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Biomedical subjects

J D Kark

Publications and source records attributed to J D Kark.

At least 55 records · Page 3Linked to original sources

Univariate and bivariate admixture analyses of serum glucose and glycated hemoglobin distributions in a Jerusalem population sample.

Univariate and bivariate analyses of fasting glucose and glycated hemoglobin (HbA1c) levels and of glucose levels 2 hours after an oral glucose load test were performed in a random sample of the Jewish population of Jerusalem, aged 25-64 years. Using ln-transformed data, we found that a mixture of two distributions fits the glucose data significantly better than a single distribution in the age groups 25-44 and 45-64 years. The fasting glucose results indicate that 1.1% of subjects aged 25-44 and 3.7% of subjects aged 45-64 without known diabetes come from an upper distribution with mean values of 154 mg/dl and 224 mg/dl, respectively. Estimates from the analysis of glucose levels after a load test indicate that an additional 2.1% of younger subjects and 3.8% of older subjects belong to a minor distribution with a high mean glucose value. The frequency distribution of HbA1c is also bimodal in all age groups. Yet the bimodality indicates that only 0.1% and 2.3% of subjects in the two age groups, respectively, come from minor distributions with mean levels of 13.0-15.7%, compared with HbA1c values of 5.0% and 5.3% for the main distributions. Using glucose levels, we found that specificity rates are consistently greater than 99%, whereas sensitivity rates vary with age. The use of cutoff points suggested by the National Diabetes Data Group (140 mg/dl for fasting glucose level and 200 mg/dl for glucose level after an oral glucose load test) indicates a lower sensitivity rate in the younger subjects with a minimal improvement among older subjects. A mixture of bivariate log-normal distributions fitted to the fasting and 2-hour glucose levels in subjects aged 45-64 indicates a larger proportion (6.3%) belonging to the minor distribution compared with those obtained when a single variable is used. Yet this combined score shows a low specificity rate. No similar improvement in separating "normal" from "abnormal" subjects is achieved when a mixture of bivariate distributions is fitted to the glucose and HbA1c variables. Admixture of glucose and HbA1c distributions is demonstrated. Bivariate analysis of these distributions does not, however, provide better discrimination of putatively abnormal subjects than univariate analysis.

Administration, Oral↗

Genetic and environmental sources of fibrinogen variability in Israeli families: the Kibbutzim Family Study.

Genetic and environmental determinants of plasma fibrinogen were investigated in a sample of 82 kindreds residing in kibbutz settlements in Israel. The sample included 223 males and 229 females ages 15-97 years. Fibrinogen levels were first adjusted for variability in sex and age. There was a significant familial aggregation of adjusted fibrinogen levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Commingling analysis implied that in this population a mixture of two normal distributions fit the adjusted fibrinogen levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex- and age-adjusted data. Heterogeneous etiologies for individual differences were suggested. There was evidence for a nontransmitted environmental major factor in addition to polygenic genes that explained the mixture of distributions. In parallel, a single recessive locus with a major effect that explained the adjusted variation in fibrinogen could not be rejected. However, when the regression model for sex and age allowed coefficients to be ousiotype (class)-specific, the recessive genetic model was rejected and the mixed environmental one was not. These results suggested that particular ousiotypes determined by the major environmental factor are associated with a steeper increase of fibrinogen with age. While at the age of 20 years, the major environmental factor contributed 10% to fibrinogen variability, and 48% was explained by polygenic loci, at 80 years of age, the major factor explained 64% and only approximately 20% was explained by polygenic factors.

Adolescent↗

Correlation of specific platelet activation markers with carotid arterial wall thickness.

Many studies have shown increased platelet activation in patients with coronary artery, cerebrovascular and peripheral vascular diseases. However, the temporal relationship between platelet activation and arterial atherosclerosis is unclear. To answer this basic question, we measured the plasma concentrations of two specific platelet activation markers, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) in 459 cases with increased carotid arterial wall thickness and 459 age-, sex-and race-matched controls selected from a cohort of 15,800 men and women, aged 45-64 who participated in the Atherosclerosis Risk in Communities Study. These participants had no acute vascular symptoms or known cardiovascular disease. The mean values of beta TG and PF4 were significantly higher in cases than in controls. However, when analyzed by quartiles using conditional logistic regression, only beta TG exhibited a significant association with carotid wall thickness, while PF4 did not. The odds ratio (OR) determined by multivariate logistic regression analysis was significantly higher for the uppermost quartile of beta TG (OR=1.7, 95% CI 1.1-2.5) compared to the lower 3 quartiles. This OR was 2.3 in white men (95% CI 1.2-4.2), 1.4 in white women (95% CI 0.6-3.0) and 1.0 in blacks (95% CI 0.4-2.5). This study indicates that plasma beta TG may be useful as a marker for early atherosclerosis in middle aged adults, particularly in white men. It also suggests that platelet activation has an independent role in the pathogenesis of atherosclerosis, although the possibility that this may be a response to carotid atherosclerosis cannot be excluded.

Biomarkers↗

Work satisfaction and health in the middle-aged and elderly.

BACKGROUND: There is evidence that occupational factors that cause psychological strain can affect physical and mental health, but findings are not consistent. METHODS: Work satisfaction was used as a convenient global index of job-related psychological strain. Relationships with general, physical and emotional health, appraised by the use of questions, were examined in workers aged > or = 50 years in a longitudinal community health study in Jerusalem. RESULTS: Positive associations were found both in 1975-1976 and in 1985-1987, with age, origin, education, sex and other variables controlled. The odds ratio in favour of poor general health was 2.8 times as high in dissatisfied workers as in very satisfied ones. Multivariate analyses suggested that the associations were not spurious ones attributable to a proneness to report both dissatisfaction and ill-health. Workers who expressed dissatisfaction in both 1975-1976 and 1985-1987 were particularly unhealthy in 1985-1987. CONCLUSIONS: The findings support the impact of work satisfaction or its determinants on current health, and suggest that persistent dissatisfaction may be especially deleterious to health.

Aged↗

Interference of immunoglobulin G (IgG) antibodies in IgA antibody determinations of Chlamydia pneumoniae by microimmunofluorescence test.

In the microimmunofluorescence test for measuring immunoglobulin A (IgA) antibodies against Chlamydia pneumoniae, removal of interfering IgG antibodies made IgA antibody reactivity patterns in 952 serum samples easier to interpret, prozone effects disappeared, and titers increased, especially in the sera with high IgG titers. IgA rheumatoid factors did not interfere in the assay.

Adult↗

Antioxidants in adipose tissue and risk of myocardial infarction: the EURAMIC Study.

Laboratory and epidemiological studies suggest that the antioxidants, vitamin E and beta-carotene, protect against coronary heart disease. In a European multicentre case-control study alpha-tocopherol and beta-carotene concentrations were measured in adipose-tissue samples collected in 1991-92 from 683 people with acute myocardial infarction and 727 controls. Mean adipose-tissue beta-carotene concentration was 0.35 microgram/g in cases and 0.42 in controls, with age-adjusted and centre-adjusted mean difference 0.07 microgram/g (95% confidence interval [CI] 0.04-0.10). Mean alpha-tocopherol concentrations were 193 micrograms/g and 192 micrograms/g for cases and controls, respectively. The age-adjusted and centre-adjusted odds ratio for risk of myocardial infarction in the lowest quintile of beta-carotene as compared with the highest was 2.62 (95% CI 1.79-3.83). Additional control for body-mass index and smoking reduced the odds ratio to 1.78 (95% CI 1.17-2.71); other established risk factors did not substantially alter this ratio. The increased risk was mainly confined to current smokers: the multivariate odds ratio in the lowest beta-carotene quintile in smokers was 2.39 (95% CI 1.35-4.25), whereas it was 1.07 for people who had never smoked. A low alpha-tocopherol concentration was not associated with risk of myocardial infarction. Our results support the hypothesis that high beta-carotene concentrations within the normal range reduce the risk of a first myocardial infarction. The findings for alpha-tocopherol are compatible with previous observations of reduced risk among vitamin E supplement users only. The consumption of beta-carotene-rich foods such as carrots and green-leaf vegetables may reduce the risk of myocardial infarction.

Adipose Tissue↗

A comparison of different matching designs in case-control studies: an empirical example using continuous exposures, continuous confounders and incidence of myocardial infarction.

The paper presents a case-control study involving a disease, exposures and several continuous confounders. The relative efficiency and validity of a fully matched design is compared with random sampling of controls. We test a viable option of a partially matched design when inability to match all study subjects on all confounders occurs. The degree of bias in the odds ratios introduced by the different designs and by the different analytic models is assessed in comparison with the estimates obtained from a total cohort, from which both cases and controls were selected. Matched designs and analytic strategies are also evaluated in terms of the variances of the odds ratios. The results indicate that matching on continuous variables may lead to a more precise estimate of odds ratio than statistical control of confounding in unmatched designs. Partial selection of controls by matching may be a useful strategy when complete matching cannot be achieved; in practice, partial matching achieves most of the benefits of full matching.

Adult↗

Plasma Lp(a), apolipoprotein(a) isoforms and acute myocardial infarction in men and women: a case-control study in the Jerusalem population.

The relationship of Lp(a) with manifestations of coronary heart disease (CHD) has not been studied extensively in women. There is little information as to the association of the unique Lp(a) apolipoprotein moiety (apo(a)) with CHD in either men or women. We therefore assessed the association of the apo(a) polymorphism and of Lp(a) with first acute myocardial infarction (MI) in a population-based case-control study in Jewish residents of Jerusalem between the ages of 25 and 64. The patients consisted of 238 men and 47 women hospitalized for a first acute MI in the 4 hospitals of Jerusalem serving the population (70% response rate among all first MI patients). The control subjects comprised 318 men and 159 women sampled from the national population registry and who were free of CHD (75% response). Lp(a) and apo(a) were measured in plasma stored at -20 degrees C for 6-24 months. Among men, plasma Lp(a) concentrations were higher in cases than controls in both univariate and multivariate analyses. The elevated risk was limited to the upper fifth of the Lp(a) distribution (unadjusted odds ratio = 1.65, P < 0.01 vs. the lower four quintiles, multivariable odds ratio = 1.82, P < 0.01). Among women, Lp(a) was not elevated in acute MI patients. Apo(a) isoforms with a B, S1 or S2 band (associated with higher Lp(a) values and having lower molecular weights) were more prevalent in female MI cases than controls (unadjusted odds ratio = 2.5, P = 0.016). This association could not be attributed to the higher Lp(a) concentrations associated with these isoforms and was not seen in men. In conclusion, our study points to an association of the apo(a) isoforms with acute MI in women, not evident in this population sample in men. Previously described associations of elevated Lp(a) with acute MI were confirmed in men but not in women. While the role of chance and inadequate statistical power cannot be excluded, the suggestion of a sex difference in the strength of these associations deserves further investigation, as does the question of whether apo(a) phenotype contributes to risk independently of Lp(a) level.

Adult↗

The role of XbaI polymorphism of the apolipoprotein B gene in determining levels and covariability of lipid and lipoprotein variables in a sample of Israeli offspring with family history of myocardial infarction.

We have determined the frequency of DNA polymorphism of the gene for human apolipoprotein B detected with XbaI in 525 Israeli offspring whose parents experienced a myocardial infarction. The relative frequencies of the X1 (8.6 kb) and X2 (5.0 kb) alleles were 0.67 and 0.33, respectively, with no significant differences between males and females and across the different origin groups. Significant variation in sex, age and body mass adjusted plasma levels of cholesterol (P = 0.02), LDL-C (P = 0.02) and apo B (P = 0.03) were associated with the XbaI polymorphism. An interaction with age was demonstrated. For young individuals a simple codominant association of the XbaI site with cholesterol and LDL-C was evident and the differences between the two homozygote groups ranged between 22 and 25 mg/dl. For individuals above age 25 these differences were about 12 mg/dl with no significant difference between the X1X2 and the X2X2 genotype groups. In our study sample the apo B XbaI polymorphism accounted for 1% of the variability of plasma cholesterol, LDL-C and apo B levels. The XbaI polymorphism also had an effect on the associations among lipid and lipoprotein variables. In conclusion, we have demonstrated an association of the apo B XbaI polymorphism with the metabolism of the apo B-containing lipoprotein particles in a sample of Israeli offspring with a family history of myocardial infarction.

Adult↗

Psychosocial stress and NK cells among members of a communal settlement.

The aim of the present study was to assess the effect of daily psychosocial stress on the human immune system. We tested 38 couples living in a communal settlement (kibbutz) under similar economic and social conditions, sharing similar housing, nutrition and health care. They were tested repeatedly over a two year period for a number of psychosocial parameters including demoralization, social support, family cohesion, adaptational hardiness and hostility. In parallel, the natural killer "NK" cell system was analysed for distinctive markers and for cytotoxic activity. The proportion of CD16+ lymphocytes was found to correlate with cytotoxic NK activity in both men and women. In contrast, the proportion of CD57+ cells correlated with that of CD16+ cells only in women while in men only the CD57+CD8-lymphocytes subset correlated with CD16+ cells. For each individual tested, the values of NK activity and NK markers obtained in tests carried out more than a year apart showed a striking correlation. In males, NK cytotoxicity correlated with hostility but was negatively correlated with family cohesion, adaptability and hardiness. The level of CD16+ and CD57+ cells correlated positively with demoralization in males only. Changes in the level of NK activity and in the level of CD16+ cells occurring in husbands during the observation period correlated positively with changes in demoralization and negatively with changes in family cohesion and adaptability. The results indicate that daily psychological stress and low family function may enhance the NK system, and that this response may differ between the sexes.

Adult↗

XbaI polymorphism of the apolipoprotein B gene and plasma lipid and lipoprotein response to dietary fat and cholesterol: a clinical trial.

A dietary trial was carried out on a group of offspring whose parents were hospitalized for an acute myocardial infarction. The XbaI Restriction Fragment Length Polymorphism (RFLP) was used to examine the genetic contribution of variation at this apo B locus to the response of lipids and lipoproteins to dietary manipulations. Twenty participants were homozygotes for the 8.0 kb fragment (X1X1), two were homozygotes for the 5.0 kb fragment (X2X2), and 15 were heterozygotes (X1X2). Subjects were randomized to a 5-week crossover study. Half began on a low SFA--cholesterol (LSC) diet for 5 weeks and, after a washout period of 4 weeks, they were placed on a high SFA--cholesterol (HSC) diet for a second period of 5 weeks. This order was reversed in the second group of participants. Significant changes in total cholesterol, LDL-C, and apo B were observed when subjects were moved from the LSC to the HSF diet. The corresponding average change induced by the dietary manipulations in X1X1 subjects compared with subjects with X2 allele were: 18.1 +/- 17.6 mg/dl and 9.5 +/- 19.6 mg/dl for total cholesterol and 15.8 +/- 15.3 mg/dl and 4.8 +/- 20.9 mg/dl for LDL-C, respectively. Our observation indicated that variation at the apo B XbaI locus may interact with baseline levels to determine individual dietary response in LDL-C level. However, the differences between the genotypic classes were not statistically significant, suggesting that the apo B XbaI locus is not a major determinant of interindividual differences in lipid and lipoprotein response to diet in this population.

Adult↗

Work-health relationships in middle-aged and elderly residents of a Jerusalem community.

Work-health relationships were examined cross-sectionally in 1886 men and women aged greater than or equal to 50 years in Jerusalem in 1985-1987, in the third round of a multipurpose longitudinal community health study. The main occupational variables were employment status, reasons for not working, and satisfaction with work. Sex and age were controlled in all comparisons. Workers were clearly healthier than nonworkers with respect to general, physical and emotional health, and people who had given up work were less healthy than those still working, whether they had stopped for health reasons, only because of their age, or only for extrinsic reasons (retrenchment or dismissal). Workers who expressed satisfaction with their work were healthier than others, the odds ratio in favour of good general health being 2.4 at 50-64 and 2.5 at greater than or equal to 65 years of age. The associations between job satisfaction and health remained apparent when education and origin were controlled. Multivariate analyses suggested that the associations were not spurious ones attributable to proneness to report both dissatisfaction and ill-health. Job dissatisfaction was not significantly associated with angina pectoris, possible myocardial infarction, or hypertension. Taken at their face value, the findings support the impact of job satisfaction or its determinants on the health of middle-aged and elderly men and women. The associations will be re-appraised in the longitudinal analysis of the study data.

Aged↗

A simplified index of physical health for use in epidemiological studies.

A battery of simple questions designed to measure physical health, in terms of ability to perform physical activities, was appraised in 1839 men and women aged greater than or equal to 50 years in a community survey in Jerusalem. The number of "Yes" answers to six questions, five of which could be skipped if the first one was answered positively, was found to be a satisfactory index, with a high degree of consistency-reliability in the total sample (Cronbach's alpha coefficient = 0.97) and in subgroups categorized by sex, age, education, or father's region of birth. The index constituted an excellent Guttman scale (coefficient of reproducibility = 0.96, coefficient of scalability = 0.94), indicating that the score serves both as a measure of physical health and as an indication of the profile of capabilities. Associations with age and other variables conformed with expectations, attesting the construct validity of the index.

Aged↗

Apo(a) isoforms predict risk for coronary heart disease. A study in six populations.

Elevated concentrations of lipoprotein(a) (Lp[a]) in plasma are associated with premature coronary heart disease (CHD). Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors as well as diseases also affect plasma Lp(a) concentrations. It is therefore unclear whether Lp(a) is a primary genetic risk factor or whether Lp(a) levels are elevated secondary to disease in CHD patients. We have analyzed apo(a) phenotypes that represent a stable genetic trait in subjects with CHD and control subjects from different populations representing a variety of ethnic groups (Tyrol, Germany, Wales, Israel, Singapore Chinese, and Singapore Indian). Despite differences in sampling design and disease definition in this multipopulation case-control study, those apo(a) isoforms associated with high Lp(a) plasma concentrations (B, S1, and S2) were more frequent in the CHD patients in each ethnic group. These differences were significant in three of the studied populations and highly significant (p < 0.001) in the pooled (total) group. Lp(a) concentrations were also measured in all groups except Germans and were found to be consistently higher in cases than in control subjects in each ethnic group. For all but one population (Israeli) the differences were significant. The effects of the apo(a) size polymorphism on Lp(a) levels were similar in CHD patients and control subjects from different populations. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) concentrations across multiple populations with large differences in CHD frequency and risk factor profiles.

Adult↗

Cigarette smoking and educational level among young Israelis upon release from military service in 1988--a public health challenge.

The prevalence of cigarette smoking was determined in a representative sample of Israeli men and women mostly aged 20-22, upon release from military service. In this sample, 47.5% of the men and 30% of the women reported themselves to be current smokers, and 46% and 26% respectively to be current regular smokers. Of the current smokers 80% of the men and 74% of the women took up smoking before entering military service. Educational level at recruitment was strongly associated with age at uptake of smoking, the prevalence of smoking and the number of cigarettes currently smoked per day. Ethnic differences in smoking prevalence after controlling for education were relatively small. Men and women with less than or equal to 11 years of schooling reported twice the smoking prevalence of those with greater than or equal to 12 years, 71 vs. 35% current smokers in men and 56% vs. 26% current smokers in women respectively. Heavy smoking of greater than or equal to 20 cigarettes per day was reported by 51% and 30% of less educated men and women, respectively, compared with 17% and 9% respectively of those with greater than or equal to 12 years of schooling. We conclude that intervention programs directed toward the prevention of uptake of smoking in adolescents should receive high public health priority in Israel, with special emphasis on adolescents prior to military service and focusing on the more susceptible segments of the young population.

Adult↗

Coffee and the immune system.

The effect of coffee consumption on the immune system, studied in 15 men and women, showed that the responses to PHA and Con A were about one-third lower during coffee drinking compared to a period of abstinence from coffee (117335, 99856 and 181236, 153315, P less than 0.004, 0.009 respectively). There was no effect on total T- or B-cells. There was no statistically significant change in the number of suppressor T-cells (20, 26; P = 0.1) or NK cells (20, 26; P = 0.014). Chemotaxis was higher in the coffee period at all concentrations. This exploratory study suggests that coffee intake modifies various measures of the immune function. The clinical relevance of the findings is not clear, and further studies aimed at delineating the constituents responsible for the effects observed are recommended.

Adult↗

An epidemiologic study of mortality among bereaved parents.

To study the health consequences of parental bereavement, we compared the mortality in two groups of bereaved Israeli parents with that in the general population. One cohort comprised the parents of all 2518 soldiers 18 to 40 years of age who were killed during the Yom Kippur War in 1973. The second consisted of the parents of 1128 men 18 to 30 years of age who died in accidents between 1971 and 1975. Both groups were followed through 1983. The comparison population was the entire population of Jewish Israelis for which sex-, age-, and calendar year-specific mortality rates were available. The 10-year age-adjusted life-table mortality was higher among fathers whose sons died in accidents rather than in war (P = 0.045), but mortality did not differ significantly between the two groups of mothers. Overall, we found no excess mortality among the bereaved parents as compared with the general population. The standardized mortality ratios for the fathers and mothers of sons killed at war were 0.91 and 0.90, respectively; for fathers and mothers whose sons died by accident, they were 1.04 and 0.91, respectively. None were significantly different from unity. There was no consistent evidence of an elevated risk of death, early or late, after the loss. Widowed and divorced parents who lost a son did have increased mortality, which was statistically significant in mothers. Our findings provide no support for the hypothesis that the loss of an adult son is associated with increased short-term or long-term mortality in married parents.

Accidents↗

Biological and cultural sources of familial resemblance in plasma lipids: a comparison between North America and Israel--the Lipid Research Clinics Program.

Heterogeneity in determinants of familial resemblance of lipid and lipoprotein levels between populations in North America and Israel was investigated using path analysis. A common protocol, identical measurement techniques, and the same statistical procedures were used in the two samples. Both genetic (h2) and cultural (c2) determinants of inheritance were significant for all lipid variables in the two studies. Genetic and cultural heritability of total cholesterol (h2 = 0.61, c2 = 0.02), low-density lipoprotein cholesterol (h2 = 0.59, c2 = 0.02), and high-density lipoprotein cholesterol (h2 = 0.55, c2 = 0.06) did not differ significantly between North America and Israel, while there was a significant difference for triglyceride (h2 = 0.41, c2 = 0.07 in North America; h2 = 0.61, c2 = 0.05 in Israel). Secondary parameters of the path model describing intrafamilial environmental relationships differed between the two countries. In particular, there was a higher correlation between marital environments in Israel for all traits except triglyceride, and a larger effect of father's environment on offspring's environment in Israel for all traits. Within both populations, variation of plasma lipids and lipoproteins was mostly explained by genetic factors and random unmeasured environmental factors. The contribution of common family environment was found to be small, though statistically significant. This is probably due to homogeneity of the distribution of familial environmental determinants within both countries.

Cholesterol↗