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Biomedical subjects

M Savolainen

Publications and source records attributed to M Savolainen.

17 recordsLinked to original sources

Safety assessment of food-contact paper and board using a battery of short-term toxicity tests: European union BIOSAFEPAPER project.

An European Union (EU)-funded project QLK1-CT-2001-00930 (BIOSAFEPAPER) involves the development, validation and intercalibration of a short-term battery of toxicological tests for the safety assessment of food-contact paper and board. Dissemination of the results to industry, legislators (e.g. DG Consumer Protection, DG Enterprises, DG Research), standardization bodies such as CEN, and consumers will create an agreed risk evaluation procedure. The project involves pre-normative research in order to establish a set of in-vitro cytotoxicity and genotoxicity tests that will be easily adaptable to food-contact fibre-based materials and have endpoints relevant to consumer safety, including sub-lethal cellular events. These tests will be performed on samples representing actual migration conditions from food-contact paper and board with respect to different foodstuffs, and should form an experimental basis for scientifically sound recommendations for a harmonized system of risk evaluation and product testing.

Animals↗

Serum lipids in schizophrenia and other functional psychoses: a general population northern Finland 1966 birth cohort survey.

OBJECTIVE: To compare fasting serum lipid concentrations of subjects with schizophrenia with a comparison group. METHOD: The study sample consists of 5654 members of the northern Finland 1966 birth cohort who participated in the field study with blood samples after overnight fasting and clinical examination in 1997-98. Total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG) and glucose were analyzed. Analysis of variance were used for comparing differences in lipids means between diagnostic categories. RESULTS: Mean fasting TC in subjects with schizophrenia was 20 mg/dl higher than in the comparison group. TC and TG levels in the group of other psychoses resembled the schizophrenia group. CONCLUSION: Blood lipid levels in subjects with schizophrenia and other functional psychoses were high. As these persons are at special risk for hyperlipidemia their lipid levels should be regularly monitored, and cholesterol lowering diet, as well as medication, should be considered.

Adult↗

Two functional variants of the superoxide dismutase genes in Finnish families with asthma.

BACKGROUND: Functional polymorphisms in the genes encoding superoxide dismutases (SOD)-that is, superoxide scavenging antioxidant enzymes-may play an important role in the development of inflammatory airway diseases such as asthma. METHODS: The allele frequencies of two missense polymorphisms of SOD genes (Ala16Val in MnSOD (SOD2) and Arg213Gly in ECSOD (SOD3)) were investigated in Finnish patients with asthma and compared with family based controls. Both variants have been shown to be functionally interesting in the lung. The polymorphism at the exon-intron 3 boundary of a third SOD, CuZnSOD (SOD1), was also included in the analysis. RESULTS: None of the SOD genetic variants studied appeared to be major genetic regulators in the development of asthma. We could exclude all models of inheritance that increased the risk of asthma more than 1.2 fold for MnSOD*Val (frequency of allele 0.74 in the population) and more than 6.6 fold for ECSOD*Gly213 (frequency of allele 0.03 in the population) compared with non-carriers. For the intronic polymorphism in CuZnSOD, a relative risk of more than 3.3 (frequency of allele 0.10 in the population) could be excluded. CONCLUSIONS: It is highly unlikely that the functionally important genetic variants Ala16Val and Arg213Gly of SODs play a major role in the genetic susceptibility of asthma.

Adolescent↗

Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism.

OBJECTIVE: Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA(1c) have been studied only among diabetics. The objective of this study was to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration. DESIGN: The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta-oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double-blind, double-dummy study for six months. PATIENTS: Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group. MEASUREMENTS: Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF-I and IGFBP-1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT. RESULTS: A small significant reduction in the GHbA(1c) concentration was observed during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C-peptide decreased by 8% both in the peroral group (P < 0.05) and in the gel group (P < 0.01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF-I and increased IGFBP-1, but these findings were not associated with the changes in glucose metabolism. CONCLUSIONS: Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.

Administration, Cutaneous↗

The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction : a substudy of the Scandinavian simvastatin survival study.

BACKGROUND: Carriers of the epsilon4 allele of the apolipoprotein E gene are at a higher risk of coronary heart disease than individuals with other genotypes. We examined whether the risk of death or a major coronary event in survivors of myocardial infarction depended on apolipoprotein E genotype and whether the benefits of treatment with simvastatin differed between genotypes. METHODS AND RESULTS: Cox proportional hazards models were used to analyze 5.5 years of follow-up data from 966 Danish and Finnish myocardial infarction survivors enrolled in the Scandinavian Simvastatin Survival Study. A total of 16% of the 166 epsilon4 carriers in the placebo group died compared with 9% of the 312 patients without the allele, which corresponds to a mortality risk ratio of 1.8 (95% confidence interval, 1.1 to 3.1). The risk ratio was unaffected by considerations of sex, age, concurrent angina, diabetes, smoking, and serum lipids in multivariate analyses. Simvastatin treatment reduced the mortality risk to 0.33 (95% confidence interval, 0.16 to 0.69) in epsilon4 carriers and to 0.66 (95% confidence interval, 0. 35 to 1.24) in other patients (P=0.23 for treatment by genotype interaction). Apolipoprotein E genotype did not predict the risk of a major coronary event. Baseline serum levels of lipoprotein(a) also predicted mortality risk and could be combined with epsilon4-carrier status to define 3 groups of patients with different prognoses and benefits from treatment. CONCLUSIONS: Myocardial infarction survivors with the epsilon4 allele have a nearly 2-fold increased risk of dying compared with other patients, and the excess mortality can be abolished by treatment with simvastatin.

Adult↗

Baroreflex sensitivity and variants of the renin angiotensin system genes.

OBJECTIVES: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND: Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS: Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS: In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS: Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.

Adult↗

Expression of interleukin-6 (IL-6) receptor gene in acute myeloblastic leukemia and response of leukemic cells to exogenous IL-6. A comparative study between cell line cells and corresponding native cells.

As interleukin (IL-6) ahs been reported to have diverse effects on acute myeloblastic leukemia (AML) blast cell growth, we investigated whether the level of IL-6 receptor (IL-6R) expression by blast cells is associated with their susceptibility to proliferate in response to exogenous IL-6. For absolute quantification of IL-6R transcript numbers, we established a quantitative IL-6R reverse transcription polymerase chain reaction (RT-PCR) method with an internal RNA standard. In the present work, two types of AML blast cells were investigated, namely autonomously growing cell line cells (n = 8) and non cultured native blast cells (n = 20), including those from which the cell lines originate. The native blast cells expressed an average of 2.8 x 10(7) +/- 1.9 x 10(7) IL-6R transcripts in one microgram of total cellular RNA, whereas the expression by the cell line cells was significantly more abundant, the value being 8.3 x 10(7) +/- 2.8 X 10(7) (P < 0.001). The proliferation responses were evaluated by exposing the cells to IL-6 (1000 U/ml) in a clonogenic cell culture assay and, in the case of the cell line cells, in a long-term suspension culture assay as well. None of the autonomously growing cell lines responded to exogenous IL-6, whereas the native blast cell showed either stimulatory, inhibitory or neutral responses. Thus, the IL-6R expression level did not predict whether the cells proliferated in response to exogenous IL-6, which shows that IL-6R quantification cannot be used as a screening test prior to possibly applying this cytokine to clinical use in AML therapy.

Adolescent↗

Methodology for security development of an electronic prescription system.

Data security is an essential requirement in all health care applications. Developers of medical information systems should utilize the existing security development and evaluation methods to foresee as many of the technical and human factors that may endanger data security as possible and apply appropriate precautions. Modern smart card technology facilitates the building of robust security framework for interorganizational shared care systems. In this article, we describe the way we utilized the existing security evaluation criteria in developing the security concept of our electronic prescription system.

Clinical Pharmacy Information Systems↗

Prevalence of carotid atherosclerosis in middle-aged hypertensive and control subjects. A cross-sectional systematic study with duplex ultrasound.

BACKGROUND: Arterial hypertension has been found to increase atherosclerotic lesions, although contradictory results have suggested that hypertension has little or no effect. These discrepancies are probably caused by differences in populations. OBJECTIVE: To examine the effect of hypertension on carotid atherosclerosis in a population-based series of patients with an established diagnosis of arterial hypertension and controls. METHODS: Carotid intima-media thickness (IMT) and plaques were evaluated with duplex ultrasound in 1031 middle-aged (aged 40-60 years) men (n = 511) and women (n = 520), 513 with arterial hypertension and 518 controls. IMT was measured in the internal carotid artery, bifurcation and proximal, middle and distal common carotid artery, determining mean and maximal values for each patient. RESULT: Male sex, age, smoking and cholesterol were the most significant risk factors for combined plaque and intima-media thickness (CPIMT); hypertension and and abnormal glucose test result were further significant risk factors. There was a significant difference in CPIMT between the hypertensive and control subjects, but this was caused by the differences in the men; there were no statistically significant differences among the women. Plaques were found more frequently in the hypertensive men than they were in their controls (62.8 versus 49.8%), the corresponding percentages for the hypertensive and control women being 38.0 and 32.1%. There was a larger proportion of male subjects with a long duration of hypertension (> or = 7 years) who had plaques and greater CPIMT than there was of those with a short duration of hypertension. CONCLUSION: Hypertension had a significant effect on CPIMT and on the prevalence of plaques in men, but its effect in women was not significant. A long duration of hypertension resulted in greater CPIMT values and a higher prevalence of plaques, particularly in men.

Adult↗

The effects of monounsaturated-fat enriched diet and polyunsaturated-fat enriched diet on lipid and glucose metabolism in subjects with impaired glucose tolerance.

OBJECTIVE AND SUBJECTS: The effects of a high-fat, monounsaturated-fat enriched (Mono) diet and a reduced-fat, polyunsaturated-fat enriched (Poly) diet on lipid and glucose metabolism were compared in 31 subjects with impaired glucose tolerance. DESIGN AND INTERVENTIONS: After 3 weeks on a Run-in diet (37; 18:11:5, indicating energy percentages from total fat; saturated:monounsaturated:polyunsaturated fatty acids in the actual diets) subjects were randomized into a Poly-diet (34; 11:10:10) or a Mono-diet (40; 11:19:8) for 8 weeks. RESULTS: In the Mono group fasting plasma glucose (mean +/- SD) was lower after the test diet than after the run-in period (6.4 +/- 1.3 vs 6.0 +/- 0.8 mmol/L, 0 vs 8 weeks, P = 0.008), but remained unchanged in the Poly group (6.2 +/- 0.6 vs 6.1 +/- 0.7 mmol/L). Glucose effectiveness (SG), insulin sensitivity index and the first phase insulin response in an intravenous glucose tolerance test did not change significantly during either of the diets, but at the end of the study SG was higher in the Mono group than in the Poly group (P = 0.013). Serum total cholesterol, LDL cholesterol, and apolipoprotein B decreased in the Mono group, while in the Poly group only serum total cholesterol decreased significantly. However, the mean changes in serum lipids and lipoproteins did not differ significantly between the groups. CONCLUSIONS: In free-living subjects with impaired glucose tolerance both the Mono-diet and the Poly-diet consumed after a saturated-fat enriched Run-in diet improved serum lipid profile and the Mono-diet seemed to improve glucose metabolism as well.

Body Mass Index↗

Experiences with mobile extracorporeal shock wave lithotriptors in northern Finland.

A total of 285 renal units in 248 patients received 424 extracorporeal shock wave lithotripsy (ESWL) treatments with mobile lithotriptors for renal and ureteric stones at Oulu University Hospital. Treatments were given approximately once a month (1-2 days) with 7-10 treatments per day. The overall success at 1-3 months was 88% (74% stone-free). Success with single renal stones was 88% (70% stone-free), that with multiple renal stones 78% (62% stone-free) and that with ureteric stones 93% (89% stone-free). Retrograde manipulation appeared to be a safe and effective treatment for patients with obstructing ureteric stones obliged to wait for the next treatment session. The most serious complication was one perirenal haematoma requiring transfusion. The results compare favourably with those achieved with fixed lithotriptors and prove that mobile lithotriptors are suitable for small centres.

Adolescent↗

Prevalence and geographical distribution of major LDL receptor gene rearrangements in Finland.

In order to determine the prevalence of major rearrangements of the low density lipoprotein (LDL) receptor gene in Finland, DNA samples of 199 unrelated Finnish patients with the heterozygous form of familial hypercholesterolaemia (FH) were examined by Southern blot analysis. The FH-Helsinki mutation, characterized by a 9.5-kb deletion in the 3'-end of the LDL receptor gene, was found in 75 (38%) of the patients. The prevalence of this mutation ranged from 26-58% in different areas of Finland. A striking exception was the North Karelia region, where only one out of 26 (4%) FH patients was found to carry the FH-Helsinki allele. Two patients were found to carry other types of large nucleotide rearrangements of the LDL receptor gene. One mutation was a 7.5-kb deletion eliminating exons 7 to 10, and the other was a 13-kb deletion covering exons 11 to 16 of the LDL receptor gene. Serum lipoprotein levels were very similar in each category of mutation, i.e. in patients with the FH-Helsinki gene, those with the two other types of deletion, and the remaining patients with as yet unknown types of LDL receptor gene defects. These results show that, even in genetically uniform populations, FH may be heterogeneous at the DNA level. DNA techniques enable an unequivocal diagnosis for almost 40% of the Finnish patients with the heterozygous form of FH.

Blotting, Southern↗

A lineshape fitting model for 1H NMR spectra of human blood plasma.

A lineshape fitting model was constructed for classifying the overlapping information in the 1H NMR spectrum of human blood plasma. A reliable assignment of the overlapping fatty acid (-CH2-)n and -CH3 resonances of the various lipoproteins (VLDL, very low density lipoprotein; LDL, low density lipoprotein; HDL high density lipoprotein) is introduced, and for the first time detailed characteristics (chemical shifts, half linewidths, and relative intensities) of the individual lipoprotein components were obtained directly from the whole plasma spectrum. This was achieved by combining the constructed lineshape fitting model and the proper 400 MHz proton NMR measurements from blood plasma of a healthy donor, from fractions of the different lipoproteins, and from plasma samples in which the lipoprotein fractions were separately added. The results suggest fair promise of future applications of the rapid and easy NMR analysis of lipoprotein distribution in various research and clinical situations.

Chemical Fractionation↗

Ethanol and lipids.

The interaction of ethanol with lipid metabolism is complex. When ethanol is present, it becomes a preferred fuel for the liver and displaces fat as a source of energy. This favors fat accumulation. In addition, the altered redox state secondary to the oxidation of ethanol promotes lipogenesis, for instance, through enhanced formation of acylglycerols. The depressed oxidative capacity of the mitochondria injured by chronic alcohol feeding also contributes to the development of the fatty liver. Accumulation of fat acts as a stimulus for the secretion of lipoproteins and the development of hyperlipemia. Hyperlipemia may also be facilitated by the proliferation of the endoplasmic reticulum after chronic ethanol consumption and the associated increase of enzymes involved in the production of triglycerides and lipoproteins. The propensity to enhance lipoprotein secretion is offset, at least in part, by a decrease in microtubules and an impairment of the secretory capacity of the liver. The level of blood lipids depends on the balance between these two opposite changes: At the early stage of alcohol abuse, when liver damage is still small, hyperlipemia will prevail, whereas the opposite occurs with severe liver injury. When hyperlipemia occurs, it involves all lipoprotein classes, including high density lipoprotein (HDL). The latter have been suggested to be responsible for the lower incidence of coronary complications of moderate drinkers compared to teetotalers, but in fact, the subtype of HDL involved (HDL3) differs from the HDL2 subtype associated with protection.

Acetaldehyde↗