocardiographic (ECG) morphology. Following flecainide administration, a ventricular tachycardia with close resemblance of the ECG morphology to sinus rhythm was induced. Proximal and distal His-bundle recordings revealed early antegrade His-bundle activation during this tachycardia. Programmed stimulation converted this tachycardia back to the clinical ventricular tachycardia with intermittent narrowing of the QRS complexes. Early His activation was evident only during the narrower complexes but not in the tachycardia beats with wide complex. Penetration of the His bundle by ventricular tachycardia, with resultant fusion from intramyocardial ventricular activation and His-Purkinje activation, could have accounted for the near normalization of the QRS morphology during the ventricular tachycardia.

Anti-Arrhythmia Agents↗

Continuing evolution of therapy for coronary artery disease. Initial results from the era of coronary angioplasty.

BACKGROUND: Survival after coronary artery bypass graft surgery (CABG) and medical therapy in patients with coronary artery disease (CAD) has been studied in both randomized trials and observational treatment comparisons. Over the past decade, the use of coronary angioplasty (PTCA) has increased dramatically, without guidance from either randomized trials or prospective observational comparisons. The purpose of this study was to describe the survival experience of a large prospective cohort of CAD patients treated with medicine, PTCA, or CABG. METHODS AND RESULTS: The study was designed as a prospective nonrandomized treatment comparison in the setting of an academic medical center (tertiary care). Subjects were 9263 patients with symptomatic CAD referred for cardiac catheterization (1984 through 1990). Patients with prior PTCA or CABG, valvular or congenital disease, nonischemic cardiomyopathy, or significant (> or = 75%) left main disease were excluded. Baseline clinical, laboratory, and catheterization data were collected prospectively in the Duke Cardiovascular Disease Databank. All patients were contacted at 6 months, 1 year, and annually thereafter (follow-up 97% complete). Cardiovascular death was the primary end point. Of this cohort, 2788 patients were treated with PTCA (2626 within 60 days) and 3422 with CABG (3080 within 60 days). Repeat or crossover revascularization procedures were counted as part of the initial treatment strategy. Kaplan-Meier survival curves (both unadjusted and adjusted for all known imbalances in baseline prognostic factors) were used to examine absolute survival differences, and treatment pair hazard ratios from the Cox model were used to summarize average relative survival benefits. For the latter, a 13-level CAD prognostic index was used to examine the relation between survival and revascularization as a function of CAD severity. The effects of revascularization on survival depended on the extent of CAD. For the least severe forms of CAD (ie, one-vessel disease), there were no survival advantages out to 5 years for revascularization over medical therapy. For intermediate levels of CAD (ie, two-vessel disease), revascularization was associated with higher survival rates than medical therapy. For less severe forms of two-vessel disease, PTCA had a small advantage over CABG, whereas for the most severe form of two-vessel disease (with a critical lesion of the proximal left anterior descending artery), CABG was superior. For the most severe forms of CAD (ie, three-vessel disease), CABG provided a consistent survival advantage over medicine. PTCA appeared prognostically equivalent to medicine in these patients, but the number of PTCA patients in this subgroup was low. CONCLUSIONS: In this first large-scale, prospective observational treatment comparison of PTCA, CABG, and medicine, we confirmed the previously reported survival advantages for CABG over medical therapy for three-vessel disease and severe two-vessel disease. For less severe CAD, the primary treatment choices are between medicine and PTCA. In these patients, there is a trend for a relative survival advantage with PTCA, although absolute survival differences were modest. In this setting, treatment decisions should be based not only on survival differences but also on symptom relief, quality of life outcomes, and patient preferences.

Angioplasty, Balloon, Coronary↗

Value of the history and physical in identifying patients at increased risk for coronary artery disease.

OBJECTIVE: To determine whether information from the physician's initial evaluation of patients with suspected coronary artery disease predicts coronary anatomy at catheterization and 3-year survival. DESIGN: Prospective validation of regression model estimates in an outpatient cohort. SETTING: University medical center. PATIENTS: A total of 1030 consecutive outpatients referred for noninvasive testing for suspected coronary artery disease; 168 of these patients subsequently underwent catheterization within 90 days. MEASUREMENTS: Information from the initial history, physical examination, electrocardiogram, and chest radiograph was used to predict coronary anatomy (the likelihood of any significant coronary disease, severe disease [left main or three-vessel], and significant left main disease) among 168 catheterized patients and to estimate 3-year survival among all patients. These estimates were compared with those based on treadmill testing. Cardiovascular testing charges were calculated for all patients. RESULTS: Predicted coronary anatomy and survival closely corresponded to actual findings. Compared with the treadmill exercise test, initial evaluation was slightly better able to distinguish patients with or without any coronary disease and was similar in the ability to identify patients at increased risk for dying or with anatomically severe disease. Based on arbitrary definitions, 37% to 66% of patients were at low risk and responsible for 31% to 56% of the charges for cardiovascular testing. CONCLUSIONS: The physician's initial evaluation, despite the subjective nature of much of the information gathered, can be used to identify patients likely to benefit from further testing. The development of strategies for cost-conscious quality care must begin with the history, physical examination, and simple laboratory testing.

Aged↗