Biomedical subjects

E J Benjamin

Publications and source records attributed to E J Benjamin.

51 records · Page 3Linked to original sources

PubMed1994

Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study.

OBJECTIVE: To determine the independent risk factors for atrial fibrillation. DESIGN: Cohort study. SETTING: The Framingham Heart Study. SUBJECTS: A total of 2090 men and 2641 women members of the original cohort, free of a history of atrial fibrillation, between the ages of 55 and 94 years. MAIN OUTCOME MEASURES: Sex-specific multiple logistic regression models to identify independent risk factors for atrial fibrillation, including age, smoking, diabetes, electrocardiographic left ventricular hypertrophy, hypertension, myocardial infarction, congestive heart failure, and valve disease. RESULTS: During up to 38 years of follow-up, 264 men and 298 women developed atrial fibrillation. After adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times greater risk of developing atrial fibrillation than women. In the full multivariable model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age was 2.1 for men and 2.2 for women (P < .0001). In addition, after multivariable adjustment, diabetes (OR, 1.4 for men and 1.6 for women), hypertension (OR, 1.5 for men and 1.4 for women), congestive heart failure (OR, 4.5 for men and 5.9 for women), and valve disease (OR, 1.8 for men and 3.4 for women) were significantly associated with risk for atrial fibrillation in both sexes. Myocardial infarction (OR, 1.4) was significantly associated with the development of atrial fibrillation in men. Women were significantly more likely than men to have valvular heart disease as a risk factor for atrial fibrillation. The multivariable models were largely unchanged after eliminating subjects with valvular heart disease. CONCLUSION: In addition to intrinsic cardiac causes such as valve disease and congestive heart failure, risk factors for cardiovascular disease also predispose to atrial fibrillation. Modification of risk factors for cardiovascular disease may have the added benefit of diminishing the incidence of atrial fibrillation.

Age Factors↗

PubMed1994

Echocardiographic predictors of nonrheumatic atrial fibrillation. The Framingham Heart Study.

BACKGROUND: Although structural heart disease is often present in patients with nonrheumatic atrial fibrillation, the echocardiographic precursors of atrial fibrillation have not been reported previously. In this elderly, population-based cohort, our objective was to examine prospectively the echocardiographic predictors of nonrheumatic atrial fibrillation. METHODS AND RESULTS: Subjects in the Framingham Heart Study were routinely evaluated with M-mode echocardiography; 1924 subjects, ranging in age from 59 to 90 years, comprised the population at risk. Cox proportional hazards modeling was used to analyze the association of selected echocardiographic features with atrial fibrillation risk after adjustment for age, sex, hypertension, coronary heart disease, congestive heart failure, diabetes, and valvular heart disease. During a mean follow-up interval of 7.2 years, 154 subjects (8.0%) developed atrial fibrillation. Multivariable stepwise analysis identified left atrial size (hazard ratio [HR] per 5-mm increment, 1.39; 95% confidence interval [CI], 1.14 to 1.68), left ventricular fractional shortening (HR per 5% decrement, 1.34; 95% CI, 1.08 to 1.66), and sum of septal and left ventricular posterior wall thickness (HR per 4-mm increment, 1.28; 95% CI, 1.03 to 1.60) as independent echocardiographic predictors of atrial fibrillation. For each of the echocardiographic predictors, risk increased progressively over successive quartiles. Moreover, risk increased markedly when highest-risk-quartile measurements for these features were present in combination; the cumulative 8-year age-adjusted atrial fibrillation rates were 7.3% and 17.0%, respectively, when one and two or more highest-risk-quartile features were present, compared with 3.7% when none was present. CONCLUSIONS: In this elderly, population-based sample, left atrial enlargement, increased left ventricular wall thickness, and reduced left ventricular fractional shortening were predictive of risk for nonrheumatic atrial fibrillation. These echocardiographic precursors offer prognostic information beyond that provided by traditional clinical atrial fibrillation risk factors.

Adult↗

PubMed1993

Impact of heart rate and PR interval on Doppler indexes of left ventricular diastolic filling in an elderly cohort (the Framingham Heart Study).

The relations of heart rate and PR interval to Doppler-derived diastolic indexes were examined in 260 men (mean age 75 years) and 462 women (mean age 76 years) from the Framingham Heart Study. Subjects receiving any antihypertensive or cardiac medications were excluded from eligibility; those with mitral stenosis or prosthesis, pacemaker, atrial fibrillation, arrhythmia, left bundle branch block, congestive heart failure, previous myocardial infarction, and technically inadequate Doppler study were also excluded. Peak velocity of early (E) and late (A) diastolic left ventricular (LV) filling, ratio of peak velocities E/A, ratio of time velocity integrals E/A, and atrial filling fraction were studied by multivariable analyses adjusting for age, sex, blood pressure, heart rate and PR interval. Heart rate was a major determinant of all 5 Doppler indexes of diastolic filling; heart rate was inversely associated with peak velocity E, E/A, and time velocity integral E/A, and was directly associated with peak velocity A and atrial filling fraction. PR interval was inversely associated with time velocity integral E/A (p < 0.01) and directly associated with atrial filling fraction. The results were largely unaltered after further adjustment for LV wall thickness, LV end-diastolic diameter and left atrial diameter (in addition to age, sex and blood pressure). Heart rate and PR interval are independent contributors to Doppler-assessed LV diastolic filling in the elderly. The atrial contribution to LV filling depends on its timing in the cardiac cycle and on heart rate. Failure to account for heart rate and PR interval may lead to inappropriate assessment of Doppler diastolic filling.

Aged↗

PubMed1993

Echocardiographic assessment of left ventricular structure and diastolic filling in elderly subjects with borderline isolated systolic hypertension (the Framingham Heart Study).

Abnormalities in left ventricular (LV) structure and function have been shown in patients with diastolic hypertension and recently in subjects with isolated systolic hypertension. The purpose of this study was to determine whether abnormalities of cardiac structure or function are present in elderly subjects with borderline isolated systolic hypertension (defined as systolic blood pressure [BP] between 140 and 159 mm Hg, and diastolic BP < 90 mm Hg). Ninety-one subjects (mean age 77 years) from the original Framingham Heart Study with untreated borderline isolated systolic hypertension, who were free of cardiovascular disease, were compared with 139 normotensive (BP < 140/90 mm Hg) subjects (mean age 76 years). Measurements included M-mode values for LV structure, and 6 Doppler indexes of LV diastolic filling. Subjects with borderline isolated systolic hypertension and the control group differed in mean systolic (147 vs 125 mm Hg) and diastolic (76 vs 70 mm Hg) BP. Borderline systolic hypertension was the most frequent form of untreated hypertension in this elderly group. The sum of LV wall thicknesses (septum+posterior wall) was significantly higher in borderline hypertensive subjects than in normotensive ones (20.5 vs 19.7 mm; p = 0.002). No difference was detected in LV internal dimension or systolic function. After adjustment for age and other clinical variables, comparisons between the groups revealed significant differences in indexes of Doppler diastolic filling. Peak velocity of early filling, and the ratio of early to late peak velocities were lower in the hypertensive group (40 vs 44 cm/s [p = 0.03] and 0.69 vs 0.76 [p = 0.01], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

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

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↗

PubMed1987

Selection of a derivative of the antiviral agent 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) with improved oral absorption.

Various diesters of 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) were screened in order to identify a derivative with improved oral absorption. The solubilities and dissolution rates decreased with increasing chain length and branching of the ester group. However, the dipropionate ester showed an anomalously faster dissolution rate. The rates of hydrolysis to DHPG in the presence of intestinal homogenates were found to increase with increasing carbon number for the straight-chain alkyl esters and decreased with branching. The shorter-chain alkyl esters were relatively more stable in intestinal homogenates than in liver homogenates. Therefore they may have a better membrane permeability than DHPG due to their intact ester group. The hydrolysis rates in human blood increased with increasing carbon number for the straight-chain alkyl esters. The dipropionate ester appeared to be the most promising derivative because of its rapid dissolution rate, slower hydrolysis in the intestine, and rapid conversion to DHPG in liver and blood.

Acyclovir↗

PubMed1985

A dual-column HPLC method for the simultaneous determination of DHPG (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) and its mono and diesters in biological samples.

A convenient method for the simultaneous determination of various DHPG species present in biological samples is presented. This method utilizes a cation exchange column (25 cm X 4.6 mm i.d.) coupled in series to a short reversed-phase column (5 cm X 4.6 mm i.d.). The mobile phase consists of methanol:0.005M ammonium phosphate buffer, pH 2.5. There is a large polarity difference between DHPG and its esters due to the non-polar side chain of the ester moiety. The simultaneous determination of the diesters, monoesters, and DHPG in these samples using only the cation exchange or the reversed-phase column is not possible without time-consuming gradient elution. In the reversed-phase mode alone, the esters are highly retained relative to DHPG, whereas the esters are only slightly retained on a cation exchange column and are insensitive to changes in pH and ionic strength of the mobile phase. However, a combination of these two columns provides interesting selectivity for these compounds and offers a unique way of controlling the retention times of these species relative to each other. The retention time of esters can be selectively altered (with respect to DHPG) by changing the composition of methanol in the mobile phase. In contrast, the retention time of DHPG is controlled by changing the buffer strength and pH of the mobile phase.

Acyclovir↗

PubMed1983

Automated high-performance liquid chromatographic column switching technique for the on-line clean-up and analysis of drugs in topical cream formulations.

The automation of a high-performance liquid chromatographic column switching technique for the on-line clean-up and analysis of drug substances in topical cream formulations is described. A short reversed-phase precolumn used for primary sample clean-up was coupled to a reversed-phase analytical column. This allowed cream samples dissolved in methanol-tetrahydrofuran to be injected directly into the analysis system without prior laborious and time-consuming clean-up procedures. This application was successfully extended to the analysis of sulconazole nitrate, and a triple corticoid cream. The effects of precolumns on some chromatographic parameters were studied.

Autoanalysis↗

PubMed1983

Characterization of spray patterns of inhalation aerosols using thin-layer chromatography.

The spray pattern of an inhalation aerosol was characterized using photography and by observing the impaction pattern on a TLC plate. The aerosol plume was conical in shape, and its cross section increased with increasing distance from the actuator. Three puffs of the aerosol, at a distance of 3 cm between actuator and the TLC plate, produced a spot that had approximately the same diameter as the cross section of the aerosol plume at that distance from the actuator. The TLC technique with these parameters was selected to develop an assay characterizing the spray pattern of an inhalation aerosol because of its specificity, simplicity, and speed.

Aerosols↗

PubMed1981

Nonsteroidal estrogens and antiestrogens: biological activity of cyclopropyl analogs of stilbene and stilbenediol.

The estrogenic, antiestrogenic, and receptor binding activity of a series of cyclopropyl analogs of stilbene and stilbenediol were determined using the uterotropic assay in the mouse and the receptor binding assay with rat uterine cytosol. One compound, 1,1-dichloro-cis-2,3-diphenylcyclopropane (II), displayed antiestrogenic activity in vivo with a low affinity for the estrogen receptor in vitro and showed tumor remission activity on 7,12-dimethylbenz(a)anthracene-induced estrogen-dependent rat mammary tumors. Compounds VIII, IV, and V (in that order) exhibited the greatest estrogen activity in the mouse and the greatest receptor binding activity in vitro. Compound VIII exhibited antifertility activity in the mouse.

Animals↗

PubMed1975

Synthesis of clyclopropyl analogs of stilbene and stilbenediol as possible antiestrogens.

Conformationally rigid analogs of stilbene and stilbenediol were prepared via gem-dichlorocyclopropyl precursors utilizing two different synthetic methods: a two-phase catalytic method and an organomercurial method. These precursors were reduced to the corresponding cyclopropyl analogs using sodium and methanol. All compounds are being tested to discriminate between estrogenic and antiestrogenic ability, to determine estrogen binding ability, and to evaluate tissue culture anticancer activity.

Catalysis↗

PubMedDate not supplied

Echocardiographic reference values for aortic root size: the Framingham Heart Study.

The objectives of this study were to develop sex-, age-, and body size-specific nomograms and partition values for upper and lower limits of M-mode echocardiographic aortic root measurements derived from a large population-based cohort. The study sample consisted of 1433 male and 1816 female participants in the Framingham Heart Study and Framingham Offspring Study who were normotensive and free of clinically apparent heart disease at the baseline examination. Aortic root measurements were obtained by M-mode echocardiography by a leading-edge to leading-edge technique. The relations of age and measures of body size with aortic root dimensions were evaluated with sex-specific correlations and multiple stepwise linear regression analyses. Age was the most important determinant of aortic root size in both men and women in the multivariable regression models. Models with age and body surface area yielded R2 values of 0.214 in men and 0.222 in women. Models with age and height yielded lower R2 values of 0.136 in men and 0.181 in women. Thus aortic root dimensions vary widely with the age, sex, and body size of individuals. Sex-specific reference nomograms of aortic root dimensions in relation to age and body size (body surface area or height) are presented to facilitate the detection of abnormalities of aortic root size.

Adult↗

PubMedDate not supplied

Reference values for Doppler indexes of left ventricular diastolic filling in the elderly.

Congestive heart failure increases in prevalence with age. A large number of elderly subjects with heart failure have either normal or slightly reduced left ventricular (LV) systolic function; their symptoms are due to diastolic LV dysfunction. Reference values for Doppler indexes of LV diastolic filling in a large sample of the very elderly (> 70) have not been reported previously. The objective of this study was to generate reference values for Doppler indexes of LV filling in a population of apparently healthy elderly men and women. A total of 1201 surviving original subjects of the Framingham Heart Study were evaluated by Doppler echocardiography. A subset of 114 rigorously selected healthy subjects (26 men and 88 women) aged 70 to 87 years (mean 76) constituted the study group. Measurements of seven commonly used Doppler indexes were obtained. Mean and 2.5, 5, 10, 25, 50, 75, 90, 95, and 97.5 percentile values for Doppler diastolic indexes were generated. Stepwise regression analyses were performed to determine the relation of diastolic LV filling to age group (70 to 74 years, 75 to 79 years, and 80 years and over), sex, and other clinical variables. Reference values for the various Doppler parameters were generated on the basis of this healthy elderly cohort. There was evidence for a slight progressive decline in indexes of LV inflow with age. In 87% of this elderly population the ratio of peak early to late velocities of LV diastolic inflow was less than 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗