PubMed Health⌕ Search

Biomedical subjects

L Ose

Publications and source records attributed to L Ose.

At least 19 recordsLinked to original sources
PubMed1992

[Lovastatin in primary hypercholesterolemia. A Norwegian multicenter study].

266 patients with primary hypercholesterolaemia were followed for 48 weeks at 27 different centres to evaluate the safety, tolerability and effect on plasma lipids of lovastatin ranging from 20 to 80 mg/day. Mean change from baseline after 12 weeks of treatment with lovastatin was -34% (CI:33-35) for total cholesterol, -42% (CI:40-43) for LDL-cholesterol, +14% (CI:12-17) for HDL-cholesterol and -14% (CI:10-18) for triglycerides. Combination therapy with cholestyramine (8-24 g/day) was optional, and was started in 89 patients from week 13. At week 48 only 25% of all patients had obtained the second objective of the study: a total cholesterol value below 5.2 mmol/l. At the same time 60% of all patients had a total cholesterol below 6.2 mmol/l. Four patients dropped out of the study owing to adverse clinical experience. Only three of these events were probably related to lovastatin. Six patients were withdrawn because of adverse laboratory experiences. One patient showed clinical signs of myositis and increase of CK. In severe primary hypercholesterolaemia combination therapy with lovastatin and a resin such as cholestyramine is required to obtain total cholesterol values below 5.2 mmol/l.

Adult↗
PubMed1992

[Quality assurance in clinical trials. Problems related to patient information].

In connection with a phase-III study of cholesterol lowering agents, a questionnaire survey was carried out on information to patients' during clinical trials. The survey included 124 patients and nine team members with different professional backgrounds. The results show that, in spite of the fact that the patients had received information in accordance with the guidelines, only 47% of them had perceived that conventional treatment would be offered to those who dropped out of the study. A test of the extent of the patients' understanding about the drugs they were taking showed that only 39% knew how the drug acted and the reasons for the chosen dosing schedule. 23% of the patients would like to have received more information, but 9% of these had problems in formulating questions to the health personnel. Anxiety was a problem for 16% of patients, especially in the early phase of the clinical study. Only half of the team-members were aware of this. 45% of the patients felt that they would disappoint the team if they expressed a wish to drop out of the study. Most of the team-members would have tried to motivate the patients to continue to participate in the trial. Based on the results of the survey, we suggest some main elements of standard procedures for providing information to patients in connection with clinical trials.

Adult↗
PubMed1992

[Triglycerides, HDL and coronary disease. Consensus conference: National Institutes of Health 1992].

The article describes the conclusions and recommendations of the panel. A review of the information on HDL-cholesterol and coronary heart disease provides considerable evidence of a causal relationship. In the case of serum triglycerides, the data are ambiguous; although strong associations are found in some studies, evidence of a causal relation is still incomplete. Seen in relation to the latest Norwegian programme for treatment of hypercholesterolemia in adults, greater emphasis should be placed on measuring HDL-cholesterol. A complete initial lipid profile should also include determination of serum triglycerides. When taking these factors into consideration, the present Norwegian recommendations seem to be appropriate for evaluating and treating hyperlipidemia.

Cholesterol, HDL↗
PubMed1992

[Familial hypercholesterolemia--intensive diet therapy combined with drug therapy].

The aim of the investigation was twofold: to study the effect of lovastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alone and in combination with other lipid lowering drugs in an open 48 week single centre study, and to study if lipid lowering drugs influence adherence to diet in adult patients with familial hypercholesterolemia. Lovastatin monotherapy (80 mg daily) for 12 weeks reduced serum cholesterol, LDL-cholesterol and triglycerides levels by 36%, 44% and 24% respectively. HDL-cholesterol level was increased by 12%. The addition of 16 g cholestyramine daily further increased the reduction of total cholesterol and LDL-cholesterol levels by 17% and 24% respectively. Addition of 1 g probucol daily decreased total cholesterol, LDL-cholesterol and HDL-cholesterol levels by 9%, 5% and 27% respectively. Addition of omega-3-fatty acids (3.6 g daily) reduced total cholesterol, LDL-cholesterol and triglycerides levels by 10%, 12% and 20% respectively. Administration of potent lipid lowering agents did not influence adherence to a diet with a mean daily fat energy of 21% (CI: 20-22), cholesterol of 177 mg (CI: 157-196) and P/S ratio of 0.75 (CI: 0.66-0.84). A significant increase in liver enzymes was recorded in only one patient. One patient was withdrawn from the study because of myositis.

Adolescent↗
PubMed1992

Short-term effects of treatment with simvastatin on testicular function in patients with heterozygous familial hypercholesterolaemia.

The effects of simvastatin 40 mg per day for 14 weeks on the pituitary-testis axis of 19 men with familial hypercholesterolaemia have been examined in a single-blind study. Simvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol and triglycerides by 45% and 30%, respectively, and significantly increased high density lipoprotein (HDL) cholesterol by 15%. The alterations, which were stable 4 weeks after the start of treatment, were not associated with any significant change in sperm quality, the seminal plasma concentrations of various sex gland products (prostate-specific acid phosphatase, polyamines, citrate, fructose, alpha-glucosidase), or the serum concentrations of cortisol, testosterone, LH, FSH, or prolactin. It is concluded that a short-term reduction in circulating LDL-cholesterol has no marked effect on testicular function or sperm quality.

Adult↗
PubMed1992

Uptake of chylomicron remnant retinyl esters in human leukocytes in vivo.

Retinoids have been successfully used in the treatment of some forms of leukaemia, suggesting that such cells have an efficient uptake mechanism for circulating retinoids. Therefore, we have studied the uptake of lipoprotein-associated retinyl esters in human leukocytes in vivo. After an oral load of 100 mumol retinyl palmitate (30,000 retinol equivalents) per square meter given to healthy adults, the concentration of retinoids in circulating leukocytes was determined. A peak was measured after 5 h, which coincided with a peak of retinyl esters in plasma. To test whether low-density lipoprotein receptors are necessary for the postprandial uptake of retinoids, we studied retinoid uptake in leukocytes from two patients homozygous for familial hypercholesterolaemia. After an oral load of retinoids we found that leukocytes from these patients took up at least as much retinoid as leukocytes in normal individuals, suggesting that uptake of chylomicron remnant retinyl esters may proceed independent of the low-density lipoprotein receptor. The expression of mRNA for the low density lipoprotein receptor-related protein, which is a putative chylomicron remnant receptor, was similar in leukocytes from a patient homozygous for familial hypercholesterolaemia and normal individuals. Six hours after vitamin A administration, recovery of unesterified retinol was 71% in normal leukocytes, however, only 9% unesterified retinol was recovered in leukocytes from the two patients with familial hypercholesterolaemia. Thus, the apparent rate of retinyl ester hydrolysis was markedly reduced in leukocytes from these patients, indicating different intracellular traffic of chylomicron remnants in normal individuals and patients homozygous for familial hypercholesterolaemia.

Biological Transport, Active↗
PubMed1992

A new polymorphism in exon 11 of the LDL receptor gene in healthy people and in familial hypercholesterolemia subjects.

We have screened exon 11 of the low density lipoprotein receptor (LDLR) gene from familial hypercholesterolemia (FH) heterozygotes for point mutations by using analysis of single strand conformation polymorphisms (SSCP). A variant pattern was observed in three out of 39 subjects. By DNA sequencing, this variant pattern was found to be due to a C-->T transition at nucleotide 1617 that affects the third base of codon 518. A PCR method was developed to screen FH heterozygotes and normal subjects for this mutation. The gene frequencies in FH heterozygotes and normal subjects were 4% and 4.5%, respectively. Thus, the mutation cannot be in linkage disequilibrium with a mutation that causes FH. Rather, the mutation may be a useful genetic marker at the LDLR locus. Haplotype analysis at the LDLR locus in two FH families where the proband possessed the mutation revealed that the mutation was on two different haplotypes. This finding is consistent with the mutation occurring at a mutational hot spot.

Base Sequence↗
PubMed1992

A 9.6 kilobase deletion in the low density lipoprotein receptor gene in Norwegian familial hypercholesterolemia subjects.

Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH-Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries.

Adolescent↗
PubMed1991

[Treatment of hypercholesterolemia in adults. A treatment program 1991].

A Norwegian programme for treatment of hypercholesterolemia in adults was published in 1988. In 1990 the Norwegian Medical Association appointed a group to modify this programme in the light of current knowledge, and taking into consideration the recommendations of the Consensus Conference on Cholesterol of October 1989. The present article presents this modified programme. When evaluating the risk of developing coronary heart disease a combined risk score should be calculated which also takes into account important risk factors other than cholesterol, such as family history, sex, age, smoking, hypertension, presence of diabetes etc. For those considered to be at high risk of developing coronary heart disease, the programme gives guidelines on how to intervene. With regard to treatment, special emphasis is placed on changing the diet.

Adult↗
PubMed1991

Dietary n-6 fatty acids inhibit the incorporation of dietary n-3 fatty acids in thrombocyte and serum phospholipids in humans: a controlled dietetic study.

The effect of a high dietary intake of n-6 fatty acids (36 g daily) vs a low intake (4-6 g daily) on the incorporation of fatty acids from a dietary supplementation of n-3 fatty acids (6 g daily) was studied for 8 weeks in 15 healthy, normolipaemic volunteers. The importance of a high (43.6) vs a low (20.6) energy percentage from fat was also investigated in the participants on a low n-6 intake. Fatty acid analyses of serum and thrombocyte phospholipids showed a marked increase in docosahexaenoic acid (22:6 (n-3), DHA) and especially eicosapentaenoic acid (20:5 (n-3), EPA) in both the high and low n-6 groups after 14 days, but the changes were significantly greater in the low n-6 diet groups. Changes of the ratio between EPA and arachidonic acid (20:4 (n-6), AA) in phospholipids followed an identical pattern in serum and thrombocytes. This indicates that thrombocytes are influenced by the fatty acid composition in serum. The results showed that incorporation of n-3 fatty acids in phospholipids was reduced by a high intake of dietary n-6 fatty acids in the cells and lipid fractions studied. The observed effect of dietary n-6 fatty acids was independent of the energy percentage provided by dietary fat. In order to obtain an optimal effect of n-3 supplementation, the intake of linoleic acid has to be considered and kept at a low level. The serum content of cholesterol was unaffected, but the concentration of triacylglycerol was reduced during the supplementation period.

Adult↗
PubMed1979

Uptake and degradation of 125I-labelled high density lipoproteins in rat liver cells in vivo and in vitro.

1. The uptake of 125I-labelled high density lipoproteins (HDL) in various organs of the rat was determined after an intravenous injection. The uptake of 125I-labelled polyvinylpyrrolidone in the same organs was determined in order to assess uptake by fluid endocytosis. The uptake/organ was highest for the liver. The adrenals showed the highest uptake/unit weight of the organs studied. The liver, the kidneys and the spleen showed comparable values for uptake/g of tissue. The uptake of 125I-labelled HDL exceeded by far that of 125I-labelled polyvinylpyrrolidone in the liver, the kidneys, the spleen and the adrenals, indicating that the uptake of 125I-labelled HDL was mediated by adsorptive endocytosis. 2. The in vivo uptake of 125I-labelled HDL was determined in purified hepatocytes and non-parenchymal cells prepared by collagenase perfusion of livers from animals after intravenous injections of 125I-labelled HDL. When expressed per cell, the hepatocytes and the non-parenchymal liver cells took up about the same amount of 125I-labelled HDL. 3. The in vitro uptake and degradation of 125I-labelled HDL in isolated rat hepatocytes was studied. The uptake at increasing concentrations of 125I-labelled HDL was saturable indicating uptake mediated through binding sites. 125I-labelled HDL were easily degraded by contaminating proteases from the perfusate. 4. Subcellular fractionation by isopycnic centrifugation indicated that the accumulation of 125I-labelled HDL did not take place in the lysosomes, but rather on the plasma membrane and possibly in the endosomes (phagosomes). 5. 125I-labelled HDL were internalized into the cells and degraded in the lysosomes. Leupetin and chloroquine, inhibitors of the lysosomal function effectively inhibited the formation of 125I-labelled acid-soluble radioactivity by the cells. Chloroquine, but not the protease inhibitor leupeptin, reduced the hydrolysis of the cholesteryl ester moiety of HDL.

Animals↗
PubMed1977

A heritable syndrome of craniosynostosis, short thin hair, dental abnormalities, and short limbs: cranioectodermal dysplasia.

Five children are reported with dolichocephaly (with sagittal suture synostosis in three), sparse, slow-growing, fine hair, epicanthal folds, hypodontia and/or microdontia, short span, brachydactyly and brachypodia, and narrow thoraces. Radiologic abnormalities were noted chiefly in the skull, chest, and limbs. Intelligence was normal. The pattern of inheritance is compatible with an autosomal recessive trait.

Abnormalities, Multiple↗
PubMed1977

Prophylactiv use of propranolol in the Marfan syndrome to prevent aortic dissection.

Twenty-five patients, 16 men and 9 women, 5-59 years of age with the Marfan syndrome and cardiac complications were started on propranolol over a 6-year period. Propranolol was used as a beta-adrenergic blocking agent to reduce myocardial contractility in an attempt thereby to stay the progression of aortic dilatation and to prevent acute dissection of the aorta. The indications for prophylactic treatment were aortic dilatation, with aortic regurgitation in most cases. It was intended to keep the pulse rate below 70 at all times or below 60 at rest. Propranolol given in daily doses of 120-160 mg caused no side effects. The mean observation time for propranolol treatment in the 25 patients was 3.0 +/- 1.8 years ranging from 1-7 years. In spite of treatment, 5 patients (1 female and 4 males) experienced acute aortic dissection of rupture with fatal outcome. This occurred in 2 patients with the asthenic type, in 2 patients with the nonasthenic type, and in 1 patient with the marfanoid hypermobility syndrome. Serial echocardiograms showed that other patients on propranolol developed increasing dilatation of the aortic root. These observations indicate that propranolol does not necessarily protect against aortic dissection nor stop the progression of the aortic dilatation when cystic medial necrosis of the aorta is already present.

Adolescent↗
PubMed1976

Serum beta-lipoprotein subfractions in polyacrylamide gel electrophoresis associated with coronary heart disease.

Subfractions of beta-lipoprotein occurred more frequently in serum from patients with coronary heart disease than in serum from patients with no sign of coronary heart disease. Two beta-lipoprotein subfractions were observed in polyacrylamide gel electrophoresis. The sera containing a beta-lipoprotein subfraction with a position close to the beta-lipoprotein band showed Lp(a) antigenic properties. Triglycerides were raised in the sera with beta-lipoprotein subfractions. The cholesterol level was significantly higher in the coronary heart disease group but was not correlated to the presence of the beta-lipoprotein subfraction. The beta-lipoprotein subfraction may possibly represent an additional risk factor in the genesis of coronary heart disease, even in the absence of other hyperlipoproteinemias.

Adolescent↗
PubMed1976

Neonatal osteomyelitis caused by group B streptococci.

A 3-week-old infant with a group B streptococcal osteomyelitis is described. On admission swelling and fluctuation were combined with local erythema in the right ankle joint region. Group B streptococci, type Ib, were isolated both from blood and from the local focus in the ankle. The diagnosis was further confirmed by X-ray examination showing a lytic lesion in the talus. The child was successfully treated with penicillin, initially in combination with kanamycin.

Ankle Joint↗