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Biomedical subjects

R Salonen

Publications and source records attributed to R Salonen.

At least 127 records · Page 7Linked to original sources

Association of corneal arcus with ultrasonographically assessed arterial wall thickness and serum lipids.

Ophthalmological examination was made for 447 hypercholesterolemic middle-aged Eastern Finnish men participating in the Kuopio Atherosclerosis Prevention Study (KAPS) in order to evaluate the prevalence of corneal arcus, its risk factors, and possible association with atherosclerosis. The degree of atherosclerosis was assessed by ultrasonographic examination of carotid and femoral arteries. Corneal arcus in either eye was observed in 51.4% of the participants. Old age and high LDL cholesterol concentration were associated with the presence of corneal arcus. Corneal arcus had a close relationship with ultrasonographically assessed atherosclerosis.

Adult↗

Biparietal diameter and crown-rump length in fetuses with Down's syndrome: implications for antenatal serum screening for Down's syndrome.

OBJECTIVES: 1. To compare the ultrasound biparietal diameter and crown-rump length of fetuses with and without Down's syndrome in the first half of pregnancy; 2. To investigate the effect of estimation of gestational age using either measure on the detection rate of serum screening for Down's syndrome. DESIGN: Matched case-control study. Cases were singleton Down's syndrome pregnancies with a biparietal diameter or a crown-rump length recorded. Five controls were matched to each case on: medical centre; the date of the ultrasound scan examination (within two years); gestational age measured as the number of days since the first day of the last menstrual period; and the ultrasound measure used (ie the biparietal diameter (the measure of choice), or the crown-rump length otherwise). If a woman had a serum screening test for Down's syndrome, the biparietal diameter or crown-rump length measurement had to be taken prior to the screening test so that the result of the test could not influence whether a scan was performed. SETTING: Ten antenatal screening centres in seven countries in Europe and North America. SUBJECTS: Two hundred and one women with singleton Down's syndrome pregnancies and 1005 women with unaffected singleton pregnancies. RESULTS: The median biparietal diameter of fetuses with Down's syndrome was identical to that among the controls (median difference 0.0 mm, 95% confidence intervals (CI) -0.5 to 0.5 mm). The estimates of gestational age based on biparietal diameter yielded a median gestational age less than that based on the women's last menstrual period: three days less for cases and two days less for controls; small but statistically significant differences probably reflected a minor systematic difference in the conversion of a biparietal diameter to a gestational age estimate. The median crown-rump length of fetuses with Down's syndrome was also identical to that among controls (median difference 0.0 mm, 95% CI-1.5 to 2.0 mm). There was no significant difference between the median gestational age estimate based on crown-rump length and that based on the women's last menstrual period. CONCLUSION: In antenatal screening for Down's syndrome the routine use of an ultrasound biparietal diameter or crown-rump length measurement to estimate gestational age will not adversely affect the detection rate. To avoid differences in gestational age estimates using the last menstrual period and the biparietal diameter influencing screening performance, separate medians should be derived for each serum marker using the two methods of estimating gestational age. The appropriate set of medians can then be used to calculate the multiple of the median value for each woman screened depending on the method used to estimate her gestational age.

Case-Control Studies↗

Prenatal diagnosis of diastrophic dysplasia with polymorphic DNA markers.

Ultrasonography is a non-invasive method for prenatal detection of diastrophic dysplasia (DTD) in the second trimester of pregnancy. As there is a need for genetic counselling as early as possible we wished to develop a method based on molecular analysis. Five fetuses in families with a previous history of DTD were studied by typing them and their relevant family members for DNA markers closely linked to the DTD gene. The DNA analyses predicted that three of the fetuses were unaffected and two affected. These results were concordant with those obtained by ultrasonography, and the phenotype of the fetus was correctly predicted in all cases. DNA analysis provides a reliable means of prenatal diagnosis in the first trimester of pregnancy.

Base Sequence↗

Ultrasound B-mode imaging in observational studies of atherosclerotic progression.

BACKGROUND: Investigations of the progression of atherosclerosis in human arteries suggest that changes in the thickness of the arterial intima-media complex, observable with B-mode ultrasonography, may precede development of atherosclerotic lesions. For epidemiological studies and clinical trials, B-mode ultrasound has the advantage that it is noninvasive, can be used in nonsymptomatic subjects, and can be carried out repeatedly, thus reducing the necessary sample size. In the Kuopio Ischaemic Heart Disease Risk Factor Study, we have assessed the reliability of B-mode ultrasound through studying intraobserver and interobserver variability. We have also investigated its predictive value by associating ultrasound observations with clinical end points, risk factors for common carotid and femoral atherosclerosis, and predictors of progression of common carotid atherosclerosis. METHODS AND RESULTS: The study of B-mode ultrasound reliability was conducted in 10 middle-aged men, with initial and two repeat scannings. The between-observer coefficient of variation was 10.5% for the first assessments by four observers. The intraobserver variability, described as the mean of the absolute difference between the first and third observations, was 0.087 mm, or 8.3% of the mean intimal-medial thickness (IMT). Ultrasonographic assessment of 1,257 men was compared with diagnostic information obtained from a prospective registry for acute myocardial infarction (AMI). The presence of any atherosclerotic findings was associated with a 3.0-fold risk of AMI. For each 0.1 mm of common carotid IMT, AMI risk increased by 11% (p < 0.001). Common carotid artery and femoral artery atherosclerosis, as assessed by mean maximal IMT, had different risk factor profiles. Age, serum low density lipoprotein cholesterol, smoking, platelet aggregability, serum copper, serum selenium (inversely), and blood hemoglobin were the strongest predictors of 2-year increase of common carotid IMT. CONCLUSIONS: On the basis of our experience and findings, the ultrasonographic assessment of common carotid atherosclerosis appears to be a feasible, reliable, valid, and cost-effective method for both population studies and clinical trials of atherosclerosis progression and regression.

Arteries↗

Autoantibody against oxidised LDL and progression of carotid atherosclerosis.

Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in serum and recognise material in atheromatous tissue. However, there has been no prospective study to assess the importance of oxidised LDL among patients with vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and native LDL in baseline serum samples of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression. Neither group had specific antibody binding to native LDL. A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003). Cases also had a greater proportion of smokers (37% vs 3%), higher LDL cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the severity of baseline atherosclerosis, the difference in antibody titre remained significant in a multifactorial logistic model (p = 0.031). Thus, the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men. Our data provide further support for a role of oxidatively modified LDL in atherogenesis.

Adult↗

The accident at Chernobyl and trisomy 21 in Finland.

Our objective was to explore whether the radiation fallout in Finland after the accident at the Chernobyl nuclear power plant in April 1986 led to an increased incidence of trisomy 21. In this geographic and temporal cohort study, the country was divided into three zones according to the amounts of radioactive fallout and internal radiation caused by two cesium isotopes. The 518 cytologically verified cases of trisomy 21 were divided into a control group (conceived before the accident), and a study group of children whose expected dates of birth were in the post-accident years 1987-1988, i.e., pregnancies commenced after May 1986. The cases were also divided into three subgroups according to the zones of radiation. There were no significant differences in prevalence of trisomy 21 between the control and study groups nor between the three zones in spite of the significant differences in the levels of radiation and in the body burden that prevailed throughout the study period. Power estimates showed that in the two zones of lower radiation, an increase of 0.5% in the prevalence would have been detected with a power of 0.85, and in the somewhat smaller zone of the highest radiation, with a power of 0.70. The study lends no further support to the view that the low radiation fallout in western Europe would have been causally associated with trisomy 21.

Accidents↗

High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men.

BACKGROUND: Iron can induce lipid peroxidation in vitro and in vivo in humans and has promoted ischemic myocardial injury in experimental animals. We tested the hypothesis that high serum ferritin concentration and high dietary iron intake are associated with an excess risk of acute myocardial infarction. METHODS AND RESULTS: Randomly selected men (n = 1,931), aged 42, 48, 54, or 60 years, who had no symptomatic coronary heart disease at entry, were examined in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland between 1984 and 1989. Fifty-one of these men experienced an acute myocardial infarction during an average follow-up of 3 years. On the basis of a Cox proportional hazards model adjusting for age, examination year, cigarette pack-years, ischemic ECG in exercise test, maximal oxygen uptake, systolic blood pressure, blood glucose, serum copper, blood leukocyte count, and serum high density lipoprotein cholesterol, apolipoprotein B, and triglyceride concentrations, men with serum ferritin greater than or equal to 200 micrograms/l had a 2.2-fold (95% CI, 1.2-4.0; p less than 0.01) risk factor-adjusted risk of acute myocardial infarction compared with men with a lower serum ferritin. An elevated serum ferritin was a strong risk factor for acute myocardial infarction in all multivariate models. This association was stronger in men with serum low density lipoprotein cholesterol concentration of 5.0 mmol/l (193 mg/dl) or more than in others. Also, dietary iron intake had a significant association with the disease risk in a Cox model with the same covariates. CONCLUSIONS: Our data suggest that a high stored iron level, as assessed by elevated serum ferritin concentration, is a risk factor for coronary heart disease.

Adult↗

Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland.

The authors investigated the association of serum copper concentration with the risk of acute myocardial infarction in 1,666 randomly selected men aged 42, 48, 54, or 60 years who had no symptomatic ischemic heart disease at entry. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study in Eastern Finland were done during 1984 to 1988. In Cox multivariate survival models adjusting for age, examination year, ischemic electrocardiogram in exercise, maximal oxygen uptake, diabetes, family history of ischemic heart disease, cigarette-years, mean systolic blood pressure, serum high density lipoprotein (HDL) cholesterol subfraction HDL2 and low density lipoprotein (LDL) cholesterol concentrations and blood leukocyte count, serum copper concentration in the two highest tertiles (1.02-1.16 mg/liter and 1.17 mg/liter or more) associated with 3.5-fold (95% confidence interval (Cl) 1.3-9.4, p less than 0.05) and 4.0-fold (95 percent Cl 1.5-10.8, p less than 0.01) risk of acute myocardial infarction. These data indicate that high copper status, reflected by elevated serum copper concentration, is an independent risk factor for ischemic heart disease.

Adult↗

Interactions of serum copper, selenium, and low density lipoprotein cholesterol in atherogenesis.

OBJECTIVE: To investigate the interactions between serum copper, selenium, and low density lipoprotein cholesterol concentrations with regard to the progression of carotid atherosclerosis. DESIGN: Longitudinal study of a cohort of middle aged men followed up for 24 months. SETTING: Epidemiological survey of the population of seven communities in eastern Finland. SUBJECTS: 126 men aged 42, 48, 54, or 60 at examination randomly selected from a population based sample of 2682 men. MAIN OUTCOME MEASURES: Increase in maximal carotid intima media thickness. RESULTS: The mean increase in the maximal common carotid intima media thickness after two years was greater in men with high serum copper concentrations (0.16 mm compared with 0.08 mm in men with concentrations less than 17.6 mumol/l; p = 0.010), those with low serum selenium concentrations (0.15 mm compared with 0.09 mm in men with concentrations greater than or equal to 1.40 mumol/l; p = 0.035), and those with raised serum low density lipoprotein cholesterol concentrations (0.15 mm compared with 0.08 mm in men with concentrations less than 4.0 mmol/l; p = 0.032) after adjustment for age and cigarette pack years in a three way analysis of covariance. A raised serum low density lipoprotein concentration was associated with accelerated progression of atherosclerosis only in men with higher than median serum copper concentrations (net difference 0.22 mm; p less than 0.001 for two way interaction), and this synergism was even more pronounced in men with serum selenium concentrations below the median value (net difference 0.41 mm; p = 0.042 for three way interaction). CONCLUSION: These data provide evidence of a synergistic effect of copper (a pro-oxidant), a low serum concentration of selenium (a cofactor of an enzyme that scavenges free radicals), and low density lipoprotein cholesterol concentration in atherogenesis.

Adult↗

DNA-based prenatal diagnosis of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1).

Eleven fetuses at risk for the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) were studied using DNA markers and the results were compared with the results of electron microscopy (EM) of chorionic villus specimens from pregnancies in the first or early second trimester of pregnancy. In four cases, the prenatal diagnosis was made independently with both methods, and in seven cases, the EM diagnosis was confirmed postnatally or from autopsy material using RFLP analysis. The two methods gave concordant results in all cases. The DNA analysis based on RFLP haplotypes also for the first time facilitates reliable carrier diagnostics. RFLP analysis based on polymorphic markers closely linked to the INCL locus is now available for prenatal diagnosis of this fatal brain disease, whose biochemical background is totally unknown and for which no treatment is available.

Chorionic Villi Sampling↗

Measurement of intima-media thickness of common carotid arteries with high-resolution B-mode ultrasonography: inter- and intra-observer variability.

High-resolution B-mode ultrasonography enables quantitative measurement of the thickness of the intima-media layer of superficial large arteries noninvasively. We investigated the inter- and intra-observer variability of this measurement in the common carotid arteries in 10 randomly selected men. The maximal right and left carotid intima-media thickness (IMT) was measured with calipers during the scanning from frozen images by four observers in a blinded fashion. Three observers also repeated the scanning and the measurements twice with a week's intervals, with no knowledge of the previous readings. The inter-observer coefficient of variation (CV) was 10.5%. The intra-observer CV (mean of right and left CCA) was 5.4-5.8% for the three observers who carried out the measurements three times. The mean absolute difference between the first and third measurement was 0.087 mm. The intra-observer variation accounted for only 4% of the total measurement variability, 96% being attributable to inter-observer variation. These data show that most of the measurement variability in ultrasonographic B-mode IMT measurements is due to differences between observers, whereas the within-observer variability over time appears proportionately very small.

Analysis of Variance↗

Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status.

We investigated the effect on platelet function of supplementing men with low antioxidant status with 600 mg ascorbic acid, 300 mg alpha-tocopherol, 27 mg beta-carotene, and 75 micrograms selenium in yeast daily. Eighty men were randomly assigned in pairs (matched for smoking, baseline antioxidant status, and time and day of entry) by use of a double-blind design to receive supplement or placebo for 5 mo. Compared with 39 control subjects, 39 antioxidant-supplemented men experienced the following net reductions during the double-blind period: 20% (P = 0.012) in serum lipid peroxides, 24% (P = 0.035) in ADP-induced platelet aggregation, 42% (P = 0.040) in the rate of ATP release during aggregation, 51% (P = 0.018) in serum (platelet-produced) thromboxane B2, and 29% (P = 0.024) in plasma beta-thromboglobulin concentration. The data support our hypothesis that antioxidant supplementation of men with low antioxidant status and high fat intake reduces lipid peroxidation, the capacity of platelets to aggregate and to produce thromboxane A2, and in vivo platelet activation.

Adenosine Triphosphate↗

Determinants of carotid intima-media thickness: a population-based ultrasonography study in eastern Finnish men.

We investigated the determinants of maximal intima-media thickness of common carotid arteries in a population-based sample of 1224 Eastern Finnish men aged 42, 48, 54 or 60 years. A high-resolution B-mode ultrasonographic examination was performed as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD). The maximal intima-media thickness (IMT) varied between 0.48 mm and 4.09 mm (mean value +/- SD, 0.94 mm +/- 0.38 mm). Age (standardized partial coefficient, beta = 0.238, P less than 0.0001), ambulatory pulse pressure (beta = 0.130, P less than 0.0001), cigarette-years of smoking (beta = 0.125, P less than 0.0001), serum LDL cholesterol concentration (beta = 0.125, P less than 0.0001), history of ischaemic heart disease (beta = 0.125, P less than 0.0001), pre-exercise systolic blood pressure (beta = 0.070, P = 0.0113) and diabetes (beta = 0.068, P = 0.0072) were most strongly associated with IMT. This study confirms the role of systolic blood pressure, smoking and serum LDL cholesterol levels as major risk factors for increased carotid intima-media thickness.

Adult↗