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Biomedical subjects

J M Karon

Publications and source records attributed to J M Karon.

46 records · Page 3Linked to original sources

Accuracy and comparability of long-term measurements of cholesterol.

Laboratories of the Lipid Research Clinics Program (LRC) maintained the accuracy of their measurements of total cholesterol by using seven pooled serum calibrators supplied by the Centers for Disease Control (CDC). Over the 11-year life of the LRC, each calibrator was prepared in succession and a target value was assigned by the CDC reference method for cholesterol. The results of a special experiment in which six of the seven calibrators were analyzed simultaneously demonstrated that the target values were accurately assigned. Deviations of the target values from the experimental means ranged from zero to 1.7% of the original target value. The experiment revealed no evidence of drift in the bias of the reference method over the life of LRC and demonstrated the accuracy, consistency, and the comparability of the values assigned to the successive calibrator pools used by the LRC laboratories during more than eight years. It demonstrated the reliability of a reference method and the suitability of frozen serum pools for maintaining an accurate measurement base for serum cholesterol.

Analysis of Variance↗

Assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure using a modified D-glucaric acid assay.

An enzyme-inhibition assay was evaluated and modified to quantify D-glucaric acid in a population exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The modified assay combined improvements described separately in previous reports, including pH adjustment by standard addition of buffers rather than by titration, an optimum pH of 2.3 for converting D-glucaric acid to 1,4-glucarolactone, and the use of the relation reciprocal of absorbance versus concentration for calculating unknowns. Reference limits for adult males were 0.06-5.90 mmol D-glucaric acid/mol creatinine and for adult females 0.87-6.23 mmol D-glucaric acid/mol creatinine. Children under the age of 15 yr had a reference range of 0-8.34 mmol D-glucaric acid/mol creatinine. Persons on anticonvulsant therapy excreted from 3 to 10 times the upper reference limits of D-glucaric acid. Urinary concentrations of D-glucaric acid in persons identified as being at high risk for exposure to 2,3,7,8-TCDD in Times Beach, Mo., were not significantly different from concentrations in those identified as being at low risk for such exposure.

Adolescent↗

Coronary risk factors and exercise test performance in asymptomatic hypercholesterolemic men: application of proportional hazards analysis.

The association of established coronary risk factors with submaximal graded treadmill exercise test performance was examined in 6,850 asymptomatic, white 34--59-year-old hypercholesterolemic men screened between 1973 and 1976 at 12 North American Lipid Research Clinics for participation in their Coronary Primary Prevention Trial. The prevalence of ischemic electrocardiographic responses (greater than or equal to 1 mm S-T segment depression) was 8.6%. The Cox proportional hazards method was adapted so as to take into account the level of exercise at which ischemic responses occurred and to which subjects without ischemic responses were exposed. The results were compared with those obtained by standard logistic regression. In both models, age, blood pressure, plasma cholesterol, and (inversely) plasma high-density lipoprotein cholesterol and alcohol consumption were significant independent predictors of an ischemic response to exercise. Surprisingly, ischemic responses were less frequent in smokers than in nonsmokers. However, when the proportional hazards method was used, cigarette smoking was weakly but significantly (p less than 0.01) predictive of an ischemic response on the treadmill. Results from this model differed from those of the logistic model because the former takes into account the reduced exercise capacity of smokers, which renders them less likely to reach workloads sufficient to induce myocardial ischemia. The proportional hazards model similarly demonstrated a possible beneficial effect of habitual physical activity which was not apparent in the logistic model. Quetelet index and plasma triglyceride were only weakly associated with the probability of an ischemic response, and did not contribute significantly to either model.

Adult↗

Estrogen use and all-cause mortality. Preliminary results from the Lipid Research Clinics Program Follow-Up Study.

The association of exogenous estrogen use and hysterectomy status with all-cause mortality was examined in 2,269 white women, aged 40 to 69 years, who had been followed up for an average of 5.6 years in the Lipid Research Clinics Program Follow-up Study. A total of 72 deaths occurred during this period. The relative risk of death in estrogen users compared with nonusers was 0.54 in gynecologically intact women, 0.34 in hysterectomized women, and 0.12 in bilaterally oophorectomized women. The risk of death in estrogen users, irrespective of hysterectomy status, was 0.37 times that in nonusers (3.4/1,000 v 9.3/1,000). The significant negative association of estrogen use with mortality persisted after multivariate adjustment for confounding factors. Hysterectomy status alone was not a significant predictor of death. Some, but not all, of the lower risk of mortality in estrogen users can be accounted for by increased levels of high-density lipoprotein cholesterol.

Adult↗

The use of epidemiologic data for personal risk assessment in health hazard/health risk appraisal programs.

Health Hazard/Health Risk Appraisal (HHA/HRA) programs employ personal risk assessment as an educational and motivational technique to encourage the adoption of healthier lifestyles by health education clients. We have reviewed the scientific basis of of the risk assessments provided in HHA/HRA. There are severe limitations in both the data and the risk estimation procedures. Various undocumented assumptions enter into the projections; several key aspects are arbitrary. Proposals for improvement of the procedure generally require data that are not available. Attention has largely focused on increasing mathematical sophistication (e.g. adjustment for competing risks) while ignoring problems in accuracy of the client data from which projections are calculated and serious questions about the health education messages implicit in the appraisal results. Health Hazard/Health Risk Appraisal programs should be candid about the limitations of the technique. Use of appraisal results for evaluation purposes is questionable. The health education messages produced by such programs deserve attention, since their appropriateness, especially for clients who are not white, middle class and middle-aged, has not been established.

Actuarial Analysis↗

In defense of matching.

This paper discusses the simplified situation of an epidemiologic study involving disease, exposure, and a single (possibly confounding) extraneous factor, all of which are dichotomous. The question is: In studying the association between disease and exposure, should the comparison group be selected by random sampling or by matching on the extraneous factor? An example is used to demonstrate the general principle that matching controls confounding in estimating the risk ratio in a follow-up study, but not in estimating the exposure odds ratio in a case-control study. Calculations based on a probability model show that, despite the possible reduction in sample size which may be associated with matching, matching will often lead to a more precise estimate of the effect measure than random sampling and is not likely to result in a significant loss in precision in situations of practical importance. Therefore, selection of the referent group by matching should be given serious consideration for both follow-up and case-control studies.

Epidemiologic Methods↗

Autoradiography of protein turnover in subcrestal versus supracrestal fibre tracts of the developing mouse periodontium.

Eighteen-day-old C57Bl mice were injected with 5 muCi/g body weight [3H]-proline and killed at intervals of 4 h to 7 wk later. Grain counts in three fibre tracts revealed that (1) half-lives of labelled protein in the developing periodontium were much shorter than those found previously for the mature periodontium , and (2) the half-life of labelled protein in the dento-gingival region was longer than the half-lives in the trans-septal and dento-alveolar fibre tracts (half-lives: dento-alveolar = 2.5 days, trans-septal = 3.8 days; dento-gingival = 7.9 days). Eight mice were given injections of [3H]-proline on days 11, 13, 15 and 17, which encompasses the formation of the three fibre tracts, and killed 4 h, 2.5, 5 and 8 wk after the last injection. All label incorporated during the formation of the periodontium had been lost by 5 wk post-injection, showing that a stable core fibre (i.e. one which is not metabolized) was not present.

Animals↗

Matching in epidemiologic studies: validity and efficiency considerations.

Validity and efficiency issues are considered with regard to the use of matching and random sampling as alternative methods of subject selection in follow-up and case-control studies. We discuss the simple situation involving dichotomous disease and exposure variables and a single dichotomous matching factor, and we consider the influence on efficiency of a possible loss of subjects due to matching constraints. The decision to match or not should be motivated by efficiency considerations. An efficiency criterion based on a comparison of confidence intervals under matching and random sampling for the effect measure of interest (the risk ratio and risk difference in follow-up studies, and the odds ratio in case-control studies) leads to the following conclusions when the sampling method does not influence the size of the comparison group. In follow-up studies, matching on a confounder is expected to lead to a gain in efficiency over random sampling, while matching on a nonconfounder is not expected to result in a loss of efficiency. In case-control studies, the same conclusions hold, except that matching is not as advantageous as in follow-up studies and can lead to a loss of efficiency in some situations (usually of little practical importance). When matching reduces the size of the comparison group, there is likely to be a meaningful gain in efficiency due to random sampling only when the matched comparison group is at most 40-50% the size of the randomly-sampled comparison group is a follow-up study, and at most 50-65% the size in a case-control study.

Follow-Up Studies↗

Population-based monitoring of an urban HIV/AIDS epidemic. Magnitude and trends in the District of Columbia.

OBJECTIVE: To assess the extent of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic in the District of Columbia and demonstrate an approach to monitoring HIV infection and projecting AIDS incidence at a community level. DESIGN: Backcalculation methods to reconstruct HIV incidence from AIDS incidence in subgroups. Results were compared with directly measured HIV seroprevalence in selected sentinel populations: childbearing women, civilian applicants for military service, and hospital patients admitted for conditions unrelated to HIV infection. RESULTS: Between the start of the epidemic in 1980 and January 1, 1991, one in 57 District of Columbia men aged 20 to 64 years was diagnosed with AIDS. Unlike the plateau projected for the nation, AIDS incidence for the District of Columbia was projected to increase by 34% between 1990 and 1994. Models of HIV infection incidence suggested two broad epidemic waves of approximately equal size. The first occurred in men who have sex with men and peaked during the period from 1982 through 1983. The second began in the mid-1980s in injecting drug users and heterosexuals. We estimated that among District of Columbia residents aged 20 to 64 years, 0.3% of white women, 2.9% of white men, 1.6% of black women, and 4.9% of black men were living with HIV infection as of January 1, 1991. These estimates are broadly consistent with survey data: among black childbearing women in their 20s, HIV prevalence doubled to 2% between the fall of 1989 and the spring of 1991; from military applicant data, we estimated that over 5% of black men born from 1951 through 1967 were HIV-positive; in the sentinel hospital, HIV prevalence rates among male patients aged 25 to 34 years were 11.3% in white men and 16.9% in black men. CONCLUSION: Backcalculation and surveys yielded quantitatively consistent estimates of HIV prevalence. Many injecting drug users and heterosexuals in the District of Columbia were infected after January 1, 1986. Similar monitoring of the epidemic in other localities is needed to focus efforts to reduce the incidence of HIV transmission.

Acquired Immunodeficiency Syndrome↗