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Biomedical subjects

G Walldius

Publications and source records attributed to G Walldius.

At least 19 recordsLinked to original sources

Apolipoprotein B and A-I in relation to serum cholesterol and triglycerides in 43,000 Swedish males and females.

Automated methods for the determination of apolipoprotein B and apolipoprotein A-I were developed, tested, and applied in screening programs of large populations to improve information about the composition and degree of hyperlipoproteinemia. Apolipoproteins B and A-I, total cholesterol, and triglyceride levels were measured in 25,659 males and 18,144 females between 20 and 79 years of age, the majority subjectively healthy. The immunoturbidimetric methods used for apolipoproteins B and A-I were shown to be stable over time, and the errors of the methods were below 7%. Apolipoprotein B correlated with total cholesterol (r = 0.86, P less than 0.001) for each age decile group and for both sexes (r = 0.82-0.87, P less than 0.001). For a subsample comparable to the large population, apolipoprotein B correlated with cholesterol in low density (i.e., the atherogenic particle), r = 0.89, P less than 0.001. The mean values for apolipoprotein B increased with age for both sexes, with much higher levels in males than in females under 50 years of age. Apolipoprotein A-I was lower in males than in females in all age-groups. At all cholesterol levels males had higher apolipoprotein B, and at the same triglyceride level, also lower apolipoprotein A-I and hence a higher B/A-I ratio than females. Using apolipoprotein B and A-I (high-density lipoprotein cholesterol) particles and adopting Swedish consensus criteria for the diagnosis of risk of ischemic heart disease, examples are given showing that many individuals, especially females, with high or borderline total serum cholesterol can be excluded from further investigation/treatment for hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia.

The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size-defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.

Adult

Correlation between computer-assisted femoral arteriography and physiological tests in hypercholesterolaemic patients: a methodological study with special reference to clinical trials.

The validity of computer-assisted femoral arteriography, for the study of regression/progression of atherosclerosis in follow-up clinical trials, was investigated by comparison with routine physiological estimates of peripheral circulatory function. Thus, in 114 hypercholesterolaemic patients, the results of aorto-femoral arteriography were compared with those of leg segmental blood pressure measurement, oscillometry, digital pulse plethysmography, and bicycle and treadmill exercise tests. In 107 patients, 18 with symptoms of peripheral vascular disease (PVD) and 89 asymptomatic, magnification arteriograms of a 20 cm segment of the right or left superficial femoral artery were obtained. These arteriograms were digitized and the following variables were calculated: arterial lumen volume (corrected for body size), per cent stenosis, and edge roughness. The correlation between arteriographic and physiological variables was investigated with a linear regression model, taking into account the possible interaction with sex, and presence or absence of symptoms of PVD. Lumen volume correlated significantly with all five physiological variables, and per cent stenosis correlated significantly with four of the physiological variables. For the roughness measure, however a significant correlation was found only with plethysmography. By using logistic multiple regression analysis linear functions of physiological variables were constructed to detect ilio-femoral arterial occlusion. The sensitivity/specificity for detection of right-sided, left-sided, and bilateral occlusion was 0.83/0.98, 0.78/0.98, and 0.60/1.00 respectively (N = 108-111). Systolic blood pressure (ankle-arm ratio) was the single variable most closely correlated to the likelihood of arterial occlusions. It is concluded that arterial lumen volume and per cent stenosis, measured for the digitized femoral arteriogram, correlate well with physiological variables, which reflect the state of atherosclerosis both in the femoral arteries and in other arterial beds including the heart, and that routine physiological tests can be used to identify patients with arterial occlusions in the iliac and femoral arteries.

Adult

Effects of nicotinic acid on glucose tolerance and glucose incorporation into adipose tissue in hypertriglyceridaemia.

Nicotinic acid 4 g daily was given to 28 weight-stable hypertriglyceridaemic patients. The aim was to study its effects on serum lipoprotein lipid levels, intravenous glucose tolerance (k-values) and glucose incorporation into subcutaneous adipose tissue (GLIAT) in vitro. The investigations were performed prior to the nicotinic acid therapy, after 6 weeks, and 6 months of drug treatment. Fasting blood glucose levels increased by 13%, whereas k-values fell by 26% after the nicotinic acid treatment. Decrease in k-values was predicted from the initial k-values (R2-value = 0.76). GLIAT increased by 76%, while in the subgroup of eight patients, treated for 6 months with nicotinic acid, GLIAT increased by 331%. The changes in k-values and GLIAT were not significantly interrelated. Serum triglyceride levels were strongly decreased. The most likely explanation for the decrease in intravenous glucose tolerance is that nicotinic acid stimulates glucose output from the liver and that this effect outweighs the stimulating effects of the drug on glucose utilization in extrahepatic tissues. The latter is reflected by the increased uptake of glucose in adipose tissue. A stimulated GLIAT, reflecting formation of alpha-glycerophosphate in adipose tissue, might contribute to the reduction of serum triglyceride levels induced by nicotinic acid, since alpha-glycerophosphate is the acceptor of fatty acids assumed to be liberated from circulating triglycerides by lipoprotein lipase.

Adipose Tissue

Effects of nicotinic acid treatment on fatty acid composition of plasma lipids and adipose tissue in hyperlipidaemia.

Effects of 6-week treatment with 4 g daily of nicotinic acid on fatty acid composition in different serum lipids and in adipose tissue glycerides were studied in 31 hyperlipidemic patients. The percentages of eight fatty acids in triglycerides, phospholipids and cholesteryl esters of whole plasma as well as in subcutaneous adipose tissue glycerides were measured. Nicotinic acid treatment produced decreases in triglyceride and total cholesterol concentrations of VLDL and LDL, whereas HDL total cholesterol levels in serum increased after drug therapy, all p less than 0.01. There were reductions in the relative contents of myristic acid in plasma phospholipids (from 0.4% to 0.3%; p less than 0.05) and cholesteryl esters (from 0.9% to 0.7%; p less than 0.001). There were decreases in the percentages of stearic acid in plasma phospholipids (from 17.0% to 15.0%) and cholesteryl esters (from 1.2% to 1.0%; both p less than 0.001). The relative contents of polyunsaturated fatty acids, mainly linoleic acid, in plasma phospholipids were increased (from 32% to 33.5%; p less than 0.05). There were reductions in the linolenic acid contents of adipose tissue (from 1.5% to 1.1%) and plasma triglycerides (from 1.1% to 0.8%), both p less than 0.05, possibly indicating increased conversion of linolenic acid to prostaglandins. There was no relationship between changes in the percentages of individual fatty acids and changes in triglyceride or total cholesterol levels of whole serum and its VLDL, LDL and HDL fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

High cholesterol and triglyceride values in Swedish males and females: increased risk of fatal myocardial infarction. First report from the AMORIS (Apolipoprotein related MOrtality RISk) study.

In over 300,000 Swedish males and females aged 20 to 79 years total cholesterol and triglycerides were measured consecutively between 1985 and 1989. In a subsample of about 35,000 individuals apolipoprotein (apo) B (indicating atherogenic) and apo A-I (anti-atherogenic) were also measured. In the age group 40-49 years, 24% of the males and 12% of the females had hypercholesterolemia (> or = 6.5 mmol/L) and 14% and 3%, respectively had hypertriglyceridemia (> or = 2.3 mmol/L). Combined hyperlipidemia occurred in this age group in 7% of the males and in 1% of the females and was more common in males. In the same age group, 21% of the males and 8% of the females had high atherogenic apo B values (> 1.5 g/L). Low apo A-I was found in the whole population (20-79 years) in 13% of the males and in 10% of the females and varied only little with age. In the AMORIS (Apolipoprotein related MOrtality RISk) study these individuals are followed prospectively. The relations between lipids and apo B and apo A-I levels and risk for fatal acute myocardial infarction (AMI) are analyzed to investigate which of these lipids/apolipoproteins best predict AMI either as single determinants or in combination. After a mean observation time of about 22 months there is a 3-6-fold increase in AMI in relation to increasing cholesterol levels in males of 40-59 years. The largest increase was seen in the 40-49-year age group. A similar relationship was also found for triglycerides and AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Lipoprotein lipase in plasma after an oral fat load: relation to free fatty acids.

Lipoprotein lipase (LPL) releases fatty acids from triglyceride-rich lipoproteins for use in cellular metabolic reactions. How this hydrolysis, which occurs at the vascular endothelium, is regulated is poorly understood. A fatty acid feedback system has been proposed by which accumulation of fatty acids impedes LPL-catalyzed hydrolysis and dissociates the enzyme from its endothelial binding sites. We examined this hypothesis in humans who were subjected to an oral fat tolerance test of a mixed-meal type. Plasma triglycerides, free fatty acids, and LPL activity were measured before and repeatedly during a 12-h period after intake of the fat load. Since soybean oil with a high content of linoleic fatty acid was the source of triglycerides, a distinction could be made between endogenous free fatty acids (FFA) and FFA derived directly from lipolysis of postprandial triglyceride-rich lipoproteins. Mean LPL activity was almost doubled (P less than 0.01) 6 h after intake of the oral fat load. The rise in LPL activity was accompanied by an increase of plasma triglycerides and linoleic free fatty acids (18:2 FFA), but not of total plasma FFA, which instead displayed a heterogeneous pattern with essentially unchanged mean levels. The postprandial response of LPL activity largely paralleled the postprandial responses of 18:2 FFA and triglycerides. The highest degree of parallelism was seen between postprandial 18:2 FFA and LPL activity levels. Furthermore, the integrated response (area under the curve, AUC) for plasma measurements of LPL correlated with the AUC for 18:2 FFA (r = 0.40, P less than 0.05), but not with the AUC for plasma triglycerides (r = 0.21, ns). The high degree of parallelism and significant correlation between postprandial plasma LPL activity and 18:2 FFA support the hypothesis of fatty acid control of endothelial LPL during physiological conditions in humans.

Dietary Fats

Simultaneous measurement of serum probucol and lipid-soluble antioxidants.

A method is described for the simultaneous measurement of probucol, retinol, tocopherols, lycopene, and carotenes by reverse phase high performance liquid chromatography. A high sensitivity was achieved by use of a microbore column and by monitoring the effluent at the optimum wavelengths of each substance with a diode array detector. The detection limits were lycopene 0.5 ng; alpha-carotene, beta-carotene, and retinol 1 ng; probucol 2 ng; alpha-tocopherol and gamma-tocopherol 15 ng. The eluent was acetonitrile-water-tetrahydrofuran 81.3:5.7:13 (v/v/v) and the flow rate was 0.4 ml/min. Quantitation was performed by use of the four internal standards retinol acetate, 2-pentanone bis(3,5-di-tert)mercaptole, alpha-tocopherol acetate, and retinol palmitate, which resemble the respective analytes in structure and/or polarity. In order to attain a reproducible recovery of particularly the carotenes, the total lipid content of the samples had to be controlled by dilution of the sample before extraction. The coefficients of variation for between-day determinations of a serum pool were 3.8% for retinol, 4.5% for probucol, 11.2% for gamma-tocopherol, 4.5% for alpha-tocopherol, 10.4% for lycopene, 8.0% for alpha-carotene, and 7.0% for beta-carotene.

Antioxidants

A comparison between nicotinic acid and acipimox in hypertriglyceridaemia--effects on serum lipids, lipoproteins, glucose tolerance and tolerability.

Serum and lipoprotein lipid levels, oral glucose tolerance and side-effects were compared in an open cross-over study of 31 non-diabetic patients with hypertriglyceridaemia (type II B and IV) before and after 6 weeks of treatment with nicotinic acid (3 g daily) and acipimox (0.75 g daily), a new nicotinic acid-like drug, respectively. Acipimox was about equally potent in reducing serum and VLDL lipid levels and in increasing HDL cholesterol levels. Acipimox had no significant negative effects on glucose metabolism measured by an oral glucose tolerance test compared with nicotinic acid, which decreased the late glucose tolerance as well as the area under the glucose curve (P less than 0.05 for the difference between the two treatments). The incidence and severity of flush or any other recorded side-effects was higher after nicotinic acid treatment than after acipimox. In addition, no effects on laboratory parameters such as liver enzymes and uric acid were seen after treatment with acipimox. The results of this study demonstrate that acipimox is a satisfactory alternative to nicotinic acid in patients with hypertriglyceridaemia.

Adult

Atherosclerosis-related measures in digitized femoral arteriograms.

Atherosclerosis is reflected in the arteriogram as narrowing of the arterial lumen and irregularity of the arterial wall. We have quantified these changes in digitized femoral arteriograms from 107 hypercholesterolaemic patients and defined 10 different measures concerning arterial diameter, cross-sectional area, stenosis and edge irregularity. We examined the precision of these measures and the correlations between them. Lumen volume and mean diameter for defined arterial segments had the highest precision and may be useful for follow-up studies. The linear correlation between the mean diameter and the square root of the lumen volume was greater than 0.99, so these two measures seem to be equivalent for all practical purposes. The measured variables could be separated into 2 groups: the measures concerning arterial diameter and lumen volume and those concerning edge irregularity and localized stenosis. The measures within each group showed strong positive mutual correlations, while the correlations between measures from different groups were negative and small. It was concluded that if the results of one measure from each group, suitably those of lumen volume and edge roughness, are known, the other described measures will add no further information about the atherosclerotic process.

Arteriosclerosis

Intralipid clearance and lipoprotein pattern in men with advanced alcoholic liver cirrhosis.

Twelve male patients with advanced alcoholic cirrhosis of the liver were found to have markedly low serum lipid and lipoprotein concentrations. Serum triglyceride and cholesterol concentrations were about 50% of matched control values. The very low density lipoprotein-triglyceride concentration was only one-third of control values and the cholesterol concentrations in very low density and low density lipoproteins were far below control values. The mean high density lipoprotein cholesterol concentration was not significantly decreased, but in three of 12 patients extremely low values were found. These findings may reflect a failure of lipoprotein synthesis secondary to a bad nutritional state and metabolic disturbances in this advanced stage of liver cirrhosis. By means of the intravenous fat tolerance test with Intralipid it could be shown that substantial amounts of triglycerides could be cleared from the plasma in these patients. However, studies on the long-term Intralipid clearance capacity have to be performed before any general recommendations about the inclusion of fat emulsions in parenteral nutrition of these patients can be made.

Aged

Effect of BM 15.075 on lipoprotein concentrations in different types of hyperlipoproteinaemia.

The four-week lipoprotein lowering effect of 0.2 g t.i.d. of BM 15.075 and of 0.5 g t.i.d. of clofibrate was studied in 29 subjects with different types of hyperlipoproteinaemia in a single blind crossover fashion. BM 15.075 decreased very low density lipoproteins (VLDL), triglycerides (TG) and cholesterol concentration in all types of hyperlipoproteinaemia the effect being dependent on initial lipoprotein concentrations. BM 15.075 decreased VLDL triglyceride concentrations on average 20% more than did clofibrate. BM 15.075 decreased low density lipoproteins (LDL) cholesterol concentrations in Type IIA and IIB but did not significantly affect this lipoprotein lipid in type IV hyperlipoproteinaemia. Regression analysis showed that the drug tended to decrease LDL cholesterol if initial concentrations were above 157 mg/100 ml and to increase initially lower levels. No significant differences between BM 15.075 and clofibrate was found in the effect of LDL cholesterol. High density lipoproteins (HDL) cholesterol concentrations were not influenced by BM 15.075. No subjective side effects were noted on BM 15.075. S-ASAT increased and alcaline phosphatases decreased on both treatments.

Benzamides