Biomedical subjects

K M Anderson

Publications and source records attributed to K M Anderson.

At least 19 recordsLinked to original sources

PubMed1995

Impact of echocardiographic left ventricular mass on mechanistic implications of exercise testing parameters.

Electrocardiographic left ventricular (LV) hypertrophy has long been known to be associated with an abnormal ST-segment response to exercise; this association has been considered to represent a false-positive finding. There is a paucity of data relating echocardiographic LV mass to exercise ST-segment responses and other exercise parameters. As part of a routine evaluation, 1,408 men and 1,618 women from the Framingham Heart Study who were free of clinical cardiac disease underwent echocardiography and exercise treadmill testing according to the Bruce protocol at the same clinic visit. Abnormal ST-segment responses were defined both by standard criteria and the delta ST/heart rate index. LV mass was calculated from M-mode echocardiography. Echocardiographic LV hypertrophy was associated with an abnormal delta ST/heart rate index (in men, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.05 to 3.01, p = 0.03; in women, OR 2.13, 95% CI 1.31 to 3.44, p = 0.002) but not with an abnormal response according to standard criteria. Echocardiographic LV hypertrophy was also associated with a lower likelihood of achieving an age-predicted target heart rate (in men, OR 0.45, 95% CI 0.31 to 0.65, p < 0.001; in women, OR 0.53, 95% CI 0.37 to 0.76, p < 0.001) and with a lower exercise capacity. Despite these associations, echocardiographic LV hypertrophy was associated with a higher peak heart rate-systolic blood pressure double product. In conclusion, echocardiographic LV hypertrophy is associated with an abnormal ST-segment response, a lower likelihood of achieving target heart rate, decreased exercise capacity, and an increased double product, which is a reflection of myocardial oxygen demand.

Adult↗

PubMed1995

Water-clear cell adenoma of the parathyroid. A case report with immunohistochemistry and electron microscopy.

We report a water-clear cell adenoma of the parathyroid gland, a lesion which to our knowledge has not been described previously. Like its rare but well-described hyperplastic counterpart, water-clear cell hyperplasia, this adenoma is composed of cells with abundant foamy-to-granular cytoplasm and mild nuclear pleomorphism. The cells form glandular structures and cell nests separated by fine fibrovascular septae. The tumor cells stain positively with anti-parathyroid hormone and show characteristic glassy and flocculate material by electron microscopy. Unlike water-clear cell hyperplasia, water-clear cell adenoma is a solitary lesion that compresses the residual nonneoplastic parathyroid gland.

Adenoma↗

PubMed1993

Decline in defibrillation thresholds.

UNLABELLED: Much research has been done to lower defibrillation thresholds (DFT) through improved waveforms and electrodes. We hypothesized that DFTs are declining steadily, as did pacing thresholds. We performed a meta-analysis of 105 reports of DFTs from 58 articles and abstracts published from 1973 to 1991. Human, dog, and pig studies were included. Transthoracic and isolated heart studies were excluded. Variables analyzed were: publication year, human study, epicardial electrodes only, multiple pathways (simultaneous or sequential), biphasic wave, subcutaneous patch, coronary sinus electrode, spring-patch combination, and catheter-based. DFTs are highly correlated with publication year (P = 0.013) and show an average drop of 0.75 joules/year by a linear univariate analysis. A linear multivariate analysis (r2 = 0.51) gave six significant variables for the DFT: epicardial electrodes only, subcutaneous patch, biphasic wave, coronary sinus electrode (each decreased DFTs), and human subject and catheter-based system (increased DFTs). CONCLUSIONS: DFTs have shown a decline over 18 years through electrode and waveform improvements. The practice of making devices with ever increasing energy ratings may eventually merit reexamination. The animal model is a useful predictor for clinical DFTs.

Animals↗

PubMed1992

Serum cholesterol level, body mass index, and the risk of colon cancer. The Framingham Study.

BACKGROUND: Some studies have linked low serum cholesterol levels to increased risk of colon cancer, particularly in men. Results have been inconsistent, with preclinical disease frequently offered to explain any apparent association. METHODS: The Framingham Study cohort of 5209 persons, initially 30-62 years of age and observed more than 30 years, was evaluated. Baseline data included lipoprotein fractions, total cholesterol levels, body mass index, alcohol intake, and cardiovascular risk variables such as cigarette smoking, hypertension, and glucose intolerance. RESULTS: In this population, colon cancer in men is related inversely to serum cholesterol levels, even when the first 10 years of follow-up are eliminated to reduce the effect of preclinical disease. This effect is concentrated in the Svedberg 0-20 fraction, corresponding to low-density lipoprotein levels. Another finding only in men is the direct relation of body mass index to colon cancer incidence. CONCLUSIONS: Combined initial low serum cholesterol levels and obesity appear to indicate a four times greater risk for colon cancer in men as compared with people with average values of both variables. The reasons for these observations are unknown.

Adult↗

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

Eicosatetraynoic and arachidonic acid-induced changes in cell membrane fluidity consonant with differences in computer-aided design-structures.

ETYA (5,8,11,14-eicosatetraynoic acid), a competitive analogue of arachidonic acid (AA), inhibits the proliferation of U937 (human monoblastoid) and PC3 (human prostate) cancer cells, without the overt cytotoxicity associated with AA at similar concentrations. The mechanism of inhibition is not established. ETYA at 100 microM acutely increased whole cell and isolated microsomal membrane fluidity of both cell lines to a greater extent than arachidonic acid. PC3 cells incubated with ETYA for 72 h evidenced increased membrane fluidity. This was measured by the fluorescence polarization parameter, R, using the probes TMA-DPH and DPH for whole cell and isolated membrane fractions, respectively. Compared with whole cells, isolated membranes yielded a 10-20-fold increase in fluorescence intensity. The intramolecular conformational profiles of both ETYA and AA were explored using a combination of molecular mechanics energy minimization and molecular dynamics simulation. While it is possible that not all of the low energy conformational states of either molecule were sampled, the large number of low-energy conformers determined for ETYA correspond to kink deformed conformers relative to the family of AA conformers. These kinks make the molecular cross sections of ETYA larger than AA and arise from the four alkyne bond geometries. This structural finding is consistent with ETYA's greater effect on membrane fluidity. Dissociation between the extent of change in membrane fluidity due to ETYA or AA and inhibition of DNA synthesis can suggest that either (A) increased fluidity and inhibition of DNA synthesis are independent, or as we believe more likely, (B) greater membrane fluidity evoked by ETYA is important for inhibiting DNA synthesis, while changes induced by AA are insufficient or differ qualitatively from those required to initiate and sustain these nonlethal events.

Arachidonic Acids↗

PubMed1992

Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.

Apolipoproteins↗

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

5,8,11,14-eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3).

Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1992

ETYA, a pleotropic membrane-active arachidonic acid analogue affects multiple signal transduction pathways in cultured transformed mammalian cells.

ETYA (5,8,11,14-eicosatetraynoic acid), an arachidonic acid analogue, inhibited DNA synthesis in human transformed U937 (monoblastoid), PC3 (prostate) and A172 (glioblastoma) cells, and partially differentiated the U937 and A172 lines. The agent is not primarily cytotoxic at the concentrations employed, based upon exclusion of trypan blue, continued attachment of PC3 and A172 cells, unchanged release of Cr51, and reversibility of inhibited thymidine incorporation after removal of ETYA. Leukotriene C4 partially reversed the suppression of U937 DNA synthesis, suggesting its modulation by leukotrienes. U937 and A172 cells partially differentiated, as judged by a number of criteria. ETYA increased whole cell and microsomal membrane fluidity, increased intracellular Ca2+ in PC3 and U937 cells, altered the distribution and activity of protein kinase C in U937 cells, and rapidly downregulated the transcription of U937 c-myc. Evidence from transmission electron microscopy consistent with oxidative stress including putative lipofuscin bodies, myelin figures and disordered mitochondrial cristae and matrices was especially evident in PC3 cells, less so in A172 and essentially absent in U937 cells. A specific 5'-lipoxygenase inhibitor, A63162 inhibited PC3 and U937 proliferation. Some of these events are believed to represent components of "signal" transduction pathways responsible for reversible inhibition of DNA synthesis and the induction of partial phenotypic differentiation in competent cells. Arachidonic acid analogues which exert selective effects on physical and functional properties of cell membranes may represent an additional class of membrane-active agents with potential anticancer activity. A subset of their activities can be duplicated by inhibitors of 5' lipoxygenase.

5,8,11,14-Eicosatetraynoic Acid↗

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↗

PubMed1992

Differential effects of ETYA, a PUFA-analogue, on prostate (PC3) and monoblastoid U937 ultrastructure; lack of correlation with reduced proliferation.

ETYA (5,8,11,14-eicosatetraynoic acid), a polyunsaturated fatty acid analogue, inhibits proliferation of PC3 and U937 cells and induces a limited differentiation in U937 cells. Human prostate PC3 cells cultured for 72 h with 40 microM ETYA in fetal calf serum contained putative lipofuscin bodies, myelin figures and mitochondria with damaged cristae and matrices. These changes were absent from human U937 monoblastoid cells incubated with ETYA in CPSR3, a semipurified serum replacement. U937 cells cultured with ETYA in fetal calf serum contained occasional lipofuscin bodies, while PC3 cells cultured in CPSR3 exhibited all of the changes described. ETYA reduced the oxygen consumption of both cell lines. Therefore we conclude: (a) The response to ETYA by cells of dissimilar developmental origin is not identical; (b) unidentified serum components can augment potential ETYA-induced oxidative stress-responses of cells; (c) inhibition of U937 proliferation by ETYA does not depend upon the morphologic changes seen in PC3 cells, which resemble sequelae of oxidative stress with excess free radicals; and (d) rapid ETYA-induced inhibition of oxygen consumption in both cell lines implies a reduced synthesis of ATP that could contribute to the reversible impairment of cellular proliferation.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1992

Three-dimensional viewing of and dosimetric calculations in Au-198 implants of the prostate.

A three-dimensional system for dosimetric calculation of radiation from interstitial brachytherapeutic implants was developed and was compared with conventional dosimetry performed with a commercial two-dimensional system. Software programs written for this study enabled the authors to place radioactive sources in the correct reconstructed anatomic locations, compute the isodose distribution around these sources, and display the isodose curves in their correct relationship to anatomic structures. Eight radiation oncologists evaluated the usefulness of both systems. Verification studies in phantoms and in 20 patients with gold-198 implants in the prostate gland showed that the experimental system was very accurate in volume reconstruction, seed localization, isodose distribution, point-dose calculation, and computation of dose-volume histograms. Although the dose depictions in the two systems matched almost exactly, statistically significant differences existed in interpretation of the dosimetric data generated by both systems. For example, the oncologists consistently believed that the dose to the prostate was lower when the three-dimensional system was used (P less than or equal to .0001).

Brachytherapy↗

PubMed1992

Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study.

We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high-density lipoprotein cholesterol levels. In regression analyses that controlled for these and other potential risk factors, HbA1c remained significantly related to CVD among women. The relative odds of CVD increased 1.39-fold (95% confidence interval 1.06-1.83) for increases in HbA1c of 1% (e.g., for HbA1c from 5 to 6%). The relationship was not weakened when known diabetic subjects or subjects taking beta-blocker or thiazide medications were excluded from analysis. In contrast, there was no significant relationship between "casual" blood glucose and prevalent CVD. Our results reveal a strong, significant, independent association between hyperglycemia, measured by HbA1c, and CVD among older women.

Aged↗

PubMed1992

Echocardiographic left ventricular hypertrophy: clinical characteristics. The Framingham Heart Study.

Recent data suggest that echocardiographic left ventricular (LV) hypertrophy is associated with increased cardiovascular morbidity and mortality. Based upon application of sex-specific echocardiographic criteria for LV hypertrophy, the clinical characteristics of 863 subjects with and 4097 subjects without LV hypertrophy are examined. Subjects with LV hypertrophy are older, more obese, have higher blood pressure, and are more likely to have pre-existing coronary artery disease. In addition subjects with LV hypertrophy have a higher prevalence of reduced echocardiographic fractional shortening. We conclude that subjects with echocardiographic LV hypertrophy are at high risk for cardiovascular disease complications by virtue of their clinical profile. Additional investigation of the benefits of therapeutic interventions directed toward the prevention or regression of LV hypertrophy is warranted.

Adolescent↗

PubMed1992

Maximum likelihood estimation for interval-censored data using a Weibull-based accelerated failure time model.

The accelerated failure time regression model is most commonly used with right-censored survival data. This report studies the use of a Weibull-based accelerated failure time regression model when left- and interval-censored data are also observed. Two alternative methods of analysis are considered. First, the maximum likelihood estimates (MLEs) for the observed censoring pattern are computed. These are compared with estimates where midpoints are substituted for left- and interval-censored data (midpoint estimator, or MDE). Simulation studies indicate that for relatively large samples there are many instances when the MLE is superior to the MDE. For samples where the hazard rate is flat or nearly so, or where the percentage of interval-censored data is small, the MDE is adequate. An example using Framingham Heart Study data is discussed.

Age Factors↗

PubMed1991

Influence of contemporary versus 30-year blood pressure levels on left ventricular mass and geometry: the Framingham Heart Study.

To determine whether long-term blood pressure levels correlate with left ventricular mass, echocardiographic measurements were performed in 152 men and 299 women who were participants in the Framingham Heart Study. All subjects were free of obesity and cardiovascular and pulmonary disease, were not taking antihypertensive medications and had echocardiographic studies that were adequate for estimating left ventricular mass. Thirty-year average systolic blood pressure was correlated with left ventricular mass (corrected for height) (r = 0.27, p less than 0.001 in men; r = 0.31, p less than 0.001 in women). Multivariate linear regression analyses taking into account age and body mass index showed 30-year average systolic blood pressure to be a significant independent predictor of left ventricular mass (p less than 0.01 in men and women). Systolic blood pressure at echocardiography was not independently associated with left ventricular mass when 30-year systolic blood pressure was entered into the multivariate model. The prevalence of left ventricular hypertrophy was associated with 30-year average systolic blood pressure (odds ratio for every 20-mm Hg increase in blood pressure: 3.20, p less than 0.05 in men; 3.27, p less than 0.001 in women). The increase in left ventricular mass associated with 30-year average systolic blood pressure reflected changes in left ventricular wall thickness but not in left ventricular internal dimension. Thirty-year average diastolic blood pressure was also correlated with left ventricular mass but to a lesser degree than was systolic blood pressure (r = 0.18, p less than 0.05 in men; r = 0.18, p less than 0.01 in women).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study.

OBJECTIVE: --To determine the relationship of varying degrees of obesity with left ventricular mass and geometry. DESIGN: --Survey. SETTING: --Population-based epidemiologic study. PARTICIPANTS AND METHODS: --M-mode echocardiograms, which were adequate for estimation of left ventricular mass, were obtained in 3922 healthy participants of the Framingham Heart Study. Measured height and weight were used to calculate body-mass index, a measure of obesity. RESULTS: --Body-mass index was strongly correlated with left ventricular mass. After adjusting for age and blood pressure, body-mass index remained a strong independent predictor of left ventricular mass, left ventricular wall thickness, and left ventricular internal dimension (P less than .01 for all). Body-mass index was associated with prevalence of echocardiographic left ventricular hypertrophy, particularly in subjects with a body-mass index exceeding 30 kg/m2. CONCLUSIONS: --Obesity is significantly correlated with left ventricular mass, even after controlling for age and blood pressure. The increase in left ventricular mass associated with increasing adiposity reflects increases in both left ventricular wall thickness and left ventricular internal dimension.

Adult↗