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Biomedical subjects

J Viikari

Publications and source records attributed to J Viikari.

At least 163 records · Page 9Linked to original sources

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part II. Lipid and glycosaminoglycan analysis of intima and inner media.

We compared the effects of mild hypercholesterolemia and repeated endotoxin infusions on the biochemical composition of aortic intima and inner media of 24 piglets divided into 4 groups 5 days after weaning: controls on normal diet (group I); normal diet and endotoxin (group II); fat-supplemented diet (group III); and fat-supplemented diet and endotoxin (group IV). It was found that mild hypercholesterolemia increased the concentration of arterial esterified cholesterol and the relative amount of the fraction containing chondroitin sulphates A and C in total glycosaminoglycans. Endotoxin infusions partly prevented the increase of serum cholesterol caused by the fat-supplemented diet but had no independent effect on the arterial biochemical composition; nor did they affect the biochemical changes caused by hypercholesterolemia. When the results of all groups were combined, chondroitin sulphates A and C showed a significant positive correlation with the concentration of arterial esterified cholesterol and the percentage of linoleic acid in arterial cholesteryl esters. Serum total cholesterol did not correlate with arterial cholesterol fractions, but the ratio of high density lipoprotein-cholesterol to total serum cholesterol showed a negative association with arterial esterified cholesterol. The present findings indicate that (1) mild hypercholesterolemia is atherogenic in young piglets, and (2) changes in arterial glycosaminoglycan composition might be one of the earliest biochemical alterations in atherogenesis.

Animals↗

Acute effects of medetomidine, a selective alpha 2-adrenoceptor agonist, on anterior pituitary hormone and cortisol secretion in man.

Single iv doses (25, 50 and 100 micrograms) of medetomidine, a selective alpha 2-adrenoceptor agonist of the imidazole type, were administered to 8 healthy male volunteers in a randomized, double-blind, placebo-controlled study. The concentration of hGH in plasma was powerfully and dose-dependently increased. The plasma level of cortisol was dose-dependently decreased, whereas TSH showed a slight but statistically significant increase. Plasma levels of PRL, FSH and LH were unaffected by the drug. Medetomidine appears to resemble other alpha 2-adrenoceptor agonists, notably clonidine, in its endocrine effects. Its high selectivity and short duration of action make it a suitable tool for studies of the physiology and pharmacology of alpha 2-adrenoceptors in man.

Adrenergic alpha-Agonists↗

Comparative evaluation of serum thyroxine, free thyroxine and thyrotropin determinations in screening of thyroid function.

We assessed a highly sensitive immunoradiometric thyrotropin (TSH) assay in screening thyroid dysfunction in 130 consecutive outpatients from a department of medicine and 224 patients from a municipal health centre. In addition to clinical examination, three routine tests were done: a thyroxine radioimmunoassay, an analogue-based free thyroxine assay and an immunoradiometric TSH assay. Triiodothyronine and the TRH test were done, if the findings were discrepant. Discrepancy existed in 24% of cases. The TSH assay had no false negative results (sensitivity 100%). Therefore TSH could screen all patients with thyroid dysfunction. Free thyroxine was the most specific assay (specificity 96%), but many subclinically or overtly hypothyroid patients would have been missed, if that assay had been used alone. We conclude that TSH(IRMA) is the best first-line measurement for thyroid dysfunction testing among outpatients. An abnormal TSH result alone is not diagnostic, but should be followed by the measurement of thyroxine or free thyroxine.

Adolescent↗

Blood pressure and excretion of sodium, potassium, calcium and magnesium in 8- and 9-year old boys from 19 European centres.

We have measured systolic and diastolic blood pressure and excretions of sodium, potassium, calcium and magnesium in groups of about 50 8- and 9-year-old boys from 19 European centres using standardized methods for the measurement of blood pressure and collection of urine, and by carrying out all analyses in one laboratory. Weight, height, pulse rate and environmental temperature were also studied. Mean systolic blood pressure ranged from 91 to 105 mm Hg and diastolic blood pressure from 51 to 66 mm Hg. Mean 24-h excretion of sodium was between 91 and 146 mmol/d, that of potassium between 29 and 60 mmol/d, that of calcium between 1.5 and 2.6 mmol/d and that of magnesium between 2.7 and 4.2 mmol/d. Mean sodium excretion tended to be lower and potassium excretion tended to be higher in the boys from the north-western parts of Europe. Relations between either systolic or diastolic blood pressure and electrolyte excretions were generally weak or absent. Most remarkable is that only the association between mean diastolic blood pressure and 24-h magnesium excretion (partial regression coefficient (b +/- s.e., -5.04 +/- 2.08 mm Hg/mmol/d) was statistically significant after adjusting for differences in creatinine excretion and environmental temperature. Mean systolic blood pressure was not significantly related with any of the variables measured. The partial regression coefficient (b +/- s.e.) for diastolic blood pressure on weight was 0.186 +/- 0.062 mm Hg/kg, on height 0.165 +/- 0.056 mm Hg/cm, on pulse rate 0.364 +/- 0.100 mm Hg/beats per min and on outside temperature -0.25 +/- 0.07 mm Hg/degrees C.

Blood Pressure↗

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part 1. Scanning and transmission electron microscopic study.

Endothelial cell damage is considered to be the primary event in atherogenesis. In this study we compared the effects of mild hypercholesterolemia and repeated E. coli endotoxin infusions on the endothelial cells of the coronary arteries of the pig. We divided 24 pigs into 4 groups: I: controls on normal diet; II: normal diet and endotoxin treatment; III: fat-supplemented diet; IV: fat-supplemented diet and endotoxin treatment. The animals on a fat-supplemented diet showed the most frequent and most severe endothelial cell damage. The damage was less when this diet was combined with endotoxin treatment. Endotoxin reduced the serum total cholesterol level (P less than 0.01). The cholesterol level correlated very significantly (P less than 0.001) with endothelial damage of the coronary arteries. Mild hypercholesterolemia (s-cholesterol 5.68 mmol/l, controls 2.28 mmol/l) was thus associated with toxic effects in the endothelial cells. The E. coli endotoxin infusions did not have any cumulative effect on the lesions.

Animals↗

Three-year tracking of serum fatty acids in Finnish boys and girls.

The composition of fatty acids in serum lipids has been shown to reflect the quality of dietary fat. In order to examine the long-term stability (tracking) of the serum (and hence dietary) fatty acid composition serum cholesteryl ester fatty acids were analysed by gas chromatography in a randomly selected population sample of 1029 Finnish boys and girls aged 3, 6, 9, 12, 15 and 18 years, and again from the same individuals 3 years later. The tracking was evaluated by calculating linear correlation coefficients for the percentages of individual fatty acids between the 2 time points. For all fatty acids the correlations were highly significant, e.g. for linoleate and arachidonate they were 0.58 and 0.61, respectively. In 1980 the means of the percentages of some fatty acids showed certain differences between the various age and sex groups; in 1983 these differences had become smaller and had largely shifted towards three years older age groups, implying that the differences were due to dietary differences between the cohorts rather than to age and sex per se. The present results indicate that serum fatty acid composition has a fairly good biological reproducibility (tracking) and suggest that age and sex as such are only minor determinants of the serum fatty acid composition.

Adolescent↗

Problems with PEG-based precipitation methods in the determination of HDL2- and HDL3-cholesterol.

In this study a comparison of two polyethylene glycol (PEG)-based precipitation methods, that is, one using PEG-6000/DS-15000 and the other using two different concentrations of PEG-20000 are presented. The total HDL-cholesterol values measured with the PEG-6000 procedure were higher (13%) than those measured with PEG-20000 (r = 0.91) in 16 pooled serum samples tested. The HDL2- and HDL3-cholesterol values measured with the two methods differed markedly from each other in spite of the moderate correlation (HDL2: r = 0.74; HDL3: r = 0.26) observed. The advantage of the PEG-20000 method as compared with the other method was its simplicity and rapidity. The separation of HDL2/HDL3 is more or less arbitrary in both methods used and further studies are needed for the estimation of optimal conditions for subclass separation.

Chemical Precipitation↗

Increased activity of serum gamma-glutamyltransferase in myotonic dystrophy.

The activity of serum gamma-glutamyltransferase (gamma-GT) and its determinants were studied in 17 patients with myotonic dystrophy. The gamma-GT activity was elevated in 11 patients and its mean value was five-fold higher than in healthy controls. The increase in gamma-GT could not be explained by factors generally known to result in a misleading elevation of gamma-GT. Most patients with elevated gamma-GT also had one or more other pathological laboratory tests related to hepatic function but none had a clinically significant liver disease. Serum gamma-GT activity was not related to the disability caused by dystrophy or to the level of serum creatine kinase suggesting that the elevation of serum gamma-GT is not an indication of a general cell membrane dysfunction. It is concluded that the increase in serum gamma-GT activity in patients with myotonic dystrophy is due to a real but mild liver involvement, which should be taken into account in the examination of these patients who often complain of gastrointestinal symptoms.

Adult↗

Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2-adrenoceptor agonist, in healthy volunteers.

1. Single intravenous doses (25, 50 and 100 micrograms) of medetomidine (MPV-785, an imidazole derivative), a selective alpha 2-adrenoceptor agonist, were administered to eight healthy male volunteers in a double-blind, placebo-controlled study. 2. The following dose-related effects, all of which were compatible with an agonistic action of the drug at alpha 2-adrenoceptors, were noted: reductions of systolic and diastolic blood pressure (maximum 18/11 mm Hg), heart rate (maximum 10 beats min-1), saliva secretion (maximum 84%) and noradrenaline levels in plasma (maximum 70%). 3. Dose-dependent sedation or impairment of vigilance was also observed, both by subjective and objective (critical flicker fusion threshold) assessments, with the highest dose actually inducing sleep in five of the subjects. 4. The observed effects were in general agreement with those previously seen after intravenous administration of the centrally acting antihypertensive alpha 2-adrenoceptor activating drug, clonidine, but of a shorter duration. 5. The relative importance of alpha 2-adrenoceptors located in peripheral tissues and in the central nervous system for the drug's cardiovascular effects could not be determined, but the high lipid solubility of the compound and the rapid onset of sedation are in favour of a major central component. 6. Medetomidine may be a useful tool for the investigation of the physiology and pharmacology of alpha 2-adrenoceptors in man. In addition, the therapeutic and diagnostic uses of the compound should be investigated in pathological conditions related to increased sympathetic neuronal activity.

Adrenergic alpha-Agonists↗

Glucagon-C-peptide test as a measure of insulin requirement in type 2 diabetes: evaluation of stopping insulin therapy in eleven patients.

The glucagon-C-peptide test was evaluated as a predictor of the requirement of insulin therapy in type 2 diabetes mellitus. Endogenous insulin secretory capacity was measured in a population of 150 insulin-treated adult diabetic patients by determining postprandial glucagon-stimulated plasma C-peptide concentration (Novo, antiserum M 1230). Eleven subjects with C-peptide levels above 1.0 nmol/l comprised the subgroup in which the previously started insulin therapy was discontinued. After an observation period of a week in hospital the metabolic control of the patients was followed in an outpatient clinic for twelve months. During the observation period one patient was managed on diet alone, eight subjects required oral hypoglycaemics agents and two required the reinstitution of insulin therapy. Mean fasting blood glucose and GHbA1 (glycosylated haemoglobin) of non-insulin dependent diabetics increased during the observation period (from 8.8 to 11.8 mmol/l, p less than 0.001, and from 12.2 to 14.1%, p less than 0.05, respectively). No significant changes were found in total or HDL-cholesterol or triglyceride levels. The findings demonstrate that the glucagon-C-peptide test can be used as an aid in judging whether the withdrawal of insulin may be considered without excessive risk of developing diabetic ketoacidosis. However, the test cannot be used as the only criterion when assessing the need for exogenous insulin in type 2 diabetes. Meticulous monitoring of blood glucose levels is necessary when insulin therapy is withdrawn, because diabetic patients with peripheral insulin resistance may not maintain satisfactory glycaemic control without exogenous insulin despite of high residual endogenous insulin secretion.

Aged↗

Serum fructosamine in the assessment of glycaemic control in diabetes mellitus.

Serum fructosamine determination was evaluated in the assessment of glycaemic control in diabetes mellitus. Intra- and inter-assay variation of the method was 0.5-0.8 and 1.5-2.9%, respectively. The fructosamine concentration in serum was found to be stable for at least 10 days independent of prevailing serum glucose concentration is stored at +4 degrees C or colder. Stability of serum fructosamine with respect to rapid fluctuations of blood glucose was of the same order as that of HbA1c. The reference interval (mean +/- 2 SD) for 92 non-diabetic individuals was 1.9-2.7 mmol/l. Good correlation was found between HbA1c and serum fructosamine (r = 0.79). Serum fructosamine and HbA1c correlated well with the mean blood glucose values of the preceding week (r = 0.88 and 0.75, respectively, p less than 0.001). Significant correlations of fructosamine and HbA1c with fasting blood glucose were also found (r = 0.53 and 0.55, respectively, p less than 0.001). Fructosamine determined simultaneously with fasting blood glucose in 65 oral glucose tolerance tests (OGTT) did not separate normal subjects from those with impaired glucose tolerance. Two of the three subjects with diabetic response in the OGTT had, however, elevated fructosamine concentrations. Determination of serum fructosamine is a technically simple, reproducible and moderately inexpensive method for the assessment of glycaemic control in diabetes mellitus. Standardization of the method is, however, not without problems. Uniformity of the calibration and assay protocol is essential for reliable interlaboratory comparison of results. Physiological states altering the rate of synthesis or elimination of serum proteins should be considered in the interpretation of fructosamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Fatty acid composition of serum cholesteryl esters in relation to serum lipids and apolipoproteins in 3-18-year-old Finnish children and adolescents.

Serum cholesteryl ester (CE) fatty acids, serum lipids and apolipoproteins were analysed from 1348 Finnish children aged from 3 to 18 years. The study was part of a comprehensive survey of coronary heart disease risk factors and their determinants in Finnish children and adolescents. The percentage of CE linoleate (18:2) had significant negative correlations with the serum concentrations of total and LDL cholesterol, triglycerides as well as apo B. The associations of HDL to CE fatty acids were weak, although there was a significant positive correlation of CE-18:2 to HDL cholesterol and apo A-I. The ratio of HDL to total cholesterol and the ratio of apo A-I to apo B increased strongly in quintiles of increasing percentage of CE-18:2. In conclusion, the present results show significant associations between serum CE fatty acid composition and the different components of serum lipoproteins among free-living Finnish children and imply a relation between the quality of dietary fats and serum lipoproteins within this population.

Adolescent↗