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Biomedical subjects

R Salonen

Publications and source records attributed to R Salonen.

At least 109 records · Page 6Linked to original sources
PubMed1994

FRAXA locus in fragile X diagnosis: family studies, prenatal diagnosis, and diagnosis of sporadic cases of mental retardation.

Three hundred eighty-seven individuals from 32 Finnish fragile X families were studied, using the probe StB12.3 [Oberlé et al., 1991: Science 252:1097-1102] for the FRAXA locus, to reveal length variations in the FMR-1 gene. As expected, the affected individuals (with few exceptions) showed a full mutation; a few affected individuals with a premutation only were found. Seventy percent of the females with a full mutation were affected. The size of the mutation remained unchanged in 6, increased in 73, and decreased in 6 female meioses. In male meioses the size was unchanged in 15 cases, increased in 2 cases, and decreased in 1 case. Prenatal diagnosis was performed in 20 cases. In 7 of these the mutation was inherited by the fetus. Four hundred sixty-four mentally retarded patients were referred to us for FRAXA analysis. In 5% of these the fragile X mutation was found. In addition to the clear cut negative or positive results there were 6 cases in which an increase of 50-80 bp was detected. These findings may represent either large normal alleles or small premutations suggesting a possible tissue mosaicism which could explain the retardation of the patients.

Amniocentesis↗
PubMed1994

Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction.

BACKGROUND: Previous studies have suggested that higher levels of regular physical activity and cardiorespiratory fitness are associated with a reduced risk of coronary heart disease. We investigated the independent associations of physical activity during leisure time and maximal oxygen uptake (a measure of cardiorespiratory fitness) with the risk of acute myocardial infarction. METHODS: During the period 1984 to 1989, we performed base-line examinations in 1453 men 42 to 60 years old who did not report having cardiovascular disease or cancer. Physical activity was assessed quantitatively with a detailed questionnaire, and maximal oxygen uptake was measured directly by exercise testing. During an average follow-up of 4.9 years, 42 of the 1166 men with normal electrocardiograms at base line had a first acute myocardial infarction. RESULTS: After adjustment for age and the year of examination, the relative hazard (risk) of myocardial infarction in the third of subjects with the highest level of physical activity (> 2.2 hours per week) was 0.31 (95 percent confidence interval, 0.12 to 0.85; P = 0.02), as compared with the third with the lowest level (P = 0.04 for linear trend over all three groups). The relative hazard in the third with the highest maximal oxygen uptake (> 2.7 liters per minute) was 0.26 (95 percent confidence interval, 0.10 to 0.68; P = 0.006) (P = 0.006 for linear trend), after adjustment for age, the year and season when the examination was performed, weight, height, and the type of respiratory-gas analyzer used. After up to 17 confounding variables were controlled for, the relative hazards for the third of subjects with the highest level of physical activity (0.34; 95 percent confidence interval, 0.12 to 0.94; P = 0.04) and maximal oxygen uptake (0.35; 95 percent confidence interval, 0.13 to 0.92; P = 0.03), as compared with the values in the lowest third, were significantly (P < 0.05) less than 1.0. CONCLUSIONS: Higher levels of both leisure-time physical activity and cardiorespiratory fitness had a strong, graded, inverse association with the risk of acute myocardial infarction, supporting the idea that lower levels of physical activity and cardiorespiratory fitness are independent risk factors for coronary heart disease.

Adult↗
PubMed1994

Down's syndrome screening in multiple pregnancies using alpha-fetoprotein and free beta hCG.

Second-trimester distributions of the free beta human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) levels in 420 twin and 19 triplet pregnancies were measured and compared with the distributions in 6661 singleton pregnancies. On average, the levels of both analytes were twice as high and over three times as high in triplets. Eight sets of twins discordant for Down's syndrome showed elevated levels of free beta hCG and reduced levels of AFP after correction of the multiple of the median for the presence of a twin pregnancy. Screening for Down's syndrome using the twin correction of the multiple of the median is expected to achieve a 51 per cent detection rate at a 5 per cent false-positive rate using these two markers.

Chorionic Gonadotropin↗
PubMed1994

Intranasal sumatriptan for the acute treatment of migraine. International Intranasal Sumatriptan Study Group.

Two double-blind, placebo-controlled, randomised, multicentre, multinational, parallel-group studies were carried out to identify the optimum dose of intranasal sumatriptan for the acute treatment of migraine. Study medication was taken as a single dose through one nostril in the first study, and as a divided dose through two nostrils in the second study. Totals of 245 and 210 patients with a history of migraine were recruited into the one- and two-nostril studies, respectively. In both studies, headache severity had significantly improved at 120 min after doses of 10-40 mg sumatriptan compared to placebo (P < 0.05) and the greatest efficacy rates were obtained with 20 mg sumatriptan. With 20 mg sumatriptan 78% and 74% of patients experienced headache relief in one- and two-nostril studies respectively. Sumatriptan was generally well tolerated, the most frequently reported event being taste disturbance. The results of the two studies are similar and indicate that administering sumatriptan as a divided dose via two nostrils confers no significant advantage over single-nostril administration.

Acute Disease↗
PubMed1994

Facilitation of experimental allergic encephalomyelitis by irradiation and virus infection: role of inflammatory cells.

Infection with an avirulent strain of Semliki Forest virus (SFV-A7) facilitates the development of experimental allergic encephalomyelitis (EAE) in a genetically resistant BALB/c mouse strain. Irradiation which is necessary for EAE induction caused a decrease in the total number of lymphocytes and an increase in CD4+/CD8+ T cell ratio in the spleen of BALB/c mice. EAE induction increased the ratio further until clinical and histological signs of EAE appeared. Entry of perivascular CD4+ and CD8+ cells preceded the onset of clinical signs and the appearance of MAC-1+ cells in the central nervous system (CNS). In the acute phase of EAE, cellular infiltrates, which were sparse, consisted mainly of MAC-1+ cells and a few CD4+ and CD8+ cells. Inflammatory cells gradually disappeared during the recovery phase. SFV-A7 infection after irradiation and EAE induction did not significantly change the CD4+/CD8+ ratio in the spleen or in the CNS infiltrates but enhanced the entry of inflammatory cell into the CNS. Similar perivascular cell influx was also seen in untreated mice infected with SFV-A7. We conclude that observed rapid reduction of splenic mononuclear cells and increase of the CD4+/CD8+ T cell ratio caused by irradiation prior EAE induction are early crucial events in disease induction in this resistant strain of mice. SFV-A7 infection, which further facilitates the development of EAE, does not induce immunoregulatory changes but provides its effect by enhancing the entry of inflammatory cells into the CNS. The combination of these two mechanisms thus effectively breaks the natural resistance against EAE in this genetically resistant mouse strain.

Animals↗
PubMed1994

Lyme borreliosis associated with complete flaccid paraplegia.

We report the case of a patient with concomitant Lyme borreliosis and acute paraplegia. The paraplegia was complete, flaccid and of upper motor neurone type. The diagnosis of borreliosis was based on the detection of large amounts of IgM and IgG borrelia antibodies in the acute phase serum and on the complete disappearance of IgM antibody during the review period. IgG borrelia antibodies were also detected in the CSF, but leakage of antibodies from the blood to the intrathecal space could not be ruled out. Lymphocytosis and increased total protein concentration in the CSF were signs compatible with neuroborreliosis. Ceftriaxone therapy effected dramatic recovery of the patient. This case suggests that borreliosis should be considered a possible cause of acute flaccid paraplegia.

Acute Disease↗
PubMed1994

Differential expression of myc, max and RB1 genes in human gliomas and glioma cell lines.

Deregulated expression of myc proto-oncogenes is implicated in several human neoplasias. We analysed the expression of c-myc, N-myc, L-myc, max and RB1 mRNAs in a panel of human gliomas and glioma cell lines and compared the findings with normal neural cells. The max and RB1 genes were included in the study because their protein products can interact with the Myc proteins, being thus putative modulators of Myc activity. Several gliomas contained c/L-myc mRNAs at levels higher than those in fetal brain, L-myc predominantly in grade II/III and c-myc in grade III gliomas. High-level N-myc expression was detected. In one small-cell glioblastoma and lower levels in five other gliomas. In contrast, glioma cell lines totally lacked N/L-myc expression. The in situ hybridisations revealed mutually exclusive topographic distribution of myc and glial fibrillary acidic protein (GFAP) mRNAs, and a lack of correlation between myc expression and proliferative activity, max and RB1 mRNAs were detected in most tumours and cell lines. The glioma cells displayed interesting alternative splicing patterns of max mRNAs encoding Max proteins which either suppress (Max) or augment (delta Max) the transforming activity of Myc. We conclude that (1) glioma cells in vivo may coexpress several myc genes, thus resembling fetal neural cells; but (2) cultured glioma cells expression only c-myc; (3) myc, max and RB1 are regulated independently in glioma cells; and (4) alternative processing of max mRNA in some glioma cells results in delta Max encoding mRNAs not seen in normal fetal brain.

Adult↗
PubMed1994

Determinants of femoral and carotid artery atherosclerosis.

OBJECTIVES: The aim of the study was to find the most important determinants of early atherosclerosis in the carotid and femoral arteries. DESIGN: Carotid and femoral maximal intima media thickness (IMT) was measured 19 months after the first of 4 risk factor measurements. SETTING: Department of Community Health and General Practice, University of Kuopio, and Occupational Health Care in Pyhäsalmi Mine, Finland. SUBJECTS: The subjects comprised 60 male volunteers aged from 32 to 65 years from amongst 277 workers at the Pyhäsalmi Mine, Finland. Subjects were invited for an ultrasound examination, in order of serum total cholesterol content, until the required figure of 60 cases was achieved. MAIN OUTCOME MEASURES: Carotid and femoral maximal intima media thickness. RESULTS: Systolic blood pressure (P < 0.01), serum total cholesterol (P < 0.01), age (P = 0.01) and pack-years smoked (P = 0.02) were independent determinants of maximal carotid artery IMT, and total cholesterol (P = 0.01), age (P = 0.03) and pack-years smoked (P = 0.01) for maximal femoral artery IMT. For the latter, plasma fibrinogen concentration (P = 0.10) was the next factor to enter the multiple regression model. Body mass index, heart rate, serum HDL cholesterol, triglycerides, urate, apolipoprotein A1, antithrombin III, lipid peroxides, vitamin E and plasma vitamin C had no significant association with either maximal carotid or femoral IMT or the mean of the carotid and femoral IMT. CONCLUSIONS: Systolic blood pressure, serum total cholesterol, age and pack-years smoked are the most important determinants of early atherosclerosis in the carotid artery and total cholesterol, age and pack-years smoked in the femoral artery. Prevention should take into consideration these findings. The role of plasma fibrinogen and oxidized low density lipoprotein would require re-evaluation in larger populations studied longitudinally.

Adult↗
PubMed1994

A new simple and rapid dual assay for AFP and free beta hCG in screening for Down syndrome.

We have evaluated a simple and rapid 2-step dual-label assay (DELFIA) for alphafetoprotein (AFP) and free beta subunit of human gonadotropin (hCG beta) in second-trimester screening for Down syndrome. Based on stored serum samples from 1059 normal control pregnancies and 72 cases of Down syndrome, we have found the mean Multiple of Median (MoM) for AFP and free hCG beta to be 0.70 and 2.31, respectively. This is slightly but not significantly better than the values for the separate assay for AFP (0.76 MoM) and for intact hCG (2.11 MoM). However, the dual assay is much simpler than the separate assays and therefore prospective comparison trials should be carried out.

Chorionic Gonadotropin↗
PubMed1994

Semliki Forest virus infects mouse brain endothelial cells and causes blood-brain barrier damage.

Induction of experimental allergic encephalomyelitis is facilitated in a genetically resistant BALB/c mouse strain by a nonpathogenic strain of a neurotropic alphavirus, Semliki Forest virus (SFV-A7). One possible explanation for this enhancement is virus infection of endothelial cells (EC), causing increased permeability of the blood-brain barrier. We have now sought evidence for virus infection of EC in vivo by immunocytochemistry and in situ hybridization. SFV-A7 antigens and RNA were detected in vascular EC and perivascular neurons in cerebellar and spinal cord white matter. Expression of viral antigens was followed by fibrinogen leakage from the blood vessels into brain parenchyma. This was shown by immunoperoxidase staining detecting fibrinogen extravascularly in central nervous system sections of infected mice. Simultaneously, expression of ICAM-1 (intercellular adhesion molecule 1) was induced on brain EC. SFV-A7 replicated in mouse brain microvascular EC in vitro and caused lysis of the cells. SFV-A7 did not induce ICAM-1 expression of mouse brain microvascular EC in vitro, while ICAM-1 was readily induced by gamma interferon and interleukin 1 beta. The observed increase of ICAM-1 expression on EC is immune mediated and not a direct effect of the virus infection. We conclude that SFV-A7 infection causes cerebral microvascular damage which contributes to the facilitation of experimental allergic encephalomyelitis in BALB/c mice.

Animals↗
PubMed1994

Ultrasonographic manifestations of common carotid atherosclerosis in elderly eastern Finnish men. Prevalence and associations with cardiovascular diseases and risk factors.

We investigated the prevalence and associations with cardiovascular symptoms, signs, and risk factors of common carotid atherosclerosis using B-mode ultrasonography in a population sample of 182 eastern Finnish men aged 70 to 89 years. Men were examined in 1989 as a part of the 30-year follow-up examination of the eastern Finnish cohort of the Seven Countries Study. The mean maximal intima-media thickness (IMT) of the right and left common carotid arteries was 1.5 mm (range, 0.7 to 5.3 mm; standard deviation, 0.7 mm). Fifty-one percent of the subjects had nonmineralized atheroma and 91% had single or multiple mineralizations in any of the arterial segments imaged. Both mean maximal IMT and nonmineralized atheromas were associated significantly (P < .05) with the presence of cerebral atherosclerosis, carotid murmur, at least one nonpalpable peripheral arterial pulse, ischemic resting electrocardiographic abnormalities, and history of coronary heart disease but not with intermittent claudication at the 30-year follow-up. No significant associations were found between carotid mineralizations and clinical cardiovascular disease. Long-term elevations of serum cholesterol and long-term smoking, measured as the number of risk factor elevations in the six examinations, were associated with the presence of nonmineralized atheroma in the elderly (in 1989). Smoking and repeatedly detected hypertension, on the other hand, had an association with the presence of mineralizations in 1989.

Adult↗
PubMed1994

Increase in oxidation resistance of atherogenic serum lipoproteins following antioxidant supplementation: a randomized double-blind placebo-controlled clinical trial.

OBJECTIVE: To test the effect of supplementation of diet with ascorbic acid, selenium, alpha-tocopherol and beta-carotene on the oxidation resistance of very low (VLDL) + low density lipoprotein (LDL). DESIGN: A randomized placebo-controlled double-masked clinical trial. SETTING: In healthy men aged 30-58 years smoking regularly 15-40 cigarettes/day. SUBJECTS: Forty subjects recruited from the general population, who all completed the study. INTERVENTION: 400 mg of slow release ascorbic acid, 100 micrograms of organic selenium, 200 mg of D-alpha-tocopheryl acetate and 30 mg of beta-carotene daily or placebo, 20 men in each group for 3 months. MAIN OUTCOME MEASURES: The oxidation resistance of VLDL + LDL measured by inducing oxidation with copper chloride and, separately, with a combination of haemin and H2O2. RESULTS: In plasma, alpha-tocopherol increased by 72%, beta-carotene by 209%, ascorbate by 45% and selenium by 20% in the supplemented men. The lag time to oxidation increased by 27% [95% confidence interval (CI) 18-35%, P < 0.001] after copper and by 29% (95% CI 12-46%, P = 0.002) after haemin plus H2O2 in the supplemented group as compared to the placebo group by t-tests. The respective net changes in the maximal oxidation velocity were a reduction of 10% (95% CI 1-21%, P = 0.037) after copper and a reduction of 15% (95% CI-1 to 30%, P = 0.070) after haemin and H2O2. CONCLUSIONS: These findings provide further confirmation for the notion that the supplementation of diet with antioxidative vitamins and selenium increases the oxidation resistance of atherogenic lipoproteins in human plasma.

Adult↗
PubMed1993

Association between plasma fibrinogen concentration and five socioeconomic indices in the Kuopio Ischemic Heart Disease Risk Factor Study.

The association between five socioeconomic indices (lifetime occupation, education, income, ownership of material possessions, and childhood socioeconomic status) and plasma fibrinogen levels was investigated in middle-aged Finnish men who were part of the Kuopio Ischemic Heart Disease Risk Factor Study. The Kuopio Ischemic Heart Disease Risk Factor Study is based on a representative age-stratified sample of 2,682 men aged 42, 48, 54, and 60 years. The data were collected between 1984 and 1989. The present analysis is restricted to the 2,011 men for whom information on fibrinogen and all covariates was available. The covariates were alcohol consumption, body mass index, physical fitness, smoking, coffee consumption, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood leukocyte count, and prevalent disease (at least one sign of ischemic heart disease, hypertension, diabetes, or previous stroke). An age-adjusted inverse association was found between levels of plasma fibrinogen and four of the five socioeconomic indices: current income, education, lifetime occupation status, and current material possessions. After adjustment for the covariates, the association persisted for education, current income, and lifetime occupation. Analysis of the joint effect of childhood and adult socioeconomic status indicated that those who were economically disadvantaged at both times had the highest fibrinogen levels, but the fibrinogen levels of those who were not poor as adults had no variation by childhood socioeconomic status.

Adult↗
PubMed1993

Three Finnish incontinentia pigmenti (IP) families with recombinations with the IP loci at Xq28 and Xp11.

The locus (IP2) for the hereditary form of incontinentia pigmenti (IP) has been mapped to Xq28 by linkage analysis. We studied three IP families with polymorphic markers in the Xq28 region. In two families we observed recombination between the marker loci and IP. In the third family no crossing overs were seen and linkage to the Xq28 region could not be excluded. The other IP locus (IP1) has been mapped to Xp11.21, because of sporadic cases of IP with X-chromosomal alterations involving Xp11.21. To check whether this locus is linked to IP in these families, we used polymorphic markers in the Xp11 region. In all three families recombinations were observed, thus excluding linkage to this locus in these IP families.

Chromosome Mapping↗
PubMed1993

A prospective study of 63 couples with a history of recurrent spontaneous abortion: contributing factors and outcome of subsequent pregnancies.

To evaluate the possible causes of recurrent spontaneous abortion (RSA) and to elucidate the prognosis for subsequent pregnancies 63 RSA patients were studied. Parental karyotyping revealed chromosomal aberrations in six of the 63 couples (4.8%). The rate of increased concentrations of antibodies against cardiolipin was comparable in the patients (10.0%) and in 30 parous controls (6.7%), as was also the occurrence of other autoantibodies (43.3 and 36.7%, respectively). Hysteroscopy revealed uterine cavity abnormalities in 11 of the 55 patients studied (20.0%). Altogether, for 35 RSA women (55.4%) investigations resulted in entirely normal findings; abnormal findings were more frequently encountered in primary aborters (56.8%) than in secondary aborters (26.9%, P < 0.05). During the follow-up period of 24.1 +/- 15.4 months, 48 patients became pregnant a total of 65 times, and the cumulative live birth rate was 62.5%. A living fetus was seen in ultrasound examination in 46 pregnancies (70.7%), whereas a blighted ovum was diagnosed in nine pregnancies (13.8%). An additional nine pregnancies aborted so suddenly that no ultrasound examination was performed, and one ectopic pregnancy was treated laparoscopically. Of the initially viable pregnancies, 13 (28.3%) ended in miscarriage and two were terminated due to fetal anomalies. Normal findings in the investigations were associated with a smaller risk for abortion (40.0%) than were abnormal findings (65.5%, P < 0.05). Of the 30 babies, six (20.0%, with babies from one twin pregnancy excluded) were growth-retarded, 9.7% were born before 37 weeks of gestation, and 22.8% of the mothers had impaired glucose tolerance during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual↗