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Biomedical subjects

E Lund

Publications and source records attributed to E Lund.

At least 199 records · Page 11Linked to original sources
PubMed1991

Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia.

Patients with heterozygous familial hypercholesterolemia (n = 12) were treated either with pravastatin, a specific inhibitor of HMG-CoA reductase, or cholestyramine, followed by a period of combined treatment with both drugs. Initially, these patients had increased serum levels of low density lipoprotein (LDL) cholesterol (8.77 +/- 0.48 mmol/l; SEM), lathosterol (5.32 +/- 0.60 mg/l), and ubiquinone (0.76 +/- 0.09 mg/l), while the serum dolichol concentration was in the normal range. Cholestyramine treatment (n = 6) decreased the levels of LDL cholesterol (-32%) and increased lathosterol (+125%), but did not change dolichol or ubiquinone levels in a significant manner. Pravastatin treatment (n = 6) decreased LDL cholesterol (-27%), lathosterol (-46%), and ubiquinone (-29%). In this case, the amount of dolichol in serum also showed a small but statistically insignificant decrease (-16%) after 12 weeks of treatment. Combined treatment with cholestyramine and pravastatin (n = 6) resulted in changes that were similar to, but less pronounced than, those observed during pravastatin treatment alone. In no case was the ratio between ubiquinone and LDL cholesterol reduced. Possible effects on hepatic cholesterol, ubiquinone, and dolichol concentrations were studied in untreated (n = 2), cholestyramine-treated (n = 2), and pravastatin-treated (n = 4) gallstone patients and no consistent changes could be observed. The results indicate that treatment with pravastatin in familial hypercholesterolemia decreases serum ubiquinone levels in proportion to the reduction in LDL cholesterol.

Adult↗
PubMed1991

Mechanism of intestinal 7 alpha-dehydroxylation of cholic acid: evidence that allo-deoxycholic acid is an inducible side-product.

We previously reported that the 7 alpha-dehydroxylation of cholic acid appears to be carried out by a multi-step pathway in intestinal anaerobic bacteria both in vitro and in vivo. The pathway is hypothesized to involve an initial oxidation of the 3 alpha-hydroxy group and the introduction of a double bond at C4-C5 generating a 3-oxo-4-cholenoic bile acid intermediate. The loss of water generates a 3-oxo-4,6-choldienoic bile acid which is reduced (three steps) yielding deoxycholic acid. We synthesized, in radiolabel, the following putative bile acid intermediates of this pathway 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acid, 7 alpha,12 alpha-dihydroxy-3-oxo-5 beta-cholanoic acid, 12 alpha-dihydroxy-3-oxo-4,6-choldienoic acid, and 12 alpha-hydroxy-3-oxo-4-cholenoic acid and showed that they could be converted to 3 alpha,12 alpha-dihydroxy-5 beta-cholanoic acid (deoxycholic acid) by whole cells or cell extracts of Eubacterium sp. VPI 12708. During studies of this pathway, we discovered the accumulation of two unidentified bile acid intermediates formed from cholic acid. These bile acids were purified by thin-layer chromatography and identified by gas-liquid chromatography-mass spectrometry as 12 alpha-hydroxy-3-oxo-5 alpha-cholanoic acid and 3 alpha,12 alpha-dihydroxy-5 alpha-cholanoic (allo-deoxycholic acid). Allo-deoxycholic acid was formed only in cell extracts prepared from bacteria induced by cholic acid, suggesting that their formation may be a branch of the cholic acid 7 alpha-dehydroxylation pathway in this bacterium.

Bile Acids and Salts↗
PubMed1990

Number of children and death from hormone-dependent cancers.

The association between number of children of current marriage reported by 431,604 women aged 45-74 years at the Norwegian Census in 1970 and mortality, at follow-up through 1985, from hormone-dependent cancers, i.e., cancers of breast, corpus uteri and ovary combined, has been investigated. The reduction in age-adjusted mortality was 9.6% (95% confidence interval; 8.3-10.9%) for each child with no deviation from linearity. Women with 8-11 children had a relative risk of 0.34 (0.25-0.47) compared to nullipara. Adjustment for age at first birth slightly changed the effect of number of children on mortality to 9.3% per child. The reduction in mortality per child was for cancer of the breast 7.2%, corpus uteri 12.2% and ovary 12.7%. Our findings indicate that having few children is a major risk factor for death from the 3 hormone-dependent cancers combined.

Age Factors↗
PubMed1990

Age at first birth, parity and risk of breast cancer: a meta-analysis of 8 studies from the Nordic countries.

Several large epidemiological studies in the Nordic countries have failed to confirm an association between age at first birth and breast cancer independent of parity. To assess whether lack of power or heterogeneity between the countries could explain this, a meta-analysis was performed of 8 population-based studies (3 cohort and 5 case-control) of breast cancer and reproductive variables in the Nordic countries, including a total of 5,568 cases. It confirmed that low parity and late age at first birth are significant and independent determinants of breast-cancer risk. Nulliparity was associated with a 30% increase in risk compared with parous women, and for every 2 births, the risk was reduced by about 16%. There was a significant trend of increasing risk with increasing age at first birth, women giving first birth after the age of 35 years having a 40% increased risk compared to those with a first birth before the age of 20 years. Tests for heterogeneity between studies were not significant for any of the examined variables. In the absence of bias, this suggests that several individual Nordic studies may have had too little power to detect the weak effect of age at first birth observed in the meta-analysis.

Breast Neoplasms↗
PubMed1990

Formation of C21 bile acids from plant sterols in the rat.

Formation of bile acids from sitosterol in bile-fistulated female Wistar rats was studied with use of 4-14C-labeled sitosterol and sitosterol labeled with 3H in specific positions. The major part (about 75%) of the 14C radioactivity recovered as bile acids in bile after intravenous administration of [4-14C]sitosterol was found to be considerably more polar than cholic acid, and only trace amounts of radioactivity had chromatographic properties similar to those of cholic acid and chenodeoxycholic acid. It was shown that polar metabolites were formed by intermediate oxidation of the 3 beta-hydroxyl group (loss of 3H from 3 alpha-3H-labeled sitosterol) and that the most polar fraction did not contain a hydroxyl group at C7 (retention of 3H in 7 alpha,7 beta-3H2-labeled sitosterol). Furthermore, the polar metabolites had lost at least the terminal 6 or 7 carbon atoms of the side chain (loss of 3H from 22,23-3H2- and 24,28-3H2-labeled sitosterol). Experiments with 3H-labeled 7 alpha-hydroxysitosterol and 4-14C-labeled 26-hydroxysitosterol showed that none of these compounds was an efficient precursor to the polar metabolites. By analysis of purified most polar products of [4-14C] sitosterol by radio-gas chromatography and the same products of 7 alpha,7 beta-[2H2]sitosterol by combined gas chromatography-mass spectrometry, two major metabolites could be identified as C21 bile acids. One metabolite had three hydroxyl groups (3 alpha, 15, and unknown), and one had two hydroxyl groups (3 alpha, 15) and one keto group. Considerably less C21 bile acids were formed from [4-14C]sitosterol in male than in female Wistar rats. The C21 bile acids formed in male rats did not contain a 15-hydroxyl group. Conversion of a [4-14C]sitosterol into C21 bile acids did also occur in adrenalectomized and ovariectomized rats, indicating that endocrine tissues are not involved. Experiments with isolated perfused liver gave direct evidence that the overall conversion of sitosterol into C21 bile acids occurs in this organ. Intravenously injected 7 alpha,7 beta-3H-labeled campesterol gave a product pattern identical to that of 4-14C-labeled sitosterol. Possible mechanisms for hepatic conversion of sitosterol and campesterol into C21 bile acids are discussed.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

[Disability pensions in Norway 1977-87].

Trends in disability pensions in Norway were studied during the period 1977-87 on the basis of the official statistics. During this period, men and women alike experienced increased risk of disability. The risk was highest for women aged 30-39 years, 103%. In 1986/87 the cumulative incidence for a disability pension up to age 67 was 59% for women and 60% for men. The increase was strongest for musculo-skeletal disorders, followed by psychiatric disorders and injuries.

Adult↗
PubMed1990

Anthropometric measures and breast cancer in young women.

Body height and weight in relation to breast cancer in women younger than 45 years were investigated in a case-control study in Sweden and Norway. The study included 317 Swedish and 105 Norwegian cases diagnosed in 1984-85 with 317 Swedish and 210 Norwegian age-matched population controls. Neither height nor body size, measured as body mass index, was associated with breast cancer. Change in body mass from the age of 20 years to 18 months before the time of diagnosis (cases) or interview (controls) had no effect on breast cancer risk. The study provides no evidence that anthropometric measures are risk factors for breast cancer in young women, indicating that the postulated inverse relationship between body mass index and pre-menopausal breast cancer could be limited to peri-menopausal women.

Adenocarcinoma↗
PubMed1990

Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer.

One-hundred and seventy patients with estrogen receptor positive (greater than or equal to 10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg x 1 daily (TAM), or with TAM 30 mg x 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg x 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Meckel's diverticula: angiographic diagnosis in patients with non-acute hemorrhage and negative scintigraphy.

Meckel's diverticula were detected by mesenteric angiography in 2 patients with unexplained gastrointestinal bleeding following negative barium, endoscopic, and scintigraphic evaluation. Abnormal, irregular, arterial branches supplied by an elongated, nonbranching ileal artery and an associated capillary stain were present in each case. Since neither diverticulum was bleeding at the time of angiography, focal contrast extravasation was not present. Superselective magnification angiography, evacuation of contrast from the urinary bladder, and careful patient positioning significantly improved the visibility of these lesions. Visceral angiography performed with meticulous attention to technical detail can be diagnostic of Meckel's diverticulum, even in the absence of acute hemorrhage.

Adolescent↗
PubMed1990

Use of oral contraceptives in relation to dietary habits and alcohol consumption.

The relationship between oral contraceptive (OC) use, dietary habits and alcohol consumption in young women was studied in Tromsø, Norway. A total of 5,800 women aged 20-39 years answered a questionnaire in 1986/1987. Women with long-term duration of OC use reported more frequent intake of meat for dinner, preferred low-fat milk and drank less coffee. For other food items such as intake of fats, fish, fruit and vegetables, no differences were found. Strong associations were found for alcohol consumption, with increasing frequency of use among long-term users of OCs. These results are discussed in relation to the possible association between OC use and breast cancer in young women.

Adult↗
PubMed1990

Weekly Adriamycin vs. 4-epidoxorubicin every second week in advanced breast cancer. A randomized trial. The Norwegian Breast Cancer Group.

One hundred and sixty-six patients with advanced breast cancer previously not treated with chemotherapy for metastatic disease were randomly allocated to 20 mg Adriamycin i.v. weekly (Awkly) as bolus injection or 50 mg 4-epidoxorubicin biweekly over a 3-h infusion time (EPIbiwkly). Of the 149 patients evaluable for response, the response rate was 36% for Awkly vs. 22% for EPIbiwkly (P = 0.10). There was no difference in response duration or survival. The main difference between the two regimens was in toxicity. Seventy per cent of Awkly patients virtually had no side-effects vs. 15% in the EPIbiwkly group. Significant differences in favour of Awkly were observed both for nausea/vomiting and alopecia.

Breast Neoplasms↗
PubMed1990

Absence of association between reproductive variables and the risk of breast cancer in young women in Sweden and Norway.

A population-based case-control study was conducted in Sweden and Norway to analyse possible associations between breast cancer occurring before the age of 45 and several different characteristics of the women's reproductive life. A total of 422 (89.2%) of all eligible patients, and 527 (80.6%) of all eligible controls were interviewed. In univariate analyses, different characteristics of child-bearing (parity, age at first birth, years between last birth and diagnosis, duration of breast-feeding, and number of induced and spontaneous abortions), measures of the fertile or ovulating period (age at menarche, years between menarche and first pregnancy, and estimates of the menstruation span) and symptoms of anovulatory cycles or infertility were all seemingly unrelated to, or at most weakly associated with breast cancer. Adjustment for possible confounding factors in multivariate analyses resulted in largely unaltered risk estimates with odds ratios close to unity and without any significant trends when the exposure variables were studied in categorised or in continuous form. We conclude that reproductive factors did not explain the occurrence of breast cancer before the age of 45 in this population.

Abortion, Spontaneous↗
PubMed1990

Long-term somatic side-effects and morbidity in testicular cancer patients.

In order to evaluate long-term somatic morbidity after treatment for testicular cancer 149 patients with NED greater than or equal to 3 years answered a questionnaire. The patients had been treated with surgery only (32 patients, radiotherapy only (39 patients), cisplatin-based chemotherapy plus surgery (46 patients) or chemotherapy plus radiotherapy with or without surgery (32 patients). Raynaud-like phenomena were the most frequent side-effect occurring significantly more often after cisplatin-based chemotherapy than after surgery or radiotherapy (33/72 patients versus 5/68 patients). Peripheral sensory 'neuropathy' was reported by 18% of all the patients. Seventeen per cent and 11% complained of pulmonary symptoms and auditory symptoms, respectively. Gastrointestinal side-effects were more frequent after any type of cytotoxic therapy than after surgery only (34/47 patients versus 5/22 patients). Twenty-six patients had fathered children after treatment. About 80% of the patients were in full time wage-earning activity when they answered the questionnaire. In conclusion, 3-7 years after treatment for testicular cancer, 30-50% of the patients had minor somatic complaints whereas serious side-effects seldom occurred.

Adolescent↗
PubMed1990

Quality of life following a false positive mammogram.

To assess how women regard having had a false positive mammogram screening exam, and the influence that this had on their quality of life, 126 such women were interviewed. Their responses were compared to those of 152 women randomly selected among screenees with a negative exam. Eighteen months after the screening the reported prevalence of anxiety about breast cancer was 29% among women with a false positive and 13% among women with a negative screening mammogram (P = 0.001). Of 30 women biopsied, 8 (27%) had pain in the breast and 10 (33%) had reduced sexual sensitivity. A false positive mammogram was described by 7 (5%) of the women as the worst thing they ever had experienced. However, most women with a false positive result regarded this experience, in retrospect, as but one of many minor stressful experiences creating a temporary decrease in quality of life. They report the same quality of life today as women with negative screening results and 98% would attend another screening. Even so, false positive results are a matter of concern, and efforts should be made to minimise this cost whenever a screening programme is conducted.

Anxiety↗
PubMed1990

Determination of serum levels of unesterified lanosterol by isotope dilution-mass spectrometry.

The synthesis of 2H3-labelled lanosterol is described. This compound was used for assay of unesterified lanosterol in serum by isotope dilution-mass spectrometry. After addition of a fixed amount of internal standard (150 ng) to a fixed amount of serum (250 microliters) the steroids were extracted with chloroform and subjected to Lipidex 5000 chromatography. The fraction containing lanosterol was eluted with methanol. This fraction was converted into trimethylsilyl derivative and subjected to mass spectrometric analysis with selected monitoring of the ions at m/z 498 (molecular ion of unlabelled lanosterol) and m/z 501 (molecular ion of 2H3-labelled lanosterol). A standard curve was used for quantification of lanosterol in serum. Under the conditions employed the coefficient of variation was less than 4%. In a recovery experiment the maximal difference between expected and found value was about 5%. Sera from 10 healthy subjects were found to have a mean concentration of lanosterol of 225 ng/ml with a SD of 63 ng/ml. Using a less accurate method for analysis of lanosterol we have shown previously that there is a high correlation between the hepatic HMG CoA reductase and the absolute and relative concentration of lanosterol in serum (concentration of lanosterol relative to cholesterol). When using the same (old) sera as in the previous investigation this could not be confirmed, most probably because of the degradation of lanosterol as a consequence of prolonged storage and/or freezing and thawing. It appears that serum lanosterol must be analysed as soon as possible after the collection of the blood sample in order to obtain accurate results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Childbearing in marriage and mortality from breast cancer in Norway.

The relationship between childbearing and mortality from breast cancer has been studied in a cohort of 822,593 currently married Norwegian women with information on parity from the Census in 1970 and follow-up till 1985. All age groups of parous women showed significant trends of decreasing mortality rates with increasing parity. Nulliparous women had the same mortality rates as uniparous women in all age groups. In a stratified analysis, for age group 45-74 years, the relative risk for uniparous women was between 3.8 and 4.5 dependent on age at first birth compared to women with 8-9 children, age at first birth before the age of 25 and last birth after the age of 30 years. In a multivariate analysis age and parity were stronger risk factors than age at first birth, while age at last birth was nonsignificant. Among women 45-74 years the population attributable risk of breast cancer mortality due to childbearing was 72%, using women with 8-9 children as the reference group. The use of different definitions of reference group for parity is discussed.

Adult↗