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Biomedical subjects

R Salonen

Publications and source records attributed to R Salonen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fetal nuchal translucency and normal chromosomes: a long-term follow-up study.

OBJECTIVE: To assess the impact of increased nuchal translucency observed during early pregnancy on the subsequent health of children with normal chromosomes, with special attention to cardiac anatomy and function. METHODS: Clinical examination and detailed cardiac evaluation were carried out in 50 chromosomally normal children at the age of 2.4-7.1 years who had had a nuchal translucency measurement of > or = 3 mm at 13-15 weeks' gestation. The data of two babies who died of heart defects were also included. RESULTS: Major cardiac defects were identified in four (8%) of the children. The growth of all children was within normal limits. One child had Noonan syndrome, one had a cleidocranial dysplasia and a third had a developmental delay together with an unrecognized syndrome. Webs in the neck region were noticed in two children, with no associated pathology. CONCLUSIONS: In chromosomally normal fetuses with increased nuchal translucency, fetal echocardiography is necessary to identify major cardiac defects. In general, the parents can be reassured that, in the great majority, postnatal development is normal.

Child↗
PubMed2001

Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study.

A number of epidemiological studies have shown an association between beta-carotene and the risk of cardiovascular diseases, whereas only a few studies are available concerning the association of lycopene with the risk of coronary events, and no studies have been undertaken concerning lycopene and stroke. Thus, we tested the hypothesis that low serum levels of lycopene are associated with increased risk of acute coronary events and stroke in middle-aged men previously free of CHD and stroke. The subjects were 725 men aged 46-64 years examined in 1991-3 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Forty-one men had either a fatal or a non-fatal acute coronary event or a stroke by December 1997. In a Cox' proportional hazard's model adjusting for examination years, age, systolic blood pressure and three nutritional factors (serum folate, beta-carotene and plasma vitamin C), men in the lowest quarter of serum lycopene levels (< or =0.07 micromol/l) had a 3.3-fold (95 % CI 1.7, 6.4, risk of acute coronary events or stroke compared with the others. Our study suggests that a low serum level of lycopene is associated with an increased risk of atherosclerotic vascular events in middle-aged men previously free of CHD and stroke.

Adult↗
PubMed2001

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men.

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.

Aged↗
PubMed2000

Role of nephrin in cell junction formation in human nephrogenesis.

Nephrin is a cell adhesion protein located at the slit diaphragm area of glomerular podocytes. Mutations in nephrin-coding gene (NPHS1) cause congenital nephrotic syndrome (NPHS1). We studied the developmental expression of nephrin, ZO-1 and P-cadherin in normal fetal kidneys and in NPHS1 kidneys. We used in situ hybridization and immunohistochemistry at light and electron microscopic levels. Nephrin and zonula occludens-1 (ZO-1) were first expressed in late S-shaped bodies. During capillary loop stage, nephrin and ZO-1 localized at the basal margin and in the cell-cell adhesion sites between developing podocytes, especially in junctions with ladder-like structures. In mature glomeruli, nephrin and ZO-1 concentrated at the slit diaphragm area. P-cadherin was first detected in ureteric buds, tubules, and vesicle stage glomeruli. Later, P-cadherin was seen at the basal margin of developing podocytes. Fetal NPHS1 kidneys with Fin-major/Fin-major genotype did not express nephrin, whereas the expression of ZO-1 and P-cadherin was comparable to that of control kidneys. Although early junctional complexes proved structurally normal, junctions with ladder-like structures and slit diaphragms were completely missing. The results indicate that nephrin is dispensable for early development of podocyte junctional complexes. However, nephrin appears to be essential for formation of junctions with ladder-like structures and slit diaphragms.

Cadherins↗
PubMed2000

Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland.

Basic research and our previous studies have suggested that mercury exposure enhances lipid peroxidation and the risk of myocardial infarction, but there are no studies concerning the association between mercury accumulation and atherosclerosis. We therefore investigated whether high hair mercury content is associated with accelerated progression of carotid atherosclerosis, determined by ultrasonographic assessment of common carotid intima-media thickness (IMT), in a prospective study among 1014 men aged 42-60 years. In a linear regression model adjusting for other atherosclerotic risk factors, high hair mercury content was one of the strongest predictors of the 4-year increase in the mean IMT (P2.81 microg/g (fifths) had an IMT increase of 0.105, 0.102, 0.113, 0.107 and 0.140 mm/4 years, respectively (P=0.041 for heterogeneity between groups). The IMT increase was 0.034 mm/4 years (31.9%) greater in the highest fifth than in the other fifths (P<0.05 for the difference). These findings suggest that mercury accumulation in the human body is associated with accelerated progression of carotid atherosclerosis.

Adult↗
PubMed2000

Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis.

OBJECTIVES: To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins. DESIGN AND SUBJECTS: Double-masked two-by-two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >/= 5.0 mmol L-1 were studied. SETTING: The population of the city of Kuopio in Eastern Finland. INTERVENTION: Twice daily either a special formulation of 91 mg of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these (CellaVie(R)) or placebo for three years. MEASUREMENTS: Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness (IMT), was calculated over semi-annual assessments. RESULTS: The average increase of the mean IMT was 0.020 mm year-1 amongst men randomized to placebo and 0.018 mm year-1 in vitamin E, 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year-1. The proportion of men with progression was reduced by 74% (95% CI 36-89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo. CONCLUSIONS: Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis-based events.

Aged↗
PubMed2000

Drug comparisons: why are they so difficult?

Comparing therapeutic agents in a drug class can be difficult. This article examines the ways in which the triptans can be and have been compared and evaluates the advantages and disadvantages of the approaches. Direct comparative trials are clearly the best method for evaluating the triptans, however, there is a scarcity of this type of data on the currently available compounds. Indirect comparison such as meta-analysis is a second method of comparing these agents but only serves as an estimate of relative efficacy or safety based on a comparison of pooled data derived from a number of different trials for each agent. Comparison of the data found in the regulatory documents represents another type of indirect comparison that can be done so long as the data is presented in a consistent format across products.

Clinical Trials as Topic↗
PubMed2000

Inter-laboratory comparison of flow-volume curve measurements as quality control procedure in the framework of an international epidemiological study (PEACE project).

The aim of this work was to describe the results of a simple quality control procedure for the flow-volume curve adopted in a multicentre epidemiological study (PEACE). In 14 centres, 8-15 individuals (n = 157) performed forced vital capacity (FVC) manoeuvres following a standard protocol with both the local spirometer/pneumotachograph and a portable spirometer (i.e. the 'reference instrument' for this study). Deviances of measurements were assessed by computing the differences (delta) between the former and the latter, the ratios of such differences on portable spirometer values (delta %) and the coefficients of variation (CV). The portable spirometer yielded lower mean AFVC and deltaFEV1 (forced in 1 sec) than local instruments (except for two and four centres, respectively). In most instances, differences were statistically significant. Absolute mean A%FVC ranged from 4.9-18.2%, while delta%FEV1 ranged from 2.3-18.5%. The Bland and Altman analysis showed a good agreement between the portable and local instruments, except for two centres, where a systematic trend towards higher individual absolute deltaFVC and deltaFEV1 was observed. The overall variability, assessed by CV, was within 6.2% and 5.1% for FVC and FEV1, respectively: it was similar to other quality control studies ranging from 2.0-5.5% for FVC and 2.2-5.8% for FEV1. Our results point out the importance of performing interlaboratory comparisons as a quality control procedure in multicentre epidemiological studies on lung function, and of stimulating manufacturers to extend the accuracy and precision of the instruments.

Adolescent↗
PubMed2000

Low plasma lycopene concentration is associated with increased intima-media thickness of the carotid artery wall.

Although a number of epidemiological studies have evaluated the association between ss-carotene and the risk of cardiovascular diseases, there has been little research on the role of lycopene, an acyclic form of ss-carotene, with regard to the risk of cardiovascular disease. We investigated the relationship between plasma concentrations of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in 520 middle-aged men and women (aged 45 to 69 years) in eastern Finland. They were examined from 1994 to 1995 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study, a randomized trial concerning the effect of vitamin E and C supplementation on atherosclerotic progression. The subjects were classified into 2 categories according to the median concentration of plasma lycopene (0.12 micromol/L in men and 0.15 micromol/L in women). Mean CCA-IMT of the right and left common carotid arteries was 1.18 mm in men and 0.95 mm in women with plasma lycopene levels lower than the median and 0.97 mm in men (P:<0.001 for difference) and 0.89 mm in women (P:=0.027 for difference) with higher levels of plasma lycopene. In ANCOVA adjusting for cardiovascular risk factors and intake of nutrients, in men, low levels of plasma lycopene were associated with a 17.8% increment in CCA-IMT (P:=0.003 for difference). In women, the difference did not remain significant after the adjustments. We conclude that low plasma lycopene concentrations are associated with early atherosclerosis, manifested as increased CCA-IMT, in middle-aged men living in eastern Finland.

Age Factors↗
PubMed2000

Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men.

We studied the long-term effects of vitamins E and C and their combination on lipid peroxidation in vivo and in vitro. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) trial is a double-masked placebo-controlled randomized clinical trial to study the effects of vitamin C (500 mg of slow release ascorbate per day), vitamin E (182 mg of RRR-alpha-tocopherol acetate per day), and the combination of both antioxidants. Lipid peroxidation measurements were carried out for 48 male participants at entry and at 12 and 36 months. Compared with placebo, vitamin E and the vitamin combination increased plasma lipid-standardized alpha-tocopherol during the first 12 months by 68.2% and 65.2% (P:<0. 001 for both), respectively, and reduced serum 7beta-hydroxycholesterol by 50.4% (P:=0.013) and 44.0% (P:=0.041), respectively. The net change of lipid standardized alpha-tocopherol was 63.8% after 36 months of vitamin E supplementation and 43.3% for the combination. Vitamin C supplementation elevated plasma total ascorbate level by 30.1% (P:=0.043) in 12 months and by 91.1% (P:=0. 001) in 36 months. Neither vitamin E, vitamin C, nor the combination influenced the urinary excretion rate of 7-hydro-8-oxo-2'-deoxyguanosine or the antioxidative capacity of plasma. Vitamin E and the combination of vitamins E and C enhanced the oxidation resistance of isolated lipoproteins and total serum lipids. Our data indicate that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation in vitro and in vivo, whereas a relatively high dose of vitamin C alone does not.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Standing at work and progression of carotid atherosclerosis.

OBJECTIVES: The association between the amount of standing at work and the progression of carotid intima media thickness (IMT) was studied among 584 active working men participating in the Kuopio Ischemic Heart Disease Risk Factor Study. METHODS: Ultrasound measurements of atherosclerotic changes in the carotid arteries were performed at the beginning of the study and after 4 years. Analyses of changes in IMT included adjustments for risk factors and stratification by base-line levels of atherosclerosis and prevalent ischemic heart disease (IHD). RESULTS: Significant relationships were found between the amount of standing at work and atherosclerotic progression. After adjustment for the heaviness of the work, psychosocial job factors, income, and biological and behavioral risk factors, the mean change in maximum IMT for those standing not at all, a little, a lot, and very much was 0.24, 0.25, 0.28, and 0.33 mm, respectively. For men with IHD the respective changes were 0.08, 0.15, 0.37, and 0.75 mm -- a 9-fold difference between the no-exposure and high-exposure group. For the men with carotid stenosis, the respective difference was 3-fold. CONCLUSIONS: These findings provide the first empirical support in a population study for the role of hemodynamic factors in the progression of atherosclerosis induced by long-term standing. Men with carotid stenosis or IHD appear especially vulnerable to the adverse effects associated with standing at work. Reducing the duration of standing at work should be considered both in the occupational rehabilitation of such patients and in the primary prevention of atherosclerosis.

Adult↗
PubMed2000

Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies.

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1999

Rapid FMR1-protein analysis of fetal blood: an enhancement of prenatal diagnostics.

Fragile-X syndrome, a frequent cause of inherited mental retardation, is characterised in almost all cases by a CGG-repeat expansion that is located within the FMR-1 gene and that prevents the expression of fragile-X mental retardation protein (FMRP). We describe a test that simultaneously allows the rapid detection of FMRP in fetal lymphocytes and distinguishes these from fetal erythrocytes. Routine molecular genetic methods fail in the rare cases where protein expression is blocked, although there is no repeat expansion. Furthermore, they are unsuitable in cases of advanced pregnancy. Our test proves extremely valuable under both these circumstances.

Female↗
PubMed1999

Assignment of the locus for hydrolethalus syndrome to a highly restricted region on 11q23-25.

Hydrolethalus syndrome is a recessively inherited lethal malformation syndrome characterized by hydrocephaly with absent midline structures of the brain, micrognathia, polydactyly, and several other abnormalities, mostly in the midline structures. Hydrolethalus syndrome was described in 1981 in Finland, where the incidence is 1:20,000. Only a few cases have been reported elsewhere, and the pathogenesis has remained unknown. Here we report the assignment of the hydrolethalus syndrome locus to chromosome 11q23-25 in Finnish families. The initial genome scan was performed using DNA samples from only 15 affected individuals. In the next step, the hydrolethalus syndrome locus was assigned to an 8.5-cM interval between markers D11S4144 and D11S1351 by linkage analysis in eight families. Finally, the critical locus could be restricted by linkage disequilibrium and haplotype analyses to a 0.5-1-cM region between markers D11S933 and D11S934. Genealogical studies performed in 40 families affected by hydrolethalus revealed no regional clustering, suggesting a relatively early introduction of the disease mutation into the Finnish population and the spreading of the mutation with the inhabitation of the late-settlement area.

Abnormalities, Multiple↗
PubMed1999

Sumatriptan is effective in the treatment of menstrual migraine: a review of prospective studies and retrospective analyses.

Menstrual migraine may be debilitating, long-lasting, and refractory to treatment. Because the efficacy and tolerability of abortive and prophylactic treatment options for menstrual migraine have generally not been evaluated in controlled clinical trials, treatment choices are often made on the basis of personal experience and anecdotal reports. This article reviews evidence from retrospective analyses and prospective studies showing that sumatriptan injection and tablets are effective and well tolerated in menstrual migraine. (1) Sumatriptan injection 6 mg was as effective in the treatment of menstrual migraine attacks as it was for nonmenstrual attacks in a retrospective analysis of data from two randomized, double-blind, placebo-controlled, parallel-group trials (n = 1104). In the menstrual migraine group, 80% of women treated with sumatriptan injection 6 mg compared with 19% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (2) Sumatriptan injection 6 mg was effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, parallel-group, two-attack study (n = 226). Across the two attacks, 70-71% of patients treating menstrual migraine attacks with sumatriptan injection 6 mg compared with 22-24% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (3) Sumatriptan tablets 100 mg were effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, crossover study in women diagnosed with menstrual migraine (n = 115). For menstrual migraine attacks, headache relief 4 h postdose was reported by 67% of sumatriptan-treated patients compared with 33% of placebo-treated patients. Sumatriptan injection and tablets were generally well tolerated in these studies, in which adverse events were characteristic of those typically observed in sumatriptan acute migraine clinical trials. These data demonstrate that sumatriptan injection and tablets are effective and well tolerated in the treatment of menstrual migraine.

Female↗