Biomedical subjects

A Andersen

Publications and source records attributed to A Andersen.

At least 73 records · Page 4Linked to original sources

PubMed1994

Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat.

To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 microM, and concentrations of 7-OH-MTX declined triphasically, showing a t1/2 alpha value of 2.45 min, a t1/2 beta value of 30.5 min, and a terminal half-life (t1/2 gamma) of 240 min. The total clearance value was 14.5 ml min-1 kg, and the postdistributional volume of distribution (V beta) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.

Animals↗

PubMed1994

Evaluation of methotrexate tissue exposure by in situ microdialysis in a rat model.

The feasibility of using a microdialysis technique to obtain pharmacokinetic data on tissue exposure to methotrexate (MTX) was investigated. Microdialysis probes were implanted in the jugular vein, femoral muscle, and liver of anesthetized male Wistar rats. MTX (100 mg/kg) was given as a bolus injection through an indwelling venous catheter, and blood samples were obtained through a second venous access and by microdialysis for a total of 6 h. Heparinized plasma, ultrafiltered plasma, and microdialysis effluent from tissue and venous probes were analyzed by high-performance liquid chromatography. Centrifugal ultrafiltration of rat plasma spiked in vitro with MTX (1-100 microM) revealed a mean binding to plasma proteins of 21%. In vitro microdialysis of this spiked plasma resulted in 23% relative recovery of the unbound fraction. In rats receiving MTX, plasma protein binding was 23% and the relative drug recovery as assessed with venous microdialysis probes was 18%. Plotting of unbound (i.e., ultrafiltrate) MTX concentrations in the blood against venous microdialysis perfusate values in the blood gave a good linear correlation with a coefficient of correlation (r2) of 0.98. There was also a linear correlation between the total MTX concentrations in venous blood and the drug levels in microdialysis samples from muscle and liver (r2 = 0.93 and 0.74, respectively). Area under the curve estimations were consistent with an MTX exposure of 30% and 46% for the muscle and liver as compared with the circulation. The present study demonstrates that the microdialysis technique can provide reproducible data on tissue exposure to MTX in an animal model and indicates that the methodology is adaptable to clinical settings.

Animals↗

PubMed1994

Cancer incidence among waitresses in Norway.

Previous studies have found high risk of cancers of the upper aerogastric tract, liver, and lung among waiters. Since approximately 75 percent of those working in the restaurant business in Norway are women, we have analyzed cancer incidence in a cohort of waitresses, to determine whether they have the same high cancer-risk as their male colleagues. The cohort consisted of 5,314 waitresses organized in the Restaurant Workers' Union between 1932 and 1978. The follow-up period was from 1959 to 1991. The standardized incidence ratio (SIR) for all causes of cancer was 1.0 (95 percent confidence interval [CI] = 0.9-1.1), based on 430 observed cases. Cancers of the tongue, mouth, pharynx, larynx, esophagus, and liver were grouped together as alcohol-associated cancers. SIR for these cancers combined was 1.1 (CI = 0.5-2.2). For lung cancer, SIR was 2.3 (CI = 1.6-3.1). Cervical cancer was also more frequent than expected, and breast cancer less frequent than expected. The larger excess of lung cancer and cervical cancer appeared in the sub-cohort working in restaurants with a license to serve alcohol. No excess risk of alcohol-associated cancers could be detected in this cohort of Norwegian waitresses. A longer follow-up period will be necessary to evaluate possible consequences of an increased alcohol consumption among younger waitresses. Waitresses in Norway are, like their male colleagues, at high risk for lung cancer.

Adult↗

PubMed1994

Homogeneity of the major outer membrane protein gene of feline Chlamydia psittaci.

Thirteen feline Chlamydia psittaci strains isolated in various countries over a 50-year period were examined by restriction mapping of the major outer membrane protein (MOMP) gene obtained after DNA amplification by the polymerase chain reaction and compared with avian, ovine and guinea pig inclusion conjunctivitis (GPIC) C psittaci strains. All the feline isolates produced a unique AluI pattern distinct from the other C psittaci strains and were characterised by a typical fragment doublet of 185/180 base pairs. Such a homogeneity argues for their genetic relatedness and suggests their clonal origin. These data demonstrate the usefulness of MOMP-gene restriction mapping in C psittaci typing.

Animals↗

PubMed1994

Human thymic epithelial cells in serum-free culture: changes in cytokine production in primary and successive culture periods.

Human thymic epithelial cells (TEC) have been cultured in a growth factor-defined serum-free medium, and their production of cytokines in primary cultures and during three subsequent culture periods was investigated. TEC produced interleukin (IL)-1 alpha, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in all culture periods, as detected by the use of ELISA and B9 cell assay. The highest concentrations of the cytokines were found in the tertiary and quaternary subculture period, but in these subcultures the production decreased progressively. There was no clear correlation between cell proliferation and cytokine production in the cultures.

Cell Division↗

PubMed1994

Incidence of cancer among workers in Norwegian hydroelectric power companies.

OBJECTIVES: The goal of this study was to examine whether exposure to electric or magnetic fields is related to cancer. METHODS: The study cohort consisted of 5088 men who had worked for at least one year between 1920 and 1991 for any of eight participating companies which produce and distribute hydroelectric power in Norway. The occupational exposure of these workers included extremely low-frequency electromagnetic fields. Incident cancer cases identified from the Cancer Registry of Norway were analyzed on the basis of the standardized incidence ratio with the Norwegian male population as reference. RESULTS: The incidence of cancer was close to unity for the cohort. The standardized incidence ratio for lymphoma was below unity, whereas those for leukemia and brain tumors were similar to those expected. Calculated cumulative exposure to electric or magnetic fields was not associated with the incidence of leukemia or brain tumors, but an excess of malignant melanoma was shown for the highest category of magnetic field exposure. An analysis of combined possible exposure to oils containing polychlorinated biphenyls and exposure to magnetic fields or possible exposure to electric sparks gave standardized incidence ratios of 265 and 280, respectively, for the higher exposure category. CONCLUSIONS: These results do not support the assumption of a possible association between exposure to electromagnetic fields and leukemia and brain tumors. The possible association between exposure to polychlorinated biphenyls or magnetic fields and risk of malignant melanoma should be further evaluated in future studies.

Electromagnetic Fields↗

PubMed1994

Cancer mortality in a historical cohort study of workers exposed to styrene.

OBJECTIVES: The goal of this study was to determine whether exposure to styrene is associated with an increased risk for neoplasms of the lymphatic and hematopoietic tissues. METHODS: A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved 40,688 workers ever employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories and environmental and biological monitoring data. Cause-specific national death rates were used as the reference. Poisson regression was applied for internal comparisons. RESULTS: Among the exposed workers, no excess was observed for mortality from all neoplasms. Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure. CONCLUSIONS: These findings leave open the possibility of an excess risk of neoplasms of the lymphatic and hematopoietic tissues among workers exposed to styrene.

Cohort Studies↗

PubMed1994

Employment as hairdresser and risk of ovarian cancer and non-Hodgkin's lymphomas among women.

The incidence of ovarian cancer and non-Hodgkin's lymphomas (NHL) between 1971 and 1985 or 1987 has been studied on the basis of cancer registry data among women employed in hairdressing or related occupations at 1970 census in Denmark, Sweden, Norway, and Finland. Overall, the standardized incidence ratio (SIR) for ovarian cancer was 1.18 (95% confidence interval, 0.98 to 1.40). The increase was present among hairdressers from Denmark (SIR, 1.23) and Finland (SIR, 1.88); whereas hairdressers from Sweden and Norway had an incidence close to expectation (SIR 0.95 and 0.96, respectively). In three of the four countries, the SIR was higher in 1971 to 1975 than in later years. The SIR for NHL was 1.20 (0.84 to 1.66); an excess was seen in Denmark (SIR, 1.92) and a decrease was found in Sweden (SIR, 0.63). In previous studies, hairdressers have been reported to be at increased risk of ovarian cancer: this study adds some evidence in favor of the presence of an association. This study also offers some support to the hypothesis of an association between exposure to hair dyes and risk of NHL, that was reported among personal users from the United States. This study, however, strongly suggests that occupational cancer risk among female hairdressers depends on temporal and geographical factors.

Adult↗

PubMed1993

Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups.

The naturally occurring sesquiterpene lactone thapsigargin is a potent and selective inhibitor of SERCA ATPases, a family of Ca(2+)-pumping ATPases present in the endoplasmic reticulum of all mammalian cells. We have studied some of the molecular features of thapsigargin responsible for its inhibitory action towards these Ca2+ ATPases. A series of thapsigargin analogues were synthesised and their inhibitory potencies determined using the uptake of 45Ca2+ in bovine cerebellar microsomes as a sensitive marker of Ca2+ ATPase activity. An attenuation of the inhibitory potency relative to the parent compound was found ranging from slight to over 3 orders of magnitude. The inhibitory activity showed a very strong configuration dependence, a major contribution from the ester groups at C3 and C10, and an apparently minor contribution from the lactone ring substituents. The data are consistent with thapsigargin fitting to a sterically discriminating cleft involving the hydrophobic transmembrane region of the ATPase, and is compatible with available kinetic evidence of thapsigargin-mediated inhibition.

Animals↗

PubMed1993

The JANUS serum bank.

The on-going JANUS project was initiated by the Norwegian Cancer Society in 1973. The serum bank comprises close to 0.5 million serum samples collected from 170,000 donors. From 2-16 consecutive samples are available from each donor. The sera are stored at -25 degrees C. At regular intervals the JANUS-collection is matched against the files of the Norwegian Cancer Registry. From 1973 to 1991 almost 5000 of the donors have developed some form of cancer. Frozen serum samples collected from a few months to 18 years prior to clinical recognition of their disease are consequently available for research purposes. The aim of the JANUS-project is to search in these premorbid sera for chemical, biochemical, immunological or other changes that might be indicative of cancer development at early stages. Gas chromatography-mass spectrometry and two-dimensional protein electrophoresis have been used to evaluate the stability of the frozen sera. Some recent findings are: CA125 is elevated several months prior to diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumour marker in subgroups of thyroid cancer; low level of selenium in serum reflects increased risk of thyroid cancer; and raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkin's disease. On-going research includes trace elements and cancer, and studies on lipid-profiles, diet and cancer. The serum bank may in principle be used for other purposes, e.g. in environmental studies. Analysis of sequential sera may determine chemical substances in the sera that might reflect differences in exposure to environmental pollutants in the period 1973-1991.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1993

Incidence of cancer among lighthouse keepers exposed to asbestos in drinking water.

The study population comprises 690 Norwegian male lighthouse keepers whose water supply came from cisterns that received rain water off asbestos-cement-tiled roofs. The asbestos-cement tiles were installed in the late 1950s, and two decades later the fiber content in the tap water was analyzed. The fiber content ranged from 1,760 to 71,350 million fibers per liter, which is significantly higher than measured in any other Norwegian public water supply. During the follow-up period, 1960-1991, no statistically significant excess risk was found for any type of cancer in the group with a latency period of 20 years or more, except for stomach cancer (11 observed cases vs. 4.57 expected, standardized incidence ratio = 241, 95% confidence interval 120-431). No cases of malignant mesothelioma were found. The study is limited by lack of knowledge as to when the tiles began to deteriorate and, thus, the magnitude of total exposure as well as by the inability to control for such potential confounding factors as diet.

Asbestos↗

PubMed1993

[New cancer disease after treatment of Hodgkin's disease].

The risk of a second cancer was assessed in 1,152 patients with Hodgkins disease who were treated at the Norwegian Radium Hospital from 1968-85. 68 patients developed a second cancer more than one year after the diagnosis of Hodgkins disease. These included nine acute non-lymphocytic leukemias, eight non-Hodgkins lymphomas and 51 solid tumours, including 11 lung cancers. The overall relative risk (observed/expected ratios) of developing a second cancer was 1.86. After 18 years the cumulative risk of developing a second cancer was 14.4% +/- 2.9%, of which 11.2% +/- 2.6% referred to solid tumours. The cumulative risk of leukemia appeared to reach a plateau level of 1.5% after 12 years while the risk of non-Hodgkins lymphomas and lung cancer continued to rise with time to 2.1% and 3.3% respectively after 18 years. The risk of developing leukemia increased after treatment with alkylating agents and Procarbazine. The risk of non-Hodgkins lymphoma was not related to any specific type of therapy. Excess lung cancer risk was noted in patients treated with radiotherapy, and the cancers appeared within the treated areas.

Adolescent↗

PubMed1993

Perinatal outcome among children of men exposed to lead and organic solvents in the printing industry.

The authors investigated the hypothesis that paternal occupational exposures at the time of conception may affect the risk of postconception events by linking records from Oslo, Norway, printers' unions and the Medical Birth Registry of Norway. The linkage yielded 6,251 infants born during the period 1967-1986. On the basis of job classification, fathers were categorized as to their exposure to lead and solvents. Odds ratios were estimated by simple and stratified analysis of tabular data and logistic regression analysis, with children whose fathers were not in lead- or solvent-exposed categories being used as the reference group. In addition, all Oslo births taking place during the same period served as an external reference for computation of standardized morbidity ratios. The adjusted odds ratio for early preterm birth (16-27 weeks) was 5.4 (95% confidence interval (CI) 1.7-17.4) for infants with paternal exposure to solvents and 8.6 (95% CI 2.7-27.3) for children whose fathers were in the lead plus solvents category. The adjusted odds ratio for all perinatal deaths was 2.4 (95% CI 1.2-4.9) for children with fathers in the lead-exposed group and 1.9 (95% CI 0.96-3.7) for children with fathers in the lead plus solvents group. An increased risk of cleft lip was demonstrated, with interaction between sex and paternal exposure to lead: The standardized morbidity ratio for boys in the two subgroups with lead exposure was 4.1 (95% CI 1.8-8.1). Paternal exposure had little impact on birth weight, intrauterine growth, or total number of birth defects. The main problems of the study were the potential for nondifferential misclassification of exposure and the fact that it was not possible to control for potentially confounding life-style factors.

Birth Weight↗

PubMed1993

Incidence of cancer among male waiters and cooks: two Norwegian cohorts.

Previous occupational survey studies have identified 'waiter' and 'cook' as possible high risk occupations for cancer. However, few cohort studies have been performed among persons in the restaurant business, and we therefore have analyzed cancer incidence in two cohorts of Norwegian waiters and cooks. The cohorts consisted of skilled male workers, 1,463 waiters and 2,582 cooks, who received their craft certificate between 1958 and 1983. The cohorts were followed from 1959 through 1991. The standardized incidence ratio (SIR) for all causes of cancer was 1.4 (95 percent confidence interval [CI] = 1.2-1.7] for waiters, and 1.1 (CI = 0.9-1.4) for cooks. Cancers of the tongue, mouth, pharynx, larynx, esophagus, and liver were grouped together as alcohol-associated cancers. SIR for these cancers combined was 5.1 (CI = 3.4-7.4) for waiters and 4.2 (CI = 2.2-7.2) for cooks. For lung cancer, SIR was 2.0 (CI = 1.3-2.9) for waiters and 0.7 (CI = 0.2-1.7) for cooks. For alcohol-associated cancers, the analysis carried out according to number of years since first employment showed a larger number of cases than expected for both occupations in all time-periods. The excess of lung cancer cases among waiters appeared after 30 years or more of employment. The study shows that waiters and cooks are at high risk of cancers associated with alcohol consumption, and that waiters, in addition, show high rates for lung cancer. The hypothesis of an occupational lung-cancer risk in cooks was not supported by this study.

Adult↗

PubMed1993

Polyunsaturated fatty acids in serum phospholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway.

We have tested the hypothesis that specific polyunsaturated fatty acids (PUFA) of the n-3 and n-6 families, as measured in serum phospholipids, are negatively associated with the risk of breast cancer. The study is based on serum samples from women who have donated blood to the Janus serum bank at the University Hospital in Oslo, Norway. It consists of sera from 87 women who developed breast cancer (cases) subsequent to blood donation and 235 women who were free of any diagnosed cancer (controls), but were of similar age and had similar blood storage time as the cases. We measured fatty acids (monounsaturated, polyunsaturated and saturated) in serum phospholipids, and made comparisons between cases and controls. The results showed that there was an inverse relation between the n-6 PUFA linoleic acid (18:2n-6) and risk of breast cancer, but this association was restricted to women who were 55 years and younger. In this age group, the relative risk (odds ratio) of women in the highest quartile of linoleic acid was 0.4 (95% confidence limits, 0.2 and 1.0) compared with women in the lowest quartile, and there was a negative trend over quartiles of linoleic acid (Mantel's chi for trend = -2.49, P < 0.02). No association was noted between the n-3 PUFA of marine oil origin and breast cancer risk. If the measured concentration of linoleic acid in serum phospholipids reliably reflects dietary intake, these data suggest that linoleic acid in the diet may decrease breast cancer risk among women at premenopausal and perimenopausal age. No similar association with n-3 unsaturated fatty acids was observed. It is noteworthy that none of the measured fatty acids (saturated or unsaturated) showed a positive association with breast cancer risk.

Breast Neoplasms↗

PubMed1993

A sensitive and simple high-performance liquid chromatographic method for the determination of mitoxantrone in plasma.

A sensitive high-performance liquid chromatographic (HPLC) method for measuring the anthracene derivative, mitoxantrone, in plasma is described. After protein precipitation with 5-sulfosalicylic acid, samples are resolved by isocratic elution from a C18 reverse phase support and quantified by ultraviolet (UV) detection. Recovery of mitoxantrone after deproteinization was > 70%. Within-run and between-day coefficients of variation (CVs) were 5.1 and 13.7%, respectively, at mitoxantrone concentrations of 20 nM (n = 6). The limit of detection was 2.5 nM and the standard curve linear up to 1 microM. Stability studies have shown that mitoxantrone is stable in spiked whole blood for 3-6 h, provided the samples are kept on ice. The drug is stable in plasma and deproteinized plasma samples for at least 24 h. The method requires few manipulations and is readily adaptable to automation.

Blood Specimen Collection↗

PubMed1993

A sensitive and simple high-performance liquid chromatographic method for the determination of doxorubicin and its metabolites in plasma.

A sensitive high-performance liquid chromatographic (HPLC) method for the measurement of doxorubicin and its metabolites in plasma is described. After precipitation with zinc sulphate and methanol, samples are resolved by isocratic elution from a C18 reverse phase support within 20 min and quantified by endogenous fluorescence. Recoveries over a concentration range from 5 to 1,000 nM of doxorubicin, doxorubicinol, doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinolone were 80-110%, while recovery for 7-deoxydoxorubicinone was approximately 60%. At concentrations of 5 nM, within-run and between-day coefficients of variation for each compound were < 8 and < 16%, respectively. Limits of detection for the compounds were 1-2 nM and standard curves were linear up to at least 1,000 nM. The drug and its metabolites are stable in deproteinized plasma samples at room temperature and in the dark for at least 24 h. The method requires few manipulations and is readily adaptable to automated analysis of large series of samples.

Chromatography, High Pressure Liquid↗

PubMed1993

Effects of growth factors on cytokine production in serum-free cultures of human thymic epithelial cells.

Human thymic epithelial cells (TEC) of medullary phenotype were cultured for 14 days in a growth factor-defined serum-free medium. The effects of added growth factors on cell numbers and the production of cytokines were investigated by separate exclusion of the various growth factors from the medium. We found that hydrocortisone stimulated cell proliferation but inhibited the differentiation of TEC and significantly reduced the production of interleukin-1 alpha, interleukin-6 and granulocyte-macrophage colony stimulating factor. Insulin was found to enhance the differentiation of TEC and the production of the three cytokines. Transferrin and choleratoxin were found to inhibit cell proliferation, but they did not affect production of the cytokines. Exclusion of epidermal growth factor, however, leads to cell death. We conclude that it is essential to exclude hydrocortisone from the medium to optimize production of cytokines, and that transferrin and choleratoxin seem to be unnecessary constituents in serum-free cultures of human TEC.

Cell Division↗