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Biomedical subjects

D Levy

Publications and source records attributed to D Levy.

At least 271 records · Page 15Linked to original sources
PubMed1993

The DA6-147 monoclonal antibody raised against the HLA-DR alpha chain identifies a cryptic epitope on the BoLA-DR alpha chain.

By combining immunoprecipitation of BoLA molecules with monoclonal antibodies raised against 2 different major histocompatibility class II antigens, TH14B and TH81A, and western blotting using the anti-HLA DR alpha monoclonal antibody DA6-147, we characterized an epitope conserved on BoLA- and HLA-DR alpha chains. This epitope, not accessible on intact cells, was revealed after cell lysis. In addition, these results allowed us to define TH14B as an anti-BoLA-DR monoclonal antibody whereas TH81A, raised against the products of a second MHC locus, is probably an anti-BoLA-DQ monoclonal antibody.

Animals↗
PubMed1992

Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham Heart Study.

OBJECTIVE: To evaluate the prevalence and prognostic significance of asymptomatic complex or frequent ventricular premature beats detected during ambulatory electrocardiographic (ECG) monitoring. DESIGN: Cohort study with a follow-up period of 4 to 6 years. SETTING: Population-based. PARTICIPANTS: Surviving patients of the original Framingham Heart Study cohort and offspring of original cohort members (2727 men and 3306 women). MEASUREMENTS: One-hour ambulatory electrocardiography. RESULTS: The age-adjusted prevalence of complex or frequent arrhythmia (more than 30 ventricular premature complexes per hour or multiform premature complexes, ventricular couplets, ventricular tachycardia, or R-on-T ventricular premature complexes) was 12% (95% Cl, 11% to 13%) in the 2425 men without clinically evident coronary heart disease and 33% (Cl, 24% to 42%) in the 302 men with coronary heart disease. The corresponding values in women (3064 without disease and 242 with disease) were 12% (Cl, 11% to 13%) and 26% (Cl, 9% to 43%). After adjusting for age and traditional risk factors for coronary heart disease in a Cox proportional hazards model, men without coronary heart disease who had complex or frequent ventricular arrhythmias were at increased risk for both all-cause mortality (relative risk, 2.30; Cl, 1.65 to 3.20) and the occurrence of myocardial infarction or death from coronary heart disease (relative risk, 2.12; Cl, 1.33 to 3.38). In men with coronary heart disease and in women with and without coronary heart disease, complex or frequent arrhythmias were not associated with an increased risk for either outcome. CONCLUSIONS: In men who do not have clinically apparent coronary heart disease, the incidental detection of ventricular arrhythmias is associated with a twofold increase in the risk for all-cause mortality and myocardial infarction or death due to coronary heart disease. The preventive and therapeutic implications of these findings await further investigation.

Adult↗
PubMed1992

Intra- and interobserver reproducibility of Doppler-assessed indexes of left ventricular diastolic function in a population-based study (the Framingham Heart Study).

The reproducibility of a variety of Doppler indexes of diastolic function in an epidemiologic setting and in atrial fibrillation have not been reported. This study examined the reproducibility of left ventricular inflow in subjects in sinus rhythm (n = 80) and atrial fibrillation (n = 12), randomly selected from the original cohort of the Framingham Heart Study. The following Doppler indexes were assessed for all subjects: peak and integral of early (E) diastolic inflow velocity, acceleration slope and time, deceleration slope and time, and pressure half-time. For subjects in sinus rhythm, the following parameters also were measured: the peak and integral of late (A) diastolic inflow velocity, ratios of peak velocities and integrals E/A, and atrial filling fraction. Intraobserver and interobserver variability were evaluated by statistical methods including Student's t test of the systematic differences (bias), percent bias, correlation coefficients, measurement precision, and percent precision. In subjects in sinus rhythm, although the interobserver bias was statistically significant for most of the parameters, it was < 10% for all but 1 parameter (acceleration time). For the peak and integral measures, the intra- and interobserver correlations were > or = 0.89, with intra- and interobserver percent precision measures within 2.2 to 13.0% of the corresponding mean values. The acceleration, deceleration and pressure half-time measures had somewhat lower correlations (interobserver correlations ranging from 0.59 to 0.96), with percent precision measures further from the corresponding means (interobserver percent precision ranging from 10.1 to 19.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Prognostic implications of subclinical left ventricular dilatation and systolic dysfunction in men free of overt cardiovascular disease (the Framingham Heart Study).

To determine the prognostic significance of asymptomatic left ventricular (LV) dilatation and LV systolic dysfunction, 1,493 men who were free of symptomatic cardiovascular disease underwent M-mode echocardiography and were then followed for a mean of 4.15 years. At baseline examination, 170 men (11.4%) had an abnormally high end-diastolic LV internal dimension (> or = 56 mm) and 76 (5.1%) had an abnormally low fractional shortening (< or = 30%). During the follow-up period, 68 men experienced 92 cardiovascular disease events. After adjusting for age and traditional cardiovascular disease risk factors in proportional-hazards analyses, fractional shortening was a significant independent predictor of cardiovascular risk (relative risk [RR] = 1.42, 95% confidence interval [CI] 1.12 to 1.81, for decrease of fractional shortening by 4%). Increased risk was also associated with combinations of low fractional shortening and high end-diastolic internal dimension (RR = 3.77, 95% CI 1.59 to 8.93) and with low percent fractional shortening with LV hypertrophy (RR = 5.93, 95% CI 1.97 to 17.85). In conclusion, subclinical LV dilatation and LV systolic dysfunction, although uncommon in men free of overt cardiovascular disease, are associated with increased risk for new cardiovascular disease events.

Adult↗
PubMed1992

[The promises of new antithrombotic agents].

Most new antithrombotic drug development projects are focused on the improvement of myocardial infarction treatment at the acute phase. New thrombolytic drugs do not seem to be as attractive as adjunctive therapy, such as antiplatelet and antithrombotic agents, as well as inhibitors of thrombin generation. The current tendency is to select very specific molecules. The difficulty in developing these drugs must not be underestimated: they will be compared to very active drugs, such as aspirin, heparin or streptokinase; the therapeutic margin of antithrombotic therapy is very narrow; a clinical benefit will have to be shown.

Animals↗
PubMed1992

Echocardiographic determinants of clinical outcome in subjects with coronary artery disease (the Framingham Heart Study).

Echocardiographic predictors of clinical outcome were examined in subjects from the Framingham Heart Study with overt coronary artery disease. The study population consisted of 185 men and 147 women with coronary artery disease who underwent M-mode echocardiography and were followed for a mean of 3.90 years. At baseline, 37 men (18.4%) and 16 women (10.9%) had reduced fractional shortening, 43 men (23.2%) and 28 women (19%) had left ventricular (LV) dilatation, and 76 men (41%) and 76 women (51.7%) had LV hypertrophy. During the follow-up period new cardiovascular disease events (coronary disease, stroke, transient ischemic attack, claudication, heart failure and deaths from cardiovascular disease) occurred in 60 men (32%) and 58 women (39%). With use of age-adjusted proportional hazards analyses, LV mass/height in men (relative risk [RR] = 1.25/50 g/m increment, 95% confidence interval [CI] 1.01 to 1.55) and LV end-diastolic diameter in women (RR = 1.36/5 mm increment, 95% CI 1.05 to 1.76) were predictors of new cardiovascular disease events. Cardiovascular risk was also associated with LV end-systolic diameter in both sexes (in men RR = 1.28/1 SD increment, 95% CI 1.02 to 1.63; in women RR = 1.40/1 standard deviation increment, 95% CI 1.09 to 1.82). Reduced fractional shortening alone (RR = 1.91, 95% CI 1.11 to 3.31) and in combination with LV dilatation (RR = 2.13, 95% CI 1.13 to 4.02) was associated with the incidence of new cardiovascular disease outcomes in men.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study)

Several formulas have been proposed to adjust the QT interval for heart rate, the most commonly used being the QT correction formula (QTc = QT/square root of RR) proposed in 1920 by Bazett. The QTc formula was derived from observations in only 39 young subjects. Recently, the adequacy of Bazett's formula has been questioned. To evaluate the heart rate QT association, the QT interval was measured on the initial baseline electrocardiogram of 5,018 subjects (2,239 men and 2,779 women) from the Framingham Heart Study with a mean age of 44 years (range 28 to 62). Persons with coronary artery disease were excluded. A linear regression model was developed for correcting QT according to RR cycle length. The large sample allowed for subdivision of the population into sex-specific deciles of RR intervals and for comparison of QT, Bazett's QTc and linear corrected QT (QTLC). The mean RR interval was 0.81 second (range 0.5 to 1.47) heart rate 74 beats/min (range 41 to 120), and mean QT was 0.35 second (range 0.24 to 0.49) in men and 0.36 second (range 0.26 to 0.48) in women. The linear regression model yielded a correction formula (for a reference RR interval of 1 second): QTLC = QT + 0.154 (1-RR) that applies for men and women. This equation corrects QT more reliably than the Bazett's formula, which overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Lower and upper limits of normal QT values in relation to RR were generated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Determinants of Doppler indexes of left ventricular diastolic function in normal subjects (the Framingham Heart Study).

Normative Doppler values and determinants of left ventricular (LV) diastolic function in healthy subjects have not been fully elucidated. Subjects from the Framingham Heart Study were examined to describe reference values and determinants of echocardiographic Doppler indexes of diastolic function. One hundred twenty-seven randomly selected, rigorously defined, normal subjects, approximately evenly distributed by sex and age from the third through the eighth decades were studied by Doppler echocardiography. Normative values for 7 frequently used Doppler indexes of LV diastolic function are presented. Doppler indexes of LV diastolic function change dramatically with age; the peak velocity of early filling divided by late filling (peak velocity E/A) ranges from a mean of 2.08 +/- 0.55 for subjects in their third decade to 0.84 +/- 0.29 for those in their eighth decade. A peak velocity E/A ratio less than 1 is abnormal in subjects aged less than 40 years, but occurs in most subjects aged greater than or equal to 70 years. The high correlations between age and Doppler indexes of LV diastolic function are not greatly attenuated after adjustment for other clinical parameters associated with diastolic function; the multivariate partial correlation coefficient between age and peak velocity E/A is -0.80 (p less than 0.0001). Heart rate, PR interval, LV systolic function, sex and systolic blood pressure are minor determinants of Doppler indexes of diastolic function. Body mass index, left atrial diameter, and LV wall thickness, internal dimension and mass have little or no association with Doppler indexes in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Mitral annular calcification and the risk of stroke in an elderly cohort.

BACKGROUND: Previous clinical studies have suggested that there is an association between mitral annular calcification and the risk of stroke, but it is unclear whether this association is independent of the traditional risk factors for stroke. We examined the relation between mitral annular calcification and the incidence of stroke in a population-based study. METHODS: Subjects in the Framingham Study receiving a routine examination underwent M-mode echocardiography to determine the presence and severity (thickness in millimeters) of mitral annular calcification. The incidence of stroke during eight years of follow-up was analyzed with a proportional-hazards model adjusting for the calcification, age, sex, systolic blood pressure, diabetes mellitus, cigarette smoking, atrial fibrillation, and coronary heart disease or congestive heart failure. RESULTS: Among 1159 subjects whose echocardiograms could be assessed for mitral annular calcification and who had no history or current evidence of stroke at the index examination (51 percent of all subjects), the prevalence of mitral annular calcification was 10.3 percent in the men and 15.8 percent in the women. Multivariate analysis demonstrated that the presence of mitral annular calcification was associated with a relative risk of stroke of 2.10 (95 percent confidence interval, 1.24 to 3.57; P = 0.006). There was a continuous relation between the incidence of stroke and the severity of mitral annular calcification; each millimeter of thickening as shown on the echocardiogram represented a relative risk of stroke of 1.24 (95 percent confidence interval, 1.12 to 1.37; P less than 0.001). Furthermore, even when subjects with coronary heart disease or congestive heart failure were excluded from the analysis, subjects with mitral annular calcification still had twice the risk of stroke. CONCLUSIONS: In an elderly, longitudinally followed population-based cohort, mitral annular calcification was associated with a doubled risk of stroke, independently of traditional risk factors for stroke. Whether such calcification contributes causally to the risk of stroke or is merely a marker of increased risk because of its association with other precursors of stroke remains unknown.

Adult↗
PubMed1992

Transport of sulfobromophthalein and taurocholate in the HepG2 cell line in relation to the expression of membrane carrier proteins.

The transport of two different classes of organic anions (cholephilic dyes; the sulfobromophthalein, BSP, and bile acids; taurocholate, TC) was investigated in the HepG2 cell line. At 37 degrees C, BSP uptake was found to be biphasic with an apparent saturative curve in the concentration range between 0-6 microM followed by a linear component up to 18 microM. Kinetic constant determination showed an apparent Km of 26.6 +/- 3.1 microM and a Vmax of 5.64 +/- 0.82 nmol BSP.min-1.mg prot-1. At 4 degrees C, uptake was linear. By subtracting this latter component from the total uptake, a saturable, carrier mediated uptake was found with an apparent Km of 3.6 +/- 1.0 microM BSP and a Vmax of 0.37 +/- 0.04 nmol BSP.min-1.mg prot-1 (m +/- SEM, n = 6). These values were fully comparable with those found in freshly isolated male hepatocyte. Immunoblot analysis of HepG2 cell plasma membrane revealed the presence of bilitranslocase when tested against a monospecific antibody against this carrier molecule. On the contrary, TC uptake was linear up to concentration of 100 microM TC. No difference was observed in the presence or absence of Na+. Immunoprecipitation analysis showed the absence of the putative carrier of TC. These data indicate that the HepG2 cell line expresses a functioning bilitranslocase-mediated system. Conversely, carrier mediated bile acid uptake is absent in line with the lack of expression of the carrier protein.

ATP-Binding Cassette Transporters↗
PubMed1992

Cancer: improving early detection and prevention. A community practice randomised trial.

OBJECTIVE: To test the impact of physician education and facilitator assisted office system interventions on cancer early detection and preventive services. DESIGN: A randomised trial of two interventions alone and in combination. SETTING AND SUBJECTS: Physicians in 98 ambulatory care practices in the United States. INTERVENTIONS: The education intervention consisted of a day long physician meeting directed at improving knowledge, attitudes, and skills relevant to cancer prevention and early detection. The office system intervention consisted of assistance from a project facilitator in establishing routines for providing needed services. These routines included division of responsibilities for providing services among physicians and their staff and the use of medical record flow sheets. MAIN OUTCOME MEASURES: The proportions of patients provided the cancer prevention and early detection services indicated annually according to the US National Cancer Institute. RESULTS: Based on cross sectional patient surveys, the office system intervention was associated with an increase in mammography, the recommendation to do breast self examination, clinical breast examination, faecal occult blood testing, advice to quit smoking, and the recommendation to decrease dietary fat. Education was associated only with an increase in mammography. Record review for a patient cohort confirmed cross sectional survey findings regarding the office system for mammography and faecal occult blood testing. CONCLUSION: Community practices assisted by a facilitator in the development and implementation of an office system can substantially improve provision of cancer early detection and preventive services.

Adult↗
PubMed1992

Is there a relationship between exercise systolic blood pressure response and left ventricular mass? The Framingham Heart Study.

OBJECTIVE: To assess the association between an exaggerated exercise systolic blood pressure response and the occurrence of left ventricular hypertrophy in healthy, normotensive individuals. DESIGN: Cross-sectional survey using M-mode echocardiography to measure left ventricular mass and to detect left ventricular hypertrophy. SETTING: The Framingham Heart Study. SUBJECTS: Eight-hundred sixty men and 1118 women were studied who were free of cardiovascular or pulmonary disease, who were not taking any antihypertensive or cardiovascular medications, and who successfully achieved at least 90% of their age-predicted maximum heart rate during a monitored exercise treadmill test. All subjects had normal baseline and exercise electrocardiograms. MEASUREMENTS AND MAIN RESULTS: Men with a peak exercise systolic blood pressure of 210 or more and women with a peak exercise systolic blood pressure of 190 or more were considered to have an "exaggerated" blood pressure response; 122 men and 67 women met these criteria. Subjects with an exaggerated exercise systolic blood pressure response had 10% higher left ventricular mass than those with a normal exercise systolic blood pressure response (in men: 115 +/- 25 compared with 105 +/- 24 g/m, P less than 0.001; in women: 86 +/- 22 compared with 73 +/- 16 g/m, P less than 0.001); they also had a higher prevalence of left ventricular hypertrophy (in men: odds ratio, 1.34, 95% CI, 1.00 to 1.80; in women: odds ratio, 2.12, CI, 1.48 to 3.03). After adjusting for age, resting systolic blood pressure, and body mass index, however, subjects with an exaggerated exercise systolic blood pressure response had only 5% higher left ventricular mass (in men: 111 +/- 2.1 compared with 106 +/- 0.8 g/m, P = 0.02; in women: 80 +/- 1.8 compared with 74 +/- 0.4 g/m, P = 0.002), and they no longer had a statistically increased prevalence of left ventricular hypertrophy (in men: odds ratio, 1.21, CI, 0.87 to 1.67; in women: odds ratio, 1.30, CI, 0.84 to 2.01). CONCLUSIONS: The apparent relation between exercise systolic blood pressure response and left ventricular mass is confounded by age, resting systolic blood pressure, and body mass; the degree of confounding is such that the biologic significance of this relationship should be questioned.

Adult↗
PubMed1992

Cerebral blood flow and metabolism in hypothermic circulatory arrest.

Although hypothermic circulatory arrest has been accepted for use in cardiovascular operations, the potential for cerebral injury exists. The mechanism of the cerebral injury remains unclear. To address these questions we studied cerebral blood flow and metabolism. Sixteen puppies were randomly assigned to undergo either 45 or 90 minutes of hypothermic circulatory arrest after perfusion/surface cooling to 13 degrees C. Cerebral blood flow, cerebral oxygen and glucose metabolism, and cerebral vascular resistance measurements were obtained at 37 degrees C, 13 degrees C, 10 minutes after reperfusion, 30 degrees C and 2 and 4 hours after hypothermic circulatory arrest. No neurologic or behavioral changes were observed in any of the long-term survivors (11/16). Metabolic and cerebral blood flow data did not differ between groups. Cerebral blood flow was significantly lower in the late postarrest measurements, whereas oxygen and glucose consumption had returned to baseline values. In the presence of low cerebral blood flow and high cerebral vascular resistance it is notable that control levels of oxygen consumption were attained by abnormally high oxygen extraction. These data strongly suggest a vulnerable interval after hypothermic circulatory arrest in which cerebral metabolism is limited by cerebral blood flow.

Animals↗
PubMed1992

Separate and joint influences of obesity and mild hypertension on left ventricular mass and geometry: the Framingham Heart Study.

Increased left ventricular mass has been shown to be a significant independent predictor of cardiovascular risk. The purpose of this study was to assess the separate and combined relations of obesity and hypertension with left ventricular mass and geometry. Echocardiographic findings in subjects in the Framingham Heart Study who were free of cardiopulmonary disease and were not taking cardiovascular medications were examined. M-mode studies that were adequate for estimating left ventricular mass were available in 624 men and 1,209 women. Height and weight measured at the time of echocardiography were used to calculate body mass index (in kg/m2), a measure of obesity. Casual sitting blood pressure measurements were obtained to detect rest hypertension. In subgroup analyses of lean normotensive, obese normotensive, lean hypertensive and obese hypertensive subjects, hypertension and obesity each had significant independent associations with left ventricular mass and wall thickness (all p less than 0.001 in men and women). Obesity was also associated with left ventricular internal diameter (p less than 0.001 in men and women). There were no synergistic influences of hypertension and obesity on any echocardiographic left ventricular variables. It is concluded that obesity and hypertension each have distinct associations with left ventricular mass and geometry. These strengths of association are additive but not synergistic.

Adult↗