Search PubMedSearch

Biomedical subjects

L Ose

Publications and source records attributed to L Ose.

At least 19 recordsLinked to original sources

[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 Six patients were withdrawn because of adverse laboratory experiences.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

[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

[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

[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

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

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

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

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

[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

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

[Identification of syndromes using a combined computer and video program].

The use of the database POSSUM (Pictures of Standard Syndromes and Undiagnosed Malformations) was evaluated over a period of 1 1/2 years in 49 children with multiple congenital anomalies. A specific diagnosis was obtained in 23 cases and POSSUM contributed significantly to a diagnosis in 13 cases. We conclude that a computerized approach is valuable in the evaluation of dysmorphic syndromes.

Abnormalities, Multiple

[Are prosecuted parents allowed the benefit of the doubt in cases of child abuse?].

The justified campaign against child abuse has unfortunately had a side effect. It has ruined the lives of some innocent parents of children with undiagnosed osteogenesis imperfecta. For 15 years, Colin Paterson and co-workers have studied a large number of patients with type IV of osteogenesis imperfecta, and have found that more than 50 per cent of them have normal radiographs of the bones at the time of the first fracture. Paterson and co-workers have also found that fractures of the ribs and skull are by no means uncommon in osteogenesis imperfecta type IV. These important observations should help, in the future, to prevent prosecution of innocent parents of children with osteogenesis imperfecta type IV, provided that the observations are not overlooked by pediatricians.

Child

[Drug therapy of hypercholesterolemia. Treatment of hypercholesterolemia in adults--a Norwegian therapeutic program 1988].

There are indications that treatment of hypercholesterolemia by means of drugs reduce risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinemia, and should be regarded as an adjunct to appropriate dietary therapy. Drug therapy should be strongly considered in patients with total cholesterol above 8-9 mmol/l on diet therapy only. Drug therapy should be considered at even lower concentrations of cholesterol when coronary heart disease is present and in familial forms of hyperlipidemia when increased risk of atherosclerosis has been documented. In patients with increased plasma concentrations of total cholesterol the drugs of choice are agents which enhance the rate of LDL catabolism (resins) or reduce the rate of LDL synthesis (nicotinic acid). Fibrates should be used when triglycerides and cholesterol are both increased. HMG CoA reductase inhibitors offer considerable promise in the therapy of patients with primary hypercholesterolemia. Probucol may be used in combination with other drugs, particularly when xanthomas are present in patients with familial hypercholesterolemia.

Humans

Dietary n-3 fatty acids and children with hyperlipidaemia.

A review of the literature shows that no studies on children with primary genetic lipid disorders have been published. Case reports are presented indicating that hyperlipidaemias presenting in children--both familial hypercholestrolaemia and disorders with secondary hyperlipidaemia (triglycerides) may benefit of the intake of n-3 fatty acids.

Adolescent

Computed tomography of a tuberculous paravertebral abscess.

Spinal tuberculosis with extensive abscess formation in a 5-year-old girl of Asian origin is reported. The role of CT in the preoperative visualisation of the different compartments of the lesion, including extra- and intraspinal extension, is discussed. At present, CT seems to be the method of choice in the preoperative study of infectious spinal and paraspinal processes.

Abscess