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Biomedical subjects

L Ose

Publications and source records attributed to L Ose.

At least 73 records · Page 4Linked to original sources
PubMed1996

Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects.

To assess the relationship between risk factors for cardiovascular disease and early atherosclerotic changes in the carotid artery, we measured carotid intima-media thickness by B-mode ultrasonography in 61 boys and 29 girls 10 to 19 years old with familial hypercholesterolemia (FH) and 30 control subjects matched for age and sex. All were nonsmokers, and all the FH adolescents had a known mutation in the LDL receptor gene. Mean intima-media thickness in the far wall of the carotid bulb was greater (P = .03) in the FH group than in the control subjects: 0.54 mm (95% confidence interval [CI], 0.52 to 0.56) versus 0.50 mm (95% CI, 0.47 to 0.52). In the entire group, mean and maximum intima-media thicknesses in the carotid bulb were positively associated with levels of apolipoprotein B and fibrinogen after control for pubertal stage (r = .19 to .24; P < .05), as was male sex. Plasma total homocysteine was similar in the FH and control groups and was associated with mean and maximum intima-media thicknesses in the far wall of the common carotid artery and carotid bulb after control for pubertal stage (r = .22 to .28; P < .05). With the exception of the relation between plasma fibrinogen level and mean carotid bulb intima-media thickness, these associations were essentially unchanged in stepwise multiple linear regression analyses, allowing for the entry of BMI and level of HDL cholesterol into the analysis. Carotid artery plaque was present in 10% of the children with FH versus none of the control subjects. Children with plaque had a higher mean cholesterol-years score than children without plaque. These findings suggest that the classic lipid and hemostatic risk factors as well as plasma total homocysteine are associated with markers of early carotid atherosclerosis from the second decade of life. B-mode ultrasonography may prove to be a useful tool in risk stratification of children with FH.

Adolescent↗
PubMed1996

Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives.

We assessed the relative importance of lipid, apo B, lipoprotein(a) [Lp(a)], and total homocysteine (tHcy) levels in children in relation to premature cardiovascular disease in family members. Parents of 381 girls and 375 boys age 8-12 y completed family history questionnaires. Nonfasting serum lipid and lipoproteins and plasma tHcy and cysteine levels were measured in the children. Serum folate and vitamin B12 levels were determined in a random subsample of 23% of the children, who participated in a food frequency interview. Children whose parents reported hypercholesterolemia had higher total and non-HDL cholesterol and apo B levels than the rest, but these levels were not associated with cardiovascular disease. tHcy levels were similar in girls and boys. tHcy was higher in children whose father, grandfather, or uncle died at age < or = 55 y of myocardial infarction or sudden cardiac arrest (n = 42) than in control children [5.92 mumol/L (95% confidence interval [CI] of 5.47-6.36) versus 5.25 mumol/L (95% CI, 5.16-5.34)], also after adjustment for socioeconomic group. Intake and serum levels of vitamin B12 and folate were within recommended or reference ranges. In a stepwise multiple regression analysis, serum folate (negative correlation), plasma creatinine, and sugar intake as percent of dietary energy (positive correlations) were significantly associated with tHcy (multiple r = 0.44, adjusted r2 = 18%; 95% CI, 5-30%). Our data show that a modest elevation in tHcy in children was related to premature cardiovascular death in their male relatives and may partly account for the contribution of family history to risk of cardiovascular disease. tHcy may be modifiable through the diet, even in children with apparently adequate vitamin nutriture.

Age of Onset↗
PubMed1996

Phytosterolaemia in a Norwegian family: diagnosis and characterization of the first Scandinavian case.

Phytosterolaemia (sitosterolaemia) is a very rare inherited sterol storage disease characterized by tendon and tuberous xanthomas and by a predisposition to atherosclerosis. We here describe the first Scandinavian case. The 14-year-old female patient was found to have markedly elevated circulating levels of plant sterols (sitosterol, sitostanol, campesterol, stigmasterol), and the levels of these sterols were 20-50 times higher than in her healthy sister and heterozygous parents. In addition to the usual serum plant sterols we found a new major sterol in the patient tentatively identified as episterol or fecosterol (24-methyliden-cholest-7 (or 8)-en-3 beta-ol). A newly developed method based on the use of deuterium labelled cholesterol and plant sterols was used to measure sterol absorption in the patient and her relatives. Absorption of sitosterol averaged 20% in the patient and ranged from 4 to 8% in the relatives. Absorption of campesterol averaged 31% in the patient and ranged from 15 to 18% in her relatives. Absorption of cholesterol averaged 63% in the patient and ranged from 35 to 45% in the relatives. Cholesterol synthesis appeared to be reduced in the patient and was 46-52% of that of her relatives.

Adolescent↗
PubMed1996

Effect of homocysteine on copper ion-catalyzed, azo compound-initiated, and mononuclear cell-mediated oxidative modification of low density lipoprotein.

Homocysteine is an independent risk factor for cardiovascular diseases. The mechanisms by which elevated plasma concentrations of homocysteine are related to the pathogenesis of atherosclerosis are not fully understood. To examine whether homocysteine is implicated in atherogenesis through the modification of low density lipoprotein (LDL), the effect of homocysteine on the oxidation of LDL was studied by three different oxidation systems. Thus, LDL was subjected to Cu(2+)-catalyzed, azo compound-initiated, and peripheral blood mononuclear cell-mediated oxidative modification. The extent of modification was assessed by measuring the formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances, and the relative electrophoretic mobility. Homocysteine at a normal plasma concentration (6 microM) showed no effect, whereas a concentration corresponding to moderate hyperhomocysteinemia (25 microM) or to concentrations seen in homocystinuria patients (100, 250, and 500 microM) protected LDL from modification of the lipid as well as of the protein moiety. One exception was observed: when the oxidation was initiated by copper ions, homocysteine at concentrations 6 and 25 microM stimulated the lipid peroxidation of LDL to a small, but statistically significant extent. High concentrations of homocysteine showed antioxidative properties as long as the thiol groups were intact, thereby delaying the onset of the oxidation. The 1,1-diphenyl-2-picrylhydracyl radical test demonstrated that homocysteine at concentrations > or = 50 microM possessed marked free radical scavenging capacity. Finally, LDL isolated from two patients with homozygous homocystinuria showed similar extent of Cu(2+)-catalyzed oxidation as LDL from a group of healthy control subjects. Taken together, our data suggest that low concentrations of homocysteine in the presence of copper ions may enhance the lipid peroxidation of LDL, whereas high concentrations of homocysteine may protect LDL against oxidative modification in the lipid as well as in the protein moiety. Thus, homocysteine-induced atherosclerosis may be explained by mechanisms other than oxidative modification of low density lipoprotein.

Adolescent↗
PubMed1995

[Treatment of hyperlipidemia. Guidelines for treatment of hyperlipidemia for secondary prevention of ischemic heart disease].

The new programme and guidelines have been developed for secondary prevention of coronary heart disease in patients with hyperlipaemia. All patients who have suffered myocardial infarction, have angina pectoris, have had a coronary by-pass, or have undergone angioplastic surgery, should have the following serum lipid profile established within one to two months: total cholesterol < 5 mmol/l, ratio total cholesterol/HDL-cholesterol < 4, LDL-cholesterol < 3 mmol/l, triglycerides < 2 mmol/l and HDL-cholesterol > 1 mmol/l in men and 1.3 mmol/l in women.

Coronary Disease↗
PubMed1995

[A rapid analysis of the lipid profile. A comparative study of different analytical methods for determination of blood lipids].

A simple and rapid analytical assay for determination of total cholesterol, HDL-cholesterol and triglycerides in capillary blood samples has been compared with established laboratory methods in a group of 41 test subjects. The new method produces results that are fully acceptable for determination of these three lipid parameters, and agree well with the results obtained in serum by established laboratory methods. The Cholestech LDX analyser may be useful for providing rapid and accurate measurements of the lipid profile, including total cholesterol, triglycerides and HDL-cholesterol. Its small size, the speed of analysis and the fact that it is easy to use make the Cholestech LDX a suitable instrument for use in out-patient clinics and primary care medicine.

Blood Chemical Analysis↗
PubMed1995

[Diagnosis and treatment of familial hypercholesterolemia in children and adolescents].

The identification and management of hyperlipidemias in children are currently limited to persons regarded as being at very high risk, such as those with familial hypercholesterolemia. Universal screening of children is not recommended, but it is important to screen the subset of children and adolescents at highest risk, i.e. those with a family history of premature cardiovascular disease or familial hypercholesterolemia. Treatment of children and adolescents with hypercholesterolemia requires a multidisciplinary approach. Cholesterol-lowering medication may be required in addition to dietary therapy in children with a history of premature coronary heart disease among close relatives.

Adolescent↗
PubMed1995

[Familial hypercholesterolemia in children. A management program. Procedures for diagnosis and treatment in our pediatric departments].

A Norwegian programme for treatment and selective screening of familial hypercholesterolaemia has been developed which takes into account family history and levels of hypercholesterolaemia. The programme includes recommendations on when and whom to screen for familial hypercholesterolaemia. With regard to treatment, special emphasis is placed on diet. The working group suggests that small lipid clinics with a dietitian should be established in some paediatric departments.

Child↗
PubMed1995

Standardization of a flow cytometric method for measurement of low-density lipoprotein receptor activity on blood mononuclear cells.

Flow cytometric methods for measurement of low-density lipoprotein (LDL) receptor activity on peripheral blood mononuclear cells (PBMC) may be used to identify patients with familial hypercholesterolemia (FH). However, cellular LDL receptor activities measured in FH heterozygotes may overlap with those of healthy subjects. Analytical variation is probably responsible for some of this overlap. We have examined several technical details that may affect analytical variation. In each analysis, we included one standard and two control cell preparations. These were cells isolated from three donors and stored in aliquots at -135 degrees C. Use of standard cells reduced between-series analytical variation of the controls by approximately 50%. Preincubation-conditions used to induce the maximum number of receptors, the concentration of fluorochrome 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-perchlorate (DiI)-LDL, labelling time, and conditions during storage of labelled cells before flow cytometry were also examined in order to reduce analytical variation. Having standardized the assay, we found among 20 healthy subjects a median receptor activity of 100% vs. 51% among 26 patients who fulfilled clinical criteria for FH. However, four of the patients showed distinctly normal receptor activities, which may suggest either the presence of some other biochemical defect or that in vivo dysfunctional receptors may be measured as normal in some patients with our assay.

Adult↗
PubMed1995

Changes in plasma apolipoprotein B-containing lipoparticle levels following therapy with fluvastatin and cholestyramine. European Fluvastatin Study Group.

Epidemiologic studies have demonstrated that apolipoprotein (apo) B-containing lipoparticles (LpE:B, LpC-III:B) are associated with the risk of coronary artery disease whereas apo A-1-containing lipoparticles (LpA-I) are protective against coronary artery disease. The effect on lipoparticle levels of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin, in combination with cholestyramine, was assessed in a double-blind randomized study. A total of 144 patients with primary hypercholesterolemia were recruited, who had successfully completed an original study comparing the effects of fluvastatin and cholestyramine on plasma lipoparticle levels. All subjects fulfilled the following inclusion criteria: plasma low density lipoprotein cholesterol (LDL-C) levels > 160 mg/dL, with premature coronary artery disease and 2 associated risk factors; or LDL-C > 190 mg/dL, no coronary artery disease, and triglycerides < 300 mg/dL, after a lipid-lowering diet. Patients were randomized to 1 of 3 combination therapy groups: fluvastatin 20 mg/day plus cholestyramine 4 g/day; fluvastatin 20 mg/day plus cholestyramine 8 g/day; and fluvastatin 20 mg/day plus cholestyramine 16 g/day. The study length was 6 weeks and patients were examined at 3-week intervals. Fluvastatin plus cholestyramine produced a significant (p < 0.001), dose-dependent reduction in levels of cholesterol (range, -29 to -34%), LDL-C (range, -30 to -44%), apo B (range, -23 to -34%), and apo E (range, -33 to -43%). LpE:B levels were also reduced (range, -19 to -26%), but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1995

[Diet and lipid status in pregnant women].

Pregnancy increases the requirement for nutrients and changes the metabolism of lipids and other compounds. We investigated the dietary composition and followed the changes in serum lipids during pregnancy among 20 women age 25-36 years. The women's diet was stable during pregnancy, but the intake of vitamin D, iron and fibre was lower than the national recommendations. Fat provided about 31% of the energy, saturated fat 12%. The total cholesterol concentration rose from 4.4 (95% confidence interval 4.2-4.6) to 7.0 mmol/l (6.5-7.5) (p < 0.0001) without changes in dietary composition. Even in this group of health-conscious, pregnant women the diet did not meet the national dietary recommendations. In addition, the composition of the fat in the diet was unfavourable. Optimal follow-up of pregnant women should include dietary counselling.

Adult↗
PubMed1995

Two novel point mutations in the EGF precursor homology domain of the LDL receptor gene causing familial hypercholesterolemia.

Familial hypercholesterolemia is caused by mutations in the low density lipoprotein (LDL) receptor gene. Analysis of single-strand conformation polymorphisms of exons 10 and 11 of the LDL receptor gene from familial hypercholesterolemia heterozygotes indicated the presence of two mutations, which were characterized by DNA sequencing. One mutation (delta N466) was a 3-bp deletion in exon 10 that deletes Asn in codon 466. The other (intron 11 +1, G-->T) was a splice donor mutation at position +1 of intron 11.

Amino Acid Sequence↗
PubMed1995

Screening for known mutations in the LDL receptor gene causing familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is caused by defective low density lipoprotein (LDL) receptors and is characterized by hypercholesterolemia and premature coronary heart disease. Two strategies can be used to identify the mutation in the LDL receptor gene underlying FH. One strategy is to search for novel mutations by DNA sequencing with or without prior mutation screening. The other strategy is to screen for known mutations. In this study we employed the latter strategy to screen 75 unrelated, Norwegian FH subjects for 38 known mutations. Three of the 38 mutations were detected in our group of FH subjects. Two subjects had FH-Padova, one had FH-Cincinnati-2 and one had FH-Gujerat. When additional unrelated FH heterozygotes were screened for the three mutations, the gene frequencies were 1.3%, 1.0% and 3.0%, respectively. In addition to identifying known mutations we also detected a novel stop codon in codon 541 (S541X). We conclude that screening for known mutations in the LDL receptor gene should be used as a complementary strategy to screening for novel mutations in order to understand the molecular genetics of FH.

Base Sequence↗
PubMed1995

Comparison of the effect of fluvastatin, an hydroxymethyl glutaryl coenzyme A reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by apolipoprotein composition.

In a double-blind, parallel-group, randomized study, the effects of fluvastatin (FLUV) 20 and 40 mg/d on lipoprotein particle levels were compared with those of cholestyramine (CME) 16 g/d. Lipoparticles were defined by apolipoprotein composition as either those containing both apolipoprotein (apo) B and apo E or CIII (lipoprotein [Lp] E-B or Lp CIII-B) or those containing apo AI alone (Lp AI) or in association with apo AII (Lp AI-AII). After an 8-week dietary stabilization period, 100 hypercholesterolemic patients were treated with FLUV 20 mg/d for 6 weeks and 40 mg/d for an additional 6 weeks and were compared with 48 hypercholesterolemic subjects treated with CME 16 g/d. Treatment with FLUV (40 mg/d) or CME (16 g/d) for 12 weeks was associated with a significant reduction in plasma cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in high-density lipoprotein (HDL) cholesterol. However, plasma triglyceride levels decreased following FLUV treatment, whereas they increased with CME. These changes were associated with a significant reduction in the levels of apo B (FLUV, -24%, P < .001; CME, -26%, P < .001), apo E (FLUV, -36%, P < .001; CME, -32%, P < .001), and apo CIII (FLUV, -21%, P < .001; CME, -6%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Efficacy of sequential hormone replacement therapy in the treatment of hypercholesterolaemia among postmenopausal women.

OBJECTIVES: To test the efficacy of hormone replacement therapy (HRT) and dietary therapy, compared to dietary therapy, in lowering LDL cholesterol levels among postmenopausal women. DESIGN: A prospective parallel randomized study of sequential 17 beta-oestradiol and norethisterone acetate or placebo for 48 weeks. SETTING: A University outpatient lipid clinic. SUBJECTS: A total of 76 postmenopausal women, aged 43-60 years, with LDL cholesterol levels > or = 4.2 mmol 1-1, treated with a lipid-lowering diet. MAIN OUTCOME MEASURES: Levels of lipids, lipoproteins, apolipoproteins, fibrinogen and glucose tolerance. RESULTS: Adherence to the diet was similar in both groups. Total and LDL cholesterol levels were reduced by 14% (95% CI, 11-17%) and 19% (95% CI, 14-23%), respectively, in the HRT group vs. 3% (95% CI, 0-7%) and 5% (95% CI, 0-11%) in the diet group. HRT reduced the levels of apolipoprotein B and lipoprotein(a). Levels of HDL cholesterol, HDL2, HDL3, triglycerides, lipoprotein populations and apolipoproteins AI and AII remained unchanged. No adverse effects on glucose tolerance or on fibrinogen levels were observed. The reduction in LDL cholesterol was positively correlated with initial levels of LDL cholesterol and negatively correlated with body mass index. CONCLUSIONS: HRT is effective in reducing elevated LDL cholesterol levels, and should be considered in the treatment of hyperlipidaemic postmenopausal women, in addition to dietary therapy.

Adult↗
PubMed1995

A novel variant of lysosomal acid lipase (Leu336-->Pro) associated with acid lipase deficiency and cholesterol ester storage disease.

Cholesterol ester storage disease (CESD) is associated with premature atherosclerosis, hepatomegaly, elevated LDL cholesterol levels, and in most cases, low HDL cholesterol levels. Previous studies have shown a G-->A mutation at the 3' splice junction of exon 8 (E8SJM) of the gene encoding lysosomal acid lipase (LAL) in two kindreds with CESD. In a Canadian-Norwegian kindred with this disease, we show this mutation in conjunction with an as yet unknown T-->C transition in exon 10 predicting a Leu336-->Pro (L336P) replacement and an A-->C transversion in exon 2 predicting a T-6P replacement in the prepeptide. Identification of the L336P rather than the T-6P replacement as the second defect underlying CESD in our patient is deduced from three lines of evidence. First, the E8SJM allele is located in cis with the mutation predicting the T-6P-encoding allele but in trans with the L336P-encoding allele; second, the L336P but not the T-6P replacement cosegregates with low LAL activity in the family; third, the T-6P replacement was found in 6 of 28 alleles from subjects with normal lysosomal acid lipase activity, suggesting that this variant represents a frequent nonfunctional polymorphism. Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD.

Adult↗
PubMed1995

Determinants of lipid levels among children with heterozygous familial hypercholesterolemia in Norway.

Three founder mutations have been discovered among individuals with familial hypercholesterolemia (FH) in Norway: FHElverum and FHSvartor, predicted to be null alleles, and FHC210G, predicted to disrupt the secondary structure of the ligand-binding domain. To clarify the effect of these and other mutations on lipid levels and parental history of premature cardiovascular disease, we examined 164 boys and girls ages 6 to 16 years with heterozygous FH. Among all children, serum cholesterol levels of the FH parent, percent body fat, pubertal stage, and serum cholesterol levels of the non-FH parent, but not apo E polymorphism, were significant determinants of LDL cholesterol levels in a stepwise multiple regression equation and explained 40% (95% confidence interval [Cl], 25% to 55%) of the variance in LDL cholesterol. Among boys, percent body fat, dietary sucrose, and apo E genotype determined 31% (95% CI, 14% to 49%) of the variance in triglyceride levels; whereas among girls, only percent body fat was associated with triglyceride levels. Percent body fat was not associated with LDL cholesterol or triglyceride levels in the FHC210G group. The children's and FH parents' lipid levels and premature cardiovascular disease among parents were similar among the null-allele and defective-protein groups and in those with an undetected mutation. These data confirm that the phenotypic expression of FH in childhood is influenced by modifiable lifestyle characteristics and by genetic factors other than the underlying mutation and raise the possibility that body fatness may interact with genotype in determining lipid levels.

Adolescent↗