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Biomedical subjects

M Nikkilä

Publications and source records attributed to M Nikkilä.

At least 19 recordsLinked to original sources

Magnetoencephalographic (MEG) localization of the auditory N400m: effects of stimulus duration.

The effects of stimulus duration on the elicitation and equivalent current dipole (ECD) localization of the auditory N400(m) were studied in two subject groups, either familiar or unfamiliar with Finnish language, using a sentence-processing paradigm with incongruent ending words of either short or long duration. Long-duration words elicited a broad response at around 400 ms, the generator location(s) of which could not be reliably determined using ECD estimation. In contrast, short-duration words elicited a sharp, strong-amplitude response at about 400 ms latency and it's source location could be reliably determined as being in the vicinity of auditory cortex. Subjects unfamiliar with the Finnish language elicited no response at the 400 ms range. Thus, the use of short-duration words appears to be an important prerequisite for the elicitation and localization of N400m. The differential amplitude behaviour of the N400m between the two subject groups further suggests that comprehension of the semantic content of the speech message is also required.

Acoustic Stimulation↗

Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease.

Oxidation of low density lipoproteins (LDL) obviously plays an important role in the pathogenesis of atherosclerosis. The purpose of the study was to determine whether antibodies against oxidized LDL are associated with coronary artery disease (CAD). We determined the serum levels of antibodies against copper-oxidized LDL by enzyme-linked immunosorbent assay in 58 patients with angiographically verified CAD and 34 controls without CAD. The mean antibody level, expressed in optical density units, was significantly higher in patients than in controls (0.150+/-0.088 versus 0.094+/-0.054, respectively; P=0.00089). In logistic regression analysis, high antibody level against oxidized LDL was associated significantly with CAD (P=0.0114), independent of age (P=0.00137), gender (P=0.0021), body mass index (P=0.5947), triglyceride concentration (P=0.9813), and total cholesterol-high density lipoprotein (HDL) cholesterol (P=0.0080) group. Similar analysis in nondiabetic subjects (n=79) and in men only (n=75) showed analogous results, with only minor changes in P values. The antibody level against oxidized LDL differed significantly between nonsmokers and smokers in CAD patients (P<0.00197) but not in controls (P=NS). In addition, the antibody level against oxidized LDL differed significantly between nonsmokers and smokers in subjects with low HDL cholesterol (</=0.9 mmol/L) but not in subjects with high HDL cholesterol (>0.9 mmol/L). In conclusion, elevated levels of antibodies against oxidized LDL were associated with CAD. The data suggest that oxidized LDL plays a role in the pathogenesis of atherosclerosis and suggest a protective function for HDL against LDL oxidation.

Aged↗

Autoantibodies against oxidised low-density lipoprotein in patients with obstructive sleep apnoea.

Autoantibodies against oxidised low-density lipoprotein (OxLDL-Abs) have been proposed to be an indicator of endothelial dysfunction and a novel tool for finding individuals with a high cardiovascular risk. In a cross-sectional study, OxLDL-Abs were measured in 297 patients with obstructive sleep apnoea (OSA) and 54 controls using an enzyme-linked immunosorbent assay. The autoantibodies were increased in patients with OSA when compared to controls (age, body mass index (BMI) and gender adjusted, p = 0.001). However, within the OSA patients, OxLDL-Abs were not related to smoking, hypertension or BMI, and there was a weak negative correlation (r = -0.16, P = 0.007) between age and levels of OxLDL-Abs. In conclusion, at present the measurement OxLDL-Abs still remains a method for basic research and is not applicable for screening of at-risk patients with OSA.

Adult↗

Women have a larger and less atherogenic low density lipoprotein particle size than men.

Some epidemiological studies have shown that serum total cholesterol increases with age. especially in women. On the other hand, the risk of coronary artery disease is smaller in women than in men. Earlier studies have shown that a small dense low density lipoprotein (LDL) is more atherogenic than a large LDL. We studied LDL size and apolipoprotein E (apo E) phenotypes in premenopausal and postmenopausal women and in men at the same age. In this study 342 subjects participating in a health screening study were examined. There were four subgroups: 40-year-old men (n = 85), 40-year-old women (n = 80), 70-year old men (n = 88) and 70-year-old women (n = 89). In the present study LDL size was larger (P < 0.01) in women (26.39 +/- 0.07 nm) than in men (25.95 +/- 0.07 nm). We found that LDL size correlated highly positively (r = 0.606; P < 0.001) with serum high density lipoprotein (HDL) concentration and inversely with serum triglyceride concentration (r = -0.627; P < 0.001). Measuring serum HDL cholesterol and triglycerides in health screening studies gives information indirectly about LDL size and its atherogenicity. Apo E phenotype was not significantly associated with serum triglycerides, but was associated with LDL size, LDL cholesterol, total cholesterol and HDL cholesterol. In our sample LDL size decreased and LDL cholesterol and total cholesterol increased according to the most prevalent apo E phenotypes in the order E2/3, E3/3, E3/4 and E4/4. Subjects with phenotype apo E4/4 had the smallest LDL size (25.70 +/- 0.19 nm), the highest total cholesterol (6.53 +/- 0.35 mmol/l) and the lowest HDL cholesterol values (1.28 +/- 0.04 mmol/l). We conclude that there was a significant interaction between sex and age in serum total cholesterol which was highest in older women. However, their LDL size was larger and their LDL is less atherogenic. Apo E phenotype had a significant influence on LDL size.

Adult↗

Apolipoprotein E polymorphism, serum lipids, myocardial infarction and severity of angiographically verified coronary artery disease in men and women.

In several populations, the apolipoprotein E (apo E) allele epsilon 4 is associated with high concentration of plasma total and low density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD). We determined the apo E phenotypes of 309 patients with angiographically verified CAD and 38 patients without CAD by isoelectric focusing and Western blotting. In men with CAD, the plasma total and LDL-cholesterol increased according to apo E phenotype in the following order: E3/2 < E3/3 < E4/3 < E4/4 (P = 0.03 for total cholesterol, P = 0.007 for LDL-cholesterol). In women, there was a similar trend (P = 0.22 for total cholesterol, P = 0.15 for LDL-cholesterol). The relative frequency of men with three vessel CAD increased (P = 0.43) together with LDL-cholesterol levels (P = 0.05) according to apo E phenotype E3/2, E3/3, E4/3, E4/4. Total and LDL-cholesterol levels were higher in patients with three vessel CAD than in patients with less serious types of CAD (P = 0.02 for total cholesterol, P = 0.007 for LDL-cholesterol). The relative frequency of patients with myocardial infarction increased according to apo E phenotype (P = 0.51). Both in men and women, there were no differences between apo E phenotypes in age at occurrence of the first myocardial infarction. The apo E allele frequencies of patients with CAD vs. without CAD were 2.3% vs. 1.3% for epsilon 2, 79.0% vs. 76.3% for epsilon 3 and 18.7% vs. 22.4% for epsilon 4. There were no statistically significant differences in apo E allele or phenotype frequencies between patients with CAD and without CAD or between patients with CAD and the general Finnish population. Our results support previous studies in suggesting that the apo E allele epsilon 4 is a risk factor for atherosclerosis, which affects plasma total and LDL-cholesterol. In addition, our results suggest that the apo E allele determines the severity of CAD.

Age Distribution↗

Postprandial plasma lipoprotein changes in relation to apolipoprotein E phenotypes and low density lipoprotein size in men with and without coronary artery disease.

Postprandial lipoprotein metabolism may play a role in the etiology of premature coronary artery disease (CAD). To determine whether apolipoprotein E (apo E) polymorphism and the size of low density lipoprotein (LDL) influence postprandial lipemia we studied 39 healthy men and 35 men with CAD. Venous blood samples were obtained before an oral fat load and 3, 5 and 7 h thereafter. Total cholesterol and high density lipoprotein (HDL) cholesterol concentrations did not change in either group during the fat load, but triglycerides increased more markedly in CAD patients compared with controls independently of apo E phenotypes. There was a positive correlation between the size of LDL and the concentration of HDL cholesterol (r = 0.541, P < 0.001); conversely, an inverse correlation was observed between LDL size and the level of fasting triglycerides (r = -0.582; P < 0.001). The patients with CAD had significantly smaller LDL particles (25.89 +/- 0.56 nm) than in controls (26.21 +/- 0.63 nm) (P < 0.05). The increase in triglyceride levels during the fat load was highest in CAD patients with a small size of LDL particles (< 25.5 nm) and lowest in controls with large LDL (> 25.5 nm). Our results suggest that the magnitude of the triglyceride response is a better indicator of CAD risk than the fasting triglyceride concentration. The best model in our logistic regression analysis selected as significant risk factors the change of triglyceride concentration from the baseline at 5 h after a fat meal and HDL cholesterol. This model classified 83% of the subjects correctly.

Adult↗

Moderate and heavy alcohol consumption have no favorable effect on lipid values.

Moderate alcohol consumption has been reported to provide protection against coronary heart disease. We studied serum lipid values in 380 men, including 184 controls (37 teetotalers and 147 moderate drinkers), 90 heavy drinkers, and 106 alcoholics. Total cholesterol values were significantly lower among alcoholics than controls (mean +/- SEM, 5.43 +/- 0.15 mmol/L [210 +/- 5.8 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]), but their high-density lipoprotein (HDL) cholesterol values were higher (1.66 +/- 0.07 mmol/L [64 +/- 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). Accordingly, there was a highly significant difference in the HDL/total cholesterol ratio (0.32 +/- 0.13 vs 0.19 +/- 0.01). Heavy drinkers had significantly higher total cholesterol values than controls (6.30 +/- 0.13 mmol/L [244 +/- 5.0 mg/dL] vs 6.01 +/- 0.08 mmol/L [232 +/- 3.1 mg/dL]); the same was true of HDL cholesterol values (1.25 +/- 0.07 mmol/L [48 +/- 2.7 mg/dL] vs 1.14 +/- 0.02 mmol/L [44 +/- 0.8 mg/dL]). No significant difference was found in the HDL/total cholesterol ratio between controls and heavy drinkers or between teetotalers and moderate drinkers. Therefore, moderate alcohol intake apparently does not change HDL/total cholesterol ratio; if moderate drinking is protective against coronary heart disease, the mechanism is probably not via lipids.

Adult↗

Elevated high-density-lipoprotein cholesterol and normal triglycerides as markers of longevity.

Serum cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides of 85 year old home-living persons were compared to those of controls and of patients who had severe coronary artery disease (CAD) at an early age. Eighty-five-year-olds had higher serum HDL cholesterol than controls and patients with CAD. Patients with severe CAD had higher serum total cholesterol and serum triglycerides and lower HDL-cholesterol than other groups. When 85-year-old persons were divided into quintiles according to serum HDL cholesterol, women with highest HDL cholesterol had lowest mortality, men with lowest HDL cholesterol had highest mortality. We conclude that elevated HDL cholesterol is correlating with longevity and low HDL cholesterol with CAD at an early age.

Aged↗

Once daily compared with twice daily administration of slow-release diltiazem as monotherapy for hypertension.

We compared the efficacy of the antihypertensive drug diltiazem in a slow release formulation administered once daily with its twice daily administration as monotherapy in 34 patients with mild to moderate essential hypertension. All subjects received placebo for three weeks before the randomised, double blind, crossover study, and their supine diastolic blood pressure (BP) ranged from 95 mmHg to 115 mmHg. After the patients had received the placebo for three weeks diltiazem was titrated in the open label treatment to either 120 mg or 180 mg twice daily until the target BP level was achieved. After the open three weeks' of treatment with diltiazem twice daily patients were allocated randomly for either once daily or twice daily administration. After a six week, double blind period, the treatment was changed according to the crossover design. With a dose of 120 mg or 180 mg twice daily patients' supine and standing BP readings were significantly lower than when they took the drug once daily. In the subgroup (n = 19) with the maximum dose of diltiazem given twice daily and once daily BP levels were lower in those subjects on twice daily treatment than in those treated once a day with the same total daily dose, the differences being significant. Administration of diltiazem once a day in a slow release formulation was not as effective as a twice daily dose when the dose titration was greatest or when compared with the same dosage (240 mg x 1/day or 120 mg x 2/day).

Adult↗

Influence of fish oil on blood lipids in coronary artery disease.

The low incidence of coronary artery disease in Greenland Eskimos may be due to their intake of seafood with a high content of n-3 polyunsaturated fatty acids which may have a hypolipidaemic effect. Results of previous studies have been controversial, depending on the dosage of fish oil and the phenotypic cause of the hyperlipoproteinaemia. In this placebo-controlled, double-blind, cross-over study, patients (n = 32) with coronary artery disease and dyslipidaemia received firstly 2.4 g eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Thereafter in the open study the same study group received 3.6 g EPA/DHA. Fish oil had no significant effect on serum cholesterol or high density lipoprotein (HDL) cholesterol. Low doses of fish oil (2.4 g EPA/DHA) reduced serum triglyceride level significantly (P less than 0.05) and more significantly (P less than 0.01) with 3.6 g EPA/DHA. The results indicated that the therapeutic effect of n-3 fatty acids as hypolipidaemic agents is greatest in patients with severe hypertriglyceridaemia (greater than 3.00 mmol/l).

Aged↗

High-density lipoprotein cholesterol and longevity.

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were studied in three groups: (1) 85 healthy subjects aged 85-89 years, (2) 62 patients without coronary artery disease aged 38-62 years, and (3) 323 patients aged 32-69 years with triple-vessel disease diagnosed by coronary angiography. The mean values for total cholesterol were significantly higher in patients with triple-vessel disease than in those without coronary artery disease and in the elderly. Total cholesterol was over 6.5 mmol/l in 32% of the elderly, in 31% of patients without coronary artery disease and in 42% of patients with triple-vessel disease, but these differences were not significant. HDL-cholesterol and the ratio of HDL/total cholesterol were significantly higher in the elderly than in the patients without coronary artery disease and patients with triple-vessel disease. Serum HDL-cholesterol was over 1.0 mmol/l in 92% of the elderly, in 69% of patients without coronary artery disease and in 46% of patients with triple-vessel disease, the differences being significant between all groups.

Adult↗

Serum cholesterol, high-density lipoprotein cholesterol and five-year survival in elderly people.

In the year 1982 serum cholesterol and high-density lipoprotein (HDL) cholesterol were measured in 535 people aged 85 years participating in a health survey screening. All subjects were living at home. During the 5-year follow-up, 186 (34.8%) of the subjects died. There was a J-shaped relation between serum cholesterol and mortality. Mortality was lowest at serum cholesterol 5.0-5.9 mmol/l for men and 7.0-7.9 mmol/l for women. The greatest mortality was observed in men with cholesterol greater than or equal to 6.0 mmol/l and in women with cholesterol greater than or equal to 8.0 mmol/l. There was a significant negative association of serum HDL cholesterol with mortality. Mortality was highest (53.3%) in men with serum HDL cholesterol less than 0.80 mmol/l. Mortality was low (16.5%) in women with serum HDL cholesterol greater than 1.8 mmol/l.

Aged↗