Migraine revolution and sumatriptan.
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Capsules↗
Biomedical subjects
R Salonen
Publications and source records attributed to R Salonen.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Triptans and coronary spasm.
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Coronary Vessels↗
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↗
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↗
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↗
Pattern of alcohol drinking and progression of atherosclerosis.
Most studies that examine the role of alcohol consumption in atherosclerosis and cardiovascular disease have overlooked the possible effect of drinking pattern. We investigated the association between the habit of heavy acute intake of beer and spirits (binging) and the 4-year progression of carotid atherosclerosis in a population-based sample of middle-aged Finnish men. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) were used to estimate changes in maximum and mean intima-media thickness (IMT) and the maximum plaque height in 764 KIHD participants who reported using beer and in 871 participants who used spirits. After adjustment for age, baseline carotid atherosclerosis, and average weekly alcohol consumption level, we observed the highest atherosclerosis progression in men who usually consumed a whole bottle of vodka or more in 1 session. For beer binging (>6 beers at a time), the magnitude of IMT progression was even higher, although this association was only marginally significant (P<0.1) because of smaller numbers. The associations were largely unaffected by adjustments for blood pressure, lipids, smoking, BMI, and medication. The magnitude of the difference was generally higher in a subgroup that was free of IHD at baseline. We conclude that the pattern of drinking associates with the progression of carotid atherosclerosis independently of the total level of alcohol consumption and risk factors.
Adult↗
Blood pressure and the progression of carotid atherosclerosis in middle-aged men.
Elevated blood pressure has consistently been associated with increased prevalence of preclinical atherosclerosis and with increased risk of clinical atherosclerotic cardiovascular disease (CVD). However, there is no prospective evidence of the association between blood pressure and the progression of preclinical atherosclerosis. We therefore investigated the relationships of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure to the 4-year increase in the measures of early carotid atherosclerosis, the mean and maximal common carotid intima-media thickness (IMT), assessed by B-mode ultrasonography, in 1026 men aged 42 to 60 years. Men with the SBP of <120, 120 to 126, 127 to 134, 135 to 143, and >143 mm Hg (fifths) had an increase in the mean IMT of 0.074, 0.090, 0.110, 0.136, and 0.158 mm per 4 years (P<0.001 for difference between groups, P<0.001 for linear trend) and in the maximal IMT of 0.212, 0.221, 0.279, 0.286, and 0.315 mm per 4 years, (P<0.001, P<0.001), respectively, adjusting for other atherosclerotic risk factors, including DBP. Also, pulse pressure, when adjusted for other risk factors including mean arterial pressure, was directly associated with the IMT increase. DBP was not independently related to the IMT increase. This is the first documentation to show that mildly elevated SBP and pulse pressure accelerate the progression of preclinical atherosclerosis. This study provides further evidence for the finding that systolic hypertension is a more important risk factor for atherosclerosis and consequent CVD than diastolic hypertension. Therefore, more attention should be paid to the level of SBP in the evaluation of CVD risk and in the treatment of hypertension.
Adult↗
Defining optimal dosing for sumatriptan tablets in the acute treatment of migraine.
Oral sumatriptan, which is a well tolerated, effective acute treatment for migraine, and is selectively available in different countries in 100 mg, 50 mg, and 25 mg tablets. The first large dose-ranging study compared the 100 mg dose to higher doses (200 mg and 300 mg) and found it to be just as efficacious and better tolerated. The first studies comparing the 100 mg dose to lower doses (25 mg and 50 mg) found them all to be similar in effectiveness and tolerability. However, a larger definitive study found that the 100 mg and 50 mg doses offered better efficacy than the 25 mg dose, whereas the 25 mg and 50 mg doses were better tolerated than the 100 mg dose. Thus the 50 mg dose appears to offer the best ratio of efficacy to tolerability. Many patients, though, prefer or require the 100 mg dose and tolerate it well. Allowed to select dosing themselves, patients tend to migrate to the 100 mg dose.
Acute Disease↗
Patient preference for oral sumatriptan 25 mg, 50 mg, or 100 mg in the acute treatment of migraine: a double-blind, randomized, crossover study. Sumatriptan Tablets S2CM11 Study Group.
BACKGROUND: Dosing recommendations for oral sumatriptan have ranged from 25 mg to 100 mg. Patient dose preferences are clinically relevant (perhaps moreso than traditional efficacy endpoints) and deserve study. METHODS: A multinational randomized double-blind crossover study was conducted over 18 weeks to assess patient dose preference, efficacy, and tolerability for oral sumatriptan (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine; 257 patients treated three attacks, using a different dose for each. RESULTS: The 100 mg dose was preferred by 35% of patients, 31% the 50 mg dose, and 25% the 25 mg dose. Efficacy and speed of action were the two main reasons given for preferring the higher doses. Compared with the 25 mg dose, the 100 mg and 50 mg doses were significantly more likely to provide headache relief at 2, 3, and 4 h after dosing and complete headache resolution at 3 and 4 h after dosing (P < 0.027). Recurrence rates were similar for the three doses, ranging from 33% to 38%, though the median time to recurrence increased with dose, from 8.5 to 11.8 h. The 25 mg, 50 mg, and 100 mg doses were all well tolerated, with adverse event incidences of 19%, 21%, and 30%, respectively. CONCLUSIONS: Patients preferred the 50 mg and 100 mg doses of oral sumatriptan to the 25 mg dose, and the higher doses were more effective against migraine; however, the 25 mg and 50 mg doses were better tolerated than the 100 mg dose. Though the 50 mg dose probably has the best effectiveness-to-tolerability ratio, some patients clearly prefer a higher dose.
Acute Disease↗
Donation of blood is associated with reduced risk of myocardial infarction. The Kuopio Ischaemic Heart Disease Risk Factor Study.
Because high body iron stores have been suggested as a risk factor for acute myocardial infarction, donation of blood could theoretically reduce the risk by lowering body iron stores. For this reason, the authors tested the hypothesis that voluntary blood donation is associated with reduced risk of acute myocardial infarction in a prospective epidemiologic follow-up study in men from eastern Finland. The subjects are all participants of the Kuopio Ischaemic Heart Disease Risk Factor Study. A cohort of 2,862 men aged 42-60 years were followed for an average of almost 9 years. One man (0.7%) out of 153 men who had donated blood in 24 months preceding the baseline examination experienced an acute myocardial infarction during 1984 to 1995, whereas 316 men (12.5%) of 2,529 non-blood donors had an acute myocardial infarction (p < 0.0001 for difference between proportions). In a Cox proportional hazards model adjusting for age, examination years and all other predictive coronary disease risk factors, blood donors had a 88% reduced risk (relative hazard = 0.12, 95% confidence interval 0.02-0.86, p = 0.035) of acute myocardial infarction, compared with non-blood donors. These findings suggest that frequent blood loss through voluntary blood donations may be associated with a reduced risk of acute myocardial infarction in middle-aged men.
Adult↗