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Biomedical subjects

Y Friedlander

Publications and source records attributed to Y Friedlander.

At least 73 records · Page 4Linked to original sources
PubMed1996

I/D polymorphism of the angiotensin-converting enzyme gene does not predict isolated systolic or systolic-diastolic hypertension in the elderly.

To determine whether insertion/deletion (I/D) polymorphism (intron 16) of the angiotensin converting-enzyme (ACE) gene is associated with isolated systolic hypertension (ISH: systolic blood pressure (BP) > or = 160, diastolic BP < 90 mm Hg) or systolic-diastolic hypertension (S-D hypertension: diastolic BP > or = 90 +/- systolic BP > or = 160 mm Hg) compared with normotensive controls (systolic BP < 160, diastolic BP < 90 mm Hg), we conducted a case-control study of 733 non-institutionalised, elderly (> or = 60 years) residents of Dubbo, NSW. Individuals were classified as: ISH (n = 167), S-D hypertension (n = 207) and normotensive control (n = 359) with age and sex matching. II, DD and ID genotypes were determined by a nested PCR strategy using DNA extracted from serum. The frequencies of D and I alleles in the control population (0.70 and 0.30 respectively) were not significantly different in the ISH group or the S-D hypertension group (chi 2: 1.7, P = 0.42). After adjustment for several potential confounders, neither genotype nor allele predicted ISH (II vs DD: odds ratio (OR): 1.06, 95% confidence interval (CI): 0.55-2.03; I vs D: 1.09, 0.82-1.46) or S-D hypertension (II vs DD: 1.19, 0.67-2.10; I vs D: 1.16, 0.89-1.52) in this elderly cohort. The I/D polymorphism of the ACE gene is not a marker for either form of hypertension in this large elderly sample.

Aged↗
PubMed1995

High-dose fluvastatin and bezafibrate combination treatment for heterozygous familial hypercholesterolemia.

This study assessed the long-term use of fluvastatin, alone or in combination with bezafibrate, in patients with severe familial hypercholesterolemia who, in a previous study, did not achieve target levels (European Atherosclerosis Society) of low density lipoprotein cholesterol (LDL-C) with fluvastatin at 60 mg/day plus bezafibrate 200 mg/day, with or without cholestyramine (CME) at 8 g/day. This open-label study comprised 3 periods: period I, 6 weeks of fluvastatin at 40 mg twice daily (at breakfast and at bedtime); period II, fluvastatin at 80 mg/day (40 mg at breakfast, 40 mg at bedtime), and bezafibrate at 200 mg/day (at lunchtime) for 6 weeks in patients not achieving LDL-C target levels; and period III, force-titration of fluvastatin to 800 mg/day (as in period II) and bezafibrate at 400 mg/day (slow release) in patients receiving combination treatment. Patients were excluded if, during the previous study, they had experienced a serious drug-related adverse event or deterioration in liver or kidney function (liver enzymes > 3 times upper limit of normal). The standard physical and laboratory evaluations were performed at regular intervals. Lipid profiles were determined from 12-hour fasting blood samples. All adverse events occurring or worsening during the study, whether spontaneously reported or elicited by questioning, and regardless of relationship to study medication, were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1995

Segregation analysis of plasma lipoprotein(a) levels in pedigrees with molecularly defined familial hypercholesterolemia.

The role of genetic and environmental factors in determining the variability in plasma lipoprotein(a) [Lp(a)] levels was investigated in 220 members of 14 families with familial hypercholesterolemia (FH) whose plasma Lp(a) levels were previously reported [Leitersdorf et al. (1991) J Lipid Res 32:1513-1519]. One hundred four subjects harbored a mutant low density lipoprotein (LDL) receptor allele as confirmed by the identification of the specific mutations in addition to the haplotype analysis reported before. Four different mutant alleles were identified, each in a defined genetic group--Druze, Christian-Arabs, Ashkenazi, and Sepharidic Jews. Sex- and age-adjusted mean plasma Lp(a) levels were significantly higher in FH family members (34.0 mg/dl) than in non-FH family members (21.1 mg/dl). Lp(a) levels were further adjusted for lipid levels and apo(a) isoforms. A mixture of two normal distributions fitted the adjusted Lp(a) levels better than did a single normal distribution. Segregation analysis indicated that a major effect of a non-transmitted environmental factor explained the mixture of distributions in addition to polygenic loci which influenced Lp(a) levels within each distribution. The major environmental factor and the polygenic loci accounted for 45% and 20% of the adjusted Lp(a) variation, respectively. Furthermore, sex, age, lipid levels, apo(a) isoform, the major environmental effect, and the unmeasured polygenes could account for 80% of the unadjusted variation of plasma Lp(a) in these families.

Adolescent↗
PubMed1995

Sibling correlations of coronary heart disease risk factors in a sample of Israeli offspring with parental history of myocardial infarction.

Sibling correlations for coronary heart disease risk factors were analyzed in 731 pairs of siblings whose parents experienced a first myocardial infarction. Sibling correlations for lipids, lipoproteins and apolipoproteins ranged from 0.29 to 0.48, with limited changes on adjustment for sex, age, education and body mass index. For most lipid variables brother-brother correlation coefficients were highest and sister-brother correlation coefficients were lowest. Sib-sib correlation coefficients for lipids, lipoproteins, blood pressure and body mass index were similar to those estimated from a random sample of Jewish families. The sibling correlations were relatively low for waist to hip ratio, triceps and suprailiac skinfolds, moderate for subscapular skinfolds and body circumference measurements and high for number of cigarettes smoked by the siblings. The sibling correlations for lipid variables showed a moderate dependency on the apolipoprotein B XbaI genotypes. Siblings living in the same household tended to have higher correlation coefficients for HDL-C, apolipoprotein B and apolipoprotein AI than those living apart. The correlation coefficients for number of cigarettes and anthropometric variables tended to be heterogeneous due to the higher correlations among siblings living apart. A clear trend of decline in sib-sib correlations for apolipoprotein AI, glucose, cigarette smoking, body mass index and circumference measurements with increased spacing between sibling's ages was indicated. This temporal trend in sibling correlations for coronary heart disease risk factors suggests that genetic and/or environmental factors may have different influences at different ages.

Adult↗
PubMed1995

Risk factors for coronary heart disease in the prospective Dubbo Study of Australian elderly.

A new prospective study of non-institutionalised Australian elderly 60 years and over commenced in Dubbo in 1988, comprising 1236 men and 1569 women. This report examines clinical and socio-demographic predictors of coronary heart disease (CHD) over a median 62 months follow-up. CHD incidence rates (ICD-9-CM codes 410-414) were higher in men than women until 79 years, thereafter, the rates for recurrent disease were higher in women. Incidence rates for recurrent disease were three-fold those for initial disease. In Cox proportional hazards analysis, the significant predictors of all CHD were: advancing age, prior CHD (relative risk (RR) = 2.50 and 2.15 in men and women, respectively), use of anti-hypertensive medication (RR = 1.92 and 1.75 in men and women, respectively). diabetes (RR = 1.67 and 1.53 in men and women, respectively), serum cholesterol, low density lipoprotein cholesterol and serum apo B in men (RR = 1.24), serum triglycerides in women (RR = 1.23), high density lipoprotein cholesterol in men (RR = 0.82), lipoprotein (a) in women (RR = 1.99), and poorer self-rating of health (RR =1.48 and 1.93 in men and women, respectively). Serum cholesterol was not predictive of CHD in men beyond 74 years. Isolated systolic hypertension predicted CHD in women (RR = 3.76), but not in men (RR = 1.20). The findings highlight key risk factors for CHD in the elderly.

Aged↗
PubMed1995

Plasma lipids and lipoproteins response to a dietary challenge: analysis of four candidate genes.

The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 63 male students. Four site polymorphisms (signal peptide insertion/deletion, XbaI, MspI and EcoRI) of the apo B gene, three RFLPs (AvaII, StuI, and HincII) of the LDL receptor gene, two SSCPs of the cholesterol 7 alpha-hydroxylase gene and the common apo E genotypes were determined. The average reductions induced by diet in participants homozygous for the absence of the XbaI restriction site (X-X-) of the apo B gene compared to those harboring this site (X+) were: 14.5 mg/dl and 9.4 mg/dl for total cholesterol (TC) (p < 0.09) and 15.5 mg/dl and 7.9 mg/dl for LDL-C (p < 0.003), respectively. Differences in dietary responsiveness among the apo E, LDL receptor and the cholesterol 7 alpha-hydroxylase genotypes were largely insignificant. Using the four apo B polymorphic sites, six unambiguous haplotypes were constructed and a model for their possible evolutionary relationship is presented. Genetic variation in the apo B gene region, as defined by haplotypes, accounted for 8.7% and 24.3% of the phenotypic variance in TC and LDL-C response to diet, respectively. Sequence analysis of a candidate locus, the putative LDL receptor binding region of apo B and its flanking sequences, was performed in two individuals, one homozygous for an apo B "hyper-responding" and another for the "lower-responding" haplotype, and no differences were found. In conclusion, haplotypes at the apo B gene locus are associated with dietary response of TC and LDL-C in young males. Yet, the sequence variation responsible for these differences is possibly located outside the putative LDL receptor binding domain.

Adolescent↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

Giant cell arteritis in Jerusalem: a 12-year epidemiological study.

The prevoting conception of the incidence of giant cell arteritis (GCA) among population underscores the very low incidence of this disease among Jews. We studied the epidemiology, ethnic background, and seasonality of GCA among the Jewish population of Jerusalem. Eighty-four patients with biopsy-proven GCA were identified in a period of 12 yr, from 1980-1991. The age, sex and period-adjusted incidence of GCA was 10.2 per 100,000 population aged > or = 50 yr, approximately 20-fold higher than that reported for the Jewish population in Israel for the years 1960-1978. The female:male ratio was 1.6. A declining trend in the annual incidence was observed for men but not for women. The incidence rate was similar among non-western and western Jews. The onset of GCA was more common during the early summer months (May-June).

Age Factors↗
PubMed1994

Low serum cholesterol is not associated with depression in the elderly: data from an Australian community study.

BACKGROUND: Low serum cholesterol may contribute to depressive symptoms in the elderly. AIMS: To test the relationship between depressive symptoms and low serum cholesterol in an elderly cohort. METHODS: This was an examination of cross-sectional data in a community study of 1237 men and 1568 women aged 60+ years in Dubbo, NSW. Quintiles of serum cholesterol were defined for men and women. The Center for Epidemiological Studies Depression Scale was used as a continuous, dependent variable in multiple regression analyses. RESULTS: Low serum cholesterol was not associated with depressive symptoms in older men or women. Health status, measured by poorer self-ratings, recent hospitalisation, higher disability levels and higher consumption of prescribed and self-prescribed drugs, predicted depressive symptoms. As well, the significance in the statistical model of financial difficulties, low self esteem, low feelings of self efficacy, the adequacy of practical help and emotional support, and recent widowhood, confirmed the importance of social origins of depressive symptoms.

Age Factors↗
PubMed1994

Analysis of steroid related complications and mortality in temporal arteritis: a 15-year survey of 43 patients.

OBJECTIVES: To analyze steroid related complications in patients with temporal arteritis (TA) and to evaluate their possible effect on survival. METHODS: Forty-three consecutive patients with TA diagnosed in one center were followed over 10 years (mean 3 years). All were treated with prednisone. Clinical response and outcome, as well as prednisone dosage and adverse effects, were recorded throughout the followup period. A standardized mortality ratio (SMR) was calculated for the whole period. RESULTS: Twenty-five patients (58%) developed major steroid related complications. The most common were fractures and severe infections. These complications were age related, occurring twice as often in patients older than 75 years compared to younger patients. Steroid related side effects were also dose related, occurring more commonly in patients starting with doses of > 40 mg/day and in patients taking high maintenance dosage. Nineteen patients died during the study period, 11 during the first year. Deaths of 7 patients were probably related to steroid treatment: Six had fatal infections and one had a fatal bleeding ulcer. The overall SMR was 2.12 (95% confidence interval 1.27-2.96), mainly due to excess mortality in the first year. CONCLUSION: Steroid treatment in TA may cause major morbidity and increased mortality. The therapeutic regimen in TA should be individualized, and the patient's age, severity of TA, and coexistent medical conditions should be considered.

Aged↗
PubMed1994

Cerebrotendinous xanthomatosis in the Israeli Druze: molecular genetics and phenotypic characteristics.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid-storage disease caused by mutations in the sterol 27 hydroxylase gene (CYP27). Clinically, a multitude of neurological, skeletal, and vascular manifestations are usually present. Premature atherosclerosis has been reported in CTX and may be related to the metabolic derangement caused by the deficiency of the enzyme. A CYP27 nonsense mutation created by the deletion of cytosine376 has been identified in four Israeli Druze CTX patients residing in the same village. Molecular screening for this mutation in families of two probands revealed a total of 10 homozygotes and 28 heterozygotes whose clinical and biochemical characteristics are described. Overall, except for tendon xanthomas, most of the clinical manifestations progress with age. The CYP27 mutation was associated with modest differences in the levels of plasma total cholesterol (TC) and LDL cholesterol (LDL-C). The distribution of plasma concentrations of TC and LDL-C in the CTX families was consistent with a polygenic model. A similar model that includes also the effects of the CYP27 genotypes was not better supported by the data. It may be concluded that, in CTX, the presence of a CYP27 mutation does not significantly affect the plasma concentrations of lipids and lipoproteins. Therefore, the reported increased prevalence of atherosclerosis in this disease must be related to other factors.

Adolescent↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Lipoprotein(a) is not associated with coronary heart disease in the elderly: cross-sectional data from the Dubbo study.

Lipoprotein(a) (Lp(a)) may be an independent risk factor for cardiovascular disease. We have examined Lp(a) concentration in 1202 males and 1512 females, aged 60 years and older, who were participants in an ongoing prospective study of cardiovascular disease in the elderly. This report relates to cross-sectional data at study entry. Median Lp(a) concentration was significantly higher in females than in males (P < 0.001), but did not vary with age. Lp(a) concentration rank was significantly correlated with total (r = 0.16, P < 0.001) and LDL cholesterol (r = 0.19, P < 0.001), but this relationship disappeared after adjustment of LDL cholesterol for Lp(a) cholesterol content. Twenty-four percent of males and 17% of females had prevalent coronary heart disease (CHD) at study entry based on non-invasive criteria. Median Lp(a) concentration was slightly higher in those subjects with CHD, compared with those without CHD, but the difference was not statistically significant (P > 0.20). In a multiple logistic model, the following variables were independent predictors of CHD in this elderly population: age, hypertension (males only), family history of CHD, HDL cholesterol and triglycerides (females only), but not total cholesterol or Lp(a). These relationships were similar whether or not the model included Lp(a) concentration. The findings do require confirmation in the prospective study now in progress.

Age Factors↗