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Biomedical subjects

R Benfante

Publications and source records attributed to R Benfante.

26 records · Page 2Linked to original sources

Is elevated serum cholesterol level a risk factor for coronary heart disease in the elderly?

Since serum cholesterol is a major component in the causal pathway of atherosclerosis, a pathological process that usually progresses with age, we have evaluated reported findings of a diminished association between serum cholesterol level and coronary heart disease in the elderly. In the Honolulu (Hawaii) Heart Program, 1480 men aged 65 years and older and free of coronary heart disease were followed up for an average of 12 years. Incidence rates of coronary heart disease increased progressively from the lowest to the highest quartile of serum cholesterol level. The independent role of serum cholesterol level as a predictor of coronary heart disease risk was evaluated with other major risk factors using a Cox multivariate regression model. The upper-lower quartile relative risk for serum cholesterol level was 1.64 (95% confidence interval, 1.14 to 2.36). The relative risk for middle-aged men was also 1.64. The results suggest that serum cholesterol level is an independent predictor of coronary heart disease, even among men older than 65 years. Thus, an elevated serum cholesterol level in the elderly should be regarded, as in middle-aged men, to be an indicator for further evaluation of lipoprotein levels and possible intervention.

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Potential bias due to prevalent diseases in prospective studies.

In prospective studies, subjects found to have the disease under investigation at the initial screening examination are commonly excluded from analyses. However, the possibility of bias due to prevalent conditions other than the disease of interest is usually not considered. In the present study, an algebraic development enables analysis of the effects of inclusion and exclusion of subjects with certain prevalent conditions upon risk estimates. Hypothetical data are presented for which an association between a risk factor and an incident disease could become null or even reversed after removing subjects with certain prevalent diseases. Bias appears even when the only association present is between risk factor and total disease incidence. Data from the Honolulu Heart Study also have been used to illustrate this finding, examining the association between coronary heart disease (CHD) incidence and smoking. Decisions regarding the inclusion or exclusion of subjects with prevalent diseases requires prior knowledge of alteration of usual risk factors levels by individuals with these diseases. Simply removing all subjects with prevalent diseases might on the contrary create bias. Therefore, people with prevalent diseases should be screened for potential alteration of their risk factor levels as a result of the diseases. The situation becomes still more complex when several risk factors and prevalent diseases need to be considered at the same time as it happens in multivariate analyses. Because this situation represents a bias, and not confounding or effect modification, controlling for the effect of prevalent diseases is not appropriate.

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Sequence-directed curvature of repetitive AluI DNA in constitutive heterochromatin of Artemia franciscana.

An Alu I family of repeated DNA sequence 113 bp in length was found to be the major component of the heterochromatin in Artemia franciscana. On the basis of the analysis of cloned oligomeric (monomer to examer) heterchromatic fragments we predicted that the sequence could produce a stable curvature in chromosomal DNA. This prediction was confirmed by polyacrylamide gel electrophoresis analysis and by electron microscope observations. The anomalous mobility of these fragments is reversed when the DNA samples are electrophoresed in the presence of distamycin A. Moreover treatment of living Artemia with this drug produces visible decondensation of heterochromatic masses in the interphase nuclei.

Animals↗

Response bias in the Honolulu Heart Program.

The 14-year incidence rates (1969-1982) for coronary heart disease, cerebrovascular disease (stroke), total mortality, and cause-specific mortality were compared between 8,006 examined and 3,130 nonexamined men of the Honolulu Heart Program using identical surveillance procedures. There was a significant decrease in examination participation with increasing age. Examined men smoked less, weighed more, had a higher level of education, and had a lower percentage of never-married status than did nonexamined men. Total mortality rates, cancer mortality rates, and coronary heart disease incidence rates were higher in nonexamined men, while there were no differences in stroke rates. The average annual response error for total mortality and coronary heart disease rates was underestimated at 8.7% and 5.4%, respectively. The differences in rates were greatest during the first half of the follow-up period and converged during the second half. By the end of 10 years, there were no differences between nonexamined and examined men for any of the endpoints studied. The pattern of convergence of rates suggests a diminishing healthy participant advantage over time. In conclusion, a response bias did occur in this study, but the effect was small and did not alter any of the earlier findings concerning the relative incidence of cardiovascular disease. Because the degree of response bias can vary widely depending on when during follow-up a particular analysis is undertaken, it is recommended that prospective studies monitor, insofar as possible, a sample of nonparticipants in order to ensure valid results.

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Mechanism of initiation of in vitro DNA synthesis by the immunopurified complex between yeast DNA polymerase I and DNA primase.

The immunopurified yeast DNA-polymerase-I--DNA-primase complex synthesizes oligo(rA) and oligo(rG) molecules that are used as primer for replication of poly(dT) and poly(dC). Neither initiation nor DNA synthesis is observed with poly(dA) and poly(dI). Nitrocellulose-filter binding shows that the enzyme complex binds to deoxypyrimidine polymers, but not to deoxypurine polymers. Although the yeast complex initiates DNA synthesis on deoxypyrimidine homopolymers, it prefers to elongate pre-existing primer molecules rather than to initiate de novo DNA replication. The size of the oligo(rA) and oligo(rG) primer molecules has been determined by urea/polyacrylamide gel electrophoresis: longer oligoribonucleotides are synthesized when their utilization is prevented by omitting dNTP. An oligodeoxythymidylate template with a chain length as short as five residues can support oligo(rA) synthesis catalyzed by the yeast DNA-polymerase--DNA-primase complex and the size of the oligoribonucleotide products synthesized with oligodeoxythymidylate of differing chain length has also been determined. The mechanistic properties of the DNA-polymerase--DNA-primase complexes, purified from different eukaryotic organisms, appear to be very similar. The possible biological implication of the studies on the mechanism and specificity of initiation of DNA synthesis in a well-defined model template system has been discussed.

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Biological and social predictors of health in an aging cohort.

A cohort of over 5000 men of Japanese ancestry, aged 46-69 and free of chronic disease at entry examination were studied for factors associated with remaining free of major chronic diseases during a 12 yr followup period. Over 1600 disease-free men were compared with 3400 individuals who developed coronary heart disease (CHD), stroke, cancer or a variety of other conditions. From more than 30 variables examined in multivariate analyses, blood pressure, obesity, cigarette smoking, alcohol consumption, serum glucose, uric acid and triglyceride, were inversely associated with staying healthy while forced vital capacity and years spent in Japan were directly associated with health. Of these nine variables, blood pressure was the strongest discriminator between healthy status and all categories of disease, while cigarette smoking and alcohol consumption were the next most important factors. This study suggests that the use of individuals who remain free of disease as a "standard" for health can facilitate the evaluation of risk factors for both total illness and a broad range of specific chronic diseases in a single population.

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Lipid and lipoprotein predictors of coronary heart disease in elderly men in the Honolulu Heart Program.

Data from the baseline and follow-up examinations of the Honolulu Heart Program (HHP) cohort of 8006 men of Japanese ancestry were used to examine several questions concerning the predictive role of lipids and lipoproteins for incident CHD. For the question "Do serum cholesterol levels measured in middle age predict incident CHD in elderly men 65 years old or older?" the answer was clearly yes. Multivariate relative risks and attributable risks for early and late onset of CHD were similar and statistically significant. For the question "Do serum cholesterol levels measured in the elderly predict subsequent CHD?" the answer again was clearly yes. Multivariate relative risks for elderly men were similar to those for middle-aged men, and attributable risks were consistently higher for elderly men. For the question "Do other lipid or lipoprotein levels measured in the elderly predict incident CHD better than serum cholesterol level?" the answer was no. Multivariate relative risks for low-density-lipoprotein (LDL) and non-high-density-lipoprotein cholesterol were similar to those for total cholesterol. HDL cholesterol was protective for incident CHD, but the patterns were not significant for the elderly. Serum triglyceride level was not a significant predictor of CHD for the elderly. The conclusion was that no matter at what age serum cholesterol was measured, it predicted subsequent CHD in the elderly men in this cohort.

Age Factors↗