RESUMEN
There is a strong association between vitamin D levels and periodontal disease based on numerous epidemiological studies. We have previously shown that experimental deficiency of serum vitamin D in mice leads to gingival inflammation and alveolar bone loss. Treatment of cultured oral epithelial cells with the active form of vitamin D, 1,25(OH)2 vitamin D3 (1,25(OH)2D3), inhibits the extracellular growth and intracellular invasion of bacteria associated with periodontal disease. Maintenance of periodontal health may be due in part to the anti-inflammatory activities of vitamin D. Furthermore, this hormone can induce the expression of an antimicrobial peptide in cultured oral epithelial cells. We have shown that oral epithelial cells are capable of converting inactive vitamin D to the active form, suggesting that topical treatment of the oral epithelium with inactive vitamin D could prevent the development of periodontitis. We subjected mice to ligature-induced periodontitis (LIP), followed by daily treatment with inactive vitamin D or 1,25(OH)2D3. Treatment with both forms led to a reduction in ligature-induced bone loss and inflammation. Gingival tissues obtained from vitamin D-treated LIP showed production of specialized proresolving mediators (SPM) of inflammation. To examine the mechanism, we demonstrated that apical treatment of 3-dimensional cultures of primary gingival epithelial cells with vitamin D prevented lipopolysaccharide-induced secretion of proinflammatory cytokines and led to a similar production of SPM. Analysis of the oral microbiome of the mice treated with vitamin D showed significant changes in resident bacteria, which reflects a shift toward health-associated species. Together, our results show that topical treatment of oral tissues with inactive vitamin D can lead to the maintenance of periodontal health through the regulation of a healthy microbiome and the stimulation of resolution of inflammation. This strongly supports the development of a safe and effective vitamin D-based topical treatment or preventive agent for periodontal inflammation and disease.
RESUMEN
Initially identified as broad-spectrum antimicrobial peptides, the members of the ß-defensin family have increasingly been observed to exhibit numerous other activities, both in vitro and in vivo, that do not always relate directly to host defense. Much research has been carried out in the oral cavity, where the presence of commensal bacteria further complicates the definition of their role. In addition to direct antimicrobial activity, ß-defensins exhibit potent chemotactic activity for a variety of innate immune cells, as well as stimulating other cells to secrete cytokines. They can also inhibit the inflammatory response, however, by the specific binding of microbe-associated molecular patterns. These patterns are also able to induce the expression of ß-defensins in gingival epithelial cells, although significant differences are observed between different species of bacteria. Together these results suggest a complex model of a host-defense related function in maintenance of bacterial homeostasis and response to pathogens. This model is complicated, however, by numerous other observations of ß-defensin involvement in cell proliferation, wound healing and cancer. Together, the in vitro, in vivo and human studies suggest that these peptides are important in the biology of the oral cavity; exactly how is still subject to speculation.
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Boca/fisiología , beta-Defensinas/fisiología , Antiinfecciosos/farmacología , Péptidos Catiónicos Antimicrobianos/fisiología , Factores Quimiotácticos/fisiología , Interacciones Huésped-Patógeno/fisiología , Humanos , Inmunidad Innata/inmunología , Interacciones Microbianas/fisiología , Neoplasias/fisiopatologíaRESUMEN
Oral epithelial cells (OEC) represent the first site of host interaction with viruses that infect the body through the oral route; however, their innate antiviral defense mechanisms yet to be defined. Previous studies have determined that OEC express pathogen-, damage-, or danger-associated molecular patterns (PAMPs or DAMPs), but their expression of key antiviral innate immune mediators, including type I interferons (type I IFN) and interferon-stimulated genes (ISGs) has not been studied extensively. We used the oral keratinocyte cell line, OKF6/TERT1, in the presence and absence of the viral mimics poly(I:C) and unmethylated CpG DNA, to define the expression of type I IFN and ISGs. We identified the basal expression of novel type I IFN genes IFNE and IFNK, while IFNB1 was induced by viral mimics, through the nuclear translocation of IRF3. Numerous ISGs were expressed at basal levels in OEC, with an apparent correlation between high expression and antiviral activity at the earlier stages of viral infection. Stimulation of OECs with poly(I:C) led to selective induction of ISGs, including MX1, BST2, PML, RSAD2, ISG15, and ZC3HAV1. Together, our results demonstrate that OECs exhibit a robust innate antiviral immune defense profile, which is primed to address a wide variety of pathogenic viruses that are transmitted orally.
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Antivirales , Expresión Génica , Interferón Tipo I , Virosis , Células Epiteliales/metabolismo , Humanos , Inmunidad Innata/genética , Interferón Tipo I/metabolismo , Interferón Tipo I/fisiología , Interferones/metabolismo , Queratinocitos/metabolismo , Proteínas de Unión al ARN , Virosis/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVE: The gingival epithelium provides the first line of defense against colonization by periodontal pathogens, both as a physical barrier and by the production of inducible innate immune mediators such as beta-defensins and pro-inflammatory cytokines. The gram-negative bacterium Aggregatibacter actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, although the bacterium is found widely in the healthy population. We hypothesized that gingival epithelial cell-derived innate immune mediators triggered in response to A. actinomycetemcomitans infection may play an important role in increased susceptibility to infection. MATERIAL AND METHODS: Primary cultures of human gingival epithelial cells were cultured in the presence of A. actinomycetemcomitans. Total mRNA was examined for the presence of innate immune markers using RT-PCR. RESULTS: We show here that the mRNA levels of human beta-defensin 2 and interleukin-8 are elevated by live cultures of a clinical isolate of A. actinomycetemcomitans in cultured gingival epithelial cells from healthy individuals, but not by A. actinomycetemcomitans lipopolysaccharide. Cells from a patient with localized aggressive periodontitis, however, did not respond to this bacterial stimulation. In contrast, the pro-inflammatory cytokine interleukin-19 was induced in cells from both localized aggressive periodontitis and healthy subjects. Examination of Toll-like receptors and associated adapter molecules indicated lower levels of Toll-like receptor 2 mRNA in the localized aggressive periodontitis patient-derived cells compared with cells from healthy subjects. CONCLUSION: These results suggest that a differential expression of innate immune response genes to A. actinomycetemcomitans in the gingival epithelium could be an underlying factor of susceptibility to localized aggressive periodontitis.
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Células Epiteliales/inmunología , Genes MHC Clase II/inmunología , Encía/citología , Pasteurellaceae/inmunología , Periodontitis/inmunología , Técnicas de Cultivo de Célula , Células Epiteliales/microbiología , Regulación Bacteriana de la Expresión Génica , Encía/inmunología , Encía/microbiología , Humanos , Interleucina-8/análisis , Periodontitis/genética , Periodontitis/microbiología , beta-Defensinas/análisisRESUMEN
The left ventricular (LV) pressure-volume (P-V) relationship is a resultant of several determinants, including initial ventricular volume, geometry, and wall stiffness. A quantitative index of one of these determinants, LV wall stiffness, was developed from a mathematical analysis of the isolated P-V relationship. Since this relationship was exponential, stiffness (dP/dV) could be expressed by the equation dP/dV = aP + b, where a and b are constants. The a constant, termed the passive elastic modulus, was independent of both pressure and volume, was modified only slightly by changes in geometry, and thus was primarily affected by changes in wall stiffness. LV wall stiffness was assessed by determination of the passive elastic modulus in eight normal canine hearts and in five hearts 1 hr after acute myocardial infarction. The value of the passive elastic modulus for the normal canine LV was found to be 0.099+/-0.006 cc(-1). In the five infarcted hearts there was a modest, but statistically insignificant, shift of the P-V curves from control, such that for the same pressure the infarcted hearts contained greater volume. However, the passive elastic modulus decreased 41% to 0.057+/-0.006 cc(-1) (P < 0.001). Thus, although LV wall stiffness may increase later in the course of myocardial infarction, it is concluded that it was significantly decreased 1 hr after infarction. Calculation of the passive elastic modulus provided a sensitive means of detecting such changes, whereas P-V curves alone were generally insensitive.
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Elasticidad , Ventrículos Cardíacos/fisiopatología , Infarto del Miocardio/fisiopatología , Animales , Volumen Cardíaco , Perros , Matemática , Modelos Biológicos , Contracción Muscular , PresiónRESUMEN
Analysis of multiple noninvasive tests offers the promise of more accurate diagnosis of coronary artery disease, but discordant test responses can occur frequently and, when observed, result in diagnostic uncertainty. Accordingly, 43 patients undergoing diagnostic coronary angiography were evaluated by noninvasive testing and the results subjected to analysis using Bayes' theorem of conditional probability. The procedures used included electrocardiographic stress testing for detection of exercise-induced ST segment depression, cardiokymographic stress testing for detection of exercise-induced precordial dyskinesis, myocardial perfusion scintigraphy for detection of exercise-induced relative regional hypoperfusion, and cardiac fluoroscopy for detection of coronary artery calcification. The probability for coronary artery disease was estimated by Bayes' theorem from each patient's age, sex, and symptom classification, and from the observed test responses. This analysis revealed a significant linear correlation between the predicted probability for coronary artery disease and the observed prevalence of angiographic disease over the entire range of probability from 0 to 100% (P less than 0.001 by linear regression). The 12 patients without angiographic disease had a mean posttest likelihood of only 7.0 +/- 2.6% despite the fact that 13 of the 60 historical and test responses were falsely "positive." In contrast, the mean posttest likelihood was 94.1 +/- 2.8% in the 31 patients with angiographic coronary artery disease, although 45 of the 155 historical and test responses were falsely "negative." In 8 of the 12 normal patients, the final posttest likelihood was under 10% and in 26 of the 31 coronary artery disease patients, it was over 90%. These estimates also correlated well with the pooled clinical judgment of five experienced cardiologists (P less than 0.001 by linear regression). The observed change in probability for disease for each of the 15 different test combinations correlated with their information content predicted according to Shannon's theorem (P less than 0.001 by linear regression). These results support the use of probability analysis in the clinical diagnosis of coronary artery disease and provide a formal basis for comparing the relative diagnostic effectiveness and cost-effectiveness of different test combinations.
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Teorema de Bayes , Enfermedad Coronaria/diagnóstico , Probabilidad , Adulto , Anciano , Enfermedad Coronaria/diagnóstico por imagen , Análisis Costo-Beneficio , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Matemática , Métodos , Persona de Mediana Edad , Modelos Teóricos , RadiografíaRESUMEN
The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by Toll-like receptor-mediated pathways. These peptides can act as microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of antimicrobial peptide activity or gene expression can result in increased susceptibility to infections. This has been observed with cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of peptides in the airway. Pathogenic virulence factors can inhibit defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of peptide gene expression in animal models, as well as the optimization of peptide-based therapeutics shows promise for the treatment and prevention of airway infectious diseases.
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Péptidos Catiónicos Antimicrobianos/fisiología , Defensinas/fisiología , Sistema Respiratorio/inmunología , Animales , Fibrosis Quística/inmunología , Modelos Animales de Enfermedad , Humanos , Lactoferrina/fisiología , Muramidasa/fisiología , Proteínas Inhibidoras de Proteinasas Secretoras , Proteínas/fisiología , Receptores Toll-Like/fisiología , Tuberculosis Pulmonar/inmunología , Virosis/inmunología , CatelicidinasRESUMEN
Sequencing of the 300 bp region of the mitochondrial cytochrome b gene was done. Genetic analysis was carried out for the first time in three exotic breeds (Giant White, Soviet Chinchilla, and German Angora) of European rabbit (Oryctolagus cuniculus) to determine intra- and interspecific variability and to measure the genetic distance. The frequencies of types of mutations (transition, transversion, deletion, and insertion) were also determined. This study throws light on matrilineage of breeds that arise due to interbreed crosses and the genetic management of a stocked rabbit breeding population.
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ADN Mitocondrial/genética , Variación Genética , Conejos/genética , Animales , Secuencia de Bases , Cartilla de ADN , Europa (Continente) , Femenino , Alemania , Masculino , Datos de Secuencia Molecular , Conejos/clasificación , Federación de Rusia , Especificidad de la EspecieRESUMEN
We report here the cloning of a human cell cycle gene capable of complementing a temperature-sensitive (ts) S-phase cell cycle mutation in a Chinese hamster cell line. Cloning was performed as follows. A human genomic library in phage lambda containing 600,000 phages was screened with labeled cDNA synthesized from an mRNA fraction enriched for the specific cell cycle gene message. Plaques containing DNA inserts which hybridized to the cDNA were picked, and their DNAs were assayed for transient complementation in DNA transformation experiments. The transient complementation assay we developed is suitable for most cell cycle genes and indeed for many genes whose products are required for cell proliferation. Of 845 phages screened, 1 contained an insert active in transient complementation of the ts cell cycle mutation. Introduction of this phage into the ts cell cycle mutant also gave rise to stable transformants which grew normally at the restrictive temperature for the ts mutant cells.
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Ciclo Celular , Interfase , Adulto , Mapeo Cromosómico , Clonación Molecular , Enzimas de Restricción del ADN , Regulación de la Expresión Génica , Genes , Prueba de Complementación Genética , Humanos , ARN Mensajero/genéticaRESUMEN
Cationic antimicrobial peptides are found in all living species. A single animal can contain >24 different antimicrobial peptides, which fall into four structural classes. These peptides are produced in large quantities at sites of infection and/or inflammation and can have broad-spectrum antibacterial, antifungal, antiviral, antiprotozoan and antisepsis properties. In addition, they interact directly with host cells to modulate the inflammatory process and innate defences.
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Antiinfecciosos/farmacología , Inmunidad Innata , Péptidos/farmacología , Secuencia de Aminoácidos , Secuencia de Bases , Cationes/farmacología , Modelos Biológicos , Datos de Secuencia Molecular , Péptidos/genéticaRESUMEN
Stepwise regression procedures are often used to identify a small set of variables that serve as important predictors of clinical outcome and to construct prediction models based on those variables. Several theoretical and practical limitations of this process are discussed and highlighted with a variety of examples from published reports. Wider appreciation of these limitations should encourage the development of more relevant models, and thereby improve the quality of clinical prediction.
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Modelos Estadísticos , Pronóstico , Análisis de RegresiónRESUMEN
OBJECTIVES: The purpose of this study was to determine whether reimbursement in direct proportion to expected therapeutic benefit is capable of improving the utilization and cost of health care. BACKGROUND: The benefit associated with a particular medical or surgical treatment varies widely from patient to patient. Nevertheless, payment to the provider of the treatment is essentially invariant under the current fee-for-service system. Under an alternative fee-for-benefit strategy, empiric data are used to construct a multivariate model to predict the expected benefit to an individual patient from a particular health care service on the basis of conventional clinical descriptors. The payers and the providers of the service then openly negotiate an explicit economic relation between expected benefit and monetary payment such that payment is directly proportional to benefit. METHODS: Computer simulations were performed to determine the potential impact of this fee-for-benefit strategy with respect to medical versus surgical treatment of coronary artery disease. RESULTS: Compared with conventional fee-for-service, fee-for-benefit resulted in a 12% improvement in patient benefit (quality-adjusted survival), a 22% reduction in provider payments and a 55% increase in cost/benefit (the ratio of benefit to payment). CONCLUSIONS: The incentives embodied in a fee-for-benefit strategy can be an effective mechanism for encouraging more appropriate health care utilization while simultaneously controlling health care costs.
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Puente de Arteria Coronaria/economía , Enfermedad Coronaria/economía , Costos de la Atención en Salud/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud/economía , Reembolso de Incentivo , Análisis Actuarial , Simulación por Computador , Puente de Arteria Coronaria/mortalidad , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/cirugía , Control de Costos , Análisis Costo-Beneficio , Honorarios Médicos/estadística & datos numéricos , Humanos , Esperanza de Vida , Modelos Econométricos , Estudios Prospectivos , Análisis de Supervivencia , Estados Unidos , Valor de la VidaRESUMEN
The clinician's decisions are subject to numerous distorting influences. Computer decision aids can help avoid these distortions by placing the clinician's limited personal experience into broader perspective through comparison with a larger repository of clinically relevant information; by making explicit the assumptions implied by his or her decisions; and by alerting the clinician whenever the decisions made do not appear consistent with these assumptions, with the available information or with the conventional rules of logic. Practical standards of performance with respect to the development, validation and clinical application of these decision aids are still in evolution, however, and a variety of ethical and legal issues have yet to be addressed. Despite the promise of computer decision aids, it remains to be seen whether their diffusion into medical practice will improve the quality and cost of health care.
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Cardiología/tendencias , Toma de Decisiones Asistida por Computador , Algoritmos , Enfermedad Coronaria/diagnóstico , Toma de Decisiones Asistida por Computador/economía , Toma de Decisiones Asistida por Computador/legislación & jurisprudencia , Toma de Decisiones Asistida por Computador/normas , Humanos , Mala Praxis , Modelos Teóricos , Aceptación de la Atención de Salud , Estadística como Asunto , Terminología como AsuntoRESUMEN
OBJECTIVES: Our goals were to develop and validate a multivariate algorithm for estimating the incremental probability of the presence of coronary artery disease. BACKGROUND: Multivariate methods, including logistic regression analysis, have been extensively applied to diagnostic exercise testing. However, few previous studies have included both an incremental design and external validation. METHODS: A retrospective collection of clinical, exercise test and catheterization data was performed involving four U.S. referral medical centers. All patients had no prior history of coronary disease and had undergone coronary angiography < or = 3 months after exercise stress testing. An algorithm was developed in one center (590 patients with a 41% prevalence of coronary artery disease) with the use of logistic regression analysis and was validated in the other three centers (1,234 patients, 70% prevalence). The algorithm incorporated pretest variables (age, gender, symptoms, diabetes, cholesterol), exercise electrocardiographic (ECG) variables (mm of ST segment depression, ST slope, peak heart rate, metabolic equivalents [METs], exercise angina) and one thallium variable. Discrimination was measured with receiver operating characteristic curve analysis. Calibration (that is, reliability) was assessed from a comparison of probability estimates and the actual prevalence of disease. RESULTS: The overall incremental receiver operating characteristic curve areas for the validation group were pretest, -0.738 +/- 0.016; postexercise ECG, 0.78 (SE 0.017); and postthallium, 0.82 (SE 0.016); p < 0.01 for both increments. Within the three validation institutions, the institution with a disease prevalence closest to that of the derivation institution had the best incremental receiver operating characteristic curve areas. There was a stepwise incremental improvement in calibration especially from exercise ECG to thallium testing. CONCLUSIONS: An incremental multivariate algorithm derived in one center reliably estimated disease probability in patients from three other centers. The incremental value of testing was best demonstrated when the derivation and validation groups had a similar disease prevalence. This algorithm may be useful in decision making that relates to the diagnosis of coronary disease.
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Algoritmos , Enfermedad Coronaria/epidemiología , Prueba de Esfuerzo , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico , Análisis Discriminante , Electrocardiografía , Estudios de Evaluación como Asunto , Prueba de Esfuerzo/estadística & datos numéricos , Humanos , Modelos Logísticos , Análisis Multivariante , Prevalencia , ProbabilidadRESUMEN
OBJECTIVE: This study was conducted to assess the utility of clinical variables in predicting the inducibility of sustained ventricular arrhythmias in a heterogeneous group of patients undergoing programmed ventricular stimulation. METHODS: Variables were considered in a simulated chronologic order to determine the incremental information added by the signal-averaged electrocardiogram (ECG) and left ventricular ejection fraction. All patients undergoing baseline programmed ventricular stimulation for induction of ventricular tachyarrhythmia during a 30-month period were included in the study. Fourteen historical, ECG, signal-averaged ECG and left ventricular wall motion variables were evaluated for their ability in predicting inducibility of a sustained ventricular arrhythmia, a "positive" event, at programmed ventricular stimulation. RESULTS: On univariate analysis of the clinical variables, comparison between patients with positive or negative results showed significant differences in 10 of the 14 clinical variables: major cardiac diagnosis, history of ventricular tachycardia, myocardial infarction by history or ECG, all five signal-averaged ECG variables, left ventricular ejection fraction and presence of left ventricular aneurysm. On multivariate analysis, five independent variables were determined to be important: history of ventricular tachycardia, historical or ECG evidence of myocardial infarction, history of loss of consciousness, filtered QRS duration on the signal-averaged ECG and left ventricular ejection fraction. However, with sequential multivariate analysis, a model based only on historical and conventional ECG data was found to do as well as a model that included signal-averaged ECG and left ventricular ejection fraction data. CONCLUSIONS: Routinely available noninvasive historical, ECG, signal-averaged ECG and left ventricular wall motion variables can be used to accurately predict the outcome of programmed ventricular stimulation. The majority of the predictive power was obtained with the routine model, using only historical and ECG data. The signal-averaged ECG and left ventricular wall motion analysis added no significant incremental information.
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Arritmias Cardíacas/epidemiología , Estimulación Cardíaca Artificial , Técnicas de Apoyo para la Decisión , Taquicardia/epidemiología , Anciano , Arritmias Cardíacas/diagnóstico , Electrocardiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Curva ROC , Factores de Riesgo , Procesamiento de Señales Asistido por Computador , Volumen Sistólico , Taquicardia/diagnósticoRESUMEN
OBJECTIVES: This study assessed the incremental value of technetium-99m myocardial single-photon emission computed tomography (SPECT) and simultaneous first-pass radionuclide angiography, when added to treadmill exercise, for prediction of the extent of coronary artery disease. BACKGROUND: Technetium-99m count statistics permit the simultaneous assessment of myocardial perfusion and function. However, whether this characteristic improves prediction of the extent of coronary artery disease remains unknown. METHODS: We studied 70 consecutive patients who had coronary angiography within 6 months of the scintigraphic study. All patients underwent a symptom-limited treadmill exercise test. Treadmill data were summarized using a previously validated score. Left ventricular ejection fraction and regional wall motion were evaluated from a first-pass radionuclide angiogram acquired at peak treadmill exercise in the anterior view. Perfusion was assessed visually. Extent of angiographic disease was expressed as the presence or absence of multivessel disease (more than two coronary artery territories with > 50% stenosis) and as a score that reflects the location of severe (> 75%) stenosis. RESULTS: Stepwise addition of scintigraphic data (perfusion first, followed by function) to the treadmill score showed significant incremental value for prediction of the angiographic score at each step; exercise ejection fraction alone was the strongest independent predictor. Discriminant accuracy for detection of multivessel disease was also improved by the addition of perfusion information to the treadmill score and addition of regional wall motion analysis to both of them. In this case, ejection fraction failed to show independent value. CONCLUSIONS: The addition of simultaneously performed sestamibi perfusion SPECT and first-pass radionuclide angiography to the treadmill exercise test significantly improved prediction of the extent of coronary artery disease.
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Enfermedad Coronaria/diagnóstico por imagen , Corazón/diagnóstico por imagen , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único , Ventriculografía de Primer Paso , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Electrocardiografía , Prueba de Esfuerzo , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Función Ventricular Izquierda/fisiologíaRESUMEN
OBJECTIVES: This study assessed the agreement of left ventricular ejection fraction determinations from two-dimensional echocardiography, radionuclide angiography and contrast cineangiography. BACKGROUND: Previously published reports suggest that two-dimensional echocardiography, radionuclide angiography and contrast cineangiography are equally acceptable methods of assessing left ventricular ejection fraction on the basis of high coefficients of correlation. However, correlation of methods does not necessarily imply agreement. METHODS: In a prospective analysis, 25 consecutive subjects all had two-dimensional echocardiography and radionuclide angiography performed within 10 days of each other in the cardiology department of metropolitan community hospital. A retrospective computer search (Medline) revealed seven studies, using the coefficient of correlation (r), comparing two-dimensional echocardiographic left ventricular ejection fraction (n = 268) with radionuclide angiographic (n = 174) or contrast cineangiographic (n = 119) left ventricular ejection fractions. RESULTS: The eight individual studies (n = 293) comparing two-dimensional echocardiography with either radionuclide angiography or contrast cineangiography exhibited coefficients of correlation ranging from 0.78 to 0.93. Agreement analysis using the method of Bland and Altman was performed by averaging the results obtained from the two techniques and determining how disparate any single ejection fraction was (with 95% confidence limits) from the mean value. Agreement ranged from 23% to 42% around the mean ejection fraction. The average lack of agreement between the two methods for all studies involved was 17%, with an average r value of 0.86. CONCLUSIONS: Left ventricular ejection fraction determinations by means of two-dimensional echocardiography, radionuclide angiography and contrast cineangiography exhibit high correlation and only moderate agreement. High correlation does not always imply high agreement. These results suggest that, when validated by agreement analysis, multiple studies may not be necessary in appropriate clinical situations, potentially reducing costs.
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Cineangiografía , Ecocardiografía , Angiografía por Radionúclidos , Volumen Sistólico , Función Ventricular Izquierda , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Imagen de Acumulación Sanguínea de Compuerta , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
A microcomputer program called CADENZA, which employs Bayes' theorem to analyze and report the results of various clinical descriptors and noninvasive tests relative to the diagnosis of coronary artery disease, was evaluated in 1,097 consecutive patients without previous myocardial infarction. With this program, each patient was characterized by a probability for coronary artery disease, based on Framingham risk factor analysis, symptom characterization, electrocardiographic stress testing, cardiokymography, cardiac fluoroscopy, thallium perfusion scintigraphy and technetium equilibrium-gated blood pool scintigraphy. A total of 11,808 probability estimates derived from various combinations of the available observations were analyzed: 2,180 in 170 patients undergoing coronary angiography and 9,628 in 969 patients who completed a 1 year follow-up for coronary events. The predicted probability of disease correlated linearly with observed angiographic prevalence in the 170 patients who subsequently had coronary angiography (prevalence = [0.001 +/- 0.011] + [0.966 +/- 0.019] X probability). The difference between probability and prevalence averaged 3.1%, and the magnitude of this correlation was not affected by the type or amount of data analyzed. The prevalence of multivessel disease in these patients increased as a monotonic function of disease probability. Below a probability of 25%, single vessel disease was slightly more common than multivessel disease. Above a probability of 75%, multivessel disease predominated. In the 969 patients followed up for 1 year from the date of testing, the incidence of cardiac death and nonfatal infarction increased as a cubic function of disease probability (from approximately 0 to 8% per year for each). Above a probability of 90%, however, the standard deviation for predicting these events was wide. These data indicate that Bayes' theorem in general--and CADENZA in particular--is an accurate, clinically applicable means for quantifying the prevalence of angiographic coronary artery disease, the risk of multivessel disease and the incidence of morbid coronary events in the year after testing.
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Enfermedad Coronaria/diagnóstico , Diagnóstico por Computador , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Microcomputadores , Persona de Mediana Edad , Programas InformáticosRESUMEN
The conventional interpretation of ejection fraction change with exercise may be limited because it does not consider the rest value, define equivocal responses or integrate wall motion data reproducibly. Thus, a format was developed for combined interpretation of rest and exercise radionuclide ejection fraction and wall motion by reviewing the reported data for the exercise responses of patients without prior myocardial infarction. The ejection fraction data of 202 normal patients and of 259 patients with coronary artery disease were first fitted to beta distributions. The true positive and false positive rates for coronary disease for each combination of rest and exercise ejection fraction were then determined directly from these distributions. A given rest/exercise ejection fraction combination was "normal" if the false positive rate was greater than the true positive rate, or "abnormal" if the true positive rate was greater than the false positive rate, and "equivocal" when the rates were similar (within a 50% confidence interval). This analytic format, which predicted an inverse relation between rest ejection fraction and the change required with exercise, was then validated prospectively in 854 patients without myocardial infarction (557 with and 297 without angiographic coronary artery disease). Using the conventional criterion of an abnormal test result (less than 0.05 absolute rise in ejection fraction with exercise or a wall motion abnormality), sensitivity was 85 +/- 2% and specificity only 42 +/- 3%. The statistical format had a sensitivity of 70 +/- 2% and specificity of 70 +/- 3%, resulting in a twofold increase in information content. This format has at least two advantages over conventional interpretation: 1) it provides an explicit definition of equivocal responses; and 2) it reproducibly integrates discordant ejection fraction and wall motion responses and allows for the combined analysis of other nonscintigraphic observations, such as age and sex.
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Gasto Cardíaco , Enfermedad Coronaria/fisiopatología , Prueba de Esfuerzo , Corazón/fisiopatología , Volumen Sistólico , Adulto , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Corazón/diagnóstico por imagen , Corazón/fisiología , Humanos , Masculino , Persona de Mediana Edad , Contracción Miocárdica , Estudios Prospectivos , Cintigrafía , Descanso , Estudios Retrospectivos , Estadística como AsuntoRESUMEN
A test is often interpreted as "normal" or "abnormal" by a single criterion, regardless of the intent of testing. The discriminate accuracy of this convention was critically analyzed using information content (I), likelihood ratio and the area under the receiver-operating characteristic curve. Three ejection fraction variables were assessed--ejection fraction at rest, exercise ejection fraction and the change in ejection fraction from rest to exercise--each relative to three intentional goals: diagnosis of coronary artery disease in 929 patients without previous myocardial infarction, prediction of multivessel disease in these same 929 patients and prediction of multivessel disease in 507 patients with previous myocardial infarction. The information content of exercise ejection fraction (IEX) was higher than for ejection fraction at rest (IR) or for the change from rest to exercise (IEX-R), and was relatively constant regardless of the goal of testing. In contrast, neither IR nor IEX-R was constant. IR was lowest for diagnosis of coronary artery disease, whereas IEX-R was highest for this same goal. These empiric observations are consistent with the quantitative relation predicted by information theory: IEX = IR + IEX-R. Thus, ejection fraction at rest has little discriminate value relative to the diagnosis of coronary artery disease, but does have value in evaluating the extent of disease in patients after myocardial infarction. Exercise ejection fraction and change in ejection fraction are nearly equally useful for purposes of diagnosis, whereas the former is most useful for functional evaluation in postinfarction patients.(ABSTRACT TRUNCATED AT 250 WORDS)