[Swollen breast in a female patient with dermatomyositis].
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Biomedical subjects
Publications and source records attributed to J Viikari.
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BACKGROUND: Apolipoprotein E (apoE) phenotype is a genetic determinant of plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations, that are classical coronary heart disease risk factors. ApoE appears in three major isoforms E2, E3, and E4, coded by corresponding alleles epsilon 2, epsilon 3, and epsilon 4. These give rise to six different phenotypes. OBJECTIVE: To study the associations of apoE phenotype with cord serum lipids (during minimal enteral nutrition), and with serum lipids of 3-year-old children. SUBJECTS AND METHODS: We determined serum lipid levels and apoE phenotypes in 206 newborns and 259 3-year-old children in connection with a larger follow-up study of atherosclerosis precursors in children and young adults. ApoE phenotyping was done directly from plasma by isoelectric focusing followed by immunoblotting. RESULTS: The effect of apoE phenotype on serum total and LDL cholesterol was significantly different in newborns and 3-year-old children (two-way ANOVA, interaction between apoE phenotype and age group: P < .001 for both). In 3-year-old children, the concentrations of serum total cholesterol and LDL cholesterol increased with apoE phenotype in the order of E3/2, E3/3, E4/3, and E4/4, in both males and females (P < .0001). On the contrary, in neonates total cholesterol and LDL cholesterol concentrations were low and did not differ significantly between apoE phenotypes (P > .05) either in males or in females. The mean serum levels of triglycerides and high density lipoprotein cholesterol did not differ between apoE phenotypes either in 3-year-old children or newborns. CONCLUSIONS: The results show that the differences in serum total and LDL cholesterol levels between apoE phenotypes are formed after birth by the influence of environmental factors and suggest that both genetic and external factors influence the levels of serum cholesterol concentrations during the first years of life.
OBJECTIVES: Tendon xanthomas cause thickening of the tendon and are an important sign in monogenic familial hypercholesterolaemia (FH). The aim of our study was to investigate the usefulness of achilles tendon sonography in detecting FH patients. Special attention was paid to structural abnormalities of the achilles tendon. DESIGN: A clinical study with methodological testing. SETTING: Patients suspected of having FH were sent to the out-patient Department of Medicine from other departments of Turku University Central Hospital and from primary care units. The patients were studied by high-frequency ultrasound before more exact typing of the lipid disorder. An additional study of normolipidaemic volunteers and a phantom study were also carried out. SUBJECTS: Forty FH patients, 51 non-FH hypercholesterolaemia patients and 41 normolipidaemic volunteers were included in the study. MAIN OUTCOME OF MEASURES: The thickness of the tendon was measured and the tendon structure and its echogenicity were recorded. RESULTS: Twenty-five out of 40 (63%) FH patients had distinctly thickened tendons (men more than 10 mm, women more than 9 mm). Thirty-six (90%) had a typical structural alteration of low or mixed echogenicity of the tendon. Three non-FH patients were found to have xanthomas on sonography. CONCLUSIONS: We conclude that ultrasonography is a sensitive method of detecting xanthomas that reveals the altered tendon structure even in xanthomatous tendons of normal thickness.
To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-[18F]-fluoro-D-glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle-1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake [789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS)]. Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of zero erucic acid rapeseed oil and olive oil on plasma fatty acid composition and serum cholesterol were studied in margarine users (n = 46). The replacement of margarine on bread by these oils accounted, on average, for 16% of the total fat and 7% of the total energy intake. Fatty acid analysis of total plasma indicated a dose-dependent rise in alpha-linolenic (alpha-LLA) and oleic acid (OA) levels during rapeseed and olive oil substitutions, respectively. Rapeseed oil substitution increased the proportion of eicosapentaenoic acid (0.4%- units, on average) in plasma phospholipids. A slight decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol (HDL-C, 4.5%, p < 0.01) led to a significantly higher HDL-C/total cholesterol (TC) ratio (1.9%-units). The results suggest a marked competitive effect for alpha-LLA, not only among plasma phospholipid fatty acids, but also in the relationships with serum lipids, since the changes in alpha-LLA, rather than in OA, were associated with those in LDL-C and the HDL-C/TC ratio. No competitive action of polyunsaturated acids comparable to rapeseed oil was found during olive oil substitution. In contrast to the rapeseed oil diet, the reduced proportion of linoleic acid (LA) in plasma phospholipids was not restored; this may be unfavorable if the habitual intake of LA is low. However, the effects on LDL-C levels were beneficial: the concentration decreased by 5.9% (p < 0.01), correlating inversely with the increase in OA. In addition, the concentration of HDL-C remained unchanged during olive oil substitution.
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Systemic infections may thicken the intima of coronary arteries and modify the serum lipid profile. Infants and children are particularly susceptible to such intimal thickening, the signs of which are more pronounced in infants who have evidence of infection at death. The topography of the thickenings, their greater size in males, and in families with a history of coronary heart disease favours the idea that the thickenings are pre-atherosclerotic. Infections modify the serum lipid pattern: serum high density lipoprotein (HDL) cholesterol concentration decreases and stays low during convalescence. Thus repeated infections might prove to be a risk factor for atherosclerosis via their effect on HDL concentration.
The composition of fatty acids in serum cholesteryl esters was analyzed with gas chromatography in 759 Finnish boys and girls aged 3-18 years in 1980 and again in the same subjects in 1983 and in 1986. The mean percentage of linoleate (18:2 n-6) increased from 50.85% in 1980 to 52.60% in 1986, while there was a decrease in myristate (14:0), palmitate (16:0), and eicosapentaenoate (20:5 n-3). The percentage of oleate (18:1) did not change. The stability (tracking) of cholesteryl ester fatty acid composition was examined by calculating linear correlation coefficients among the percentages of each fatty acid at the three study points. For linoleate, 3- and 6-year tracking correlations were 0.59-0.61 and 0.50, respectively; they were of about the same magnitude for arachidonate (20:4 n-6) and lower for the other fatty acids. Results indicate that the serum cholesteryl ester fatty acid composition has somewhat lower tracking than the total cholesterol concentration. The changes in the mean fatty acid composition of the study population obviously reflect a shift from saturated to unsaturated dietary fats.
The effects of zero-erucic acid rapeseed oil and rapeseed oil-containing margarine on plasma fatty acid composition and serum cholesterol were studied in butter users (n 43). Compliance to the substitution was followed by fatty acid analysis of total plasma and plasma phospholipids. The amount of substitute fats represented, on average, 21% of total fat and 8% of total energy intake. Changes in the relative fatty acid composition of plasma phospholipids indicated further fatty acid metabolism, and were closely related to the serum cholesterol level. The reduction in saturated fatty acids led to a significant increase in the proportion of n-3 and n-6 polyunsaturated fatty acids (PUFA) with the rapeseed oil diet, whereas the margarine caused a significant rise in n-6 PUFA only. The increase in the proportions of the two PUFA families occurred in accordance with their competitive order, most completely with the rapeseed oil diet. When butter was replaced by rapeseed oil, low-density-lipoprotein-cholesterol decreased by an average of 9.1% without a reduction in high-density-lipoprotein-cholesterol. During margarine substitution the reduction was 5.2%, on average. Of the plasma phospholipids, alpha-linolenic acid and the linoleic:stearic acid ratio, but not oleic acid, were the components most significantly correlated with serum cholesterol levels or the decrease in these levels. The results show that rapeseed oil can act primarily as a source of essential fatty acids, rather than that of monoenes, in the diet of butter users.
Eight hundred seventy-six men and women with diastolic blood pressure (DBP) of 95-115 mm Hg during a 4-week placebo period were included in a multicenter trial; 479 patients had previously been treated for hypertension. The patients were randomized to receive isradipine or metoprolol; both groups were comparable for age, weight, height, smoking habits, and duration of hypertension. By the end of the placebo period, 79 patients did not fulfill the final entry criteria and were withdrawn. The isradipine group consisted of 398 patients (164 women and 234 men), and the metoprolol group consisted of 399 patients (173 women and 226 men). The initial dose of isradipine was 1.25 mg twice daily (b.i.d.), and the initial dose of metoprolol was 50 mg b.i.d.; the doses were doubled after 4 weeks if DBP had not decreased to less than or equal to 90 mm Hg. After 8 weeks, the isradipine group began combination therapy with metoprolol 50 mg b.i.d. and the metoprolol group began combination therapy with isradipine 1.25 mg b.i.d. if DBP was not less than or equal to 90 mm Hg. After 8 weeks monotherapy, mean BP (MBP) was reduced by 13/11 mm Hg (161/104 to 148/93) in the isradipine group and by 15/12 mm Hg (160/103 to 145/91) in the metoprolol group. Monotherapy with isradipine normalized DBP to less than or equal to 90 mm Hg in 52% with a mean dose of 4.26 mg daily, and monotherapy with metoprolol normalized DBP in 58% with a mean dose of 155 mg daily.1+
Blood glycated haemoglobin (HbAlc), serum fructosamine (FA), serum glycated albumin (GA), and serum glycated total protein (GTP) were determined in 61 subjects (19 pregnant women with gestational diabetes, 24 pregnant women with insulin-dependent diabetes mellitus [IDDM] and 18 nonpregnant subjects with IDDM). FA, GA, and GTP correlated with HbAlc similarly (r = 0.791, 0.816, and 0.794, respectively, p < 0.001). In a subgroup of 22 subjects data on blood glucose home monitoring was recorded and used for calculating mean blood glucose as an index of average glycaemia preceding sampling of the glycation products. Mean blood glucose levels preceding sampling of HbAlc by 2 months and FA, GA, or GTP by three weeks correlated significantly with HbAlc (r = 0.668, p < 0.001) and GA (r = 0.441, p < 0.05) whereas no significant correlation was found between mean blood glucose and FA (r = 0.003) or GTP (r = 0.252). In conclusion, such methods which measure specifically the non-enzymatic glycation of a single species of protein (i.e. FPLC for HbAlc and affinity chromatography for GA) are to be preferred for assessing glycaemia.
This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 micrograms increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI. The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p less than 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) micrograms and for Group II 220 (61) micrograms] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p less than 0.01, n = 29) and total T4 (r = -0.51, p less than 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-M(R). The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95). In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness.
The percentage compositions of fatty acids in serum cholesteryl esters and phospholipids were analysed with gas chromatography in 759 nine- to 24-year-old Finns. The correlations of serum fatty acids with dietary fat intake data were calculated from a 48-h recall survey. The dietary P/S ratio had correlations of r = 0.50 and r = 0.40 with linoleate (18:2) in serum cholesteryl esters and phospholipids, respectively. The intake of fish and fish products correlated positively with the percentages of eicosapentaenoate (20:5 n-3) and docosahexaenoate (22:6 n-3) in both cholesteryl esters and phospholipids. Dietary intake of saturated fat correlated positively with the percentages of all saturated fatty acids in cholesteryl esters and with myristate (14:0) in phospholipids. The intake of monounsaturated fats did not correlate positively with serum monoenes. In conclusion, the dietary P/S ratio is well reflected in the fatty acid composition of serum cholesteryl esters and phospholipids, the intake of saturated fats less well, and the intake of monounsaturated fats not at all.
Serum total cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were studied in paired sera from 23 patients (16 boys) with Kawasaki disease (KD) during acute illness and in 35 patients (21 boys) 5.4 to 7.7 years after KD. Total cholesterol and HDL cholesterol concentrations were significantly lower (paired t test, p = 0.0001) in samples taken within 30 days of the onset of illness (3.32 +/- 0.85 mmol/L (128 +/- 33 mg/dl) and 0.54 +/- 0.25 mmol/L (20.8 +/- 9.7 mg/dl) than in the second samples taken 2 to 16 months after onset of disease (4.16 +/- 0.93 mmol/L (161 +/- 35 mg/dl) and 1.24 +/- 0.35 mmol/L (47.2 +/- 13.9 mg/dl). The lowest total cholesterol levels were observed in samples taken 6 to 9 days after the onset of KD (p = 0.019). No correlations were seen between the highest erythrocyte sedimentation rate, C-reactive protein, or thrombocyte counts and the acute or convalescent cholesterol levels. In patients studied 5.4 to 7.7 years after recovery from KD, the mean total cholesterol concentrations were still lower than in healthy Finnish children. In girls the HDL cholesterol concentrations were similar, whereas 3 of the 18 boys studied had HDL cholesterol values more than 2 SDs below the mean for healthy boys. There was no correlation between the serum cholesterol concentrations and coronary artery abnormalities. These data lead us to infer that KD does not cause such permanent changes in cholesterol metabolism as to be considered a risk factor for atherosclerosis beyond that caused by the disease itself.
The prevalence of obesity in Finnish children, adolescents and young adults aged three to 24 years was estimated in three surveys performed within the multicentre project, "Cardiovascular Risk in Young Finns" (1980, 1983, 1986). Obesity was defined as either body mass index (weight/height) or skinfold thickness (triceps or subscapular) or both greater than 90th percentiles of age and sex-specific reference data for white children. Its mean prevalences among 9- to 18-year old boys and girls in three surveys (95% confidence limits) were 3.6% (3.1-4.2) and 2.1% (1.7-2.6) as estimated in terms of body mass index and triceps skinfold thickness or 4.3% (3.9-4.9) and 2.6% (2.2-3.1) according to body mass index and subscapular skinfold thickness. Thus the 9- to 18-year old boys were on average more often obese than the girls, but no statistically significant changes in the prevalence of obesity were observed over the period 1980-1986. Body mass index and triceps or subscapular skinfold thicknesses vary in sensitivity as indicators of obesity.
A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n = 3554) and the apolipoproteins A-I and B measured (n = 1355). Two follow-up studies were carried out in 1983 (n = 2851) and 1986 (n = 2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-I and B were measured again in 1986 (n = 1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980's from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9- to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3-24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.