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Biomedical subjects

O Wiklund

Publications and source records attributed to O Wiklund.

At least 19 recordsLinked to original sources
PubMed1992

Prognosis in hypertensives with acute myocardial infarction.

OBJECTIVES: A previous history of hypertension is overrepresented among patients with ischaemic heart disease. The present study aims at describing the influence of a previous history of hypertension upon the prognosis among patients hospitalized due to acute myocardial infarction. DESIGN: Patients were followed for 1 year. Mortality and morbidity are described during hospitalization and after discharge from hospital. SETTING: Sahlgrenska Hospital, serving half of the area of Gothenburg in Sweden. PATIENTS: All patients admitted to Sahlgrenska Hospital during 21 months due to acute myocardial infarction regardless of age and whether they were admitted to the coronary care unit. RESULTS: Among all patients with confirmed acute myocardial infarction (n = 917) a previous history of hypertension was reported in 324 patients. Hypertensives more frequently had a previous history of acute myocardial infarction, angina pectoris, congestive heart failure and diabetes mellitus. Their mortality during hospitalization was similar to that in normotensives. However, the total mortality during 1 year of follow-up was 35% in hypertensives and 25% for normotensives (P < 0.01), and a previous history of hypertension was an independent risk indicator for death after discharge from hospital. Place and mode of death appeared similar in normotensives and hypertensives. Reinfarction was twice as common in hypertensives as in normotensives, and a previous history of hypertension was an independent risk indicator for reinfarction. CONCLUSIONS: Among patients with acute myocardial infarction a previous history of hypertension indicates a poor prognosis, one-third of patients dying and one-quarter developing reinfarction during the first year after onset of acute myocardial infarction.

Aged↗
PubMed1992

Characteristics and prognosis of patients with acute myocardial infarction in relation to whether they were treated in the coronary care unit or in another ward.

The characteristics and the prognosis in 921 consecutive patients with acute myocardial infarction (AMI) admitted to one single hospital are described and related to whether they were treated in the coronary care unit or not. Patients treated in the coronary care unit (n = 779) had a 1-year mortality rate of 26% as compared with 41% for patients treated in general wards (n = 115; p < 0.001) and 74% for patients treated in the intensive care unit (n = 27; p < 0.001). Patients treated outside the coronary care unit had a different risk factor pattern including a higher age and a higher prevalence of a previous cardiovascular disease. Independent clinical risk indicators for death among patients in the coronary care unit were in order of significance, high age (p < 0.001), arrhythmia on admission (p < 0.01), acute congestive heart failure on admission (p < 0.01) and a history of diabetes mellitus (p < 0.05). In patients treated in general wards, the only risk indicator for death was a history of congestive heart failure.

Aged↗
PubMed1992

Arterial wall thickness in familial hypercholesterolemia. Ultrasound measurement of intima-media thickness in the common carotid artery.

B-mode ultrasound was used to noninvasively determine wall thickness and lumen diameter in the common carotid artery in patients with familial hypercholesterolemia (n = 53) and in a control group (n = 53). The controls were matched for sex, age, height, and weight, and all had a serum cholesterol level below 6.5 mmol/l. The study was performed to evaluate whether the patients had a thicker arterial wall compared with that of the control group. Wall thickness was determined as the combined intima-media thickness of the far wall and is presented as the mean and maximum thickness of a 10-mm-long section of the common carotid artery. The difference between the groups was 0.13 mm in mean wall thickness (p less than 0.001; 95% confidence interval, 0.07-0.18 mm) and 0.20 mm in maximum wall thickness (p less than 0.001; 95% confidence interval, 0.09-0.23 mm). Fifty of the subjects were examined twice to estimate the interobserver variability. The coefficients of variation for mean and maximum wall thickness were 10.2% and 8.9%, respectively. The two study groups were well matched and differed only in lipid levels. Thus, there is reason to believe that the difference in wall thickness can be explained by the background of familial hypercholesterolemia and the increased cholesterol levels.

Adult↗
PubMed1991

Early prediction of acute myocardial infarction from clinical history, examination and electrocardiogram in the emergency room.

The possibility of early prediction of acute myocardial infarction (AMI) was assessed in 7,157 consecutive patients coming to our emergency room during a 21-month period with chest pain or other symptoms suggestive of AMI. Of these patients 921 developed an AMI during the first 3 days in the hospital. Of the 4,690 patients admitted to hospital, 1,576 (34%) had a normal admission electrocardiogram, and 90 of these (6%) developed AMI. Of 1,964 patients with an abnormal electrocardiogram without signs of acute ischemia (42% of those admitted), 268 (14%) developed AMI, and 563 (51%) of 1,109 patients with acute ischemia on the electrocardiogram (24%) developed AMI. All patients were prospectively classified in the emergency room on the basis of history, clinical examination and electrocardiogram into 1 of 4 categories, according to the initial degree of suspicion of AMI. Of 279 admitted patients judged to have an obvious AMI (6% of the 4,690), 245 (88%) actually developed AMI; of 1,426 with a strong suspicion of AMI (30%), 478 (34%) developed one; of 2,519 with a vague suspicion of AMI (54%), 192 (8%) developed one; and of 466 with no suspicion of AMI (10%), 6 (1%) developed one. Thus, only a low percentage of the patients with a normal initial electrocardiogram or a vague initial suspicion of AMI developed a confirmed AMI.

Electrocardiography↗
PubMed1991

Modifications of low-density lipoprotein induced by arterial proteoglycans and chondroitin-6-sulfate.

Association of low-density lipoproteins (LDL) with arterial chondroitin sulfate proteoglycans (CSPG) appears to contribute to their deposition in the extracellular intimal compartment and to its internalization by macrophages. CSPG and LDL interact by ionic bridges with formation of soluble and insoluble complexes. We studied the alterations on LDL structure induced by its association with arterial CSPG and other glycosaminoglycans (GAG). In soluble complexes, at low and at physiological ionic strength, arterial CSPG and sulfated GAG modify the kinetics of apoB-100 proteolysis by trypsin. However, less marked alterations in the peptide patterns were observed with proteinase V8 and almost none with thermolysin. This is indirect evidence that the presence of CSPG and GAG modified the exposure of polar regions of apoB-100 in LDL. Competitive binding experiments with agarose-bound heparin and soluble GAG also suggest that after formation of insoluble complexes with arterial CSPG and resolubilization the exposure of Lys, Arg-rich segments of apoB-100 is increased. Results from differential scanning calorimetry and differential thermal spectrophotometry showed that the CSPG and GAG-induced modifications reduced the thermal stability of the surface and core in LDL. If present in vivo, the structural alterations of polar segments of the LDL protein moiety may influence the outcome of its interaction with the arterial mesenchyma.

Apolipoprotein B-100↗
PubMed1991

Isolation of cell populations from arterial tissue, using monoclonal antibodies and magnetic microspheres.

In the present study we describe a method for the isolation of cell populations from human and rabbit atherosclerotic tissue, using monoclonal antibodies against cell surface antigen and magnetic microspheres. Atherosclerotic tissue was digested with proteolytic enzymes. The heterogeneous cell suspensions from human tissue were incubated with monoclonal antibodies: anti-Leu-4 (T lymphocytes), anti-Leu-M3 (macrophages) and anti-HLA-DR (HLA-DR expressing cells). The rabbit aortic cells were incubated with RAM11 (rabbit macrophages) antibody. The rosetting procedure was carried out by mixing antibody treated cells with magnetic monodisperse particles coated with a secondary antibody (goat anti-mouse IgG). Morphologically, homogeneous foam cell populations were isolated with anti-Leu-M3 and RAM11. From rabbit atherosclerotic aorta about 2 X 10(5) RAM11 positive cells were recovered/g tissue. The specificity was tested comparing with FACS analysis. A high degree of specificity was obtained while the FACS detected about 30% more cells than were isolated by immune depletion. The lipids of isolated macrophage derived foam cells from rabbit aorta were dominated by cholesterol ester (42%) and smaller amounts of unesterified cholesterol (17%) or triglycerides (3%). These experiments indicate that immunomagnetic fractionation of cells will be a useful method for studies of the composition and metabolism of different cell populations of atherosclerotic tissue.

Animals↗
PubMed1991

One-year mortality rate after discharge from hospital in relation to whether or not a confirmed myocardial infarction was developed.

Consecutive patients admitted to our hospital with suspected acute myocardial infarction during 21 months were prospectively evaluated. One-year mortality after discharge from hospital was related to whether or not an infarction developed (infarct versus non-infarct patients). Of patients discharged alive after developing an infarct, there was a mortality of 17% (n = 777) versus 12% (n = 1830) (P less than 0.001) for all patients not developing infarction. In a high risk group (any of the following: age greater than or equal to 75 years, previous history of myocardial infarction, diabetes mellitus or congestive heart failure) patients developing infarction had a mortality of 24% (n = 457) versus 17% (n = 1221) for those who did not (P less than 0.001). In a low risk group (none of the high risk criteria), the corresponding mortality was 8% (n = 316) for patients suffering infarction and 3% (n = 603) for those not having infarction (P less than 0.001). The difference in mortality between patients with and without infarction was most marked in women (21% vs 11%; P less than 0.01) and in hypertensives (25% vs 12%; P less than 0.001), but less marked in men (16% vs 13%; NS) and in patients without hypertension (13% vs 12%; NS). Among patients not suffering infarction, mortality was particularly high in those with previous congestive heart failure (23%) and diabetes mellitus (21%).

Age Factors↗
PubMed1991

Serum lipids and lipoproteins in relation to restenosis after coronary angioplasty.

Restenosis after coronary angioplasty (PTCA) is a major problem, limiting the long-term efficacy of the procedure. Lipoprotein levels are associated with the development of atherosclerosis and may also be associated with restenosis. In this study the serum levels of cholesterol (CH), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were analysed in 157 patients undergoing 161 PTCA procedures. Follow-up coronary angiograms were performed after 6.0 +/- 4.3 months. The restenosis rate was 33%. Treatment with aspirin and a residual stenosis of 25-49% immediately after successful PTCA were the only variables associated with restenosis (P less than 0.05), otherwise the clinical and angiographic characteristics were similar with and without restenosis. There was no relationship between restenosis and the levels of CH, TG, HDL or LDL (P greater than 0.05). In univariate and multivariate analysis of males (n = 121) and females (n = 40) separately, restenosis was associated with low HDL in men and high HDL in women (P less than 0.05), but not with CH, TG or LDL (P greater than 0.05). We conclude that the serum levels of CH, TG and LDL do not seem to be related to restenosis after PTCA. It is suggested that low HDL in males and high HDL in females is related to restenosis.

Adult↗
PubMed1991

Modification of copper-catalyzed oxidation of low density lipoprotein by proteoglycans and glycosaminoglycans.

Chondroitin sulfate proteoglycans (CSPG) appear to contribute to retention of low density lipoproteins (LDL) in atherosclerotic lesions. In vitro, CSPG and glycosaminoglycans (GAG) modify LDL structure and increase its uptake by macrophages. This latter effect appears related to increased exposure of arginine- and lysine-rich segments of apoB-100. We explored whether alterations of LDL induced by human arterial CSPG and purified GAG alter the lipoprotein susceptibility to transition metals-catalyzed oxidation. Human LDL was complexed with human arterial CSPG and dissociated by raising the ionic strength. The nonaggregated, CSPG- and GAG-treated LDL was subjected to oxidation by micromolar amounts of Cu+, Cu2+, Fe2+, and Fe3+. This treatment increased LDL susceptibility to Cu2+ oxidation 3- to 5-times, as indicated by the degradation rate of phospholipids and cholesteryl esters and formation rates of dienes and thiobarbituric acid-reacting substances (TBARS). Also, human macrophages degraded the CSPG-treated, Cu2+-oxidized LDL 3- to 6-times faster than native LDL similarly treated. No enhancement of oxidation was observed with Fe2+, Fe3+, and Cu+. Quenching of the LDL intrinsic fluorescence by Cu2+ showed that heparin, CSPG, and chondroitin-6-SO4 pretreatment increased the access of Cu2+ to hydrophobic chromophores, probably tryptophan, 6- to 7-, 3- to 4-, and 2- to 3-fold, respectively. Also, the affinity constant (Ka) of LDL for Cu2+ was increased from 0.12 microM to 0.20 microM by the treatment with CSPG and GAG. These results and evaluation of the fraction of surface-accessible LDL chromophores to acrylamide quenching suggest that the increased susceptibility to oxidation may be associated with an increase in the access of Cu2+ to hydrophobic regions in LDL caused by treatment with CSPG and GAG. This effect was not detected with Cu+, Fe2+, or Fe3+. The phenomenon may contribute to acceleration of the oxidative modifications of LDL in cell culture models and in vivo.

Aorta↗
PubMed1991

Uptake and degradation of low density lipoproteins in atherosclerotic rabbit aorta: role of local LDL modification.

The uptake of native and modified low density lipoprotein (LDL) in foam cells in atherosclerotic tissue was studied in an in vitro perfusion system for rabbit aorta. Experimental atherosclerosis was induced in rabbits by a combination of cholesterol feeding and mechanical injury. The aorta was perfused in an incubation chamber. A trace-label, radioiodinated tyramine-cellobiose, was used to study cellular uptake of lipoproteins. After perfusion, the tissue was digested and cells were isolated by centrifugation in a density gradient. About 40 times more LDL per cell was accumulated in the foam cell fraction than in the smooth muscle cell fraction. When the cellular uptake of LDL and acetylated LDL (AcLDL) was compared, about 4 times more AcLDL than LDL was taken up by the foam cells, suggesting that the scavenger receptor is expressed in these cells. In a competition experiment, the uptake of LDL into foam cells was reduced by 70% when a tenfold excess of AcLDL was added. This experiment suggests that native LDL is taken up by the same mechanism as AcLDL. The accumulation of radiolabeled LDL in plaques and in foam cells was reduced by 30-55% by adding vitamin E (0.1 mg/ml) to the system. These studies show an uptake of LDL by foam cells in the atherosclerotic tissue. Furthermore, these cells seem to express the scavenger receptor. The competition experiment would suggest that native LDL is taken up by the scavenger receptor. The observation that an antioxidant, vitamin E, may decrease this uptake suggests that oxidative modification of LDL is of importance for this process.

Acetylation↗
PubMed1990

The assembly and secretion of apoB 100 containing lipoproteins in Hep G2 cells. Evidence for different sites for protein synthesis and lipoprotein assembly.

Pulse-chase studies combined with subcellular fractionation indicated that LpB 100 (i.e. the apoprotein B (apoB) 100 containing lipoproteins) was released to the lumen of the secretory pathway in a subcellular fraction enriched in smooth vesicles, and referred to as SMF (the smooth membrane fraction). The migration of SMF during gradient ultracentrifugation as well as kinetic studies indicated that the fraction was derived from a pre-Golgi compartment, probably the smooth endoplasmic reticulum (ER). Only small amounts of LpB 100 could be detected during these pulse-chase experiments in the subcellular fractions derived from the rough endoplasmatic reticulum (RER). SMF contained the major amount of the diacylglycerol acyltransferase activity present in the ER, while the major amount of membrane bound apoB 100 was present in the RER. Pulse-chase studies of the intracellular transfer of apoB 100 demonstrated the formation of a large membrane-bound preassembly pool in the ER, while no significant amount of apoB 100 radioactivity was present in the membrane of the Golgi apparatus. The maximal radioactivity of LpB 100, recovered from the ER or the Golgi lumen, was small compared with the radioactivity recovered from the ER membrane, indicating that the assembled LpB 100 rapidly leaves the cells. This in turn indicates that the rate-limiting step in the secretion of apoB 100 was the transfer of the protein from the ER membrane to the LpB 100 in the lumen. A portion of the intracellular pool of apoB 100 was not secreted but underwent posttranslational degradation.

Acetylglucosaminidase↗
PubMed1990

Apolipoprotein(a) and ischaemic heart disease in familial hypercholesterolaemia.

Serum concentrations of apolipoprotein(a) were measured in patients with heterozygous familial hypercholesterolaemia. The levels in 47 patients were a median of 2.5 times higher than those in controls matched for age and sex (240 [range 25-1245] vs 97 [7-1040] mg/l). Among patients with familial hypercholesterolaemia apo(a) levels were higher in those with (n = 48) than in those without (n = 72) ischaemic heart disease (283 [18-1245] vs 144 [7-741] mg/l); both in univariate and multivariate analysis serum apo(a) was the most significant variable distinguishing between the groups. Despite reducing LDL cholesterol by 30%, treatment with cholestyramine or pravastatin did not reduce apo(a) levels in these patients. These findings support the concept that apo(a) concentration is a genetic trait predisposing to ischaemic heart disease and imply that it may be useful in the identification of familial hypercholesterolaemia patients at high risk of coronary disease.

Adult↗
PubMed1990

Effect of short-term beta blockade on serum lipid levels and on the interaction of LDL with human arterial proteoglycans.

In view of conflicting evidence suggesting that beta-blockers have an anti-atherogenic effect as well as induce a potentially atherogenic lipoprotein profile, the effects of a short term beta-blockade on serum lipoproteins were studied in 39 healthy volunteers. Because the interaction of LDL with arterial proteoglycans appears to play a role in lipoprotein accumulation during atherogenesis, the effects of metoprolol and atenolol on low density lipoprotein interaction with human aortic proteoglycans were included in the study. We could confirm that the beta-blockers caused a decrease in HDL cholesterol and an increase in triglycerides, both potentially undesirable effects. In addition, however they induced a significant decrease in the in vitro LDL affinity for arterial proteoglycans. Since there appears to be a strong association between LDL reactivity with proteoglycans and risk for myocardial infarction, this effect of the beta-blockers may be an anti-atherogenic effect which overrides other effects on the lipoprotein pattern.

Adult↗
PubMed1990

Transfer of lipoproteins from plasma to the cell populations of the normal and atherosclerotic arterial tissue.

It appears that retention of lipoproteins rather than increased influx is the basis for lipoprotein deposition in arterial tissue during atherogenesis. Binding of lipoproteins to arterial proteoglycans is mediated by a peptide sequence considered to be involved in the interaction between the lipoproteins and the lipoprotein receptor. Consequently, in the presence of an excess of arterial proteoglycan, receptor-mediated cellular uptake of LDL is inhibited. However, LDL which has been precipitated by proteoglycan and subsequently resolubilized is taken up more avidly than native LDL, both in macrophages and in smooth muscle cells. This appears to be due to selection by the proteoglycans of a more reactive fraction of LDL. This fraction has a smaller molecular size and less surface phospholipids. As smaller LDL particles also have a higher transfer rate into the arterial tissue they may be particularly atherogenic. Low density lipoproteins appear to be taken up with higher affinity by arterial macrophages than by smooth muscle cells. The selective transfer of the LDL to macrophages can be inhibited by alpha-tocopherol, suggesting that oxidative modification may be involved in this process. The role of foam cells in atherogenesis is discussed in the context of the energy requirements of the arterial wall.

Animals↗
PubMed1990

Treatment of familial hypercholesterolaemia: a controlled trial of the effects of pravastatin or cholestyramine therapy on lipoprotein and apolipoprotein levels.

The efficacy and safety of a new, selective inhibitor of cholesterol synthesis, pravastatin, and the bile acid-binding resin, cholestyramine, were compared in a randomized, double-blind study of 120 patients with familial hypercholesterolaemia. After a run-in period of 8-10 weeks with assessment of dietary habits, the patients were treated with pravastatin + placebo, placebo + cholestyramine, or placebo alone. Active pravastatin therapy was initiated with 10 mg b.i.d. for 6 weeks, and was increased to 20 mg b.i.d. for the following 6 weeks. Cholestyramine was given at 24 g d-1, or the highest tolerable dose. After 6 weeks of therapy, serum total and LDL cholesterol levels were reduced by 17% and 21%, respectively, on pravastatin treatment, whereas the corresponding reductions with cholestyramine treatment were 24% and 30%, respectively. With an increased dose of pravastatin, serum and LDL cholesterol concentrations were reduced by 23% and 28%, respectively, after 12 weeks; the effect of cholestyramine was unchanged. HDL cholesterol levels increased in response to pravastatin, by 7% and 9% after 6 and 12 weeks, respectively. Concomitant changes in the concentrations of apolipoproteins B and AI were observed. Three patients discontinued the study because of side-effects: two subjects were treated with pravastatin and one was given placebo. The prevalence of side-effects (including laboratory abnormalities) was 35% for pravastatin, 30% for placebo, and 53% (significantly higher) for cholestyramine. We conclude that pravastatin, in a 40 mg daily dose, is as effective as cholestyramine in lowering LDL cholesterol in familial hypercholesterolaemia. Since the frequency of side-effects is higher with cholestyramine, pravastatin offers a promising alternative for the therapy of this genetic disease.

Adult↗