Biomedical subjects

K M Anderson

Publications and source records attributed to K M Anderson.

At least 91 records · Page 5Linked to original sources

PubMed1994

Parametric approaches to quality-adjusted survival analysis. International Breast Cancer Study Group.

We present a parametric methodology for performing quality-of-life-adjusted survival analysis using multivariate censored survival data. It represents a generalization of the nonparametric Q-TWiST method (Quality-adjusted Time without Symptoms and Toxicity). The event times correspond to transitions between states of health that differ in terms of quality of life. Each transition is governed by a competing risks model where the health states are the competing risks. Overall survival is the sum of the amount of time spent in each health state. The first step of the proposed methodology consists of defining a quality function that assigns a "score" to a life having given health state transitions. It is a composite measure of both quantity and quality of life. In general, the quality function assigns a small value to a short life with poor quality and a high value to a long life with good quality. In the second step, parametric survival models are fit to the data. This is done by repeatedly modeling the conditional cause-specific hazard functions given the previous transitions. Covariates are incorporated by accelerated failure time regression, and the model parameters are estimated by maximum likelihood. Lastly, the modeling results are used to estimate the expectation of quality functions. Standard errors and confidence intervals are computed using the bootstrap and delta methods. The results are useful for simultaneously evaluating treatments in terms of quantity and quality of life. To demonstrate the proposed methods, we perform an analysis of data from the International Breast Cancer Study Group Trial V, which compared short-duration chemotherapy versus long-duration chemotherapy in the treatment of node-positive breast cancer. The events studied are: (1) the end of treatment toxicity, (2) disease recurrence, and (3) overall survival.

Breast Neoplasms↗

PubMed1993

Induction of apoptosis in blood cells from a patient with acute myelogenous leukemia by SC41661A, a selective inhibitor of 5-lipoxygenase.

Participation of leukotriene products in normal ex vivo hematopoiesis is well established. With increasingly specific inhibitors of lipoxygenases, it becomes possible to more closely define any participation of their biosynthetic products in these events. We cultured chronic myelogenous leukemia cells from the peripheral blood of several patients in blast crisis with three inhibitors of lipoxygenases: ETYA, and the more selective A63162 (Abbott) or SC41661A (Searle). All three agents reduced labelling of DNA with H3 thymidine measured at 4 h and reduced cell numbers by 72 h. An antisense deoxyoligonucleotide to the 5-lipoxygenase mRNA 'start' codon inhibited DNA synthesis at 24 h, as did two control oligonucleotides. Marked nuclear ultrastructural changes characteristic of apoptosis were induced by SC41661A in a subset of cells with the ultrastructure of promyelocytes. Whether this response characterizes a common pattern of this subset of leukemic cells to SC41661A, if damage to mitochondria with reduced function of bcl-2 protooncogene product located at that site might have contributed or some other mechanism was responsible, and if inhibition of 5-lipoxygenase activity was involved, are questions to be decided in the future.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1993

Safety and antiplatelet effect of murine monoclonal antibody 7E3 Fab directed against platelet glycoprotein IIb/IIIa in patients undergoing elective coronary angioplasty.

BACKGROUND: Excessive platelet deposition at the site of arterial damage due to coronary angioplasty plays an important role in the pathophysiology of both abrupt closure and restenosis after that procedure. Even aspirin, a relatively weak platelet antagonist, decreases the complications of coronary angioplasty. This study was designed to provide preliminary safety and efficacy data on the use of a much more powerful antiplatelet agent, m7E3 Fab, a prototype murine monoclonal antibody fragment that binds directly to the platelet glycoprotein IIb/IIIa receptor mediating aggregation in patients undergoing coronary angioplasty. METHODS: Twenty-three patients referred for elective coronary angioplasty who met prespecified criteria designed to minimize risk of bleeding received, in groups of four to six patients, escalating bolus doses of 0.15 to 0.35 mg/kg of this agent immediately before coronary angioplasty. Heparin was administered in the usual manner, but aspirin was withheld for 24 hours before coronary angioplasty and until bleeding times and platelet aggregation had returned to normal after angioplasty. Glycoprotein IIb/IIIa binding site occupation, platelet aggregation response to 20 microM of adenosine diphosphate, and data on bleeding times were acquired at baseline and at 2, 6, 24, 48 and 72 hours after m7E3 Fab administration. Clinical safety and efficacy were also monitored throughout the time of hospitalization, and delayed antimurine immune responses were assayed. Five similar patients received aspirin (325 mg orally per day) but otherwise received the same treatment, thus serving as controls. RESULTS: Treatment with m7E3 Fab resulted in a dose-dependent occupation of binding sites to a maximum of 93% at 2 hours in the highest-dose groups, with an associated graded inhibition of platelet aggregation and increase in bleeding time significantly exceeding that seen in control patients, with a gradual recovery over 6 to 48 hours. Percutaneous transluminal coronary angioplasty was successfully performed in 18 of 21 patients (86%) in whom it was attempted. Arterial and venous sheath removal 24 hours after m7E3 Fab dosing was largely uneventful. No thrombotic complications were seen, and only one patient (excluding a patient who underwent uneventful urgent bypass surgery) had bleeding severe enough to require packed red cell transfusion. Eight patients (36%) developed late antibody titers against m7E3 Fab. CONCLUSIONS: This murine monoclonal antibody provides potent antiaggregatory action and thus may be useful in preventing thrombotic complications of coronary angioplasty, but studies of its safety and efficacy during longer infusions and with larger numbers of patients are needed. Less immunogenic forms of the antibody may be more clinically useful.

Angioplasty, Balloon, Coronary↗

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↗

PubMed1993

Morphological and biochemical analysis of angiotensin II internalization in cultured rat aortic smooth muscle cells.

The intracellular pathway and kinetics of angiotensin II (ANG II) internalization are not well understood. We developed a biologically active ANG II-colloidal gold complex to qualitatively examine, by transmission electron microscopy, the ultrastructural details of ANG II binding and internalization in cultured rat aortic vascular smooth muscle cells (VSMC). To quantitatively evaluate ANG II internalization, we analyzed intracellular accumulation of 125I-labeled ANG II. These studies show that ANG II is internalized by VSMC in a time- and temperature-dependent fashion with a half time of < 2 min at 37 degrees C. Initially, ANG II binds diffusely over the entire cell surface. After binding, the ANG II receptors aggregate in coated pits that transform into small intracellular vesicles. By 60 min after internalization, gold particles are evident within large lysosome-like vesicles deep within the cell. ANG II-gold binding and internalization were selective: control probe (no ANG II) did not internalize; losartan potassium effectively competed for ANG II-gold binding and internalization.

Angiotensin II↗

PubMed1993

Survival after the onset of congestive heart failure in Framingham Heart Study subjects.

BACKGROUND: Relatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting. METHODS AND RESULTS: Proportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0 +/- 10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3 +/- 7.6 years in the 1950s, 65.9 +/- 7.9 years in the 1960s, 71.6 +/- 9.4 years in the 1970s, and 76.4 +/- 10.0 years in the 1980s; p < 0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26). CONCLUSIONS: CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.

Age Factors↗

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↗